WO2000047109A1 - Devices and methods for frequent measurement of an analyte present in a biological system - Google Patents

Devices and methods for frequent measurement of an analyte present in a biological system Download PDF

Info

Publication number
WO2000047109A1
WO2000047109A1 PCT/US2000/003693 US0003693W WO0047109A1 WO 2000047109 A1 WO2000047109 A1 WO 2000047109A1 US 0003693 W US0003693 W US 0003693W WO 0047109 A1 WO0047109 A1 WO 0047109A1
Authority
WO
WIPO (PCT)
Prior art keywords
monitoring system
component
analyte
components
sampling
Prior art date
Application number
PCT/US2000/003693
Other languages
French (fr)
Inventor
Thomas E. Conn
Russell Ford
Russell O. Potts
Pravin L. Soni
Janet A. Tamada
Michael J. Tierney
Original Assignee
Cygnus, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cygnus, Inc. filed Critical Cygnus, Inc.
Priority to JP2000598064A priority Critical patent/JP2002536103A/en
Priority to AU33630/00A priority patent/AU3363000A/en
Priority to CA002365609A priority patent/CA2365609A1/en
Priority to EP00911792A priority patent/EP1135052A1/en
Publication of WO2000047109A1 publication Critical patent/WO2000047109A1/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/68Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/6802Sensor mounted on worn items
    • A61B5/681Wristwatch-type devices
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0002Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network
    • A61B5/0031Implanted circuitry
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14532Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14546Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring analytes not otherwise provided for, e.g. ions, cytochromes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/48Other medical applications
    • A61B5/4836Diagnosis combined with treatment in closed-loop systems or methods
    • A61B5/4839Diagnosis combined with treatment in closed-loop systems or methods combined with drug delivery
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/68Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/683Means for maintaining contact with the body
    • A61B5/6831Straps, bands or harnesses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0002Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network

Definitions

  • the present invention is in the field of medical devices. More particularly it relates to methods and devices for measuring an analyte present in a biological system.
  • the invention includes a monitoring system for frequently measuring an analyte present in a biological system, said monitoring system comprising,
  • a transdermal or transmucosal sampling mechanism for extracting the analyte from the biological system, wherein said sampling mechanism is adapted for extracting the analyte across a skin or mucosal surface of said biological system;
  • sensing mechanism in operative contact with the analyte extracted by the sampling mechanism, wherein said sensing mechanism obtains a signal from the extracted analyte and said signal is specifically related to the analyte;
  • the sampling mechanism is iontophoresis, electroosmosis, sonophoresis, microdialysis, suction and passive diffusion.
  • the first component further comprises a computing mechanism that converts the signal from the extracted analyte to an output indicative of the amount of analyte extracted by the sampling mechanism.
  • the output can be communicated to the second component for display.
  • the second component receives the signal from the first component, wherein the second component further comprises a computing mechanism that converts the signal from the extracted analyte to an output indicative of the amount of analyte extracted by the sampling mechanism and wherein the second component displays said output.
  • the first and second mechanisms for providing operative communication can comprise a wire-like connection, wireless communication technology or a combination of wirelike and wireless technologies.
  • Wireless communication technology can employ, for example electromagnetic waves (e.g, low frequency electromagnetic waves in a frequency range of about 1 Hz. to about 1 Mega Hz; medium frequency electromagnetic waves in a frequency range of about 1 Mega Hz. to about 500 Mega Hz or high frequency electromagnetic waves in a frequency range of about 500 Mega Hz. to about 5 Giga Hz); capacitance coupling between the biological system and the biological system's environment; inductive coupling; infrared coupling; high frequency acoustic energy or combinations thereof.
  • electromagnetic waves e.g, low frequency electromagnetic waves in a frequency range of about 1 Hz. to about 1 Mega Hz; medium frequency electromagnetic waves in a frequency range of about 1 Mega Hz. to about 500 Mega Hz or high frequency electromagnetic waves in a frequency range of about 500 Mega Hz. to about 5 Giga Hz
  • the second component of the monitoring system relays command signals to the first component, for example, signals to control operation of the sensing mechanism or signals to control operation of the sampling mechanism.
  • the second component can store analyte-related data.
  • the analyte is glucose.
  • the biological system is a mammal, for example a human.
  • the monitoring system as described herein that further comprises (c) a third component comprising
  • a third mechanism for providing operative communication with the first and second components can be implanted in the biological system (e.g., subcutaneously) or, alternatively, can be external to the biological system.
  • the analyte is glucose and the delivery device comprises an insulin pump.
  • the communication between first and second components and the third component is wireless, for example, one or more of the wireless technologies described herein.
  • the invention includes a monitoring system described herein that further comprises
  • a modem or personal computer (i) a modem or personal computer; and (ii) a third mechanism for providing operative communication with the first and second components.
  • the modem or personal computer is remote from the biological system and the communication between the first and second components and the third component is wireless.
  • the modem or personal computer may also be operably linked to a wide area network (WAN), for example the internet.
  • WAN wide area network
  • the analyte is glucose.
  • Figures 1 A to IL show representative embodiments of a monitoring system of the present invention which has at least two components.
  • Figures 1 A through IH depict a two component system while Figures II through IL depict a system having three components.
  • the present mvention relates to monitoring systems generally used for extracting small amounts of a target analyte from the biological system, and then sensing and/or quantifying the concentration of the target analyte. Unlike previous devices, the sampling/sensing mechanism and user interface are found on separate components.
  • the present invention relates to a monitoring system with at least two components, in which a first component comprises sampling mechanism and sensing mechanism that are used to extract and detect an analyte, for example, glucose, and a second component that receives the analyte data from the first component, conducts data processing on the analyte data to determine an analyte concentration and then displays the analyte concentration data.
  • microprocessor functions e.g., control of sampling/sensing, different aspects of data manipulation or recording
  • microprocessing components may be located in one or the other of the at least two components.
  • the second component of the monitoring system can assume many forms, including, but not limited to, the following: a watch, a credit card-shaped device (e.g., a "smart card” or “universal card” having a built-in microprocessor as described for example in U.S. Patent No. 5,892,661), a pager-like device, cell phone- like device, or other such device that communicates information to the user visually, audibly, or kinesthetically.
  • an insulin delivery unit e.g., insulin pump
  • an insulin delivery unit is included in the system.
  • Insulin delivery units both implantable and external, are known in the art and described, for example, in U.S. Patent Numbers 5,995,860; 5,112,614 and 5,062,841.
  • the insulin delivery unit is in communication (e.g., wire-like or wireless communication) with the extracting and/or sensing mechanism such that the sensing mechanism can control the insulin pump and regulate delivery of a suitable amount of insulin to the subj ect.
  • Advantages of separating the first component (e.g., including the biosensor and iontophoresis functions) from the second component (e.g., including some microprocessor and display functions) include greater flexibility, discretion, privacy and convenience to the user.
  • Having a small and lightweight measurement unit allows placement of the two components of the system on a wider range of body sites, for example, the first component may be placed on the abdomen or upper arm.
  • This wider range of placement options may improve the accuracy through optimal extraction site selection (e.g., torso rather than extremities) and greater temperature stability (e.g., via the insulating effects of clothing).
  • the collection and sensing assembly will be able to be placed on a greater range of body sites.
  • a smaller and less obtrusive microprocessor and display unit provides a convenient and discrete system by which to monitor analytes.
  • the biosensor readouts and control signals will be relayed via wire-like or wireless technology between the collection and sensing assembly and the display unit which could take the form of a small watch, a pager, or a credit card-sized device.
  • This system also provides the ability to relay an alert message or signal during nighttime use, for example, to a site remote from the subject being monitored.
  • the two components of the device can be in operative communication via a wire or cable-like connection.
  • the mechanism for providing operative communication between the two components is wireless.
  • Figures 1A to IH show exemplary embodiments of monitoring systems having two components.
  • Figures II to IL show exemplary embodiments of monitoring systems having three components. These exemplary embodiments are described in further detail below.
  • analyte and target analyte are used herein to denote any physiological analyte of interest that is a specific substance or component that is being detected and/or measured in a chemical, physical, enzymatic, or optical analysis.
  • a detectable signal e.g., a chemical signal or electrochemical signal
  • the terms “analyte” and “substance” are used interchangeably herein, and are intended to have the same meaning, and thus encompass any substance of interest.
  • the analyte is a physiological analyte of interest, for example, glucose, or a chemical that has a physiological action, for example, a drug or pharmacological agent.
  • a “sampling device,” “sampling mechanism” or “sampling system” refers to any device for obtaining a sample from a biological system for the purpose of determining the concentration of an analyte of interest.
  • biological systems include any biological system from which the analyte of interest can be extracted, including, but not limited to, blood, interstitial fluid, perspiration and tears.
  • a “biological system” includes both living and artificially maintained systems.
  • the term “sampling” mechanism refers to extraction of a substance from the biological system, generally across a membrane such as skin or mucosa.
  • the membrane can be natural or artificial, and can be of plant or animal nature, such as natural or artificial skin, blood vessel tissue, intestinal tissue, and the like.
  • sampling mechanism are in operative contact with a "reservoir,” or “collection reservoir,” wherein the sampling mechanism is used for extracting the analyte from the biological system into the reservoir to obtain the analyte in the reservoir.
  • sampling techniques include iontophoresis, sonophoresis, suction, electroporation, thermal poration, passive diffusion, microfme (miniature) lances or cannulas, subcutaneous implants or insertions, and laser devices.
  • Iontophoretic sampling devices are described, for example, in International Publication No. WO 97/24059, published 10 July 1997; European Patent Application EP 0942 278, published 15 September 1999; International Publication No. WO 96/00110, published 4 January 1996; International Publication No. WO 97/10499, published 2 March 1997; U.S. Patent Numbers 5,279,543; 5,362,307; 5,730,714;
  • Sonophoresis uses ultrasound to increase the permeability of the skin (see, e.g., Menon et al. (1994) Skin Pharmacology 7:130-139).
  • An exemplary sonophoresis sampling system is described in International Publication No. WO 91/12772, published 5 September 1991.
  • the term "collection reservoir” is used to describe any suitable containment mechanism for containing a sample extracted from a biological system.
  • the collection reservoir can be a receptacle containing a material which is ionically conductive (e.g., water with ions therein), or alternatively, it can be a material, such as, a sponge-like material or hydrophilic polymer, used to keep the water in place or to contain the water.
  • a hydrogel for example, in the form of a disk or pad. Hydrogels are typically referred to as "collection inserts.”
  • Other suitable collection reservoirs include, but are not limited to, tubes, vials, capillary collection devices, cannulas, and miniaturized etched, ablated or molded flow paths.
  • a “housing” for the sampling system can include suitable electronics (e.g., microprocessor, memory, display and other circuit components) and power sources for operating the sampling system in an automatic fashion.
  • a “monitoring system,” as used herein, refers to a system useful for frequently measuring a physiological analyte present in a biological system. Such a system typically includes, but is not limited to, sampling mechanism, sensing mechanism, and a microprocessor mechanism in operative communication with the sampling mechanism and the sensing mechanism.
  • the term "frequent measurement” intends a series of two or more measurements obtained from a particular biological system, which measurements are obtained using a single device maintained in operative contact with the biological system over the time period (e.g, second, minute or hour intervals) in which the series of measurements is obtained.
  • the term thus includes continual and continuous measurements.
  • the term "subject” encompasses any warm-blooded animal, particularly including a member of the class Mammalia such as, without limitation, humans and nonhuman primates such as chimpanzees and other apes and monkey species; farm animals such as cattle, sheep, pigs, goats and horses; domestic mammals such as dogs and cats; laboratory animals including rodents such as mice, rats and guinea pigs, and the like.
  • the term does not denote a particular age or sex. Thus, adult and newborn subjects, whether male or female, are intended to be covered.
  • transdermal includes both transdermal and transmucosal techniques, i.e., extraction of a target analyte across skin or mucosal tissue. Aspects of the invention which are described herein in the context of "transdermal,” unless otherwise specified, are meant to apply to both transdermal and transmucosal techniques.
  • transdermal extraction or “transdermally extracted” intends any sampling method, which entails extracting and/or transporting an analyte from beneath a tissue surface across skin or mucosal tissue.
  • the term thus includes extraction of an analyte using iontophoresis (reverse iontophoresis), electroosmosis, sonophoresis (see, e.g., U.S. Patent No. 5,636,632), microdialysis, suction, and passive diffusion.
  • iontophoresis reverse iontophoresis
  • electroosmosis electroosmosis
  • sonophoresis see, e.g., U.S. Patent No. 5,636,632
  • microdialysis e.g., suction, and passive diffusion.
  • These methods can, of course, be coupled with application of skin penetration enhancers or skin permeability enhancing technique such as various substances or physical methods such as tape stripping or pricking with micro-needles.
  • transdermally extracted also encompasses extraction techniques which employ thermal poration, laser microporation, electroporation, micro fine lances, microfine canulas, subcutaneous implants or insertions, and the like.
  • iontophoresis intends a method for transporting substances across tissue by way of an application of electrical energy to the tissue.
  • a reservoir is provided at the tissue surface to serve as a container of material to be transported.
  • Iontophoresis can be carried out using standard methods known to those of skill in the art, for example, by establishing an electrical potential using a direct current (DC) between fixed anode and cathode "iontophoretic electrodes," alternating a direct current between anode and cathode iontophoretic electrodes, or using a more complex waveform such as applying a current with alternating polarity (AP) between iontophoretic electrodes (so that each electrode is alternately an anode or a cathode), as described for example in U.S. Patent Numbers 5,771,890 and 6,023,629.
  • DC direct current
  • AP alternating alternating polarity
  • reverse iontophoresis refers to the movement of a substance from a biological fluid across a membrane by way of an applied electric potential or current.
  • a reservoir is provided at the tissue surface to receive the extracted material, as used in the Gluco Watch® (Cygnus, Inc., Redwood City, CA) glucose monitor (See, e.g., Tanada et al. (1999) JAMA 282:1839-1844).
  • Electroosmosis refers to the movement of a substance through a membrane by way of an electric field-induced convective flow.
  • the terms iontophoresis, reverse iontophoresis, and electroosmosis will be used interchangeably herein to refer to movement of any ionically charged or uncharged substance across a membrane (e.g., an epithelial membrane) upon application of an electric potential to the membrane through an ionically conductive medium.
  • sensing device encompasses any device that can be used to measure the concentration of an analyte, or derivative thereof, of interest.
  • Preferred sensing devices for detecting blood analytes generally include electrochemical devices, optical and chemical devices and combinations thereof.
  • electrochemical devices include the Clark electrode system (see, e.g., Updike, et al., (1967) Nature 214:986-988), and other amperometric, coulometric, or potentiometric electrochemical devices.
  • optical devices include conventional enzyme-based reactions as used in the Lifescan® (Johnson and Johnson, New Brunswick, NJ) glucose monitor (see, e.g., U.S. Patent 4,935,346 to Phillips, et al.).
  • a “biosensor” or “biosensor device” includes, but is not limited to, a “sensor element” which includes, but is not limited to, a “biosensor electrode” or “sensing electrode” or “working electrode” which refers to the electrode that is monitored to determine the amount of electrical signal at a point in time or over a given time period, which signal is then correlated with the concentration of a chemical compound.
  • the sensing electrode comprises a reactive surface which converts the analyte, or a derivative thereof, to electrical signal.
  • the reactive surface can be comprised of any electrically conductive material such as, but not limited to, platinum-group metals (including, platinum, palladium, rhodium, ruthenium, osmium, and iridium), nickel, copper, silver, and carbon, as well as, oxides, dioxides, combinations or alloys thereof.
  • platinum-group metals including, platinum, palladium, rhodium, ruthenium, osmium, and iridium
  • nickel copper
  • silver and carbon
  • oxides, dioxides, combinations or alloys thereof oxides, dioxides, combinations or alloys thereof.
  • the “sensor element” can include components in addition to a biosensor electrode, for example, it can include a “reference electrode,” and a “counter electrode.”
  • the term “reference electrode” is used herein to mean an electrode that provides a reference potential, e.g., a potential can be established between a reference electrode and a working electrode.
  • the term “counter electrode” is used herein to mean an electrode in an electrochemical circuit which acts as a current source or sink to complete the electrochemical circuit. Although it is not essential that a counter electrode be employed where a reference electrode is included in the circuit and the electrode is capable of performing the function of a counter electrode, it is preferred to have separate counter and reference electrodes because the reference potential provided by the reference electrode is most stable when it is at equilibrium. If the reference electrode is required to act further as a counter electrode, the current flowing through the reference electrode may disturb this equilibrium. Consequently, separate electrodes functioning as counter and reference electrodes are most preferred.
  • the "counter electrode” of the "sensor element” comprises a "bimodal electrode.”
  • the term “bimodal electrode” as used herein typically refers to an electrode which is capable of functioning non-simultaneously as, for example, both the counter electrode (of the “sensor element") and the iontophoretic electrode (of the “sampling mechanism") as described, for example, U.S. Patent No. 5,954,685.
  • reactive surface and “reactive face” are used interchangeably herein to mean the surface of the sensing electrode that: (1) is in contact with the surface of an electrolyte containing material (e.g. gel) which contains an analyte or through which an analyte, or a derivative thereof, flows from a source thereof; (2) is comprised of a catalytic material (e.g., carbon, platinum, palladium, rhodium, ruthenium, or nickel and/or oxides, dioxides and combinations or alloys thereof) or a material that provides sites for electrochemical reaction; (3) converts a chemical signal (e.g.
  • an electrical signal e.g., an electrical current
  • an electrical signal e.g., an electrical current
  • an electrical signal e.g., an electrical current
  • An "ionically conductive material” refers to any material that provides ionic conductivity, and through which electrochemically active species can diffuse.
  • the ionically conductive material can be, for example, a solid, liquid, or semi-solid (e.g., in the form of a gel) material that contains an electrolyte, which can be composed primarily of water and ions (e.g., sodium chloride), and generally comprises 50% or more water by weight.
  • the material can be in the form of a gel, a sponge or pad (e.g., soaked with an electrolytic solution), or any other material that can contain an electrolyte and allow passage therethrough of electrochemically active species, especially the analyte of interest.
  • physiological effect encompasses effects produced in the subject that achieve the intended purpose of a therapy.
  • a physiological effect mechanism that the symptoms of the subject being treated are prevented or alleviated.
  • a physiological effect would be one that results in the prolongation of survival in a patient.
  • collection assembly refers to any structure that can be used to collect the analyte of interest.
  • autosensor assembly refers to any structure capable of sensing the analyte of interest.
  • the structures may be comprised of several layers, for example, a collection reservoir, a mask layer, liners and/or a retaining layer where the layers are held in appropriate, functional relationship to each other.
  • the autosensor assembly may also include liners. Exemplary collection assemblies and autosensor structures are described, for example, in International Publication WO 99/58190, published 18 November 1999; and U.S. Patent Numbers 5,735,273 and 5,827,183.
  • substantially planar as used herein, includes a planar surface that contacts a slightly curved surface, for example, a forearm or upper arm of a subject.
  • a “substantially planar” surface is, for example, a surface having a shape to which skin can conform, i.e., contacting between the skin and the surface.
  • printed is meant a substantially uniform deposition of an electrode formulation onto one surface of a substrate (i.e., the base support). It will be appreciated by those skilled in the art that a variety of techniques may be used to effect substantially uniform deposition of a material onto a substrate, e.g., Gravure-type printing, extrusion coating, screen coating, spraying, painting, or the like.
  • user interface refers to any means or mechanism that interacts (e.g., provides or exchanges information) with any one of a user's senses.
  • suitable interfaces include visual displays (e.g., LCD displays); tactile or mechanical signals (e.g., vibrations, alarms, buttons, etc.) and auditory signals (e.g., alarm or speaker).
  • microprocessor refers to any type of device that functions as a microcontroller and also includes any type of programmable logic, for example, Flexible Program Gate Array (FPGA).
  • FPGA Flexible Program Gate Array
  • the term “wire-like” refers to communications involving the transport of signals from one location to another using a wire, cable or other solid object. Examples include the transport of electric charge and/or voltage on metallic wires and the transport of light energy on fiber optic cables.
  • the term “wireless” refers to communications involving the transport of signals from one location to another without the use of wires or cables. Examples include, but are not limited to: the transport of signals through space via electromagnetic waves; the transport of signals through air via pressure waves (e.g., acoustic signals); the transport of signals through space via magnetic fields; the transport of signals through space via electric fields; and combinations of one or more of the foregoing.
  • the term “transceiver” refers to any device which is capable of functioning as both a transmitter and a receiver of signals. An integrated transceiver system is described, for example, in U.S. Patent No. 5,930,686.
  • the present invention is based on the novel concept of separating an analyte monitoring system into at least two components.
  • the first component samples (extracts) and senses (detects) the analyte of interest while the second component includes a user interface.
  • Data processing on the analyte data can be performed by the first component, the second component or both.
  • Additional components for example, an alarm or a drug delivery unit, can also be included.
  • Particular components of the subject invention are described below. It is to be understood that the various forms of different embodiments of the invention may be combined.
  • the present invention relates to a monitoring system, for frequently measuring an analyte present in a biological system, comprising a measurement unit (e.g., sampling mechanism and sensing mechanism) in operative communication with a second component (e.g., a user interface).
  • a measurement unit e.g., sampling mechanism and sensing mechanism
  • a second component e.g., a user interface
  • Further components can be included in the system as well, for example, a third component having display mechanism (display unit), a delivery unit and/or electronic file data serving mechanism.
  • the communication connection between the components can be a wire-like connection (e.g., a wire or multi-wire cable).
  • operative communications between the components is a wireless link, i.e. provided by a "virtual cable," for example, a telemetry link. This wireless link can be uni- or bi-directional between the two components. In the case of more than two components, links can be a combination of wire-like and wireless.
  • This monitoring system comprising at least two components relays biosensor information from the measurement unit to the user interface for subsequent analysis and display. It can also relay command signals and information from the user interface to the measurement unit in order to control sensing (e.g. , the biosensor) and sampling (e.g., iontophoresis) functions; data processing (e.g., calibration values); and event logging (e.g., meals, exercise, etc.).
  • additional components for example, an insulin delivery unit can be included.
  • the insulin delivery unit can receive commands from the measuring system and deliver suitable amounts of insulin.
  • the monitoring system of the present invention comprises at least two components, as shown for example in the Figures.
  • the first component typically includes both sampling and sensing mechanism and, optionally, a power source and a controller (microprocessor).
  • the sampling/sensing mechanism is placed on the skin, e.g., for example for transdermal or transmucosal sampling/sensing.
  • one or more aspects of the sampling/sensing mechanisms can be implanted, for example, subcutaneously into a user.
  • the sampling mechanism can comprise sampling (e.g., iontophoretic) electrodes that are used to perform frequent transdermal or transmucosal sampling of an analyte of interest (e.g., glucose).
  • the sensing mechanism can comprise biosensor electrodes (see, e.g., European Patent Application EP 0942 278, published 15 September 1999).
  • the sensing mechanism is typically in operative contact with the extracted analyte and obtains a signal from the extracted analyte. The signal is specifically related to the analyte.
  • the first component provides the mechanism to sample and sense the presence of an analyte, for example by detecting electrochemical signals produced at the biosensor electrode surfaces.
  • Consumable collection assemblies that provide sampling and sensing functions are described, for example in International Publication WO 99/58190, published 18 November 1999.
  • the analyte to be monitored by the invention described herein can be any specific substance or component that one is desirous of detecting and/or measuring in a chemical, physical, enzymatic, or optical analysis.
  • Such analytes include, but are not limited to, amino acids, enzyme substrates or products indicating a disease state or condition, other markers of disease states or conditions, drugs of abuse, therapeutic and/or pharmacologic agents (e.g., theophylline, anti-HIV drugs, lithium, anti- epileptic drugs, cyclosporin, chemotherapeutics), electrolytes, physiological analytes of interest (e.g., urate/uric acid, carbonate, calcium, potassium, sodium, chloride, bicarbonate (CO 2 ), glucose, urea (blood urea nitrogen), lactate/lactic acid, hydroxybutyrate, cholesterol, triglycerides, creatine, creatinine, insulin, hematocrit, and hemoglobin), blood gases (carbon dioxide, oxygen, pH), lipid
  • the analyte is a physiological analyte of interest, for example glucose, or a chemical that has a physiological action, for example a drug or pharmacological agent.
  • the analyte is detected by specific enzyme systems.
  • specific enzyme systems for example, in the case of glucose, the enzyme glucose oxidase catalyzes a redox reaction which produces hydrogen peroxide from glucose and oxygen.
  • glucose oxidase catalyzes a redox reaction which produces hydrogen peroxide from glucose and oxygen.
  • a number of other analyte-specific enzyme systems can be used in the invention, which enzyme systems operate on much the same general techniques.
  • a biosensor electrode that detects hydrogen peroxide can be used to detect ethanol using an alcohol oxidase enzyme system, or similarly uric acid with urate oxidase system, cholesterol with a cholesterol oxidase system, and theophylline with a xanthine oxidase system.
  • the oxidase enzyme (used for hydrogen peroxidase-based detection) can be replaced with another redox system, for example, the dehydrogenase-enzyme NAD-NADH, which offers a separate route to detecting additional analytes.
  • Dehydrogenase-based sensors can use working electrodes made of gold or carbon (via mediated chemistry). Examples of analytes suitable for this type of monitoring include, but are not limited to, cholesterol, ethanol, hydroxybutyrate, phenylalanine and triglycerides.
  • the enzyme can be eliminated and detection can rely on direct electrochemical or potentiometric detection of an analyte.
  • Such analytes include, without limitation, heavy metals (e.g., cobalt, iron, lead, nickel, zinc), oxygen, carbonate/carbon dioxide, chloride, fluoride, lithium, pH, potassium, sodium, and urea.
  • the sampling system described herein can be used for therapeutic drug monitoring, for example, monitoring anti-epileptic drugs (e.g., phenytion), chemotherapy (e.g., adriamycin), hyperactivity (e.g., ritalin), and anti-organ-rejection (e.g., cyclosporin).
  • anti-epileptic drugs e.g., phenytion
  • chemotherapy e.g., adriamycin
  • hyperactivity e.g., ritalin
  • anti-organ-rejection e.g., cyclosporin
  • test solutions having known concentrations of alcohol, uric acid, cholesterol, or theophylline may be used herein.
  • the solutions may contain additives, diluents, solubilizers, and the like, that do not interfere with detection of the analyte of interest by the sampling system.
  • the sampling mechanism is based on transdermal extraction. Measurement and/or sampling with the monitoring system can be carried out in a frequent manner. Frequent measurements allow for closer monitoring of target analyte concentration fluctuations. More specifically, an analyte monitoring system is used to measure changes in analyte levels in an animal subject over a wide range of analyte concentrations. The device can be contacted with the biological system for extended periods of time, and automatically obtains frequent glucose samples in order to measure glucose concentration at various selected intervals. Sampling is carried out by extracting an analyte (e.g., glucose) through the skin of the patient.
  • an analyte e.g., glucose
  • an iontophoretic current is applied to a surface of the skin of a subject.
  • ions or charged molecules pull along other uncharged molecules or particles such as glucose which are drawn into a collection reservoir placed on the surface of the skin.
  • the collection reservoir may comprise any ionically conductive material and is preferably in the form of a hydrogel which is comprised of a hydrophilic material, water and an electrolyte.
  • the sampling device can operate in an alternating polarity mode necessitating the presence of first and second bimodal electrodes and two collection reservoirs.
  • Each bi-modal electrode serves two functions depending on the phase of the operation: (1) an electro-osmotic electrode (or iontophoretic electrode) used to electrically draw analyte from a source into a collection reservoir comprising water and an electrolyte, and to the area of the electrode subassembly; and (2) as a counter electrode to the first sensing electrode (described below) at which the chemical compound is catalytically converted at the face of the sensing electrode to produce an electrical signal. Alternating polarity is described, for example, in U.S. Patent No. 5,954,685.
  • the iontophoresis (e.g., bi-modal) electrode is preferably comprised of
  • the electrodes are formulated using analytical- or electronic-grade reagents and solvents and are provided such that they are not susceptible to attack (e.g., plasticization) by components in the surrounding environment.
  • the electrochemical reaction which occurs at the surface of this electrode serves as a facile source or sink for electrical current.
  • Ag/AgCl electrodes known in the art are capable of repeatedly forming a reversible couple which operates without unwanted electrochemical side reactions (which may give rise to changes in pH, and liberation of hydrogen and oxygen due to water hydrolysis).
  • a sensing mechanism for sensing the analyte of interest is also included in the present invention, and can be, for example, based on electrochemical detection techniques.
  • the sensing mechanism obtains a signal from the extracted analyte that is specifically related to that analyte.
  • a variety of sensing mechanism find use in the present invention, for example, in the case of the analyte glucose, the collection reservoir may further contain an enzyme which catalyzes a reaction of glucose to form an easily detectable species.
  • the enzyme is preferably glucose oxidase (GOx) which catalyzes the reaction between glucose and oxygen and results in the production of hydrogen peroxide.
  • the hydrogen peroxide reacts at a catalytic surface of a biosensor electrode, resulting in the generation of electrons which create a detectable biosensor current (raw signal).
  • Suitable biosensor electrodes are described, for example, in EP 0 942 278.
  • the biosensor electrodes are constructed of any suitable material, for example, platinum and graphite.
  • the sensor element can also include a reference electrode, and a counter electrode, a mask layer; a retaining layer and/or one or more liners.
  • Suitable configurations e.g., flexibility, shape, degree of sealing, degree of isolation of components, degree of occlusivity, adhesion to target surface and/or electrodes
  • Suitable configurations can be readily determined by the skilled artisan in view of the teachings herein and devices known in the art, for example as described in EP 0 942 278 and WO 99/58190.
  • extraction and sensing of the analyte may be conducted using a measurement sample which selectively favors analyte-specific signal components over signal components due to interfering species, for example by (a) employing a differential signal process which subtracts non- analyte signal components from the analyte signal; (b) employing a delay step which is performed between the sampling (extraction) and sensing steps; (c) employing a selective electrochemical detection process performed during the sensing step; (d) employing a purge step, performed after the sensing step; (e) employing a charge segregation step or (f) any combination of (a) through (e).
  • sampling and sensing mechanisms can be combined into one structure.
  • the sampling and/or sensing electrode compositions may be affixed to a suitable rigid or flexible nonconductive surface.
  • a silver (Ag) underlayer is first applied to the surface in order to provide uniform conduction.
  • the Ag/AgCl electrode composition is then applied over the Ag underlayer in any suitable pattern or geometry using various thin film techniques, such as sputtering, evaporation, vapor phase deposition, or the like, or using various thick film techniques, such as film laminating, electroplating, or the like.
  • the Ag/AgCl composition can be applied using screen printing, pad printing, inkjet methods, transfer roll printing, or similar techniques. (See, e.g., WO 99/58190).
  • the general operation of an iontophoretic sampling and sensing system is the cyclical repetition of two phases: (1) a reverse-iontophoretic phase, followed by a (2) sensing phase.
  • the reverse iontophoretic phase the first bimodal electrode acts as an iontophoretic cathode and the second bimodal electrode acts as an iontophoretic anode to complete the circuit.
  • Analyte e.g., glucose
  • the reservoirs for example, a hydrogel.
  • the iontophoretic cu ⁇ ent is turned off.
  • the sensing phase in the case of glucose, a potential is applied between the reference electrode and the sensing electrode.
  • the chemical signal reacts catalytically on the catalytic face of the first sensing electrode producing an electrical current, while the first bi-modal electrode acts as a counter electrode to complete the electrical circuit.
  • the reference and sensing electrodes, as well as, the bimodal electrode described above are typically connected to a standard potentiostat circuit during sensing.
  • the electrode sub-assembly can be operated by electrically connecting the bimodal electrodes such that each electrode is capable of functioning as both an iontophoretic electrode and counter electrode along with appropriate sensing electrode(s) and reference electrode(s), to create standard potentiostat circuitry.
  • a potentiostat is an electrical circuit used in electrochemical measurements in three electrode electrochemical cells.
  • a potential is applied between the reference electrode and the sensing electrode.
  • the current generated at the sensing electrode flows through circuitry to the counter electrode (i.e., no current flows through the reference electrode to alter its equilibrium potential).
  • Two independent potentiostat circuits can be used to operate the two biosensors.
  • the electrical current measured at the sensing electrode subassembly is the current that is correlated with an amount of chemical signal.
  • a power source e.g., one or more rechargeable and/or nonrechargeable batteries
  • the power source provides sufficient power to apply an electric potential (either direct current or a more complex waveform) between the two iontophoretic (sampling) electrodes such that current flows from the first iontophoretic electrode, through the first conductive medium into the skin or mucosal surface, and then back out through the second conductive medium to the second iontophoretic electrode.
  • the current flow is sufficient to extract substances including an analyte of interest through the skin into one or both of the collection reservoirs.
  • the electric potential may be applied using any suitable technique, for example, the applied current density may be in the range of about 0.01 to 0.5 mA/cm 2 .
  • the power source provides a cu ⁇ ent flow to the first bi-modal electrode to facilitate the extraction of the chemical signal into the reservoir.
  • the power source is used to provide voltage to the first sensing electrode to drive the conversion of chemical signals retained in the reservoir to electrical signals at the catalytic face of the sensing electrode.
  • the power source also maintains a fixed potential at the electrode where, for example, hydrogen peroxide is converted to molecular oxygen, hydrogen ions, and electrons, which is compared with the potential of the reference electrode during the sensing phase. While one sensing electrode is operating in the sensing mode it is electrically connected to the adjacent bimodal electrode which acts as a counter electrode at which electrons generated at the sensing electrode are consumed.
  • Non- limiting examples of suitable sources of power include printed batteries, film batteries, moldable batteries, coin cell batteries, prismatic batteries, or cylindrical batteries.
  • Printed batteries can be incorporated into the monitoring system, for instance in the first component during printing of the biosensor.
  • the biosensor is printed onto a .005 inch thick PET film substrate.
  • the printed battery can be deposited onto this same substrate using similar thick-film print processes.
  • Anode, insulator material, electrolyte, cathode and encapsulant material can be deposited in sequential steps to create the battery.
  • Electrode materials can be deposited in charged states, such as by charging a printing screen during deposition of the electrode layers, thereby avoiding the need to charge the battery after deposition.
  • film batteries can be assembled with the other components of the sampling/sensing device using, for example, Solid State SystemTM lithium-ion solid polymer rechargeable batteries from Ultralife Batteries Inc., Newark, NY. Thin film batteries and moldable batteries from solid electrodes and/or solid electrolytes can also be used, such as the "RHISS" technology from ECR Corporation, Rehovot, Israel. Coin-cell, prismatic, or cylindrical batteries, for example using nickel metal hydride, various lithium, alkaline, zinc-air, chemistries, may also be used and are commercially available, for example from Panaxonic Industrial, Secaucus, NJ, Narta Batteries Inc., Elmsford, ⁇ Y.
  • Solid State SystemTM lithium-ion solid polymer rechargeable batteries from Ultralife Batteries Inc., Newark, NY.
  • Thin film batteries and moldable batteries from solid electrodes and/or solid electrolytes can also be used, such as the "RHISS" technology from ECR Corporation, Rehovot, Israel.
  • these and other power sources can also be incorporated into the second component to provide the necessary power to run the user interface and/or microprocessing functions contained in the second component.
  • selection and implementation of a suitable power source can be readily determined by one of skill in the art in view of one or more of the following factors: the method of extraction (sampling), for example, iontophoresis, sonophoresis, etc.; the nature of the user interface; the method of sensing, for example, with biosensor electrodes; manufacturability; energy density; energy capacity; cost; charging time; self- discharging characteristics; environmental concerns; government regulations; safety; and user preference.
  • the second component of the at least two component monitoring system comprises a user interface and, typically, one or more controller (microprocessor) functions. Additional components such as suitable electronics (e.g., microprocessing, memory, display and other circuit components), a power source, an alarm and the like can also be included in the user interface.
  • suitable electronics e.g., microprocessing, memory, display and other circuit components
  • a power source e.g., a battery, or a battery, or the like
  • the user interface may provide numerical readouts, other visual indication of analyte concentration (e.g., a ⁇ ows), or visual instruction actions (e.g., take medication, eat or drink). Buttons on the user interface may provide the ability to supply information needed to calibrate and/or otherwise control the device.
  • the first component provides the necessary elements to drive the extraction and sensing of the analyte.
  • the sensing electronics then communicate the results (data) of extraction and sensing to the second component (user interface) where microprocessing functions process the data and/or display such data to the user.
  • Algorithms capable of data manipulation are known to those of skill in the art. Suitable algorithms useful in processing data (e.g., predicting physiological values, signal processing, predicting concentration, and the like) are described, for example, in International Publication WO 99/58973, published 18 November 1999 and International Publication WO 99/58050, published 18 November 1999.
  • Serial Number 09/198,039, filed 30 September 1998 describes how a Mixtures of Experts algorithm can be used predict a concentration of an analyte of interest.
  • one or more functions of the microprocessor e.g., data manipulation, calibration, etc.
  • one or more of the sampling and sensing functions of the first component are controlled by the second component.
  • the operation of the sampling device can be controlled by a controller (e.g., a microprocessor with one or more components located in the second component of the monitoring system), which is in operable communication with the sampling electrodes, the sensor electrodes, the power supply, as well as optional temperature and/or conductance sensing elements, a display, and other electronics.
  • the user interface (second component) may take a variety of configurations, for example, a credit card like device (e.g., "smartcard"), a watch, pager, or cell phone device that includes memory, a display such as a liquid crystal display (LCD) and buttons. The buttons can be used to control what is displayed and record events occurring during use of the product (e.g., meals, exercise, insulin doses).
  • the user interface may also be a remote device such as a personal computer or network.
  • Figure 1 A shows one embodiment of the present invention in which the first component is worn on the torso (next to the skin) and the user interface is worn as a watch.
  • the first component (sampling/sensing) relays data about the analyte of interest to the second component (user interface) which then displays the data.
  • the first component includes microprocessing functions that control sampling and sensing and, in addition, can include data processing functions.
  • the data obtained (and/or processed) by the first component is then transmitted via wireless communication (see Section IV below) to the user interface for display.
  • Figure IB shows an embodiment similar to that of Figure 1 A where the first component is worn on the torso and the second component takes the form of a watch.
  • the first component relays information about the analyte to the second component, which contains microprocessing functions (e.g., data processing) and display capabilities.
  • microprocessing functions e.g., data processing
  • Figure 1C depicts yet another embodiment where the first component is worn on the torso and the second component is worn as a pager-like device, shown on the belt of the user in Figure lC.
  • the second component includes buttons and display panel.
  • the first and second components are in two-way communication with one another. Because of two-way communication, the user has the ability to control the first component with the second component, for example, using the buttons to control collection and sensing intervals and/or data manipulation.
  • the first component will also generally include microprocessing function, for example to control sampling and sensing functions, collect and/or relay data to the second component.
  • Figure ID depicts an embodiment of the present invention in which the first component includes virtually all the microprocessing functions (e.g., control of sampling/sensing, data manipulation, calibration, etc.).
  • the first component is worn next to the skin, for example, under the clothing on the torso.
  • the first component includes a display panel and buttons (e.g., for controlling the microprocessor and/or display).
  • the first component relays data to the second component for display.
  • the second component is depicted as a watchlike structure and includes a display panel, buttons (e.g., for determining what data is displayed and how it is displayed), and electronics controlling the display.
  • Figure IE depicts yet another embodiment where the first and second components are in two-way communication with one another.
  • the first component is pictured as being worn by the user on the arm and the second component is depicted as a pager-like device on the belt.
  • the second component includes a display panel and buttons. Because the components are in two-way communication, microprocessing functions can be divided between these components in any number of ways.
  • the second component can control the sampling/sensing of the first component (e.g., collection intervals, calibration, etc), receive analyte data from the first component, manipulate and display the analyte data.
  • buttons allow for the user to interface with the monitoring system, for example to control one or more of these aspects.
  • the first component can contain the control functions for sampling/sensing and, optionally, calibration and/or data manipulation. This data can then be transmitted to the second component for further manipulations, if necessary, and display.
  • Figure IF shows an embodiment of the present invention depicting the two way wireless communication between the first component (labeled "sensor” in the Figure) and the second component (depicted as a watch in the Figure).
  • the user interface includes buttons, microcontroller functions and, in addition, is capable of displaying time, date and analyte data to the user.
  • the sensor will typically be placed next to the skin and the watch worn around the wrist of the user.
  • Figure 1G shows another embodiment having bi-directional wireless communication between the sensor (first component) and user interface (second component), depicted in the Figure as a pager-type device.
  • the user interface e.g., pager-type device
  • the pager-type device will also be capable of sending auditory and/or tactile (e.g., vibrational) signals to the user regarding analyte data, time, etc.
  • the sensor component is typically be placed next to the skin of the user and the pager-type device worn outside the clothes or carried in a purse, bag, briefcase or the like.
  • Figure IH shows another embodiment having bi-directional wireless communication between the sensor (first component) and user interface (second component), depicted in the Figure as a credit card-type device.
  • the user interface e.g., credit card
  • the user interface includes buttons, microcontroller functions and, in addition, is capable of visually displaying time, date and analyte data to the user. Further, the user interface can also be designed to include other information about the user.
  • the credit card device will also be capable of sending auditory and/or tactile (e.g., vibrational) signals to the user regarding analyte data, time, etc.
  • the sensor component is typically be placed next to the skin of the user and the credit card device worn outside in the pocket or carried in the wallet of the user.
  • the at least two components of the present invention are preferably in operative communication with one another.
  • the operative communication can include, for example, the following: one-way communication from the biosensor (e.g., the first component) to the user interface (e.g., a second component), or two-way communications between the first component and the second component.
  • Communication with third or more components with either first or second component can be one-way or two-way depending on the particular type of information being communicated.
  • the at least two components of the monitoring system have two-way communications.
  • any of the communication means (devices) described herein can be used to maintain operative communication between the at least two components and any other additional components (e.g., alarm, remote modem or PC, display, or delivery unit).
  • Mechanism for providing operative communication between the two components include, but are not limited to, the following: 1) One-way communication from the sensing mechanism (first component) to the display electronics (second component).
  • the second component can include mechanism for data storage, user inputs, and the ability to upload information to a host computer. 2) Similar to (1), but with data storage, user inputs, and upload to host computer from the first component.
  • Two-way communications between the first and second components, where data storage, user inputs, and upload to host computer can either (a) all be in either the first or second component, or (b) split in any combination between the two sets of electronics (i.e., the first and second components).
  • a host device for data upload or automatic reporting to healthcare provider via telephone, internet, or wireless communications.
  • a bedside receiver that automatically reports to a patient's personal physician. This same bedside device could also function as a telephone.
  • wireless communications technologies for example, short range communication, i.e., less than or equal to 3 meters, or longer range
  • wireless communications technologies for example, short range communication, i.e., less than or equal to 3 meters, or longer range
  • -Electromagnetic waves including but not limited to, low frequency electromagnetic waves (frequency range about 1 Hz - 1 Mega Hz); medium frequency electromagnetic waves (frequency range about 1 Mega Hz - 500 Mega Hz); and high frequency electromagnetic waves (frequency range about 500 Mega Hz - 20 Giga Hz).
  • LF low frequency
  • MF medium frequency
  • HF high frequency
  • VHF very high frequency
  • UHF ultra high frequency
  • SHF super high frequency
  • EHF extra high frequency
  • Capacitance coupling between, for example, a subject's body and the environment/air (frequency range about 1 Hz - 1 Mega Hz); - Inductive coupling (i.e., time varying magnetic field; not freely propagating electromagnetic wave);
  • Infrared coupling using infrared light, e.g., as in low speed communications links to computers and personal digital assistants
  • infrared light e.g., as in low speed communications links to computers and personal digital assistants
  • the communication between the at least two components is a wireless link.
  • Wireless links allow for the uploading of data from the monitoring system to a personal computer or personal digital assistant (having the necessary receiver electronics) for viewing by the user, family member, medical care team or researchers.
  • wire-like links can also be used for this purpose, wireless links are prefe ⁇ ed to enhance user convenience.
  • electromagnetic waves such as radio frequency with carrier bands from 20 kilo Hertz to 20 Giga Hertz (see, e.g., Freihe ⁇ (1998) Medical Device and Diagnostic Industry, Aug:83-93); capacitance coupling; inductive coupling, infrared coupling, high frequency acoustic energy and frequency hopping schemes.
  • wireless communications are provided by electromagnetic waves (radio-frequency).
  • the selection of which carrier frequency can be readily determined by one of skill in the art in view of range (e.g., distance between sensing mechanism and user interface), blocking by the human body and clothes, power consumption, bandwidth, noise susceptibility, antenna size, FCC regulations, selected communication protocol, cost and availability of starting materials.
  • Two-way paging electronics and networks, for example RF (radio-frequency) transceivers also find use in the present invention, for example technology manufactured and commercially available from High Desert RDN, Rupert, ID; RF Monolithics, Inc., Dallas, TX; and Motorola, Inc.
  • the miniature, spread spectrum transceiver known as the RF-SOI sensor transceiverTM (High Desert RDN, Rupert, ID) requires less than .5 volts of electrical power while providing a sensor or analysis host device the ability to gather and transceive data in real time.
  • Short-range wireless data communications are also commercially available, for example, the wireless data transceiver systems designed and available from RF Monolithics, Inc., Dallas, TX.
  • Two-way paging devices e.g., ReFlex® paging hardware and service (Motorola, Inc.) are also available.
  • a file server for example, a file server that is part of a wide area network (WAN) such as the internet.
  • the information on the file server can then be readily accessed using standard web browsing software with appropriate security features implemented for confidentiality.
  • cellular and/or cordless telephone networks can be used to transfer the data to a file server for access. See, e.g., U.S. Patent Numbers 5,838,730 and 5,574,775.
  • Wireless communications for local area networks (LAN) are described, for example, in U.S. Patent Numbers 5,875,186 and 5,987,033.
  • U.S. Patent No. 5,077,753 and www.bluetooth.com for descriptions of Bluetooth technology, a wireless communication technology for data and voice.
  • the wireless link (e.g., communication mechanism) is established by capacitance coupling, for example using a technology called Personal Area Network (PAN; WO 96/36134, N. Gershenfeld, et al., published 14 November 1996).
  • PAN Personal Area Network
  • This technology is an example of capacitance coupling involving the use of the human body to carry cu ⁇ ent, and thus information, from one device to another. These devices have to be either in direct contact, or in close proximity, to the body.
  • a low frequency carrier e.g., below 1 MHz, is used to transmit the information.
  • Advantages of PAN include that it may require less energy for data transmission, the potential of better control over security of transmitted information, and the use of simple low cost electronics.
  • inductive coupling can also be used to establish wireless communication abilities between the two components of the monitoring system described herein.
  • Inductive coupling usually requires that the communicating components be in relatively close physical proximity to each other.
  • Suitable inductive coupling technology is described, for example, in U.S. Patent Number 5,882,300 to Malinouskas, issued March 16, 1999 directed to a wireless patient monitoring apparatus that employs inductive coupling.
  • Wireless systems that make use of infrared coupling are also known and described, for example in U.S. Patent Numbers 5,103,108 and 5,027,834, as are wireless communication systems that make use of high frequency acoustic energy (e.g., ultrasound).
  • Ultrasonic wireless communications typically use frequencies between about 100 KHz and 1.0 MHz (see, e.g., U.S. Patent No. 5,982,297).
  • the present invention may also include, in addition to the first and second components, other additional components, for example, additional display units, alarm mechanisms and or delivery units such as pumps.
  • Alarm mechanisms could be used to warn the user when the concentration of the analyte gets above or below a preset threshold value.
  • the alarm will be remote from (and in communication with) the first and second components, while in other embodiments, the alarm can be included within the structure of the first or second components.
  • a component comprising a delivery unit capable of delivering a substance (e.g., therapeutic substance) to the subject is included in the present invention.
  • the substance delivered to the subject will of course depend on the analyte being monitored. For instance, in the case where glucose is the analyte, the delivery unit will preferably deliver insulin.
  • this information can be relayed to the delivery unit.
  • Microprocessing functions within the delivery unit can then determine the appropriate amount of therapeutic substance to be delivered to the subject.
  • the determination of the amount of therapeutic substance to be delivered by the delivery unit can be made by any of the components of the system, for example by the first or second components following appropriate data collection and analysis.
  • the delivery unit can be automatically controlled by the first and/or second components of the monitoring system.
  • the user can have input as to the amount of substance delivered by the delivery unit. For example, after reviewing the display of data obtained from the sampling/sensing component, the user can determine the amount of substance to be delivered and transmit appropriate instructions (e.g., via programming the microprocessing functions of the user interface) to the delivery unit.
  • Suitable delivery units for example, insulin pumps are described in the art. See, e.g., U.S. Patent Nos.
  • Implantable glucose monitoring-telemetry devices have also been described, see, e.g., U.S. Patent Number 4,703,756; Atanasov et al. (1997) Biosensors & Bioelectronics 12:669-679; Black et al. (1996) Sensors and Actuators B3 147-153; McKean and Gough (1988) IEEE Transactions on Biomedical Engineering 35:526-532.
  • the delivery unit may be implantable or external to the subject.
  • the present invention includes embodiments having one or more additional components (e.g., both alarm and delivery unit).
  • the additional component(s) are preferably in operably communication with at least one of the first and second components.
  • the nature of the communication between the additional component(s) and the first and/or second components can be readily determined by a skilled artisan using the communications mechanisms and factors described herein, for example, whether the additional component a separate structure, whether it is implanted or external, the nature of the microprocessor(s) in the components and the like.
  • the communication between the additional(s) components is wireless.
  • Figure II depicts an embodiment of the present invention which includes three separate components: a sampling/sensing mechanism ("sensor”); a user interface (depicted as a credit card) and a drug delivery unit ("insulin pump”).
  • sensor sampling/sensing mechanism
  • user interface displayed as a credit card
  • insulin pump drug delivery unit
  • all three components have bi-directional wireless communication abilities with each of the other elements. This allows, for example, for a feedback loop to be established between the sensor and the insulin pump without input from the user.
  • the sensor component samples and senses the analyte (e.g., glucose) and microcontroller functions in either the insulin pump or the sensor analyze and translate the data into the amount of insulin required to be administered to the user.
  • analyte e.g., glucose
  • the bi-directional wireless communication abilities also allow for situations in which the user controls the amount of insulin infused by the pump, for example, taking into account meals, exercise or other factors.
  • the credit card can include a variety of functions (e.g., date, time, analyte data, other information) and can employ a variety of display mechanisms (e.g., visual, auditory or tactile).
  • the sensor is preferably worn next to the skin while the credit card can be carried in a pocket or wallet.
  • the insulin pump is preferably at least partially implanted (e.g., subcutaneously) in the user.
  • Figure 1 J depicts an embodiment similar to that of Figure II except that the user interface is depicted as a watch rather than a credit card.
  • Figure IK depicts a three component, bi-directional wireless communication system as described for Figure II, except that the user interface is a pager-type device.
  • Figure IL depicts an embodiment of the present invention which includes three separate components: a sampling/sensing mechanism ("sensor"); a user interface (depicted as a watch) and a remote modem.
  • the modem receives information from the sensor and user interface.
  • the user interface and sensor will also be in communication with one another.
  • the presence of a remove modem allows the sharing of data between the user and variety of other interested parties.
  • the modem can be linked to a wide area network (WAN) such as the internet and transmitted to secure file server for accessed using, for example, web browsing software (with appropriate security measures) by a doctor or hospital personnel.
  • WAN wide area network
  • the watch can include a variety of functions (e.g., date, time, analyte data, other information) and can employ a variety of display mechanisms (e.g., visual, auditory or tactile).
  • the sensor is preferably worn next to the skin while the watch is worn on the wrist.

Abstract

Devices and methods are provided for frequently measuring the concentration of an analyte present in a biological system. A monitoring system having at least two components is employed in order to allow separation of data collection from data processing and display. Such separation allows greater flexibility and convenience for the user.

Description

DEVICES AND METHODS FOR FREQUENT MEASUREMENT OF AN ANALYTE PRESENT IN A BIOLOGICAL SYSTEM
Technical Field
The present invention is in the field of medical devices. More particularly it relates to methods and devices for measuring an analyte present in a biological system.
Background
Self-monitoring of blood glucose is a critical part of managing diabetes. However, present procedures for obtaining such information are invasive, painful and provide only periodic measurements. Standard methods of measuring involve the use of painful and cumbersome finger stick blood tests. Thus, development of a painless and automatic approach would represent a significant improvement in the quality of life for people with diabetes. Further, a tight glucose control regimen, which uses frequent glucose measurements to guide the administration of insulin or oral hypoglycemic agents, leads to a substantial decrease in the long-term complications of diabetes. See, Diabetes Control and Complication Trial Research Group (1993) N. Engl. J. Med. 329:997-1036.
Summary of the Invention
In one aspect, the invention includes a monitoring system for frequently measuring an analyte present in a biological system, said monitoring system comprising,
(a) a first component comprising
(i) a transdermal or transmucosal sampling mechanism for extracting the analyte from the biological system, wherein said sampling mechanism is adapted for extracting the analyte across a skin or mucosal surface of said biological system;
(ii) sensing mechanism in operative contact with the analyte extracted by the sampling mechanism, wherein said sensing mechanism obtains a signal from the extracted analyte and said signal is specifically related to the analyte; and
(iii) first mechanism for providing operative communication with a second component of the monitoring system; and (b) a second component comprising
(i) a user interface; and
(ii) second mechanism for providing operative communication with the first component.
In certain embodiments, the sampling mechanism is iontophoresis, electroosmosis, sonophoresis, microdialysis, suction and passive diffusion. In certam embodiments, the first component further comprises a computing mechanism that converts the signal from the extracted analyte to an output indicative of the amount of analyte extracted by the sampling mechanism. The output can be communicated to the second component for display. Further, in other embodiments, the second component receives the signal from the first component, wherein the second component further comprises a computing mechanism that converts the signal from the extracted analyte to an output indicative of the amount of analyte extracted by the sampling mechanism and wherein the second component displays said output. The first and second mechanisms for providing operative communication can comprise a wire-like connection, wireless communication technology or a combination of wirelike and wireless technologies. Wireless communication technology can employ, for example electromagnetic waves (e.g, low frequency electromagnetic waves in a frequency range of about 1 Hz. to about 1 Mega Hz; medium frequency electromagnetic waves in a frequency range of about 1 Mega Hz. to about 500 Mega Hz or high frequency electromagnetic waves in a frequency range of about 500 Mega Hz. to about 5 Giga Hz); capacitance coupling between the biological system and the biological system's environment; inductive coupling; infrared coupling; high frequency acoustic energy or combinations thereof. In still further embodiments, the second component of the monitoring system relays command signals to the first component, for example, signals to control operation of the sensing mechanism or signals to control operation of the sampling mechanism. In certain embodiments, the second component can store analyte-related data. In yet another embodiments, the analyte is glucose. In certain embodiments, the biological system is a mammal, for example a human.
In yet another aspect of the invention, the monitoring system as described herein that further comprises (c) a third component comprising
(i) a delivery device; and
(ii) a third mechanism for providing operative communication with the first and second components. The delivery device can be implanted in the biological system (e.g., subcutaneously) or, alternatively, can be external to the biological system. In certain embodiments, the analyte is glucose and the delivery device comprises an insulin pump. In certain embodiments, the communication between first and second components and the third component is wireless, for example, one or more of the wireless technologies described herein.
In yet another aspect, the invention includes a monitoring system described herein that further comprises
(c) a third component comprising
(i) a modem or personal computer; and (ii) a third mechanism for providing operative communication with the first and second components. In certain embodiments, the modem or personal computer is remote from the biological system and the communication between the first and second components and the third component is wireless. The modem or personal computer may also be operably linked to a wide area network (WAN), for example the internet. In certain embodiments, the analyte is glucose. These and other embodiments of the present invention will readily occur to those of ordinary skill in the art in view of the disclosure herein. Brief Description of the Figures
Figures 1 A to IL show representative embodiments of a monitoring system of the present invention which has at least two components. Figures 1 A through IH depict a two component system while Figures II through IL depict a system having three components.
Detailed Description of the Invention
Before describing the present invention in detail, it is to be understood that this invention is not limited to particular formulations or process parameters, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments of the invention only, and is not intended to be limiting.
The present mvention relates to monitoring systems generally used for extracting small amounts of a target analyte from the biological system, and then sensing and/or quantifying the concentration of the target analyte. Unlike previous devices, the sampling/sensing mechanism and user interface are found on separate components. Thus, the present invention relates to a monitoring system with at least two components, in which a first component comprises sampling mechanism and sensing mechanism that are used to extract and detect an analyte, for example, glucose, and a second component that receives the analyte data from the first component, conducts data processing on the analyte data to determine an analyte concentration and then displays the analyte concentration data. Typically, microprocessor functions (e.g., control of sampling/sensing, different aspects of data manipulation or recording) are found in both components. Alternatively, microprocessing components may be located in one or the other of the at least two components. The second component of the monitoring system can assume many forms, including, but not limited to, the following: a watch, a credit card-shaped device (e.g., a "smart card" or "universal card" having a built-in microprocessor as described for example in U.S. Patent No. 5,892,661), a pager-like device, cell phone- like device, or other such device that communicates information to the user visually, audibly, or kinesthetically. Further, additional components may be added to the system, for example, a third component comprising a display of analyte values or an alarm related to analyte concentration, may be employed. In certain embodiments, an insulin delivery unit (e.g., insulin pump) is included in the system. Insulin delivery units, both implantable and external, are known in the art and described, for example, in U.S. Patent Numbers 5,995,860; 5,112,614 and 5,062,841. Preferably, when included as a component of the present invention, the insulin delivery unit is in communication (e.g., wire-like or wireless communication) with the extracting and/or sensing mechanism such that the sensing mechanism can control the insulin pump and regulate delivery of a suitable amount of insulin to the subj ect.
Advantages of separating the first component (e.g., including the biosensor and iontophoresis functions) from the second component (e.g., including some microprocessor and display functions) include greater flexibility, discretion, privacy and convenience to the user. Having a small and lightweight measurement unit allows placement of the two components of the system on a wider range of body sites, for example, the first component may be placed on the abdomen or upper arm. This wider range of placement options may improve the accuracy through optimal extraction site selection (e.g., torso rather than extremities) and greater temperature stability (e.g., via the insulating effects of clothing). Thus, the collection and sensing assembly will be able to be placed on a greater range of body sites. Similarly, a smaller and less obtrusive microprocessor and display unit (the second component) provides a convenient and discrete system by which to monitor analytes. The biosensor readouts and control signals will be relayed via wire-like or wireless technology between the collection and sensing assembly and the display unit which could take the form of a small watch, a pager, or a credit card-sized device. This system also provides the ability to relay an alert message or signal during nighttime use, for example, to a site remote from the subject being monitored.
In one embodiment, the two components of the device can be in operative communication via a wire or cable-like connection. In preferred embodiments, the mechanism for providing operative communication between the two components is wireless. Figures 1A to IH show exemplary embodiments of monitoring systems having two components. Figures II to IL show exemplary embodiments of monitoring systems having three components. These exemplary embodiments are described in further detail below.
I. Definitions It must be noted that, as used in this specification and the appended claims, the singular forms "a", "an" and "the" include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to "a binder" includes a mixture of two or more such binders, reference to "an analyte" includes mixtures of analytes, and the like. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although any methods and materials similar or equivalent to those described herein can be used in the practice for testing of the present invention, the preferred materials and methods are described herein. In describing and claiming the present invention, the following terminology will be used in accordance with the definitions set out below.
The terms "analyte" and "target analyte" are used herein to denote any physiological analyte of interest that is a specific substance or component that is being detected and/or measured in a chemical, physical, enzymatic, or optical analysis. A detectable signal (e.g., a chemical signal or electrochemical signal) can be obtained, either directly or indirectly, from such an analyte or derivatives thereof. Furthermore, the terms "analyte" and "substance" are used interchangeably herein, and are intended to have the same meaning, and thus encompass any substance of interest. In preferred embodiments, the analyte is a physiological analyte of interest, for example, glucose, or a chemical that has a physiological action, for example, a drug or pharmacological agent.
A "sampling device," "sampling mechanism" or "sampling system" refers to any device for obtaining a sample from a biological system for the purpose of determining the concentration of an analyte of interest. Such "biological systems" include any biological system from which the analyte of interest can be extracted, including, but not limited to, blood, interstitial fluid, perspiration and tears. Further, a "biological system" includes both living and artificially maintained systems. As used herein, the term "sampling" mechanism refers to extraction of a substance from the biological system, generally across a membrane such as skin or mucosa. The membrane can be natural or artificial, and can be of plant or animal nature, such as natural or artificial skin, blood vessel tissue, intestinal tissue, and the like. Typically, the sampling mechanism are in operative contact with a "reservoir," or "collection reservoir," wherein the sampling mechanism is used for extracting the analyte from the biological system into the reservoir to obtain the analyte in the reservoir. Non- limiting examples of sampling techniques include iontophoresis, sonophoresis, suction, electroporation, thermal poration, passive diffusion, microfme (miniature) lances or cannulas, subcutaneous implants or insertions, and laser devices. Iontophoretic sampling devices are described, for example, in International Publication No. WO 97/24059, published 10 July 1997; European Patent Application EP 0942 278, published 15 September 1999; International Publication No. WO 96/00110, published 4 January 1996; International Publication No. WO 97/10499, published 2 March 1997; U.S. Patent Numbers 5,279,543; 5,362,307; 5,730,714;
5,771,890; 5,989,409; 5,735,273; 5,827,183; 5,954,685 and 6,023,629. Sonophoresis uses ultrasound to increase the permeability of the skin (see, e.g., Menon et al. (1994) Skin Pharmacology 7:130-139). An exemplary sonophoresis sampling system is described in International Publication No. WO 91/12772, published 5 September 1991. Passive diffusion sampling devices are described, for example, in International Publication Nos.: WO 97/38126 (published 16 October 1997); WO 97/42888, WO 97/42886, WO 97/42885, and WO 97/42882 (all published 20 November 1997); and WO 97/43962 (published 27 November 1997). Laser devices use a small laser beam to create one or more micropores in the uppermost layer of the patient's skin (see, e.g., Jacques et al. (1978) J. Invest. Dermatology 88:88-93; International Publication WO 99/44507, published 1999 September 10; International Publication WO 99/44638, published 1999 September 10; and International Publication WO 99/40848, published 1999 August 19.
The term "collection reservoir" is used to describe any suitable containment mechanism for containing a sample extracted from a biological system. For example, the collection reservoir can be a receptacle containing a material which is ionically conductive (e.g., water with ions therein), or alternatively, it can be a material, such as, a sponge-like material or hydrophilic polymer, used to keep the water in place or to contain the water. Such collection reservoirs can be in the form of a hydrogel (for example, in the form of a disk or pad). Hydrogels are typically referred to as "collection inserts." Other suitable collection reservoirs include, but are not limited to, tubes, vials, capillary collection devices, cannulas, and miniaturized etched, ablated or molded flow paths.
A "housing" for the sampling system can include suitable electronics (e.g., microprocessor, memory, display and other circuit components) and power sources for operating the sampling system in an automatic fashion. A "monitoring system," as used herein, refers to a system useful for frequently measuring a physiological analyte present in a biological system. Such a system typically includes, but is not limited to, sampling mechanism, sensing mechanism, and a microprocessor mechanism in operative communication with the sampling mechanism and the sensing mechanism. As used herein, the term "frequent measurement" intends a series of two or more measurements obtained from a particular biological system, which measurements are obtained using a single device maintained in operative contact with the biological system over the time period (e.g, second, minute or hour intervals) in which the series of measurements is obtained. The term thus includes continual and continuous measurements. The term "subject" encompasses any warm-blooded animal, particularly including a member of the class Mammalia such as, without limitation, humans and nonhuman primates such as chimpanzees and other apes and monkey species; farm animals such as cattle, sheep, pigs, goats and horses; domestic mammals such as dogs and cats; laboratory animals including rodents such as mice, rats and guinea pigs, and the like. The term does not denote a particular age or sex. Thus, adult and newborn subjects, whether male or female, are intended to be covered.
The term "transdermal," as used herein, includes both transdermal and transmucosal techniques, i.e., extraction of a target analyte across skin or mucosal tissue. Aspects of the invention which are described herein in the context of "transdermal," unless otherwise specified, are meant to apply to both transdermal and transmucosal techniques. The term "transdermal extraction," or "transdermally extracted" intends any sampling method, which entails extracting and/or transporting an analyte from beneath a tissue surface across skin or mucosal tissue. The term thus includes extraction of an analyte using iontophoresis (reverse iontophoresis), electroosmosis, sonophoresis (see, e.g., U.S. Patent No. 5,636,632), microdialysis, suction, and passive diffusion. These methods can, of course, be coupled with application of skin penetration enhancers or skin permeability enhancing technique such as various substances or physical methods such as tape stripping or pricking with micro-needles. The term "transdermally extracted" also encompasses extraction techniques which employ thermal poration, laser microporation, electroporation, micro fine lances, microfine canulas, subcutaneous implants or insertions, and the like.
The term "iontophoresis" intends a method for transporting substances across tissue by way of an application of electrical energy to the tissue. In conventional iontophoresis, a reservoir is provided at the tissue surface to serve as a container of material to be transported. Iontophoresis can be carried out using standard methods known to those of skill in the art, for example, by establishing an electrical potential using a direct current (DC) between fixed anode and cathode "iontophoretic electrodes," alternating a direct current between anode and cathode iontophoretic electrodes, or using a more complex waveform such as applying a current with alternating polarity (AP) between iontophoretic electrodes (so that each electrode is alternately an anode or a cathode), as described for example in U.S. Patent Numbers 5,771,890 and 6,023,629.
The term "reverse iontophoresis" refers to the movement of a substance from a biological fluid across a membrane by way of an applied electric potential or current. In reverse iontophoresis, a reservoir is provided at the tissue surface to receive the extracted material, as used in the Gluco Watch® (Cygnus, Inc., Redwood City, CA) glucose monitor (See, e.g., Tanada et al. (1999) JAMA 282:1839-1844).
"Electroosmosis" refers to the movement of a substance through a membrane by way of an electric field-induced convective flow. The terms iontophoresis, reverse iontophoresis, and electroosmosis, will be used interchangeably herein to refer to movement of any ionically charged or uncharged substance across a membrane (e.g., an epithelial membrane) upon application of an electric potential to the membrane through an ionically conductive medium.
The term "sensing device," "sensing mechanism," or "biosensor device" encompasses any device that can be used to measure the concentration of an analyte, or derivative thereof, of interest. Preferred sensing devices for detecting blood analytes generally include electrochemical devices, optical and chemical devices and combinations thereof. Examples of electrochemical devices include the Clark electrode system (see, e.g., Updike, et al., (1967) Nature 214:986-988), and other amperometric, coulometric, or potentiometric electrochemical devices. Examples of optical devices include conventional enzyme-based reactions as used in the Lifescan® (Johnson and Johnson, New Brunswick, NJ) glucose monitor (see, e.g., U.S. Patent 4,935,346 to Phillips, et al.).
A "biosensor" or "biosensor device" includes, but is not limited to, a "sensor element" which includes, but is not limited to, a "biosensor electrode" or "sensing electrode" or "working electrode" which refers to the electrode that is monitored to determine the amount of electrical signal at a point in time or over a given time period, which signal is then correlated with the concentration of a chemical compound. The sensing electrode comprises a reactive surface which converts the analyte, or a derivative thereof, to electrical signal. The reactive surface can be comprised of any electrically conductive material such as, but not limited to, platinum-group metals (including, platinum, palladium, rhodium, ruthenium, osmium, and iridium), nickel, copper, silver, and carbon, as well as, oxides, dioxides, combinations or alloys thereof. Some catalytic materials, membranes, and fabrication technologies suitable for the construction of amperometric biosensors are described by Newman, J.D., et al.(1995) Analytical Chemistry 67:4594-4599.
The "sensor element" can include components in addition to a biosensor electrode, for example, it can include a "reference electrode," and a "counter electrode." The term "reference electrode" is used herein to mean an electrode that provides a reference potential, e.g., a potential can be established between a reference electrode and a working electrode. The term "counter electrode" is used herein to mean an electrode in an electrochemical circuit which acts as a current source or sink to complete the electrochemical circuit. Although it is not essential that a counter electrode be employed where a reference electrode is included in the circuit and the electrode is capable of performing the function of a counter electrode, it is preferred to have separate counter and reference electrodes because the reference potential provided by the reference electrode is most stable when it is at equilibrium. If the reference electrode is required to act further as a counter electrode, the current flowing through the reference electrode may disturb this equilibrium. Consequently, separate electrodes functioning as counter and reference electrodes are most preferred.
In one embodiment, the "counter electrode" of the "sensor element" comprises a "bimodal electrode." The term "bimodal electrode" as used herein typically refers to an electrode which is capable of functioning non-simultaneously as, for example, both the counter electrode (of the "sensor element") and the iontophoretic electrode (of the "sampling mechanism") as described, for example, U.S. Patent No. 5,954,685.
The terms "reactive surface," and "reactive face" are used interchangeably herein to mean the surface of the sensing electrode that: (1) is in contact with the surface of an electrolyte containing material (e.g. gel) which contains an analyte or through which an analyte, or a derivative thereof, flows from a source thereof; (2) is comprised of a catalytic material (e.g., carbon, platinum, palladium, rhodium, ruthenium, or nickel and/or oxides, dioxides and combinations or alloys thereof) or a material that provides sites for electrochemical reaction; (3) converts a chemical signal (e.g. hydrogen peroxide) into an electrical signal (e.g., an electrical current); and (4) defines the electrode surface area that, when composed of a reactive material, is sufficient to drive the electrochemical reaction at a rate sufficient to generate a detectable, reproducibly measurable, electrical signal that is correlatable with the amount of analyte present in the electrolyte. An "ionically conductive material" refers to any material that provides ionic conductivity, and through which electrochemically active species can diffuse. The ionically conductive material can be, for example, a solid, liquid, or semi-solid (e.g., in the form of a gel) material that contains an electrolyte, which can be composed primarily of water and ions (e.g., sodium chloride), and generally comprises 50% or more water by weight. The material can be in the form of a gel, a sponge or pad (e.g., soaked with an electrolytic solution), or any other material that can contain an electrolyte and allow passage therethrough of electrochemically active species, especially the analyte of interest.
The term "physiological effect" encompasses effects produced in the subject that achieve the intended purpose of a therapy. In preferred embodiments, a physiological effect mechanism that the symptoms of the subject being treated are prevented or alleviated. For example, a physiological effect would be one that results in the prolongation of survival in a patient.
The terms "collection assembly," as used herein, refers to any structure that can be used to collect the analyte of interest. Similarly, an "autosensor assembly" refers to any structure capable of sensing the analyte of interest. The structures may be comprised of several layers, for example, a collection reservoir, a mask layer, liners and/or a retaining layer where the layers are held in appropriate, functional relationship to each other. The autosensor assembly may also include liners. Exemplary collection assemblies and autosensor structures are described, for example, in International Publication WO 99/58190, published 18 November 1999; and U.S. Patent Numbers 5,735,273 and 5,827,183.
"Substantially planar" as used herein, includes a planar surface that contacts a slightly curved surface, for example, a forearm or upper arm of a subject. A "substantially planar" surface is, for example, a surface having a shape to which skin can conform, i.e., contacting between the skin and the surface.
By the term "printed" as used herein is meant a substantially uniform deposition of an electrode formulation onto one surface of a substrate (i.e., the base support). It will be appreciated by those skilled in the art that a variety of techniques may be used to effect substantially uniform deposition of a material onto a substrate, e.g., Gravure-type printing, extrusion coating, screen coating, spraying, painting, or the like.
The term "user interface" refers to any means or mechanism that interacts (e.g., provides or exchanges information) with any one of a user's senses. Non- limiting examples of suitable interfaces include visual displays (e.g., LCD displays); tactile or mechanical signals (e.g., vibrations, alarms, buttons, etc.) and auditory signals (e.g., alarm or speaker). The term "microprocessor" refers to any type of device that functions as a microcontroller and also includes any type of programmable logic, for example, Flexible Program Gate Array (FPGA).
As used herein, the term "wire-like" refers to communications involving the transport of signals from one location to another using a wire, cable or other solid object. Examples include the transport of electric charge and/or voltage on metallic wires and the transport of light energy on fiber optic cables. The term "wireless" refers to communications involving the transport of signals from one location to another without the use of wires or cables. Examples include, but are not limited to: the transport of signals through space via electromagnetic waves; the transport of signals through air via pressure waves (e.g., acoustic signals); the transport of signals through space via magnetic fields; the transport of signals through space via electric fields; and combinations of one or more of the foregoing. The term "transceiver" refers to any device which is capable of functioning as both a transmitter and a receiver of signals. An integrated transceiver system is described, for example, in U.S. Patent No. 5,930,686.
II. General Overview
The present invention is based on the novel concept of separating an analyte monitoring system into at least two components. The first component samples (extracts) and senses (detects) the analyte of interest while the second component includes a user interface. Data processing on the analyte data can be performed by the first component, the second component or both. Additional components, for example, an alarm or a drug delivery unit, can also be included. Particular components of the subject invention are described below. It is to be understood that the various forms of different embodiments of the invention may be combined.
Thus, the present invention relates to a monitoring system, for frequently measuring an analyte present in a biological system, comprising a measurement unit (e.g., sampling mechanism and sensing mechanism) in operative communication with a second component (e.g., a user interface). Further components can be included in the system as well, for example, a third component having display mechanism (display unit), a delivery unit and/or electronic file data serving mechanism. Providing such a system in at least two parts imparts greater flexibility and convenience to the user. In one embodiment, the communication connection between the components can be a wire-like connection (e.g., a wire or multi-wire cable). In a preferred embodiment, operative communications between the components is a wireless link, i.e. provided by a "virtual cable," for example, a telemetry link. This wireless link can be uni- or bi-directional between the two components. In the case of more than two components, links can be a combination of wire-like and wireless.
This monitoring system comprising at least two components relays biosensor information from the measurement unit to the user interface for subsequent analysis and display. It can also relay command signals and information from the user interface to the measurement unit in order to control sensing (e.g. , the biosensor) and sampling (e.g., iontophoresis) functions; data processing (e.g., calibration values); and event logging (e.g., meals, exercise, etc.). In some embodiments, additional components, for example, an insulin delivery unit can be included. The insulin delivery unit can receive commands from the measuring system and deliver suitable amounts of insulin.
III. Sampling Mechanism and Sensing Mechanism The monitoring system of the present invention comprises at least two components, as shown for example in the Figures. The first component typically includes both sampling and sensing mechanism and, optionally, a power source and a controller (microprocessor). In one aspect, the sampling/sensing mechanism is placed on the skin, e.g., for example for transdermal or transmucosal sampling/sensing. Alternatively, one or more aspects of the sampling/sensing mechanisms can be implanted, for example, subcutaneously into a user. In a preferred embodiment, the sampling mechanism can comprise sampling (e.g., iontophoretic) electrodes that are used to perform frequent transdermal or transmucosal sampling of an analyte of interest (e.g., glucose). The sensing mechanism can comprise biosensor electrodes (see, e.g., European Patent Application EP 0942 278, published 15 September 1999). The sensing mechanism is typically in operative contact with the extracted analyte and obtains a signal from the extracted analyte. The signal is specifically related to the analyte. Thus, the first component provides the mechanism to sample and sense the presence of an analyte, for example by detecting electrochemical signals produced at the biosensor electrode surfaces. Consumable collection assemblies that provide sampling and sensing functions are described, for example in International Publication WO 99/58190, published 18 November 1999.
A. Analytes
The analyte to be monitored by the invention described herein can be any specific substance or component that one is desirous of detecting and/or measuring in a chemical, physical, enzymatic, or optical analysis. Such analytes include, but are not limited to, amino acids, enzyme substrates or products indicating a disease state or condition, other markers of disease states or conditions, drugs of abuse, therapeutic and/or pharmacologic agents (e.g., theophylline, anti-HIV drugs, lithium, anti- epileptic drugs, cyclosporin, chemotherapeutics), electrolytes, physiological analytes of interest (e.g., urate/uric acid, carbonate, calcium, potassium, sodium, chloride, bicarbonate (CO2), glucose, urea (blood urea nitrogen), lactate/lactic acid, hydroxybutyrate, cholesterol, triglycerides, creatine, creatinine, insulin, hematocrit, and hemoglobin), blood gases (carbon dioxide, oxygen, pH), lipids, heavy metals (e.g., lead, copper), and the like. In preferred embodiments, the analyte is a physiological analyte of interest, for example glucose, or a chemical that has a physiological action, for example a drug or pharmacological agent. In one embodiment, the analyte is detected by specific enzyme systems. For example, in the case of glucose, the enzyme glucose oxidase catalyzes a redox reaction which produces hydrogen peroxide from glucose and oxygen. A number of other analyte-specific enzyme systems can be used in the invention, which enzyme systems operate on much the same general techniques. For example, a biosensor electrode that detects hydrogen peroxide can be used to detect ethanol using an alcohol oxidase enzyme system, or similarly uric acid with urate oxidase system, cholesterol with a cholesterol oxidase system, and theophylline with a xanthine oxidase system.
In addition, the oxidase enzyme (used for hydrogen peroxidase-based detection) can be replaced with another redox system, for example, the dehydrogenase-enzyme NAD-NADH, which offers a separate route to detecting additional analytes. Dehydrogenase-based sensors can use working electrodes made of gold or carbon (via mediated chemistry). Examples of analytes suitable for this type of monitoring include, but are not limited to, cholesterol, ethanol, hydroxybutyrate, phenylalanine and triglycerides. Further, the enzyme can be eliminated and detection can rely on direct electrochemical or potentiometric detection of an analyte. Such analytes include, without limitation, heavy metals (e.g., cobalt, iron, lead, nickel, zinc), oxygen, carbonate/carbon dioxide, chloride, fluoride, lithium, pH, potassium, sodium, and urea. Also, the sampling system described herein can be used for therapeutic drug monitoring, for example, monitoring anti-epileptic drugs (e.g., phenytion), chemotherapy (e.g., adriamycin), hyperactivity (e.g., ritalin), and anti-organ-rejection (e.g., cyclosporin).
Appropriate formulations of analyte test solutions can be employed and are readily determined by one of skill in the art. For example, test solutions having known concentrations of alcohol, uric acid, cholesterol, or theophylline may be used herein. The solutions may contain additives, diluents, solubilizers, and the like, that do not interfere with detection of the analyte of interest by the sampling system.
Therefore, it is to be understood that, although discussed primary with respect to glucose herein, the present invention is also applicable to the monitoring of other analytes of interest.
B. Sampling Mechanism
Typically, the sampling mechanism is based on transdermal extraction. Measurement and/or sampling with the monitoring system can be carried out in a frequent manner. Frequent measurements allow for closer monitoring of target analyte concentration fluctuations. More specifically, an analyte monitoring system is used to measure changes in analyte levels in an animal subject over a wide range of analyte concentrations. The device can be contacted with the biological system for extended periods of time, and automatically obtains frequent glucose samples in order to measure glucose concentration at various selected intervals. Sampling is carried out by extracting an analyte (e.g., glucose) through the skin of the patient. It is to be understood that extraction of the analyte can be conducted using a variety of methods, for example, iontophoresis, sonophoresis, suction, electroporation, thermal poration, passive diffusion, microfine (miniature) lances or cannulas, subcutaneous implants or insertions, laser devices and other methods known to those of skill in the art. In one aspect, an iontophoretic current is applied to a surface of the skin of a subject. When the current is applied, ions or charged molecules pull along other uncharged molecules or particles such as glucose which are drawn into a collection reservoir placed on the surface of the skin. The collection reservoir may comprise any ionically conductive material and is preferably in the form of a hydrogel which is comprised of a hydrophilic material, water and an electrolyte. In one aspect, the sampling device can operate in an alternating polarity mode necessitating the presence of first and second bimodal electrodes and two collection reservoirs. Each bi-modal electrode serves two functions depending on the phase of the operation: (1) an electro-osmotic electrode (or iontophoretic electrode) used to electrically draw analyte from a source into a collection reservoir comprising water and an electrolyte, and to the area of the electrode subassembly; and (2) as a counter electrode to the first sensing electrode (described below) at which the chemical compound is catalytically converted at the face of the sensing electrode to produce an electrical signal. Alternating polarity is described, for example, in U.S. Patent No. 5,954,685. The iontophoresis (e.g., bi-modal) electrode is preferably comprised of
Ag/AgCl, described for example in U.S. Patent No. 5,954,685 and International Publication WO 99/58190. Preferably, the electrodes are formulated using analytical- or electronic-grade reagents and solvents and are provided such that they are not susceptible to attack (e.g., plasticization) by components in the surrounding environment. The electrochemical reaction which occurs at the surface of this electrode serves as a facile source or sink for electrical current. With regard to operation for extended periods of time, Ag/AgCl electrodes known in the art are capable of repeatedly forming a reversible couple which operates without unwanted electrochemical side reactions (which may give rise to changes in pH, and liberation of hydrogen and oxygen due to water hydrolysis). C. Sensing Mechanism
As noted above, a sensing mechanism for sensing the analyte of interest is also included in the present invention, and can be, for example, based on electrochemical detection techniques. The sensing mechanism obtains a signal from the extracted analyte that is specifically related to that analyte. A variety of sensing mechanism find use in the present invention, for example, in the case of the analyte glucose, the collection reservoir may further contain an enzyme which catalyzes a reaction of glucose to form an easily detectable species. The enzyme is preferably glucose oxidase (GOx) which catalyzes the reaction between glucose and oxygen and results in the production of hydrogen peroxide. The hydrogen peroxide reacts at a catalytic surface of a biosensor electrode, resulting in the generation of electrons which create a detectable biosensor current (raw signal).
Suitable biosensor electrodes are described, for example, in EP 0 942 278. In brief, the biosensor electrodes are constructed of any suitable material, for example, platinum and graphite. The sensor element can also include a reference electrode, and a counter electrode, a mask layer; a retaining layer and/or one or more liners. Suitable configurations (e.g., flexibility, shape, degree of sealing, degree of isolation of components, degree of occlusivity, adhesion to target surface and/or electrodes) can be readily determined by the skilled artisan in view of the teachings herein and devices known in the art, for example as described in EP 0 942 278 and WO 99/58190.
In addition, it may be desirable to configure the sampling/sensing mechanisms (or employ measurement techniques) in such a way that the effect of interfering species on the sensor is reduced. As described for example in International Publication WO 99/58051 , published 18 November 1999, extraction and sensing of the analyte may be conducted using a measurement sample which selectively favors analyte-specific signal components over signal components due to interfering species, for example by (a) employing a differential signal process which subtracts non- analyte signal components from the analyte signal; (b) employing a delay step which is performed between the sampling (extraction) and sensing steps; (c) employing a selective electrochemical detection process performed during the sensing step; (d) employing a purge step, performed after the sensing step; (e) employing a charge segregation step or (f) any combination of (a) through (e).
The sampling and sensing mechanisms can be combined into one structure. For example, once formulated, the sampling and/or sensing electrode compositions may be affixed to a suitable rigid or flexible nonconductive surface. For example, a silver (Ag) underlayer is first applied to the surface in order to provide uniform conduction. The Ag/AgCl electrode composition is then applied over the Ag underlayer in any suitable pattern or geometry using various thin film techniques, such as sputtering, evaporation, vapor phase deposition, or the like, or using various thick film techniques, such as film laminating, electroplating, or the like.
Alternatively, the Ag/AgCl composition can be applied using screen printing, pad printing, inkjet methods, transfer roll printing, or similar techniques. (See, e.g., WO 99/58190).
The general operation of an iontophoretic sampling and sensing system is the cyclical repetition of two phases: (1) a reverse-iontophoretic phase, followed by a (2) sensing phase. During the reverse iontophoretic phase, the first bimodal electrode acts as an iontophoretic cathode and the second bimodal electrode acts as an iontophoretic anode to complete the circuit. Analyte (e.g., glucose) is collected in the reservoirs, for example, a hydrogel. At the end of the reverse iontophoretic phase, the iontophoretic cuπent is turned off. During the sensing phase, in the case of glucose, a potential is applied between the reference electrode and the sensing electrode. The chemical signal reacts catalytically on the catalytic face of the first sensing electrode producing an electrical current, while the first bi-modal electrode acts as a counter electrode to complete the electrical circuit. The reference and sensing electrodes, as well as, the bimodal electrode described above are typically connected to a standard potentiostat circuit during sensing. The electrode sub-assembly can be operated by electrically connecting the bimodal electrodes such that each electrode is capable of functioning as both an iontophoretic electrode and counter electrode along with appropriate sensing electrode(s) and reference electrode(s), to create standard potentiostat circuitry.
A potentiostat is an electrical circuit used in electrochemical measurements in three electrode electrochemical cells. A potential is applied between the reference electrode and the sensing electrode. The current generated at the sensing electrode flows through circuitry to the counter electrode (i.e., no current flows through the reference electrode to alter its equilibrium potential). Two independent potentiostat circuits can be used to operate the two biosensors. For the purpose of the present system, the electrical current measured at the sensing electrode subassembly is the current that is correlated with an amount of chemical signal.
D. Power Source
A power source (e.g., one or more rechargeable and/or nonrechargeable batteries) can be disposed within the first and/or second components of the monitoring system. For example, in embodiments involving iontophoresis, the power source provides sufficient power to apply an electric potential (either direct current or a more complex waveform) between the two iontophoretic (sampling) electrodes such that current flows from the first iontophoretic electrode, through the first conductive medium into the skin or mucosal surface, and then back out through the second conductive medium to the second iontophoretic electrode. The current flow is sufficient to extract substances including an analyte of interest through the skin into one or both of the collection reservoirs. The electric potential may be applied using any suitable technique, for example, the applied current density may be in the range of about 0.01 to 0.5 mA/cm2.
Similarly, during the reverse iontophoretic phase, the power source provides a cuπent flow to the first bi-modal electrode to facilitate the extraction of the chemical signal into the reservoir. During the sensing phase, the power source is used to provide voltage to the first sensing electrode to drive the conversion of chemical signals retained in the reservoir to electrical signals at the catalytic face of the sensing electrode. The power source also maintains a fixed potential at the electrode where, for example, hydrogen peroxide is converted to molecular oxygen, hydrogen ions, and electrons, which is compared with the potential of the reference electrode during the sensing phase. While one sensing electrode is operating in the sensing mode it is electrically connected to the adjacent bimodal electrode which acts as a counter electrode at which electrons generated at the sensing electrode are consumed. Non- limiting examples of suitable sources of power include printed batteries, film batteries, moldable batteries, coin cell batteries, prismatic batteries, or cylindrical batteries. Printed batteries can be incorporated into the monitoring system, for instance in the first component during printing of the biosensor. In a representative embodiment, the biosensor is printed onto a .005 inch thick PET film substrate. The printed battery can be deposited onto this same substrate using similar thick-film print processes. Anode, insulator material, electrolyte, cathode and encapsulant material can be deposited in sequential steps to create the battery. Electrode materials can be deposited in charged states, such as by charging a printing screen during deposition of the electrode layers, thereby avoiding the need to charge the battery after deposition. Alternatively, film batteries can be assembled with the other components of the sampling/sensing device using, for example, Solid State System™ lithium-ion solid polymer rechargeable batteries from Ultralife Batteries Inc., Newark, NY. Thin film batteries and moldable batteries from solid electrodes and/or solid electrolytes can also be used, such as the "RHISS" technology from ECR Corporation, Rehovot, Israel. Coin-cell, prismatic, or cylindrical batteries, for example using nickel metal hydride, various lithium, alkaline, zinc-air, chemistries, may also be used and are commercially available, for example from Panaxonic Industrial, Secaucus, NJ, Narta Batteries Inc., Elmsford, ΝY. It is to be understood that these and other power sources can also be incorporated into the second component to provide the necessary power to run the user interface and/or microprocessing functions contained in the second component. Thus, selection and implementation of a suitable power source can be readily determined by one of skill in the art in view of one or more of the following factors: the method of extraction (sampling), for example, iontophoresis, sonophoresis, etc.; the nature of the user interface; the method of sensing, for example, with biosensor electrodes; manufacturability; energy density; energy capacity; cost; charging time; self- discharging characteristics; environmental concerns; government regulations; safety; and user preference. III. User Interface
The second component of the at least two component monitoring system comprises a user interface and, typically, one or more controller (microprocessor) functions. Additional components such as suitable electronics (e.g., microprocessing, memory, display and other circuit components), a power source, an alarm and the like can also be included in the user interface. The user interface may provide numerical readouts, other visual indication of analyte concentration (e.g., aπows), or visual instruction actions (e.g., take medication, eat or drink). Buttons on the user interface may provide the ability to supply information needed to calibrate and/or otherwise control the device.
In one aspect, the first component provides the necessary elements to drive the extraction and sensing of the analyte. The sensing electronics then communicate the results (data) of extraction and sensing to the second component (user interface) where microprocessing functions process the data and/or display such data to the user. Algorithms (programs) capable of data manipulation are known to those of skill in the art. Suitable algorithms useful in processing data (e.g., predicting physiological values, signal processing, predicting concentration, and the like) are described, for example, in International Publication WO 99/58973, published 18 November 1999 and International Publication WO 99/58050, published 18 November 1999. In addition, co-pending, co-owned U.S. Serial Number 09/198,039, filed 30 September 1998, describes how a Mixtures of Experts algorithm can be used predict a concentration of an analyte of interest. Further, it will be apparent that in alternative embodiments, one or more functions of the microprocessor (e.g., data manipulation, calibration, etc.) can be located within the second component. In another aspect, one or more of the sampling and sensing functions of the first component are controlled by the second component. For example the operation of the sampling device can be controlled by a controller (e.g., a microprocessor with one or more components located in the second component of the monitoring system), which is in operable communication with the sampling electrodes, the sensor electrodes, the power supply, as well as optional temperature and/or conductance sensing elements, a display, and other electronics. The user interface (second component) may take a variety of configurations, for example, a credit card like device (e.g., "smartcard"), a watch, pager, or cell phone device that includes memory, a display such as a liquid crystal display (LCD) and buttons. The buttons can be used to control what is displayed and record events occurring during use of the product (e.g., meals, exercise, insulin doses). The user interface may also be a remote device such as a personal computer or network.
Turning now to the specific embodiments shown in the Figures, Figure 1 A shows one embodiment of the present invention in which the first component is worn on the torso (next to the skin) and the user interface is worn as a watch. In this embodiment, the first component (sampling/sensing) relays data about the analyte of interest to the second component (user interface) which then displays the data. In this embodiment, the first component includes microprocessing functions that control sampling and sensing and, in addition, can include data processing functions. The data obtained (and/or processed) by the first component is then transmitted via wireless communication (see Section IV below) to the user interface for display.
Figure IB shows an embodiment similar to that of Figure 1 A where the first component is worn on the torso and the second component takes the form of a watch. In this embodiment, the first component relays information about the analyte to the second component, which contains microprocessing functions (e.g., data processing) and display capabilities.
Figure 1C depicts yet another embodiment where the first component is worn on the torso and the second component is worn as a pager-like device, shown on the belt of the user in Figure lC. The second component includes buttons and display panel. Further, the first and second components are in two-way communication with one another. Because of two-way communication, the user has the ability to control the first component with the second component, for example, using the buttons to control collection and sensing intervals and/or data manipulation. The first component will also generally include microprocessing function, for example to control sampling and sensing functions, collect and/or relay data to the second component.
Figure ID depicts an embodiment of the present invention in which the first component includes virtually all the microprocessing functions (e.g., control of sampling/sensing, data manipulation, calibration, etc.). The first component is worn next to the skin, for example, under the clothing on the torso. As shown in Figure ID, the first component includes a display panel and buttons (e.g., for controlling the microprocessor and/or display). In this embodiment, the first component relays data to the second component for display. The second component is depicted as a watchlike structure and includes a display panel, buttons (e.g., for determining what data is displayed and how it is displayed), and electronics controlling the display.
Figure IE depicts yet another embodiment where the first and second components are in two-way communication with one another. The first component is pictured as being worn by the user on the arm and the second component is depicted as a pager-like device on the belt. The second component includes a display panel and buttons. Because the components are in two-way communication, microprocessing functions can be divided between these components in any number of ways. For example, the second component can control the sampling/sensing of the first component (e.g., collection intervals, calibration, etc), receive analyte data from the first component, manipulate and display the analyte data. Further, buttons allow for the user to interface with the monitoring system, for example to control one or more of these aspects. Alternatively, the first component can contain the control functions for sampling/sensing and, optionally, calibration and/or data manipulation. This data can then be transmitted to the second component for further manipulations, if necessary, and display.
Figure IF shows an embodiment of the present invention depicting the two way wireless communication between the first component (labeled "sensor" in the Figure) and the second component (depicted as a watch in the Figure). The user interface includes buttons, microcontroller functions and, in addition, is capable of displaying time, date and analyte data to the user. The sensor will typically be placed next to the skin and the watch worn around the wrist of the user.
Figure 1G shows another embodiment having bi-directional wireless communication between the sensor (first component) and user interface (second component), depicted in the Figure as a pager-type device. Similar to the embodiment shown in Figure IF, the user interface (e.g., pager-type device) includes buttons, microcontroller functions and, in addition, is capable of visually displaying time, date and analyte data to the user. In some embodiments, the pager-type device will also be capable of sending auditory and/or tactile (e.g., vibrational) signals to the user regarding analyte data, time, etc. The sensor component is typically be placed next to the skin of the user and the pager-type device worn outside the clothes or carried in a purse, bag, briefcase or the like.
Figure IH shows another embodiment having bi-directional wireless communication between the sensor (first component) and user interface (second component), depicted in the Figure as a credit card-type device. Similar to the embodiment shown in Figures IF and 1G, the user interface (e.g., credit card) includes buttons, microcontroller functions and, in addition, is capable of visually displaying time, date and analyte data to the user. Further, the user interface can also be designed to include other information about the user. In some embodiments, the credit card device will also be capable of sending auditory and/or tactile (e.g., vibrational) signals to the user regarding analyte data, time, etc. The sensor component is typically be placed next to the skin of the user and the credit card device worn outside in the pocket or carried in the wallet of the user.
IV. Communication Between Components
The at least two components of the present invention are preferably in operative communication with one another. The operative communication can include, for example, the following: one-way communication from the biosensor (e.g., the first component) to the user interface (e.g., a second component), or two-way communications between the first component and the second component. Communication with third or more components with either first or second component can be one-way or two-way depending on the particular type of information being communicated. Preferably, the at least two components of the monitoring system have two-way communications. Furthermore, any of the communication means (devices) described herein can be used to maintain operative communication between the at least two components and any other additional components (e.g., alarm, remote modem or PC, display, or delivery unit).
Mechanism for providing operative communication between the two components include, but are not limited to, the following: 1) One-way communication from the sensing mechanism (first component) to the display electronics (second component). The second component can include mechanism for data storage, user inputs, and the ability to upload information to a host computer. 2) Similar to (1), but with data storage, user inputs, and upload to host computer from the first component.
3) Two-way communications (send and receive) between the first and second components, where data storage, user inputs, and upload to host computer can either (a) all be in either the first or second component, or (b) split in any combination between the two sets of electronics (i.e., the first and second components).
4) (1), (2), or (3) with wireless communications link between the two components.
5) (4) with wired or wireless communications to a host device for data upload or automatic reporting to healthcare provider via telephone, internet, or wireless communications. For example, a bedside receiver that automatically reports to a patient's personal physician. This same bedside device could also function as a telephone.
6) (4) with any of the following wireless communications technologies (for example, short range communication, i.e., less than or equal to 3 meters, or longer range), including but not limited to:
-Electromagnetic waves, including but not limited to, low frequency electromagnetic waves (frequency range about 1 Hz - 1 Mega Hz); medium frequency electromagnetic waves (frequency range about 1 Mega Hz - 500 Mega Hz); and high frequency electromagnetic waves (frequency range about 500 Mega Hz - 20 Giga Hz). Further, it is to be understood that such ranges for electromagnetic waves are approximate and may be subdivided into further categories, for example, by the FCC, which indicates that low frequency (LF) ranges between about 30 kHz and about 300 kHz; medium frequency (MF) ranges between about 300 kHz and about 3 Mega Hz (MHz); high frequency (HF) ranges between about 3 MHz and about 30 MHz; very high frequency (VHF) ranges between about 30 MHz and about 300 MHz; ultra high frequency (UHF) ranges between about 300 MHz and 3 Giga Hz (GHz); super high frequency (SHF) ranges between about 3 GHz and about 30 GHz; and extra high frequency (EHF) ranges between about 30 GHz and about 300 GHz.
- Capacitance coupling between, for example, a subject's body and the environment/air (frequency range about 1 Hz - 1 Mega Hz); - Inductive coupling (i.e., time varying magnetic field; not freely propagating electromagnetic wave);
- Close coupled inductive (i.e., inductive but so weak that it works only at very short range). This would likely require bringing the two components (e.g., a display device and sensor electronics) in close proximity whenever the data needs to be displayed;
- Brief electrical contact whenever data is needed at the display;
- Infrared coupling (using infrared light, e.g., as in low speed communications links to computers and personal digital assistants), and
- High frequency acoustic energy. 7) (5) with any of the links mentioned in (6).
8) combinations and modifications of (l)-(7), above. Preferably, the communication between the at least two components is a wireless link. Wireless links allow for the uploading of data from the monitoring system to a personal computer or personal digital assistant (having the necessary receiver electronics) for viewing by the user, family member, medical care team or researchers. Although wire-like links can also be used for this purpose, wireless links are prefeπed to enhance user convenience.
A variety of approaches are available for such wireless communication including, but not limited to, electromagnetic waves such as radio frequency with carrier bands from 20 kilo Hertz to 20 Giga Hertz (see, e.g., Freiheπ (1998) Medical Device and Diagnostic Industry, Aug:83-93); capacitance coupling; inductive coupling, infrared coupling, high frequency acoustic energy and frequency hopping schemes.
In one aspect, wireless communications are provided by electromagnetic waves (radio-frequency). The selection of which carrier frequency can be readily determined by one of skill in the art in view of range (e.g., distance between sensing mechanism and user interface), blocking by the human body and clothes, power consumption, bandwidth, noise susceptibility, antenna size, FCC regulations, selected communication protocol, cost and availability of starting materials. Two-way paging electronics and networks, for example RF (radio-frequency) transceivers, also find use in the present invention, for example technology manufactured and commercially available from High Desert RDN, Rupert, ID; RF Monolithics, Inc., Dallas, TX; and Motorola, Inc. In particular, the miniature, spread spectrum transceiver known as the RF-SOI sensor transceiver™ (High Desert RDN, Rupert, ID) requires less than .5 volts of electrical power while providing a sensor or analysis host device the ability to gather and transceive data in real time. Short-range wireless data communications are also commercially available, for example, the wireless data transceiver systems designed and available from RF Monolithics, Inc., Dallas, TX. Two-way paging devices, e.g., ReFlex® paging hardware and service (Motorola, Inc.) are also available. These technologies can be used to transmit the data from the monitoring system to a file server (for example, a file server that is part of a wide area network (WAN) such as the internet). The information on the file server can then be readily accessed using standard web browsing software with appropriate security features implemented for confidentiality. In addition, cellular and/or cordless telephone networks can be used to transfer the data to a file server for access. See, e.g., U.S. Patent Numbers 5,838,730 and 5,574,775. Wireless communications for local area networks (LAN) are described, for example, in U.S. Patent Numbers 5,875,186 and 5,987,033. U.S. Patent No. 5,077,753 and www.bluetooth.com for descriptions of Bluetooth technology, a wireless communication technology for data and voice.
In another embodiment, the wireless link (e.g., communication mechanism) is established by capacitance coupling, for example using a technology called Personal Area Network (PAN; WO 96/36134, N. Gershenfeld, et al., published 14 November 1996). This technology is an example of capacitance coupling involving the use of the human body to carry cuπent, and thus information, from one device to another. These devices have to be either in direct contact, or in close proximity, to the body. A low frequency carrier, e.g., below 1 MHz, is used to transmit the information. Advantages of PAN include that it may require less energy for data transmission, the potential of better control over security of transmitted information, and the use of simple low cost electronics. As noted above, inductive coupling can also be used to establish wireless communication abilities between the two components of the monitoring system described herein. Inductive coupling usually requires that the communicating components be in relatively close physical proximity to each other. Suitable inductive coupling technology is described, for example, in U.S. Patent Number 5,882,300 to Malinouskas, issued March 16, 1999 directed to a wireless patient monitoring apparatus that employs inductive coupling. Wireless systems that make use of infrared coupling are also known and described, for example in U.S. Patent Numbers 5,103,108 and 5,027,834, as are wireless communication systems that make use of high frequency acoustic energy (e.g., ultrasound). Ultrasonic wireless communications typically use frequencies between about 100 KHz and 1.0 MHz (see, e.g., U.S. Patent No. 5,982,297).
V. Additional Components The present invention may also include, in addition to the first and second components, other additional components, for example, additional display units, alarm mechanisms and or delivery units such as pumps. Alarm mechanisms could be used to warn the user when the concentration of the analyte gets above or below a preset threshold value. In certain embodiments, the alarm will be remote from (and in communication with) the first and second components, while in other embodiments, the alarm can be included within the structure of the first or second components.
In certain embodiments, a component comprising a delivery unit capable of delivering a substance (e.g., therapeutic substance) to the subject is included in the present invention. The substance delivered to the subject will of course depend on the analyte being monitored. For instance, in the case where glucose is the analyte, the delivery unit will preferably deliver insulin. Thus, in certain embodiments, after the sampling/sensing mechanism determines the concentration of the analyte of interest, this information can be relayed to the delivery unit. Microprocessing functions within the delivery unit can then determine the appropriate amount of therapeutic substance to be delivered to the subject. Alternatively, it will be apparent that the determination of the amount of therapeutic substance to be delivered by the delivery unit can be made by any of the components of the system, for example by the first or second components following appropriate data collection and analysis. Thus, in certain embodiments, the delivery unit can be automatically controlled by the first and/or second components of the monitoring system. In addition, in some embodiments, the user can have input as to the amount of substance delivered by the delivery unit. For example, after reviewing the display of data obtained from the sampling/sensing component, the user can determine the amount of substance to be delivered and transmit appropriate instructions (e.g., via programming the microprocessing functions of the user interface) to the delivery unit. Suitable delivery units, for example, insulin pumps are described in the art. See, e.g., U.S. Patent Nos. 5,112,614; 5,995,860; and 5,062,841. Implantable glucose monitoring-telemetry devices have also been described, see, e.g., U.S. Patent Number 4,703,756; Atanasov et al. (1997) Biosensors & Bioelectronics 12:669-679; Black et al. (1996) Sensors and Actuators B3 147-153; McKean and Gough (1988) IEEE Transactions on Biomedical Engineering 35:526-532. The delivery unit may be implantable or external to the subject.
Further, it is to be understood that the present invention includes embodiments having one or more additional components (e.g., both alarm and delivery unit). It will also be apparent that the additional component(s) are preferably in operably communication with at least one of the first and second components. The nature of the communication between the additional component(s) and the first and/or second components can be readily determined by a skilled artisan using the communications mechanisms and factors described herein, for example, whether the additional component a separate structure, whether it is implanted or external, the nature of the microprocessor(s) in the components and the like. Preferably, the communication between the additional(s) components is wireless.
Exemplary embodiments of a monitoring system having three components are shown in Figures II to IL. Figure II depicts an embodiment of the present invention which includes three separate components: a sampling/sensing mechanism ("sensor"); a user interface (depicted as a credit card) and a drug delivery unit ("insulin pump"). As depicted in the Figure, all three components have bi-directional wireless communication abilities with each of the other elements. This allows, for example, for a feedback loop to be established between the sensor and the insulin pump without input from the user. The sensor component samples and senses the analyte (e.g., glucose) and microcontroller functions in either the insulin pump or the sensor analyze and translate the data into the amount of insulin required to be administered to the user. Further, the bi-directional wireless communication abilities also allow for situations in which the user controls the amount of insulin infused by the pump, for example, taking into account meals, exercise or other factors. As described above, the credit card can include a variety of functions (e.g., date, time, analyte data, other information) and can employ a variety of display mechanisms (e.g., visual, auditory or tactile). The sensor is preferably worn next to the skin while the credit card can be carried in a pocket or wallet. The insulin pump is preferably at least partially implanted (e.g., subcutaneously) in the user.
Figure 1 J depicts an embodiment similar to that of Figure II except that the user interface is depicted as a watch rather than a credit card. Similarly, Figure IK depicts a three component, bi-directional wireless communication system as described for Figure II, except that the user interface is a pager-type device.
Figure IL depicts an embodiment of the present invention which includes three separate components: a sampling/sensing mechanism ("sensor"); a user interface (depicted as a watch) and a remote modem. As depicted in the Figure, the modem receives information from the sensor and user interface. It is to be understood that, in some embodiments, the user interface and sensor will also be in communication with one another. The presence of a remove modem allows the sharing of data between the user and variety of other interested parties. For example, the modem can be linked to a wide area network (WAN) such as the internet and transmitted to secure file server for accessed using, for example, web browsing software (with appropriate security measures) by a doctor or hospital personnel. As described above, the watch can include a variety of functions (e.g., date, time, analyte data, other information) and can employ a variety of display mechanisms (e.g., visual, auditory or tactile). The sensor is preferably worn next to the skin while the watch is worn on the wrist.
Although prefeπed embodiments of the subject invention have been described in some detail, it is understood that obvious variations can be made without departing from the spirit and the scope of the invention as defined by the appended claims.

Claims

What is claimed is:
1. A monitoring system for frequently measuring an analyte present in a biological system, said monitoring system comprising, (a) a first component comprising
(i) a transdermal or transmucosal sampling mechanism for extracting the analyte from the biological system, wherein said sampling mechanism is adapted for extracting the analyte across a skin or mucosal surface of said biological system; (ii) sensing mechanism in operative contact with the analyte extracted by the sampling mechanism, wherein said sensing mechanism obtains a signal from the extracted analyte and said signal is specifically related to the analyte; and
(iii) first mechanism for providing operative communication with a second component of the monitoring system; and (b) a second component comprising (i) a user interface; and
(ii) second mechanism for providing operative communication with the first component.
2. The monitoring system of claim 1, wherein the sampling mechanism is selected from the group consisting of iontophoresis, electroosmosis, sonophoresis, microdialysis, suction and passive diffusion.
3. The monitoring system of claim 2, wherein the sampling mechanism is iontophoresis.
4. The monitoring system according to any one of claims 1 to 3, wherein the first component further comprises a computing mechanism that converts the signal from the extracted analyte to an output indicative of the amount of analyte extracted by the sampling mechanism.
5. The monitoring system of claim 4, wherein the output is communicated to the second component for display.
6. The monitoring system according to any one of claims 1-3, wherein the second component receives the signal from the first component, wherein the second component further comprises a computing mechanism that converts the signal from the extracted analyte to an output indicative of the amount of analyte extracted by the sampling mechanism and wherein the second component displays said output.
7. The monitoring system of claim 1 , wherein the first and second mechanism for providing operative communication comprise a wire-like connection.
8. The monitoring system of claim 1 , wherein the first and second mechanism for providing operative communication comprise a wireless communication technology.
9. The monitoring system of claim 8, wherein the wireless communication technology employs electromagnetic waves.
10. The monitoring system of claim 9, wherein the wireless communication technology employs low frequency electromagnetic waves in a frequency range of about 1 Hz. to about 1 Mega Hz.
11. The monitoring system of claim 9, wherein the wireless communication technology employs medium frequency electromagnetic waves in a frequency range of about 1 Mega Hz. to about 500 Mega Hz.
12. The monitoring system of claim 9, wherein the wireless communication technology employs high frequency electromagnetic waves in a frequency range of about 500 Mega Hz. to about 5 Giga Hz.
13. The monitoring system of claim 8, wherein the wireless communication technology employs capacitance coupling between the biological system and the biological system's environment.
14. The monitoring system of claim 8, wherein the wireless communication technology employs inductive coupling.
15. The monitoring system of claim 8, wherein the wireless communication technology employs infrared coupling.
16. The monitoring system of claim 8, wherein the wireless communication technology employs high frequency acoustic energy.
17. The monitoring system of claim 1 , wherein the second component relays command signals to the first component.
18. The monitoring system of claim 17, wherein the command signals include signals to control operation of the sensing mechanism.
19. The monitoring system of claim 17 or 18, wherein the command signals include signals to control operation of the sampling mechanism.
20. The monitoring system of claim 1, wherein the second component can store analyte-related data.
21. The monitoring system of any of the preceding claims, wherein the analyte is glucose.
22. The monitoring system of any of the preceding claims, wherein said biological system is a mammal.
23. The monitoring system of claim 22, wherein said mammal is a human.
24. The monitoring system according to any one of claims 1-23, further comprising
(c) a third component comprising (i) a delivery device; and (ii) a third mechanism for providing operative communication with the first and second components.
25. The monitoring system of claim 24, wherein the delivery device is implanted in the biological system.
26. The monitoring system of claim 24, wherein the delivery device is external in the biological system.
27. The monitoring system of claim 24, wherein the analyte is glucose and the delivery device comprises an insulin pump.
28. The monitoring system of claim 24, wherein the communication between first and second components and the third component is wireless.
29. The monitoring system according to any one of claims 1 to 23, further comprising
(c) a third component comprising
(i) a modem or personal computer; and (ii) a third mechanism for providing operative communication with the first and second components.
30. The monitoring system of claim 29, wherein the modem or personal computer is remote from the biological system.
31. The monitoring system of claim 29, wherein the analyte is glucose.
32. The monitoring system of claim 29, wherein the communication between first and second components and the third component is wireless.
33. The monitoring system of claim 29, wherein the modem or personal computer is operably linked to a wide area network (WAN).
PCT/US2000/003693 1999-02-12 2000-02-11 Devices and methods for frequent measurement of an analyte present in a biological system WO2000047109A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP2000598064A JP2002536103A (en) 1999-02-12 2000-02-11 Devices and methods for frequent measurement of analytes present in biological systems
AU33630/00A AU3363000A (en) 1999-02-12 2000-02-11 Devices and methods for frequent measurement of an analyte present in a biological system
CA002365609A CA2365609A1 (en) 1999-02-12 2000-02-11 Devices and methods for frequent measurement of an analyte present in a biological system
EP00911792A EP1135052A1 (en) 1999-02-12 2000-02-11 Devices and methods for frequent measurement of an analyte present in a biological system

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US11991899P 1999-02-12 1999-02-12
US60/119,918 1999-02-12

Publications (1)

Publication Number Publication Date
WO2000047109A1 true WO2000047109A1 (en) 2000-08-17

Family

ID=22387177

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/003693 WO2000047109A1 (en) 1999-02-12 2000-02-11 Devices and methods for frequent measurement of an analyte present in a biological system

Country Status (6)

Country Link
US (2) US6561978B1 (en)
EP (1) EP1135052A1 (en)
JP (1) JP2002536103A (en)
AU (1) AU3363000A (en)
CA (1) CA2365609A1 (en)
WO (1) WO2000047109A1 (en)

Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002017210A2 (en) * 2000-08-18 2002-02-28 Cygnus, Inc. Formulation and manipulation of databases of analyte and associated values
WO2002015778A1 (en) * 2000-08-18 2002-02-28 Cygnus, Inc. Analyte monitoring device alarm augmentation system
WO2002018936A2 (en) * 2000-08-28 2002-03-07 Cygnus, Inc. Methods of monitoring glucose levels in a subject and uses thereof
WO2002032502A1 (en) * 2000-10-16 2002-04-25 Remon Medical Technologies Ltd. Acoustic switch and apparatus and methods for using acoustic switches within a body
WO2002094092A1 (en) * 2001-05-18 2002-11-28 Polymer Technology Systems, Inc. Body fluid test apparatus with detachably mounted portable tester
US6561978B1 (en) 1999-02-12 2003-05-13 Cygnus, Inc. Devices and methods for frequent measurement of an analyte present in a biological system
US6595919B2 (en) 1998-05-13 2003-07-22 Cygnus, Inc. Device for signal processing for measurement of physiological analytes
EP1350460A2 (en) * 2002-03-25 2003-10-08 Matsushita Electric Industrial Co., Ltd. Vital sign detection sensor and sensor controlling device
WO2003082098A2 (en) 2002-03-22 2003-10-09 Cygnus, Inc. Improving performance of an analyte monitoring device
EP1395172A2 (en) * 2001-05-18 2004-03-10 SPECTRX, Inc. System and method for monitoring or treating a health condition
EP1410206A1 (en) * 2001-02-15 2004-04-21 I-Medik, Inc. Wireless internet bio-telemetry monitoring system and interface
WO2004008956A3 (en) * 2002-07-24 2004-04-22 Medtronic Minimed Inc System for providing blood glucose measurements to an infusion device
WO2004062493A1 (en) * 2003-01-06 2004-07-29 Optiscan Biomedical Corporation Wearable device for measuring analyte concentration
WO2004066834A1 (en) * 2003-01-31 2004-08-12 Medtronic, Inc. Patient monitoring device with multi-antenna receiver
EP1468109A1 (en) * 2001-12-17 2004-10-20 Powderject Research Limited Non- or minimally invasive monitoring methods
US6925393B1 (en) * 1999-11-18 2005-08-02 Roche Diagnostics Gmbh System for the extrapolation of glucose concentration
US6931328B2 (en) 2002-11-08 2005-08-16 Optiscan Biomedical Corp. Analyte detection system with software download capabilities
US7024248B2 (en) 2000-10-16 2006-04-04 Remon Medical Technologies Ltd Systems and methods for communicating with implantable devices
WO2007021892A1 (en) * 2005-08-16 2007-02-22 Medtronic Minimed, Inc. Hand-held controller device for an infusion pump
US7272433B2 (en) 2001-04-30 2007-09-18 Medtronic, Inc. Transcutaneous monitor and method of use, using therapeutic output from an implanted medical device
WO2008016486A2 (en) * 2006-07-31 2008-02-07 Medtronic Minimed, Inc. Watch controller for a medical device
JP2008522703A (en) * 2004-12-13 2008-07-03 コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ Mobile monitoring
USRE42378E1 (en) 2000-10-16 2011-05-17 Remon Medical Technologies, Ltd. Implantable pressure sensors and methods for making and using them
US8622954B2 (en) 2002-12-19 2014-01-07 Medtronic Minimed, Inc. Relay device for transferring information between a sensor system and a fluid delivery system
US8663201B2 (en) 2005-08-16 2014-03-04 Medtronic Minimed, Inc. Infusion device
WO2014045451A1 (en) * 2012-09-24 2014-03-27 テルモ株式会社 Sensor unit and measurement system
US8852099B2 (en) 2004-09-17 2014-10-07 Cardiac Pacemakers, Inc. Systems and methods for deriving relative physiologic measurements
US8934972B2 (en) 2000-10-16 2015-01-13 Remon Medical Technologies, Ltd. Acoustically powered implantable stimulating device
EP1423046B2 (en) 2001-08-13 2015-03-25 Novo Nordisk A/S Portable device of communicating medical data information
US9024582B2 (en) 2008-10-27 2015-05-05 Cardiac Pacemakers, Inc. Methods and systems for recharging an implanted device by delivering a section of a charging device adjacent the implanted device within a body
US10016134B2 (en) 2001-08-13 2018-07-10 Novo Nordisk A/S Portable device and method of communicating medical data information

Families Citing this family (555)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6036924A (en) 1997-12-04 2000-03-14 Hewlett-Packard Company Cassette of lancet cartridges for sampling blood
US6391005B1 (en) 1998-03-30 2002-05-21 Agilent Technologies, Inc. Apparatus and method for penetration with shaft having a sensor for sensing penetration depth
US8465425B2 (en) 1998-04-30 2013-06-18 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8346337B2 (en) 1998-04-30 2013-01-01 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8974386B2 (en) 1998-04-30 2015-03-10 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US6175752B1 (en) 1998-04-30 2001-01-16 Therasense, Inc. Analyte monitoring device and methods of use
US8688188B2 (en) 1998-04-30 2014-04-01 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US6949816B2 (en) 2003-04-21 2005-09-27 Motorola, Inc. Semiconductor component having first surface area for electrically coupling to a semiconductor chip and second surface area for electrically coupling to a substrate, and method of manufacturing same
US8480580B2 (en) 1998-04-30 2013-07-09 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US9066695B2 (en) 1998-04-30 2015-06-30 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US6045501A (en) * 1998-08-28 2000-04-04 Celgene Corporation Methods for delivering a drug to a patient while preventing the exposure of a foetus or other contraindicated individual to the drug
US10973397B2 (en) 1999-03-01 2021-04-13 West View Research, Llc Computerized information collection and processing apparatus
US8636648B2 (en) 1999-03-01 2014-01-28 West View Research, Llc Endoscopic smart probe
US20040064084A1 (en) * 1999-08-23 2004-04-01 Hisamitsu Pharmaceutical Co., Inc. Iontophoresis system
US6733446B2 (en) * 2000-01-21 2004-05-11 Medtronic Minimed, Inc. Ambulatory medical apparatus and method using a telemetry system with predefined reception listening periods
US8715177B2 (en) * 2000-10-06 2014-05-06 Ip Holdings, Inc. Intelligent drug delivery appliance
US6315720B1 (en) * 2000-10-23 2001-11-13 Celgene Corporation Methods for delivering a drug to a patient while avoiding the occurrence of an adverse side effect known or suspected of being caused by the drug
US6632175B1 (en) * 2000-11-08 2003-10-14 Hewlett-Packard Development Company, L.P. Swallowable data recorder capsule medical device
US6929636B1 (en) * 2000-11-08 2005-08-16 Hewlett-Packard Development Company, L.P. Internal drug dispenser capsule medical device
US8641644B2 (en) 2000-11-21 2014-02-04 Sanofi-Aventis Deutschland Gmbh Blood testing apparatus having a rotatable cartridge with multiple lancing elements and testing means
US6645142B2 (en) * 2000-12-01 2003-11-11 Optiscan Biomedical Corporation Glucose monitoring instrument having network connectivity
EP1216651A1 (en) * 2000-12-21 2002-06-26 BrainLAB AG Wireless medical acquisition and treatment system
US6560471B1 (en) 2001-01-02 2003-05-06 Therasense, Inc. Analyte monitoring device and methods of use
US7041468B2 (en) 2001-04-02 2006-05-09 Therasense, Inc. Blood glucose tracking apparatus and methods
JP4498636B2 (en) 2001-04-27 2010-07-07 日本サーモスタット株式会社 Thermostat device
JP3768435B2 (en) * 2001-05-16 2006-04-19 東芝テック株式会社 Blood glucose level measuring device
ATE485766T1 (en) 2001-06-12 2010-11-15 Pelikan Technologies Inc ELECTRICAL ACTUATING ELEMENT FOR A LANCET
US9427532B2 (en) 2001-06-12 2016-08-30 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
ATE497731T1 (en) 2001-06-12 2011-02-15 Pelikan Technologies Inc DEVICE FOR INCREASING THE SUCCESS RATE OF BLOOD YIELD OBTAINED BY A FINGER PICK
CA2448905C (en) 2001-06-12 2010-09-07 Pelikan Technologies, Inc. Blood sampling apparatus and method
US7316700B2 (en) 2001-06-12 2008-01-08 Pelikan Technologies, Inc. Self optimizing lancing device with adaptation means to temporal variations in cutaneous properties
US8337419B2 (en) 2002-04-19 2012-12-25 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
WO2002100254A2 (en) 2001-06-12 2002-12-19 Pelikan Technologies, Inc. Method and apparatus for lancet launching device integrated onto a blood-sampling cartridge
US7025774B2 (en) 2001-06-12 2006-04-11 Pelikan Technologies, Inc. Tissue penetration device
US9795747B2 (en) 2010-06-02 2017-10-24 Sanofi-Aventis Deutschland Gmbh Methods and apparatus for lancet actuation
US9226699B2 (en) 2002-04-19 2016-01-05 Sanofi-Aventis Deutschland Gmbh Body fluid sampling module with a continuous compression tissue interface surface
US7344507B2 (en) 2002-04-19 2008-03-18 Pelikan Technologies, Inc. Method and apparatus for lancet actuation
US7981056B2 (en) 2002-04-19 2011-07-19 Pelikan Technologies, Inc. Methods and apparatus for lancet actuation
WO2003000127A2 (en) * 2001-06-22 2003-01-03 Cygnus, Inc. Method for improving the performance of an analyte monitoring system
CN1311781C (en) * 2001-08-20 2007-04-25 因弗内斯医疗有限公司 Wireless diabetes management devices and methods for using the same
DE10142019A1 (en) * 2001-08-28 2003-03-20 Philips Corp Intellectual Pty Circuit arrangement for demodulating signals
US6989891B2 (en) 2001-11-08 2006-01-24 Optiscan Biomedical Corporation Device and method for in vitro determination of analyte concentrations within body fluids
US20030224782A1 (en) * 2002-02-11 2003-12-04 Dougherty Angus O. Method and system of connecting broadband wireless systems to wireline serving area interfaces
US8010174B2 (en) 2003-08-22 2011-08-30 Dexcom, Inc. Systems and methods for replacing signal artifacts in a glucose sensor data stream
US9282925B2 (en) 2002-02-12 2016-03-15 Dexcom, Inc. Systems and methods for replacing signal artifacts in a glucose sensor data stream
US9247901B2 (en) 2003-08-22 2016-02-02 Dexcom, Inc. Systems and methods for replacing signal artifacts in a glucose sensor data stream
US8260393B2 (en) 2003-07-25 2012-09-04 Dexcom, Inc. Systems and methods for replacing signal data artifacts in a glucose sensor data stream
MXPA04008713A (en) * 2002-03-08 2006-02-24 Sensys Medical Inc Compact apparatus for noninvasive measurement of glucose through near-infrared spectroscopy.
US8579831B2 (en) 2002-04-19 2013-11-12 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US7674232B2 (en) 2002-04-19 2010-03-09 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7491178B2 (en) 2002-04-19 2009-02-17 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8784335B2 (en) 2002-04-19 2014-07-22 Sanofi-Aventis Deutschland Gmbh Body fluid sampling device with a capacitive sensor
US7226461B2 (en) 2002-04-19 2007-06-05 Pelikan Technologies, Inc. Method and apparatus for a multi-use body fluid sampling device with sterility barrier release
US7901362B2 (en) 2002-04-19 2011-03-08 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7909778B2 (en) 2002-04-19 2011-03-22 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US9248267B2 (en) 2002-04-19 2016-02-02 Sanofi-Aventis Deustchland Gmbh Tissue penetration device
US7892183B2 (en) 2002-04-19 2011-02-22 Pelikan Technologies, Inc. Method and apparatus for body fluid sampling and analyte sensing
US9795334B2 (en) 2002-04-19 2017-10-24 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US8702624B2 (en) 2006-09-29 2014-04-22 Sanofi-Aventis Deutschland Gmbh Analyte measurement device with a single shot actuator
US8221334B2 (en) 2002-04-19 2012-07-17 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US7547287B2 (en) 2002-04-19 2009-06-16 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7331931B2 (en) 2002-04-19 2008-02-19 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7976476B2 (en) 2002-04-19 2011-07-12 Pelikan Technologies, Inc. Device and method for variable speed lancet
US7232451B2 (en) 2002-04-19 2007-06-19 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7291117B2 (en) 2002-04-19 2007-11-06 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US9314194B2 (en) 2002-04-19 2016-04-19 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US8267870B2 (en) 2002-04-19 2012-09-18 Sanofi-Aventis Deutschland Gmbh Method and apparatus for body fluid sampling with hybrid actuation
US7371247B2 (en) 2002-04-19 2008-05-13 Pelikan Technologies, Inc Method and apparatus for penetrating tissue
US7717863B2 (en) 2002-04-19 2010-05-18 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7229458B2 (en) 2002-04-19 2007-06-12 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7648468B2 (en) 2002-04-19 2010-01-19 Pelikon Technologies, Inc. Method and apparatus for penetrating tissue
US7297122B2 (en) 2002-04-19 2007-11-20 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8512276B2 (en) * 2002-07-24 2013-08-20 Medtronic Minimed, Inc. System for providing blood glucose measurements to an infusion device
US7993108B2 (en) 2002-10-09 2011-08-09 Abbott Diabetes Care Inc. Variable volume, shape memory actuated insulin dispensing pump
EP1552146B1 (en) 2002-10-09 2011-04-20 Abbott Diabetes Care Inc. Fluid delivery device, system and method
US7727181B2 (en) * 2002-10-09 2010-06-01 Abbott Diabetes Care Inc. Fluid delivery device with autocalibration
US9740817B1 (en) 2002-10-18 2017-08-22 Dennis Sunga Fernandez Apparatus for biological sensing and alerting of pharmaco-genomic mutation
US7381184B2 (en) 2002-11-05 2008-06-03 Abbott Diabetes Care Inc. Sensor inserter assembly
US8574895B2 (en) 2002-12-30 2013-11-05 Sanofi-Aventis Deutschland Gmbh Method and apparatus using optical techniques to measure analyte levels
EP1578262A4 (en) 2002-12-31 2007-12-05 Therasense Inc Continuous glucose monitoring system and methods of use
EP1589334B1 (en) * 2003-01-27 2014-01-22 Terumo Kabushiki Kaisha Body fluid component analyzing system
NZ523948A (en) * 2003-01-30 2006-08-31 Sensortec Ltd Animal control system
JP4381705B2 (en) * 2003-03-26 2009-12-09 シスメックス株式会社 Transcutaneous analyte extraction system and analysis system, and transcutaneous analyte extraction method and analysis method
US7679407B2 (en) 2003-04-28 2010-03-16 Abbott Diabetes Care Inc. Method and apparatus for providing peak detection circuitry for data communication systems
WO2004107964A2 (en) 2003-06-06 2004-12-16 Pelikan Technologies, Inc. Blood harvesting device with electronic control
US7258673B2 (en) * 2003-06-06 2007-08-21 Lifescan, Inc Devices, systems and methods for extracting bodily fluid and monitoring an analyte therein
US8460243B2 (en) 2003-06-10 2013-06-11 Abbott Diabetes Care Inc. Glucose measuring module and insulin pump combination
US8066639B2 (en) 2003-06-10 2011-11-29 Abbott Diabetes Care Inc. Glucose measuring device for use in personal area network
WO2006001797A1 (en) 2004-06-14 2006-01-05 Pelikan Technologies, Inc. Low pain penetrating
MXPA05013747A (en) * 2003-06-20 2006-03-08 Hoffmann La Roche Devices and methods relating to electrochemical biosensors.
US8148164B2 (en) 2003-06-20 2012-04-03 Roche Diagnostics Operations, Inc. System and method for determining the concentration of an analyte in a sample fluid
ES2681398T3 (en) * 2003-06-20 2018-09-12 F. Hoffmann-La Roche Ag Test strip with widened sample reception chamber
US8679853B2 (en) 2003-06-20 2014-03-25 Roche Diagnostics Operations, Inc. Biosensor with laser-sealed capillary space and method of making
US7722536B2 (en) * 2003-07-15 2010-05-25 Abbott Diabetes Care Inc. Glucose measuring device integrated into a holster for a personal area network device
US7761130B2 (en) * 2003-07-25 2010-07-20 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US7467003B2 (en) * 2003-12-05 2008-12-16 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US7460898B2 (en) * 2003-12-05 2008-12-02 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US7366556B2 (en) 2003-12-05 2008-04-29 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US7424318B2 (en) 2003-12-05 2008-09-09 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US8423113B2 (en) 2003-07-25 2013-04-16 Dexcom, Inc. Systems and methods for processing sensor data
US8060173B2 (en) 2003-08-01 2011-11-15 Dexcom, Inc. System and methods for processing analyte sensor data
US20190357827A1 (en) 2003-08-01 2019-11-28 Dexcom, Inc. Analyte sensor
US7986986B2 (en) 2003-08-01 2011-07-26 Dexcom, Inc. System and methods for processing analyte sensor data
US8369919B2 (en) 2003-08-01 2013-02-05 Dexcom, Inc. Systems and methods for processing sensor data
US8886273B2 (en) 2003-08-01 2014-11-11 Dexcom, Inc. Analyte sensor
US7774145B2 (en) 2003-08-01 2010-08-10 Dexcom, Inc. Transcutaneous analyte sensor
US20100168543A1 (en) 2003-08-01 2010-07-01 Dexcom, Inc. System and methods for processing analyte sensor data
US8761856B2 (en) 2003-08-01 2014-06-24 Dexcom, Inc. System and methods for processing analyte sensor data
US7591801B2 (en) 2004-02-26 2009-09-22 Dexcom, Inc. Integrated delivery device for continuous glucose sensor
US9135402B2 (en) 2007-12-17 2015-09-15 Dexcom, Inc. Systems and methods for processing sensor data
US8275437B2 (en) 2003-08-01 2012-09-25 Dexcom, Inc. Transcutaneous analyte sensor
US7494465B2 (en) 2004-07-13 2009-02-24 Dexcom, Inc. Transcutaneous analyte sensor
US8160669B2 (en) 2003-08-01 2012-04-17 Dexcom, Inc. Transcutaneous analyte sensor
US20050033133A1 (en) * 2003-08-06 2005-02-10 Clifford Kraft Implantable chip medical diagnostic device for bodily fluids
WO2005018443A1 (en) * 2003-08-15 2005-03-03 Animas Technologies Llc Microprocessors, devices, and methods for use in monitoring of physiological analytes
US7189341B2 (en) * 2003-08-15 2007-03-13 Animas Technologies, Llc Electrochemical sensor ink compositions, electrodes, and uses thereof
US8346482B2 (en) * 2003-08-22 2013-01-01 Fernandez Dennis S Integrated biosensor and simulation system for diagnosis and therapy
US7920906B2 (en) 2005-03-10 2011-04-05 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US20140121989A1 (en) 2003-08-22 2014-05-01 Dexcom, Inc. Systems and methods for processing analyte sensor data
EP1671096A4 (en) 2003-09-29 2009-09-16 Pelikan Technologies Inc Method and apparatus for an improved sample capture device
EP1680014A4 (en) 2003-10-14 2009-01-21 Pelikan Technologies Inc Method and apparatus for a variable user interface
US7299082B2 (en) 2003-10-31 2007-11-20 Abbott Diabetes Care, Inc. Method of calibrating an analyte-measurement device, and associated methods, devices and systems
USD914881S1 (en) 2003-11-05 2021-03-30 Abbott Diabetes Care Inc. Analyte sensor electronic mount
WO2005051170A2 (en) 2003-11-19 2005-06-09 Dexcom, Inc. Integrated receiver for continuous analyte sensor
US9247900B2 (en) 2004-07-13 2016-02-02 Dexcom, Inc. Analyte sensor
DE10354833A1 (en) * 2003-11-24 2005-06-23 Liedtke, Rainer K., Dr. Dermal diagnostic patch systems with active transponders
EP2239567B1 (en) 2003-12-05 2015-09-02 DexCom, Inc. Calibration techniques for a continuous analyte sensor
US8287453B2 (en) 2003-12-05 2012-10-16 Dexcom, Inc. Analyte sensor
US8774886B2 (en) 2006-10-04 2014-07-08 Dexcom, Inc. Analyte sensor
US8364231B2 (en) 2006-10-04 2013-01-29 Dexcom, Inc. Analyte sensor
US8423114B2 (en) 2006-10-04 2013-04-16 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
US11633133B2 (en) 2003-12-05 2023-04-25 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
WO2005057174A2 (en) * 2003-12-08 2005-06-23 Rosenthal Robert D Method and apparatus for low blood glucose level detection
EP2329763B1 (en) 2003-12-09 2017-06-21 DexCom, Inc. Signal processing for continuous analyte sensor
EP1706026B1 (en) 2003-12-31 2017-03-01 Sanofi-Aventis Deutschland GmbH Method and apparatus for improving fluidic flow and sample capture
US7822454B1 (en) 2005-01-03 2010-10-26 Pelikan Technologies, Inc. Fluid sampling device with improved analyte detecting member configuration
US8942779B2 (en) 2004-02-05 2015-01-27 Early Sense Ltd. Monitoring a condition of a subject
US10194810B2 (en) 2004-02-05 2019-02-05 Earlysense Ltd. Monitoring a condition of a subject
US8491492B2 (en) 2004-02-05 2013-07-23 Earlysense Ltd. Monitoring a condition of a subject
US20070118054A1 (en) * 2005-11-01 2007-05-24 Earlysense Ltd. Methods and systems for monitoring patients for clinical episodes
US8403865B2 (en) 2004-02-05 2013-03-26 Earlysense Ltd. Prediction and monitoring of clinical episodes
US7077810B2 (en) 2004-02-05 2006-07-18 Earlysense Ltd. Techniques for prediction and monitoring of respiration-manifested clinical episodes
WO2005089103A2 (en) 2004-02-17 2005-09-29 Therasense, Inc. Method and system for providing data communication in continuous glucose monitoring and management system
US8808228B2 (en) * 2004-02-26 2014-08-19 Dexcom, Inc. Integrated medicament delivery device for use with continuous analyte sensor
ES2614629T3 (en) * 2004-03-17 2017-06-01 Kennecott Utah Copper Llc Wireless monitoring of electrolytic cells with ultra-low bus voltage
US7470356B2 (en) * 2004-03-17 2008-12-30 Kennecott Utah Copper Corporation Wireless monitoring of two or more electrolytic cells using one monitoring device
US8828203B2 (en) 2004-05-20 2014-09-09 Sanofi-Aventis Deutschland Gmbh Printable hydrogels for biosensors
US20100209897A1 (en) * 2004-05-28 2010-08-19 David Scott Utley Intraoral behavior monitoring and aversion devices and methods
EP1765194A4 (en) 2004-06-03 2010-09-29 Pelikan Technologies Inc Method and apparatus for a fluid sampling device
CA2572455C (en) 2004-06-04 2014-10-28 Therasense, Inc. Diabetes care host-client architecture and data management system
US7857760B2 (en) * 2004-07-13 2010-12-28 Dexcom, Inc. Analyte sensor
US20060270922A1 (en) 2004-07-13 2006-11-30 Brauker James H Analyte sensor
US7783333B2 (en) 2004-07-13 2010-08-24 Dexcom, Inc. Transcutaneous medical device with variable stiffness
US7310544B2 (en) 2004-07-13 2007-12-18 Dexcom, Inc. Methods and systems for inserting a transcutaneous analyte sensor
US7344500B2 (en) * 2004-07-27 2008-03-18 Medtronic Minimed, Inc. Sensing system with auxiliary display
US8073548B2 (en) * 2004-08-24 2011-12-06 Sensors For Medicine And Science, Inc. Wristband or other type of band having an adjustable antenna for use with a sensor reader
CN101040286B (en) * 2004-09-30 2012-10-03 皇家飞利浦电子股份有限公司 System for automatic continuous and reliable patient identification for association of wireless medical devices to patients
US9259175B2 (en) 2006-10-23 2016-02-16 Abbott Diabetes Care, Inc. Flexible patch for fluid delivery and monitoring body analytes
US8512243B2 (en) 2005-09-30 2013-08-20 Abbott Diabetes Care Inc. Integrated introducer and transmitter assembly and methods of use
US7697967B2 (en) 2005-12-28 2010-04-13 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor insertion
US7883464B2 (en) 2005-09-30 2011-02-08 Abbott Diabetes Care Inc. Integrated transmitter unit and sensor introducer mechanism and methods of use
US9788771B2 (en) 2006-10-23 2017-10-17 Abbott Diabetes Care Inc. Variable speed sensor insertion devices and methods of use
US20090105569A1 (en) 2006-04-28 2009-04-23 Abbott Diabetes Care, Inc. Introducer Assembly and Methods of Use
US8333714B2 (en) 2006-09-10 2012-12-18 Abbott Diabetes Care Inc. Method and system for providing an integrated analyte sensor insertion device and data processing unit
US9743862B2 (en) 2011-03-31 2017-08-29 Abbott Diabetes Care Inc. Systems and methods for transcutaneously implanting medical devices
US8571624B2 (en) 2004-12-29 2013-10-29 Abbott Diabetes Care Inc. Method and apparatus for mounting a data transmission device in a communication system
US10226207B2 (en) 2004-12-29 2019-03-12 Abbott Diabetes Care Inc. Sensor inserter having introducer
US8029441B2 (en) 2006-02-28 2011-10-04 Abbott Diabetes Care Inc. Analyte sensor transmitter unit configuration for a data monitoring and management system
US9398882B2 (en) 2005-09-30 2016-07-26 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor and data processing device
US9572534B2 (en) 2010-06-29 2017-02-21 Abbott Diabetes Care Inc. Devices, systems and methods for on-skin or on-body mounting of medical devices
US9636450B2 (en) 2007-02-19 2017-05-02 Udo Hoss Pump system modular components for delivering medication and analyte sensing at seperate insertion sites
US7731657B2 (en) 2005-08-30 2010-06-08 Abbott Diabetes Care Inc. Analyte sensor introducer and methods of use
US8652831B2 (en) 2004-12-30 2014-02-18 Sanofi-Aventis Deutschland Gmbh Method and apparatus for analyte measurement test time
ITBO20050002A1 (en) * 2005-01-04 2006-07-05 Giacomo Vespasiani METHOD AND SYSTEM FOR INTERACTIVE MANAGEMENT OF DATA CONCERNING AN INSULIN THERAPY IN SELF-CONTROL FOR A DIABETIC PATIENT
US20060166629A1 (en) * 2005-01-24 2006-07-27 Therasense, Inc. Method and apparatus for providing EMC Class-B compliant RF transmitter for data monitoring an detection systems
US7547281B2 (en) 2005-02-01 2009-06-16 Medtronic Minimed, Inc. Algorithm sensor augmented bolus estimator for semi-closed loop infusion system
US7545272B2 (en) 2005-02-08 2009-06-09 Therasense, Inc. RF tag on test strips, test strip vials and boxes
US7785258B2 (en) * 2005-10-06 2010-08-31 Optiscan Biomedical Corporation System and method for determining a treatment dose for a patient
US8251907B2 (en) 2005-02-14 2012-08-28 Optiscan Biomedical Corporation System and method for determining a treatment dose for a patient
US8133178B2 (en) 2006-02-22 2012-03-13 Dexcom, Inc. Analyte sensor
EP1863559A4 (en) 2005-03-21 2008-07-30 Abbott Diabetes Care Inc Method and system for providing integrated medication infusion and analyte monitoring system
GB2425601B (en) * 2005-04-26 2008-01-30 Bio Nano Sensium Technologies Sensor configuration
US8112240B2 (en) 2005-04-29 2012-02-07 Abbott Diabetes Care Inc. Method and apparatus for providing leak detection in data monitoring and management systems
US7768408B2 (en) 2005-05-17 2010-08-03 Abbott Diabetes Care Inc. Method and system for providing data management in data monitoring system
US7509156B2 (en) * 2005-05-18 2009-03-24 Clarian Health Partners, Inc. System for managing glucose levels in patients with diabetes or hyperglycemia
US7620437B2 (en) 2005-06-03 2009-11-17 Abbott Diabetes Care Inc. Method and apparatus for providing rechargeable power in data monitoring and management systems
US8251904B2 (en) 2005-06-09 2012-08-28 Roche Diagnostics Operations, Inc. Device and method for insulin dosing
US20070060870A1 (en) * 2005-08-16 2007-03-15 Tolle Mike Charles V Controller device for an infusion pump
US7737581B2 (en) * 2005-08-16 2010-06-15 Medtronic Minimed, Inc. Method and apparatus for predicting end of battery life
EP1921980A4 (en) 2005-08-31 2010-03-10 Univ Virginia Improving the accuracy of continuous glucose sensors
US20070196456A1 (en) * 2005-09-15 2007-08-23 Visible Assets, Inc. Smart patch
US7756561B2 (en) 2005-09-30 2010-07-13 Abbott Diabetes Care Inc. Method and apparatus for providing rechargeable power in data monitoring and management systems
US8880138B2 (en) 2005-09-30 2014-11-04 Abbott Diabetes Care Inc. Device for channeling fluid and methods of use
US9521968B2 (en) 2005-09-30 2016-12-20 Abbott Diabetes Care Inc. Analyte sensor retention mechanism and methods of use
US7583190B2 (en) 2005-10-31 2009-09-01 Abbott Diabetes Care Inc. Method and apparatus for providing data communication in data monitoring and management systems
DE102005052507A1 (en) * 2005-11-03 2007-05-16 Medwatchdog Gmbh & Co Kg Pocket size medical monitoring and notification device
US7766829B2 (en) 2005-11-04 2010-08-03 Abbott Diabetes Care Inc. Method and system for providing basal profile modification in analyte monitoring and management systems
DE102006051562A1 (en) * 2005-11-15 2007-05-16 Weinmann G Geraete Med Signal emitter for forming signals from measured physiological variable values, especially to control therapeutic devices, by detecting electromagnetic waves passed through or reflected from sample
US7963917B2 (en) * 2005-12-05 2011-06-21 Echo Therapeutics, Inc. System and method for continuous non-invasive glucose monitoring
DE102005059149A1 (en) 2005-12-12 2007-06-14 Ident Technology Ag Communication system e.g. mobile telephone, for carrying out data transfer, has transfer system with interface units, where transfer system is formed such that signal transmission takes place based on field electrical interaction effect
EP1795117A1 (en) * 2005-12-12 2007-06-13 F. Hoffmann-La Roche AG Patient device with remote user interface
EP1795116A1 (en) 2005-12-12 2007-06-13 F. Hoffmann-La Roche AG System with portable patient device and external operating unit
EP1968691A4 (en) * 2005-12-14 2012-01-25 Welch Allyn Inc Medical device wireless adapter
US11298058B2 (en) 2005-12-28 2022-04-12 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor insertion
EP1968432A4 (en) 2005-12-28 2009-10-21 Abbott Diabetes Care Inc Medical device insertion
US7736310B2 (en) 2006-01-30 2010-06-15 Abbott Diabetes Care Inc. On-body medical device securement
US8344966B2 (en) 2006-01-31 2013-01-01 Abbott Diabetes Care Inc. Method and system for providing a fault tolerant display unit in an electronic device
WO2007097754A1 (en) 2006-02-22 2007-08-30 Dexcom, Inc. Analyte sensor
US7826879B2 (en) 2006-02-28 2010-11-02 Abbott Diabetes Care Inc. Analyte sensors and methods of use
US7885698B2 (en) 2006-02-28 2011-02-08 Abbott Diabetes Care Inc. Method and system for providing continuous calibration of implantable analyte sensors
KR100794721B1 (en) * 2006-03-02 2008-01-15 이상문 Real-time diagnostic system employing a non-invasive method to analyze the electro-magnetic field radiated from a subject and the variation thereof
EP1991110B1 (en) 2006-03-09 2018-11-07 DexCom, Inc. Systems and methods for processing analyte sensor data
EP1839566A1 (en) * 2006-03-29 2007-10-03 F. Hoffmann-La Roche AG Method and assembly for the observation of a medical instrument.
US9392969B2 (en) 2008-08-31 2016-07-19 Abbott Diabetes Care Inc. Closed loop control and signal attenuation detection
US8140312B2 (en) 2007-05-14 2012-03-20 Abbott Diabetes Care Inc. Method and system for determining analyte levels
US9675290B2 (en) 2012-10-30 2017-06-13 Abbott Diabetes Care Inc. Sensitivity calibration of in vivo sensors used to measure analyte concentration
US8473022B2 (en) 2008-01-31 2013-06-25 Abbott Diabetes Care Inc. Analyte sensor with time lag compensation
US8346335B2 (en) 2008-03-28 2013-01-01 Abbott Diabetes Care Inc. Analyte sensor calibration management
US8226891B2 (en) 2006-03-31 2012-07-24 Abbott Diabetes Care Inc. Analyte monitoring devices and methods therefor
US7618369B2 (en) 2006-10-02 2009-11-17 Abbott Diabetes Care Inc. Method and system for dynamically updating calibration parameters for an analyte sensor
US7801582B2 (en) 2006-03-31 2010-09-21 Abbott Diabetes Care Inc. Analyte monitoring and management system and methods therefor
US7620438B2 (en) 2006-03-31 2009-11-17 Abbott Diabetes Care Inc. Method and system for powering an electronic device
US8224415B2 (en) 2009-01-29 2012-07-17 Abbott Diabetes Care Inc. Method and device for providing offset model based calibration for analyte sensor
US9326709B2 (en) 2010-03-10 2016-05-03 Abbott Diabetes Care Inc. Systems, devices and methods for managing glucose levels
US7630748B2 (en) 2006-10-25 2009-12-08 Abbott Diabetes Care Inc. Method and system for providing analyte monitoring
US8219173B2 (en) 2008-09-30 2012-07-10 Abbott Diabetes Care Inc. Optimizing analyte sensor calibration
US7653425B2 (en) 2006-08-09 2010-01-26 Abbott Diabetes Care Inc. Method and system for providing calibration of an analyte sensor in an analyte monitoring system
US8374668B1 (en) 2007-10-23 2013-02-12 Abbott Diabetes Care Inc. Analyte sensor with lag compensation
US20070270671A1 (en) * 2006-04-10 2007-11-22 Vivometrics, Inc. Physiological signal processing devices and associated processing methods
US8073008B2 (en) 2006-04-28 2011-12-06 Medtronic Minimed, Inc. Subnetwork synchronization and variable transmit synchronization techniques for a wireless medical device network
US7942844B2 (en) 2006-04-28 2011-05-17 Medtronic Minimed, Inc. Remote monitoring for networked fluid infusion systems
US20080071158A1 (en) 2006-06-07 2008-03-20 Abbott Diabetes Care, Inc. Analyte monitoring system and method
US20070284262A1 (en) * 2006-06-09 2007-12-13 Eugene Yanjun You Method of Detecting Shorts and Bad Contacts in an Electrolytic Cell
US9119582B2 (en) 2006-06-30 2015-09-01 Abbott Diabetes Care, Inc. Integrated analyte sensor and infusion device and methods therefor
US7965180B2 (en) 2006-09-28 2011-06-21 Semiconductor Energy Laboratory Co., Ltd. Wireless sensor device
US7831287B2 (en) 2006-10-04 2010-11-09 Dexcom, Inc. Dual electrode system for a continuous analyte sensor
CA2667639A1 (en) 2006-10-26 2008-05-02 Abbott Diabetes Care Inc. Method, system and computer program product for real-time detection of sensitivity decline in analyte sensors
US8579853B2 (en) 2006-10-31 2013-11-12 Abbott Diabetes Care Inc. Infusion devices and methods
US20080119710A1 (en) * 2006-10-31 2008-05-22 Abbott Diabetes Care, Inc. Medical devices and methods of using the same
EP1922986A1 (en) * 2006-11-15 2008-05-21 Roche Diagnostics GmbH Device for in vivo measurement of glucose
US20080201173A1 (en) * 2006-12-05 2008-08-21 Toyohiro Takehara Methods for delivering a drug to a patient while restricting access to the drug by patients for whom the drug may be contraindicated
US20080139910A1 (en) * 2006-12-06 2008-06-12 Metronic Minimed, Inc. Analyte sensor and method of using the same
US20080214919A1 (en) * 2006-12-26 2008-09-04 Lifescan, Inc. System and method for implementation of glycemic control protocols
DE102007003341B4 (en) * 2007-01-17 2018-01-04 Eyesense Ag Eyepiece sensor and measuring system for detecting an analyte in an eye fluid
US7936463B2 (en) * 2007-02-05 2011-05-03 Palo Alto Research Center Incorporated Containing analyte in optical cavity structures
US7852490B2 (en) * 2007-02-05 2010-12-14 Palo Alto Research Center Incorporated Implanting optical cavity structures
US7633629B2 (en) * 2007-02-05 2009-12-15 Palo Alto Research Center Incorporated Tuning optical cavities
US8121857B2 (en) 2007-02-15 2012-02-21 Abbott Diabetes Care Inc. Device and method for automatic data acquisition and/or detection
US20080199894A1 (en) 2007-02-15 2008-08-21 Abbott Diabetes Care, Inc. Device and method for automatic data acquisition and/or detection
US8732188B2 (en) 2007-02-18 2014-05-20 Abbott Diabetes Care Inc. Method and system for providing contextual based medication dosage determination
US8930203B2 (en) 2007-02-18 2015-01-06 Abbott Diabetes Care Inc. Multi-function analyte test device and methods therefor
US8123686B2 (en) 2007-03-01 2012-02-28 Abbott Diabetes Care Inc. Method and apparatus for providing rolling data in communication systems
US9220837B2 (en) * 2007-03-19 2015-12-29 Insuline Medical Ltd. Method and device for drug delivery
MX2009010000A (en) * 2007-03-19 2010-03-17 Insuline Medical Ltd Drug delivery device.
WO2009081262A1 (en) 2007-12-18 2009-07-02 Insuline Medical Ltd. Drug delivery device with sensor for closed-loop operation
EP2136863A2 (en) * 2007-03-19 2009-12-30 Insuline Medical Ltd. Device for drug delivery and associated connections thereto
US8622991B2 (en) 2007-03-19 2014-01-07 Insuline Medical Ltd. Method and device for drug delivery
WO2008130895A2 (en) 2007-04-14 2008-10-30 Abbott Diabetes Care, Inc. Method and apparatus for providing dynamic multi-stage signal amplification in a medical device
US8140142B2 (en) 2007-04-14 2012-03-20 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in medical communication system
WO2008130896A1 (en) 2007-04-14 2008-10-30 Abbott Diabetes Care, Inc. Method and apparatus for providing data processing and control in medical communication system
EP2146625B1 (en) 2007-04-14 2019-08-14 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in medical communication system
US9615780B2 (en) 2007-04-14 2017-04-11 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in medical communication system
EP4108162A1 (en) 2007-04-14 2022-12-28 Abbott Diabetes Care, Inc. Method and apparatus for providing data processing and control in medical communication system
US8585607B2 (en) 2007-05-02 2013-11-19 Earlysense Ltd. Monitoring, predicting and treating clinical episodes
US8821418B2 (en) 2007-05-02 2014-09-02 Earlysense Ltd. Monitoring, predicting and treating clinical episodes
US8461985B2 (en) 2007-05-08 2013-06-11 Abbott Diabetes Care Inc. Analyte monitoring system and methods
US8665091B2 (en) 2007-05-08 2014-03-04 Abbott Diabetes Care Inc. Method and device for determining elapsed sensor life
US7928850B2 (en) 2007-05-08 2011-04-19 Abbott Diabetes Care Inc. Analyte monitoring system and methods
US8456301B2 (en) 2007-05-08 2013-06-04 Abbott Diabetes Care Inc. Analyte monitoring system and methods
US8600681B2 (en) 2007-05-14 2013-12-03 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US8103471B2 (en) 2007-05-14 2012-01-24 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US8444560B2 (en) 2007-05-14 2013-05-21 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US8260558B2 (en) 2007-05-14 2012-09-04 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US10002233B2 (en) 2007-05-14 2018-06-19 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US8560038B2 (en) 2007-05-14 2013-10-15 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US7996158B2 (en) 2007-05-14 2011-08-09 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US8239166B2 (en) 2007-05-14 2012-08-07 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US9125548B2 (en) 2007-05-14 2015-09-08 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
US20100145175A1 (en) * 2008-08-22 2010-06-10 Soldo Monnett H Systems and methods for verification of sample integrity
US8597190B2 (en) 2007-05-18 2013-12-03 Optiscan Biomedical Corporation Monitoring systems and methods with fast initialization
US8417311B2 (en) * 2008-09-12 2013-04-09 Optiscan Biomedical Corporation Fluid component analysis system and method for glucose monitoring and control
WO2008150917A1 (en) 2007-05-31 2008-12-11 Abbott Diabetes Care, Inc. Insertion devices and methods
EP2152350A4 (en) 2007-06-08 2013-03-27 Dexcom Inc Integrated medicament delivery device for use with continuous analyte sensor
CA2690870C (en) 2007-06-21 2017-07-11 Abbott Diabetes Care Inc. Health monitor
EP3533387A3 (en) 2007-06-21 2019-11-13 Abbott Diabetes Care, Inc. Health management devices and methods
US20080318193A1 (en) * 2007-06-25 2008-12-25 Lifescan Scotland, Ltd. Medical training aid device for training a user in recognition of the user's bodily fluid analyte concentration and concentration trends via user-perceived sensations
US8160900B2 (en) 2007-06-29 2012-04-17 Abbott Diabetes Care Inc. Analyte monitoring and management device and method to analyze the frequency of user interaction with the device
US8268638B2 (en) 2007-07-18 2012-09-18 Advantageous Systems, Llc Methods and apparatuses for detecting analytes in biological fluid of an animal
US8834366B2 (en) 2007-07-31 2014-09-16 Abbott Diabetes Care Inc. Method and apparatus for providing analyte sensor calibration
US7768386B2 (en) 2007-07-31 2010-08-03 Abbott Diabetes Care Inc. Method and apparatus for providing data processing and control in a medical communication system
WO2009021039A1 (en) * 2007-08-06 2009-02-12 University Of Kentucky Research Foundation Device for detection of molecules of interest
EP2227132B1 (en) 2007-10-09 2023-03-08 DexCom, Inc. Integrated insulin delivery system with continuous glucose sensor
MX2010003855A (en) 2007-10-10 2010-04-27 Optiscan Biomedical Corp Fluid component analysis system and method for glucose monitoring and control.
WO2009049245A1 (en) * 2007-10-11 2009-04-16 Optiscan Biomedical Corporation Synchronization and configuration of patient monitoring devices
US8409093B2 (en) 2007-10-23 2013-04-02 Abbott Diabetes Care Inc. Assessing measures of glycemic variability
US8377031B2 (en) 2007-10-23 2013-02-19 Abbott Diabetes Care Inc. Closed loop control system with safety parameters and methods
US8216138B1 (en) 2007-10-23 2012-07-10 Abbott Diabetes Care Inc. Correlation of alternative site blood and interstitial fluid glucose concentrations to venous glucose concentration
US8417312B2 (en) 2007-10-25 2013-04-09 Dexcom, Inc. Systems and methods for processing sensor data
US8320983B2 (en) 2007-12-17 2012-11-27 Palo Alto Research Center Incorporated Controlling transfer of objects affecting optical characteristics
US8290559B2 (en) 2007-12-17 2012-10-16 Dexcom, Inc. Systems and methods for processing sensor data
US20090164239A1 (en) 2007-12-19 2009-06-25 Abbott Diabetes Care, Inc. Dynamic Display Of Glucose Information
EP2241032B1 (en) * 2007-12-20 2018-02-28 Koninklijke Philips N.V. Capacitive sensing and communicating
US8313467B2 (en) 2007-12-27 2012-11-20 Medtronic Minimed, Inc. Reservoir pressure equalization systems and methods
US8229535B2 (en) 2008-02-21 2012-07-24 Dexcom, Inc. Systems and methods for blood glucose monitoring and alert delivery
TWI368188B (en) * 2008-03-18 2012-07-11 Univ Nat Taiwan Intra-body biomedical communication system (ibc) and the method use of
US11730407B2 (en) 2008-03-28 2023-08-22 Dexcom, Inc. Polymer membranes for continuous analyte sensors
EP3659628A1 (en) 2008-04-10 2020-06-03 Abbott Diabetes Care, Inc. Method and system for sterilizing an analyte sensor
EP2265324B1 (en) 2008-04-11 2015-01-28 Sanofi-Aventis Deutschland GmbH Integrated analyte measurement system
WO2009132275A2 (en) * 2008-04-25 2009-10-29 Celgene Corporation Methods for delivering a drug to a patient while restricting access to the drug by patients for whom the drug may be contraindicated
US8882684B2 (en) 2008-05-12 2014-11-11 Earlysense Ltd. Monitoring, predicting and treating clinical episodes
US9883809B2 (en) 2008-05-01 2018-02-06 Earlysense Ltd. Monitoring, predicting and treating clinical episodes
US8924159B2 (en) 2008-05-30 2014-12-30 Abbott Diabetes Care Inc. Method and apparatus for providing glycemic control
US7826382B2 (en) 2008-05-30 2010-11-02 Abbott Diabetes Care Inc. Close proximity communication device and methods
US8591410B2 (en) 2008-05-30 2013-11-26 Abbott Diabetes Care Inc. Method and apparatus for providing glycemic control
US8876755B2 (en) 2008-07-14 2014-11-04 Abbott Diabetes Care Inc. Closed loop control system interface and methods
US7959598B2 (en) 2008-08-20 2011-06-14 Asante Solutions, Inc. Infusion pump systems and methods
US9943644B2 (en) 2008-08-31 2018-04-17 Abbott Diabetes Care Inc. Closed loop control with reference measurement and methods thereof
US8734422B2 (en) 2008-08-31 2014-05-27 Abbott Diabetes Care Inc. Closed loop control with improved alarm functions
US20100057040A1 (en) 2008-08-31 2010-03-04 Abbott Diabetes Care, Inc. Robust Closed Loop Control And Methods
US8622988B2 (en) 2008-08-31 2014-01-07 Abbott Diabetes Care Inc. Variable rate closed loop control and methods
US8986208B2 (en) 2008-09-30 2015-03-24 Abbott Diabetes Care Inc. Analyte sensor sensitivity attenuation mitigation
US8208973B2 (en) 2008-11-05 2012-06-26 Medtronic Minimed, Inc. System and method for variable beacon timing with wireless devices
MX2011004817A (en) 2008-11-07 2011-07-28 Insuline Medical Ltd Device and method for drug delivery.
US9326707B2 (en) 2008-11-10 2016-05-03 Abbott Diabetes Care Inc. Alarm characterization for analyte monitoring devices and systems
EP2208458A1 (en) * 2009-01-14 2010-07-21 Roche Diagnostics GmbH Medical monitoring network
US8103456B2 (en) 2009-01-29 2012-01-24 Abbott Diabetes Care Inc. Method and device for early signal attenuation detection using blood glucose measurements
US9375169B2 (en) 2009-01-30 2016-06-28 Sanofi-Aventis Deutschland Gmbh Cam drive for managing disposable penetrating member actions with a single motor and motor and control system
US20100198196A1 (en) * 2009-01-30 2010-08-05 Abbott Diabetes Care, Inc. Therapy Delivery Device Programming Tool
US8560082B2 (en) 2009-01-30 2013-10-15 Abbott Diabetes Care Inc. Computerized determination of insulin pump therapy parameters using real time and retrospective data processing
US9402544B2 (en) 2009-02-03 2016-08-02 Abbott Diabetes Care Inc. Analyte sensor and apparatus for insertion of the sensor
US9250106B2 (en) 2009-02-27 2016-02-02 Tandem Diabetes Care, Inc. Methods and devices for determination of flow reservoir volume
WO2010099490A2 (en) 2009-02-27 2010-09-02 Tandem Diabetes Care, Inc. Methods and devices for determination of flow reservoir volume
WO2010111660A1 (en) 2009-03-27 2010-09-30 Dexcom, Inc. Methods and systems for promoting glucose management
US8497777B2 (en) 2009-04-15 2013-07-30 Abbott Diabetes Care Inc. Analyte monitoring system having an alert
WO2010121229A1 (en) 2009-04-16 2010-10-21 Abbott Diabetes Care Inc. Analyte sensor calibration management
US8467972B2 (en) 2009-04-28 2013-06-18 Abbott Diabetes Care Inc. Closed loop blood glucose control algorithm analysis
WO2010127050A1 (en) 2009-04-28 2010-11-04 Abbott Diabetes Care Inc. Error detection in critical repeating data in a wireless sensor system
US8368556B2 (en) 2009-04-29 2013-02-05 Abbott Diabetes Care Inc. Method and system for providing data communication in continuous glucose monitoring and management system
US8483967B2 (en) 2009-04-29 2013-07-09 Abbott Diabetes Care Inc. Method and system for providing real time analyte sensor calibration with retrospective backfill
WO2010138856A1 (en) 2009-05-29 2010-12-02 Abbott Diabetes Care Inc. Medical device antenna systems having external antenna configurations
US20100331645A1 (en) * 2009-06-25 2010-12-30 Roche Diagnostics Operations, Inc. Methods and systems for wireless communication between a blood glucose meter and a portable communication device
US8613892B2 (en) 2009-06-30 2013-12-24 Abbott Diabetes Care Inc. Analyte meter with a moveable head and methods of using the same
US9237864B2 (en) 2009-07-02 2016-01-19 Dexcom, Inc. Analyte sensors and methods of manufacturing same
US9351677B2 (en) 2009-07-02 2016-05-31 Dexcom, Inc. Analyte sensor with increased reference capacity
US8344847B2 (en) 2009-07-09 2013-01-01 Medtronic Minimed, Inc. Coordination of control commands in a medical device system having at least one therapy delivery device and at least one wireless controller device
EP3689237B1 (en) 2009-07-23 2021-05-19 Abbott Diabetes Care, Inc. Method of manufacturing and system for continuous analyte measurement
ES2888427T3 (en) 2009-07-23 2022-01-04 Abbott Diabetes Care Inc Real-time management of data related to the physiological control of glucose levels
EP3284494A1 (en) 2009-07-30 2018-02-21 Tandem Diabetes Care, Inc. Portable infusion pump system
WO2011014851A1 (en) 2009-07-31 2011-02-03 Abbott Diabetes Care Inc. Method and apparatus for providing analyte monitoring system calibration accuracy
US8993331B2 (en) 2009-08-31 2015-03-31 Abbott Diabetes Care Inc. Analyte monitoring system and methods for managing power and noise
EP2473098A4 (en) 2009-08-31 2014-04-09 Abbott Diabetes Care Inc Analyte signal processing device and methods
ES2952361T3 (en) 2009-08-31 2023-10-31 Abbott Diabetes Care Inc Displays for a medical device
CN102473276B (en) * 2009-08-31 2016-04-13 雅培糖尿病护理公司 Medical treatment device and method
US8487758B2 (en) 2009-09-02 2013-07-16 Medtronic Minimed, Inc. Medical device having an intelligent alerting scheme, and related operating methods
WO2011041469A1 (en) 2009-09-29 2011-04-07 Abbott Diabetes Care Inc. Method and apparatus for providing notification function in analyte monitoring systems
WO2011041531A1 (en) 2009-09-30 2011-04-07 Abbott Diabetes Care Inc. Interconnect for on-body analyte monitoring device
US20110082711A1 (en) 2009-10-06 2011-04-07 Masimo Laboratories, Inc. Personal digital assistant or organizer for monitoring glucose levels
US9675275B2 (en) 2009-10-24 2017-06-13 Carrot Sense, Inc. Extracorporeal devices and methods for facilitating cessation of undesired behaviors
US9420971B2 (en) 2009-10-24 2016-08-23 Carrot Sense, Inc. Extracorporeal devices and methods for facilitating cessation of undesired behaviors
EP2494323A4 (en) 2009-10-30 2014-07-16 Abbott Diabetes Care Inc Method and apparatus for detecting false hypoglycemic conditions
US8386042B2 (en) 2009-11-03 2013-02-26 Medtronic Minimed, Inc. Omnidirectional accelerometer device and medical device incorporating same
US20110152634A1 (en) * 2009-12-17 2011-06-23 Jeff Thew Measuring Human Biological Fluid Levels
US8574201B2 (en) 2009-12-22 2013-11-05 Medtronic Minimed, Inc. Syringe piston with check valve seal
US8755269B2 (en) 2009-12-23 2014-06-17 Medtronic Minimed, Inc. Ranking and switching of wireless channels in a body area network of medical devices
USD924406S1 (en) 2010-02-01 2021-07-06 Abbott Diabetes Care Inc. Analyte sensor inserter
US20110225008A1 (en) * 2010-03-09 2011-09-15 Respira Dv, Llc Self-Similar Medical Communications System
WO2011162843A1 (en) 2010-03-24 2011-12-29 Abbott Diabetes Care Inc. Medical device inserters and processes of inserting and using medical devices
US8965476B2 (en) 2010-04-16 2015-02-24 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
ES2464773T3 (en) 2010-04-23 2014-06-04 F. Hoffmann-La Roche Ag Method to generate a medical network
US8635046B2 (en) 2010-06-23 2014-01-21 Abbott Diabetes Care Inc. Method and system for evaluating analyte sensor response characteristics
US10092229B2 (en) 2010-06-29 2018-10-09 Abbott Diabetes Care Inc. Calibration of analyte measurement system
US11064921B2 (en) 2010-06-29 2021-07-20 Abbott Diabetes Care Inc. Devices, systems and methods for on-skin or on-body mounting of medical devices
EP2624745A4 (en) 2010-10-07 2018-05-23 Abbott Diabetes Care, Inc. Analyte monitoring devices and methods
RU2603704C2 (en) * 2010-10-11 2016-11-27 Эдленс Бикен, Инк. Non powered concepts for a wire frame of fluid filled lenses
US8603033B2 (en) 2010-10-15 2013-12-10 Medtronic Minimed, Inc. Medical device and related assembly having an offset element for a piezoelectric speaker
US8603032B2 (en) 2010-10-15 2013-12-10 Medtronic Minimed, Inc. Medical device with membrane keypad sealing element, and related manufacturing method
US8562565B2 (en) 2010-10-15 2013-10-22 Medtronic Minimed, Inc. Battery shock absorber for a portable medical device
US8474332B2 (en) 2010-10-20 2013-07-02 Medtronic Minimed, Inc. Sensor assembly and medical device incorporating same
US8495918B2 (en) 2010-10-20 2013-07-30 Medtronic Minimed, Inc. Sensor assembly and medical device incorporating same
US8479595B2 (en) 2010-10-20 2013-07-09 Medtronic Minimed, Inc. Sensor assembly and medical device incorporating same
US10292625B2 (en) 2010-12-07 2019-05-21 Earlysense Ltd. Monitoring a sleeping subject
EP2465415B1 (en) * 2010-12-20 2013-07-03 General Electric Company Single-use biomedical sensors
US8690855B2 (en) * 2010-12-22 2014-04-08 Medtronic Minimed, Inc. Fluid reservoir seating procedure for a fluid infusion device
US8469942B2 (en) 2010-12-22 2013-06-25 Medtronic Minimed, Inc. Occlusion detection for a fluid infusion device
US8197444B1 (en) 2010-12-22 2012-06-12 Medtronic Minimed, Inc. Monitoring the seating status of a fluid reservoir in a fluid infusion device
US8628510B2 (en) 2010-12-22 2014-01-14 Medtronic Minimed, Inc. Monitoring the operating health of a force sensor in a fluid infusion device
US20120197090A1 (en) * 2011-02-01 2012-08-02 Pensiero Medical Electronics Corp. Biomedical device with near field communication (nfc) function and method thereof for user identification, biomedical data measurement, biomedical data upload/download, biomedical data management, and remote medical care
US8900206B2 (en) 2011-02-22 2014-12-02 Medtronic Minimed, Inc. Pressure vented fluid reservoir for a fluid infusion device
US9283318B2 (en) 2011-02-22 2016-03-15 Medtronic Minimed, Inc. Flanged sealing element and needle guide pin assembly for a fluid infusion device having a needled fluid reservoir
US9463309B2 (en) 2011-02-22 2016-10-11 Medtronic Minimed, Inc. Sealing assembly and structure for a fluid infusion device having a needled fluid reservoir
US9393399B2 (en) 2011-02-22 2016-07-19 Medtronic Minimed, Inc. Sealing assembly for a fluid reservoir of a fluid infusion device
US10136845B2 (en) 2011-02-28 2018-11-27 Abbott Diabetes Care Inc. Devices, systems, and methods associated with analyte monitoring devices and devices incorporating the same
US8614596B2 (en) 2011-02-28 2013-12-24 Medtronic Minimed, Inc. Systems and methods for initializing a voltage bus and medical devices incorporating same
CA3177983A1 (en) 2011-02-28 2012-11-15 Abbott Diabetes Care Inc. Devices, systems, and methods associated with analyte monitoring devices and devices incorporating the same
US9101305B2 (en) 2011-03-09 2015-08-11 Medtronic Minimed, Inc. Glucose sensor product and related manufacturing and packaging methods
US9018893B2 (en) 2011-03-18 2015-04-28 Medtronic Minimed, Inc. Power control techniques for an electronic device
US8564447B2 (en) 2011-03-18 2013-10-22 Medtronic Minimed, Inc. Battery life indication techniques for an electronic device
WO2012142502A2 (en) 2011-04-15 2012-10-18 Dexcom Inc. Advanced analyte sensor calibration and error detection
US9622691B2 (en) 2011-10-31 2017-04-18 Abbott Diabetes Care Inc. Model based variable risk false glucose threshold alarm prevention mechanism
WO2013066873A1 (en) 2011-10-31 2013-05-10 Abbott Diabetes Care Inc. Electronic devices having integrated reset systems and methods thereof
WO2013070794A2 (en) 2011-11-07 2013-05-16 Abbott Diabetes Care Inc. Analyte monitoring device and methods
US8710993B2 (en) 2011-11-23 2014-04-29 Abbott Diabetes Care Inc. Mitigating single point failure of devices in an analyte monitoring system and methods thereof
US9317656B2 (en) 2011-11-23 2016-04-19 Abbott Diabetes Care Inc. Compatibility mechanisms for devices in a continuous analyte monitoring system and methods thereof
WO2013078426A2 (en) 2011-11-25 2013-05-30 Abbott Diabetes Care Inc. Analyte monitoring system and methods of use
US9402570B2 (en) 2011-12-11 2016-08-02 Abbott Diabetes Care Inc. Analyte sensor devices, connections, and methods
US9610401B2 (en) 2012-01-13 2017-04-04 Medtronic Minimed, Inc. Infusion set component with modular fluid channel element
US8603026B2 (en) 2012-03-20 2013-12-10 Medtronic Minimed, Inc. Dynamic pulse-width modulation motor control and medical device incorporating same
US8523803B1 (en) 2012-03-20 2013-09-03 Medtronic Minimed, Inc. Motor health monitoring and medical device incorporating same
US8603027B2 (en) 2012-03-20 2013-12-10 Medtronic Minimed, Inc. Occlusion detection using pulse-width modulation and medical device incorporating same
US9180242B2 (en) 2012-05-17 2015-11-10 Tandem Diabetes Care, Inc. Methods and devices for multiple fluid transfer
US20130338629A1 (en) 2012-06-07 2013-12-19 Medtronic Minimed, Inc. Diabetes therapy management system for recommending basal pattern adjustments
US9333292B2 (en) 2012-06-26 2016-05-10 Medtronic Minimed, Inc. Mechanically actuated fluid infusion device
US8808269B2 (en) 2012-08-21 2014-08-19 Medtronic Minimed, Inc. Reservoir plunger position monitoring and medical device incorporating same
US9662445B2 (en) 2012-08-30 2017-05-30 Medtronic Minimed, Inc. Regulating entry into a closed-loop operating mode of an insulin infusion system
US10496797B2 (en) 2012-08-30 2019-12-03 Medtronic Minimed, Inc. Blood glucose validation for a closed-loop operating mode of an insulin infusion system
US9878096B2 (en) 2012-08-30 2018-01-30 Medtronic Minimed, Inc. Generation of target glucose values for a closed-loop operating mode of an insulin infusion system
US10132793B2 (en) 2012-08-30 2018-11-20 Abbott Diabetes Care Inc. Dropout detection in continuous analyte monitoring data during data excursions
US9849239B2 (en) 2012-08-30 2017-12-26 Medtronic Minimed, Inc. Generation and application of an insulin limit for a closed-loop operating mode of an insulin infusion system
US10130767B2 (en) 2012-08-30 2018-11-20 Medtronic Minimed, Inc. Sensor model supervisor for a closed-loop insulin infusion system
US9364609B2 (en) 2012-08-30 2016-06-14 Medtronic Minimed, Inc. Insulin on board compensation for a closed-loop insulin infusion system
US9623179B2 (en) 2012-08-30 2017-04-18 Medtronic Minimed, Inc. Safeguarding techniques for a closed-loop insulin infusion system
US9968306B2 (en) 2012-09-17 2018-05-15 Abbott Diabetes Care Inc. Methods and apparatuses for providing adverse condition notification with enhanced wireless communication range in analyte monitoring systems
EP2901153A4 (en) 2012-09-26 2016-04-27 Abbott Diabetes Care Inc Method and apparatus for improving lag correction during in vivo measurement of analyte concentration with analyte concentration variability and range data
US8870818B2 (en) 2012-11-15 2014-10-28 Medtronic Minimed, Inc. Systems and methods for alignment and detection of a consumable component
US9522223B2 (en) 2013-01-18 2016-12-20 Medtronic Minimed, Inc. Systems for fluid reservoir retention
US9033924B2 (en) 2013-01-18 2015-05-19 Medtronic Minimed, Inc. Systems for fluid reservoir retention
US9107994B2 (en) 2013-01-18 2015-08-18 Medtronic Minimed, Inc. Systems for fluid reservoir retention
US9308321B2 (en) 2013-02-18 2016-04-12 Medtronic Minimed, Inc. Infusion device having gear assembly initialization
US9520050B2 (en) * 2013-03-04 2016-12-13 Revolar, Inc. Interchangeable personal security device with a communication accessory
CA2941334A1 (en) 2013-03-04 2014-09-12 Revolar, Inc. An interchangeable personal security device
US9173998B2 (en) 2013-03-14 2015-11-03 Tandem Diabetes Care, Inc. System and method for detecting occlusions in an infusion pump
US10076285B2 (en) 2013-03-15 2018-09-18 Abbott Diabetes Care Inc. Sensor fault detection using analyte sensor data pattern comparison
US9474475B1 (en) 2013-03-15 2016-10-25 Abbott Diabetes Care Inc. Multi-rate analyte sensor data collection with sample rate configurable signal processing
US9486171B2 (en) 2013-03-15 2016-11-08 Tandem Diabetes Care, Inc. Predictive calibration
US10433773B1 (en) 2013-03-15 2019-10-08 Abbott Diabetes Care Inc. Noise rejection methods and apparatus for sparsely sampled analyte sensor data
US8920381B2 (en) 2013-04-12 2014-12-30 Medtronic Minimed, Inc. Infusion set with improved bore configuration
US9433731B2 (en) 2013-07-19 2016-09-06 Medtronic Minimed, Inc. Detecting unintentional motor motion and infusion device incorporating same
US9402949B2 (en) 2013-08-13 2016-08-02 Medtronic Minimed, Inc. Detecting conditions associated with medical device operations using matched filters
US9880528B2 (en) 2013-08-21 2018-01-30 Medtronic Minimed, Inc. Medical devices and related updating methods and systems
US9889257B2 (en) 2013-08-21 2018-02-13 Medtronic Minimed, Inc. Systems and methods for updating medical devices
US9259528B2 (en) 2013-08-22 2016-02-16 Medtronic Minimed, Inc. Fluid infusion device with safety coupling
IN2013MU02808A (en) 2013-08-28 2015-07-03 Indian Inst Technology
EP3041528A4 (en) 2013-09-06 2017-04-26 Tandem Diabetes Care, Inc. System and method for mitigating risk in automated medicament dosing
US9565718B2 (en) 2013-09-10 2017-02-07 Tandem Diabetes Care, Inc. System and method for detecting and transmitting medical device alarm with a smartphone application
US9750877B2 (en) 2013-12-11 2017-09-05 Medtronic Minimed, Inc. Predicted time to assess and/or control a glycemic state
US9750878B2 (en) 2013-12-11 2017-09-05 Medtronic Minimed, Inc. Closed-loop control of glucose according to a predicted blood glucose trajectory
US10105488B2 (en) 2013-12-12 2018-10-23 Medtronic Minimed, Inc. Predictive infusion device operations and related methods and systems
US9849240B2 (en) 2013-12-12 2017-12-26 Medtronic Minimed, Inc. Data modification for predictive operations and devices incorporating same
US9694132B2 (en) 2013-12-19 2017-07-04 Medtronic Minimed, Inc. Insertion device for insertion set
CA2933166C (en) 2013-12-31 2020-10-27 Abbott Diabetes Care Inc. Self-powered analyte sensor and devices using the same
US9626315B2 (en) 2014-01-13 2017-04-18 Senseonics, Incorporated Remotely powered, multisite sensing system with a shared, two-wire bus for power and communication
US10872048B2 (en) 2014-01-13 2020-12-22 Senseonics, Incorporated Remotely-powered sensing system with multiple sensing devices
GB2523989B (en) 2014-01-30 2020-07-29 Insulet Netherlands B V Therapeutic product delivery system and method of pairing
US9399096B2 (en) 2014-02-06 2016-07-26 Medtronic Minimed, Inc. Automatic closed-loop control adjustments and infusion systems incorporating same
US9861748B2 (en) 2014-02-06 2018-01-09 Medtronic Minimed, Inc. User-configurable closed-loop notifications and infusion systems incorporating same
SG11201607411RA (en) 2014-03-07 2016-10-28 Univ Texas Tri-electrode apparatus and methods for molecular analysis
US9610402B2 (en) 2014-03-24 2017-04-04 Medtronic Minimed, Inc. Transcutaneous conduit insertion mechanism with a living hinge for use with a fluid infusion patch pump device
US20170185748A1 (en) 2014-03-30 2017-06-29 Abbott Diabetes Care Inc. Method and Apparatus for Determining Meal Start and Peak Events in Analyte Monitoring Systems
US10001450B2 (en) 2014-04-18 2018-06-19 Medtronic Minimed, Inc. Nonlinear mapping technique for a physiological characteristic sensor
US10232113B2 (en) 2014-04-24 2019-03-19 Medtronic Minimed, Inc. Infusion devices and related methods and systems for regulating insulin on board
US10275572B2 (en) 2014-05-01 2019-04-30 Medtronic Minimed, Inc. Detecting blockage of a reservoir cavity during a seating operation of a fluid infusion device
US9681828B2 (en) 2014-05-01 2017-06-20 Medtronic Minimed, Inc. Physiological characteristic sensors and methods for forming such sensors
US10152049B2 (en) 2014-05-19 2018-12-11 Medtronic Minimed, Inc. Glucose sensor health monitoring and related methods and systems
US10007765B2 (en) 2014-05-19 2018-06-26 Medtronic Minimed, Inc. Adaptive signal processing for infusion devices and related methods and systems
US10274349B2 (en) 2014-05-19 2019-04-30 Medtronic Minimed, Inc. Calibration factor adjustments for infusion devices and related methods and systems
HUE059012T2 (en) * 2014-05-20 2022-09-28 Hoffmann La Roche A method for producing a sterilized subcutaneous access device and a sterilized subcutaneous access device
US9833563B2 (en) 2014-09-26 2017-12-05 Medtronic Minimed, Inc. Systems for managing reservoir chamber pressure
US9839753B2 (en) 2014-09-26 2017-12-12 Medtronic Minimed, Inc. Systems for managing reservoir chamber pressure
US10279126B2 (en) 2014-10-07 2019-05-07 Medtronic Minimed, Inc. Fluid conduit assembly with gas trapping filter in the fluid flow path
WO2016065190A1 (en) 2014-10-23 2016-04-28 Abbott Diabetes Care Inc. Electrodes having at least one sensing structure and methods for making and using the same
US9833564B2 (en) 2014-11-25 2017-12-05 Medtronic Minimed, Inc. Fluid conduit assembly with air venting features
US10195341B2 (en) 2014-11-26 2019-02-05 Medtronic Minimed, Inc. Systems and methods for fluid infusion device with automatic reservoir fill
US9987420B2 (en) 2014-11-26 2018-06-05 Medtronic Minimed, Inc. Systems and methods for fluid infusion device with automatic reservoir fill
US9636453B2 (en) 2014-12-04 2017-05-02 Medtronic Minimed, Inc. Advance diagnosis of infusion device operating mode viability
US9943645B2 (en) 2014-12-04 2018-04-17 Medtronic Minimed, Inc. Methods for operating mode transitions and related infusion devices and systems
US9937292B2 (en) 2014-12-09 2018-04-10 Medtronic Minimed, Inc. Systems for filling a fluid infusion device reservoir
US10307535B2 (en) 2014-12-19 2019-06-04 Medtronic Minimed, Inc. Infusion devices and related methods and systems for preemptive alerting
US10265031B2 (en) 2014-12-19 2019-04-23 Medtronic Minimed, Inc. Infusion devices and related methods and systems for automatic alert clearing
EP3236850A4 (en) * 2014-12-23 2018-07-18 Ent. Services Development Corporation LP Detection of allergen exposure
EP3258991B1 (en) 2015-02-18 2020-10-21 Insulet Corporation Fluid delivery and infusion devices, and methods of use thereof
US10307528B2 (en) 2015-03-09 2019-06-04 Medtronic Minimed, Inc. Extensible infusion devices and related methods
CN104739419A (en) * 2015-03-19 2015-07-01 深圳市一体太赫兹科技有限公司 System for regulating blood sugars
US10449298B2 (en) 2015-03-26 2019-10-22 Medtronic Minimed, Inc. Fluid injection devices and related methods
US10413200B2 (en) 2015-04-06 2019-09-17 Thomas Jefferson University Implantable vital sign sensor
US10335043B2 (en) 2015-04-06 2019-07-02 Thomas Jefferson University Implantable vital sign sensor
US11330987B2 (en) 2015-04-06 2022-05-17 Thomas Jefferson University Implantable vital sign sensor
US11000195B2 (en) 2015-04-06 2021-05-11 Thomas Jefferson University Implantable vital sign sensor
US10206572B1 (en) 2017-10-10 2019-02-19 Carrot, Inc. Systems and methods for quantification of, and prediction of smoking behavior
US10306922B2 (en) 2015-04-07 2019-06-04 Carrot, Inc. Systems and methods for quantification of, and prediction of smoking behavior
US10213139B2 (en) 2015-05-14 2019-02-26 Abbott Diabetes Care Inc. Systems, devices, and methods for assembling an applicator and sensor control device
CA2984939A1 (en) 2015-05-14 2016-11-17 Abbott Diabetes Care Inc. Compact medical device inserters and related systems and methods
US10137243B2 (en) 2015-05-26 2018-11-27 Medtronic Minimed, Inc. Infusion devices with distributed motor control and related operating methods
US9999721B2 (en) 2015-05-26 2018-06-19 Medtronic Minimed, Inc. Error handling in infusion devices with distributed motor control and related operating methods
US10575767B2 (en) 2015-05-29 2020-03-03 Medtronic Minimed, Inc. Method for monitoring an analyte, analyte sensor and analyte monitoring apparatus
US9993594B2 (en) 2015-06-22 2018-06-12 Medtronic Minimed, Inc. Occlusion detection techniques for a fluid infusion device having a rotary pump mechanism and rotor position sensors
US10010668B2 (en) 2015-06-22 2018-07-03 Medtronic Minimed, Inc. Occlusion detection techniques for a fluid infusion device having a rotary pump mechanism and a force sensor
US9879668B2 (en) 2015-06-22 2018-01-30 Medtronic Minimed, Inc. Occlusion detection techniques for a fluid infusion device having a rotary pump mechanism and an optical sensor
US9878095B2 (en) 2015-06-22 2018-01-30 Medtronic Minimed, Inc. Occlusion detection techniques for a fluid infusion device having a rotary pump mechanism and multiple sensor contact elements
US9987425B2 (en) 2015-06-22 2018-06-05 Medtronic Minimed, Inc. Occlusion detection techniques for a fluid infusion device having a rotary pump mechanism and sensor contact elements
US11553883B2 (en) 2015-07-10 2023-01-17 Abbott Diabetes Care Inc. System, device and method of dynamic glucose profile response to physiological parameters
US10478557B2 (en) 2015-08-21 2019-11-19 Medtronic Minimed, Inc. Personalized parameter modeling methods and related devices and systems
US10463297B2 (en) 2015-08-21 2019-11-05 Medtronic Minimed, Inc. Personalized event detection methods and related devices and systems
US10867012B2 (en) 2015-08-21 2020-12-15 Medtronic Minimed, Inc. Data analytics and insight delivery for the management and control of diabetes
US10201657B2 (en) 2015-08-21 2019-02-12 Medtronic Minimed, Inc. Methods for providing sensor site rotation feedback and related infusion devices and systems
US10293108B2 (en) 2015-08-21 2019-05-21 Medtronic Minimed, Inc. Infusion devices and related patient ratio adjustment methods
US10117992B2 (en) 2015-09-29 2018-11-06 Medtronic Minimed, Inc. Infusion devices and related rescue detection methods
ES2575234B1 (en) * 2015-09-30 2017-04-05 Dispositivos No Invasivos Para Diagnosis, S.L. Non-invasive insulin delivery team
US20180271423A1 (en) * 2015-10-07 2018-09-27 The University Of Toledo A biosensor device to detect target analytes in situ, in vivo, and/or in real time, and methods of making and using the same
US11666702B2 (en) 2015-10-19 2023-06-06 Medtronic Minimed, Inc. Medical devices and related event pattern treatment recommendation methods
US11501867B2 (en) 2015-10-19 2022-11-15 Medtronic Minimed, Inc. Medical devices and related event pattern presentation methods
US10146911B2 (en) 2015-10-23 2018-12-04 Medtronic Minimed, Inc. Medical devices and related methods and systems for data transfer
US10037722B2 (en) 2015-11-03 2018-07-31 Medtronic Minimed, Inc. Detecting breakage in a display element
US10449306B2 (en) 2015-11-25 2019-10-22 Medtronics Minimed, Inc. Systems for fluid delivery with wicking membrane
US10275573B2 (en) 2016-01-13 2019-04-30 Bigfoot Biomedical, Inc. User interface for diabetes management system
US10780223B2 (en) 2016-01-14 2020-09-22 Bigfoot Biomedical, Inc. Adjusting insulin delivery rates
US10589038B2 (en) 2016-04-27 2020-03-17 Medtronic Minimed, Inc. Set connector systems for venting a fluid reservoir
EP4191423A1 (en) * 2016-09-20 2023-06-07 Senseonics, Incorporated Remotely-powered sensing system with multiple sensing devices
EP3515535A1 (en) 2016-09-23 2019-07-31 Insulet Corporation Fluid delivery device with sensor
US11097051B2 (en) 2016-11-04 2021-08-24 Medtronic Minimed, Inc. Methods and apparatus for detecting and reacting to insufficient hypoglycemia response
WO2018096631A1 (en) 2016-11-24 2018-05-31 オリンパス株式会社 Data processing device, computer readable medium, data processing method, and program
US10238030B2 (en) 2016-12-06 2019-03-26 Medtronic Minimed, Inc. Wireless medical device with a complementary split ring resonator arrangement for suppression of electromagnetic interference
US10272201B2 (en) 2016-12-22 2019-04-30 Medtronic Minimed, Inc. Insertion site monitoring methods and related infusion devices and systems
WO2018132578A1 (en) 2017-01-11 2018-07-19 Tandem Diabetes Care, Inc. Electromagnetic signal-based infusion pump control
WO2018136898A1 (en) 2017-01-23 2018-07-26 Abbott Diabetes Care Inc. Systems, devices and methods for analyte sensor insertion
US10532165B2 (en) 2017-01-30 2020-01-14 Medtronic Minimed, Inc. Fluid reservoir and systems for filling a fluid reservoir of a fluid infusion device
US10500135B2 (en) 2017-01-30 2019-12-10 Medtronic Minimed, Inc. Fluid reservoir and systems for filling a fluid reservoir of a fluid infusion device
US10363365B2 (en) 2017-02-07 2019-07-30 Medtronic Minimed, Inc. Infusion devices and related consumable calibration methods
US10552580B2 (en) 2017-02-07 2020-02-04 Medtronic Minimed, Inc. Infusion system consumables and related calibration methods
US10646649B2 (en) 2017-02-21 2020-05-12 Medtronic Minimed, Inc. Infusion devices and fluid identification apparatuses and methods
US11207463B2 (en) 2017-02-21 2021-12-28 Medtronic Minimed, Inc. Apparatuses, systems, and methods for identifying an infusate in a reservoir of an infusion device
WO2018175489A1 (en) 2017-03-21 2018-09-27 Abbott Diabetes Care Inc. Methods, devices and system for providing diabetic condition diagnosis and therapy
US10057395B1 (en) 2017-08-27 2018-08-21 Carydean Enterprises LLC Case for a mobile electronic device
US10035010B1 (en) 2017-09-28 2018-07-31 Carydean Enterprises LLC Systems and methods for drug delivery
US11331022B2 (en) 2017-10-24 2022-05-17 Dexcom, Inc. Pre-connected analyte sensors
CA3077720A1 (en) 2017-10-24 2019-05-02 Dexcom, Inc. Pre-connected analyte sensors
WO2019213493A1 (en) 2018-05-04 2019-11-07 Insulet Corporation Safety constraints for a control algorithm-based drug delivery system
US10852268B2 (en) 2018-08-29 2020-12-01 Medtronic, Inc. Electrochemical sensor including multiple work electrodes and common reference electrode
US11744492B2 (en) 2018-08-29 2023-09-05 Medtronic, Inc. Electrochemical sensor including multiple work electrodes and common reference electrode
CN112789070A (en) 2018-09-28 2021-05-11 英赛罗公司 Mode of activity of the artificial pancreas System
EP3864668A1 (en) 2018-10-11 2021-08-18 Insulet Corporation Event detection for drug delivery system
WO2020171838A1 (en) 2019-02-19 2020-08-27 Tandem Diabetes Care, Inc. System and method of pairing an infusion pump with a remote control device
US11305057B2 (en) 2019-03-26 2022-04-19 Tandem Diabetes Care, Inc. Method and system of operating an infusion pump with a remote control device
USD1002852S1 (en) 2019-06-06 2023-10-24 Abbott Diabetes Care Inc. Analyte sensor device
US11801344B2 (en) 2019-09-13 2023-10-31 Insulet Corporation Blood glucose rate of change modulation of meal and correction insulin bolus quantity
US11833329B2 (en) 2019-12-20 2023-12-05 Insulet Corporation Techniques for improved automatic drug delivery performance using delivery tendencies from past delivery history and use patterns
AU2020416271A1 (en) 2019-12-30 2022-08-25 JNTL Consumer Health I (Switzerland) GmbH Systems and methods for assisting individuals in a behavioral-change program
US11551802B2 (en) 2020-02-11 2023-01-10 Insulet Corporation Early meal detection and calorie intake detection
US11547800B2 (en) 2020-02-12 2023-01-10 Insulet Corporation User parameter dependent cost function for personalized reduction of hypoglycemia and/or hyperglycemia in a closed loop artificial pancreas system
US11324889B2 (en) 2020-02-14 2022-05-10 Insulet Corporation Compensation for missing readings from a glucose monitor in an automated insulin delivery system
US11607493B2 (en) 2020-04-06 2023-03-21 Insulet Corporation Initial total daily insulin setting for user onboarding
US11684716B2 (en) 2020-07-31 2023-06-27 Insulet Corporation Techniques to reduce risk of occlusions in drug delivery systems
USD999913S1 (en) 2020-12-21 2023-09-26 Abbott Diabetes Care Inc Analyte sensor inserter
US11904140B2 (en) 2021-03-10 2024-02-20 Insulet Corporation Adaptable asymmetric medicament cost component in a control system for medicament delivery
US11738144B2 (en) 2021-09-27 2023-08-29 Insulet Corporation Techniques enabling adaptation of parameters in aid systems by user input
US11439754B1 (en) 2021-12-01 2022-09-13 Insulet Corporation Optimizing embedded formulations for drug delivery

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995007048A1 (en) * 1993-09-04 1995-03-16 Marcus Besson Wireless medical diagnosis and monitoring equipment
WO1995028878A1 (en) * 1994-04-25 1995-11-02 Minimed Inc. Infusion pump and glucose sensor assembly
EP0680727A1 (en) * 1994-05-05 1995-11-08 Roche Diagnostics GmbH Analysing system for monitoring the concentration of an analyte in the blood of a patient
WO1996000110A1 (en) * 1994-06-24 1996-01-04 Cygnus, Inc. Iontophoretic sampling device and method

Family Cites Families (65)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4178916A (en) 1977-09-26 1979-12-18 Mcnamara Elger W Diabetic insulin alarm system
US4509531A (en) 1982-07-28 1985-04-09 Teledyne Industries, Inc. Personal physiological monitor
DE3501534A1 (en) 1984-09-22 1986-05-15 Walter Ing.(grad.) 7758 Meersburg Holzer METHOD AND DEVICE FOR DOSING INSULIN OR SIMILAR LONG-TERM MEDICINES
US4703756A (en) 1986-05-06 1987-11-03 The Regents Of The University Of California Complete glucose monitoring system with an implantable, telemetered sensor module
US4796636A (en) * 1987-09-10 1989-01-10 Nippon Colin Co., Ltd. Noninvasive reflectance oximeter
US5362307A (en) 1989-01-24 1994-11-08 The Regents Of The University Of California Method for the iontophoretic non-invasive-determination of the in vivo concentration level of an inorganic or organic substance
WO1989006989A1 (en) 1988-01-29 1989-08-10 The Regents Of The University Of California Iontophoretic non-invasive sampling or delivery device
US5062841A (en) 1988-08-12 1991-11-05 The Regents Of The University Of California Implantable, self-regulating mechanochemical insulin pump
US5063081A (en) * 1988-11-14 1991-11-05 I-Stat Corporation Method of manufacturing a plurality of uniform microfabricated sensing devices having an immobilized ligand receptor
US5112614A (en) 1989-09-14 1992-05-12 Alza Corporation Implantable delivery dispenser
US5140985A (en) 1989-12-11 1992-08-25 Schroeder Jon M Noninvasive blood glucose measuring device
US5115805A (en) 1990-02-23 1992-05-26 Cygnus Therapeutic Systems Ultrasound-enhanced delivery of materials into and through the skin
US5077753A (en) 1990-04-09 1991-12-31 Proxim, Inc. Radio communication system using spread spectrum techniques
US5113869A (en) * 1990-08-21 1992-05-19 Telectronics Pacing Systems, Inc. Implantable ambulatory electrocardiogram monitor
US5956501A (en) 1997-01-10 1999-09-21 Health Hero Network, Inc. Disease simulation system and method
US5558638A (en) 1993-04-30 1996-09-24 Healthdyne, Inc. Patient monitor and support system
AU7210894A (en) 1993-06-25 1995-01-17 Xircom, Inc. Virtual carrier detection for wireless local area network with distributed control
CA2167393A1 (en) 1993-07-16 1995-01-26 Nooshin T. Azimi Noninvasive glucose monitor
US5363632A (en) * 1993-08-13 1994-11-15 Equine Textiles, Inc. Equine athletic boot with inflatable U-shaped bladder
AU7828694A (en) * 1993-08-24 1995-03-22 Mark R. Robinson A robust accurate non-invasive analyte monitor
US5692501A (en) 1993-09-20 1997-12-02 Minturn; Paul Scientific wellness personal/clinical/laboratory assessments, profile and health risk managment system with insurability rankings on cross-correlated 10-point optical health/fitness/wellness scales
US5485847A (en) * 1993-10-08 1996-01-23 Nellcor Puritan Bennett Incorporated Pulse oximeter using a virtual trigger for heart rate synchronization
US5458140A (en) * 1993-11-15 1995-10-17 Non-Invasive Monitoring Company (Nimco) Enhancement of transdermal monitoring applications with ultrasound and chemical enhancers
US5417222A (en) * 1994-01-21 1995-05-23 Hewlett-Packard Company Patient monitoring system
EP0672427A1 (en) 1994-03-17 1995-09-20 Siemens-Elema AB System for infusion of medicine into the body of a patient
US5771890A (en) 1994-06-24 1998-06-30 Cygnus, Inc. Device and method for sampling of substances using alternating polarity
US5462051A (en) * 1994-08-31 1995-10-31 Colin Corporation Medical communication system
IE72524B1 (en) 1994-11-04 1997-04-23 Elan Med Tech Analyte-controlled liquid delivery device and analyte monitor
BR9608465A (en) 1995-05-08 1998-12-29 Massachusetts Inst Technology Wireless communication system and computer system
US5721783A (en) * 1995-06-07 1998-02-24 Anderson; James C. Hearing aid with wireless remote processor
US5995860A (en) 1995-07-06 1999-11-30 Thomas Jefferson University Implantable sensor and system for measurement and control of blood constituent levels
DK0840597T3 (en) 1995-07-12 2004-01-26 Cygnus Therapeutic Systems hydrogel
US5989409A (en) 1995-09-11 1999-11-23 Cygnus, Inc. Method for glucose sensing
US5735273A (en) 1995-09-12 1998-04-07 Cygnus, Inc. Chemical signal-impermeable mask
US5741211A (en) 1995-10-26 1998-04-21 Medtronic, Inc. System and method for continuous monitoring of diabetes-related blood constituents
JP3316820B2 (en) 1995-12-28 2002-08-19 シィグナス インコーポレィティド Apparatus and method for continuous monitoring of a physiological analyte of a subject
US5954685A (en) 1996-05-24 1999-09-21 Cygnus, Inc. Electrochemical sensor with dual purpose electrode
AU3596597A (en) * 1996-07-08 1998-02-02 Animas Corporation Implantable sensor and system for in vivo measurement and control of fluid constituent levels
US5882300A (en) 1996-11-07 1999-03-16 Spacelabs Medical, Inc. Wireless patient monitoring apparatus using inductive coupling
US6032119A (en) 1997-01-16 2000-02-29 Health Hero Network, Inc. Personalized display of health information
US6159147A (en) 1997-02-28 2000-12-12 Qrs Diagnostics, Llc Personal computer card for collection of real-time biological data
US6139718A (en) 1997-03-25 2000-10-31 Cygnus, Inc. Electrode with improved signal to noise ratio
US6277067B1 (en) * 1997-04-04 2001-08-21 Kerry L. Blair Method and portable colposcope useful in cervical cancer detection
JP3523021B2 (en) 1997-06-20 2004-04-26 株式会社吉野工業所 Container
US6018674A (en) * 1997-08-11 2000-01-25 Datex-Ohmeda, Inc. Fast-turnoff photodiodes with switched-gain preamplifiers in photoplethysmographic measurement instruments
US5982297A (en) 1997-10-08 1999-11-09 The Aerospace Corporation Ultrasonic data communication system
FI107080B (en) 1997-10-27 2001-05-31 Nokia Mobile Phones Ltd measuring device
WO1999040848A1 (en) 1998-02-17 1999-08-19 Abbott Laboratories Interstitial fluid collection and monitoring device
US6059736A (en) * 1998-02-24 2000-05-09 Tapper; Robert Sensor controlled analysis and therapeutic delivery system
US6134461A (en) 1998-03-04 2000-10-17 E. Heller & Company Electrochemical analyte
US6587705B1 (en) 1998-03-13 2003-07-01 Lynn Kim Biosensor, iontophoretic sampling system, and methods of use thereof
US6024699A (en) * 1998-03-13 2000-02-15 Healthware Corporation Systems, methods and computer program products for monitoring, diagnosing and treating medical conditions of remotely located patients
US6175752B1 (en) 1998-04-30 2001-01-16 Therasense, Inc. Analyte monitoring device and methods of use
CA2311487C (en) 1998-05-13 2004-02-10 Cygnus, Inc. Signal processing for measurement of physiological analytes
CA2329411C (en) 1998-05-13 2004-01-27 Cygnus, Inc. Collection assemblies for transdermal sampling system
CA2332112C (en) 1998-05-13 2004-02-10 Cygnus, Inc. Monitoring of physiological analytes
US6272364B1 (en) 1998-05-13 2001-08-07 Cygnus, Inc. Method and device for predicting physiological values
US6248067B1 (en) * 1999-02-05 2001-06-19 Minimed Inc. Analyte sensor and holter-type monitor system and method of using the same
CA2365609A1 (en) * 1999-02-12 2000-08-17 Cygnus, Inc. Devices and methods for frequent measurement of an analyte present in a biological system
US6416471B1 (en) 1999-04-15 2002-07-09 Nexan Limited Portable remote patient telemonitoring system
US6454708B1 (en) 1999-04-15 2002-09-24 Nexan Limited Portable remote patient telemonitoring system using a memory card or smart card
US6442410B1 (en) 1999-06-10 2002-08-27 Georgia Tech Research Corp. Non-invasive blood glucose measurement system and method using optical refractometry
US6277071B1 (en) 1999-06-25 2001-08-21 Delphi Health Systems, Inc. Chronic disease monitor
US6221011B1 (en) 1999-07-26 2001-04-24 Cardiac Intelligence Corporation System and method for determining a reference baseline of individual patient status for use in an automated collection and analysis patient care system
US6196046B1 (en) 1999-08-25 2001-03-06 Optiscan Biomedical Corporation Devices and methods for calibration of a thermal gradient spectrometer

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995007048A1 (en) * 1993-09-04 1995-03-16 Marcus Besson Wireless medical diagnosis and monitoring equipment
WO1995028878A1 (en) * 1994-04-25 1995-11-02 Minimed Inc. Infusion pump and glucose sensor assembly
EP0680727A1 (en) * 1994-05-05 1995-11-08 Roche Diagnostics GmbH Analysing system for monitoring the concentration of an analyte in the blood of a patient
WO1996000110A1 (en) * 1994-06-24 1996-01-04 Cygnus, Inc. Iontophoretic sampling device and method

Cited By (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6595919B2 (en) 1998-05-13 2003-07-22 Cygnus, Inc. Device for signal processing for measurement of physiological analytes
US7295867B2 (en) 1998-05-13 2007-11-13 Animas Corporation Signal processing for measurement of physiological analytes
US7163511B2 (en) 1999-02-12 2007-01-16 Animas Technologies, Llc Devices and methods for frequent measurement of an analyte present in a biological system
US6561978B1 (en) 1999-02-12 2003-05-13 Cygnus, Inc. Devices and methods for frequent measurement of an analyte present in a biological system
US6925393B1 (en) * 1999-11-18 2005-08-02 Roche Diagnostics Gmbh System for the extrapolation of glucose concentration
US6633772B2 (en) 2000-08-18 2003-10-14 Cygnus, Inc. Formulation and manipulation of databases of analyte and associated values
WO2002015778A1 (en) * 2000-08-18 2002-02-28 Cygnus, Inc. Analyte monitoring device alarm augmentation system
WO2002017210A2 (en) * 2000-08-18 2002-02-28 Cygnus, Inc. Formulation and manipulation of databases of analyte and associated values
US7024236B2 (en) 2000-08-18 2006-04-04 Animas Technologies Llc Formulation and manipulation of databases of analyte and associated values
WO2002017210A3 (en) * 2000-08-18 2003-03-27 Cygnus Therapeutic Systems Formulation and manipulation of databases of analyte and associated values
US6941163B2 (en) 2000-08-18 2005-09-06 Cygnus, Inc. Formulation and manipulation of databases of analyte and associated values
US7228163B2 (en) 2000-08-28 2007-06-05 Animas Technologies, Llc Methods of monitoring glucose levels in a subject and uses thereof
WO2002018936A3 (en) * 2000-08-28 2003-03-27 Cygnus Therapeutic Systems Methods of monitoring glucose levels in a subject and uses thereof
US6862466B2 (en) 2000-08-28 2005-03-01 Cygnus, Inc. Methods of monitoring glucose levels in a subject and uses thereof
WO2002018936A2 (en) * 2000-08-28 2002-03-07 Cygnus, Inc. Methods of monitoring glucose levels in a subject and uses thereof
EP2272562A1 (en) * 2000-10-16 2011-01-12 Remon Medical Technologies Ltd. Acoustic switch and apparatus for using acoustic switches within a body
USRE42378E1 (en) 2000-10-16 2011-05-17 Remon Medical Technologies, Ltd. Implantable pressure sensors and methods for making and using them
US8934972B2 (en) 2000-10-16 2015-01-13 Remon Medical Technologies, Ltd. Acoustically powered implantable stimulating device
US7024248B2 (en) 2000-10-16 2006-04-04 Remon Medical Technologies Ltd Systems and methods for communicating with implantable devices
WO2002032502A1 (en) * 2000-10-16 2002-04-25 Remon Medical Technologies Ltd. Acoustic switch and apparatus and methods for using acoustic switches within a body
EP1410206A1 (en) * 2001-02-15 2004-04-21 I-Medik, Inc. Wireless internet bio-telemetry monitoring system and interface
EP1410206A4 (en) * 2001-02-15 2006-08-09 Medik Inc I Wireless internet bio-telemetry monitoring system and interface
US7272433B2 (en) 2001-04-30 2007-09-18 Medtronic, Inc. Transcutaneous monitor and method of use, using therapeutic output from an implanted medical device
EP1395172A4 (en) * 2001-05-18 2006-03-22 Spectrx Inc System and method for monitoring or treating a health condition
EP1395172A2 (en) * 2001-05-18 2004-03-10 SPECTRX, Inc. System and method for monitoring or treating a health condition
US6849237B2 (en) 2001-05-18 2005-02-01 Polymer Technology Systems, Inc. Body fluid test apparatus with detachably mounted portable tester
WO2002094092A1 (en) * 2001-05-18 2002-11-28 Polymer Technology Systems, Inc. Body fluid test apparatus with detachably mounted portable tester
US10016134B2 (en) 2001-08-13 2018-07-10 Novo Nordisk A/S Portable device and method of communicating medical data information
EP1423046B2 (en) 2001-08-13 2015-03-25 Novo Nordisk A/S Portable device of communicating medical data information
EP1468109A4 (en) * 2001-12-17 2005-01-12 Powderject Res Ltd Non- or minimally invasive monitoring methods
EP1468109A1 (en) * 2001-12-17 2004-10-20 Powderject Research Limited Non- or minimally invasive monitoring methods
WO2003082098A2 (en) 2002-03-22 2003-10-09 Cygnus, Inc. Improving performance of an analyte monitoring device
EP1350460A3 (en) * 2002-03-25 2004-03-10 Matsushita Electric Industrial Co., Ltd. Vital sign detection sensor and sensor controlling device
EP1350460A2 (en) * 2002-03-25 2003-10-08 Matsushita Electric Industrial Co., Ltd. Vital sign detection sensor and sensor controlling device
WO2004008956A3 (en) * 2002-07-24 2004-04-22 Medtronic Minimed Inc System for providing blood glucose measurements to an infusion device
US8568357B2 (en) 2002-07-24 2013-10-29 Medtronic Minimed, Inc. System for providing blood glucose measurements to an infusion device
US8192395B2 (en) 2002-07-24 2012-06-05 Medtronic Minimed, Inc. System for providing blood glucose measurements to an infusion device
US6931328B2 (en) 2002-11-08 2005-08-16 Optiscan Biomedical Corp. Analyte detection system with software download capabilities
US8622954B2 (en) 2002-12-19 2014-01-07 Medtronic Minimed, Inc. Relay device for transferring information between a sensor system and a fluid delivery system
WO2004062493A1 (en) * 2003-01-06 2004-07-29 Optiscan Biomedical Corporation Wearable device for measuring analyte concentration
US7149581B2 (en) 2003-01-31 2006-12-12 Medtronic, Inc. Patient monitoring device with multi-antenna receiver
WO2004066834A1 (en) * 2003-01-31 2004-08-12 Medtronic, Inc. Patient monitoring device with multi-antenna receiver
US8852099B2 (en) 2004-09-17 2014-10-07 Cardiac Pacemakers, Inc. Systems and methods for deriving relative physiologic measurements
JP2008522703A (en) * 2004-12-13 2008-07-03 コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ Mobile monitoring
US8663201B2 (en) 2005-08-16 2014-03-04 Medtronic Minimed, Inc. Infusion device
WO2007021892A1 (en) * 2005-08-16 2007-02-22 Medtronic Minimed, Inc. Hand-held controller device for an infusion pump
WO2008016486A3 (en) * 2006-07-31 2008-04-10 Medtronic Minimed Inc Watch controller for a medical device
WO2008016486A2 (en) * 2006-07-31 2008-02-07 Medtronic Minimed, Inc. Watch controller for a medical device
US9024582B2 (en) 2008-10-27 2015-05-05 Cardiac Pacemakers, Inc. Methods and systems for recharging an implanted device by delivering a section of a charging device adjacent the implanted device within a body
WO2014045451A1 (en) * 2012-09-24 2014-03-27 テルモ株式会社 Sensor unit and measurement system

Also Published As

Publication number Publication date
EP1135052A1 (en) 2001-09-26
US20030144581A1 (en) 2003-07-31
US7163511B2 (en) 2007-01-16
AU3363000A (en) 2000-08-29
US6561978B1 (en) 2003-05-13
JP2002536103A (en) 2002-10-29
CA2365609A1 (en) 2000-08-17

Similar Documents

Publication Publication Date Title
US6561978B1 (en) Devices and methods for frequent measurement of an analyte present in a biological system
US6553244B2 (en) Analyte monitoring device alarm augmentation system
JP3454789B2 (en) Method and device for predicting physiological values
CA2346055C (en) Method and device for predicting physiological values
US6180416B1 (en) Method and device for predicting physiological values
US7699775B2 (en) Methods for estimating analyte-related signals, microprocessors comprising programming to control performance of the methods, and analyte monitoring devices employing the methods
US6999810B2 (en) Biosensor and methods of use thereof
EP1309271A1 (en) Methods and devices for prediction of hypoglycemic events
US20220233116A1 (en) Systems, devices, and methods related to ketone sensors

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
ENP Entry into the national phase

Ref country code: JP

Ref document number: 2000 598064

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: 2000911792

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2000911792

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2365609

Country of ref document: CA

Ref country code: CA

Ref document number: 2365609

Kind code of ref document: A

Format of ref document f/p: F

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWR Wipo information: refused in national office

Ref document number: 2000911792

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 2000911792

Country of ref document: EP