WO2005028358A2

WO2005028358A2 - Liquid delivery and flow measurement system and method

Info

Publication number: WO2005028358A2
Application number: PCT/US2004/030100
Authority: WO
Inventors: Burton H. Sage, Jr.; David Gillett; Brian Catanzaro
Original assignee: Therafuse, Inc.
Priority date: 2003-09-16
Filing date: 2004-09-15
Publication date: 2005-03-31
Also published as: EP1677869A2; WO2005028358A3

Abstract

A device and method for accurate delivery of a liquid is described. The device comprises a flow channel through which the liquid flows. During manufacture or at some other point prior to the delivery of the liquid, the flow channel is characterized in terms of one or more properties of flow of a liquid through the channel. This characterization is stored in such a way that the flow channel charaterization is available to the liquid delivery device at time of use. At time of use, the liquid delivery system reads the stored flow channel characterization and uses the stored flow channel characterization for safe and accurate delivery of the liquid. Moreover, systems and methods for measuring the flow of a fluid along a passageway are disclosed. A heat source applies thermal energy to a portion of the fluid thereby elevating its temperature and decreasing its density. An optical sensing means

Description

LIQUID DELIVERY AND FLOW MEASUREMENT SYSTEM AND METHOD

[0001] This application is a continuation-in-part and claims priority to and claims subject matter disclosed in copending U.S. Patent Application number 10/662,871 entitled Compensating Liquid Delivery System and Method, filed on September 16, 2003, and U.S. Patent Application number 10/786,562 entitled Liquid Metering System filed on February 26, 2004, the contents of these applications being incorporated by reference herein in their entirety.

[0002] This application also incorporates by reference in their entirety the contents of U.S. Patent application numbers 10/146,588 filed May 15, 2002 and 10/600,296 filed June 20, 2003, which is a continuation-in-part of U.S. Patent Application number 09/867,003 filed May 29, 2001, now U.S. Patent No 6,582,393, issued June 24, 20O3. the contents of all of these applications being incorporated by reference herein in their entirety. This application also incorporates by reference in their entirety the contents U.S. Patent No 6,582,393, issued June 24, 2003.

FIELD OF THE INVENTION

[0003] This invention relates generally to liquid delivery systems and more particularly to compensating infusion systems, the measurement of properties of fluids moving in a passageway and the measurement of the flow rate of a fluid.

BACKGROUND OF THE INVENTION

[0004] Accurate delivery of liquids, particularly in the field of infusion of medical liquids, and especially in the field of IV infusion of pharmaceuticals, is becoming more and more critical as the potency of infusible therapeutic agents continues to increase. Historically, IV infusions were performed with the active ingredient dissolved in an appropriate vehicle hanging in a bag from a pole above the patient. Such gravity bag infusion, while able to provide the medical liquid to the patient in a continuous fashion, suffered from accuracy problems. Because the driving force is derived from the distance the solution in the bag is above the infusion site, the driving force would change with any change in distance, such as when the bag empties of solution, when the patient moved from a prone position to lying on a side, and especially when the patient arose from bed.

[0005] The rate of infusion would also change with temperature due to changes in the viscosity of the medical liquid, and could drastically change when different medical liquids were used. Further, the rate of infusion would change significantly when different infusion sets were used due to the manufacturing tolerances of the inside diameter of the flow tube. While the user of a gravity bag infusion set could adjust the infusion rate using a roller clamp on the tube and counting the drips per second in a drip chamber included in the infusion set, the accuracy of such an adjustment was qualitative at best.

[0006] To overcome these limitations, positive displacement pumps have replaced gravity bags for the infusion of medical liquids, especially for those liquids where precise control of the delivery rate is important. These positive displacement pumps include syringe pumps, where the volume of fluid to be infused is relatively small and peristaltic pumps where the volume of the medical liquid to be infused is relatively large. Positive displacement pumps are designed in such a way that a fixed volume of liquid is delivered independent of the pressure required to deliver the liquid or the viscosity of the delivered liquid. With these two variables removed, infusion pumps overcame two of the major obstacles to accurate delivery which are inherent in gravity bag infusion systems.

[0007] These positive displacement medical liquid infusion systems are "open-loop" systems in that they rely on the dimensional accuracy of system components to achieve accurate delivery. For syringe pumps, for example, the accuracy of delivery is mainly dependent on the inside diameter of the barrel of the syringe in use. Since the accuracy depends on the square of the inside diameter, it is important to manufacture these syringes with close tolerances. For peristaltic pumps, the accuracy of delivery depends on the inside diameter of the flow tube at the site where the peristaltic pumping occurs. Again, the delivery accuracy depends on the inside diameter of the flow tube to the second power, so manufacturing tolerances are relatively tight.

[0008] If system components are used that are outside of the specification range, such positive displacement systems will inaccurately deliver the medical liquid. In such an instance, there is no provision to correct or compensate for the out of range dimension. In an attempt to address this problem, closed loop medical liquid infusion systems have been described (see, e.g., Frank U.S. Patent No. 5,211,626). This system measures the flow rate of the medical liquid along the flow channel and then adjusts the position of a proportional valve to achieve the desired flow rate. This closed loop system, however, fails to distinguish between changes in flow rate due to temperature, viscosity, or flow channel dimensions. Because the flow rate has differing exponential dependence for these flow rate variables, the calculated valve adjustment is usually incorrect, resulting in inaccurate infusion of the medical liquid. [0009] Despite the transition from simple and inexpensive gravity bags, the complicated and expensive infusion pumps typically fail to achieve highly accurate delivery or to provide evidence that the desired drug delivery is occurring or has occurred (other than that the motor is operating or has operated). The actual flow rate remains unverified and uncompensated.

[0010] Many methods of measuring the flow rate of fluids, and in particular the rate of infusion of a pharmaceutical to a patient are known. Best known are positive displacement systems (see above) wherein a known volume of fluid is moved over time independent of other system parameters such as pressure and liquid viscosity. Today, the most commonly used positive displacement pump for accurate infusion of a pharmaceutical to a patient is the syringe pump. A motor moves a plunger down the barrel of a syringe with tightly controlled manufacturing tolerances on inside diameter. The rate of advance of the plunger times the time of advance times the cross-sectional area of the syringe determines the volume of fluid infused. This positive displacement method is used, for example, in the MiniMed Model 508 insulin pump, which typically has a retail price in excess of 5,000.00 U.S. Dollars. A second example of a positive displacement system is the peristaltic pump, where rollers placed against a flexible conduit roll along the conduit to move the fluid down the conduit. In peristaltic pumps, enough force is applied to the liquid in the flexible conduit to eliminate any dependence on pressure and viscosity. However, the volume of liquid dispensed remains dependent on the volume of fluid in the tubing, which depends on the square of the inside diameter of the elastomeric tubing. Since the manufacturing tolerance on the inside diameter of economic elastomeric tubing is on the order of +/- 10%, the delivery accuracy is limited to +/- 20%. Peristaltic pumps are also expensive, but somewhat less expensive than syringe pumps. [0011] Given the expense of these positive displacement pumps, and the need to find less expensive systems for accurate delivery of pharmaceuticals, other devices and methods have been proposed to maintain the required level of accuracy while reducing the cost. It is clear that many of these proposed systems achieve the goal of reduced expense. However, the problem that these proposed schemes face is that they do not achieve an improved accuracy of delivery of the pharmaceutical. For example, in a liquid dispensing system with a pressurized liquid container where the pressure on the liquid forces it along the conduit, the parameters dictating the flow include the pressure that is causing the liquid to flow, the inside diameter of the conduit along which the liquid is flowing, the length of the conduit, and the viscosity of the liquid, which is in turn dependent on the temperature of the liquid. This problem is further compounded by the fact that the dependence on the inside diameter of the conduit is a fourth power dependence. In many delivery systems of this type, the pressure on the liquid decreases as the amount of liquid in the container decreases, leading to a reduction in the flow rate. The solution to this pressure decrease is known. O 'Boyle in US Patent 4,874,386 teaches a liquid dispensing device that accurately controls the pressure in this type of dispensing system by incorporating a constant pressure spring. But the dimensions of the flow conduit, its cross section, and the temperature for viscosity control are left uncontrolled, with the result of inaccurate dispensing of the fluid.

[0012] In order to overcome the situation of having to manufacture dispensing system components to higher tolerances than is economically feasible, other methods of measuring the liquid flow rate have been taught. If the actual flow rate is measurable, the flow rate may be adjusted to the desired flow rate. Or, if an accurate total volume rather than flow rate is required, the required time of flow may be calculated using the actual flow rate to achieve the desired volume. [0013] In general, the different types of liquid flow measuring systems can be divided into two classes — those that require contact with the liquid to measure the flow, and those that measure the flow without requiring contact with the liquid. Flow measuring systems in the first class include a) turbines, where the angular speed of the propeller in the stream is a measure of flow rate, b) pressure drop systems, where the pressure difference across a flow resistor is used to calculate the flow rate, and c) certain forms of "thermal time of flight" systems where elements that add heat to the stream and measure heat in the stream are used to measure flow rate. Examples of these "thermal time of flight" systems are taught by Miller, Jr. in US Patent No. 4,532,811, the contents of which are incorporated by reference herein in their entirety, and by Jerman in US Patent No. 5,533,412, the contents of which are incorporated by reference herein in their entirety. However, in many liquid delivery systems, the conduit along which the liquid flows requires frequent replacement and, in the case of pharmaceutical infusion systems, the total flow path must also be kept sterile. In this first class of types of flow meters, the added complexity of adding components, and their necessary leads and connectors to the replaceable conduits, causes the replacement conduits to be expensive. And if these additional components are added to a reusable portion of the dispensing system, the replacement of the liquid container, or addition of fresh liquid to an existing container opens the flow path to an unsterile environment. For these reasons, attention has been paid to the second class of flow meters — those that do not require contact with the liquid in the conduit and add complexity to the conduit.

[0014] Kerlin, Jr, in US Patent No. 4,777,368, the contents of which are incorporated by reference herein in their entirety, teaches a method and apparatus for non-contact measurement of the velocity of a moving mass. In an embodiment of the invention, an infrared heat source raises the temperature of an element of the moving mass and an infrared detector, viewing this element of the moving mass at a later time, detects the heated element and records the time required for the moving mass to move from heater to detector. Given the physical separation of the heater and the detector, the speed of the moving mass may be calculated. Kerlin makes reference to the use of this concept for liquids as well as solids. Goldberg, in US Patent 4,938,079, the contents of which are incorporated by reference herein in their entirety, teaches the same basic concept as Kerlin, Jr. with the modification that microwave energy is used to heat the liquid within a conduit and a microwave detector is used to sense the heated liquid downstream from the heater. Frank et al in US Patent No. 5,211,626 (briefly discussed above), the contents of which are incorporated by reference herein in their entirety, also teaches a thermal time of flight flow metering method, and while at least one infrared detector is used to detect the heated liquid, the liquid is heated by thermal contact with the liquid through the wall of the conduit. [0015] In the teachings of US Patent No. 4,777,368, the contents of which are incorporated by reference herein in their entirety, US Patent No. 4,938,079, the contents of which are also incorporated by reference herein in their entirety, and US Patent No. 5,211,626, the contents of which are incorporated by reference herein in their entirety, there are additional practical considerations that make these teachings difficult to reduce to practice in cost-effective commercial products. The first of these practical aspects is the heating of the portion of the liquid to be sensed. Due to the high heat capacity and the rapid thermal diffusivity of many liquids of commercial importance, and especially water, which is the base of virtually all pharmaceutical infusion fluids, heating the liquid fast enough to realize an operational flow meter is very difficult. Kerlin, Jr. in US Patent No. 4,777,368, implicitly recognizes this by advocating a high power CO2 laser. Neither Frank in US Patent No. 5,211,626, nor Goldberg, in US Patent No. 4,938,368, the contents of which are incorporated by reference herein in their entirety, recognize this problem. And the problem is especially acute for Frank since his teachings require the heat to pass through the wall of the conduit by conduction, which is especially time-consuming and lossy. One solution to this problem, which is not alluded to in any of these three teachings, is to stop the flow of the liquid and to heat the liquid while it is stationary. The flow rate is measured by restarting flow once the liquid is heated. The two advantages of stopping the flow to heat the liquid is that the total mass of liquid that must be heated is greatly reduced and the heat pulse is relatively confined in position along the conduit. This solution is taught in US Patent No. 6,582,393 which, as noted above, the contents of which are incorporated by reference herein in their entirety,. [0016] The second practical aspect that makes some prior devices difficult to commercialize is the mode of detecting the heat pulse. Many pharmaceutical solutions, especially protein solutions such as insulin, degrade at temperatures above room temperature, and begin to denature at temperatures above 40 degrees centigrade. An exemplary temperature rise that might avoid such a problem would be less than 5 centigrade degrees above ambient.

[0017] Detection methods relying on detecting the infrared radiation from such a small change in temperature usually need to operate in the far infrared where detectors are either too slow to respond to the heated liquid or must be cooled, making them large, energy consuming and expensive. Yin and Templin in US Patent Nos. 6,386,050, the contents of which are incorporated by reference herein in their entirety, teach an improved thermal time of flight flow monitor that uses a visible light source to detect the presence of heated liquid. In this way, the need for far infrared detectors is avoided. While this method of Yin and Templin may obviate the need for far infrared detectors, it requires a passageway with walls that are essentially optically smooth and flat. Such passageways are relatively expensive, making them unsuitable for systems that need disposable fluid passageways such as drug infusion systems. [0018] Thus there continues to be a need for improved devices and methods for accurate and economical measurement of liquid flow in liquid dispensing systems, especially in the area of infusion of pharmaceutical solutions.

SUMMARY OF THE INVENTION

[0019] In accordance with one embodiment of the present invention, a device for delivering liquid via a flow channel is disclosed. The device includes a memory having a stored value indicative of a flow characteristic of the flow channel, a controller that generates a flow control signal based on the stored value, and a valve responsive to the flow control signal for controlling flow of the liquid. [0020] In accordance with another embodiment, a method of manufacturing a liquid delivery device is disclosed. The method includes (i) coupling a portion of a flow channel of the device to a flow sensor of the device, providing a predetermined liquid for flow through the flow channel, measuring flow-related data of the flow of the predetermined liquid through the flow channel using the flow sensor, and calculating a value of the flow characteristic of the flow channel based on the flow-related data, and storing the value in a memory of the liquid delivery device. [0021] In accordance with yet another embodiment, a method is disclosed for delivering a liquid via a flow channel at a desired flow rate. Flow-related data of the liquid in the flow channel is measured, and a memory is accessed for a flow characteristic of the flow channel stored therein. A value of the flow rate of the liquid is calculated based on the flow-related data and the stored characteristic value, and the calculated value of the flow rate is compared to the desired flow rate. A valve is then controlled to achieve the desired flow rate.

[0022] In some embodiments of the present invention, an accurate system and method of measuring velocity of a liquid in a conduit is used. Thus, an object of some embodiments of the current invention is to provide an accurate, inexpensive, and practical system and method for measuring the velocity of a liquid in a conduit. [0023] It is a further object of some of the embodiments of the present invention to use this system and method for measuring the velocity of a liquid in a conduit to infuse pharmaceutical solutions. This velocity may be used for either accurate delivery of the pharmaceutical solutions or, when zero flow rate is measured, to detect occlusions in the delivery system.

[0024] It is yet another object of some embodiments of the current invention to provide an accurate, inexpensive and practical system and method for detecting and measuring the temperature of a liquid in a conduit.

[0025] Moreover, some embodiments according to the present invention provide for a device and method for measuring the time of flight and or the velocity of a fluid moving in a conduit. The fluid may be a material in the gaseous state or in the liquid state. The apparatus includes a passageway, a portion of which transmits optical radiation. The optical radiation may be ultraviolet, visible, or infrared. A source of heat is positioned to heat a portion of the fluid at a first location in the passageway. The fluid may be in motion or at rest. The heated portion of the fluid as it flows downstream has physical dimensions that are small compared to the dimensions of the cross-section of the passageway. In this context, a small physical dimension is one such that at its edges, the temperature profile of the heated portion results in no substantial increase in temperature at the passageway wall. Downstream from this first location at a second location a light source directs a beam of coherent light onto the fluid in the passageway. The heated portion of the liquid flows through the illumination at the second location, creating a phase object in the beam of illumination. At the second location, a portion of the illumination is diffracted due to the phase object created by the change in density of the heated portion of the liquid. A detector is positioned to detect a change in intensity of the illumination due to the diffraction of the illumination when the heated portion of the fluid passes through the illumination.

[0026] The heating of the portion of the fluid at the first location may occur at a first time. The detection of the heated portion of the fluid when it passes through the illumination at the downstream second location occurs at a second later time. When the time difference between the second time and the first time (the thermal time of flight) is divided into the distance of separation between the first location and the second location, a velocity of the liquid is calculated.

[0027] Other aspects and advantages of some of the embodiments of the present invention will become apparent from the following detailed description and drawings of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 is a schematic representation of a drug delivery system involving a patient receiving intravenous therapy from a gravity bag.

[0029] Figure 2 is a schematic representation of an infusion set of the drug delivery system of Figure 1 having a flow channel, the flow characteristic of which is used in connection with the teachings of one or more embodiments of the present invention. [0030] Figure 3 is a schematic representation of a flow regulator of the drug delivery system of Figure 1 where the flow regulator is mated with a flow cell inserted into the infusion line in accordance with the teachings of one embodiment of the present invention.

[0031] Figure 4 is a schematic representation of a liquid delivery device in accordance with one embodiment of the present invention.

[0032] Figure 5 is a schematic representation of a flow regulator of the drug delivery system of Figure 1 where the flow regulator is mated with a flow cell inserted into the infusion line in accordance with the teachings of a second embodiment of the present invention.

[0033] Figure 6 is a schematic representation of a manufacturing fixture of the flow channel of figure 6 where the flow characteristic of the flow channel is measured in accordance with the teachings of the present invention.

[0034] Figure 7 presents a functional block diagram of a liquid dispensing system with a flow meter designed according to the invention.

[0035] Figure 8 is a schematic of an optical schematic of the liquid flow meter of figure 6 showing an increment of liquid being heated.

[0036] Figure 9 is a schematic of an optical schematic of the liquid flow meter of figure 6 showing a heated increment of fluid flowing toward a position where it can be detected by diffraction of light.

[0037] Figure 10 is a schematic of an optical schematic of the liquid flow meter of figure 6 showing the heated increment of fluid in a position where it can be detected by diffraction of light.

[0038] Figure 11 presents a time sequence of the output of a line array detector showing the far field pattern of light before, during, and after the passage or presence of a heated increment of liquid.

[0039] Figure 12 presents the output of a line array detector showing the far field pattern of light at a time before the passage of the heated fluid and at a time during the passage of the heated fluid. DETAILED DESCRIPTION OF SOME EMBODIMENTS

[0040] In accordance with the practice of one embodiment of the invention, a liquid delivery system is disclosed that provides accurate delivery of the liquid despite variability in one or more factors otherwise determinative of flow rate, such as by way of example and not by way of limitation, the dimensions of flow system components, driving force (e.g., pressure), and fluid viscosity. Compensating for such variables enables, for instance, cost-efficient, accurate delivery of infusible medical fluids from a gravity bag without the use of a positive displacement infusion pump. It is noted that practice of the present invention is not limited to the IV or continuous infusion context. One or more embodiments of the invention has applicability to the delivery of a broad range of medical fluid and non-medical fluid contexts in either a continuous or discontinuous (e.g., pulsed) manner. Moreover, one of the advantages of the degree to which the disclosed device and method provides compensated liquid, delivery is the ability to use the same infusion device for accurate delivery of a number of liquids without the need to reconfigure, recalibrate or otherwise modify the device in preparation for use.

[0041] In accordance with one embodiment, a drug delivery device is disclosed for use with an infusion set that contains a flow channel having a flow characteristic that is predetermined via, for example, measurement during manufacture or during a calibration step. The drug delivery device has a memory in which the predetermined flow characteristic is stored prior to use or operation of the device. At time of operation or use, the infusion set is mated with a flow regulator capable of reading trie stored flow characteristic and further capable of making similar measurements during use. A valve in the flow regulator is controlled based on the flow measurements an the stored flow characteristic to achieve a desired flow rate.

[0042] Reference is made to Figures 1 and 2. Shown in Figure 1 is a drug infusiotx system for providing intravenous therapy using a gravity bag 11 joined to an infusion set 12 and flowing through a flow regulator 13 to an infusion site 14 at the patient (not shown). Gravity bag 11 may contain any liquid or liquid formulation (e.g., a medicament) in an appropriate vehicle. The gravity bag in one embodiment of the present invention cab be put into service with an appropriate distance of the fluid above the patient's heart to insure acceptable fluid flow. The gravity bag 11 and infusion set 12 may be constructed as is well known in the art with materials used for fabrication in an IV infusion context, such as by way of example and not by limitation, silicones, polyvinyl chlorides and polyolefϊns.

[0043] Figure 2 shows infusion set 12 in greater detail. Infusion set 12 may include a drip chamber (not shown) for visual evidence of fluid flow as is well known in the art. In one embodiment, infusion set 12 includes flow channel assembly 23. Flow channel assembly 23 comprises a flow channel 24 through which the medical liquid flows to the patient. Flow channel 24 also comprises read write memory 25 for storing a characteristic of liquid flow measured during manufacture or otherwise prior to operation.

[0044] With reference now to Figure 3, flow regulator 13 is shown mated to infusion set 12 at the location on infusion set 12 where flow channel assembly 23 is located. This mating can be, in some embodiments, made with a latching mechanism, which may be mechanical or magnetic as is well known in the art, so that the various components of flow regulator 13 and flow channel 23 are held in place once the mating has occurred. Once properly mated, some embodiments of flow regulator 13 are capable of making measurements of properties of flow in flow channel 24. Some examples of methods of making measurements of properties of flow are described in co-pending and commonly assigned Application Serial No. 10/600,296 (entitled "Compensating Drug Delivery System"), the contents of which is incorporated by reference in its entirety.

[0045] Access to the patient's body at infusion site 14 is made with a body access device (not shown) which may by way of example and not by limitation, be a traditional stainless steel needle or may soft-set catheters placed with a catheter inserter or may be an array of microneedles.

[0046] Figure 3 shows in greater detail the portion of infusion set 12 where flow channel assembly 23 mates with flow regulator 13. h one embodiment, flow channel assembly 23 is recessed to receive a flow sensor 27 such that it accurately registers with flow sensor 27. Such recesses may be conical in shape, or rectangular with slanted sides, as is well known in the art, so that once mated, optical components (not shown) in flow sensor 27 are aligned with flow channel 24 to make measurements of flow and held in that alignment.

[0047] In use, flow sensor 27 makes measurements of properties of flow along flow channel 24. Such properties include, but are not limited to volumetric flow rate, the velocity of the fluid flow, and the time required for an increment of volume to flow a prescribed distance along the flow channel (time of flight). Some methods and devices for measuring time of flight of fluids are described in detail in the above- identified application.

[0048] Flow channel 24 also is coupled to read/write memory 25 as shown in Figures 2 and 3. In accordance with one embodiment, during manufacture of flow channel 24, a flow sensor essentially identical to flow sensor 27 was used to measure flow properties of a standardized fluid in flow channel 24. In one method of manufacture, the following steps would be used. 1) Flow channel 24 would be fabricated. 2) Read/write memory device 25 would be fabricated. 3) Flow channel 24 and read/write memory device 25 would be assembled into flow channel assembly 23. 4) Flow channel assembly 23 would be mounted in a flow measurement fixture (not shown) and flow properties of flow channel 24 would be measured. 5) The measured flow properties of flow channel 24 would then be stored in read/write memory device 25. Some examples of read/write memories are an RFID (radio frequency identification) chip and a bar code, although other forms of read/write memories may be used. An RFID chip or a bar code might permit the flow properties to be read at time of use without making electrical contact with flow channel assembly 23. 6) Flow channel assembly 23 would be removed from the flow measurement fixture. 7) Flow channel assembly 23 would be cleaned and dried and assembled into infusion set 12.

[0049] At time of use, read/write memory reader 26 of flow regulator 13 reads the flow properties in read/write memory 25. In use, flow sensor 27 makes measurements of some or all of the same flow properties measured during manufacture of the medicament to be delivered. Using the flow measurements of the standardized fluid from read/write memory 25, and the flow measurements of the medicament to be delivered, the actual flow rate can be matched to the flow rate desired by the user, achieving highly accurate delivery of the medicament to the patient in accordance with the calculations set forth herein.

[0050] The flow or processing of information in the compensating drug delivery device is shown in Figure 4. Once flow regulator 13 is mated to infusion set 12, read/write memory reader 26 of flow regulator 13 reads the stored flow characteristics in memory 25 of infusion set 12. During use or operation, when a medical liquid is flowing from gravity bag 11 to the patient at infusion site 14, flow sensor 27 makes measurements of the same flow characteristic and provides the flow characteristic information or data to controller 28. Controller 28 determines, by way of example and not by limitation, through the use of calculations or a look up table, information regarding flow of the medical liquid based on the characteristic stored in memory 25 and the measurement of the characteristic made by flow sensor 27 during use. Using these calculations, controller 28 controls flow control valve 22 to achieve the require flow of the medical liquid to the patient.

[0051] The calculations made by controller 28 can be made in the context of the following principles. In other embodiments of the present invention, some or all of the results of the calculations can be achieved through the use of look up tables. For fluids in laminar flow in a channel with a circular cross section, the volumetric flow rate Q is given by the Poiseuille's equation: Q = πPA² (1) 8τ L

Where Q = flow rate in volume per time P = Pressure A = flow channel effective cross sectional area η = fluid viscosity L = flow channel length [0052] Flow rate Q is also given by AV where again A is the effective cross sectional area of the circular flow tube and V is the average velocity of flow of the fluid down the channel. Please note the use of the words effective and average. This usage is due to the fact that no flow channel is perfectly round or has exactly the same cross sectional area at all points along the flow channel. Because of this variation in cross sectional area, the velocity of the liquid will not be exactly the same at all points along the channel. Note further that A can be expressed in terms of an effective radius R such that A=πR² or in terms of an effective diameter D such that A=πD²/4. [0053] The velocity of flow in a channel can be approximated by the "Thermal Time of Flight" method, described in US patent 6,582,393, the contents of which are incorporated herein by reference in its entirety. In general, the fluid is heated at one point along the channel, and the heated fluid is detected downstream by a heat sensor. The velocity is calculated by measuring the distance downstream from the point of heating to the point of detection and dividing that distance by the elapsed time between heating the fluid and detecting the heated fluid. Letting X equal the separation distance between the point of heating and the point of detection, and T equal the measured time of flight, the flow rate Q = AX/T.

[0054] In a drug delivery system where a reusable flow regulator is mated with a flow channel on a disposable infusion set, the flow regulator might be used with a plurality of unknown flow channels. Given routine manufacturing tolerances of flow channels, their cross sectional area may vary as much as 25%. Further, by way of example and not by limitation, when the source of medicament is a gravity bag, the height of the liquid above the infusion site may vary as well as the height of the liquid surface in the bag. Thus the driving pressure from the elevated fluid will vary. Further still, an intravenous infusion system should provide accurate delivery of many different medicaments which have a wide viscosity range. Thus, some or all of the variables that determine the actual flow rate, such as byway of example: flow channel cross section area, pressure, and viscosity, are all generally unknown. The final variable, the length of the flow tube, can be accurately set during manufacture, and will not be considered further here. (However, the present invention can be used to address variations in tube length as well.) [0055] To address this problem, the following method may be used. In the laboratory, a nominal or standard flow system that is identical or substantially identical to the planned production system except for manufacturing tolerances of the flow tube cross section area is set up. Using the standard AAMI (Association for the Advancement of Medical Instrumentation) protocol, the flow rate through this standard system is measured by weighing the amount of a standard fluid that has been delivered for a fixed period of time. The temperature of the liquid (to establish its viscosity), and the driving pressure are also set at nominal or standard values. A flow tube is also selected to be a reference standard.

[0056] Letting the subscript o denote the nominal, standard or predetermined flow condition, Poiseuille's equation for the nominal or standard setup is given, by: Qo = πPoA₀ ² (2)

[0057] For a randomly selected flow channel measured under these conditions, wherein the subscript 1 is used to denote a randomly selected flow channel, the flow rate is:

Qi ^ πPoAr (3) 8r?₀L [0058] By dividing these two equations, the following useful result is obtained:

[0059] And, using the relationship Q = AX/T, which can be used since pressure and viscosity have been set at standard conditions, it can be shown that

[0060] Thus the flow rate for the randomly selected tube can be determined as Q^ QoTo lΛ² (6)

[0061] The above equation gives the flow rate in the randomly selected tube in terms of the flow rate in the nominal or standard tube, the measured time of flight in the standard tube, and the measured time of flight in the randomly selected tube given the nominal or standard pressure and the nominal liquid at nominal tempera-ture. [0062] A manufacturing fixture 60 that may be used to measure Ti is shown in figure 6. Standard fluid 61 is shown in pressurized container 62. Temperature T₀ is established for the standard fluid flowing through the flow channel being measured 63 and pressure P₀ is established for causing the standard fluid to flow through the flow channel 63. Flow channel 63 is temporarily mated with flow sensor 64 and standard fluid 61 caused to flow through channel 63 and finally to waste through waste pipe 68. When standard fluid 61 is flowing through flow channel 63, time of flight Ti is measured. A manufacturing fixture with many essentially identical flow sensors and the same number of mating sites for flow channels could be created such that Ti for many flow channels could be measured at the same time. Processor 65 calculates Qi using Ti, Qo, and T₀ and loads all four factors into read/write memory 66 using read/write memory writer 67. Factors Q₀ and T₀ may also be carried as part of the programming in flow regulator 13. In some embodiments of the present invention, these measurements may be used, by way of example and not by limitation, for the purposes of quality control; rejecting flow channels where the measured time of flight and flow rate are outside established specification ranges. Read/write memory 66 may also contain inventory information such as date of manufacture, expiration date, lot number, and other such quality control information as may be necessary. This information would also be written into read/write memory 66 by read/write memory writer 67.

[0063] When infusion set 12 with flow channel 24 is mated with flow regulator 13 as shown in figure 3, read/write memory reader 26, which reads the information stored in read/write memory 25, reads Ti and flow rate Q . As a practical matter, the acceptable specification ranges for Qi would be set higher than any expected delivery rate for the infusion system because flow control valve 22 can only be closed from its open position, not opened further so that partial closing of valve 22 achieves the desired flow rate.

[0064] In use with an unknown fluid at an unknown pressure, flow sensor 27 would measure an actual time of flight T_a. Using the equation Q = AX/T, the actual flow rate Q_a can be calculated as Q_a = QιTι/T_a since the terms A and X are common. [0065] In some embodiments for intravenous drug delivery, the compensating drug delivery system of the invention is then used in the following way as shown in Figure 1. Using infusion set 12, gravity bag 11 , and roller clamp 18, the infusion set is primed. Once the medication to be delivered appears at the output of infusion set 12, roller clamp 18 would be closed. Flow regulator 13, which has been set to the OFF condition (Position 1 in figure 1), is then mated to flow channel assembly 23 on the infusion set. The Set function of flow regulator 23 is then selected (position 2 of flow regulator 23 in figure 1). This setting causes flow control valve 22 to fully close. Roller clamp 18 is now opened. No flow from the end of infusion set 12 verifies that control valve 22 is closed. The user now sets the end of infusion set 12 in the vein of the patient at infusion site 14 (not shown) and selects the desired flow rate for the medication in gravity bag 11 using the keypad on flow regulator 13. Once the flow rate is selected, the user selects a Run mode (position 3 on flow regulator 13). Once in this Run mode, controller 28 of the flow regulator 13 generates a flow control signal to begin to open flow control valve 22 while directing the flow sensor 27 to make very frequent measurements of time of flight or other such flow parameter as may be appropriate. Since values of Qi and T₁ are stored and available via read/write memory 25 and read/write memory reader 26, and sensor 27 is measuring time of flight T_a, for every measurement of T_a, controller 28 can calculate the actual flow rate Q_a. Based on the actual flow rate, and assuming that the actual flow rate is not the flow rate selected by the user, controller 28 sends a signal to flow control valve 22 to open or close. Flow sensor 27 continues making time of flight measurements, and controller 28 continues to calculate the actual flow rate and adjusting flow control valve 22 until the actual flow rate Q_a matches the selected flow rate within the accuracy limitations of the system. In this embodiment for intravenous delivery of a liquid medicine, once the calculated flow rate is within the required limits of the set flow rate, flow regulator 13 can enter a flow rate maintenance mode, reducing the frequency of measurements of the time of flight to conserve power. [0066] In other embodiments of the present invention, a volume value can be used and thus stored in the memory. For example, a volume value can be determined by multiplying Qi and Ti together. This could result, by way of example, in a memory that only needs to store one value.

[0067] In yet other embodiment of the present invention, an effective cross- sectional area, radius, or diameter of the flow channel can be used and stored in a memory to practice the present invention. In such an embodiment, the memory could store a velocity value which could be multiplied with the just mentioned effective dimensions and, if need be, other geometric values, to obtain a value that can be divided by the time of flight to obtain the value for the volume flow rate through the flow channel.

[0068] i the maintenance mode, any changes in temperature, which cause viscosity changes, or any changes in pressure, such as the patient elevating themselves in bed, will cause changes in the flow rate. Since flow regulator 13 is making time of flight measurements with flow sensor 27, the system will detect these changes and adjust flow control valve 22 by either opening the valve slightly, by way of example only, as in the case of lower pressure, or closing the valve slightly, such as, by way of example only, in the case of a higher temperature which reduces the viscosity of the solution, to maintain the selected flow rate. It should be understood from the foregoing that the valve 22 is in some embodiments a proportional or other valve that provides for suitable flow modifications. The valve described by Frank in US patent number 5,211,626 could be a suitable choice, the contents of US patent number 5,211,626 being incorporated by reference herein in its entirety.

[0069] The read/write memory 25 may be RFID chip MCRF 355/360 manufactured by Microchip Technology, Inc. of Chandler, AZ. or any other memory capable of storing and providing data of the aforementioned type in typical read/write fashion. Controller 28 may be any standard microprocessor as is known in the art. [0070] Practice of the present invention is not limited to the TV or continuous liquid flow context as described in the above embodiments. Sage, in US Patent 6,582,393 describes a device and method for measuring flow rate and compensating for flow system variables that accommodates the different exponential dependence of flow system variables on flow rate. In the device of Sage, a read/write memory could be included in the device, coupled to the flow channel as in the current invention, to provide the described geometric data. When used in such a system, the possible need to know properties of the medicament solution and the pressure under which the medicament solution is stored might be eliminated. Thus, in such a system, the reservoir could be pressurized at time of use rather than having to be manufactured at a pressure and having to have a reservoir that would maintain this pressure during storage.

[0071] Yet another embodiment is shown in figure 5. Figure_.5 shows valve assembly 22 controlling flow of the fluid through infusion set 12. Valve assembly 22 is controlled by controller 28 and receives flow characteristics of flow channel 24 from read/write memory 25 as read by read/write memory reader 26. The device of figure 5 is particularly useful when the liquid to be infused is known, such that its viscosity vs. temperature characteristic is known, and when this known drug is contained in a reservoir under mechanical pressure wherein the pressure profile as the reservoir empties is known, hi such a case, flow rate sensor 27 as shown in figure 3 is not needed. When infusion set 12 is mated to flow regulator 13, read/write memory reader 26 reads the flow characteristic from read/write memory 25. Based on calculations performed by controller 28 using the theory developed above, especially equation (1) with a viscosity calculated given the reading from a temperature sensor (not shown) and the viscosity profile of the known drug, and with a pressure based on the amount of the known drug remaining in the reservoir as calculated from the delivery history for this reservoir, the actual flow rate may be closely predicted. This predicted flow rate may be compared to the desired flow rate selected by the user, and control valve 22 may be adjusted such that the predicted flow rate matches the desired flow rate within the accuracy limits of the device. Alternately, using the periodic method of achieving a desired flow rate as described by Sage in US patent number 6,582,393, the time that an on off valve is open or closed during a delivery cycle may be adjusted to achieve the desired dosing profile, which may be a constant flow rate or a flow rate profile stored in the device.

[0072] By way of example, this embodiment could be practiced by receiving data from a memory having a flow characteristic of the flow channel stored therein, providing viscosity information of the selected liquid, providing information related to the pressure causing the selected liquid to flow along the flow channel, determining a value of the flow rate of the selected liquid based on the stored flow characteristic, the viscosity information and the pressure information, comparing the determined flow rate to the desired flow rate, and controlling a valve to achieve the desired flow rate.

[0073] Regarding accuracy, it is believed that some embodiments of the present invention can enable a volumetric flow rate of a fluid passing through a flow channel to be determined to within 3% of its actual value, while refined embodiments can be practiced that will permit determination to within or substantially within 2%, 1%, 0.15%, 0.5%, 0.25% and 0.1 percent or even greater of its actual value. In. other embodiments of the invention, the fluid flow can be controlled to these values as well. [0074] In other embodiments of the present invention, highly volumetric flow rates can be determined with high accuracy, by way of example and not by limitation, to the rates just mentioned, without utilizing actual dimensions of the interior of the flow channel. For example, in some embodiments of the present invention, it will not be necessary to measure the actual inner diameter of the flow channel, or to determine the approximate inner diameter of the flow channel based on, for example, engineering design drawings, etc.

[0075] Some embodiments of the present invention utilize a fully automatic flow rate determination system. That is, by way of example and not by limitation, other than the need for a human to interface the infusion set with the flow regulator and to perform other ancillary steps, flow rate can be determined without human intervention. However, in other embodiments of the present invention, the present invention can be practiced with human assistance alone or in combination with an automated system.

[0076] The present invention also comprises software and firmware that is written/created to practice any and all features/steps of the present invention. Still further, while the above embodiments are described in terms of an infusion set having a simple memory from which data is extracted and/or information can be obtained, other embodiments can utilize an infusion set that contains one or more of the determining elements of the flow regulator, as well as other elements. Indeed, some embodiments can be practiced where the flow regulator and the infusion set are a "one piece" system. In such an embodiment, by way of example and not by limitation, the one piece system could be disposable. [0077] It is noted that while at least some of the embodiments described above are described in terms of reading a memory of the infusion set, other embodiments can be practiced where the infusion set transmits or conveys data to the flow regulator. Still other embodiments can utilize both. Thus, some embodiments of the present invention can be practiced with a regulator that receives data from a memory, where receive data includes both active reading of a memory and reception of data transmitted to the receiver.

[0078] In some embodiments of the present invention, the flow sensor 27 may utilize an optical flow meter. One embodiment of an optical flow meter according to the present invention will be described in terms of a liquid dispensing system for use in infusion of pharmaceutical solutions, but may be applied in a number of contexts outside of the pharmaceutical space, such as monitoring the flow of liquids in liquid chromatography systems or in monitoring the flow of liquids in a carburetion system, and including non-liquid applications. Figure 7 shows a block diagram of a system for infusing pharmaceuticals. The liquid to be dispensed is contained in pressurized reservoir 110. When pinch tube member 114 is moved away from stop 112, conduit 111 is opened and the liquid is free to flow down conduit 111 to the flow outlet, which may include one or more microneedles (not shown). When pinch tube member 114 presses conduit 111 against stop 112, stopping flow, the liquid is not free to move down the conduit 111 to the flow outlet.

[0079] At a selected time, microprocessor 117 signals heating element 113 to heat a portion of the liquid at its location along the conduit 111. Once the portion of the liquid is heated, the pinch tube member 114 is moved away from the conduit 111, for example, by and instruction from microprocessor 117 to pinch tube actuator 115 which rotates cam 18 such that pinch tube member 114 moves away from flow tube 111, and the liquid begins to flow. Alternately, at a selected time microprocessor 117 signals pinch tube actuator 115 and cam 118 to open flow tube 111 by moving pinch tube member 114 away from flow tube 111. Once the fluid is flowing in flow tube 111, microprocessor 117 signals heating element 113 to heat a portion of the liquid at its location along the conduit. [0080] At some later time after the heating of this portion of the liquid, the heated portion of the liquid passes heat sensor 116 where the heated portion is detected. The time required for the heated portion of the liquid to move from the location of the heater 113 to the heat sensor 116 is measured. Additionally, the velocity of the liquid may be calculated by dividing the distance between the heating element 113 and the heat sensor 16 by the measured elapsed time.

[0081] An embodiment of the invention is shown in further detail in figures 8 tlirough 10. In figure 8, flow tube 111 is now shown with flow tube walls 151 and passageway 152. Flow along the passageway can be laminar, but may be non-laminar as long as the flow profile is such that the velocity of flow in the center of the passageway is higher than the velocity of flow near the walls of the passageway. A beam generated by heat source 161 is focused by lens 121 such that the heating element of heat source 161 is focused at location 143 in passageway 152 to heat increment of liquid 131. Optical rays indicated generally at 141 illustrate this focusing. As can be seen in figure 8, the heated increment of liquid 131 is small compared to the dimensions of passageway 152 in flow tube 111. Heat source 161 may be any source of optical radiation which is capable of being focused by lens 121 such as a laser or tungsten filament or thermal emitter. Such optical radiations include, but are not limited to, infra red and ultraviolet radiation. Still further, embodiments using other sources of radiation, such as microwave radiation, maybe used to practice the present invention. Heat source 161 can be an infrared laser, and further can be a solid state infrared laser that emits energy of a wavelength where the fluid is relatively highly absorbing. When the fluid is water, the absorption bands are located near 1470 nm, 1900 nm, and 3000 nm.

[0082] As can be further seen in figure 8, a second optical source 162 is located downstream of optical source 161. Pinch tube member 114 may be positioned between optical sources 161 and 162 (not shown in figures 8 through 10 but shown in figure 7), or both optical sources may be upstream or downstream of pinch tube member 114 (not shown). A beam generated by optical source 162 is focused into a region of passageway 152 by lens 122. Optical rays indicated generally at 142 illustrate this focusing. Rays 142 after passing through the liquid at location 144 are then collected by lens 123. The lens 123 is placed along the optical axis 170 formed by rays 142 a distance of one focal length from location 144, although other embodiments may utilize a distance of less than one focal length or more than one focal length. Detector 163 is also placed on the optical axis 170 formed by rays 142 to collect a portion of the light from optical source 162. Optical axis 170 is shown passing through passageway 152 along a path perpendicular to passageway 152. Perpendicular passage through the passageway is advantageous in some embodiments, but not required in other embodiments. Optical axis 170 may pass 'through the passageway at other angles. Optical source 162 can be a visible laser, but may be any coherent source with sufficiently long coherence length. [0083] Figure 9 is essentially the same as figure 8 except that Figure 9 shows heated increment of liquid 131 downstream from position 143 where it was heated. As can be seen in Figure 9, heated increment of fluid has grown in size due to the diffusion of heat from the original heated volume to the cooler surrounding liquid. Despite this increase in size, the heated increment of fluid remains localized near the center of passageway 152.

[0084] Figure 10 is also essentially the same as Figure 9 except that Figure 10 shows heated increment of liquid 131 further downstream and at location 144 where it passes through the focal point of optical rays 142 from optical source 62. At this point, light from optical source 162 is diffracted, changing the intensity of light at detector 163.

[0085] The change in intensity can be sensed, detected, or measured in a number of ways known in the art. For example, one may process the output of detector 163 by placing a threshold detector in the circuit that receives the output of the detector. In such an embodiment, the presence of heated increment of fluid 131 would be determined when the detector output exceeded the threshold. Further by way of example, one may process the output of detector 163 using a peak detector. In such an exemplary embodiment, the presence of heated increment of fluid 31 would be determined when the detector output reached a peak value. Alternatively, by way of example, one may record the output of the detector using an analog to digital converter as is known in the art and store the digitized signal. In this way a number of mathematical properties of the signal can be calculated. These include, but are not limited to the centroid of the signal, the width of the signal, and any number of moments of the signal. These properties may be used to locate the signal in time and to characterize the signal for use in determining the point in time that best represents when the heated increment of fluid passed detector 163. It is noted here that the heated increment of fluid 131 can be considered to have a centroid of diffraction, where the greatest diffraction of a beam passed through the heated increment occurs. [0086] The sequence of figures 8, 9, & 10 illustrate an important aspect of the invention. Shown schematically in figures 8, 9, & 10 is the shape of the heated increment when the average liquid velocity is relatively high and the parabolic velocity profile of laminar flow with the highest flow velocities in the center of the tube results in the heated portions of the fluid nearest the center of the tube being transported downstream relatively quickly, hi this case, the heated increment loses most of its heat to surrounding liquid and loses an insignificant amount of heat through the passageway wall. Under these circumstances, the temperature profile of the liquid across the passageway downstream from the heating location will be non- uniform with the highest temperatures in the center of the passageway. Stated slightly differently, the heated increment of liquid raises the temperature of the liquid at the wall of the passageway an insignificant amount since most of the heat is carried downstream in the center of the tube. This aspect of insignificant temperature rise at the wall during movement of the heated increment downstream is especially true at the sensing region.

[0087] Contrast this effect of the highest temperature liquid staying near the center of the passageway at relatively high average flow rates with the effect at relatively low average flow rates. At relatively low average flow rates, by thermal diffusion, the heat will flow to the walls of the passageway and escape through the walls of the passageway. Very little heat is carried downstream by the liquid. At relatively low average flow rates, then, a significant temperature rise occurs at the wall of the passageway. Whether the average flow rate is relatively high or relatively low is determined by the thermal diffiisivity of the liquid and the geometry of a given passageway. If the time required for the heat to move to the passageway wall perpendicular to the direction of flow is greater than the time required for the stream to carry the heated liquid the same distance downstream, then the average flow rate is relatively high. Otherwise, the average flow rate is relatively low. This invention is well suited to systems with relatively high average flow rates as defined here. Note well, however, that the average flow rate is highly dependent on the dimensions of the passageway. A system with a relatively low average flow rate with one set of passageway dimensions (length and inside diameter or if the passageway is square or rectangular, the height and width) may become a system with a relatively high average flow rate with another set of passageway dimensions. [0088] In a system with a relatively high flow rate, that is, one where the heat introduced into the fluid does not leave the fluid primarily through the walls of the passageway but instead primarily stays in the fluid, the temperature profile is such that the hottest fluid is at or near the center of the passageway. Still, it is noted that other embodiments of the present invention may be practiced where heat does leave through the walls, as long as the fluid retains a sufficient amount of heat such that diffraction maybe used to analyze the flow of fluid. This is especially true when flow along the passageway is laminar. The contours of heated increment 131 as shown in figures 8, 9, and 10 are then interpretable as isotherms, that is, points of equal temperature./ As can be seen from the profiles shown in figures 8, 9, and 10, there are high temperature gradients along paths from unheated fluid to the hottest portions of the heated fluid increments. As the temperature of the fluid changes, so does the density of the fluid. From an optics point of view, these density variations represent regions where the phase of an incident light beam is changed. These density variations diffract an incident beam resulting in variations in the intensity of the beam as it proceeds from the passageway.

[0089] Figure 11 shows data from a prototype of the liquid metering system and, more particularly, a diffraction pattern generated after the liquid has been illuminated by the light source 162. This prototype system comprised a semiconductor heat laser operating at 1.47 microns with an exit aperture of 1 micron by 5 microns. This semiconductor laser illuminated the fluid flowing in a passageway, the passageway having dimensions of 50 microns by 50 microns. The heat laser was focused so that it perpendicularly illuminated a cylinder through the passageway about 20 microns in diameter. The sense laser was a 630 nm semiconductor laser focused on the passageway 200 microns downstream of the heat laser. The size of the focused spot was about 30 microns in diameter. When the liquid passing down the passageway is all the same temperature, there is a time invariant diffraction pattern. The diffraction pattern changes upon interaction with the heated increment of liquid. To obtain figures 11 & 23, a line array of photodiodes has been used as detector 163 in Figure 10 and has been placed so that the axis of the line array is perpendicular to both the illumination axis and the passageway. A sequence of 165 data sequences of the line array is shown in Figure 11, with the first output shown at the top of Figure 11, and the final output, output 165, shown at the bottom. Each output shows the intensity of the light at the position of detector 163 in Figure 10 for each of the 1012 individual detectors of the line aπay. Each line output, from the top of Figure 11 to the bottom of figure 11, represents the intensity of the light at subsequent increments of time, each increment representing one hundred microseconds, hi the experiment shown in Figure 11, the liquid is moving in the passageway, and the liquid was heated for about one millisecond. As can be seen from Figure 11, the heated increment of liquid appears at location 144 about a millisecond and a half after being heated, as evidenced by the much broader pattern of light due to the diffraction caused by the presence of the heated increment of liquid. If detector 163 were positioned along and centered on axis 170 as shown in Figure 10 (at approximately pixel position 500), detector 163 would detect a lower intensity of light due to the passage of the heated increment of liquid, as represented by less bright pixels shown between about pixel positions 400 to 500. If detector 163 were placed off axis 170 in the location of pixels 325 through 375, the passage of the heated increment of liquid would result in an increase in light intensity at detector 163.

[0090] Figure 12 shows the intensity of illumination at detector location 63 of two selected sequences from the 165 sequences of the output of the line array shown in figure 11. The intensity profile labeled "heated" was selected from those sequences between sequence 112 and sequence 120. The sequence labeled "unheated" was selected from those sequences up to sequence 112. As can be seen from these sequences, placing a detector on axis 170, represented by pixel 0 in Figure 12, would result in a signal that decreases in intensity as the heated increment passes. Alternate locations for an "on-axis" detector would be at pixel locations from about location - 100 to location +10. This "on-axis" detector may be sized to cover as many or as few of these pixels as may provide the signal with the highest signal to noise. Alternately, detector 163 may be placed off axis, such as in the direction of negative pixels as shown in figure 12 from about pixel -200 to pixel -100. Detector 163 at this location would detect an increased signal when the heated increment passed through the beam from light source 162. This "off-axis" detector may be sized to cover as many or as few of these pixels as may provide the signal with the highest signal to noise. [0091] The optical sensor shown in figures 8 through 10 operates in the following way. At a desired point in time, light source 162 is activated to heat a small increment of liquid at location 143. The liquid may or may not be flowing at this time. If the liquid is not flowing, flow is initiated at a known time after the liquid is heated. Heated increment of liquid 131 then flows along the passageway, as shown in Figure 9, expanding as it flows due to thermal diffusion. At some later time it reaches location 144 in passageway 152 as shown in Figure 10. However, heated increment 31 has not yet expanded to the point where the temperature of the liquid is raised significantly at passageway wall 151, if at all. Because heated increment 132 has an elevated temperature relative to other nearby regions of the liquid in passageway 152, the density of the liquid in liquid increment 132 is lower than the liquid in nearby regions of passageway 152. hi this way heated increment 132 represents an optical phase object and causes light from optical source 162 to be diffracted as it passes location 144. The diffraction of the light from optical source 162 due to the passage of phase object 132 through the light from optical source 162 at location 144 causes a change in the far-field intensity pattern of light source 162. By placing lens 123 one focal length from location 144 along the optical axis of rays 142 from optical source 162, this far-field intensity pattern can be imaged at detector 163. In this way detector 163 will sense the passing of phase object 132 due to the change in the far- field intensity pattern caused by phase object 132. Detector 163 may be placed on optical axis 70, where it would detect a decrease in light intensity as the heated increment passes, or off axis 170 perpendicular to both optical axis 170 and the axis formed by the passageway, where it would detect an increase in light intensity. [0092] In figures 8 through 10, the separation distance of locations 143 and 144 is either predetennined, known or measured, h a first embodiment, the fluid is not flowing when an increment of fluid is heated by heat source 161. Shortly after heating the increment of fluid, flow is started. The time required for the heated increment of fluid to flow from location 43 where it was heated to location 144 where it is detected is measured as the elapsed time from the time of starting fluid flow to the time of detection of the heated increment at location 144. This time interval is termed the thermal time of flight. The velocity of the fluid may be calculated by dividing the thermal time of flight into the separation distance. [0093] In a second embodiment of figures 8 through 10, the fluid is flowing at the time an increment of fluid is heated at location 143. At a desired time after initiation of flow, an increment of fluid is heated, and the elapsed time from time of heating to time of detection at location 144 is measured to determine the thermal time of flight. The velocity of the fluid may be calculated by dividing the thermal time of flight into the separation distance.

[0094] Further embodiments may be envisioned to take advantage of the invention. In one such embodiment, a second optical source and detector pair for detecting the heated increment of liquid is located at a third location downstream of location 44 in figures 8 through 10. In such an embodiment, the thermal time of flight may be measured as the elapsed time for the heated increment to move from location 144 to the third location further downstream. And the fluid velocity may be calculated as the thermal time of flight divided into the distance of separation of the two optical source detector pairs.

[0095] In any of the possible embodiments of the invention, the details of the passageway are not critical as long as the walls of the passageway where the fluid is heated allows sufficient energy to pass such that the fluid is heated or, where the heated fluid is sensed, allows sufficient illumination to pass tlirough such that the coherence of the beam is maintained and the heated increment is sensed. The passageway may be circular, or square, or even rectangular. The passageway may be made of any of a multitude of glasses or from any of a number of engineering polymers.

[0096] The descriptions of the optical systems set forth herein are meant to be illustrative and not definitive. Persons skilled in the art may be able to provide variations on the basic design of these optical systems in the detecting and measuring of a heat pulse in a liquid in a conduit and the subsequent measurement of the flow of the liquid in the conduit.

[0097] Further, the descriptions of the optical systems and metering systems herein may be implemented in combination with the teachings of one or more of the above referenced patents incorporated herein by reference to deliver/dispense liquid. For example, the metering systems and optical systems described herein can be used in combination with the liquid delivery components described in those patents. [0098] The foregoing are but a few of the ways and techniques in which a characteristic of flow in a channel measured during manufacture (or at some other pre-use point in time) can be used to compensate for differences in actual flow of the same or different liquid at time of use. Those of ordinary skill in the relevant art will recognize other beneficial application of these techniques in improving drug and other liquid delivery. Any of the disclosed designs and techniques could be combined with other disclosed designs and techniques to further improve the accuracy of liquid delivery by infusion.

Claims

WHAT IS CLAIMED IS:

1. A device for delivering liquid via a flow channel comprising: a flow channel; a memory having a stored value indicative of a flow characteristic of the flow channel; a controller that generates a flow control signal based on the stored value; and a valve responsive to the flow control signal adapted to control flow of the liquid through the flow channel.

2. The device of claim 1 wherein the stored value of the flow characteristic is based on empirical data relating to the specific flow channel of the device.

3. The device of claim 1, wherein the memory has a second stored value indicative of a second flow characteristic.

4. The device of claim 1, wherein the flow channel is part of an infusion set and the controller is part of a flow regulator coupled to the infusion set.

5. The device of claim 1, wherein the flow characteristic is a physical characteristic of the flow channel.

6. The device of claim 5, wherein the physical characteristic is selected from the group consisting of an effective cross-sectional area of the flow channel, an effective radius of the flow channel, and an effective diameter of the flow channel.

7. The device of claim 1, wherein the flow characteristic is a volumetric flow rate value of a fluid previously passed through the flow channel.

8. The device of claim 7, wherein the memory also has a stored value indicative of a velocity of the fluid previously passed through the flow channel.

9. The device of claim 1, wherein the valve is a proportional valve.

10. The device of claim 1, wherein the valve is an on/off valve.

11. The device of claim 4, wherein the flow regulator is adapted to be uncoupled from the infusion set.

12. The device of claim 4 wherein the flow regulator comprises a time-of- flight sensor.

13. The device of claim 4, wherein the flow regulator is adapted to receive data relating to a viscosity of a liquid that will be passed through the flow channel.

14. A method of manufacturing a liquid delivery device, comprising: passing a liquid through a flow channel; measuring flow-related data of the flow of the liquid through the flow channel; determining a value of a flow characteristic of the flow channel based on the flow-related data; and storing at least one of the value of the flow characteristic and a value based on the flow characteristic in a memory of the liquid delivery device.

15. The method of claim 14, wherein measuring flow-related data includes making a time-of-flight measurement.

16. The method of claim 15, wherein determining the value comprises using a predetermined pressure and a predetermined viscosity value.

17. The method of claim 16, wherein the flow characteristic is a physical characteristic of the flow channel.

18. The method of claim 17, wherein the physical characteristic is selected from the group consisting of an effective cross-sectional area, an effective diameter, and an effective radius of the flow channel.

19. The method of claim 14, wherein the flow characteristic is a volumetric flow rate of the liquid passed through the flow channel.

20. The method of claim 14, wherein the flow characteristic is a time of flight of the liquid passed through the flow channel.

21. The method of claim 14, further comprising storing a second value in the memory, wherein value is a time of flight of the liquid passed through the flow channel.

22. The method of claim 14, wherein the flow characteristic is a fluid volume value, the volume value being a value relating to a volumetric flow rate value and a time of flight value relating to liquid passed through the flow channel.

23. The method of claim 14, wherein the flow channel is part of an infusion set.

24. The method of claim 14, further comprising manufacturing an infusion set by placing a tube in fluid communication with the infusion channel, wherein the tube is in fluid communication with an infusion bag.

25. The method of claim 24, further comprising placing a liquid medicament into the infusion bag.

26. The method of claim 14, wherein the flow related data is time-of-flight data.

27. A method of delivering a liquid via a flow channel, the method comprising: measuring flow-related data of the liquid flowing through a flow channel; receiving data from a memory having a flow characteristic of the flow channel stored therein; determining a value of the flow of the liquid based on the flow-related data and the stored flow characteristic, and controlling a valve based on the calculated value of flow to control the flow of liquid through the flow channel.

28. A method of delivering a liquid via a flow channel at a desired flow rate, the method comprising: measuring flow-related data of the liquid passing through the flow channel; receiving data from a memory having a flow characteristic of the flow channel stored therein; determining a value of the flow rate of the liquid based on the flow-related data and the stored characteristic value; comparing the determined value of the flow rate to the desired flow rate; and controlling a valve to achieve the desired flow rate.

29. A method of delivering a selected liquid via a flow channel at a desired flow rate, the method comprising: receiving data from a memory having a flow characteristic of the flow channel stored therein; providing viscosity information of the selected liquid; providing information related to the pressure causing the selected liquid to flow along the flow channel; determining a value of the flow rate of the selected liquid based on the stored flow characteristic, the viscosity information and the pressure information; comparing the determined flow rate to the desired flow rate; and controlling a valve to achieve the desired flow rate.

30. The method of claim 29, wherein the method is practiced without measuring the velocity of the liquid passing through the flow channel.

31. A device for delivering liquid via a flow channel, the device comprising: a flow channel; and a memory having a stored value indicative of a flow characteristic of the flow channel; wherein the device is adapted to at least one of transfer the stored value from the memory and permit reading of the stored value to enable the volumetric flow rate of a liquid flowing through the flow channel to be determined.

32. The device of claim 31 , wherein the device is adapted to enable the volumetric flow rate to be determined to within 1% of its actual value.

33. The device of claim 32, wherein the device is adapted to enable the volumetric flow rate to be determined to within 0.75 % of its actual value.

34. The device of claim 33, wherein the device is adapted to enable the volumetric flow rate to be determined to within 0.5 % of its actual value.

35. The device of claim 34, wherein the device is adapted to enable the volumetric flow rate to determined to within 0.25 % of its actual value.

36. The device of claim 35, wherein the device is adapted to enable the volumetric flow rate to be determined to within 0.1 % of its actual value.

37. The device of claim 31, wherein the device is adapted to enable the volumetric flow rate to be determined without utilizing actual dimensions of the interior of the flow channel.

38. The device of claim 31 , wherein actual dimensions include design dimensions.

39. The device of claim 31, wherein the stored value is based on empirical data relating to the specific flow channel of the device.

40. The device of claim 39, wherein the memory has a plurality of stored values, wherein the device is adapted to at least one of transfer the stored values from the memory and permit reading of the stored values to enable the volumetric flow rate of a liquid flowing through the flow channel to be determined, wherein the plurality of values are based on empirical data relating to the specific flow channel of the device; wherein at least one of the values is a volumetric flow rate value and at least one of the values is a time of flight value, the volumetric flow rate value and the time value being values relating to fluid previously conducted tlirough the flow channel.

41. The device of claim 39, wherein the value is a volume value, the volume value being a value relating to a volumetric flow rate value and a time of flight value relating to fluid previously conducted through the flow channel.

42. The device of claim 39, wherein the memory has a plurality of stored values, wherein the device is adapted to at least one of transfer the stored values from the memory and permit reading of the stored values to enable the volumetric flow rate of a liquid flowing through the flow channel to be determined, wherein the plurality of values are based on empirical data relating to the specific flow channel of the device, wherein at least one of the values is at least one of an effective cross-sectional area of the flow channel, an effective radius of the flow channel, and an effective diameter of the flow channel, and wherein at least one of the values is a velocity of fluid value relating to velocity of a fluid conducted through the flow channel.

43. The device of claim 31 , wherein the flow channel and memory are parts of an infusion set.

44. A device for controlling the delivery of liquid via a flow channel, the device comprising: a valve adapted to control the flow of fluid through a fluid conduit in fluid communication with a flow channel; and at least one of a data receiver adapted to receive a value indicative of a flow characteristic of the flow channel; wherein the device is adapted to determine the volumetric flow rate of a liquid flowing through the flow channel utilizing the received value; and wherein the device is adapted to automatically control the flow of fluid through the flow channel based on the determined volumetric flow rate.

45. The device of claim 44, wherein the fluid conduit is the flow channel.

46. The device of claim 44, wherein the device is adapted to determine the volumetric flow rate to within 1% of its actual value.

47. The device of claim 46, wherein the device is adapted to determine the volumetric flow rate to within 0.75% of its actual value.

48. The device of claim 47, wherein the device is adapted to determine the volumetric flow rate to within 0.5% of its actual value.

49. The device of claim 48, wherein the device is adapted to determine the volumetric flow rate to within 0.25% of its actual value.

50. The device of claim 49, wherein the device is adapted to determine the volumetric flow rate to within 0.1% of its actual value.

51. The device of claim 44, wherein the device is adapted to enable the volumetric flow rate to be determined without utilizing actual dimensions of the interior of the flow channel.

52. The device of claim 51, wherein actual dimensions include design dimensions.

53. The device of claim 44, wherein the value is based on empirical data relating to the specific flow channel through which the flow of fluid is controlled.

54. The device of claim 53, wherein the device is adapted to at least one of read and receive a plurality of values, wherein the device is adapted to determine the volumetric flow rate of a liquid flowing through the flow channel utilizing the received values, wherein the plurality of values are based on empirical data relating to the specific flow channel through which the flow of fluid is controlled, wherein at least one of the values is a volumetric flow rate value and at least one of the values is a time of flight value, the volumetric flow rate value and the time value being ^'values relating to fluid previously conducted through the flow channel.

55. The device of claim 53, wherein the value is a volume value, trie volume value being a value relating to a volumetric flow rate value and a time of flight value relating to fluid previously conducted through the flow channel.

56. The device of claim 53, wherein the device is adapted to at least one of read and receive a plurality of values, wherein the device is adapted to determine the volumetric flow rate of a liquid flowing through the flow channel utilizing the received values, wherein the plurality of values are based on empirical data relating to the specific flow channel through which the flow of fluid is controlled, wherein at least one of the values is at least one of an effective cross-sectional area of the flow channel, an effective radius of the flow channel, and an effective diameter of the flow channel, and wherein at least one of the values is a velocity of fluid value relating to velocity of a fluid previously conducted through the flow channel.

57. The device of claim 54, wherein the flow channel and memory are parts of an infusion set, and wherein the device is adapted to interface with the infusion set.

58. The device of claim 54, further comprising a flow sensor.

59. The device of claim 58, wherein the flow sensor is a time of flight sensor.

60. A system for monitoring fluid flow through a passageway comprising: a) a heater that heats a portion of the fluid in the passageway; b) a light source that generates a beam of light that illuminates the fluid in the passageway; and c) a light detector positioned to receive a portion of the beam, wherein the detector measures a change in the intensity of the beam caused by diffraction of the beam when the heated portion of the fluid passes through the beam.

61. The system of claim 60 wherein the beam has an axis and the light detector is positioned along the axis such that the light detector measures a decreased intensity with the passage of the heated portion of the fluid.

62. The system of claim 60 wherein the beam has an axis and the light detector is displaced from the axis such that the light detector measures an increased intensity with the passage of the heated portion of the fluid.

63. The system of claim 60 wherein the beam has an axis and the fluid in the passageway has a non-uniform temperature profile along the axis when the heated portion of the fluid passes through the beam.

64. The system of claim 60 wherein the heater is an infrared laser.

65. The system of claim 60 wherein the fluid is a liquid.

66. The system of claim 60 wherein the heater is positioned a known distance upstream of the location where the beam passes through the passageway.

67. The system of claim 66 further comprising a processor that measures a time period between heating of the portion of the fluid and detection of the passage of the heated portion of the fluid by the light detector.

68. The system of claim 67 wherein the processor calculates a velocity of the fluid from the time period and the known distance between the heater and the light source.

69. system for monitoring fluid flow comprising: a) a passageway along which the fluid may flow such that the average flow rate is relatively high, b) a heat source that heats a portion of the fluid in the passageway at a first position along the passageway, c) a source that generates a light beam that illuminates the fluid in the passageway at a second position downstream from the first position, and d) a light detector positioned to receive illumination from the source and to detect a change in intensity of the received illumination when the heated portion of the fluid passes through the beam.

70. The system of claim 69 wherein the beam has an axis and the light detector is positioned along the axis such that the light detector measures a decreased intensity with the passage of the heated portion of the fluid.

71. The system of claim 69 wherein the beam has an axis and the light detector is displaced from the axis such that the light detector measures an increased intensity with the passage of the heated portion of the fluid.

72. The system of claim 69 wherein the beam has an axis and the fluid in the passageway has a non-uniform temperature profile along the axis when the heated portion of the fluid passes through the beam.

73. The system of claim 69 further comprising a processor that measures a time period between heating of the portion of the fluid and detection of the passage of the heated portion of the fluid by the light detector.

74. The system of claim 73 wherein the processor calculates a velocity of the fluid from the time period and the known distance between the heater and the light source.

75. The system of claim 69 further comprising a second light source- detector pair positioned downstream of the first-named light source and the first- named light detector such that the processor measures a time period between detection of the passage of the heated portion of the fluid by the first-named light detector and detection of the passage of the heated portion of the fluid by the second light source- light detector pair.

76. A system for monitoring flow of a liquid through a passageway, comprising: a heat laser that generates a first beam directed toward the passageway wherein the first beam is focused to a region at a first location within the passageway such that a localized portion of the liquid in the passageway is heated and the liquid in the passageway has a non-uniform temperature cross-section; a sense laser that generates a second beam directed toward and focused on the passageway at a second location downstream from the first location such that the heated localized portion of the liquid will be illuminated by the second beam when the heated localized portion flows through the second beam; and a light detector positioned to receive a portion of the second beam when the heated localized portion of the liquid passes through the second beam.

77. The system of claim 76 wherein the second beam has an axis and the light detector is positioned along the axis such that the light detector measures a decreased intensity with the passage of the localized portion of the liquid.

78. The system of claim 76 wherein the second beam has an axis and the light detector is displaced from the axis such that the light detector measures an increased intensity with the passage of the localized portion of the liquid.

79. A method of measuring flow of a liquid in a passageway, the method comprising: a) heating a portion of the liquid in the passageway at a first position, b) directing a beam of light from an optical source into the liquid in the passageway at a second position downstream from the first position, and c) detecting a change in intensity in of the light from the optical source caused by diffraction of a portion of the beam when the heated portion of the fluid passes through the beam.

80. The method of claim 79 wherein the beam has an axis and the detecting action comprises measuring a decreased intensity with the passage of the heated portion of the fluid with a detector place on the axis.

81. The method of claim 79 wherein the beam has an axis and the detecting action comprises measuring an increased intensity with the passage of the heated portion of the fluid with a detector displaced from the axis.

82. The method of claim 79 further comprising measuring a time period between the heating action and detection of the passage of the heated portion of the fluid by the light detector.

83. The method of claim 82 further comprising calculating a velocity of the fluid from the time period and a distance between the first and second positions.

84. The system of claim 60, wherein the light detector is positioned to receive substantially all of a portion of the beam that passes through the entire passageway, wherein the detector measures a change in the intensity of a localized portion of the received beam caused by diffraction of the beam induced by the heated portion of the fluid.

85. A device for delivery of a liquid medicament to a subject comprising: a system for monitoring fluid flow through a passageway according to claim

60; and a valve for starting and stopping liquid flow in the flow tube in a periodic manner based on information from the system.

86. A device for delivery of a liquid medicament to a subject comprising: a system for monitoring fluid flow through a passageway according to claim

60 or 68; and a valve for starting and stopping liquid flow in the flow tube in a periodic manner based on information from the system.

87. A device for delivery of a liquid medicament to a subject comprising: a system for monitoring fluid flow through a passageway according to claim 69; and a valve for starting and stopping liquid flow in the flow tube in a periodic manner based on information from the system.

88. A device for delivery of a liquid medicament to a subject comprising: a system for monitoring fluid flow througli a passageway according to claim

75; and a valve for starting and stopping liquid flow in the flow tube in a periodic manner based on information from the system.

89. A device for delivery of a liquid medicament to a subject comprising: a system for monitoring fluid flow through a passageway according to claim

76; and a valve for starting and stopping liquid flow in the flow tube in a periodic manner based on information from the system.

90. The method of claim 79 further comprising starting and stopping the fluid based on the detected change in intensity.

91. The method of claim 82 further comprising starting and stopping the fluid based on the calculated velocity.

92. The system of claim 76 wherein the light detector senses or measures a change in the intensity of the second beam.

93. A system for monitoring fluid flow through a passageway comprising: a) a heater that heats a portion of the fluid in the passageway; b) a light source that generates a beam of light that illuminates the fluid in the passageway; and c) a light detector positioned to receive a portion of the beam, wherein the detector senses a change in the intensity of the beam caused by diffraction of the beam induced by the heated portion of the fluid.

94. The system of claim 93 wherein the beam has an axis and the light detector is positioned along the axis such that the light detector senses a decreased intensity with the passage of the heated portion of the fluid.

95. The system of claim 93 wherein the beam has an axis and the light detector is displaced from the axis such that the light detector senses an increased intensity with the passage of the heated portion of the fluid.

96. The system of claim 93 wherein the beam has an axis and the fluid in the passageway has a non-uniform temperature profile along the axis when the heated portion of the fluid passes tlirough the beam.

97. The system of claim 93 wherein the heater is positioned a known distance upstream of the location where the beam passes through the passageway.

98. The system of claim 97 further comprising a processor that measures a time period between heating of the portion of the fluid and detection of the passage of the heated portion of the fluid by the light detector.

99. The system of claim 98 wherein the processor calculates a velocity of the fluid from the time period and the known distance between the heater and the light source.

100. The system of claim 76 wherein the second beam has an axis and the light detector is positioned along the axis such that the light detector senses a decreased intensity with the passage of the localized portion of the liquid.

101. The system of claim 76 wherein the second beam has an axis and the light detector is displaced from the axis such that the light detector senses an increased intensity with the passage of the localized portion of the liquid.

102. A method of measuring flow of a liquid in a passageway, the method comprising: a) heating a portion of the liquid in the passageway at a first position, b) directing a beam of light from an optical source into the liquid in the passageway at a second position downstream from the first position, and c) measuring a change in intensity in of the light from the optical source caused by diffraction of a portion of the beam when the heated portion of the fluid passes through the beam.

103. The method of claim 102 wherein the beam has an axis and the measuring action comprises measuring a decreased intensity with the passage of the heated portion of the fluid with a detector place on the axis.

104. The method of claim 102 wherein the beam has an axis and the measuring action comprises measuring an increased intensity with the passage of the heated portion of the fluid with a detector displaced from the axis.

105. The method of claim 102 further comprising measuring a time period between the heating action and the measurement of the change of intensity.

106. The method of claim 105 further comprising calculating a velocity of the fluid from the time period and a distance between the first and second positions.

107. The system of claim 93, wherein the light detector is positioned to receive substantially all of a portion of the beam that passes through the entire passageway, wherein the detector senses a change in the intensity of a localized I portion of the received beam caused by diffraction of the beam induced by the heated portion of the fluid.

108. A device for delivery of a liquid medicament to a subject comprising: a system for monitoring fluid flow through a passageway according to claim

93; and a valve for starting and stopping liquid flow in the flow tube in a periodic manner based on information from the system.

109. A device for delivery of a liquid medicament to a subject comprising: a system for monitoring fluid flow through a passageway according to claim

99; and a valve for starting and stopping liquid flow in the flow tube in a periodic manner based on information from the system.

110. The method of claim 102 further comprising starting and stopping the fluid based on the detected change in intensity.

111. The method of claim 106 further comprising starting and stopping the fluid based on the calculated velocity.