US20080023634A1 - Non-invasive detection of analytes in a comples matrix - Google Patents
Non-invasive detection of analytes in a comples matrix Download PDFInfo
- Publication number
- US20080023634A1 US20080023634A1 US11/620,101 US62010107A US2008023634A1 US 20080023634 A1 US20080023634 A1 US 20080023634A1 US 62010107 A US62010107 A US 62010107A US 2008023634 A1 US2008023634 A1 US 2008023634A1
- Authority
- US
- United States
- Prior art keywords
- analytical
- specimen
- wavelength
- radiation
- spectral range
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000001514 detection method Methods 0.000 title 1
- 239000011159 matrix material Substances 0.000 title 1
- 230000005855 radiation Effects 0.000 claims abstract description 63
- 239000012491 analyte Substances 0.000 claims abstract description 30
- 238000000034 method Methods 0.000 claims abstract description 24
- 230000003595 spectral effect Effects 0.000 claims description 36
- 230000000747 cardiac effect Effects 0.000 claims description 11
- 230000001678 irradiating effect Effects 0.000 claims 2
- 238000001228 spectrum Methods 0.000 abstract description 3
- 239000008280 blood Substances 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 11
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 10
- 239000008103 glucose Substances 0.000 description 10
- 238000005259 measurement Methods 0.000 description 9
- 238000000862 absorption spectrum Methods 0.000 description 5
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000002238 attenuated effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000005540 biological transmission Effects 0.000 description 3
- 239000000835 fiber Substances 0.000 description 3
- 239000004065 semiconductor Substances 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 239000005371 ZBLAN Substances 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 229910052788 barium Inorganic materials 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 210000003811 finger Anatomy 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 229910052746 lanthanum Inorganic materials 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052726 zirconium Inorganic materials 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 229910000530 Gallium indium arsenide Inorganic materials 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229910000661 Mercury cadmium telluride Inorganic materials 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 238000004159 blood analysis Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- -1 glucose Chemical class 0.000 description 1
- FZLIPJUXYLNCLC-UHFFFAOYSA-N lanthanum atom Chemical compound [La] FZLIPJUXYLNCLC-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000491 multivariate analysis Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 229910052594 sapphire Inorganic materials 0.000 description 1
- 239000010980 sapphire Substances 0.000 description 1
- SBIBMFFZSBJNJF-UHFFFAOYSA-N selenium;zinc Chemical compound [Se]=[Zn] SBIBMFFZSBJNJF-UHFFFAOYSA-N 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000003813 thumb Anatomy 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
- A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
- G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
- G01J3/28—Investigating the spectrum
- G01J3/42—Absorption spectrometry; Double beam spectrometry; Flicker spectrometry; Reflection spectrometry
- G01J3/433—Modulation spectrometry; Derivative spectrometry
- G01J3/4338—Frequency modulated spectrometry
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
Definitions
- the present invention relates to the determination of the concentration of various analytes of interest in various complex matrices.
- the invention is applicable in a broad range of chemical analyses in a variety of fields including, but not limited to, non-invasive blood analysis and other medical applications, food and pharmaceutical industries, environmental monitoring, industrial safety, etc.
- non-invasive blood analysis and other medical applications including, but not limited to, non-invasive blood analysis and other medical applications, food and pharmaceutical industries, environmental monitoring, industrial safety, etc.
- blood glucose concentration and measurements of cholesterol and tryglicerides concentrations in blood are of significant importance.
- a method and system for determining the concentration of analytes of interest in complex matrices for example, glucose in blood
- Analytical radiation is generated and directed onto a portion of a specimen containing the analytes of interest.
- the wavelength of the analytical radiation is scanned over a broad analytical spectral range and over a relatively short duration of diagnostic time.
- the analytical radiation attenuated by the specimen is collected.
- the amount of collected radiation attenuated by the specimen is correlated to the concentration of the analyte of interest in the specimen.
- the concentration of the analyte of interest in the specimen then may then be displayed on an output display device as well as used as input into an analyte control device, such as an insulin pump.
- Multivariate analysis techniques may be used to relate measured spectra to the concentration of the analyte of interest.
- inventions of the present invention may be utilized to overcome the problem of insufficient signal-to-noise ratio in measurements of glucose and other analytes of interest in the specimen.
- An increase in signal-to-noise ratio allows measurements to be taken within a relatively short duration of diagnostic time, which helps to eliminate problems associated with hardware and specimen noise.
- some compounds e.g., glucose
- FIG. 1 is a schematic diagram of a system for detecting an analyte in a specimen according to an embodiment of the present invention.
- specimens according to the present invention may comprise biological or non-biological specimens.
- Biological specimens according to the present invention include, but are not limited to, specimens characterized by a cardiac cycle.
- a variety of non-biological specimens are contemplated by the present invention including, but not limited to, water, food, air, etc.
- Analytes of interest may include components ordinarily present in the specimen of interest, e.g., glucose in blood or tissue, or components that represent pollutants or contaminants in a specimen of interest.
- the system 10 comprises a radiation source 20 and a detector 40 .
- both the radiation source 20 and the detector 40 are portable and rugged.
- the radiation source 20 may be, for example, a laser, an optical parametric oscillator (OPO), or a light emitting diode (LED).
- the radiation source 20 may be a single broadly tunable laser. Suitable lasers, include, but are not limited to, a semiconductor laser diode, a fiber laser, a solid state laser, a quantum cascade laser, or a color center laser. Semiconductor lasers are compact and power efficient and allow the system 10 to be more readily portable. Cr doped ZnSe, ZnS, or CdS lasers are also contemplated because of particular advantages in the context of wavelength scanning.
- the radiation source 20 is an external cavity semiconductor laser diode.
- the radiation source 20 may employ the Littman-Metcalf, Littrow, or any other suitable external cavity configuration.
- the radiation source 20 is configured to generate analytical radiation and scan over an analytical spectral range.
- the analyte of interest present within the specimen 30 has unique absorption spectrum within the analytical spectral range.
- glucose in blood is characterized by an absorption spectrum that includes absorption lines at about 1.56 ⁇ m, 2.15 ⁇ m, 2.27 ⁇ m, and 2.32 ⁇ m, each within a source spectral range of between 900 nm and 2700 nm.
- the radiation source 20 scans a wavelength of the analytical radiation over the analytical spectral range over a predetermined diagnostic time period.
- the duration of the diagnostic time period is relatively short.
- the diagnostic time period is no greater than the duration of the cardiac period of the specimen.
- a cardiac period of a human typically ranges from about 0.3 to about 2 seconds.
- the duration of the diagnostic time period is a fraction of the cardiac period (e.g., less than one half of the cardiac period).
- the duration of the diagnostic time period may be 0.01 second in the case of determining blood glucose concentration in a human.
- the analytical radiation emitted by the radiation source 20 may define a relatively narrow spectral line with a width of less than about 20 nm.
- the spectral line width is about 1 nm.
- the analytical spectral range may from between about 900 nm and about 2700 nm and should be broad enough to discriminate the contributions of any other analytes present in the specimen 30 . In the case of blood glucose, the range is broad enough to discriminate from the contributions of the other analytes in the human body, such as, for example, urea, proteins and other similar analytes.
- An analytical spectral range from about 2050 nm to about 2400 nm may be suitable in many contexts.
- the radiation source 20 in addition, may also be configured to control the width of the analytical spectral range.
- the radiation source 20 delivers the analytical radiation to the specimen 30 .
- the detector 40 collects the radiation reflected from, scattered from, or transmitted through the specimen 30 of the analytical radiation. Collection of radiation transmitted through the specimen 30 is most suitable for specimen areas that are relatively thin. For example, if the specimen 30 is human, the transmissions can be collected from the ear, the web area between the thumb and index finger, skin pinch on the back of the hand, or in any other similar thin area of the body where transmissions may be collected through the specimen 30 . Radiation reflected or scattered from a nail of a finger or toe is another potential site of collection of the analytical radiation if the specimen 30 is human.
- the radiation source 20 may be configured to utilize optics to aid in directing the analytical radiation onto the specimen 30 .
- the detector 40 may also be configured to utilize optics to aid in collections of the attenuated analytical radiation from the specimen 30 .
- conduits are used to deliver the analytical radiation to the specimen 30 as well as to collect the reflected, scattered, or transmitted radiation from the specimen 30 .
- a conduit 24 delivers the analytical radiation from the source 20 to the specimen 30 .
- Another conduit 32 collects the reflected, scattered, or transmitted radiation from the specimen 30 to the detector 40 .
- the conduits 24 , 32 may be, for example, a fiber optic bundle. Because the conduits 24 , 32 need to be highly transparent for wavelengths as long as 2700 nm, the material used for the conduits 24 , 32 can be for example, ultra-low OH silica, quartz, sapphire, ZBLAN glass, or any similar suitable material. ZBLAN is fluorine combined with the metals zirconium, barium, lanthanum, aluminum, and sodium (Zr, Ba, La, Al, and Na, hence its name). The use of the fiber optic bundle conduits 24 , 32 has the advantage of allowing for relatively remote placement of the system 10 .
- the conduits 24 , 32 may also be air, the tissue of the specimen 30 itself, or any suitable transmission medium.
- the detector 40 may be a single detector or a multi-channel detector array.
- the detector 40 may have a high sensitivity to the wavelength of analytical radiation used.
- the detector 40 may be, for example, PbS, HgCdTe, HgCdZnTe, InGaAsSb/AlGaAsSb, or any other suitable detector for the wavelength of analytical radiation used.
- the detector 40 may be an extended InGaAs pin photodiode for detecting measurements in the analytical spectral ranges of between about 1000 nm and about 2600 nm.
- An alternative, more economical detector 40 is a silicon photodiode, which is particularly useful where the analytical spectral range is less than about 1000 nm.
- the detector 40 may be cooled by using, for example, a cryogenic or thermoelectric cooler.
- the radiation source 20 and the detector 40 are configured such that the intensity of the analytical radiation received by the detector 40 is subject to attenuation by the analyte within at least a portion of the analytical spectral range. This attenuation is recorded as a function of wavelength.
- the detector 40 is configured to receive the analytical radiation and generate a signal indicative of attenuation of the analytical radiation over at least a portion of the analytical spectral range.
- An analog-to-digital converter 42 may be provided to convert the signal indicative of attenuation of the analytical radiation into a digital signal.
- the system 10 may also contain a processor 44 .
- the processor 44 may be configured to receive the digital signal indicative of attenuation of the analytical radiation from the analog-to-digital converter 42 .
- the processor 44 determines the absorption spectrum in the analytical spectral range wherein the analyte of interest has a distinct absorption spectrum.
- the processor 44 correlates the absorption spectrum of the analytical radiation with an analyte of interest in the specimen 30 to arrive at the concentration of the analyte of interest in the specimen 30 .
- the processor 44 then transfers the concentration value to an output/control device 50 or another device external to the system 10 .
- the output/control device 50 may be an output display device which then displays the concentration of the analyte of interest.
- the output/control device 50 may be an analyte control device that is configured to react in accordance to the inputted concentration of the analyte of interest by adjusting the levels of analyte of interest concentration in the specimen 30 .
- the analyte control device can be, for example, an insulin pump when the analyte of interest is blood glucose, but any other similar control device can be used.
- the processor 44 utilizes step scanning. With step scanning, the radiation source 20 is fixed at a single wavelength. The signals from the radiation source 20 are accumulated and averaged by the processor 44 until the desired signal-to-noise ratio is established. The signal-to-noise ratio may be established by calculation, measurement, input, or by any suitable means of establishing a signal-to-noise ratio. After the desired signal-to-noise ratio is established, the radiation source 20 moves to the next wavelength and the process is repeated until the desired signal-to-noise ratio is established at the next wavelength. This process continues over the target spectral range. For example, signals from ten distinct wavelengths between 2.1 ⁇ m and 2.4 ⁇ m may be accumulated and averaged by the processor 44 .
- the radiation source 20 scans across the entire analytical spectral range over a very short time duration, usually within a fraction of the cardiac period if the specimen 30 is biological and characterized by a cardiac period.
- the processor 44 collects the measurements across the entire analytical spectral range and determines the signal-to-noise ratio. The process of scanning across the entire analytical spectral range over a very short time duration is repeated until the desired signal-to-noise ratio is achieved.
Abstract
A system and method for determining the concentration of analytes of interest in complex matrices is provided. According to one aspect of the present invention, near-infrared analytical radiation is generally directed onto a portion of a specimen containing the analyte of interest. A wavelength of the analytical radiation is scanned over the specimen over a broad range of frequencies and over a short duration of diagnostic time. A spectrum of radiation is transmitted through, reflected from or scattered from the specimen and collected by a detector. The concentration of the analyte of interest in the specimen is determined by the radiation collected by the detector.
Description
- This application is a continuation of U.S. patent application Ser. No. 10/745,092, filed Dec. 23, 2003 (PRN 0001 PA), now U.S. Pat. No. ______, which application claims the benefit of U.S. Provisional Application Ser. No. 60/436,761, filed Dec. 27, 2002.
- The present invention relates to the determination of the concentration of various analytes of interest in various complex matrices. The invention is applicable in a broad range of chemical analyses in a variety of fields including, but not limited to, non-invasive blood analysis and other medical applications, food and pharmaceutical industries, environmental monitoring, industrial safety, etc. In the analysis of blood, blood glucose concentration and measurements of cholesterol and tryglicerides concentrations in blood are of significant importance.
- In accordance with one embodiment of the present invention, a method and system for determining the concentration of analytes of interest in complex matrices, for example, glucose in blood, is provided. Analytical radiation is generated and directed onto a portion of a specimen containing the analytes of interest. The wavelength of the analytical radiation is scanned over a broad analytical spectral range and over a relatively short duration of diagnostic time. The analytical radiation attenuated by the specimen is collected. Subsequently, the amount of collected radiation attenuated by the specimen is correlated to the concentration of the analyte of interest in the specimen. The concentration of the analyte of interest in the specimen then may then be displayed on an output display device as well as used as input into an analyte control device, such as an insulin pump. Multivariate analysis techniques may be used to relate measured spectra to the concentration of the analyte of interest.
- Other embodiments of the present invention may be utilized to overcome the problem of insufficient signal-to-noise ratio in measurements of glucose and other analytes of interest in the specimen. An increase in signal-to-noise ratio allows measurements to be taken within a relatively short duration of diagnostic time, which helps to eliminate problems associated with hardware and specimen noise.
- It is an object of the present invention to meet the well perceived need for a simple and reliable method of measurements of analytes in complex matrices, as well as the need for a portable, rugged device for non-invasive measurements of blood constituents, in particular, blood glucose monitoring in diabetic subjects.
- It is another object of the present invention to use the present invention in contexts where the rather weak absorptivity of some compounds, e.g., glucose, imposes challenging requirements on the signal-to-noise ratio in the spectra for analysis.
- Other objects of the present invention will be apparent in light of the description of the invention embodied herein.
- The following detailed description of specific embodiments of the present invention can be best understood when read in conjunction with the following drawing in which:
-
FIG. 1 is a schematic diagram of a system for detecting an analyte in a specimen according to an embodiment of the present invention. - In the following detailed description of the preferred embodiments, reference is made to the accompanying drawing that forms a part hereof, and in which is shown by way of illustration, and not by way of limitation, a specific embodiment in which the invention may be practiced. It is to be understood that other embodiments may be utilized and that logical, mechanical and electrical changes may be made without departing from the spirit and scope of the present invention.
- Referring to
FIG. 1 , asystem 10 for detecting an analyte in aspecimen 30 according to an embodiment of the present invention is illustrated. It is contemplated that specimens according to the present invention may comprise biological or non-biological specimens. Biological specimens according to the present invention include, but are not limited to, specimens characterized by a cardiac cycle. A variety of non-biological specimens are contemplated by the present invention including, but not limited to, water, food, air, etc. Analytes of interest may include components ordinarily present in the specimen of interest, e.g., glucose in blood or tissue, or components that represent pollutants or contaminants in a specimen of interest. - The
system 10 comprises aradiation source 20 and adetector 40. In one embodiment, both theradiation source 20 and thedetector 40 are portable and rugged. Theradiation source 20 may be, for example, a laser, an optical parametric oscillator (OPO), or a light emitting diode (LED). Theradiation source 20 may be a single broadly tunable laser. Suitable lasers, include, but are not limited to, a semiconductor laser diode, a fiber laser, a solid state laser, a quantum cascade laser, or a color center laser. Semiconductor lasers are compact and power efficient and allow thesystem 10 to be more readily portable. Cr doped ZnSe, ZnS, or CdS lasers are also contemplated because of particular advantages in the context of wavelength scanning. In one embodiment, theradiation source 20 is an external cavity semiconductor laser diode. In addition, theradiation source 20 may employ the Littman-Metcalf, Littrow, or any other suitable external cavity configuration. - The
radiation source 20 is configured to generate analytical radiation and scan over an analytical spectral range. The analyte of interest present within thespecimen 30 has unique absorption spectrum within the analytical spectral range. For example, glucose in blood is characterized by an absorption spectrum that includes absorption lines at about 1.56 μm, 2.15 μm, 2.27 μm, and 2.32 μm, each within a source spectral range of between 900 nm and 2700 nm. - In one embodiment of the present invention, the
radiation source 20 scans a wavelength of the analytical radiation over the analytical spectral range over a predetermined diagnostic time period. The duration of the diagnostic time period is relatively short. For example, in embodiments where the specimen is biological and is characterized by a cardiac cycle, the diagnostic time period is no greater than the duration of the cardiac period of the specimen. For example, a cardiac period of a human typically ranges from about 0.3 to about 2 seconds. Typically, the duration of the diagnostic time period is a fraction of the cardiac period (e.g., less than one half of the cardiac period). For example, the duration of the diagnostic time period may be 0.01 second in the case of determining blood glucose concentration in a human. - The analytical radiation emitted by the
radiation source 20 may define a relatively narrow spectral line with a width of less than about 20 nm. Preferably, the spectral line width is about 1 nm. The analytical spectral range may from between about 900 nm and about 2700 nm and should be broad enough to discriminate the contributions of any other analytes present in thespecimen 30. In the case of blood glucose, the range is broad enough to discriminate from the contributions of the other analytes in the human body, such as, for example, urea, proteins and other similar analytes. An analytical spectral range from about 2050 nm to about 2400 nm may be suitable in many contexts. Theradiation source 20, in addition, may also be configured to control the width of the analytical spectral range. - The
radiation source 20 delivers the analytical radiation to thespecimen 30. Thedetector 40, in turn, collects the radiation reflected from, scattered from, or transmitted through thespecimen 30 of the analytical radiation. Collection of radiation transmitted through thespecimen 30 is most suitable for specimen areas that are relatively thin. For example, if thespecimen 30 is human, the transmissions can be collected from the ear, the web area between the thumb and index finger, skin pinch on the back of the hand, or in any other similar thin area of the body where transmissions may be collected through thespecimen 30. Radiation reflected or scattered from a nail of a finger or toe is another potential site of collection of the analytical radiation if thespecimen 30 is human. - In another embodiment, the
radiation source 20 may be configured to utilize optics to aid in directing the analytical radiation onto thespecimen 30. In the same vein, thedetector 40 may also be configured to utilize optics to aid in collections of the attenuated analytical radiation from thespecimen 30. - In yet another embodiment, conduits are used to deliver the analytical radiation to the
specimen 30 as well as to collect the reflected, scattered, or transmitted radiation from thespecimen 30. Aconduit 24 delivers the analytical radiation from thesource 20 to thespecimen 30. Anotherconduit 32 collects the reflected, scattered, or transmitted radiation from thespecimen 30 to thedetector 40. - The
conduits conduits conduits optic bundle conduits system 10. Theconduits specimen 30 itself, or any suitable transmission medium. - The
detector 40 may be a single detector or a multi-channel detector array. Thedetector 40 may have a high sensitivity to the wavelength of analytical radiation used. Thedetector 40 may be, for example, PbS, HgCdTe, HgCdZnTe, InGaAsSb/AlGaAsSb, or any other suitable detector for the wavelength of analytical radiation used. For example, thedetector 40 may be an extended InGaAs pin photodiode for detecting measurements in the analytical spectral ranges of between about 1000 nm and about 2600 nm. An alternative, moreeconomical detector 40 is a silicon photodiode, which is particularly useful where the analytical spectral range is less than about 1000 nm. For increased sensitivity, thedetector 40 may be cooled by using, for example, a cryogenic or thermoelectric cooler. - The
radiation source 20 and thedetector 40 are configured such that the intensity of the analytical radiation received by thedetector 40 is subject to attenuation by the analyte within at least a portion of the analytical spectral range. This attenuation is recorded as a function of wavelength. Thedetector 40 is configured to receive the analytical radiation and generate a signal indicative of attenuation of the analytical radiation over at least a portion of the analytical spectral range. An analog-to-digital converter 42 may be provided to convert the signal indicative of attenuation of the analytical radiation into a digital signal. - The
system 10 may also contain aprocessor 44. Theprocessor 44 may be configured to receive the digital signal indicative of attenuation of the analytical radiation from the analog-to-digital converter 42. Theprocessor 44 determines the absorption spectrum in the analytical spectral range wherein the analyte of interest has a distinct absorption spectrum. Theprocessor 44 correlates the absorption spectrum of the analytical radiation with an analyte of interest in thespecimen 30 to arrive at the concentration of the analyte of interest in thespecimen 30. - The
processor 44 then transfers the concentration value to an output/control device 50 or another device external to thesystem 10. The output/control device 50 may be an output display device which then displays the concentration of the analyte of interest. Alternatively, or additionally, the output/control device 50 may be an analyte control device that is configured to react in accordance to the inputted concentration of the analyte of interest by adjusting the levels of analyte of interest concentration in thespecimen 30. The analyte control device can be, for example, an insulin pump when the analyte of interest is blood glucose, but any other similar control device can be used. - In one embodiment of the present invention, the
processor 44 utilizes step scanning. With step scanning, theradiation source 20 is fixed at a single wavelength. The signals from theradiation source 20 are accumulated and averaged by theprocessor 44 until the desired signal-to-noise ratio is established. The signal-to-noise ratio may be established by calculation, measurement, input, or by any suitable means of establishing a signal-to-noise ratio. After the desired signal-to-noise ratio is established, theradiation source 20 moves to the next wavelength and the process is repeated until the desired signal-to-noise ratio is established at the next wavelength. This process continues over the target spectral range. For example, signals from ten distinct wavelengths between 2.1 μm and 2.4 μm may be accumulated and averaged by theprocessor 44. - In another embodiment, the
radiation source 20 scans across the entire analytical spectral range over a very short time duration, usually within a fraction of the cardiac period if thespecimen 30 is biological and characterized by a cardiac period. Theprocessor 44, in turn, collects the measurements across the entire analytical spectral range and determines the signal-to-noise ratio. The process of scanning across the entire analytical spectral range over a very short time duration is repeated until the desired signal-to-noise ratio is achieved. By taking the measurements within a fraction of the cardiac period, this technique results in an essentially static testing environment, helping to eliminate hardware and specimen noise, thereby, resulting in increased signal quality. - It is noted that terms like “preferably,” “commonly,” and “typically” are not utilized herein to limit the scope of the claimed invention or to imply that certain features are critical, essential, or even important to the structure or function of the claimed invention. Rather, these terms are merely intended to highlight alternative or additional features that may or may not be utilized in a particular embodiment of the present invention.
- Having described the invention in detail and by reference to specific embodiments thereof, it will be apparent that modifications and variations are possible without departing from the scope of the invention defined in the appended claims. More specifically, although some aspects of the present invention are identified herein as preferred or particularly advantageous, it is contemplated that the present invention is not necessarily limited to these preferred aspects of the invention.
Claims (12)
1. A method for determining the concentration of an analyte in a specimen, the method comprising:
generating analytical radiation characterized by a spectral line width less than about 20 nm;
irradiating the specimen with the analytical radiation while scanning a wavelength of the analytical radiation over an analytical spectral range of at least about 350 nm, wherein the analytical spectral range lies between about 900 nm and about 2700 nm;
detecting attenuation of the analytical radiation by the specimen over the analytical spectral range;
providing an indication of the attenuation of the analytical radiation as a function of wavelength;
correlating the attenuation with predetermined characteristics of the analyte to determine the concentration of the analyte in the specimen; and
generating an output signal indicative of the concentration.
2. A method as claimed in claim 1 wherein the wavelength of the analytical radiation defines a spectral width of less than about 1 nm.
3. A method as claimed in claim 1 wherein a width of the analytical spectral range is controlled to be broad enough to discriminate the contributions of the analyte from other analytes present in the specimen.
4. A method as claimed in claim 1 wherein the specimen is irradiated with the analytical radiation while scanning the wavelength of the analytical radiation over the analytical spectral range a plurality of times prior to generating the output signal indicative of the concentration.
5. A method as claimed in claim 4 wherein the specimen comprises a biological specimen characterized by a cardiac period and the wavelength of the analytical radiation is scanned over the analytical spectral range within a fraction of the cardiac period.
6. A method as claimed in claim 1 wherein the wavelength scanning is controlled in wavelength steps and the wavelength of the analytical radiation moves from one wavelength to the next within the spectral range after a desired signal-to-noise ratio in detecting the attenuation exceeds a given value.
7. A method as claimed in claim 1 wherein a signal-to-noise ratio associated with the attenuation signal is established and the scanning of the wavelength over the analytical spectral range is repeated until the signal-to-noise ratio exceeds a given value.
8. A method as claimed in claim 1 wherein a signal-to-noise ratio associated with the attenuation signal is established and the scanning of the wavelength over the analytical spectral range is maintained until the signal-to-noise ratio exceeds a given value.
9. A method as claimed in claim 1 wherein the method further comprises displaying the concentration of the analyte.
10. A method as claimed in claim 1 wherein the method further comprises controlling an external device as a function of the output signal.
11. A method as claimed in claim 10 wherein the external device is controlled to adjust the concentration of the analyte of interest in the specimen as function of the output signal.
12. A method for detecting an analyte in a specimen, the method comprising:
generating analytical radiation characterized by a spectral line width of about 1 nm;
irradiating the specimen with the analytical radiation while scanning a wavelength of the analytical radiation over an analytical spectral range of at least about 350 nm, wherein a width of the analytical spectral range is controlled to be broad enough to discriminate the contributions of the analyte from other analytes present in the specimen and the analytical spectral range lies between about 900 nm and about 2700 nm;
detecting attenuation of the analytical radiation by the specimen over the analytical spectral range wherein a signal-to-noise ratio associated with the attenuation signal is established and the scanning of the wavelength over the analytical spectral range is maintained until the signal-to-noise ratio exceeds a given value;
providing an indication of the attenuation of the analytical radiation as a function of wavelength;
correlating the attenuation with predetermined characteristics of the analyte to determine the concentration of the analyte in the specimen;
generating an output signal indicative of the concentration; and
displaying the concentration of the analyte or controlling an external device as a function of the output signal.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/620,101 US20080023634A1 (en) | 2002-12-27 | 2007-01-05 | Non-invasive detection of analytes in a comples matrix |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US43676102P | 2002-12-27 | 2002-12-27 | |
US10/745,092 US7174198B2 (en) | 2002-12-27 | 2003-12-23 | Non-invasive detection of analytes in a complex matrix |
US11/620,101 US20080023634A1 (en) | 2002-12-27 | 2007-01-05 | Non-invasive detection of analytes in a comples matrix |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/745,092 Continuation US7174198B2 (en) | 2002-12-27 | 2003-12-23 | Non-invasive detection of analytes in a complex matrix |
Publications (1)
Publication Number | Publication Date |
---|---|
US20080023634A1 true US20080023634A1 (en) | 2008-01-31 |
Family
ID=32717860
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/745,092 Expired - Fee Related US7174198B2 (en) | 2002-12-27 | 2003-12-23 | Non-invasive detection of analytes in a complex matrix |
US11/620,101 Abandoned US20080023634A1 (en) | 2002-12-27 | 2007-01-05 | Non-invasive detection of analytes in a comples matrix |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/745,092 Expired - Fee Related US7174198B2 (en) | 2002-12-27 | 2003-12-23 | Non-invasive detection of analytes in a complex matrix |
Country Status (1)
Country | Link |
---|---|
US (2) | US7174198B2 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109959455A (en) * | 2019-03-13 | 2019-07-02 | 浙江大学 | One kind is based on lensless static infrared target scanned imagery device and method |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7174198B2 (en) * | 2002-12-27 | 2007-02-06 | Igor Trofimov | Non-invasive detection of analytes in a complex matrix |
US8133194B2 (en) * | 2006-02-22 | 2012-03-13 | Henry Ford Health System | System and method for delivery of regional citrate anticoagulation to extracorporeal blood circuits |
US8211048B2 (en) * | 2006-02-22 | 2012-07-03 | Henry Ford Health System | System and method for delivery of regional citrate anticoagulation to extracorporeal blood circuits |
US7729734B2 (en) * | 2006-03-07 | 2010-06-01 | Andreas Mandelis | Non-invasive biothermophotonic sensor for blood glucose monitoring |
US20110009720A1 (en) * | 2006-11-02 | 2011-01-13 | Kislaya Kunjan | Continuous whole blood glucose monitor |
US8260556B2 (en) * | 2008-08-21 | 2012-09-04 | Bio-Rad Laboratories, Inc. | Calibration surface method for determination on of analyte ratios |
US8649835B2 (en) * | 2009-11-17 | 2014-02-11 | Andreas Mandelis | Method of performing wavelength modulated differential laser photothermal radiometry with high sensitivity |
US8536529B2 (en) | 2010-10-13 | 2013-09-17 | The Boeing Company | Non-contact surface chemistry measurement apparatus and method |
WO2016154613A1 (en) * | 2015-03-26 | 2016-09-29 | President And Fellows Of Harvard College | Methods for biological analytes separation and identification |
CN205958453U (en) * | 2016-08-19 | 2017-02-15 | 深圳市前海康启源科技有限公司 | Glucose concentration detection device |
Citations (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3983507A (en) * | 1975-01-06 | 1976-09-28 | Research Corporation | Tunable laser systems and method |
US4200808A (en) * | 1978-01-30 | 1980-04-29 | Quanta-Ray, Inc. | Continuously tunable wideband coherent infrared source |
US4225233A (en) * | 1978-02-02 | 1980-09-30 | The Trustees Of Boston University | Rapid scan spectrophotometer |
US4349907A (en) * | 1980-04-23 | 1982-09-14 | The United Stated Of America As Represented By The Department Of Energy | Broadly tunable picosecond IR source |
US4655225A (en) * | 1985-04-18 | 1987-04-07 | Kurabo Industries Ltd. | Spectrophotometric method and apparatus for the non-invasive |
US4975581A (en) * | 1989-06-21 | 1990-12-04 | University Of New Mexico | Method of and apparatus for determining the similarity of a biological analyte from a model constructed from known biological fluids |
US5028787A (en) * | 1989-01-19 | 1991-07-02 | Futrex, Inc. | Non-invasive measurement of blood glucose |
US5070874A (en) * | 1990-01-30 | 1991-12-10 | Biocontrol Technology, Inc. | Non-invasive determination of glucose concentration in body of patients |
US5086229A (en) * | 1989-01-19 | 1992-02-04 | Futrex, Inc. | Non-invasive measurement of blood glucose |
US5137023A (en) * | 1990-04-19 | 1992-08-11 | Worcester Polytechnic Institute | Method and apparatus for monitoring blood analytes noninvasively by pulsatile photoplethysmography |
US5144630A (en) * | 1991-07-29 | 1992-09-01 | Jtt International, Inc. | Multiwavelength solid state laser using frequency conversion techniques |
US5267152A (en) * | 1989-10-28 | 1993-11-30 | Yang Won S | Non-invasive method and apparatus for measuring blood glucose concentration |
US5348003A (en) * | 1992-09-03 | 1994-09-20 | Sirraya, Inc. | Method and apparatus for chemical analysis |
US5360004A (en) * | 1992-12-09 | 1994-11-01 | Diasense, Inc. | Non-invasive determination of analyte concentration using non-continuous radiation |
US5361758A (en) * | 1988-06-09 | 1994-11-08 | Cme Telemetrix Inc. | Method and device for measuring concentration levels of blood constituents non-invasively |
US5460177A (en) * | 1993-05-07 | 1995-10-24 | Diasense, Inc. | Method for non-invasive measurement of concentration of analytes in blood using continuous spectrum radiation |
US5529755A (en) * | 1994-02-22 | 1996-06-25 | Minolta Co., Ltd. | Apparatus for measuring a glucose concentration |
US5703364A (en) * | 1996-02-15 | 1997-12-30 | Futrex, Inc. | Method and apparatus for near-infrared quantitative analysis |
US5747806A (en) * | 1996-02-02 | 1998-05-05 | Instrumentation Metrics, Inc | Method and apparatus for multi-spectral analysis in noninvasive nir spectroscopy |
US5910109A (en) * | 1997-02-20 | 1999-06-08 | Emerging Technology Systems, Llc | Non-invasive glucose measuring device and method for measuring blood glucose |
US6043492A (en) * | 1997-10-27 | 2000-03-28 | Industrial Technology Research Institute | Non-invasive blood glucose meter |
US6049727A (en) * | 1996-07-08 | 2000-04-11 | Animas Corporation | Implantable sensor and system for in vivo measurement and control of fluid constituent levels |
US6097975A (en) * | 1998-05-13 | 2000-08-01 | Biosensor, Inc. | Apparatus and method for noninvasive glucose measurement |
US6151517A (en) * | 1999-01-22 | 2000-11-21 | Futrex Inc. | Method and apparatus for noninvasive quantitative measurement of blood analytes |
US6425865B1 (en) * | 1998-06-12 | 2002-07-30 | The University Of British Columbia | Robotically assisted medical ultrasound |
US6438147B1 (en) * | 1996-07-26 | 2002-08-20 | Perkin Elmer Instruments Llc | Tunable external cavity diode laser |
US6573737B1 (en) * | 2000-03-10 | 2003-06-03 | The Trustees Of Princeton University | Method and apparatus for non-contact measurement of electrical properties of materials |
US20050043606A1 (en) * | 2001-09-25 | 2005-02-24 | Eliahu Pewzner | Multiparametric apparatus for monitoring multiple tissue vitality parameters |
US7174198B2 (en) * | 2002-12-27 | 2007-02-06 | Igor Trofimov | Non-invasive detection of analytes in a complex matrix |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5735273A (en) * | 1995-09-12 | 1998-04-07 | Cygnus, Inc. | Chemical signal-impermeable mask |
-
2003
- 2003-12-23 US US10/745,092 patent/US7174198B2/en not_active Expired - Fee Related
-
2007
- 2007-01-05 US US11/620,101 patent/US20080023634A1/en not_active Abandoned
Patent Citations (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3983507A (en) * | 1975-01-06 | 1976-09-28 | Research Corporation | Tunable laser systems and method |
US4200808A (en) * | 1978-01-30 | 1980-04-29 | Quanta-Ray, Inc. | Continuously tunable wideband coherent infrared source |
US4225233A (en) * | 1978-02-02 | 1980-09-30 | The Trustees Of Boston University | Rapid scan spectrophotometer |
US4349907A (en) * | 1980-04-23 | 1982-09-14 | The United Stated Of America As Represented By The Department Of Energy | Broadly tunable picosecond IR source |
US4655225A (en) * | 1985-04-18 | 1987-04-07 | Kurabo Industries Ltd. | Spectrophotometric method and apparatus for the non-invasive |
US5361758A (en) * | 1988-06-09 | 1994-11-08 | Cme Telemetrix Inc. | Method and device for measuring concentration levels of blood constituents non-invasively |
US5028787A (en) * | 1989-01-19 | 1991-07-02 | Futrex, Inc. | Non-invasive measurement of blood glucose |
US5086229A (en) * | 1989-01-19 | 1992-02-04 | Futrex, Inc. | Non-invasive measurement of blood glucose |
US4975581A (en) * | 1989-06-21 | 1990-12-04 | University Of New Mexico | Method of and apparatus for determining the similarity of a biological analyte from a model constructed from known biological fluids |
US5267152A (en) * | 1989-10-28 | 1993-11-30 | Yang Won S | Non-invasive method and apparatus for measuring blood glucose concentration |
US5070874A (en) * | 1990-01-30 | 1991-12-10 | Biocontrol Technology, Inc. | Non-invasive determination of glucose concentration in body of patients |
US5137023A (en) * | 1990-04-19 | 1992-08-11 | Worcester Polytechnic Institute | Method and apparatus for monitoring blood analytes noninvasively by pulsatile photoplethysmography |
US5144630A (en) * | 1991-07-29 | 1992-09-01 | Jtt International, Inc. | Multiwavelength solid state laser using frequency conversion techniques |
US5348003A (en) * | 1992-09-03 | 1994-09-20 | Sirraya, Inc. | Method and apparatus for chemical analysis |
US5360004A (en) * | 1992-12-09 | 1994-11-01 | Diasense, Inc. | Non-invasive determination of analyte concentration using non-continuous radiation |
US5460177A (en) * | 1993-05-07 | 1995-10-24 | Diasense, Inc. | Method for non-invasive measurement of concentration of analytes in blood using continuous spectrum radiation |
US5529755A (en) * | 1994-02-22 | 1996-06-25 | Minolta Co., Ltd. | Apparatus for measuring a glucose concentration |
US5747806A (en) * | 1996-02-02 | 1998-05-05 | Instrumentation Metrics, Inc | Method and apparatus for multi-spectral analysis in noninvasive nir spectroscopy |
US5703364A (en) * | 1996-02-15 | 1997-12-30 | Futrex, Inc. | Method and apparatus for near-infrared quantitative analysis |
US6049727A (en) * | 1996-07-08 | 2000-04-11 | Animas Corporation | Implantable sensor and system for in vivo measurement and control of fluid constituent levels |
US6438147B1 (en) * | 1996-07-26 | 2002-08-20 | Perkin Elmer Instruments Llc | Tunable external cavity diode laser |
US5910109A (en) * | 1997-02-20 | 1999-06-08 | Emerging Technology Systems, Llc | Non-invasive glucose measuring device and method for measuring blood glucose |
US6043492A (en) * | 1997-10-27 | 2000-03-28 | Industrial Technology Research Institute | Non-invasive blood glucose meter |
US6097975A (en) * | 1998-05-13 | 2000-08-01 | Biosensor, Inc. | Apparatus and method for noninvasive glucose measurement |
US6425865B1 (en) * | 1998-06-12 | 2002-07-30 | The University Of British Columbia | Robotically assisted medical ultrasound |
US6151517A (en) * | 1999-01-22 | 2000-11-21 | Futrex Inc. | Method and apparatus for noninvasive quantitative measurement of blood analytes |
US6573737B1 (en) * | 2000-03-10 | 2003-06-03 | The Trustees Of Princeton University | Method and apparatus for non-contact measurement of electrical properties of materials |
US20050043606A1 (en) * | 2001-09-25 | 2005-02-24 | Eliahu Pewzner | Multiparametric apparatus for monitoring multiple tissue vitality parameters |
US7174198B2 (en) * | 2002-12-27 | 2007-02-06 | Igor Trofimov | Non-invasive detection of analytes in a complex matrix |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109959455A (en) * | 2019-03-13 | 2019-07-02 | 浙江大学 | One kind is based on lensless static infrared target scanned imagery device and method |
Also Published As
Publication number | Publication date |
---|---|
US7174198B2 (en) | 2007-02-06 |
US20040135085A1 (en) | 2004-07-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20080023634A1 (en) | Non-invasive detection of analytes in a comples matrix | |
US6167290A (en) | Method and apparatus of non-invasive measurement of human/animal blood glucose and other metabolites | |
US6064897A (en) | Sensor utilizing Raman spectroscopy for non-invasive monitoring of analytes in biological fluid and method of use | |
JP3643842B2 (en) | Glucose concentration testing device | |
US5383452A (en) | Method, apparatus and procedure for non-invasive monitoring blood glucose by measuring the polarization ratio of blood luminescence | |
JP3686422B2 (en) | Measurement of tissue analyte by infrared rays | |
US8886268B2 (en) | Living body information measuring apparatus | |
US5348002A (en) | Method and apparatus for material analysis | |
US20020161289A1 (en) | Detector array for optical spectrographs | |
EP0670143A1 (en) | Blood sugar level non-invasion measuring method and measuring instrument therefor | |
US8306594B2 (en) | Transmission fluorometer | |
EP1460413B1 (en) | Method and apparatus for in vitro or in vivo measurement of a concentration of a component | |
US20060211926A1 (en) | Non-invasive Raman measurement apparatus with broadband spectral correction | |
US6625480B2 (en) | Apparatus and method for measuring a concentration of a component of a target material | |
Koo et al. | Reagentless blood analysis by near-infrared Raman spectroscopy | |
US20230148312A1 (en) | Device for non-invasive blood glucose concentration measurement | |
Itzkan et al. | Reagentless diagnostics; Near-IR Raman spectroscopy | |
JPH08189891A (en) | Non-invasive biochemical measuring device |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |