EP0609341A1 - Procede et appareil de determination non-invasive d'analytes sanguins - Google Patents

Procede et appareil de determination non-invasive d'analytes sanguins

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Publication number
EP0609341A1
EP0609341A1 EP92922310A EP92922310A EP0609341A1 EP 0609341 A1 EP0609341 A1 EP 0609341A1 EP 92922310 A EP92922310 A EP 92922310A EP 92922310 A EP92922310 A EP 92922310A EP 0609341 A1 EP0609341 A1 EP 0609341A1
Authority
EP
European Patent Office
Prior art keywords
animal
concentration
analytes
light
blood
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.)
Withdrawn
Application number
EP92922310A
Other languages
German (de)
English (en)
Inventor
Alastair Roy Macgregor
Robert Martin Pettigrew
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Scientific Generics Ltd
Original Assignee
Scientific Generics Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GB919122045A external-priority patent/GB9122045D0/en
Priority claimed from GB929207149A external-priority patent/GB9207149D0/en
Application filed by Scientific Generics Ltd filed Critical Scientific Generics Ltd
Publication of EP0609341A1 publication Critical patent/EP0609341A1/fr
Withdrawn legal-status Critical Current

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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
    • A61B5/14558—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 by polarisation
    • 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

Definitions

  • This invention relates to the determination of blood analytes by a non-invasive method.
  • the method itself is a general one, and can be used for a wide variety of materials present in blood, it is of particular interest in the non-invasive measurement of substances of interest in diabetes, such as glucose and glycated haemoglobin.
  • Blood glucose level testing is almost universally regarded as the first line in maintaining the control of diabetes. Typically, it may be desirable for the blood glucose level of a diabetic patient to be monitored several times during a day.
  • the most common method of blood glucose level testing in current practice uses test strips to which a blood sample is applied. This requires a small blood sample to be withdrawn, usually by pricking the finger. The strips are usually tested using a portable battery operated glucose meter which reads the strips quantitatively. Obviously, it is undesirable for repeated blood samples to be taken from patients, and much interest has focused in recent years on non-invasive techniques for blood measurement.
  • NIR near infrared region
  • EP-A-0160768 discloses a technique for measuring glucose by a non-invasive infrared technique in which a body part (typically a finger) is irradiated with one or more pairs of wavelengths in the region of from 1000 to 2700 n , and detecting the transmitted or reflected radiation.
  • a broad band optical source is filtered to produce desired wavelengths one after the other.
  • the wavelengths are chosen such that the intensity of collected light at at least one wavelength depends on the glucose concentration present, while the collected intensity at at least one other wavelength is in principle independent of the glucose concentration present.
  • the intensity measurements are converted to measure the glucose concentration by standard techniques of NIR spectroscopy.
  • the wavelengths ⁇ _ are chosen from 1575, 1765, 2100, and 2270 ⁇ 15 nm.
  • O/90/07905 also relates to the determination of blood glucose, using NIR.
  • a body part again generally a finger, is irradiated using NIR of a number of different frequencies using an array of light emitting diodes (LEDs).
  • LEDs light emitting diodes
  • Interference filters are employed to restrict the response of each detector and/or the emission of each LED to a particular NIR band, and calibration algorithms are used to relate glucose levels to a linear combination of the detected bands.
  • the use of a greater number of wavelengths improves sensitivity, and enables accuracy to be improved over the device of EP-A-0160768.
  • a method for determining non- invasively the presence and/or concentration of blood analytes in an animal which method comprises,
  • the front surface of the eye has a number of advantages over other surfaces which have previously been proposed for non-invasive NIR spectroscopy for blood analyte (in particular glucose) determination.
  • blood analyte in particular glucose
  • the eye tends to have a very stable temperature, as compared with many other parts of the body
  • the eye has a number of other advantages for such measurement.
  • the front surface of the eye (the white of the eye), and the adjoining tissues (for example, in the corner of the eye) are particularly well supplied at their surface with blood vessels.
  • the superficiality of the blood vessels in the eye enables reflection spectral measurements to be made from the eye at wavelengths which would be unsuitable for other body parts. This is because the blood vessels in other body parts are situated sufficiently far below the tissue surface that infrared radiation does not penetrate to them in significant amounts.
  • a further advantage of the surface ocular tissue is that it is relatively simple in structure and does not give rise to high levels of scattering.
  • An additional advantage of carrying out measurement on the eye is that, because the surface is relatively smooth and is maintained in a moist condition, specular reflection occurs at relatively well defined angles, and it is therefore relatively easy to separate specular refection from diffuse reflection. It is the defuse reflection which carries the bulk of the spectral information representative of blood analyte levels.
  • means In order to be able to determine reflected light from the front surface of the eye, means must be provided both for illuminating the said front surface, and for detecting light which is diffusely reflected (backscattered) from the illuminated surface. It is also necessary to provide means of locating either or both of the illuminating means and the detecting means, with respect to the facial features of the individual concerned.
  • apparatus for determining non-invasively the presence and/or concentration of blood analytes in an animal comprising:-
  • the said surface is the front surface of the eye
  • the apparatus includes means for locating the illumination means and/or the detecting means in a fixed location with respect to facial features of the animal.
  • the location means may preferably be a molding shaped to fit the particular face contours of the individual, for example the eye socket and/or nose of the individual.
  • a "standard" assembly carrying the illumination means and detecting means may be provided, and adapted to be fixed in a defined location to a molding shaped to the facial contours of the particular individual in question, so that, after the molding has been produced for that individual, the device may thereafter reproducibly be located in the same place.
  • the device may be specially adapted so as to focus on the edge regions of the eye which are particularly strongly supplied with blood vessels, and in particular the inner and outer corners of the eye.
  • the device is provided with means for minimising the effects of specular reflection. In one embodiment, this may be done by so positioning the illumination means and the detector on the device so that specular reflection is substantially eliminated.
  • the device may be so orientated as to ensure that specularly reflected light does not reach the detector.
  • the- detector may be such as to be capable of detecting spatial variations in the reflected signal.
  • the detector may include a CCD array. The provision of such an array enables the location of the specular reflection to be readily ascertained, and, once ascertained, compensation may be applied to minimise its affects (for example by ignoring entirely the region in space in which the specular reflection occurs).
  • means are provided for discriminating between diffuse reflection and specular reflection from the eye surface based on the extent of polarization of the light on reflection.
  • This may take the form of a polarizer associated with either the illumination means, the detecting means, or both, so orientated as to minimize the signal obtained from specular reflection.
  • a polariser may be inserted in the light beam to linearly polarise the light incident on the eye perpendicular to the plane of incidence.
  • An analyser also consisting of a polariser, may be inserted in the beam following its reflection from the eye. This polariser is orientated so as to block specularly reflected light from the eye.
  • the analyser may be crossed with respect to the polariser. Circularly polarised light might also be used.
  • a wave plate may also be used in conjunction with polarising elements.
  • a further aspect of the invention is concerned with the nature of the instrument itself, and of the NIR bands which are detected.
  • the device disclosed in WO90/079O5 indicates the desirability of measuring absorption at a number of points in the NIR spectrum, and combining the results obtained from these points in order to obtain quantitative results which indicate more accurately the presence of analytes present.
  • This reference relies however on the use of individual LEDs and/or detectors. This results in a device which is mechanically very complex, and therefore difficult and expensive to produce.
  • WO90/079O5 describes measurements made at wavelengths of up to about llOOnm, a region of the spectrum which is detectable using low-cost silicon detectors.
  • glucose absorption in this region is very weak, and the absorptions overlap very strongly with water absorption.
  • detectors for use at longer wavelengths are more expensive, and the use of individual detectors for each absorption band is therefore very expensive if longer wavelengths are to be detected.
  • the device in question was viewed as something of a curiosity when it was proposed in the mid-60s, and so far as we are aware it has never been produced commercially.
  • apparatus for determining non-invasively the presence and/or concentration of blood analytes in an animal co prising -
  • the apparatus may preferably be used in accordance with the first aspect of the invention for carrying out measurements on the front part of the eye, but may also be employed on other body surfaces.
  • the modulating means preferably includes a rotatable grating, means for rotating the grating, and means for producing an image of the grating on the grating, at a position which is displaced in the plane of the grating from the position of the grating by an amount dependent upon the wavelength of the light forming the image.
  • the means for producing an image of the grating on the grating preferably includes a dispersing element, for example a prism.
  • spectral measurements should be taken at many wavelengths, particularly when determining the concentration of blood analytes present in small amounts.
  • Standard analytical techniques may be utilized for deriving concentration data from the spectral measurements made, for example multiple linear regression, partial least squares, or principal components regression.
  • infrared signals obtained from an animal in order to determine blood analytes may be enhanced by determining the variation of the said spectrum which is in phase with the pulse of the animal. Similar techniques are conventionally used in so called “pulse oximetry", which are employed to determine blood oxygen content optically. So far as we are aware however, no proposal has ever been made hitherto to enhance the sensitivity of blood analyte determination by infrared spectroscopy by using similar techniques linked to the coronary pulse. Accordingly, in a further aspect of the invention, there is provided apparatus for determining non- invasively the presence and/or concentration of blood analytes in an animal comprising:-
  • a further aspect of the invention provides a method of determining non-invasively the presence and/or concentration of blood analytes in an animal comprising:- a. illuminating a surface of the body of the animal with infrared radiation b. detecting infrared radiation reflected from the said surface and analyzing the spectrum of the said reflected radiation to determine the presence and/or concentration of the said analytes, characterised in that the method includes the step of detecting the pulse of the animal, and determining the variation of the said spectrum which is in phase with the said pulse.
  • This aspect of the invention is of most benefit when the NIR spectrum determination is carried out on a part of the body to which the blood supply is highly pulsatile, for example a finger or an ear lobe.
  • the blood supply to the front surface of the eye is relatively non-pulsatile, and therefore this method is of limited value when applied to the front surface of the eye. It is however a benefit to employ this aspect of the invention with the aspect of the invention discussed earlier, relating to the modulation of the light employed, in accordance with its wavelengths.
  • Figure 1 is a schematic diagram of a device according to the invention for measuring blood glucose levels
  • Figure 2 is a schematic plan view of a device according to the invention
  • Figure 3 is a section on AA of Figure 2;
  • Figure 4 is a side view of the device of Figure 2;
  • Figure 5 is a schematic representation of the instrument in use;
  • Figure 6 illustrates an arrangement for decreasing specular reflection in a device according to Figures 1 and 2;
  • Figure 7 is a schematic representation of an alternative embodiment, for minimising specular reflection
  • Figure 8 illustrates a further alternative method
  • Figure 9 is a schematic diagram of the so called “mock interferometer", for modulating a light beam at a frequency dependent upon its wavelengths;
  • Figure 10 is a schematic diagram of the incorporation of such a modulation device into a device according to the invention for ocular blood analyte determination; and Figure 11 is a more detailed schematic representation of a device according to the invention incorporating means for modulating a light beam.
  • Figure 1 is a schematic diagram, illustrating the major components for - carrying out glucose measurements on the front surface of the eye, according to the preferred embodiment of the invention.
  • the apparatus of Figure 1 includes a light source 1 (typically a filament lamp such as a tungsten/ halogen lamp), reflector 2, and collimating lens 3, for producing a parallel light beam.
  • the parallel light beam is passed through a light modulator 4, which will be described in more detail hereinafter, which modulates the light beam, at a modulation frequency which is dependent upon the wavelength of the light.
  • the modulated light beam 7 passes through a beam splitter 8, and focusing lens 9, which focuses the modulated beam on the front surface 10 of the eye, for measuring the concentration of blood analytes.
  • the arrangement is such that the focused beam impinges upon an edge region of the eye, which is particularly well suffused with surface blood vessels.
  • Diffusely reflected light from the surface 10 is collected by lens 9, and passes back through beam splitter 8, to be focused by lens 11, on detector 12.
  • a processing unit 5 is provided, linked to detector 12 and to light modulator 4.
  • Processing unit 5 includes a number of electronic filtering circuits, so that the intensity of light reflections at a plurality of modulation frequencies (and consequently at a plurality of infrared wavelengths) may be detected.
  • the detector 12 may be preferably a non-imaging concentrator.
  • the processing unit 5 may take the form of a "licroprocessor, and appropriate software.
  • Processor unit 5 also includes means for carrying out analysis of the resulting absorption bands detected, using for example multiple linear regression, partial least squares, or principal components regression.
  • the device may also include a pulse detector 6, which enables the pulse of the individual to be detected.
  • a pulse detector 6 which enables the pulse of the individual to be detected.
  • the pulse detector 6 may be of any form conventionally used for pulse oxi etry. Pulse oximetry is a technique for determining the oxygenation of blood using optical absorption measurements on a body part.
  • the red or infrared absorption of a body part is measured at two wavelengths one of which is chosen because it is absorbed equally by oxyhaemoglobin (oxygenated haemoglobin) and deoxyhaemoglobin (deoxygenated haemoglobin) and another because it is absorbed strongly by one form of haemoglobin but only weakly by the other.
  • a pulse oximeter monitors the absorption of the tissue at the two wavelengths caused by increases and decreases in the volume of-the blood present in the tissue.
  • the pulsatile component of the absorption is due primarily to the blood in the tissue rather than the surrounding tissues.
  • the ratio of amplitudes of the two pulsatile signals provides a measure of the oxygenation of the tissue.
  • Processor 5 includes a phase-sensitive detector, linked with the input from pulse detector 6, such that only the component of the detected signal which varies in phase with the detected pulse is passed to the detection circuitry.
  • the processor 5 is capable of separating the static and alternating (pulsatile) components of the optical spectrum.
  • the pulsatile component of the spectrum is strongly correlated to the blood absorption spectrum, and thus provides a good basis on which to carry out the calculation of blood analyte concentration.
  • Figures 2 to 5 illustrate the external appearance of a practical embodiment of a portable device according to the invention.
  • the device of Figures 2 to 4 comprises a body
  • the components within body 20 are configured such that the focused beam intended to impinge on the front surface of the eye passes through an aperture 21 in the body 20.
  • a screw-threaded adaptor 22 to which is affixed by means of the screwthread a moulding 23, which is shaped to the facial contours of the user, and includes a flexible eye and nose piece.
  • the shape of the molding 23 ensures that the device is located correctly with regard to the particular facial features of the individual, and that the light beam impinges on the desired location on the front of the eye.
  • a sculpted hand grip 24 is provided for the convenience of the user.
  • the upper surface of the body 20 carries a start button 25, operated by the user, and an LCD screen 26 for displaying the measurements obtained.
  • any other detection system capable of obtaining an infrared spectrum from the front surface of the eye may be employed, for example a Fourier Transform spectrometer.
  • specularly reflected light contains far less spectral information about the blood than light which is diffusely reflected (backscattered)
  • a simple arrangement is illustrated in Figure 6.
  • the spatial arrangement is simply arranged so that the focused light beam impinges upon the eye surface at a point 10 where the curvature is such that specular reflection tends to be away from the detection system.
  • the light modulator and processor unit have been omitted, for clarity.
  • detector 12 is a CCD imaging device, having an array of detection points.
  • the arrangement includes a beam stop 13 for limiting the width of the collimating beam to enable the detector to gather light from a larger range of angles than is occupied by the specular reflection.
  • the modulator and processing unit are not shown, for clarity.
  • the processing means 5 is programmed and arranged so as to locate the region on the detector 12 at which the specular reflection is received. Normally, the specular reflection will be relatively sharp and produce an intense signal, and it is therefore a straightforward matter to determine the point at which the specular reflection occurs, and to give a lower weighting (or a zero weighting) to the signal received from that region of the detector.
  • Figure 8 shows an alternative means of suppressing the effects of specular reflection, on the basis of the light polarisation. Only the components of the system relevant to this aspect are shown in Figure 8, for clarity.
  • a polariser 33 is inserted, to polarise the light incident on the eye.
  • the polariser may be a linear polariser, orientated for example to polarise the light perpendicular to the plane of incidence, or a circular polariser.
  • an analyzer 30 is positioned between lens 31 and lens 32, so as to block specularly reflected light from the eye.
  • a waveplate may also be used in conjunction with the polarising elements.
  • Figure 9 is a schematic representation of the so called "mock interferometer” referred to in the reference by Lawrence Mertz, mentioned above, and illustrates the way in which a simple mechanical arrangement can be utilized to modulate a light beam at a frequency which depends upon its wavelengths.
  • a schematic representation of a simple mechanism incorporating such a device in an analyzer in accordance with the invention is illustrated in Figure 10.
  • an optical grating 40 having a spacing of approximately ten lines per millimetre is located in a rotating mount, and light is passed through the grating, and focused by a lens 42.
  • a mirror backed dispersing prism 44 reflects the light beam through the lens 42, and forms an image of the grating on the grating surface. Because the position of the image on the grating is dependent upon the wavelengths of the light, the coincidence of the grating lines and image lines, and therefore the chopping or modulation frequency, it is also dependent upon the wavelengths.
  • Figure 10 shows schematically how such a device may be incorporated into a device according to the invention, the same reference numbers being used as in Figure 1.
  • Figure 11 A more detailed schematic representation of such a device is illustrated in Figure 11. Again, the same reference numbers being used as in Figure 1.
  • the device includes a polychromatic light source 1 (a tungsten halogen filament lamp), and a reflector 2 and •collimating lens 3 as in Figure 1.
  • the collimated light beam then passes through a light modulator, comprising a disc 40, on the surface of which is an optical grating.
  • the grating may be either a phase grating or an amplitude grating, and has a spacing which is large compared to the wavelength of light (typically a spacing of the order of ten line pairs per millimetre).
  • Disc 40 is rotated at a constant speed by means of an electric motor 41.
  • An optical system comprising lenses 42, mirrors 43, and a dispersing element 44, is arranged so as to form an image of the rotating grating on the surface of the grating itself.
  • the lenses 42 are separated from each other by the sum of their focal lengths f, and are positioned such that the grating is in the focal planes of the lenses closest to it.
  • the position of the image on the disc 40 depends upon the amount by which the light is dispersed by element 44, and thus upon the wavelength of the light in question.
  • the light which is transmitted by the grating is chopped or modulated, at a frequency which varies cyclically, but which depends upon the translation of the image in relation to the grating, and thus upon the wavelength of the light.
  • the modulated light passes through beam splitter 8 and lens 9, is reflected from the front surface of the eye (or any other suitable body part), and detected by detector 12.
  • Electrical signals from the detector are then analyzed by dividing them into frequency "bins" in a known manner, for example using electronic filters, such as discrete RC circuits tuned to the frequencies of interest, or a lock- amplifier and frequency synthesizer.
  • electronic filters such as discrete RC circuits tuned to the frequencies of interest, or a lock- amplifier and frequency synthesizer.
  • the reflection spectrum of the eye may be obtained by transforming the time varying signal using a Fourier transform with a non-uniform sampling interval (see Lawrence Mertz "Transformations in Optics", John Wylie & Sons, Inc., New York, 1965).
  • a particularly advantageous feature of this type of arrangement is the high optical throughput of the device, as there is no need for the light to pass through a slit. High throughput is a significant advantage for a battery powered instrument, as it minimises the electrical power consumption of the device. It also minimises the time required to make a measurement of analyte concentration to a particular accuracy.
  • the modulation method discussed above is particularly advantageous when utilized in a device for scanning the front surface of the eye, it also has advantages for analyte determination using other parts of the body, for example the retina, choroid, optic nerve head (optic disc), finger, earlobe, lip, or other tissue with a good blood supply.
  • the optic nerve head can be advantageous in some circumstances, because of its good blood supply and pulse, good optical access to blood perfused tissue, very stable temperature, lack of pigmentation, and the ability to use simple optical arrangements taking advantage of the optics of the eye.
  • the levels of glucose in the aqueous humor and difficulty in obtaining sufficient light levels restrict the usefulness of the back of the eye in this context.
  • some forms of eye disease, such as cataracts make utilization of the retina, choroid or optic nerve head difficult.
  • the wavelength and strength of water absorptions in the near infrared portion of the spectrum vary with temperature.
  • the phenomenon adds to the difficulty of developing a reliable calibration algorithm for the determination of blood analyte concentrations.
  • the temperature of the body part under investigation is measured, by measurement of the NIR absorption of water in the region in question.
  • temperature can be measured using a thermistor, thermocouple, or other conventional means.
  • the heating or cooling mechanism which might be an electrical resistor or thermoelectric element respectively, is linked to a temperature sensor, such as those described above, by means of a feedback loop. It is preferable to raise the body temperature rather than to cool it because the body temperature rarely increases by much, whereas it may cool considerably, and because increasing the temperature of the body part increases the amount of blood in the tissue and increases the strength of the pulsatile component of the flow, as shown in "Noninvasive Pulse Oximetry Utilising Skin Reflectance Photoplethysmography", Y. Mendelson and B.D.
  • heating of the body part may be achieved by utilising the infrared radiation employed for the spectral determination to heat the body part under investigation.
  • the simplicity of the device means that measurements can be made of a large number of wavelengths, using suitable calibration algorithms. Different wavelengths can be used for different population groups, or even for different individuals, further enhancing the ability of the instrument to measure accurately the blood glucose or other blood analyte concentration.
  • the instrument itself can be used for the purposes of calibration.
  • the derivation of appropriate calibration algorithms for various blood analytes is simply a matter of deriving a suitably large data set for known patients of varying blood analyte concentration, and obtaining appropriate correlations between absorption at various frequencies, and the blood analyte concentrations, using any of the techniques noted above.
  • the methods disclosed may also be employed in the determination of other blood analytes, for example alcohols and in particular ethanol, urea, total and high density cholesterol, haemoglobin, oxyhaemoglobin, low and high density lipoproteins, triglycerides, total protein, albumin, and globulins in serum.

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Abstract

On décrit un appareil et un procédé pour déterminer de manière non-invasive la présence et/ou la concentration d'analytes sanguins tels que le glucose chez un animal, et en particulier chez un être humain. L'appareil comprend une source lumineuse (1) destinée à produire un rayon lumineux polychromatique et des éléments (4) pour moduler le rayon lumineux polychromatique de telle sorte que la fréquence de modulation dépende de la longueur d'onde de la lumière dans le rayon. On suscite le rayon lumineux modulé pour quil se heurte à une partie du corps, de préférence la surface frontale (10) de l'oeil de l'animal de façon à ce que les analytes sanguins réagissent réciproquement au rayon lumineux et perturbent la répartition spectrale de la lumière dans le rayon. Les informations spectrales sont extraites du rayon lumineux obtenu, en détachant le rayon au niveau d'une pluralité de fréquences de modulation. Les mesures peuvent être liées à des mesures d'impulsions de manière similaire à l'oxymétrie d'impulsion. Le rayon lumineux peut également être utilisé pour chauffer la partie du corps à une température désirée. Un moulage (23) localise la source lumineuse et le détecteur à un endroit fixe par rapport à la physionomie de l'animal. Différents procédés, tels que l'utilisation de polariseurs et de détecteurs CCD, sont proposés afin de minimiser l'effet de réflexion spéculaire.
EP92922310A 1991-10-17 1992-10-16 Procede et appareil de determination non-invasive d'analytes sanguins Withdrawn EP0609341A1 (fr)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
GB919122045A GB9122045D0 (en) 1991-10-17 1991-10-17 A novel means of non-invasively measuring blood glucose concentration
GB9122045 1991-10-17
GB919125471A GB9125471D0 (en) 1991-10-17 1991-11-29 A novel means of non-invasively measuring blood glucose concentration
GB9125471 1991-11-29
GB929207149A GB9207149D0 (en) 1992-04-01 1992-04-01 An improved instrument for measuring blood oxygen in deep arterial blood
GB9207149 1992-04-01
PCT/GB1992/001894 WO1993007801A1 (fr) 1991-10-17 1992-10-16 Procede et appareil de determination non-invasive d'analytes sanguins

Publications (1)

Publication Number Publication Date
EP0609341A1 true EP0609341A1 (fr) 1994-08-10

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EP92922310A Withdrawn EP0609341A1 (fr) 1991-10-17 1992-10-16 Procede et appareil de determination non-invasive d'analytes sanguins

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EP (1) EP0609341A1 (fr)
JP (1) JPH07508426A (fr)
WO (1) WO1993007801A1 (fr)

Families Citing this family (81)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5203328A (en) * 1991-07-17 1993-04-20 Georgia Tech Research Corporation Apparatus and methods for quantitatively measuring molecular changes in the ocular lens
US6411832B1 (en) * 1992-07-15 2002-06-25 Optix Lp Method of improving reproducibility of non-invasive measurements
US5433197A (en) * 1992-09-04 1995-07-18 Stark; Edward W. Non-invasive glucose measurement method and apparatus
US5553613A (en) * 1994-08-17 1996-09-10 Pfizer Inc. Non invasive blood analyte sensor
US5553617A (en) * 1995-01-20 1996-09-10 Hughes Aircraft Company Noninvasive method and apparatus for determining body chemistry
US5743262A (en) * 1995-06-07 1998-04-28 Masimo Corporation Blood glucose monitoring system
US5655530A (en) * 1995-08-09 1997-08-12 Rio Grande Medical Technologies, Inc. Method for non-invasive blood analyte measurement with improved optical interface
US6240306B1 (en) 1995-08-09 2001-05-29 Rio Grande Medical Technologies, Inc. Method and apparatus for non-invasive blood analyte measurement with fluid compartment equilibration
US6152876A (en) * 1997-04-18 2000-11-28 Rio Grande Medical Technologies, Inc. Method for non-invasive blood analyte measurement with improved optical interface
US6212424B1 (en) 1998-10-29 2001-04-03 Rio Grande Medical Technologies, Inc. Apparatus and method for determination of the adequacy of dialysis by non-invasive near-infrared spectroscopy
DE19538372A1 (de) * 1995-10-14 1997-04-17 Laser & Med Tech Gmbh Nicht invasive Glukosemessung
AP931A (en) * 1995-10-23 2001-02-02 Cytometrics Inc Method and apparatus for reflected imaging analysis.
US5748308A (en) * 1996-02-02 1998-05-05 Abbott Laboratories Programmable standard for use in an apparatus and process for the noninvasive measurement of optically absorbing compounds
JP3599878B2 (ja) * 1996-03-01 2004-12-08 テルモ株式会社 血糖計
US5788632A (en) * 1996-03-19 1998-08-04 Abbott Laboratories Apparatus and process for the non-invasive measurement of optically active compounds
US6544193B2 (en) 1996-09-04 2003-04-08 Marcio Marc Abreu Noninvasive measurement of chemical substances
US6527716B1 (en) 1997-12-30 2003-03-04 Altea Technologies, Inc. Microporation of tissue for delivery of bioactive agents
US6560352B2 (en) 1999-10-08 2003-05-06 Lumidigm, Inc. Apparatus and method of biometric identification or verification of individuals using optical spectroscopy
US6628809B1 (en) 1999-10-08 2003-09-30 Lumidigm, Inc. Apparatus and method for identification of individuals by near-infrared spectrum
US7890158B2 (en) 2001-06-05 2011-02-15 Lumidigm, Inc. Apparatus and method of biometric determination using specialized optical spectroscopy systems
JPH11123195A (ja) * 1997-08-22 1999-05-11 Kdk Corp 生体測定方法及び装置
NL1007011C2 (nl) * 1997-09-11 1999-03-12 Rijksuniversiteit Inrichting voor het meten van de fluorescentie van de cornea van een oog.
US6070093A (en) 1997-12-02 2000-05-30 Abbott Laboratories Multiplex sensor and method of use
JP3543923B2 (ja) * 1997-12-25 2004-07-21 富士写真フイルム株式会社 グルコース濃度測定装置
AU2989699A (en) * 1998-03-05 1999-09-20 Universal Health-Watch, Inc. Apparatus to non-invasively measure glucose or other constituents in aqueous humor using infra-red spectroscopy
US6241663B1 (en) 1998-05-18 2001-06-05 Abbott Laboratories Method for improving non-invasive determination of the concentration of analytes in a biological sample
US6662031B1 (en) 1998-05-18 2003-12-09 Abbott Laboratoies Method and device for the noninvasive determination of hemoglobin and hematocrit
US7043287B1 (en) 1998-05-18 2006-05-09 Abbott Laboratories Method for modulating light penetration depth in tissue and diagnostic applications using same
US6526298B1 (en) 1998-05-18 2003-02-25 Abbott Laboratories Method for the non-invasive determination of analytes in a selected volume of tissue
US6662030B2 (en) 1998-05-18 2003-12-09 Abbott Laboratories Non-invasive sensor having controllable temperature feature
US7098037B2 (en) 1998-10-13 2006-08-29 Inlight Solutions, Inc. Accommodating subject and instrument variations in spectroscopic determinations
US6157041A (en) * 1998-10-13 2000-12-05 Rio Grande Medical Technologies, Inc. Methods and apparatus for tailoring spectroscopic calibration models
US6441388B1 (en) 1998-10-13 2002-08-27 Rio Grande Medical Technologies, Inc. Methods and apparatus for spectroscopic calibration model transfer
US20030078499A1 (en) 1999-08-12 2003-04-24 Eppstein Jonathan A. Microporation of tissue for delivery of bioactive agents
AU3213500A (en) * 1999-09-17 2001-04-24 Walter K. Proniewicz Noninvasive measurement of blood sugar level
US6494576B1 (en) 1999-09-30 2002-12-17 L'esperance, Jr. Francis A. Method and apparatus for spectrophotometry of the eye
US6816605B2 (en) 1999-10-08 2004-11-09 Lumidigm, Inc. Methods and systems for biometric identification of individuals using linear optical spectroscopy
US6640117B2 (en) 2000-09-26 2003-10-28 Sensys Medical, Inc. Method and apparatus for minimizing spectral effects attributable to tissue state variations during NIR-based non-invasive blood analyte determination
US6650915B2 (en) * 2001-09-13 2003-11-18 Fovioptics, Inc. Non-invasive measurement of blood analytes using photodynamics
WO2003077970A2 (fr) 2002-03-11 2003-09-25 Altea Therapeutics Corporation Dispositif transdermique a actionneur integre, procedes de fabrication et d'utilisation de celui-ci
US9918665B2 (en) 2002-03-11 2018-03-20 Nitto Denko Corporation Transdermal porator and patch system and method for using same
US7668350B2 (en) 2003-04-04 2010-02-23 Lumidigm, Inc. Comparative texture analysis of tissue for biometric spoof detection
ATE492001T1 (de) * 2003-04-04 2011-01-15 Lumidigm Inc Multispektralbiometriesensor
US7460696B2 (en) 2004-06-01 2008-12-02 Lumidigm, Inc. Multispectral imaging biometrics
US7751594B2 (en) 2003-04-04 2010-07-06 Lumidigm, Inc. White-light spectral biometric sensors
WO2005007215A2 (fr) 2003-07-09 2005-01-27 Glucolight Corporation Procede et appareil d'oxymetrie de tissu
GB2407378B (en) 2003-10-24 2006-09-06 Lein Applied Diagnostics Ltd Ocular property measuring apparatus and method therefor
US8016811B2 (en) 2003-10-24 2011-09-13 Altea Therapeutics Corporation Method for transdermal delivery of permeant substances
GB2409033C (en) 2003-12-12 2006-05-24 Lein Applied Diagnostics Ltd Extended focal region measuring apparatus and method
US7510849B2 (en) 2004-01-29 2009-03-31 Glucolight Corporation OCT based method for diagnosis and therapy
US8229185B2 (en) 2004-06-01 2012-07-24 Lumidigm, Inc. Hygienic biometric sensors
US7254429B2 (en) 2004-08-11 2007-08-07 Glucolight Corporation Method and apparatus for monitoring glucose levels in a biological tissue
US8036727B2 (en) 2004-08-11 2011-10-11 Glt Acquisition Corp. Methods for noninvasively measuring analyte levels in a subject
US8787630B2 (en) 2004-08-11 2014-07-22 Lumidigm, Inc. Multispectral barcode imaging
US7822452B2 (en) 2004-08-11 2010-10-26 Glt Acquisition Corp. Method for data reduction and calibration of an OCT-based blood glucose monitor
US7801338B2 (en) 2005-04-27 2010-09-21 Lumidigm, Inc. Multispectral biometric sensors
US8175346B2 (en) 2006-07-19 2012-05-08 Lumidigm, Inc. Whole-hand multispectral biometric imaging
US8355545B2 (en) 2007-04-10 2013-01-15 Lumidigm, Inc. Biometric detection using spatial, temporal, and/or spectral techniques
US7995808B2 (en) 2006-07-19 2011-08-09 Lumidigm, Inc. Contactless multispectral biometric capture
WO2008100329A2 (fr) 2006-07-19 2008-08-21 Lumidigm, Inc. Dispositif d'imagerie multispectral multibiométrique
US7801339B2 (en) 2006-07-31 2010-09-21 Lumidigm, Inc. Biometrics with spatiospectral spoof detection
US7804984B2 (en) 2006-07-31 2010-09-28 Lumidigm, Inc. Spatial-spectral fingerprint spoof detection
EP2120713A2 (fr) 2007-03-21 2009-11-25 Lumidigm, Inc. Biométrie à base de caractéristiques localement cohérentes
GB2451443B (en) 2007-07-30 2012-12-26 Lein Applied Diagnostics Ltd Optical measurement apparatus and method therefor
GB2451441B (en) 2007-07-30 2012-07-11 Lein Applied Diagnostics Ltd Optical alignment apparatus and method thereof
GB2457302B (en) 2008-02-11 2013-04-10 Lein Applied Diagnostics Ltd Measurement apparatus and method therefor
US8364218B2 (en) 2008-02-11 2013-01-29 Glucovista, Inc. Apparatus and method for non-invasive measurement of the concentration of a substance in subjects blood
US8219169B2 (en) * 2008-02-11 2012-07-10 Glucovista Inc. Apparatus and method using light retro-reflected from a retina to non-invasively measure the blood concentration of a substance
US8768423B2 (en) 2008-03-04 2014-07-01 Glt Acquisition Corp. Multispot monitoring for use in optical coherence tomography
US7896498B2 (en) 2009-03-30 2011-03-01 Ottawa Hospital Research Institute Apparatus and method for optical measurements
US8731250B2 (en) 2009-08-26 2014-05-20 Lumidigm, Inc. Multiplexed biometric imaging
US8570149B2 (en) 2010-03-16 2013-10-29 Lumidigm, Inc. Biometric imaging using an optical adaptive interface
JP2014010093A (ja) 2012-07-02 2014-01-20 Seiko Epson Corp 分光画像撮像装置
WO2014137357A1 (fr) * 2013-03-08 2014-09-12 Alethus, Inc. Détection optique sélective de substances présentes dans des tissus et des milieux troubles et utilisation à des fins d'analyse non invasive
US9597021B1 (en) 2014-01-14 2017-03-21 Analytics For Life Noninvasive method for estimating glucose, glycosylated hemoglobin and other blood constituents
WO2016054079A1 (fr) 2014-09-29 2016-04-07 Zyomed Corp. Systèmes et procédés pour la détection et la mesure du glucose sanguin du sang et d'autres analytes à l'aide du calcul de collision
JP2017018483A (ja) * 2015-07-14 2017-01-26 オリンパス株式会社 医療用プローブ
JP2019506205A (ja) * 2015-12-31 2019-03-07 ウェア２ビー リミテッド 生理学的測定値の非侵襲的監視のための装置、システム、および方法
US9554738B1 (en) 2016-03-30 2017-01-31 Zyomed Corp. Spectroscopic tomography systems and methods for noninvasive detection and measurement of analytes using collision computing
CN110545725A (zh) * 2017-04-18 2019-12-06 兴和株式会社 计算血液的吸收光谱的信息处理方法、信息处理装置和程序
EP3581092A1 (fr) * 2018-06-12 2019-12-18 Koninklijke Philips N.V. Système et procédé permettant de déterminer au moins un signe vital d'une personne

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4014321A (en) * 1974-11-25 1977-03-29 March Wayne F Non-invasive glucose sensor system
US4350163A (en) * 1980-05-29 1982-09-21 Ford Jr Norman C Method and apparatus for analyzing contaminants in aqueous humor
US5025785A (en) * 1982-09-10 1991-06-25 Weiss Jeffrey N Diabetes detection method
CA2028261C (fr) * 1989-10-28 1995-01-17 Won Suck Yang Methode et appareil non effractifs pour mesurer le taux de glycemie
US5054487A (en) * 1990-02-02 1991-10-08 Boston Advanced Technologies, Inc. Laser systems for material analysis based on reflectance ratio detection

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9307801A1 *

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