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WO2001010294A1 - Procede et dispositif pour la mesure non invasive de composants sanguins et de parametres cliniques - Google Patents

Procede et dispositif pour la mesure non invasive de composants sanguins et de parametres cliniques Download PDF

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Publication number
WO2001010294A1
WO2001010294A1 PCT/EP2000/005445 EP0005445W WO0110294A1 WO 2001010294 A1 WO2001010294 A1 WO 2001010294A1 EP 0005445 W EP0005445 W EP 0005445W WO 0110294 A1 WO0110294 A1 WO 0110294A1
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WO
WIPO (PCT)
Prior art keywords
blood
skin sample
skin
measurement
glucose
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Application number
PCT/EP2000/005445
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German (de)
English (en)
Inventor
Herbert Michael Heise
Original Assignee
Gesellschaft zur Förderung der Spektrochemie und angewandten Spektroskopie e.V.
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Priority to AU56814/00A priority Critical patent/AU5681400A/en
Publication of WO2001010294A1 publication Critical patent/WO2001010294A1/fr

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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 or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or 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 or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
    • A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue for measuring glucose, e.g. by tissue impedance measurement

Definitions

  • the invention relates to a method and an apparatus for the non-invasive measurement of blood components and clinical parameters, in particular for glucose measurement, with the aid of optical spectroscopy of skin tissue in the visible, infrared or ultraviolet spectral range.
  • the concentration of the analytes is in a wide range, which depends on the substance group.
  • the blood components are queried: substrates such as the well-known blood sugar (glucose), blood lipids, cholesterol and others, as well as the various enzymes and electrolytes.
  • substrates such as the well-known blood sugar (glucose), blood lipids, cholesterol and others, as well as the various enzymes and electrolytes.
  • the immunological determinations represent an important division. Furthermore, hormones and metabolites (metabolic products) are examined.
  • spectroscopy in which the interaction of electromagnetic radiation of different wavelengths with the body tissue or the analysis sample is used.
  • magnetic resonance spectroscopy is used for detailed imaging on the patient, but also for the analysis of physiological processes in the organism. Here measuring frequencies up to 400 MHz and higher are used.
  • pulse oximetry uses visible and infrared light to determine the oxygen saturation of the blood, more precisely the hemoglobin in the red blood cells.
  • Infrared spectroscopy in particular has been improved in recent years. Infrared spectroscopy preferably uses radiation with a longer wavelength than visible light between 780 n and 1,000 ⁇ . Substance spectra of the infrared spectral range maintain a high level of information regarding component identification and quantification. In so-called absorption spectroscopy, the different components of a sample each absorb certain radiation components of different wavelengths according to their specific spectrum, which can be measured with a suitable spectrometer.
  • the instrumental developments and so-called chemometric evaluation techniques now also enable the quantitative analysis of multi-component systems, such as those that represent human blood or liquids derived from it. With novel measuring techniques, quantitative analyzes of components in parts per thousand and lower can be carried out in these biotic aqueous samples.
  • non-invasive, transcutaneous blood diagnostics can also be carried out by measuring body tissue or tissue components.
  • this is desirable and important for patients with metabolic disorders, in particular due to diabetes mellitus.
  • This is a disease in which there is a lack or complete absence of the insulin hormone produced in the pancreas or insufficient insulin activity in the body. Out For this reason, sufficient utilization of sugar as the most important source of energy for the human body can no longer be guaranteed. Accordingly, the blood sugar concentration, which is otherwise regulated in healthy people by the body within relatively narrow limits, rises and falls.
  • the hormone concentrations of insulin and glucagon in the blood plasma which are released in healthy people by the islet cells of the pancreas depending on the blood glucose concentration, play an important role here.
  • the carbohydrate intake via food intake is a disturbance variable in the control loop.
  • the liver is an important organ for homeostasis (maintaining balance) of the blood glucose concentration, since it can convert glucose directly to the reserve carbohydrate glycogen (insulin-dependent), this too low Reduces blood sugar levels again to provide glucose, which is induced by an increased release of glucagon. If the blood glucose concentration rises above a certain elevated value, glucose is also excreted via the kidneys. The rate of entry of glucose for most body cells, and thus consumption, is determined by the insulin concentration.
  • Diabetes is a widespread disease. About 5% of the population of the Federal Republic of Germany suffer from diabetes mellitus. It is estimated that a total of more than 650,000 patients require insulin. There are approximately 30,000,000 diabetics worldwide, and the trend is rising. This disease is currently not curable, but sensible and conscious behavior by the patient can prevent medical complications in the long term. These include disorders in the micro and later also the macro circulation of the blood, which means e.g. Kidney damage and blindness are caused. The disease and its costs cause about a third of all health care costs.
  • the diabetic tries to replicate the natural control loop in order to keep the blood sugar concentration close to the normal value of healthy people, which is naturally dimension is only possible with restrictions.
  • Current blood glucose meters are equipped with test strips and require blood samples to be taken. Because of their necessity, the possibility of determining blood glucose is severely restricted. With the so-called intensified insulin therapy, the diabetic has to check his blood sugar level several times a day. Many people refrain from doing this because they fear the pain of finger pricking before taking blood or the possibility of infection, especially in diabetic children, the daily ritual for measuring blood glucose is a problem.
  • Another strategy uses the so-called classic modeling, for which all components contributing to the measured and evaluated sample spectrum must be known with their spectra. An adjustment with these by minimizing the error squares provides concentration estimates.
  • a useful pretreatment to simplify IR skin spectra is the so-called orthogonalization against, for example, certain factor spectra, which can be used to model the spectral variance. Some main components (factor spectra) are dominated by the tissue water in the examined skin volume (see HM Heise, Medical Applications of Infrared Spectrosco- py, microchim. Acta (Suppl.) 14, 67-77 (1997). However, all of these known methods have so far not been able to provide precise blood glucose concentration values, particularly in the hypoglycemic range, ie in the hypoglycemic range.
  • the object of the invention is therefore to provide a solution with which accurate measurement results in the non-invasive measurement of blood components by means of infrared spectroscopy are also possible in the hypoglycemic range.
  • This object is achieved according to the invention in a method of the type mentioned at the outset by measuring the blood volume and the metabolic state of the skin sample in addition to measuring glucose on the skin sample and determining the blood glucose concentration on the basis of these measured values (metabolic state) and the measured tissue glucose concentration.
  • the blood flow in the skin sample is preferably increased in order to minimize the gradient in the glucose concentration present in the blood vessel space and tissue.
  • the method according to the invention is based on the knowledge that important knowledge of the microcirculation and physiology of the skin is essential in order to improve the measuring technology known and used to date.
  • the skin measurements in the infrared have in particular the problem that the water-soluble glucose, for example, is located in different compartments of the skin tissue, the intravascular, the interstitial (cell space) and the intracellular space.
  • the proportion of skin circulation can be increased and standardized, which also results in a rapid "steady state” response.
  • the glucose concentrations in the compartments involved in the integral skin measurement can take place and otherwise existing systematic errors in the correlation of the capillary blood glucose with the integrally measured glucose can be avoided.
  • the skin sample is subjected to heat during the measurement, which can be implemented in a simple manner. Maintaining a constant skin temperature that is higher than normal body temperature is taken into account.
  • the contact pressure of the measuring probe on the skin sample is preferably kept repeatably low during the measurement in order to obtain reproducible results.
  • the blood volume can be determined by measuring the skin spectrum, which provides information about the blood ('blood spectrum') and evaluating it, for example to determine the total hemoglobin content, the hematocrit value or the blood plasma proteins.
  • the blood volume is made up of the proportion of cellular components (mainly red blood cells that contain hemoglobin) and the blood plasma.
  • the total hemaglobin can then be used to determine the blood volume and to normalize the glucose level.
  • the total water of the spectroscopic skin volume is also to be used here. This determination can suitably be carried out in the same spectral range in which the glucose to be determined or other metabolites are measured. This information, blood volume and tissue water can still be used to control the pressure of the probe.
  • the degree of oxygenation of the blood can then be determined from the evaluation of the blood spectrum via, for example, hemoglobin / oxyhemoglobin, which provides an indication of the metabolic state of the examined skin tissue.
  • An improved measurement of the metabolic state of the examined skin sample is possible by measuring the pulse spectrum (in the arterial space) and the integral blood space, which is used to determine the arteriovenous difference in the degree of oxygenation (AVD), which provides an indication of the metabolic activity of the examined tissue is proportional to the consumption of oxygen and glucose.
  • ATD arteriovenous difference in the degree of oxygenation
  • This is based on the oxygen-dependent oxidation of glucose to CO 2 and water, which in the end is physiologically carried out by the body tissue and runs via intermediates.
  • the gradients in the vascular space suggest the gradient in the interstitial space between the capillary blood vessels.
  • the gradients in the extravascular space are crucially dependent on the capillary density, the metabolic rate and the rate of diffusion.
  • the development of future mean tissue glucose in the short-term range can be determined in advance if the changes in blood glucose concentration are evenly steady.
  • the current change in concentration can be changed by changing the blood volume. mens, e.g. by applying heat to the skin, which is important in the event that the blood concentration changes relatively suddenly, e.g. after carbohydrate intake in liquid form such as in fruit juices, so that glucose then appears in batches in the blood space, or if increased glucose is taken from the blood compartment via the liver.
  • the blood spectrum in the visible, short-wave or long-wave near infrared range is advantageously measured with the aid of optical spectroscopy, as is known per se, for example from pulse oximetry (see, for example, MJ Hayes, PR Smith, quantitative evaluation of photo pliethysmographic artefact reduction for pulse oximetry, Proc. SPIE 3570, 138-147 (1998) and literature cited therein).
  • pulse oximetry see, for example, MJ Hayes, PR Smith, quantitative evaluation of photo pliethysmographic artefact reduction for pulse oximetry, Proc. SPIE 3570, 138-147 (1998) and literature cited therein.
  • Either the same spectrometer that is used for glucose measurement can be used for this, or an additional spectrometer can also be used.
  • the measurement can be carried out multivariate or by selecting at least two wavelengths, the latter also being able to be implemented simply using optical filters.
  • One method uses the blood volume determined via the total hemoglobin and the degree of oxygenation within the spectroscopic Skin volume.
  • a further embodiment of the measuring device is obtained by measuring and evaluating the integrally measured and the pulsatile portion that detects the arterial vascular space, so that the arteriovenous difference in the oxygen saturation of the blood can be determined. The metabolic state can be better determined with this.
  • An extension also determines the flow rate of the blood in the blood vessels via a laser Doppler measurement, which allows the metabolic rate in the tissue to be determined.
  • oxygen saturation for example, pyruvate or lactate concentrations or other substances involved in the metabolism can be used, provided that they can be detected non-invasively by spectroscopy.
  • the respective insulin concentration can be calculated, for example, when using continuously working insulin pumps for the diabetic, the distribution volumes for the insulin in the blood plasma and in the interstitium being required.
  • invasive blood glucose control measurements are also included in the determination of the blood glucose concentration.
  • Such a regular invasive blood glucose control measurement is to be provided in particular if the body tissue parts to be measured are to be changed in order to take into account their proportion, for example of sugars bound to large biomolecules, such as in the case of glycoproteins, also in the calibration and evaluation received.
  • a proportion of the sugars specially bound in the blood can be determined, for example, by means of a glycohemoglobin analysis.
  • the blood glucose profile determined in previous measurements is taken into account in the respective new measurement for determining the blood glucose concentration.
  • quasi-continuous measurements are made, whereby the sampling of the temporal blood glucose profile is achieved, but also spot measurements are possible.
  • the temporal tissue glucose gradient is determined using at least two measurements. The deviations of the integral tissue glucose from the blood glucose concentration are corrected, for example, using suitable digital filters, the blood volume and the measured metabolic state being taken in as parameters, as described above.
  • the invention also proposes a device for the non-invasive measurement of blood components and clinical parameters, in particular for glucose measurement, by means of the optical spectroscopy of skin tissue in the visible, infrared or ultraviolet spectral range with an irradiation device, a measuring device for the skin sample optically connected thereto and one of the the skin sample is reflected by radiation detection device with evaluation unit for determining the glucose concentration, which is characterized in that the evaluation unit is additionally set up for determining the metabolic state and the blood volume of the skin sample and for determining the blood glucose concentration from the measured values.
  • the measuring device is provided with a heating device for applying heat to the skin sample.
  • the measuring device has an ellipsoid of rotation mirror for guiding the radiation reflected from the skin sample to the detector device.
  • the area of the irradiated area of the skin sample is adjustable is.
  • the distance between the illuminated area of the skin sample and the detection area can thus be set, so that regulation of the photon penetration depth is possible. This has proven to be important in order to avoid that the photons penetrate into the subcutaneous fatty tissue and thereby falsify the measurement results.
  • the extinction size can also be controlled by the lighting spot size that can be adjusted for lighting.
  • the detector device can additionally be provided with a changeable concentric diaphragm or circular disk, so that radiation components scattered back from the skin reach the detector device from certain solid angle regions, which have different mean tissue penetration depths.
  • the skin spectrum measured in this way is dominated by the upper layer of the epidermis by flat photons penetrating the tissue.
  • the signal portion of the blood-bearing epidermis layer can be optimized by means of differential spectroscopy, that is to say the formation of a difference from the skin spectrum measured integrally over the entire accessible solid angle range.
  • the measuring device for irradiating the skin sample and for transporting the reflected radiation to the detector device has glass fibers or glass fiber bundles, which in are arranged at an angle or parallel to each other.
  • the glass fiber bundles are preferably arranged concentrically.
  • a distance is provided between the glass fibers or the glass fiber bundles for irradiating the skin sample and for transporting the reflected radiation to the detector device.
  • Fig. 2c difference spectra of different skin samples between normal versus strong probe contact pressure of the sensor head on the skin sample
  • FIG. 3 shows a simplified representation of a device according to the invention according to a first embodiment
  • Fig. 4 shows the basic structure of an irradiation device
  • Fig. 5 shows another device.
  • tissue glucose concentration profiles are inevitably measured, which differ considerably from the relevant blood glucose concentration profiles, so that incorrect results are obtained, particularly in the area of hypoglycaemia (hypoglycemic range) leads to unacceptable errors.
  • glucose signals are measured which are of different origins, so to speak, originating from different compartments of the skin tissue, the intravascular, the interstitial (cell interspace) and the intercellular space.
  • a blood spectrum is also measured according to the invention, which also contains the information about the total skin water content, which provides the blood volume for normalization .
  • An evaluation of the blood spectrum also enables the degree of oxygenation to be calculated, which provides an indication of the metabolic state and blood flow in the skin sample.
  • a more detailed information can be obtained from a simultaneous measurement of the pulse spectrum (arterial space) and the integral blood space.
  • the arteriovenous difference (AVD) of the oxygen saturation of the blood can be determined from the evaluation of both spectra (or of at least two wavelengths), which provides an indication of the metabolic activity of the examined tissue (metabolic turnover).
  • the blood flow velocity is also determined in a design according to the invention using a laser Doppler method.
  • the blood flow in the skin sample can be increased in the method according to the invention, which can be achieved, for example, by applying heat to the skin sample.
  • the arterio-venous difference in the glucose concentration is then small, which is synonymous with low gradients on the one hand in the vascular space and on the other hand in the interstitial tissue space, this being achieved in the last-mentioned compartment only after a prolonged increase in blood flow, adapted to the transport speeds in the tissue , This procedure is preferred for potash
  • the skin tissue spectra are used because in the physiologically stationary area, taking into account the metabolic activity, there is a fixed functional relationship to the invasively determined blood glucose concentration, that is to say obtained from blood samples, to the mean glucose tissue concentration.
  • the method described provides enormous stability and repeatability of the blood glucose measurements, which allows an integral tissue measurement, e.g. to be able to measure reliably in the lower blood glucose concentration range (hypoglycaemia). Avoiding hypoglycaemia is vital for diabetics. Instead of glucose, other metabolites or other parameters, e.g. the pH value can be determined reliably.
  • a measurement quality required for the physician and patient for low-concentration blood components, which can also be found in other physiological compartments, can be achieved by means of non-invasive spectroscopic measurement methods.
  • Fig. 2a the skin spectra recorded with diffuse reflection measurement technology are one shown to each person.
  • the absorption bands below 600 nm are mainly assigned to oxyhemoglobin, the intensities of which are proportional to the amount of blood.
  • 2b shows the influence of a direct heat application to the lip skin by placing a probe body thermostated at 42 ° (the respective difference spectra of a series of the recorded lip spectrum are shown after 2 minutes).
  • the skin spectrum obtained after 2 min was used as the reference spectrum.
  • the establishment of equilibrium with increased blood flow is hereby shown.
  • the contact pressure of the measuring probe on the skin sample is preferably kept repeatably low during the measurement in order to obtain reproducible results.
  • 2c shows the influence of strong pressure changes on the skin by means of a fiber optic probe, which shows the importance of a reproducible sensor pad.
  • a device 3 according to the invention is shown by way of example in FIG. 3, which initially has an irradiation device (here IR spectrometer), which is not shown in detail, the IR radiation originating from this is indicated by reference number 4.
  • IR spectrometer irradiation device
  • other radiation devices can also be used, as is shown in principle in FIG. 4.
  • thermal radiation sources, LEDs or fiber amplifiers can also be used; an interferometer, a monochromator, an AOTF or optical filter can also be used as spectral apparatus; the use of diode lasers is also possible, in which case the spectral apparatus can be dispensed with.
  • a measuring device for a skin sample 5 is optically connected to the IR spectrometer provided in FIG. 3.
  • this measuring device consists of a rotating ellipsoid mirror 6 with further mirrors 7, 8 and a lens 9, the beam paths being shown.
  • a heating device (not shown) and a device are provided which ensure a reproducible low contact pressure on the skin sample.
  • a device is e.g. described in DE 42 42 083 AI.
  • a detector device 10 which collects the radiation reflected by the skin sample 5.
  • This detector device 10 can be modified with a variable see aperture or circular disc, which are not shown, are provided, with which radiation components from certain solid angle regions reach the detector device which have different mean tissue penetration depths.
  • the detector device 10 is connected to an evaluation unit for determining the glucose concentration, which is not shown. This evaluation unit is additionally set up to determine the blood volume and the metabolic state of the skin sample and to determine the blood glucose concentration from the measured values.
  • the measuring device has an optical fiber bundle or an optical fiber 11 leading from the radiation source (arrow 4), which is placed on the skin sample 5.
  • the radiation diffusely reflected by the skin sample 5 is partially absorbed by a further fiber bundle 12 or a fiber and directed to the detector device (not shown).
  • the fiber bundles 11 and 12 are arranged at an angle to one another in order to collect as much reflected radiation as possible.
  • individual optical fibers can also be taken into account, which lead to a second spectral apparatus.
  • FIGS. 3, 4 and 5 only show preferred configurations.

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Abstract

L'invention concerne un procédé pour la mesure non invasive de composants sanguins et de paramètres cliniques, en particulier pour la mesure du glucose, par spectroscopie optique de tissus cutanés, dans le domaine spectral visible, infrarouge ou ultraviolet, et a pour but d'obtenir des résultats de mesure précis également dans les cas d'hypoglycémie. Ce but est atteint grâce à l'invention, laquelle est caractérisée en ce qu'en plus de la mesure du glucose sur l'échantillon de peau, on mesure également le volume du sang et l'état métabolique de l'échantillon, et en ce qu'en se basant sur ces valeurs mesurées et sur la concentration en glucose mesurée dans les tissus, on détermine la concentration en glucose dans le sang.
PCT/EP2000/005445 1999-08-10 2000-06-14 Procede et dispositif pour la mesure non invasive de composants sanguins et de parametres cliniques WO2001010294A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU56814/00A AU5681400A (en) 1999-08-10 2000-06-14 Method and device for measuring blood fractions and clinical parameters in a non-invasive manner

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE1999137699 DE19937699C1 (de) 1999-08-10 1999-08-10 Verfahren und Vorrichtung zur nichtinvasiven Messung von Blutbestandteilen und klinischen Parametern
DE19937699.9 1999-08-10

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WO2001010294A1 true WO2001010294A1 (fr) 2001-02-15

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6958039B2 (en) 2003-05-02 2005-10-25 Oculir, Inc. Method and instruments for non-invasive analyte measurement
US6968222B2 (en) 2003-05-02 2005-11-22 Oculir, Inc. Methods and device for non-invasive analyte measurement
US6975892B2 (en) 2003-10-21 2005-12-13 Oculir, Inc. Methods for non-invasive analyte measurement from the conjunctiva
US7283242B2 (en) 2003-04-11 2007-10-16 Thornton Robert L Optical spectroscopy apparatus and method for measurement of analyte concentrations or other such species in a specimen employing a semiconductor laser-pumped, small-cavity fiber laser
US7596403B2 (en) 2004-06-30 2009-09-29 Given Imaging Ltd. System and method for determining path lengths through a body lumen
US7633621B2 (en) 2003-04-11 2009-12-15 Thornton Robert L Method for measurement of analyte concentrations and semiconductor laser-pumped, small-cavity fiber lasers for such measurements and other applications

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US5068536A (en) 1989-01-19 1991-11-26 Futrex, Inc. Method for providing custom calibration for near infrared instruments for measurement of blood glucose
WO1993012712A1 (fr) * 1991-12-31 1993-07-08 Vivascan Corporation Procede de detection de constituant sanguin basee sur l'analyse spectrale differentielle
WO1993017621A1 (fr) * 1992-03-12 1993-09-16 Wong Jacob Y Mesure des composants chimiques du sang par emission infrarouge stimulee
EP0586025A2 (fr) 1992-07-06 1994-03-09 Robinson, Mark R. Mesure fiable et non-invasif de gaz sanguins
DE4242083A1 (de) 1992-12-14 1994-06-16 Marbach Hermann Dipl Ing Sensorvorrichtung zur Messung der Interaktion infraroter Strahlung mit menschlicher Haut
EP0623308A1 (fr) * 1993-05-07 1994-11-09 Diasense, Inc. Mesure non-invasive de la concentration de constituants du sang
DE19518511A1 (de) * 1994-05-20 1995-11-23 Hermann Dipl Ing Kuenst Transcutane, unblutige Konzentrationsbestimmung von Substanzen im Blut
EP0903571A2 (fr) * 1997-09-19 1999-03-24 Matsushita Electric Industrial Co., Ltd. Dispositif et procédé de détermination de la concentration de substances particulières
WO2000001295A1 (fr) * 1998-07-07 2000-01-13 Lightouch Medical, Inc. Processus de modulation tissulaire destine a l'analyse spectroscopique quantitative non invasive in vivo des tissus

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JP4212007B2 (ja) * 1996-11-26 2009-01-21 パナソニック電工株式会社 血液成分濃度の分析装置

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5068536A (en) 1989-01-19 1991-11-26 Futrex, Inc. Method for providing custom calibration for near infrared instruments for 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
WO1993012712A1 (fr) * 1991-12-31 1993-07-08 Vivascan Corporation Procede de detection de constituant sanguin basee sur l'analyse spectrale differentielle
WO1993017621A1 (fr) * 1992-03-12 1993-09-16 Wong Jacob Y Mesure des composants chimiques du sang par emission infrarouge stimulee
EP0586025A2 (fr) 1992-07-06 1994-03-09 Robinson, Mark R. Mesure fiable et non-invasif de gaz sanguins
DE4242083A1 (de) 1992-12-14 1994-06-16 Marbach Hermann Dipl Ing Sensorvorrichtung zur Messung der Interaktion infraroter Strahlung mit menschlicher Haut
EP0623308A1 (fr) * 1993-05-07 1994-11-09 Diasense, Inc. Mesure non-invasive de la concentration de constituants du sang
DE19518511A1 (de) * 1994-05-20 1995-11-23 Hermann Dipl Ing Kuenst Transcutane, unblutige Konzentrationsbestimmung von Substanzen im Blut
EP0903571A2 (fr) * 1997-09-19 1999-03-24 Matsushita Electric Industrial Co., Ltd. Dispositif et procédé de détermination de la concentration de substances particulières
WO2000001295A1 (fr) * 1998-07-07 2000-01-13 Lightouch Medical, Inc. Processus de modulation tissulaire destine a l'analyse spectroscopique quantitative non invasive in vivo des tissus

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7283242B2 (en) 2003-04-11 2007-10-16 Thornton Robert L Optical spectroscopy apparatus and method for measurement of analyte concentrations or other such species in a specimen employing a semiconductor laser-pumped, small-cavity fiber laser
US7633621B2 (en) 2003-04-11 2009-12-15 Thornton Robert L Method for measurement of analyte concentrations and semiconductor laser-pumped, small-cavity fiber lasers for such measurements and other applications
US6958039B2 (en) 2003-05-02 2005-10-25 Oculir, Inc. Method and instruments for non-invasive analyte measurement
US6968222B2 (en) 2003-05-02 2005-11-22 Oculir, Inc. Methods and device for non-invasive analyte measurement
US6975892B2 (en) 2003-10-21 2005-12-13 Oculir, Inc. Methods for non-invasive analyte measurement from the conjunctiva
US7596403B2 (en) 2004-06-30 2009-09-29 Given Imaging Ltd. System and method for determining path lengths through a body lumen

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DE19937699C1 (de) 2001-11-22

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