WO2008152604A1 - Mesures de spectroscopie - Google Patents

Mesures de spectroscopie Download PDF

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Publication number
WO2008152604A1
WO2008152604A1 PCT/IB2008/052337 IB2008052337W WO2008152604A1 WO 2008152604 A1 WO2008152604 A1 WO 2008152604A1 IB 2008052337 W IB2008052337 W IB 2008052337W WO 2008152604 A1 WO2008152604 A1 WO 2008152604A1
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Prior art keywords
substance
concentration
light
spectroscopy
interferometry
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PCT/IB2008/052337
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English (en)
Inventor
Markus Laubscher
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Koninklijke Philips NV
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Koninklijke Philips Electronics NV
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    • 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
    • A61B5/1495—Calibrating or testing of in-vivo probes
    • 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
    • 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
    • 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
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N21/49—Scattering, i.e. diffuse reflection within a body or fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2560/00—Constructional details of operational features of apparatus; Accessories for medical measuring apparatus
    • A61B2560/02—Operational features
    • A61B2560/0223—Operational features of calibration, e.g. protocols for calibrating sensors

Definitions

  • the invention relates to spectroscopy measurements of the concentration of a substance in a scattering medium.
  • Spectroscopy may be used to measure the concentration of a substance in a scattering medium.
  • a light beam is sent on the medium and the light that has interacted with the medium (either backscattered or transmitted) is collected, so as to deduce an absorbance spectrum.
  • the concentration of the target substance can be deduced from the absorbance spectrum by means of a mathematical model, making use of the known spectral characteristics of the substances contained within the medium.
  • the scattering medium may be the skin of a person.
  • Spectroscopy on skin permits to estimate the person's blood concentration of a substance, in vivo and non- invasively.
  • a type of spectroscopy that may be used is Near Infra-Red spectroscopy, in which near infrared (NIR) light or infrared light is irradiated on skin. Such a light is used because it penetrates more easily in the skin and is not immediately absorbed or heavily scattered.
  • NIR spectroscopy is for instance used for determining the glucose concentration in blood.
  • US 6, 110, 522 describes a method for analyzing a blood glucose concentration, comprising emitting a light radiation from a NIR light source.
  • the water concentration is evaluated within the particular probed skin volume, wherein the light is irradiated.
  • This probed skin volume may for instance be an earlobe or a finger tip.
  • the water concentration can only be determined as an average over the probed skin volume and the evaluated water concentration is considered constant during measurements. Then, using the known absorption spectrum of pure water, the acquired absorbance spectrum of the skin volume is corrected, either directly (by signal subtraction) or indirectly via a statistical data treatment.
  • pressure may be applied to the skin volume, therefore pushing the water out of the probed skin volume and changing the concentration thereof;
  • the water concentration may be different.
  • a method for calculating, for a scattering medium comprising at least a first substance and a second substance, the concentration of the first substance, by applying a mathematical model to an absorbance spectrum of the scattering medium obtained by spectroscopy comprising: a) measuring the concentration of the second substance by interferometry and b) using the concentration of the second substance to correct the contribution of the second substance in the calculation of the concentration of the first substance.
  • spectroscopy and interferometry are combined for the measurement of the concentration of the first substance, taking into account the contribution of the second substance in the calculation of the concentration of the first substance.
  • interferometry permits to map out the pathlength distribution of light within the medium, that is to say, how the photons of the light irradiated on the medium travel within said medium.
  • This information on the pathlength distribution of detected light offers good indications on the probed medium volume; it allows determining the extent and depth of the probed medium volume. Furthermore, it offers an independent way of determining the concentration of the second substance within the medium. Indeed, the knowledge of the pathlength distribution permits to get information on:
  • spectroscopy permits to obtain the absorbance spectrum of the medium, which can lead to a calculation of the concentration of the first substance, corrected thanks to the value of the concentration of the second substance within the medium.
  • concentration of the first substance within the medium is therefore more accurately calculated.
  • step b) above comprises correcting the absorbance spectrum of the scattering medium with a spectrum of the second substance, corresponding to its concentration, and applying the mathematical model to the corrected spectrum.
  • the method comprises:
  • step b) above comprises using the concentration of the second substance as an additional input into the mathematical model, so that the mathematical model corrects the contribution of the second substance in the calculation of the concentration of the first substance.
  • the method comprises:
  • spectroscopy and interferometry are performed simultaneously and on the same scattering medium's position and/or volume.
  • the scattering medium is skin.
  • the first substance is glucose and the second substance is water.
  • spectroscopy is near infrared spectroscopy.
  • interferometry is low coherence interferometry.
  • the invention also relates to a device for implementing the method above, comprising a spectroscopy light source, an interferometry light source, means for measuring the absorbance spectrum of the scattering medium and means for performing interferometry measurements.
  • the device comprises means for calculating and preferably for automatically calculating the concentration of the second substance with the interferometry measurements and means for using and preferably for automatically using it to correct the contribution of the second substance in the calculation of the concentration of the first substance.
  • the device comprises a single detector for measuring the absorbance spectrum and for performing interferometry measurements
  • Fig.1 is a schematic block diagram representing a device for implementing a first embodiment of the method of the invention.
  • - Fig.2 is a schematic block diagram representing a device for implementing a second embodiment of the method of the invention.
  • the invention will be described in relation to particular embodiments, where the concentration of glucose in blood is measured in vivo, within the skin of a person.
  • the method of the invention could also be applied to an animal.
  • the probed skin volume designates the volume of skin irradiated by light for the measurements. It can be, for instance, an earlobe, a fingertip, an arm or any other suitable part of the body.
  • the probed skin volume is irradiated with an incident light and spectroscopy is performed with the light that has interacted with the probed skin volume; this light is scattered light that may either be backscattered light or transmitted light.
  • measurements are made on backscattered light.
  • measurements could also be performed on transmitted light; the person skilled in the art shall transpose easily.
  • the light used for spectroscopy is near infrared (NIR) or infrared light.
  • NIR spectroscopy will be used to designate such a spectroscopy, wherein either near infrared or infrared light is used.
  • NIR spectroscopy is performed in a conventional manner.
  • the backscattered or transmitted light is gathered within a spectrometer, where diffuse reflectance/transmission is measured. Taking the logarithm of this reflectance/transmission permits to get an absorbance spectrum of the probed skin volume.
  • the interferometry performed on the probed skin volume is low coherence interferometry, which will be designated as LCI.
  • LCI on the one hand
  • NIR spectroscopy on the other hand
  • the invention relates to their combination in a certain application (measuring the concentration of a substance in a scattering medium).
  • LCI and NIR spectroscopy will not be very detailed in the present description, since the person skilled in the art is able to implement them on his own.
  • a device 1 for implementing the time-domain method of the invention comprises a light source 2 for performing NIR spectroscopy, which will be designated as the NIR light source 2, and a light source 3 for performing LCI, which will be designated as the LCI light source 3.
  • the NIR light source 2 is a source emitting light in the near infrared or in the infrared; light is emitted into a fiber 4.
  • the LCI light source 3 is a light source with low temporal coherence, such as a white light (e.g., a LED (Light Emitting Diode), a SLD (Super Luminescent Diode), a supercontinuum source or an halogen lamp) or a high specification femtosecond laser.
  • the light source 3 is a SLD; light is emitted into a fiber 5.
  • the LCI light source 3 is tuned on a wavelength close to the absorption band of water. With such a wavelength, the main optical phenomenon is absorption, while scattering is very low and can be neglected. Therefore, it can be considered that the intensity decrease of the light from the LCI light source 3, when it passes through the probed skin volume, is due exclusively to absorption and not to scattering.
  • the chosen wavelength should not be too far within the absorption band of water, otherwise the light would be entirely absorbed and no light would be detected.
  • the fibers 4, 5 collecting light from the light sources 2, 3 enter a first coupler 6, where both light beams are coupled into a single light beam. At the output of the coupler 6, this light beam is split into two paths: a reference path 7 and an absorbing path 8, for the purpose of LCI.
  • the reference path 7 (which can also be referred to as a "reference arm”) is a path where light is guided, through a first fiber 7a, to a reference mirror 9, is reflected on it and is collected into a second fiber 7b, which enters a second coupler 10.
  • the reference mirror 9 is movable so as to change the pathlength of the reference path 7.
  • the absorbing path 8 is a path where light is guided, through a first fiber 8a, to the skin volume 11 to be measured; light enters the skin, is partly absorbed and scattered by it (and particularly by the water and glucose contained in it) and is collected into a second fiber 8b, which enters the second coupler 10.
  • the coupler 10 In the coupler 10, light coming from the reference path 7 and the absorbing path 8 are mixed, in order to interfere, so as to permit LCI to be performed. This resulting interfered light beam is divided into a fiber 12 guiding the light to a spectrometer 13, where NIR spectroscopy can be performed, and a fiber 14 guiding the light to a photodetector 15, where LCI can be performed.
  • the reference mirror 9 is a means to change the pathlength of the reference path 7.
  • Other means could be used, known by the person skilled in the art. Two major distinctive approaches can be contemplated: firstly, the complete, continuous scanning; secondly, the discrete multiple length dithering.
  • RSOD Rapid Scanning Optical Delay
  • discrete multiple length dithering only a small number of discrete pathlengths are measured for analysis. This can be accomplished, for instance, by an optical circulator, fiber splitter(s), short range piezo-mounted mirrors for length dithering only (amplitude of a few wavelengths), an optical circulator, a cavity formed by a piezo-mounted mirror or a Bragg array for multiple reflections.
  • the light sources 2, 3 are operated simultaneously.
  • the light beam comprises two components: the component coming from the NIR light source (NIR component) and the component coming from the LCI light source (LCI component).
  • NIR component the component coming from the NIR light source
  • LCI component the component coming from the LCI light source
  • the object of the method is to measure the backscattering signals of the NIR component and the interference signals of the LCI component.
  • the NIR light source 2 is spatially incoherent, there will be no interference of the NIR component of the signal.
  • the NIR light source 2 is spatially coherent (e.g., if it is a "white laser"), then, interference of the NIR light will also occur. This will be of no influence on the signals detected by the spectrometer 13 since, with the moving reference mirror 9, the interference signal at the spectrometer 13 will be averaged out in time to result in a spectrum without signs of interference.
  • both light sources generate a modulated signal, while the only interesting modulated signal is the one coming from the LCI light source 3.
  • the frequency of the modulation depends on the central wavelength of the spectrum and the signals can be separated with electronic frequency filtering if the central wavelengths are not too close. Otherwise, an optical filter can be used to eliminate the majority of the NIR light that is not at the wavelengths of the LCI light source 3. Finally, if this still generates too much overlapping signals, the light sources 2, 3 can be operated sequentially in time. According to another embodiment, the NIR light is guided along a path where it does not go to the reference mirror 9 and therefore does not interfere.
  • the light beam enters the spectrometer 13, on the one hand, the photodetector 15, on the other hand.
  • the light beam is filtered before entering the spectrometer 13 and the photodetector 15 to better distinguish the interesting component of the light to be measured.
  • a filter 16 is provided between the second coupler 10 and the spectrometer 13 to filter the light coming from the LCI light source 3, so that light coming from the NIR light source 2 is analyzed within the spectrometer 13.
  • a filter 17 is provided between the second coupler 10 and the photodetector 15 to filter the light coming from the NIR light source 2, so that light coming from the LCI light source 3 is analyzed within the photodetector 15.
  • the filters 16, 17 are not per se essential in the described embodiment, but improve the detection sensitivity. Especially, the filter 16 before the spectrometer 13 will block or attenuate the relatively strong radiation of the LCI light source 3 that might otherwise lead to saturation of parts of the spectrometer 13.
  • the photodetector 15 will be much less influenced by the NIR light source 2, as the light intensity per wavelength is much lower than the one of the LCI light source 3.
  • the NIR light source 2 is spatially incoherent and therefore does not give rise to a modulated signal like the LCI light source 3.
  • the spectrometer 13 detects the multiple scattering of the NIR light in the probed skin volume 11. More precisely, it measures the diffuse reflectance (or transmission) of the backscattered (or transmitted) NIR light; the logarithm of this diffuse reflectance is a value proportional to the absorbance spectrum; an absorbance spectrum of the probed skin volume 11 can therefore be obtained with the measured diffuse reflectance.
  • the features of the absorbance spectrum are due to the scattering and absorption of light by all the components in the probed skin volume, in particular glucose and water. This spectrum is the basis for the calculation of the glucose concentration.
  • the light measured in the photodetector 15 is the light coming from the LCI light source 3.
  • the part of this light which is guided along the absorbing path 8 is absorbed in the probed skin volume 11.
  • the reference mirror 9 is moved, so that the pathlength of the reference path 7 is changed.
  • the pathlength of the reference path 7 is changed in a sequential manner, usually periodically, in a manner known by the person skilled in the art.
  • the light from the reference path 7 interferes with the light from the absorbing path 8. Since the pathlength of the reference path 7 is sequentially changed, the signal of these interferences also changes; this is because the reference pathlength is changed sequentially, in time, that this embodiment is called the time-domain embodiment.
  • the interference patterns contain information on how the light is absorbed in the absorbing path 8.
  • the LCI light source 3 Since the LCI light source 3 is tuned near or in the absorption band of water, the information gathered by LCI is mainly influenced by water; the influence of the other substances within the probed skin volume 11 can be neglected; it can therefore be considered that the results are exclusively due to the presence of water.
  • the photodetector 15 detects the intensity of the light coming out of the coupler 10. Therefore, a diagram is obtained, with the intensity of light as a function of the pathlength, that is to say, a measure of the number of photons that have traveled a certain path in the skin. This number of photons decreases exponentially according to Lambert-Beer's law.
  • the signal received on the photodetector 15 can be decomposed into a continuous signal and an alternating signal;
  • the interesting part for LCI, where the information can be found, is the alternating part, since when the pathlength of the reference path 7 is changed, the amplitude of the alternating part is changed.
  • the envelop of those amplitudes, that is to say, the amplitude of the detected interference signal envelop, as a function of the pathlength, is an exponential curve following the Lambert-Beer's law.
  • the Lambert-Beer's law reads as follow:
  • I the intensity of the detected signal
  • I 0 the intensity of the incident light
  • ⁇ the absorption coefficient
  • X the path length
  • ⁇ the molar extinction coefficient
  • c the concentration of absorbing species in the material, that is to say, with the approximations which have been made (water is the predominant absorber), the concentration of water in the probed skin volume.
  • the information on water is used to improve the quality of the calculation of the glucose concentration.
  • the concentration of water is used to correct the contribution of water in the calculation of the glucose concentration.
  • the calculation is corrected by directly correcting the absorbance spectrum of skin with a spectrum of water, corresponding to its concentration, and then applying a mathematical model to this corrected spectrum.
  • the calculation is corrected by using the concentration of water as an additional input to an adapted mathematical model, so that the mathematical model corrects the contribution of water in the calculation of the concentration of glucose, the mathematical model having, as inputs, the absorbance spectrum of skin and the concentration of water.
  • Chemometrics Society defines chemometrics as the science of relating measurements made on a chemical system or process to the state of the system via application of mathematical or statistical methods.
  • a chemometric mathematical model is used to relate an absorbance spectrum to the value of the glucose concentration.
  • the mathematical model may be developed with a "partial least squares" (PLS) regression method, well known by the person skilled in the art.
  • PLS partial least squares
  • NIR measurements are performed on skin samples of which the concentration of glucose is known by another way.
  • the objective of the PLS- regression method is to calculate the vector, called the regression vector, which represents the translation between an absorbance spectrum and the corresponding concentration of glucose.
  • Each substance here glucose
  • An absorbance spectrum is represented by a vector.
  • To develop the model several absorbance spectra are measured on skin samples, which have known calibrated glucose concentrations. On the one hand, all those spectra are gathered into a matrix, which we will call the calibration matrix.
  • the corresponding calibrated glucose concentrations are gathered into a vector, where each element corresponds to a calibrated glucose concentration; we will call this vector the calibration vector.
  • the PLS-regression method is then applied in order to calculate the regression vector, which represents the translation from the calibration matrix to the calibration vector.
  • the regression vector is obtained, it is possible to perform measurements on unknown skin samples and deduce therefrom the glucose concentration of those skin samples. Indeed, spectroscopy is performed, providing an absorbance spectrum, which can be represented in the form of a vector, which is taken as the input of the mathematical model. With the model, the vector of the absorbance spectrum is multiplied by the regression vector, this multiplication resulting in the value of the glucose concentration in the measured skin sample.
  • the concentration of glucose can be calculated therefrom with high sensibility, since its contribution appears clearly and is not masked by the peaks of the highly absorbing water. More precisely, this corrected absorbance spectrum is used as the entry of a chemometric mathematical model, so as to obtain the glucose concentration.
  • this mathematical model has to have been developed before, with calibration skin samples.
  • the calculated regression vector will be different from the regression vector described above for the prior art mathematical model because, according to this embodiment, the regression vector has to be applied on an absorbance spectrum from which the main peaks of water have been removed.
  • the development of the regression vector is done with calibration skin samples for which the glucose as well as the water concentrations are known. NIR spectroscopy is performed on each calibration sample, in order to get an absorbance spectrum. A certain spectrum - corresponding to the concentration of water - is subtracted from this absorbance spectrum in order to obtain a corrected absorbance spectrum.
  • the corrected absorbance spectra are filled into a calibration matrix; this calibration matrix is a matrix of data corresponding to corrected calibration absorbance spectra.
  • the calibration vector comprises the glucose concentrations of the calibration skin samples.
  • the regression vector is calculated as the vector representing the translation from the calibration matrix to the calibration vector.
  • the corrected absorbance spectrum of the probed skin volume 11 is entered as an input of the chemometric mathematical model which has been developed as explained just above, where it is multiplied by the regression vector, resulting in the value of the glucose concentration in the probed skin volume 11.
  • the LCI calculated water concentration is used as an additional input for the chemometric mathematical model that serves to calculate the glucose concentration with the NIR spectroscopy information.
  • the mathematical model therefore corrects the contribution of water in its calculation of the glucose concentration.
  • a regression vector has to be calculated for the mathematical model in order to permit, by inputting a measured absorbance spectrum and a measured water concentration, to obtain the glucose concentration of the probed skin volume 11.
  • the regression vector has to take into account the water concentration in its calculation of the glucose concentration.
  • the development of the regression vector is done with calibration skin samples for which the glucose as well as the water concentrations are known; samples with various glucose concentrations as well as various water concentrations are tested. NIR spectroscopy measurements and LCI measurements are performed on these calibration samples, in order to fill a calibration matrix, which comprises the absorbance spectra data as well as the corresponding water concentrations of those calibration samples. Compared to the calibration matrixes that have been presented above, this calibration matrix has an additional dimension corresponding to the water concentration data.
  • the calibration vector comprises the glucose concentrations of the calibration skin samples.
  • the regression vector is calculated as the vector representing the translation from the calibration matrix to the calibration vector. It also has one more dimension than before, since it takes into account the concentration of water as an input.
  • the absorbance spectrum and the water concentration are entered as inputs into the chemometric mathematical model, as a vector, which is multiplied by the regression vector, resulting in the value of the glucose concentration.
  • the whole water spectrum could be used for the development step of the regression vector, thus using a calibration matrix having double size.
  • a calibration matrix having double size Such an embodiment will not be further developed herein.
  • the concentration of water is calculated meanwhile the absorbance spectrum of the probed skin volume is obtained.
  • LCI permits an independent way of measuring the concentration of water; the correction may be made at the right moment and the variations of the concentration of water within the probed skin volume 11 (due to pressure, between different measurements, etc.) are taken into account "in real time”.
  • the spectroscopy measurements can in fact be performed just before, just after or during the LCI measurements. In the described embodiments of the invention, both measurements are performed simultaneously.
  • the device 1 may comprise means arranged for automatically calculating the concentration of water with the results of LCI and automatically using the concentration of water to correct the contribution of water in the calculation of the glucose concentration, whatever the calculation embodiment is (correcting the absorbance spectrum or using the water concentration as an additional input for the mathematical model).
  • lights from the NIR light source 2 and the LCI light source 3 are combined into one light beam irradiated onto the skin through the fiber 8a.
  • the light sources 2, 3 are operated sequentially, both being guided by the fiber 8a.
  • Two different fibers may also be provided for the irradiation of the skin, each fiber for a particular light source 2, 3.
  • a device 1' for implementing the Fourier-domain method of the invention comprises a NIR light source 2' and a LCI light source 3', emitting into fibers 4', 5' in a very similar manner as above.
  • the fibers 4', 5' enter a first coupler 6', where both light beams are coupled into a single light beam.
  • this light beam is split into two paths: a reference path T and an absorbing path 8', for the purpose of LCI.
  • a reference mirror 9' is provided on the reference path 7'; this mirror is fixed. Lights from both paths 7', 8' are mixed within a second coupler 10', so as to interfere.
  • This resulting interfered light beam is divided into a first fiber 12' guiding the light to a collimation lens 18 which directs the light to a first grating 19, and a second fiber 14' guiding the light to a collimation lens 20 which directs the light to a second grating 21.
  • the gratings 19, 21 are means for dispersing light and that any equivalent means (such as, for instance, prisms) could be used.
  • the light, dispersed by the gratings 19, 21, is directed to a detector array 22.
  • the LCI measurement is based on the acquisition of a "channeled" spectrum. No moving parts in this reference path 7' are needed and this is why the mirror 9' is fixed.
  • the detector array 22 directly measures the light spectrum.
  • Concerning LCI this spectrum is Fourier-transformed in order to obtain a representation that corresponds to the time-domain measurement (light intensity as a function of the pathlength). This in turn is fitted with an exponential decay in order to extract the water absorption (Lambert-Beer's law), as explained for the time-domain embodiment.
  • Concerning NIR spectroscopy the absorbance spectrum is directly measured on the detector array 22.
  • results of LCI are used for correcting the contribution of water in the calculation of the concentration of glucose in the probed skin volume 11. Again, several embodiments could be contemplated, for instance the two calculation embodiments presented above.
  • a single detector 22 is provided for the measurement of both NIR and LCI signals.
  • the spectrum of the LCI light source 3' is much narrower (about IOnm) than that of the NIR light source 2 (about lOOOnm); therefore, in order to still use the same detector 22 for both signals, it is necessary to employ two different gratings 19, 21. Using the same detector 22 provides cost advantages.
  • NIR and LCI signals cannot be measured simultaneously on the detector array 22. Hence, they have to be alternated in time, so that measurements of LCI and NIR spectra can be performed sequentially. This can be achieved, for instance, by pulsing the LCI light source 3' and/or chopping/shutting the NIR light source 2', with triggered spectra acquisition. Any means may be contemplated so that LCI and NIR spectroscopy measurements are alternated in time. As well as before, attention should be paid to interferences of the light from the NIR light source 2' and the device 1' should be set up in such a way that these interferences are not a problem for getting the absorbance spectrum of the probed skin volume 11.
  • Fourier-domain measurements have a higher sensitivity than time-domain measurements, offering the possibility to measure over longer optical pathlengths.
  • Each spectral acquisition provides absorption measurements for all pathlengths.
  • each detector being associated with a grating 19, 21.
  • the light sources 2', 3' and the measurements do not need to be alternated in time.
  • the described Fourier-domain embodiment is contemplated with a configuration where the same fiber is used for coupling the light into the skin and detecting the scattered light.
  • a different fiber is used for guiding each type of light.
  • a computer program may be stored/distributed on a suitable medium, such as an optical storage medium or a solid- state medium supplied together with or as part of other hardware, but may also be distributed in other forms, such as via the Internet or other wired or wireless telecommunication systems. Any reference signs in the claims should not be construed as limiting the scope.

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Abstract

La présente invention concerne un procédé permettant de calculer, pour un milieu de diffusion comportant au moins une première substance et une seconde substance, la concentration de la première substance, par application d'un modèle mathématique à un spectre d'absorbance du milieu de diffusion obtenu par spectroscopie (13). Le procédé comprend : a) la mesure de la concentration de la seconde substance par interférométrie (15), et b) l'utilisation de la concentration de la seconde substance pour corriger la contribution de la seconde substance dans le calcul de la concentration de la première substance. Grâce à l'invention, la concentration de la première substance est mesurée avec une plus grande précision.
PCT/IB2008/052337 2007-06-15 2008-06-13 Mesures de spectroscopie Ceased WO2008152604A1 (fr)

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EP07301111.6 2007-06-15
EP07301111 2007-06-15

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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WO2003052391A1 (fr) * 2001-12-14 2003-06-26 Optiscan Biomedical Corporation Procede spectroscopique permettant de determiner une concentration d'analytes dans un echantillon
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