EP1887923A1 - Mesure non invasive d'analytes sanguins par spectroscopie d'emission thermique - Google Patents

Mesure non invasive d'analytes sanguins par spectroscopie d'emission thermique

Info

Publication number
EP1887923A1
EP1887923A1 EP06744989A EP06744989A EP1887923A1 EP 1887923 A1 EP1887923 A1 EP 1887923A1 EP 06744989 A EP06744989 A EP 06744989A EP 06744989 A EP06744989 A EP 06744989A EP 1887923 A1 EP1887923 A1 EP 1887923A1
Authority
EP
European Patent Office
Prior art keywords
thermal emission
analyte
glucose
optical element
wavelengths
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Withdrawn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
EP06744989A
Other languages
German (de)
English (en)
Inventor
Antonius c/o Société Civile SPID VAN GOGH
Maarten Société Civile SPID VAN HERPEN
Marcello Société Civile SPID BALISTRERI
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.)
Koninklijke Philips NV
Original Assignee
Koninklijke Philips Electronics NV
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
Application filed by Koninklijke Philips Electronics NV filed Critical Koninklijke Philips Electronics NV
Priority to EP06744989A priority Critical patent/EP1887923A1/fr
Publication of EP1887923A1 publication Critical patent/EP1887923A1/fr
Withdrawn legal-status Critical Current

Links

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
    • A61B5/14532—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/01—Measuring temperature of body parts ; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue
    • A61B5/015—By temperature mapping of body part

Definitions

  • the present invention relates to the non- invasive measurement of blood constituents, and particularly but not exclusively to the non-invasive measurement of blood glucose concentrations.
  • a blood sample is typically taken from a patient and transferred to a lab or handheld device, where it is analysed. This presents an obvious discomfort to patients, particularly young children, and the sample taken from the patient can become contaminated resulting in the need for additional blood samples to be taken.
  • TES Thermal Emission Spectroscopy
  • the standard deviation should be ⁇ 0.4mM or ⁇ 7.5mg/dl.
  • the standard deviation should be ⁇ 10%, e.g. for a physiological range of glucose of 3-30 mM and an average value between 10-15mM, the standard deviation should be ⁇ 1.0-1.5 mM. Malchoff et al found an averaged standard deviation of 1.5mM in the range 50-450mg/dl.
  • an analyte concentration e.g. glucose concentration
  • a system for non-invasive measurement of an analyte concentration in body tissue comprising means for detecting a thermal emission spectrum emitted by said body tissue, interference filtering means for spatially separating said thermal emission spectrum to create a plurality of spectral patterns and measuring in respect of each of a plurality of said spectral patterns a spectral intensity at a first, reference set of wavelengths, and a second set of wavelengths dependent on the analyte being measured, and determining therefrom the concentration of said analyte.
  • the present invention facilitates the measurement of the reference or analyte signal at more than one wavelength, preferably at a plurality of wavelengths, in various parts of the spectrum in a low cost manner.
  • This flexibility has two advantages. First, measuring the reference and glucose signals at a plurality of wavelengths and in other parts of the spectrum means that more information is obtained, resulting in a better accuracy of the glucose concentration.
  • measuring parts of the spectrum containing information of other analytes allows for the correction for the interference from other analytes, thereby further increasing the accuracy of the measurement. Accordingly, the extraction of information relating to other analytes enables the invention to be applied in the determination of other analyte concentrations, e.g. haemoglobin or cholesterol.
  • said system comprises a thermal emission spectroscopy system.
  • said interference filtering means comprises a spatial light modulator.
  • said interference filtering means comprises a multivariate optical element.
  • said multivariate optical element comprises a liquid crystal display.
  • said multivariate optical element comprises a digital mirror display.
  • said multivariate optical element comprises a liquid crystal on silicon display.
  • said thermal emission spectrum is detected using a photodetector.
  • said system utilises multivariate calibration methods such as partial least squares regression.
  • said analyte is glucose, haemoglobin, or oxygenated haemoglobin.
  • MHC metabolic heat conformation
  • [Glucose concentration] Function[Heat generated, Blood flow rate, Hb, HbOi] where Hb and HbO 2 represent the haemoglobin and oxygenated haemoglobin concentrations, respectively.
  • MHC means may be integrated or otherwise provided in the TES system defined above.
  • the factors influencing the glucose concentration measurements are different for each of the TES and MHC methods, because TES gives a direct glucose concentration measurement and MHC gives an indirect measurement. Accordingly, inaccuracies in the glucose measurement are recognised when there is a large discrepancy between the MHC and TES measurements
  • said thermal emission spectroscopy system incorporates a metabolic heat conformation method for independently determining blood glucose concentration.
  • said metabolic heat conformation method comprises self-mixing interferometry.
  • said glucose concentration measurement determined using thermal emission spectroscopy, and said glucose concentration measurement determined using the metabolic heat conformation method are compared to determine the accuracy in the glucose concentration measurement.
  • the heat generated from said body tissue is determined using the Planck energy distribution formula.
  • Figure 1 is a schematic representation of a thermal emission spectroscopy based glucose sensor in accordance with the first embodiment of the present invention
  • Figure 2 is a schematic representation of the thermal emission spectroscope and self- mixing interferometric unit, in accordance with the second embodiment of the present invention.
  • Figure 3 is a schematic representation of the self-mixing interferometric apparatus.
  • TES thermal emission spectroscopy
  • SLM spatial light modulator
  • LCOS liquid crystal on a silicon display
  • the blackbody radiation 13 i.e. thermal emission spectrum
  • the grating 12 splits the spatially mixed spectrum of wavelengths 13 and spatially re-arranges the spectrum in order of the wavelengths constituting the spectrum.
  • This "organised spectrum” 14 is then focussed onto the SLM 11 by a first lens system 15.
  • the various parts of the organised spectrum 14 can be analysed by assigning grey levels to specific pixels of the SLM 11. For example, making a collection of pixels black at a given location on the SLM 11, will prevent those wavelengths of the
  • “organised spectrum” 14 incident upon the blackened pixels, from passing through the SLM 11. Conversely, making a collection of pixels white will allow those wavelengths incident thereon to pass through the SLM 11.
  • the wavelengths passing through the SLM 11 are focussed onto a detector 16 using a second lens system 17. In this manner, parts of the spectrum 14 can be transmitted and others blocked.
  • glucose signature spectral bands and spectral bands for reference measurements can be measured sequentially.
  • the present embodiment is also amenable to multivariate calibration methods such as partial least squares regression. Such methods take into account the variation in the entire thermal emission spectrum 13 signal to allow the maximum amount of information to be extracted from the spectrum.
  • the multivariate calibration procedure produces a regression vector where r( ⁇ n ) is a weighting function as applied to wavelength X n of the thermal emission spectrum 13, for the analyte of interest, e.g. glucose.
  • X n the wavelength of the thermal emission spectrum 13
  • the analyte of interest e.g. glucose.
  • Wavelengths Xi to X n correspond to those wavelengths present in the emission spectrum.
  • Subsequently taking the inner product of the regression vector with the measured thermal emission spectrum s [s( ⁇ i),....,s( ⁇ n )] gives the concentration of the analyte of interest, in this case glucose.
  • the multivariate calibration method proceeds by displaying the weighting factors r( ⁇ i) to r( ⁇ n ) on the pixels of the SLM 11 and subsequently focussing those wavelengths transmitted through the SLM 11 onto the detector 16 using the second lens system 17.
  • other desired signal patterns can also be extracted by displaying other regression vectors on the SLM 11.
  • the SLM 11 acts as a so-called Multivariate Optical Element (MOE).
  • MOE Multivariate Optical Element
  • this embodiment contains no moving parts; selecting spectral regions or changing regression vectors is all done electronically.
  • the present invention has been exemplified by the non- invasive measurement of blood glucose concentration, the skilled addressee will also recognise its potential in measuring the concentration of other blood constituents, such as haemoglobin and oxygenated-haemoglobin.
  • a system for measuring the blood glucose levels in a tissue sample i.e. a finger 20.
  • the system incorporates a thermal emission spectroscopy based device 10, and a self-mixing interferometry unit 30 as applied to the Metabolic Heat Conformation (MHC) method.
  • the system may further comprise thermometers to measure for example the room and skin temperature.
  • the blood flow rate is determined using the self-mixing interferometry unit as identified in figure 2, and shown in detail in figure 3.
  • the unit comprises a laser cavity 31, a lens system 32 to focus the laser beam 33 onto the tissue sample, i.e. the finger tip surface 20, and a photodetector 34.
  • the laser beam 33 is focussed onto a focal plane which contains a surface 35 to which the finger 20 is applied. This ensures the surface of the finger 20 is suitably positioned at the focal plane of the lens system 32.
  • the beam emanating from the laser cavity 31 reflects off the surface of the finger 20 and is entrained back into the laser cavity 31 by the lens system 32.
  • the interference of the laser beam 33 with the reflected beam within the laser cavity 31, sets up power fluctuations in the laser output, which is measured using the photodetector 34.
  • the technique bears the name self-mixing interferometry due to the fact that the light reflected back into the laser cavity 31 interferes with the light resonating within the cavity.
  • the resulting signal from the photodetector 34 will be a constant in time (zero if DC filtered). If the finger 20 moves, or the amount of blood changes in the finger 20, then the amount of reflected light is changed and this will create fluctuations in the laser 31. The measured fluctuations will mirror these movements, and so the heartbeat will be an implicit part of the signal.
  • the signal on the photodetector 34 can also be understood on the basis of the speckle pattern when the blood flows. If no blood flows in the finger 20, then the speckle pattern will remain constant and the signal will be constant. When the blood flows, the speckle pattern will change in proportion to the blood flow velocity. The larger the velocity of the blood, the faster it changes the speckle pattern and the faster the signal on the photodetector 34 will oscillate (the oscillation period being typically between 0.1ms and 2ms). Thus, if the pattern is Fourier transformed, then as the signal oscillation rate increases, so will the number of high frequency components in the transform. By measuring the signal from the photodetector 34, the heartbeat and blood velocity can be measured simultaneously.
  • the direct optical determination of blood velocity provides a more accurate determination of the blood velocity than the known thermal diffusion method associated with the MHC method and also provides for a more rapid measurement.
  • the blood glucose concentration can be determined.
  • the TES device can be used to determine the blood glucose, Hb and HbO 2 concentrations as described in the first embodiment.
  • the TES measurement system can also be used to determine the heat generated in the skin, using the temperature dependence of the blackbody curve given by the Planck energy distribution formula:
  • TES gives a direct glucose measurement
  • MHC method gives an indirect measurement
  • the factors influencing the glucose measurements are different. Therefore the independent measurements can be compared to improve accuracy and combined to provide an average for the blood glucose concentration.

Abstract

L'invention concerne un système pour mesurer une concentration d'un analyte, de manière non invasive, dans un tissu corporel. Ce système comprend un moyen (16) pour détecter un spectre d'émission thermique (13) émis par le tissu corporel, par exemple un doigt, et un moyen de filtrage d'interférence (11) qui sert à séparer spatialement le spectre d'émission thermique afin de créer une pluralité de motifs spectraux, et à mesurer, par rapport à chacun de ces motifs spectraux, une intensité spectrale, pour un premier ensemble de longueurs d'ondes de référence, et pour un deuxième ensemble de longueurs d'onde, en fonction de l'analyte mesuré. La concentration de l'analyte est alors déterminée à partir des premières mesures spectrales.
EP06744989A 2005-05-24 2006-05-19 Mesure non invasive d'analytes sanguins par spectroscopie d'emission thermique Withdrawn EP1887923A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP06744989A EP1887923A1 (fr) 2005-05-24 2006-05-19 Mesure non invasive d'analytes sanguins par spectroscopie d'emission thermique

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP05300402 2005-05-24
EP06744989A EP1887923A1 (fr) 2005-05-24 2006-05-19 Mesure non invasive d'analytes sanguins par spectroscopie d'emission thermique
PCT/IB2006/051601 WO2006126154A1 (fr) 2005-05-24 2006-05-19 Mesure non invasive d'analytes sanguins par spectroscopie d'emission thermique

Publications (1)

Publication Number Publication Date
EP1887923A1 true EP1887923A1 (fr) 2008-02-20

Family

ID=36954139

Family Applications (1)

Application Number Title Priority Date Filing Date
EP06744989A Withdrawn EP1887923A1 (fr) 2005-05-24 2006-05-19 Mesure non invasive d'analytes sanguins par spectroscopie d'emission thermique

Country Status (4)

Country Link
EP (1) EP1887923A1 (fr)
JP (1) JP2008545515A (fr)
CN (1) CN101179983A (fr)
WO (1) WO2006126154A1 (fr)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100096551A1 (en) * 2006-12-28 2010-04-22 Koninklijke Philips Electronics N.V. Spectroscopy measurements
US8140272B2 (en) 2008-03-27 2012-03-20 Nellcor Puritan Bennett Llc System and method for unmixing spectroscopic observations with nonnegative matrix factorization
WO2018089383A1 (fr) * 2016-11-08 2018-05-17 University Of Southern California Système imageur hyperspectral
KR102505234B1 (ko) 2018-04-12 2023-03-03 삼성전자주식회사 공간 광 변조기를 이용한 생체 정보 검출을 위한 방법, 전자 장치 및 저장 매체

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2084923A1 (fr) * 1991-12-20 1993-06-21 Ronald E. Stafford Spectrometre a modulateur de lumiere spatial
US5435309A (en) * 1993-08-10 1995-07-25 Thomas; Edward V. Systematic wavelength selection for improved multivariate spectral analysis
US6025597A (en) * 1995-10-17 2000-02-15 Optiscan Biomedical Corporation Non-invasive infrared absorption spectrometer for measuring glucose or other constituents in a human or other body
US5666956A (en) * 1996-05-20 1997-09-16 Buchert; Janusz Michal Instrument and method for non-invasive monitoring of human tissue analyte by measuring the body's infrared radiation

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2006126154A1 *

Also Published As

Publication number Publication date
JP2008545515A (ja) 2008-12-18
WO2006126154A1 (fr) 2006-11-30
CN101179983A (zh) 2008-05-14

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