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WO2025150099A1 - Dispositif de mesure non invasif - Google Patents

Dispositif de mesure non invasif

Info

Publication number
WO2025150099A1
WO2025150099A1 PCT/JP2024/000206 JP2024000206W WO2025150099A1 WO 2025150099 A1 WO2025150099 A1 WO 2025150099A1 JP 2024000206 W JP2024000206 W JP 2024000206W WO 2025150099 A1 WO2025150099 A1 WO 2025150099A1
Authority
WO
WIPO (PCT)
Prior art keywords
light
ring
skin tissue
optical system
excitation light
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.)
Pending
Application number
PCT/JP2024/000206
Other languages
English (en)
Japanese (ja)
Inventor
若峰 郭
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.)
Healthcare Vision Co Ltd
Original Assignee
Healthcare Vision Co 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
Application filed by Healthcare Vision Co Ltd filed Critical Healthcare Vision Co Ltd
Priority to PCT/JP2024/000206 priority Critical patent/WO2025150099A1/fr
Publication of WO2025150099A1 publication Critical patent/WO2025150099A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements
    • 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

Definitions

  • the present invention relates to a non-invasive measurement device.
  • Raman spectroscopy blood glucose measurement is a non-invasive method that uses light to selectively detect the specific chemical structure of glucose.
  • the measurement principle is to detect light generated by the Raman scattering process, and the glucose concentration is estimated by the intensity of the light.
  • the intensity obtained is very weak, which is a major factor that prevents glucose measurement in interstitial fluid deep in the skin.
  • a method for extracting signals from deep areas a method has been considered that uses Raman scattering with an excitation light source in the wavelength range of 700 nm to 1200 nm, known as a biological window.
  • SORS spatially offset Raman spectroscopy
  • the non-invasive measurement device comprises: A light source unit that emits excitation light; an irradiation optical system that irradiates the skin tissue with the excitation light; a detection optical system for collecting Raman scattered light from the skin tissue; a spectrometer for dispersing the Raman scattered light; an analyzer that measures a blood glucose level by analyzing a spectroscopic signal obtained by the spectrometer; Equipped with the irradiation optical system forms a cross-sectional shape of the excitation light into a ring shape and irradiates the excitation light onto the skin tissue;
  • the detection optical system is disposed at a position for detecting return light from the skin tissue at the center of the ring-shaped beam spot irradiated onto the skin tissue.
  • FIG. 1 is a diagram illustrating a configuration of a non-invasive blood glucose measuring device according to an embodiment of the present invention.
  • 1 is a diagram showing a trajectory of return light on a cross section of a sample when excitation light is incident thereon from a non-invasive blood glucose measuring device according to an embodiment of the present invention.
  • FIG. FIG. 2 is a diagram showing return light on a sample surface when excitation light is incident thereon from a non-invasive blood glucose measuring device according to an embodiment of the present invention.
  • 13A and 13B are diagrams showing the intensity distribution of light detected when the ring width of the annular beam profile is changed.
  • 13A and 13B are diagrams showing the intensity distribution of light detected when the ring width of the annular beam profile is changed.
  • FIG. 13A and 13B are diagrams showing the intensity distribution of light detected when the ring width of the annular beam profile is changed.
  • 13A and 13B are diagrams showing the intensity distribution of light detected when the inner radius of the ring of the annular beam profile is changed.
  • FIG. 13 is a diagram showing another example of the detection optical system of the non-invasive blood glucose measuring device.
  • the collimating lens 110 prevents the light emitted from the light source unit 10 from spreading, and shapes it into parallel light with a specified beam diameter.
  • Bandpass filter 113 is a filter that selectively transmits light of a specific wavelength.
  • a specific example of bandpass filter 113 is a laser line filter.
  • a laser line filter is a narrow bandpass filter with the laser wavelength as its center wavelength, and is used to cut the base of the wavelength band of the laser light to sharpen the spectrum of the laser light and reduce background light.
  • the dichroic mirror 12 reflects the excitation light and guides it to the sample 2, while transmitting the Raman scattered light, which has a different wavelength from the excitation light, and directing it to the detection optical system 13.
  • the detection optical system 13 is an optical system for collecting Raman scattered light generated by irradiation of the sample 2 with excitation light through the irradiation optical system 11, removing the excitation light, and focusing the light on the spectrometer 14.
  • the detection optical system 13 is disposed at a position on the surface of the sample 2 a predetermined distance away from the position where the excitation light is irradiated from the irradiation optical system 11 to the sample 2, so as to detect Raman scattered light from the dermis layer in the skin tissue of the sample 2.
  • the detection optical system 13 includes an objective lens 130, an edge filter 131, and a focusing lens 132.
  • the objective lens 130 simultaneously collects the excitation light and Rayleigh scattered light in addition to the Raman scattered light among the return light from the sample 2. Therefore, an edge filter 131 is provided at the next stage.
  • the edge filter 131 is a long-pass edge filter that removes the excitation light and Rayleigh scattered light so that they are not transmitted to the spectrometer 14.
  • the analytical device 15 is a computer such as a personal computer, and includes a processor that processes data according to a control program, a main memory that functions as a work area for the processor, and an auxiliary memory for storing data for a long period of time.
  • the analytical device 15 calculates the concentration of glucose contained in the sample 2 based on the spectroscopic signal input from the photodetector 140 of the spectrometer 14.
  • the excitation light 31 incident on the sample 2 from the light source unit 10 of the non-invasive blood glucose measuring device 1 through the irradiation optical system 11 is incident from a direction perpendicular to the surface of the sample 2.
  • the excitation light 31 is a ring-shaped cross-sectional shape formed by the ring-shaped forming unit 112. Therefore, since a ring-shaped beam spot is formed on the surface of the sample 2, in FIG. 2B, the incidence position 33 of the excitation light 31 is ring-shaped, and the incidence position 33 in the y-axis direction shown in FIG. 2A is two points.
  • the scattered light travels through the skin tissue while diffusing, and returns to the skin surface.
  • the arrows indicate the path from the incident position 33 of the excitation light 31 to the point where the scattered light scattered inside the skin tissue is emitted to the skin surface as return light.
  • the scattered light scattered inside the skin tissue travels a longer distance inside the skin tissue according to the depth of the skin tissue it passes through, and the position where it is emitted from the skin surface as return light 32 moves away from the incident position 33 of the excitation light.
  • FIG. 2A the arrows indicate the path from the incident position 33 of the excitation light 31 to the point where the scattered light scattered inside the skin tissue is emitted to the skin surface as return light.
  • the light scattered inside the skin tissue returns to a position on the circumference of the skin surface that is a predetermined radius away from the incident position 33 of the excitation light 31 on the skin surface, which is the skin surface, centered on the incident position 33 of the excitation light 31 on the skin surface. Therefore, if the layer of skin tissue through which the scattered light passes is shallow, the position where the return light 32 is emitted from the skin surface is not so far from the incident position 33. On the other hand, when the layer of skin tissue through which the scattered light passes is deep, the position where the return light 32 is emitted from the skin surface is farther away from the incident position 33 than when the layer of skin tissue through which the scattered light passes is shallow.
  • the scattered light has unique characteristics depending on the substance contained in the layer through which it passes.
  • the detection position of the return light 32 it is possible to obtain Raman scattered light according to the substance of the layer to be detected.
  • the scattered light generated by interaction with the components contained in the interstitial fluid of the dermis layer 21 is indicated by solid arrows.
  • the scattered light generated by interaction with the components contained in the interstitial fluid is emitted at a position a distance d away from the incident position 33 of the excitation light 31 in the x-y plane.
  • the detection position 34 by the detection optical system 13 is set to match the emission position of the return light 32 indicated by the solid arrow, and the detection optical system 13 collects the return light 32 as collected light 35.
  • the detection optical system 13 does not collect the autofluorescence from the melanin layer 22, and the autofluorescence is removed from the collected light 35.
  • the edge filter 131 removes the excitation light and Rayleigh scattered light from the collected light 35, and only the Raman scattered light is input to the spectrometer 14.
  • the spectrometer 14 separates the supplied Raman scattered light by wavelength, guides it to the light receiving surface of the photodetector 140, and outputs a light detection signal that indicates the intensity distribution for each wavelength.
  • the signal output from the photodetector 140 is input to the analysis device 15.
  • Figure 3 shows the light intensity distribution detected by photodetector 140 for light rays returning after passing through the epidermis and dermis layers of skin tissue when the inner diameter of the annular beam profile is kept constant and the ring width is narrowed. Shown here is the intensity distribution of detected light when the ring width is set to 0.45 mm and when it is set to an even narrower ring width of 0.335 mm. Comparing the two, the detected light intensity 41 from the epidermis layer does not change much even when the ring width is narrowed, whereas the detected light intensity 42 from the dermis layer increases as the ring width is narrowed.
  • Figure 5 shows the light intensity distribution when the ring width is narrower than that of Figure 3.
  • the detected light intensity distribution is shown when the ring width is set to 0.26 mm and 0.12 mm, which are narrower than 0.335 mm.
  • the detected light intensity 42 from the dermis layer is increased compared to when the ring width is 0.335 mm.
  • the detected light intensity 42 from the dermis layer is increased when the ring width is 0.12 mm compared to when the ring width is 0.26 mm. From this, it can be seen that the narrower the ring width, the more scattered light from the dermis layer can be obtained.
  • the objective lens 130 may collect light that is reflected by the surface of the skin tissue, such as excitation light or other external light. Therefore, in order to prevent the entry of diffusely reflected light rays into the objective lens 130, a diffuse reflection prevention wall may be provided in the detection optical system 13.
  • Figure 7 shows a configuration in which the objective lens 130 is provided with a diffuse reflection intrusion prevention wall 133.
  • the objective lens 130 is provided between the dichroic mirror 12 and the sample 2, which is skin tissue, and the diffuse reflection intrusion prevention wall 133 is provided between the objective lens 130 and the sample 2.
  • the diffuse reflection intrusion prevention wall 133 has a conical shape with an inner wall surface formed into a mortar shape.
  • An opening 1330 is provided in the portion of the diffuse reflection intrusion prevention wall 133 facing the objective lens 130, and the objective surface of the objective lens 130 is covered by the inner wall of the diffuse reflection intrusion prevention wall 133 through the opening 1330.
  • the present invention can be widely applied to non-invasive blood glucose measuring devices that use spatially offset Raman spectroscopy to obtain Raman signals from interstitial fluid that has the same glucose concentration as that in blood.
  • Non-invasive blood glucose measuring device 2 Sample (skin tissue), 10 Light source unit, 11 Irradiation optical system, 12 Dichroic mirror, 13 Detection optical system, 14 Spectrometer, 15 Analysis device, 20 Epidermis layer, 21 Dermis layer, 22 Melanin layer, 31 Excitation light, 32 Return light, 33 Incident position, 34 Detection position, 35 Collected light, 41 Detected light intensity from epidermis layer, 42 Detected light intensity from dermis layer, 110 Collimator lens, 111 Beam expander, 112 Ring forming unit, 113 Band pass filter, 114 Projection lens, 130 Objective lens, 131 Edge filter, 132 Condenser lens, 133 Diffuse reflection prevention wall, 140 Photodetector, 1330, 1331 Aperture.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Biomedical Technology (AREA)
  • Medical Informatics (AREA)
  • Veterinary Medicine (AREA)
  • Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Heart & Thoracic Surgery (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • Optics & Photonics (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Biophysics (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)

Abstract

Un dispositif de mesure non invasif selon la présente invention comprend : une unité de source de lumière (10) qui émet une lumière d'excitation ; un système optique d'irradiation (11) qui irradie le tissu cutané (2) avec la lumière d'excitation ; un système optique de détection (13) qui collecte la lumière diffusée par effet Raman à partir du tissu cutané (2) ; un spectroscope (14) qui disperse la lumière diffusée par effet Raman ; et un dispositif d'analyse (15) qui analyse un signal spectral obtenu suite à la dispersion par le spectroscope (14) et mesure un taux de glycémie. Le système optique d'irradiation (11) met en forme la section transversale de la lumière d'excitation en un anneau et irradie le tissu cutané (2) avec la lumière d'excitation, et le système optique de détection (13) est positionné de façon à détecter la lumière renvoyée par une partie du tissu cutané (2) qui est la partie centrale d'un point de faisceau en forme d'anneau irradié sur le tissu cutané (2).
PCT/JP2024/000206 2024-01-09 2024-01-09 Dispositif de mesure non invasif Pending WO2025150099A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/JP2024/000206 WO2025150099A1 (fr) 2024-01-09 2024-01-09 Dispositif de mesure non invasif

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/JP2024/000206 WO2025150099A1 (fr) 2024-01-09 2024-01-09 Dispositif de mesure non invasif

Publications (1)

Publication Number Publication Date
WO2025150099A1 true WO2025150099A1 (fr) 2025-07-17

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2024/000206 Pending WO2025150099A1 (fr) 2024-01-09 2024-01-09 Dispositif de mesure non invasif

Country Status (1)

Country Link
WO (1) WO2025150099A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008522697A (ja) * 2004-12-09 2008-07-03 ザ サイエンス アンド テクノロジー ファシリティーズ カウンシル 表面下組織および流体のラマン分光解析
CN102928394A (zh) * 2012-10-16 2013-02-13 江苏学府医疗科技有限公司 一种便携式拉曼光谱无创伤血糖仪
US20130090537A1 (en) * 2011-10-07 2013-04-11 2M Engineering Limited Blood glucose sensor
US20210181019A1 (en) * 2019-12-13 2021-06-17 Samsung Electronics Co., Ltd. Compact raman sensor and apparatus for estimating bio-component
JP2023550206A (ja) * 2020-10-23 2023-11-30 アールエスピー システムズ エー／エス 被分析物の存在または濃度の非侵襲的インビボ（生体内）測定のためのラマンプローブおよび装置および方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008522697A (ja) * 2004-12-09 2008-07-03 ザ サイエンス アンド テクノロジー ファシリティーズ カウンシル 表面下組織および流体のラマン分光解析
US20130090537A1 (en) * 2011-10-07 2013-04-11 2M Engineering Limited Blood glucose sensor
CN102928394A (zh) * 2012-10-16 2013-02-13 江苏学府医疗科技有限公司 一种便携式拉曼光谱无创伤血糖仪
US20210181019A1 (en) * 2019-12-13 2021-06-17 Samsung Electronics Co., Ltd. Compact raman sensor and apparatus for estimating bio-component
JP2023550206A (ja) * 2020-10-23 2023-11-30 アールエスピー システムズ エー／エス 被分析物の存在または濃度の非侵襲的インビボ（生体内）測定のためのラマンプローブおよび装置および方法

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