Non-invasive measurement device

Abstract

This non-invasive measurement device comprises: a light source unit that emits excitation light; a probe (11) having an irradiation unit (111) that irradiates the inside of a living subject with the excitation light from a predetermined site of the living subject; a detection unit (13) that detects transmitted light that has passed through the inside of the living subject from the predetermined site; and a reflective wall (121) disposed in close contact with an area around the predetermined site from which the light passes through the inside of the living subject, and between the irradiation unit (111) and the detection unit (13) to cover the area, the reflective wall (121) having a reflective surface that reflects light emitted out of the living subject toward the living subject.

Description

Non-invasive measurement devices

[0001] The present invention relates to a non-invasive measurement device.

[0002] In contrast to invasive methods that require blood sampling to measure blood glucose levels, there are non-invasive methods that use infrared light and do not require blood sampling. 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 the light generated by the Raman scattering process, and the glucose concentration is estimated based on the intensity of that light.

[0003] A non-invasive measurement method that is not affected by the light penetration characteristics or structural complexity of skin and body tissues involves irradiating a wide area of ​​the inside of the skin with near-infrared light via a ball lens and acquiring signals with high sensitivity. However, because this method does not uniformly illuminate the entire area of ​​body tissue, there is an issue that the characteristics of the acquired signal change depending on the location of the target sample, the localization of components, movement, and the pressure of the probe.

[0004] For example, the blood measurement device used in the invention disclosed in Patent Document 1 irradiates a living body with laser light and guides Raman scattered light from the living body to a spectroscope. The spectrum of the Raman scattered light is detected by a detector using light of each wavelength dispersed by the spectroscope, and the detected multiple spectra are integrated to calculate the blood glucose concentration in the blood from the integrated spectrum.

[0005] JP 2017-83433 A

[0006] However, a signal processing method that integrates only signal components with common characteristics leads to a decrease in signal utilization efficiency in the process of extracting only the common signal components, and significantly extends the time required for measurement.

[0007] The present invention has been made in consideration of the above, and aims to reduce measurement time, acquire stable signals that are not affected by the complexity of skin or body tissue without reducing signal utilization, and improve the speed and accuracy of optical measurement.

[0008] The non-invasive measurement device according to the present invention comprises: a light source unit that emits excitation light; a probe having an irradiation unit that irradiates the excitation light into the living body from a predetermined site of the living body; a detection unit that detects transmitted light that passes through the living body from the predetermined site; and a reflective wall between the irradiation unit and the detection unit that tightly covers the periphery of the predetermined site that passes through the living body and has a reflective surface that reflects light emitted outside the living body toward the inside of the living body.

[0009] According to the present invention, a reflective wall is provided between the irradiation unit and the detection unit, tightly covering the periphery of a predetermined portion that passes through the living body and having a reflective surface that reflects light emitted outside the living body back into the living body. This reduces measurement time, and enables stable acquisition of signals that are not affected by the complexity of skin or body tissue without reducing signal utilization, thereby increasing the speed and accuracy of optical measurement.

[0010] While the present invention has been described with reference to exemplary embodiments, it is to be understood that the invention is not limited to the disclosed exemplary embodiments.

[0011] The non-invasive measuring device according to the embodiment of the present invention is a device that detects transmitted Raman scattered light in accordance with the structure of the tissue of a subject and evaluates components in blood.

[0012] FIG. 1 is a diagram showing the configuration of a noninvasive measurement device 1. The noninvasive measurement device 1 analyzes the concentration of substances contained in skin tissue based on Raman scattered light generated in the skin tissue by irradiation with excitation light. In this embodiment, the device particularly detects glycated proteins such as glycated hemoglobin (HbA1c) and glycated albumin (GA) from within blood vessels. The noninvasive measurement device 1 includes a light source unit 10, a probe 11, a finger insertion unit 12, a detection unit 13, and an analyzer 14. This device is capable of acquiring signals from body tissue with high efficiency and stably acquiring signals deep within body tissue by utilizing the characteristics of multiple reflections of light.

[0013] The light source unit 10 is a light source that emits excitation light. Because Raman scattering light generated in skin tissue in vivo by irradiation with excitation light tends to be weak, the light source unit 10 is preferably a light source that emits high-intensity excitation light. Furthermore, glycated hemoglobin (HbA1c) and glycated albumin (GA) are polymers, and due to their molecular size, they cannot pass through blood vessel walls and flow into interstitial fluid. Therefore, signals from blood present deep in the skin must be acquired with high sensitivity. To achieve high penetration deep into the skin, wavelengths of 830, 860, and 1064 nm are used, with 1064 nm being the optimal excitation wavelength, as it is not affected by background light due to autofluorescence. Examples of such light sources include semiconductor lasers and solid-state lasers. The light source unit 10 may also be an LED (light-emitting diode).

[0014] The probe 11 is a spectroscopic probe used in a spectroscopic analysis instrument, and is a fiber probe using multiple optical fibers. Light emitted from the light source unit 10 is guided into the probe 11. A cylindrical finger insertion unit 12 is provided at the tip of the probe 11. The finger insertion unit 12 is designed so that a finger 15 of a subject's hand is inserted into the hollow portion of the cylinder. An opening is also provided on the side of the cylinder so that the tip of the probe 11 is exposed to the hollow portion. When the subject inserts a finger into the finger insertion unit 12, light emitted from the light source unit 10 is irradiated toward the finger 15 from the irradiation unit 111 of the probe 11, which is exposed to the hollow portion through the opening.

[0015] The finger insertion section 12 is covered with a wall having an opening in the insertion direction of the finger 15, and when the finger 15 is inserted, the inner wall surface is in close contact with the finger 15. An opening is provided in the wall opposite the opening through which the tip of the probe 11 is exposed, so that the detection section 13, which detects transmitted light that is irradiated from the irradiation section 111 of the probe 11 and transmitted through the skin tissue of the finger 15, is exposed. Therefore, the finger insertion section 12 serves to fix the finger 15 so that the position at which the light from the irradiation section 111 of the probe 11 is irradiated onto the finger 15 does not move. In addition, the wall surface constituting the finger insertion section 12 serves as a reflective wall that reflects light that is reflected and scattered within the skin tissue and attempts to exit to the outside, and guides it to the detection section 13, as will be described later.

[0016] The detection unit 13 includes a spectroscopic element and a photodetector (not shown) that separate the incident light into wavelengths. The spectroscopic element separates the Raman scattered light irradiated from the irradiation unit 111 of the probe 11 and transmitted through the skin tissue of the finger into wavelengths, and guides the light to the light-receiving surface of the photodetector. Methods for separating light into wavelengths include, for example, a dispersive spectrometer that utilizes the diffraction of light and a Fourier transform spectrometer that utilizes the coherence of light. A dispersive spectrometer is composed of a collimating mirror, a focusing mirror, and a diffraction grating, and disperses light by utilizing the diffraction and interference caused by the diffraction grating. A Fourier transform spectrometer uses an interferometer to measure the interference waveform of light. The measured interference waveform is Fourier transformed to measure the light spectrum for each wavelength. A Michelson interferometer, composed of a reference mirror, a sample mirror, and an optical branching filter, is used as the interferometer.

[0017] The photodetector has a plurality of light-receiving elements on its light-receiving surface. Raman scattered light is incident on the light-receiving surface of the photodetector. When the photodetector receives the Raman scattered light from the spectroscopic element, the light-receiving elements convert the light of each wavelength into an electrical signal and output a light detection signal indicating the intensity distribution for each wavelength. For example, a photodiode, a CCD (Charge Coupled Device), a CMOS (Complementary Metal Oxide Semiconductor), or the like is used as the photodetector. The spectroscopic signal output from the photodetector is input to the analyzing device 14.

[0018] The analyzer 14 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, an auxiliary memory for storing data for a long period of time, etc. The analyzer calculates the concentrations of HbA1c and GA contained in the skin tissue based on the spectroscopic signals input from the photodetector of the detection unit 13.

[0019] FIG. 2 is a diagram showing the details of the tip portion of the probe 11, as viewed from the direction in which the finger 15 is inserted.

[0020] A light source unit 10 such as a laser is connected to the probe 11, and excitation light from the light source unit 10 is transmitted. A band-pass filter 20 is coupled to an irradiation unit 111 at the tip of the probe 11. This band-pass filter 20 is a filter that selectively transmits light of a specific wavelength. The excitation light output from the probe 11 is band-passed by the band-pass filter 20 and passes through the skin tissue of the finger 15. The band-pass filter 20 also does not transmit light in the opposite direction to the light output from the probe 11, i.e., light reflected from the surface of the finger 15 or skin tissue, but reflects it toward the skin tissue. In other words, light reflected from the skin tissue is returned to the skin tissue. Therefore, the light irradiated toward the skin tissue efficiently passes through the skin tissue, and Raman scattered light from the skin tissue can be efficiently detected.

[0021] The finger insertion section 12 has a reflective wall 121 formed by a wall surface covering the hollow section. The reflective wall 121 is arranged to surround the irradiation section 111 at the tip of the probe 11 and the detection section 13. The inner wall surface, which serves as a reflective surface, is curved and has an arc shape when viewed from the insertion direction of the finger 15. The inner wall surface is made of gold, a highly reflective material, and is mirror-finished. Note that any highly reflective material, such as silver or aluminum, may be used instead of gold. When light irradiated from the probe 11 is reflected and scattered within the skin tissue and travels in a different direction rather than toward the detection section 13, the light is reflected several times by the inner wall surface and collected at the detection section 13. In other words, the reflective wall 121 constituting the finger insertion section 12 serves to guide Raman scattered light within the skin tissue of the finger 15 to the detection section 13.

[0022] The inner wall surface is not limited to a mirror finish, and may be formed as a rough surface having irregularities, for example. By forming the inner wall surface as a rough surface, light that has come toward the inner wall surface is diffused, and the light that passes through the skin tissue of the finger 15 is made uniform, so that the Raman scattered light can be guided to the detection unit 13. Furthermore, the irregularities may be provided with an inclined surface in the direction toward the detection unit 13. This makes it possible to reduce the amount of transmitted light that escapes to the outside from the opening of the finger insertion unit 12, which does not have a reflective wall 121 and through which the finger 15 is inserted.

[0023] Furthermore, the inner wall surface is formed in a cylindrical shape in the insertion direction of the finger 15, but instead, it may be formed in a curved shape that is close to a sphere. By making the surfaces parallel to the insertion direction of the finger 15 as well as the other directions curved, it is possible to prevent the transmitted light from escaping to the outside and to guide the Raman scattered light to the detection unit 13. However, the curved surfaces other than the surfaces parallel to the insertion direction of the finger 15 are formed to an extent that does not hinder the insertion of the finger 15 and does not hinder the finger 15 from coming into close contact with the inner wall surface.

[0024] The condenser lens 21 is provided in an opening of the reflecting wall 121 that constitutes the finger insertion section 12. Light that has passed through the finger 15 is collected by the condenser lens 21 and guided to a spectroscope in the detection section 13. The condenser lens 21 has a high numerical aperture so that it can collect a large amount of light.

[0025] The operation of detecting Raman scattered light from skin tissue using the above configuration will now be described. The subject inserts the finger 15 into the finger insertion section 12, moves the finger 15 to a position where it is in close contact with the reflecting wall 121, and then fixes it in place. The excitation light output from the light source section 10 via the probe 11 and bandpass filter 20 is incident on the skin tissue of the finger 15 inserted into the finger insertion section 12. As the incident excitation light passes through the skin tissue, it interacts with components contained in the blood in the dermis layer, for example, to generate Raman scattered light with a wavelength different from that of the excitation light and Rayleigh scattered light with the same wavelength as the wavelength of the excitation light.

[0026] Skin tissue has an epidermal layer on the surface, and a dermal layer below the epidermal layer. The epidermal layer is approximately 0.1 to 0.3 mm thick and does not contain nerves or blood vessels. The dermal layer is approximately 1 to 2 mm thick and is home to capillaries, nerves, and lymphatic vessels. The dermal layer contains interstitial fluid, a bodily fluid between cells. Glucose in the blood diffuses into the interstitial fluid through the capillary walls and is transported from the interstitial fluid to tissue cells. HbA1c and GA are present in the blood. HbA1c is a type of glycated protein in which blood sugar binds to hemoglobin, a protein found in red blood cells. GA is a type of glycated protein in which blood sugar binds to albumin, a protein found in serum. However, because HbA1c and GA are high molecular weight molecules, they do not pass through blood vessel walls and remain in the blood. The higher the blood glucose level, the greater the amount of glucose bound to hemoglobin and albumin; therefore, these are used as diagnostic markers to indicate hyperglycemic conditions. Therefore, blood glucose levels can be determined by measuring HbA1c and GA contained in blood fluid. To achieve this, it is necessary to ensure that the irradiated light reaches as far as possible into the blood vessel walls deep within the skin, and to obtain as much scattered light as possible from the blood present within the blood vessel walls deep within the skin.

[0027] The scattered light travels through the skin tissue while diffusing, reaching deeper positions in the skin tissue, and then travels further inside, passing through the skin tissue and being emitted to the outside. The scattered light that passes through the finger and is emitted is collected by the condenser lens 21 and guided to the detection unit 13. However, because the scattered light travels through the skin tissue while diffusing, not all of the light necessarily travels toward the detection unit 13. In addition, some light is reflected by the skin surface before entering the skin tissue. This includes scattered light traveling from the skin tissue toward the probe 11 and reflected light reflected by the skin surface and returning to the probe 11. As described above, the irradiation unit 111 at the tip of the probe 11 is provided with a band-pass filter 20, which reflects light returning toward the irradiation unit 111 of the probe 11 without allowing it to enter the probe 11. The reflected light again enters the skin tissue and passes through the skin tissue, generating Raman scattered light, which then travels through the skin tissue while diffusing.

[0028] In addition to light traveling toward the irradiation unit 111 of the probe 11, some of the scattered light traveling within the skin tissue also exits the skin tissue from a direction different from the direction of the detection unit 13. If this light leaks to the outside and is not detected by the detection unit 13, the light collection efficiency decreases, making it impossible to acquire signals from blood deep within the skin tissue with high sensitivity. The finger 15 is surrounded by a reflective wall 121, which prevents scattered light from leaking to the outside. The reflective wall 121 is in close contact with the finger 15 and is formed in an arc shape when viewed from the insertion direction of the finger 15. Scattered light traveling from within the skin tissue toward the outside of the skin tissue collides with the reflective surface of the reflective wall 121. The colliding light is reflected by the reflective surface and returned to the skin tissue. The light returned to the skin tissue travels again while diffusing within the skin tissue, and again collides with the reflective wall 121 and is reflected. The scattered light travels deep into the skin tissue while being reflected several times by the reflecting wall 121 and is collected by the detecting unit 13. In this way, the scattered light is reflected by the reflecting wall 121, preventing light loss due to external emission. Furthermore, by repeatedly undergoing diffuse reflection by the reflecting wall 121, the light from the probe 11 is spatially integrated and diffused uniformly within the skin tissue of the finger 15, irradiating the entire skin tissue widely, and finally being collected by the detecting unit.

[0029] Of the scattered light incident on the detection unit 13 via the condenser lens 21, Rayleigh scattered light is removed by an edge filter provided in the detection unit 13, and only Raman scattered light is input to a spectroscope in the detection unit 13. The spectroscope separates the supplied Raman scattered light by wavelength, guides it to the light-receiving surface of a photodetector in the detection unit 13, and outputs a photodetection signal indicating the intensity distribution for each wavelength. The signal output from the photodetector is input to the analysis device 14.

[0030] When the analyzer 14 receives the spectrum from the photodetector, it performs a determination process to determine whether the spectrum is a waveform specific to HbA1c or GA based on the waveform pattern in the spectrum. If the determination process determines that the waveform is HbA1c or GA, it acquires the peaks of HbA1c or GA. The concentrations of HbA1c or GA are measured based on the peaks of HbA1c or GA in the acquired Raman spectrum.

[0031] In this embodiment, the measurement site has been described using the skin tissue of the finger 15 as an example, but there is no particular limitation as long as the measurement site can be covered by the reflective wall 121, and it may be, for example, the lips or earlobes.

[0032] In the present embodiment, the spectrum of light transmitted through finger 15 is detected using a spectroscope, and the blood glucose level is measured from the peak value of the detected spectrum. However, this is not limiting, and for example, the transmitted light may be detected by a photodetector to determine the absorbance at a specific wavelength, and the blood glucose level may be measured from the determined value. In this case, detection unit 13 does not require a spectroscope.

[0033] Furthermore, in this embodiment, a method for measuring HbA1c and GA in blood has been described as an example, but the present invention is not limited to this and may also be used as a method for measuring the amount of other biological substances in biological tissue.

[0034] It should be noted that the present invention is susceptible to various embodiments and modifications without departing from the broad spirit and scope of the present invention. Furthermore, the above-described embodiment is intended to illustrate one example of the present invention and does not limit the scope of the present invention. The above-described embodiments and modifications can be combined in any manner. Furthermore, even if some of the constituent elements of the embodiment are omitted as necessary, they will still fall within the scope of the technical idea of ​​the present invention.

[0035] In addition, this application claims priority based on Japanese Patent Application No. 2023-25899 filed on February 22, 2023, and the specification, claims, and drawings of Japanese Patent Application No. 2023-25899 are incorporated herein by reference.

[0036] The present invention can be widely applied to non-invasive measurement devices that irradiate a living body with excitation light and detect the transmitted light that passes through the living body.

[0037] 1 Non-invasive measurement device, 10 Light source unit, 11 Probe, 12 Finger insertion unit, 13 Detection unit, 14 Analysis device, 15 Finger, 20 Band-pass filter, 21 Condenser lens, 111 Irradiation unit, 121 Reflection wall

Claims

1. a light source unit that emits excitation light; a probe having an irradiation unit that irradiates the excitation light into the living body from a predetermined site of the living body; a detection unit that detects transmitted light that passes through the living body from the predetermined site; a reflecting wall between the irradiation unit and the detection unit, which tightly covers the periphery of the predetermined portion that passes through the living body and has a reflecting surface that reflects the light emitted outside the living body toward the inside of the living body; A non-invasive measurement device comprising:

2. The reflecting surface is formed in a curved shape. The non-invasive measurement device according to claim 1 .

3. The predetermined portion is a finger, and the reflective wall constitutes a finger insertion portion into which the finger is inserted. The non-invasive measurement device according to claim 1 .

4. The reflecting surface is formed in an arc shape with respect to the direction in which the finger is inserted. The non-invasive measurement device according to claim 1 .

5. a band-pass filter provided in the irradiation unit of the probe, which selectively transmits light of a specific wavelength among the light irradiated from the probe and reflects light emitted outside the living body; The non-invasive measurement device according to any one of claims 1 to 4.