Non-invasive measurement device

Abstract

This non-invasive measurement apparatus comprises: a light source unit; a probe (11) that emits excitation light to a skin tissue (2) and collects Raman scattered light; a spectrometer; and an analysis device. The probe (11) includes: a transmission optical fiber (111) that transmits the excitation light coming from the light source unit; a detection optical fiber (112) that is provided around the transmission optical fiber (111) and collects Raman scattered light; and a ball lens (110) that is provided at a tip end portion, and that comes into contact with the skin tissue (2) to emit the excitation light to a dermis layer (21) and collect Raman scattered light coming from the dermis layer (21). The detection optical fiber (112) is provided at a position where Raman scattered light can be collected by the ball lens (110) and autofluorescence coming from a melanin layer (22) cannot be collected.

Description

Technical Field

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

Background Art

[0002] As a method for measuring blood glucose levels, there is a non-invasive measurement method using infrared light that does not require blood collection, in contrast to invasive measurement methods that require blood collection. Raman spectroscopic blood glucose measurement is a non-invasive measurement method that uses light to selectively detect the specific chemical structure of glucose. Its measurement principle is based on detecting light generated by the Raman scattering process, and estimates glucose concentration based on the intensity of the light. However, the obtained intensity is extremely weak, which has been a major factor hindering the measurement of glucose in interstitial fluid deep in the skin. As a method for extracting deep-layer signals, excitation light sources in the wavelength range of 700 nm to 1200 nm, called the biological window, have been used. In particular, 800 nm to 1000 nm is a band with a deep light penetration depth, and methods have been adopted that use 785 nm, 830 nm, or 860 nm as the excitation light source to capture glucose signals generated in the 900 nm to 1000 nm band.

[0003] For example, the blood measurement device used in the invention disclosed in Patent Document 1 irradiates a living body with laser light of 785 nm, and guides Raman scattered light from the living body to a spectrometer. A detector detects the spectrum of the Raman scattered light using light of each wavelength separated by the spectrometer, the plurality of detected spectra are integrated, and the blood glucose concentration in blood is calculated from the integrated spectrum.

Prior Art Literature

Patent Literature

[0004]

Patent Document 1

Summary of the Invention

Problem to be Solved by the Invention

[0005] However, not only is the signal weak, but autofluorescence emitted from the skin, particularly the melanin layer in the space between the epidermis and dermis, significantly distorts the waveform of the obtained Raman signal, hindering the quantitative evaluation of glucose concentration. While signal processing methods and fluorescence signal cancellation techniques have been proposed to reduce the effects of autofluorescence, few methods have been proposed to remove the fluorescence itself from the original signal, and no fundamental solutions have been made to address issues such as the dynamic range of the detector and the effects of shot noise.

[0006] The present invention has been made in view of the above, and aims to provide a measuring device suitable for non-invasive measurement that selectively excites interstitial fluid present in the dermis and does not capture autofluorescence generated in the melanin layer. [Means for solving the problem]

[0007] The non-invasive measurement device according to the present invention is A light source unit that emits excitation light, A probe that irradiates skin tissue with the excitation light and collects Raman scattered light from the skin tissue, A spectrometer that spectrally analyzes the Raman scattered light and outputs a spectral signal, An analytical device for analyzing the aforementioned spectral signal, Equipped with, The aforementioned probe A transmission optical fiber for transmitting the excitation light from the light source unit, A detection optical fiber is provided around the aforementioned transmission optical fiber to collect the Raman scattered light, A ball lens is provided at the tip of the transmission optical fiber and the detection optical fiber, which contacts the skin tissue to irradiate the dermis with the excitation light and collects the Raman scattered light from the dermis. Equipped with, The optical fiber for detection is positioned at a location where the Raman scattered light is focused by the ball lens, and where autofluorescence from the melanin layer is not focused. [Effects of the Invention]

[0008] According to the present invention, a ball lens irradiates the dermis with excitation light, and a detection optical fiber is positioned at a location where the Raman scattered light is focused by the ball lens, and at a location where autofluorescence from the melanin layer is not focused. This provides a measuring device suitable for non-invasive measurement that selectively excites the interstitial fluid present in the dermis and does not detect autofluorescence generated in the melanin layer. [Brief explanation of the drawing]

[0009] [Figure 1] This figure illustrates the configuration of a non-invasive measurement device according to an embodiment of the present invention. [Figure 2] This figure illustrates both ends of the probe of a non-invasive measuring device according to an embodiment of the present invention. [Figure 3] This is a cross-sectional view of the tip of the probe of a non-invasive measuring device according to an embodiment of the present invention. [Modes for carrying out the invention]

[0010] The non-invasive measurement device according to an embodiment of the present invention selectively excites interstitial fluid present in the dermis layer using a near-lens illumination method with a ball lens, and acquires the signal with high efficiency. Furthermore, in addition to the ball lens, it is combined with a spatial offset detection method that creates a distance between the excitation position and the signal detection position. This makes it possible to remove autofluorescence from deep within the skin from the collected light and selectively detect signals only from the dermis layer without significantly distorting the waveform of the Raman scattering signal.

[0011] Figure 1 shows the configuration of the non-invasive measurement device 1. The non-invasive measurement device 1 analyzes the concentration of substances contained in the skin tissue 2 based on Raman scattered light generated in the skin tissue 2 by irradiation with excitation light. The non-invasive measurement device 1 comprises a light source unit 10, a probe 11, a spectrometer 12, and an analyzer 13.

[0012] The light source unit 10 is a light source that emits excitation light. Since the Raman scattered light generated in the skin tissue 2 by irradiation with excitation light tends to be weak, it is preferable that the light source unit 10 be a light source that emits high-intensity excitation light. Furthermore, since the concentration of glucose contained in the skin tissue 2 is calculated based on the wavelength of the excitation light, it is preferable that the light source unit 10 be a light source that emits single-wavelength excitation light. 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). The wavelength of the excitation light is, for example, a single wavelength selected from 785 nm, 830 nm, and 860 nm.

[0013] Probe 11 is a spectroscopic probe used in a spectroscopic analysis instrument, and is a fiber probe using multiple optical fibers. A ball lens 110 is attached to the tip of probe 11. When measuring blood glucose in interstitial fluid, the ball lens 110 attached to the tip of probe 11 is placed in contact with the surface of the skin tissue 2.

[0014] The spectrometer 12 has a spectroscopic element and a photodetector 120 that decompose incident light into wavelengths. The spectroscopic element separates the Raman scattered light supplied from the skin tissue 2 via the probe 11 into wavelengths and guides them to the light-receiving surface of the photodetector 120. As methods for decomposing light into wavelengths, for example, there are dispersive spectrometers that utilize the diffraction of light and Fourier transform spectrometers that utilize the coherence of light. Dispersive spectrometers consist of a collimating mirror, a focusing mirror, and a diffraction grating, and perform spectral analysis using diffraction and interference by the diffraction grating. Fourier transform spectrometers measure the interference waveform of light using an interferometer. The measured interference waveform is Fourier transformed, and the spectrum of light for each wavelength is measured. As an interferometer, a Michelson interferometer consisting of a reference mirror, a sample mirror, and an optical branching filter is used.

[0015] The photodetector 120 includes a plurality of light-receiving elements on a light-receiving surface thereof. Raman scattered light is incident on the light-receiving surface of the photodetector 120. When the photodetector 120 receives Raman scattered light from the spectroscopic element, the light-receiving elements convert light of each wavelength into electrical signals, and output a photodetection signal indicating an intensity distribution for each wavelength. As the photodetector 120, for example, a photodiode, a CCD (Charge Coupled Device), a CMOS (Complementary Metal Oxide Semiconductor), or the like is used. The spectral signal output from the photodetector 120 is input to the analyzer 13.

[0016] The analyzer 13 is a computer such as a personal computer, and includes a processor that processes data according to a control program, a main storage unit that functions as a work area for the processor, an auxiliary storage unit for storing data over a long period of time, and the like. The analyzer calculates the concentration of glucose contained in the skin tissue 2 based on the spectral signal input from the photodetector 120 of the spectrometer.

[0017] Figure 2 is a diagram showing details of both end portions of the probe 11, and an intermediate portion of the probe 11 is omitted by a wavy line. One end of the probe 11 is the tip end of the probe 11 that abuts on a detection target to irradiate and collect light, and the figure shows a state where the tip end of the probe 11 abuts on the surface of the skin tissue 2. A ball lens 110 is provided at the tip end of the probe 11 as a condensing lens that focuses the output light from the light source unit 10 emitted from an excitation channel into the skin tissue 2, and guides scattered light from the skin tissue 2 to a detection channel in the probe 11. The other end of the probe 11 is the rear end of the probe 11 connected to the light source unit 10 and the spectrometer 12, and receives the output light from the light source unit 10 and outputs detection light from the detection target to the spectrometer 12. The probe 11 is constituted by a bundle of a plurality of optical fibers.

[0018] FIG. 3 is a cross-sectional view of the distal end portion of the probe 11. As shown in FIG. 2 and FIG. 3, one transmission optical fiber 111 is provided at the center as an excitation channel. Around the excitation channel, eight detection optical fibers 112 are provided annularly as detection channels centered on the transmission optical fiber 111, spaced apart by a predetermined radius.

[0019] A laser or the like serving as the light source unit 10 is connected to the transmission optical fiber 111 constituting the excitation channel, and excitation light from the light source unit 10 is transmitted therethrough. A band-pass filter 113 is coupled to the rear end portion of the transmission optical fiber 111. The band-pass filter 113 is a filter that selectively transmits light of a specific wavelength. The excitation light output from the light source unit 10 is band-passed by the band-pass filter 113 and introduced into the transmission optical fiber 111, which is the excitation channel of the probe 11.

[0020] The detection optical fibers 112 constituting the detection channel are arranged spaced apart from the transmission optical fiber 111 by a predetermined radial distance so as to selectively detect a signal only from the dermal layer 21 in the skin tissue 2. Specifically, the distance between the excitation position and the detection position, that is, the distance between the transmission optical fiber 111 and the detection optical fiber 112 is set to 100 μm to 2000 μm. An edge filter 114 is coupled to the rear end portion of the detection optical fiber 112. The edge filter 114 is a filter that removes Rayleigh scattered light. Light detected from the skin tissue 2 is collected, and Raman scattered light from which Rayleigh scattered light has been removed by the edge filter 114 is output to a spectrometer.

[0021] A ball lens 110 is coupled to the distal end portion of the probe 11. The ball lens 110 has a shorter focal length than a convex lens and collects light over a large angle range. The ball lens 110 is brought into contact with the surface of the skin tissue 2, focuses the excitation light from the excitation channel to irradiate the inside of the skin tissue 2, and outputs Raman scattered light from the skin tissue 2 toward the detection channel. In order to dominantly illuminate the dermal layer 21, the diameter of the ball lens 110 is set to 3 to 15 mm.

[0022] The living skin tissue 2 into which the ball lens 110 makes contact has an epidermal layer 20 on its surface, and a dermis layer 21 beneath the epidermal layer 20. The epidermal layer 20 is approximately 0.1-0.3 mm thick and does not contain nerves or blood vessels. The dermis layer 21 is approximately 1-2 mm thick and contains capillaries, nerves, and lymphatic vessels. The dermis layer 21 contains interstitial fluid, which is the fluid between cells. Glucose in the blood diffuses into the interstitial fluid via the capillary walls and is transported from the interstitial fluid to the cells of the tissue. Blood glucose levels can be determined by measuring the glucose contained in this interstitial fluid. Between the epidermal layer 20 and the dermis layer 21 is a melanin layer 22 that produces melanin pigment.

[0023] The detection operation of Raman scattered light from the skin tissue 2 in the above configuration will now be explained. The excitation light output from the transmission optical fiber 111, which is the excitation light channel of the probe 11, is incident on the skin tissue 2 via the ball lens 110. The incident excitation light is focused by the ball lens 110 into the dermis layer 21 within the skin tissue 2. In the dermis layer 21, Raman scattered light with a different wavelength from the excitation light is generated from components contained in the interstitial fluid, as well as Rayleigh scattered light with the same wavelength as the excitation light.

[0024] The scattered light travels through the interior of the skin tissue 2, diffusing as it goes, and returns to the surface of the skin tissue 2. Here, the light scattered to deeper locations within the skin tissue 2 returns to a position on the circumference of the surface of the skin tissue 2, which is a plane perpendicular to the direction of incidence with respect to the point where the excitation light entered the surface of the skin tissue 2, at a predetermined radius. In Figure 2, the scattered light generated by interaction with components contained in the interstitial fluid of the dermis 21 is shown by the solid arrows. The scattered light generated by interaction with components contained in the interstitial fluid is emitted at a position in the x-axis direction that is further away from the point where the excitation light entered.

[0025] The excitation light is irradiated onto the dermis 21, but since the melanin layer 22 is located immediately above the dermis 21, the excitation light is also irradiated onto the melanin layer 22. The melanin layer 22 absorbs the excitation light and generates autofluorescence. The autofluorescence from the melanin layer 22 travels through the skin tissue 2 and is emitted from the surface of the skin tissue 2. Here, the autofluorescence from the melanin layer 22 is emitted from a position on the circumference of the surface of the skin tissue 2, which is a plane perpendicular to the direction of incidence with respect to the point of incidence of the excitation light on the surface of the skin tissue 2, at a predetermined radius. However, since the melanin layer 22 is located at a shallower position within the skin tissue 2 compared to the dermis 21, the radius of the circumference is shorter than in the case of scattered light produced by interaction with components contained in the interstitial fluid, and the light is emitted from near the point of incidence of the excitation light. In Figure 2, the autofluorescence from the melanin layer 22 is indicated by a dashed arrow. The autofluorescence from the melanin layer 22 is emitted from a position closer to the incident position of the excitation light in the x-axis direction than the scattered light produced by interaction with components contained in the interstitial fluid.

[0026] Light emitted from the surface of the skin tissue 2 is incident on the ball lens 110. The incident light passes through the ball lens 110 and is focused toward the end of the probe 11. The position of the light incident on the end of the probe 11 changes according to the position of the light emitted from the surface of the skin tissue 2.

[0027] The scattered light generated by the interaction with components contained in the interstitial fluid enters the ball lens 110 from the surface of the skin tissue 2, as shown by the solid line in Figure 2. The ball lens 110 focuses the scattered light, and the light enters the detection optical fiber 112 in the probe 11. In other words, the distance between the position of the transmission optical fiber 111, which is the excitation position, and the position of the detection optical fiber 112, which is the detection position, is set so that the scattered light enters the detection optical fiber 112.

[0028] In contrast, the autofluorescence from the melanin layer 22 is emitted from a position on the surface of the skin tissue 2 that is closer to the incident position of the excitation light than the scattered light, and is incident on the ball lens 110 as shown by the dashed line in Figure 2. Since the incident position of the autofluorescence to the ball lens 110 is inside the incident position of the scattered light, the autofluorescence focused by the ball lens 110 is directed inward from the detection optical fiber 112 and is not incident on the detection optical fiber 112. In other words, the distance between the position of the transmission optical fiber 111, which is the excitation position, and the position of the detection optical fiber 112, which is the detection position, is set so that the autofluorescence does not incident on the detection optical fiber 112. Therefore, the autofluorescence from the melanin layer 22 is removed from the collected light.

[0029] Scattered light incident on the detection optical fiber 112 has its Rayleigh scattered light removed by an edge filter 114 coupled to the trailing end of the detection optical fiber 112, and only Raman scattered light is input to the spectrometer 12. The spectrometer 12 separates the supplied Raman scattered light by wavelength, guides it to the light-receiving surface of the photodetector 120, and outputs a photodetection signal showing the intensity distribution for each wavelength. The signal output from the photodetector 120 is input to the analyzer 13.

[0030] When the analyzer 13 receives a spectrum from the photodetector 120, it performs a determination process to determine whether or not the waveform is characteristic of glucose based on the waveform pattern in the spectrum. If the determination process determines that it is a glucose waveform, it acquires the glucose peak. Based on the glucose peak in the acquired Raman spectrum, it measures the glucose concentration.

[0031] Furthermore, the present invention allows for various embodiments and modifications without departing from the broad spirit and scope of the invention. The embodiments described above are for illustrating one example of the present invention and do not limit the scope of the invention. The above embodiments and modifications can be combined arbitrarily. Moreover, the invention remains within the scope of the technical idea of ​​the present invention even if some of the constituent elements of the embodiments are omitted as needed.

[0032] This application claims priority based on Japanese Patent Application No. 2023-32780, filed on March 3, 2023, and incorporates the entire specification, claims, and drawings of Japanese Patent Application No. 2023-32780 by reference within this specification. [Industrial applicability]

[0033] The present invention can be widely applied to non-invasive measurement devices that irradiate a living organism with excitation light and detect transmitted light that passes through the living organism. [Explanation of Symbols]

[0034] 1 Non-invasive measurement device, 2 Skin tissue, 10 Light source unit, 11 Probe, 12 Spectrometer, 13 Analyst, 20 Epidermal layer, 21 Dermal layer, 22 Melanin layer, 110 Ball lens, 111 Optical fiber for transmission, 112 Optical fiber for detection, 113 Bandpass filter, 114 Edge filter, 120 Photodetector.

Claims

1. A light source unit that emits excitation light, A probe that irradiates skin tissue with the excitation light and collects Raman scattered light from the skin tissue, A spectrometer that spectrally analyzes the Raman scattered light and outputs a spectral signal, An analytical device for analyzing the aforementioned spectral signal, Equipped with, The aforementioned probe A transmission optical fiber for transmitting the excitation light from the light source unit, A detection optical fiber is provided around the aforementioned transmission optical fiber to collect the Raman scattered light, A ball lens is provided at the tip of the transmission optical fiber and the detection optical fiber, which contacts the skin tissue to irradiate the dermis with the excitation light and collects the Raman scattered light from the dermis. Equipped with, The optical fiber for detection is positioned at a location where the Raman scattered light is focused by the ball lens, and where autofluorescence from the melanin layer is not focused. Non-invasive measurement device.

2. The diameter of the ball lens is 3-15 mm. The distance between the transmission optical fiber and the detection optical fiber is 100 μm to 2000 μm. The non-invasive measuring device according to claim 1.

3. By measuring the glucose contained in the interstitial fluid of the dermis layer from the aforementioned Raman scattered light, the blood glucose level is determined. A non-invasive measuring device according to claim 1 or 2.

Images