JPH1147120A - Noninvasive biological component observation method and device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To enable trace amounts to be measured stably by reducing noise components. SOLUTION: When biological components are measured by applying light of plural wavelengths to a living body 7 from a light source 1 via a spectral diffraction device 2 and an optical fiber 3, receiving the light scattered and reflected by the living body 7 on a photocell 5 via a fiber 4, converting the same into an electrical signal, and sampling the signal into an analytical display device 6, a matching material 8 in liquid or gel form is applied to the surfaces of contact between the optical fibers 3, 4 and the living body 7 to prevent reflected and scattered light at an interface except an air layer portions of contact.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method and an apparatus for observing non-invasive components in a living body.

[0002]

2. Description of the Related Art A non-invasive device for analyzing components or measuring the concentration of a living body by irradiating the living body with visible light, near infrared light or infrared light, and analyzing the spectrum of the transmitted light or reflected light. Is well known. Further, an optical fiber is used for transmitting and receiving light, and the fiber probe is brought into contact with a human body (Japanese Patent Laid-Open No. 5-161628).
No.) and a device in which a finger is pressed against a transparent window member (Japanese Patent Application Laid-Open No. 7-506987).

[0003]

In any of the above cases, as shown in FIG. 2, an air layer 9 exists in a space formed by irregularities on the surfaces of the glass or fibers 3 and 4 and the surface of the living body 7, and the contact state of the air layer 9 exists. Changes with each measurement. The reflected and scattered light at the air interface becomes a noise component in the measurement,
The change in state will prevent a stable and reproducible measurement. Further, there is a problem that adverse effects are caused when observing trace components such as a decrease in the effective incident amount.

The present invention has been made in view of the above problems, and has as its object to provide a noninvasive biological component observation method and apparatus capable of reducing noise components and performing stable trace measurement.

[0005]

A non-invasive living body component observation method according to the present invention irradiates a living body with light of a plurality of wavelengths from a light irradiating means through a light transmitting member which comes into contact with the living body, and transmits the light from inside the living body. A method of receiving scattered reflected light or transmitted light with a light receiving element via a light transmitting member that comes into contact with a living body and converting the light into an electric signal, and observing a biological component based on the electric signal, comprising the steps of: A liquid or gel-like matching material is interposed between the two.

A non-invasive biological component observation apparatus according to the present invention includes a light irradiating means for irradiating a living body with light of a plurality of wavelengths, and receives scattered reflected light or transmitted light from inside the living body and converts the light into an electric signal. A light receiving element to be converted, and a light transmissive member that comes into contact with a light projecting portion to the living body or a light emitting portion from the living body, between the light transmitting member and the living body,
A liquid or gel-like matching material is interposed.

The reflected and scattered light at the interface increases as the difference between the refractive indices on both sides of the interface increases, and increases as the unevenness increases. Applying a liquid, gel, cream, or solid (paste) substance to the surface of the living body eliminates the air layer on the surface of the living body, reduces the difference in refractive index on the surface of the living body, reduces scattering and reflection, and reduces apparent irregularities. Can be smaller. Therefore, stable measurement can be performed without being affected by a change in the state of the air layer every measurement. Further, since the amount of scattered and reflected light is reduced and the amount of incident light is increased, a smaller amount of measurement can be performed.

If the refractive index of the matching substance is between that of the surface of the living body and the refractive index of the surface of the light transmitting member, the reflected and scattered light at the interface on the light transmitting member side can be reduced, and the efficiency is the most efficient. Become. In addition, since the spectrum of a living body is mainly composed of the spectrum of water, the influence on the measured spectrum can be reduced by selecting a substance containing no water as the matching substance.

Further, if the matching substance has a characteristic absorption peak and its wavelength is different from the absorption wavelength of the substance to be measured or is at a wavelength where the absorption of the substance to be measured is small, or if such a substance is mixed. If so, the amount of application can be known from the absorption intensity at that wavelength. If the applied amount can be checked, it is possible to correct the influence of the matching substance contained in the measured spectrum of the sample on the spectrum.

Further, it is very difficult to always apply the matching material in the same amount and thickness, and it may be difficult to distinguish between a change in the spectrum when the amount of the matching material applied changes and a change in the living body itself. If the actual coating amount is known and can be corrected, an accurate spectrum without the effect of coating can be obtained. Further, as described above, the spectrum of the living body is mainly composed of the spectrum of water, and the absorption sharply increases from 1400 nm. Therefore, if a substance having an absorption peak at a shorter wavelength is used as the matching substance, better correction can be performed.

Further, using the absorption intensity or the amount of application of the matching substance obtained in this way, when the amount of application is below a certain value, the amount of the liquid / gel-like substance is insufficient, forgotten to apply, or specified. It is determined that the substance is different from the substance, and an error occurs. Alternatively, defective measurement can be prevented in advance by instructing repainting and re-measurement.

[0012]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described in more detail with reference to embodiments. FIG. 1 is a diagram showing a schematic configuration of a non-invasive biological component observation device according to an embodiment of the present invention. This biological component observation device includes a light source 1 and a spectroscopic device 2
And an optical fiber 3 for projecting light and an optical fiber 4 for receiving light
, A light receiving element 5, and an analysis display device 6. The light source 1 includes a power supply 11 and a halogen lamp 12. The spectroscopic device 2 includes a diffraction grating 13, a slit 14, and the like. The light receiving element 5 is an InGaAs element 1
5. It has a power supply 16. The analysis display device 6 includes a computer 17 and an LCD display element 18.

Light of a plurality of wavelengths emitted from the light source 1 is divided by the spectroscope 2 for each wavelength, sent to the surface of the living body 7 through the optical fiber 3, and enters the living body 7 therefrom.
The light that has entered the living body 7 travels while being scattered and absorbed by the substance in the living body 7, and exits again from the surface of the living body 7. Light coming out of the living body 7 passes through the optical fiber 4,
The light is received by the light receiving element 5, converted into an electric signal, and taken into the computer 17 of the analysis display device 6. The computer 17 analyzes the light intensity for each wavelength to determine the concentration of the substance in the living body 7. The analysis result is displayed on the LC of the analysis display device 6.
It is displayed on the D display element 18.

The light source 1 may emit a single light having a plurality of wavelengths like a halogen lamp shown here.
A plurality of light sources emitting a substantially single wavelength, such as D and a laser, may be used. The spectroscopic device 2 may use a filter or an acousto-optic device. Further, here, the spectroscopic device 2 is arranged to disperse light before entering the living body 7, but may be arranged to disperse light coming out of the living body 7.

The light receiving element is, in addition to the InGaAs element, a Si element, PbS or PTM (photomultiplier tube) depending on the wavelength.
And the like. Further, in a device that disperses light emitted from the living body 7, a device in which light receiving elements are arranged in an array, such as a CCD or a linear image sensor, may be used. In the biological component observation device of FIG. 1, the optical fibers 3 and 4 are used to guide light to the surface of the living body 7 and take out light from the living body 7. 4 himself. However, as shown in FIGS. 3 and 4, the present invention can be applied to a biological component observation device that does not use an optical fiber. 3 and 4, the light transmitting member 1 passes through the light source 1 and the spectroscopic device 2.
The light emitted from the living body 7 to the living body 7 is scattered and absorbed in the living body 7, and the light coming out of the living body 7 is received by the light receiving element 5 through the light transmitting member 10. The light transmitting member 10 used here is a window made of glass, sapphire, or the like that is transparent to light.

The biological component observation device shown in FIG.
Although the upper light projecting surface and the light receiving surface are of the reflective type on the same side,
As shown in FIG. 5, a transmission type biological component observation in which the light emitting part and the light receiving part, that is, the end face of the light emitting optical fiber 3 and the end face of the light receiving optical fiber 4 are opposite to the living body 7. The present invention can be applied to an apparatus. The optical fiber 3 of FIGS.
4 and the contact portion between the light transmitting member 10 and the surface of the living body 7 shown in FIGS.
Is applied. The matching material 8 prevents reflection and scattered light at the boundary surface except for the air layer at the contact portion. When the matching material 8 is not applied, the contact portion between the light transmitting member and the surface of the living body has an air layer due to unevenness of the surface. Light reflection and scattered light increase as the difference in refractive index between the two sides at the interface increases. The refractive index of the cell membrane is described in Reference (J.
According to S. Maier, SAWalker, ed., Opt. Lett. 19, 2062 (1994)], it is 1.35-1.46. On the other hand, in contrast to 1 in the case of air, even when simple water is used as the matching substance, the difference in the refractive index is 1.333 (wavelength 588 nm), and the difference in the refractive index from the living body is small. Light that enters increases and light that becomes a noise component decreases. Furthermore, it is less affected by changes in surface conditions and contact conditions for each measurement,
A stable measurement can be performed every time. The above applies to both the side of projecting light to the living body and the side of receiving light from the living body. Such matching materials include liquid, cream, and solid forms.

The material applied before contact may be on the living body side or on the fiber side. In general, the unevenness of the surface is larger on the living body side, and therefore, it is preferable to apply it on the living body side in terms of removing the air layer. On the other hand, when coating is performed on the light transmitting member, automation of the coating operation is facilitated. FIG. 6 shows a difference in measurement variation of the absorption spectrum between when the matching material is applied and when it is not applied. In FIG. 6, a graph A indicates that the matching material is not applied, and a graph B indicates that the matching material is applied. The horizontal axis represents the wavelength, and the vertical axis represents the degree of variation (standard deviation) of the measured value at each wavelength when spectrum measurement is performed many times. It can be seen that the measurement dispersion is smaller in the measurement where the matching substance is applied.

In the above description, the difference in the refractive index between the living body and the matching material has been considered, but the smaller the difference in the refractive index between the light transmitting member and the matching material is, the better. When the light transmitting member is, for example, BK7, the refractive index is 1.517 (wavelength 588 nm), and the difference in the refractive index is smaller in water than in air. Furthermore, if the refractive index of the matching substance is between the refractive index of the living body and the refractive index of the light transmitting member, the influence at the interface can be minimized. For example,
Silicon oil Shin-Etsu Silicone KF56 (trade name) has a refractive index of 1.5.

Many of the components of living organisms are water. FIG. 7 shows a diffuse reflection absorption spectrum of a living body from visible to near infrared. As can be seen from the figure, water is mostly absorbed, and the analysis of components other than water depends on how accurately information embedded in the water absorption spectrum is extracted. In particular, the absorption of water is extremely large in the near infrared and infrared regions of 1400 nm or more. Therefore, when the matching substance is almost made of water, it becomes impossible to distinguish between the absorption spectrum of the matching substance and the absorption spectrum of the living body. That is, when there is a change in the measured spectrum, it cannot be determined whether the change is due to a change inside the living body or a change in the applied amount of the matching substance. It is very difficult to keep the application amount of the matching material constant except when automatically applying it by a machine. Therefore, if a substance that does not contain moisture and does not have strong absorption at the absorption wavelength of the component to be measured is used as the matching substance, measurement that is not affected by variations in the coating amount can be performed. When the measurement target component is glucose, the absorption spectrum of glucose has a peak near 1600 nm as shown in FIG. 8, and therefore, for example, silicon oil (FIG. 9) or heavy water (FIG. 10) having no strong absorption there. Is mentioned.

Even in the case of a matching substance containing water or having an absorption at the same wavelength as the absorption wavelength of the component to be measured, if there is an absorption peak even at a wavelength where the biological absorption is small, the matching substance is determined based on the value. Can be corrected. For example, when a matching material having an absorption spectrum as shown in FIG. 11 is used, the influence amount of the matching material is determined from the absorption amount at a wavelength of 700 nm, and the amount of the matching material is subtracted from the entire wavelength. Can be obtained. In particular, since the absorption of water sharply increases at 1400 nm or more, 500 to
A matching material having an absorption peak at 1400 nm is preferred.

It is possible to judge the quality of the measurement by using the application state analyzed from the characteristic absorption wavelength of the matching material. For example, as shown in FIG. 12, after the matching substance is applied to the light transmitting member or the surface of the living body (ST1), measurement is performed (ST2), and based on the obtained absorption spectrum, whether the amount of the matching substance applied is appropriate, that is, the characteristic wavelength It is determined whether or not the absorption amount or the application amount estimated therefrom is within a predetermined range (ST3).
Then, the analysis value is displayed (ST4). When the absorption amount or the application amount is out of the set range, it is displayed that the application is small (ST5) or the application is large (ST6). If the amount is out of the setting range, it may be that the substance is not applied, a substance different from the specified substance is applied, the amount of application is insufficient, or the amount of application is too large. , And the output or display of the measured value can be prevented. Also,
As shown in FIG. 13, an error is displayed (ST7) instead of the measured value display, and it is possible to prompt the user to perform the re-measurement.

As shown in FIG. 14, a message to instruct re-measurement may be displayed (ST8), or the mode of re-measurement may be automatically shifted after the display. As shown in FIG. 15, when no further coating is performed, an instruction to re-apply may be issued (ST9).

[0023]

According to the first and second aspects of the present invention, a liquid or gel-like matching substance is interposed between the light transmitting member and the living body.
By eliminating the air layer on the surface of the living body and reducing the refractive index difference on the surface of the living body, scattering and reflection can be reduced and apparent irregularities can be reduced. Therefore, stable measurement can be performed without being affected by a change in the state of the air layer at each measurement. Further, since the amount of scattered and reflected light decreases and the amount of incident light increases, a smaller amount of measurement can be performed.

According to the third aspect of the present invention, the refractive index of the matching substance is set between the refractive index of the surface of the living body and the refractive index of the surface of the light transmitting member. The reflected and scattered light can be reduced, and the efficiency becomes the highest. Further, according to the invention of claim 4, since the matching substance is a substance containing no water, the influence on the spectrum of the living body mainly consisting of the spectrum of water can be reduced.

According to the fifth aspect of the present invention, since the matching substance has an absorption wavelength different from the absorption wavelength of the substance to be measured or has an absorption peak at a wavelength having a small absorption of the substance to be measured, The amount of application can be known from the absorption intensity of the product. According to the invention of claim 6, since the absorption peak of the matching substance is from 500 nm to 1400 nm, the absorption peak of the living body sharply increases from 1400 nm and has an absorption peak at a short wavelength. With a matching material, better correction can be made.

According to the seventh aspect of the invention, since the absorption intensity peculiar to the matching substance is analyzed and the influence of the matching substance on the biological spectrum is corrected, the actual application amount can be determined. As a result, an accurate spectrum free from the influence of coating can be obtained. Claims 8, 9, and 1
According to the present invention, the degree of application of the matching substance is determined, the quality of the measurement is determined, and the processing is performed based on the result. Can be prevented in advance.

[Brief description of the drawings]

FIG. 1 is a diagram showing a schematic configuration of a non-invasive biological component observation device according to an embodiment of the present invention.

FIG. 2 is a diagram illustrating that an air layer is formed on a contact surface between an optical fiber used in a biological component observation device and a biological surface.

FIG. 3 is a diagram showing a schematic configuration of a non-invasive biological component observation device according to another embodiment of the present invention.

FIG. 4 is a diagram showing a schematic configuration of a non-invasive biological component observation device according to still another embodiment of the present invention.

FIG. 5 is a diagram showing a schematic configuration of a non-invasive biological component observation device according to still another embodiment of the present invention.

FIG. 6 is a graph showing a difference in measured values depending on the presence or absence of a matching substance.

FIG. 7 is a diagram showing an absorption spectrum of a human body.

FIG. 8 is a diagram showing an absorption spectrum of glucose powder.

FIG. 9 is a diagram showing an absorption spectrum of silicon.

FIG. 10 shows an absorption spectrum of heavy water.

FIG. 11 shows an absorption spectrum of red jelly.

FIG. 12 is a flowchart showing the determination of the application state of the matching material and the subsequent processing.

FIG. 13 is a flowchart showing another example of the determination of the application state of the matching substance and the subsequent processing.

FIG. 14 is a flowchart showing still another example of the determination of the application state of the matching substance and the subsequent processing.

FIG. 15 is a flowchart showing still another example of the determination of the application state of the matching material and the subsequent processing.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Light source 2 Spectroscope 3 Optical fiber 4 Optical fiber 5 Light receiving element 6 Analysis display device 7 Biological body 8 Matching substance

 ──────────────────────────────────────────────────続 き Continued from the front page (72) Inventor Yusaku Sakota 24th Yamanouchi Yamanoshitamachi, Ukyo-ku, Kyoto Inside Omron Life Science Laboratory Co., Ltd.

Claims (13)

[Claims] 1. A living body is irradiated with light of a plurality of wavelengths from a light irradiating means through a light transmitting member which comes into contact with a living body, and scattered reflected light or transmitted light from inside the living body is passed through a light transmitting member which comes into contact with the living body. In the non-invasive biological component observation method of observing a biological component by using the light receiving element and converting it into an electric signal and observing a biological component using the electric signal, a liquid or gel-like matching substance is interposed between the light transmitting member and the living body. A non-invasive biological component observation method, characterized in that: 2. A light irradiating means for irradiating a living body with light of a plurality of wavelengths, a light receiving element for receiving scattered reflected light or transmitted light from inside the living body and converting the scattered light or transmitted light into an electric signal, and light projection onto the living body A non-invasive biological component observation device having a light transmitting member in contact with a light emitting part from a part or a living body, wherein a liquid or gel-like matching substance is interposed between the light transmitting member and the living body. Non-invasive biological component observation device. 3. The non-invasive biological component observation device according to claim 2, wherein the matching substance has a refractive index that is a numerical value between the refractive index of the living body and the refractive index of the light transmitting member. 4. The non-invasive biological component observation device according to claim 2, wherein the matching substance is a substance containing no water. 5. The non-invasive biological component observation apparatus according to claim 2, wherein the matching substance has an absorption peak wavelength at a wavelength different from or smaller than the absorption wavelength of the substance to be measured. 6. The non-invasive biological component observation apparatus according to claim 5, wherein the absorption peak of the matching substance is in a visible / near-infrared light region of 500 nm to 1400 nm. 7. The non-invasive biological component observation apparatus according to claim 2, further comprising a correction means for analyzing an absorption intensity at an absorption wavelength peculiar to the matching substance and correcting an influence of the matching substance on a biological spectrum. 8. An analysis means for analyzing the degree of application of the matching substance from a measured spectrum, a quality judgment means for judging the quality of the measurement based on the obtained analysis result, and a notifying means for notifying the judgment result. 3. The non-invasive biological component observation device according to claim 2, wherein: 9. The non-invasive biological component observation device according to claim 8, wherein an error is output based on the determination result. 10. The non-invasive biological component observation device according to claim 8, wherein an excessive amount or an excessive amount is output based on the result of the determination. 11. The non-invasive biological component observation device according to claim 8, wherein a forget-to-paint is output based on the determination result. 12. The noninvasive biological component observation device according to claim 8, wherein a recoating instruction is output according to the result of the determination. 13. The non-invasive biological component observation device according to claim 8, wherein a re-measurement instruction is output according to the determination result.