JPH11178799A - Vital method and device for analyzing superficial tissue of organism - Google Patents

Abstract

PROBLEM TO BE SOLVED: To simply an surely analyze the transmitted light system of a superficial tissue of an organism. SOLUTION: This method is a method for analyzing the nature of a superficial tissue 11 of a living body, preferably a skin tissue or a mucosal tissue and more preferably a corium tissue or a subcutaneous tissue in the skin tissue or a mucosal proper layer and a subsmucous layer in the mucosal tissue by absorbing light. Spectroscopic analysis is executed by elevating a part of the tissue 11 of the living body and executing a light receiving and emitting operation to a light incident part from a light emitting part opposed through the elevated part. As light is transmitted through the elevated part by elevating a part of the living body, a device where the light emitting part and the light incident part are opposed at a small interval can be used and the measurement is possible even though the output of the light is small.

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 analyzing surface tissue of a living body by a spectroscopic analysis method in which a light beam having a wavelength belonging to the ultraviolet to infrared region is made incident on a substance, and the chemical component of the substance is analyzed from the transmitted light. , Specifically, analyzing the surface tissue of mammals such as humans and cattle, amphibians, birds and other animals and plants, that is, the surface tissue having a layered structure,
For example, quantitative analysis of water, glucose, fructose, calcium, sodium, cholesterol, fat, protein,
The present invention relates to an analysis method and a device for performing quantitative and qualitative analysis of physical properties such as skin elasticity, abrasion, and freshness.

[0002]

2. Description of the Related Art Spectral analysis utilizing ultraviolet light to infrared light is currently used in a wide range of fields. Although the physical properties related to light absorption differ depending on the wavelength used, the excitation of electrons in the ultraviolet region, the resonance of molecular vibration in the infrared region, and the harmonics of the resonance of molecular vibration in the near infrared region can be measured.
An analysis can be performed based on these.

[0003] Among these wavelengths, near-infrared spectroscopy, which performs quantitative and qualitative analysis of substances using near-infrared light adjacent to the visible region, has recently been used in various fields including the agricultural field. Have recently begun, and recently are non-invasive in the biological field,
It is attracting attention as a harmless analysis method. Near-infrared spectroscopy is a method of irradiating a substance with light having a wavelength of 0.8 μm to 2.5 μm to a substance and analyzing the transmitted or reflected light spectrum. This near-infrared spectroscopy uses low-energy electromagnetic waves and does not damage the sample. It can be applied to samples in various states, such as solids, powders, fibers, liquids, and gases. Infrared light has the advantage that the absorption intensity of water is weaker, and analysis in aqueous solution is possible.

[0004] However, when near-infrared light is used, the absorption signal is very weak compared to infrared light because of dealing with harmonics, and has the disadvantage that the assignment of the band is not clear. For this reason, near-infrared spectroscopy analyzes the quantification,
For the purpose of qualification, a technique called "chemometrics" is used. This is a method of performing chemical analysis using multivariate analysis methods and statistical analysis methods. It has evolved with the development of computers, and recent near-infrared spectroscopy uses multivariate analysis methods such as principal component regression analysis or PLS regression analysis. It is often performed using. Attempts have also been made to apply neural networks and the like to analysis.

[0005] A moisture meter is a conventional example in which near-infrared spectroscopy is used for chemical component analysis. Although several types of moisture analyzers using near-infrared light are currently available on the market, simple moisture quantification in the early days was based on the absorbance at 1.93 μm of water absorption and the neutral wavelength of 2.08 μm, which is not related to the absorption of substances. Is performed using a calibration curve obtained in advance by a simple regression equation between the difference in absorbance at step (differential absorbance) and water. In the actual measurement, the difference in absorbance is measured, and the moisture content of the substance is measured by comparing with a calibration curve. However, since the water content measurement is performed by irradiating the surface of the substance with light and detecting the reflected light, there is no ability to selectively detect the water content inside the surface layer tissue. Therefore, it is difficult to analyze an object to be measured having a concentration distribution in the depth direction, such as a biological tissue.

As an attempt to analyze the chemical composition or physical properties of living tissue by using near-infrared rays, there is the development of optical CT, which has not yet been put to practical use. Optical CT is not intended to analyze the surface tissue of living organisms, but NMs using X-ray CT scans and nuclear magnetic resonance are currently in practical use.
This is to capture a tomographic image such as R using near-infrared light.

[0007] In the development of optical CT, it is very important to determine the transmission path of light reaching the light-receiving probe from the light-emitting probe in the substance. As shown in FIG. It has been confirmed both experimentally and by simulation using a numerical analysis method that the transmitted light passes through a so-called “banana shape” when arranged parallel to the measurement object 11.

Here, by utilizing the property of taking such a light transmission path and adjusting the interval between the light emitting probe and the light receiving probe, it is possible to perform a spectroscopic analysis of a living tissue at a target depth. As an analysis using the transmission method, there is a conventional example in which the oxygen saturation and plethysmogram in blood are obtained by using a portion where the shape of a living body is convex, such as a finger or an earlobe. However, these transmission methods are based on the use of near-infrared light in the wavelength range of 0.7 to 1.3 μm belonging to the second and third harmonics of the fundamental vibration of molecules having excellent permeability in living organisms. It is difficult to use the wavelength belonging to the range of 1.4 to 2.5 μm belonging to the fundamental vibration of the molecule or the first harmonic, because of its transmittance, and it is difficult to measure by the transmission method in the wavelength range of 1.4 to 2.5 μm. In the case of performing, it is necessary to break a living tissue and process it into a sample having a thickness of about 1 mm. For this reason, it is usually used for measurement by a (diffuse) reflection method. However, when used for (diffuse) reflection measurements:
Although the near-infrared light of 4 to 2.5 μm is inferior in transmittance to the near-infrared light of 0.7 to 1.3 μm used for transmission measurement,
The absorption signal in living tissue is large, and it is suitable for quantitative and qualitative analysis that expects high accuracy. The use of a high-intensity light source such as a laser beam can cover poor transmittance, but when applied to living organisms, tissue damage such as burns may occur, and costs may be reduced. Would be an expensive device.

[0009]

When quantitative or qualitative analysis of chemical components or physical properties of skin tissue is performed using (diffuse) reflected light like light CT, incident light from the light emitting means depends on the light receiving and emitting intervals. On the other hand, since the light returned to the light receiving means is about 1/100 or less, or about 1 / 1,000 or less, there is a problem that it is necessary to input light of high intensity to perform accurate spectral analysis. . It goes without saying that when performing analysis with high-intensity near-infrared light, it is premised that it is difficult to perform analysis with high light intensity due to the possibility of damage or burns on living tissue.

In the case of analyzing a complex tissue in which thin tissues such as skin tissues and mucous membranes are laminated and controlling the light emission interval at a specific tissue or at a specific depth, the scattering coefficient of the tissue may be increased. There is also a possibility of analyzing transmitted light in an unintended part due to individual differences in absorption coefficients and the like. The present invention makes it possible to use quantitative and qualitative analysis of chemical components or physical properties of living body surface tissues (biological epithelial tissues) such as cortical tissues and mucous membranes in a transmission system even with light having a wavelength that is inferior in transmission. It is an object of the present invention to provide an analysis method and an analysis method that can be performed in a state where the influence of a part is small. In particular, a relatively ordinary light source such as an ordinary halogen lamp, a light emitting diode (LED), or a laser diode, an ordinary light receiving element such as a photodiode made of Si, Ge, or InGaAs, and a simple light condensing means as the light emitting / receiving means. It is an object of the present invention to provide a low-cost analysis method and apparatus which can easily perform a spectroscopic analysis on a sample and easily assemble a measurement part for receiving and emitting light from a living tissue.

In addition, by using transmitted light for analysis,
An object of the present invention is to provide an analysis method and an apparatus in which it is easy to specify a tissue through which light is transmitted as compared with the case of using (diffuse) reflected light, and it is also easy to simulate the light transmission state.

[0012]

Means for Solving the Problems The method for analyzing the surface tissue of a living body according to the present invention is characterized in that the surface tissue of a living body, preferably a skin tissue or a mucosal tissue, more preferably a dermal tissue or a subcutaneous tissue in the skin tissue is absorbed by light absorption. This is a method for analyzing the properties of the lamina propria and the submucosa in a tissue or mucosal tissue, in which a portion of the surface tissue of a living body is raised, and light is emitted from a light emitting portion facing the body through the raised portion. It is characterized in that spectroscopic analysis is performed by performing light receiving and emitting operations on the incident part.

In order to raise a part of the surface tissue of a living body and transmit light to the raised portion, 1.4 to 2.5
The biological transmission spectrum analysis is performed even in a wavelength range inferior in biological tissue, such as near-infrared light of about μm (so-called fundamental vibration of a molecule, the first harmonic region) or a wavelength region of 0.7 μm or less (ultraviolet region). That can be
If the light is in a wavelength region having a good transmittance such as 0.7 to 1.3 μm, the biological transmission spectrum can be analyzed with light having a weaker intensity than the conventional method.

It is most preferable to arrange the light receiving and emitting means so that their optical axes coincide with each other. However, since the surface tissue of the living body (epithelial tissue) is a scattering substance, the optical axes are coincident in a vacuum or in a vacuum. It is not necessary to be strict as in the air, and if the amount of incident light to the light receiving means is ensured, it is sufficient if the light is substantially at the opposite position, and is not limited to the 180 ° position.

It is preferable to use a light emitting and receiving means in which the distance between the light emitting part and the light incident part is 5 mm or less, preferably 2 mm or less. Within 5mm from the convex top end,
It is preferable that the thickness be within 2 mm. When the living body surface tissue is human skin tissue, as shown in FIG. 16, it is composed of epidermis A, dermis B, and subcutaneous tissue C. When the skin tissue, especially dermis tissue B is to be raised, the site to be raised For example, in the case of the dermis in the inner part of the human forearm, the epidermis layer thickness is 0.1 to 0.
This is because the dermis layer thickness is about 0.5 to 1.0 mm at about 2 mm.

Elevating a part of the surface tissue of a living body is
The living body surface tissue may be pinched and raised, or the living body surface tissue may be raised by pressing pressure caused by abutting a measurement unit provided with light emitting and receiving means on the living body surface tissue. In addition, the human forearm inner part is one of the parts that are suitable for analysis in a living body with small individual differences in humans, but the part to be measured is not limited to the forearm inner part, and the abdomen and chest Also suitable are the parts covered with clothing and mucous membrane parts such as the mouth. Especially,
The abdomen and chest are measured continuously or intermittently in the cortical tissue.
It is most suitable as a part for performing time measurement.

The organization performing the analysis depends on the purpose,
Using dermis is often effective. For the purpose of analyzing the dermis, the subcutaneous tissue under the dermis contains a lot of adipose tissue, etc., and when analyzing the properties in the dermal tissue, it becomes a disturbance. Raising the tissue allows for analysis with better accuracy and reproducibility.
The analysis is performed by spectroscopic analysis of the raised skin tissue. The wavelength range used for spectroscopic analysis is near infrared light in the wavelength range of 1.3 to 2.5 μm, more preferably 1.4 to 1.8 μm, or 2.0 to 2.4 μm. This is because a sufficient signal can be obtained even in the minute raised skin tissue as described above and, unlike ultraviolet rays, there is almost no toxicity to the living body.

The apparatus for analyzing the surface tissue of a living body according to the present invention can be used to analyze the surface tissue of a living body, preferably a skin tissue or a mucosal tissue, more preferably a dermal tissue, a subcutaneous tissue or a mucous tissue in the skin tissue. A device for analyzing the properties of the lamina propria and the submucosa of the living body, comprising means for raising a part of the surface tissue of a living body and guiding it between a light emitting part and a light incident part in the light receiving and emitting means. It is characterized by having

As a means for raising a part of the surface tissue of the living body, there are grooves on the inner wall surface which oppose the light emitting portion and the light incident portion, and displacement between the light emitting portion and the light incident portion which face each other. Possible displacing means, rollers, reduced pressure suction means and the like can be suitably used. At least one of the light emitting portion and the light incident portion can use a slit having a width of 1 mm or less, preferably 0.5 mm or less, and more preferably 0.2 mm in width, an optical fiber, or an optical fiber bundle. When an optical fiber bundle is used, it is preferable that a plurality of optical fiber strands are arranged in a sheet shape, and in particular, a device provided with a support for maintaining the shape of the sheet-like optical fiber bundle. The light emitting portion and the light incident portion may be made detachable.

The optical fiber (optical fiber bundle) has a wire diameter of 75 to 750 μm, preferably 250 μm.
The following are suitable: An optical fiber having a wire diameter of about 200 μm is easy to assemble and is suitable for producing a sheet-like optical fiber bundle. It is desirable that the thickness of the sheet-like portion of the sheet-like optical fiber bundle is 0.5 mm or less, more preferably 0.3 mm or less.

When a support is used for the sheet-like optical fiber bundle to prevent its breakage and to make the optical axis of the light receiving / emitting means easy to match, the thickness of the sheet-like optical fiber bundle provided with the support is preferably 1.5 mm or less, and more preferably 1.5 mm or less. 1.0m
m or less. By performing the spectroscopic analysis as described above, it becomes possible to analyze chemical components in skin tissue, particularly dermal tissue. The absorbance signal obtained by the spectroscopic analysis is numerically calculated by an arithmetic unit to calculate a target component concentration.
The calculation of the component concentration is performed using a calibration curve or a calibration equation. The calibration curve or the calibration equation is obtained in advance by calibration for analyzing the absorption spectra of an individual or a plurality of subjects in various states. Analysis is a method of performing quantitative and qualitative analysis using multivariate analysis or statistical analysis. In near-infrared spectroscopy, principal component regression analysis or P
This is performed using a multivariate analysis method such as LS regression analysis.

In the spectrum measurement, light from a light source such as a halogen lamp is separated into light of an arbitrary wavelength using an optical filter such as an interference filter, or light of a plurality of wavelengths is combined by combining a monochromatic light source such as an LED or a laser diode. A method of measuring the absorbance, or a method of continuously analyzing the light from a light source such as a halogen lamp using a diffraction grating or a Fourier transform method (FT-IR method) as in a normal spectral analysis method. The method required may be used.

The analysis of the surface tissue of a living body according to the present invention is not limited to the analysis of chemical components in human dermis tissue, but may be used, for example, for the analysis of the epithelial tissue of livestock or mammals such as cattle and pigs or mammals. it can. The properties of the living body surface tissue (epithelial tissue) of the organism to be analyzed in the present invention utilize the correlation between the blood components and the epithelial tissue properties (particularly the dermal tissue properties) in mammals, in addition to the component concentrations and physical properties of the part to be analyzed. It is also possible to estimate the concentration of the blood component. In humans, glucose concentration is a substance having a high correlation between blood components and surface tissue properties (particularly dermal tissue properties). Therefore, it can be said that the present invention is an analysis method suitable for estimating human blood glucose concentration.

[0024]

EXAMPLES-Example 1-An apparatus for analyzing surface tissue of a living body in this example is for quantifying glucose concentration in human skin tissue, and comprises a 150 W halogen lamp as shown in FIG. The optical fiber bundle 4 and the diffraction grating unit 2 transmit the light from the light source 1 to the skin tissue 11 and transmit the light transmitted through the skin tissue 11 to the diffraction grating unit 2 containing the flat field type diffraction grating through the slit 3. It comprises an array type light receiving element unit 5 for receiving the split light, and an arithmetic unit 6 for performing quantitative analysis based on signals from the light receiving element unit 5 to quantify the glucose concentration. The light receiving element unit 5 is an array type in which 256 InGaAs photodiodes having a light receiving sensitivity range of 0.9 to 2.1 μm at room temperature are arranged linearly and cooled by a Peltier element. The received light signal is A / D converted by an A / D conversion board 9 with 16-bit accuracy, and recorded by an arithmetic unit 6 composed of a personal computer. In the figure, reference numeral 8 denotes a reflecting mirror, 7 denotes a lens, and 10 denotes a measuring unit serving as a light receiving / emitting end.

The glucose concentration determination performed by the arithmetic unit 6 is performed using a calibration equation (calibration curve) using an absorption spectrum belonging to the near-infrared region of 1.4 μm to 1.8 μm. The calibration equation used in this example was an equation obtained by PLS regression analysis. This calibration equation is obtained in advance by an experiment using the analyzer of the present embodiment, the absorption spectrum measured from the skin tissues of a plurality of subjects is used as an explanatory variable, and the actually measured glucose concentration in the dermal cell fluid is used as the target variable, and PLS is used as the target variable. It is determined by regression analysis.

The optical fiber bundle 4 used in the present embodiment is obtained by bundling 14 optical fiber wires 12 having a cladding diameter of 200 μm in a sheet shape as shown in FIG. Used as the measurement end of the fiber bundle for use. The measuring section 10 of the optical fiber bundle 4 has a light receiving and emitting optical fiber bundle 4 arranged through a groove D cut in a V-shape as shown in FIG. 1A. V-shaped groove D has a width Dw of 1.5 m
m, the depth Dt is 1.5 mm, and the light receiving / emitting optical fiber bundle 4 is arranged so that its measuring end (light emitting part and light incident part) comes to the uppermost position of the groove D.

The measurement is performed by pressing the measuring unit 10 against the living tissue 11. By pressing the measuring unit 10 against the living tissue 11, the periphery of the V-shaped groove D is depressed and a part of the living tissue 11 is raised in the groove D as shown in FIG. The bundle 4 measures the absorption spectrum of the raised tissue. Since the living tissue is a scatterer, unlike in a vacuum or in the air, a sufficient amount of light can be secured even if the optical axis is slightly shifted as in the present embodiment.

Since the optical fiber bundles 4 arranged in a sheet shape that can be easily assembled as in the present embodiment make it possible to carry out the spectral analysis of the skin tissue by the transmission method, it is easier than the conventional (diffuse) reflection type measurement. Analysis with a small amount of light becomes possible. Alternatively, even with the optical fiber bundle 4 composed of a small number of optical fiber strands, sufficient transmitted light can be obtained, which can lead to cost reduction.
In addition, since the analysis is performed using light transmitted through the raised portion, it is easy to specify a light transmission path, and measurement accuracy and reproducibility can be improved. Furthermore, since the glucose concentration in the skin tissue is analyzed non-invasively and the blood glucose concentration highly correlated with the glucose concentration in the skin tissue is estimated, the subject is compared with the blood sampling type analysis method. The burden is small, and there is almost no pain associated with the measurement.

Embodiment 2 The configuration of the optical fiber bundle 4 other than the measuring unit 10 is the same as that of Embodiment 1. As shown in FIG. 4, the optical fiber bundle 4 for receiving and emitting light is arranged in the measuring unit 10 via a groove D cut into a U-shape as shown in FIG. 4. The optical fiber bundle 4 is obtained by bundling 14 optical fiber wires having a cladding diameter of 200 μm in a sheet shape, and mirror-finish the end of the optical fiber bundle with a polishing machine. The groove D cut into a U-shape has a width Dw of 2 mm and a depth Dt of 2 mm, and the light receiving / emitting optical fiber bundle 4 is arranged so that the optical axes coincide at the uppermost position of the groove D. By arranging the light receiving and emitting means in this manner, a larger amount of light can be received by the light receiving means.

Embodiment 3 The configuration of the optical fiber bundle 4 other than the measuring unit 10 is the same as that of Embodiment 1. As shown in FIG. 5, the measuring unit 10 also serves as a support 14 for protecting the sheet-like portion of the optical fiber bundle 4, and changes the width of the measuring end on the circumference by opening and closing the sheet-like portion. Displacement means 1
6 is provided. The displacement means 16 is a leaf spring whose end is fixed to the measuring unit 10, and the opening / closing operation is performed so that the measuring end draws a circle around the vicinity of the fixed part. The measurement is performed by pressing the living tissue 11 against the measuring unit 10. When the measuring unit 10 is in a non-weighted state, the measuring end interval Dw1 of the optical fiber is about 3 mm as shown in FIG. 5B, and the living tissue 11 comes into contact with the measuring end of the optical fiber bundle 4 during measurement. At the same time, the skin tissue of the contact portion is pinched, and the pinching is completed when the living tissue 11 collides with the main body of the measurement unit 10 as shown in FIG. The distance Dw2 between the measurement ends of the optical fiber at the time when the skin tissue is pinched is about 1 m.
m.

By using the optical fiber bundles 4 arranged in a sheet shape as a means for sandwiching the skin tissue, the transmission spectrum analysis of the skin tissue with a simple configuration has become possible. In addition, in the present embodiment, in the operation of lightly pressing the living tissue against the measurement unit at the time of measurement, since the skin tissue can be raised, the measurement is very easy,
If the measurement site is located at the same position, the amount of skin picked up (raised) is constant, and measurement with good reproducibility is possible. In addition, there is almost no pain associated with the raised skin.

Embodiment 4 The configuration of the measuring section 10 is the same as that shown in Embodiment 3, but here, a support 14 arranged below the optical fiber is provided.
As shown in FIG.
It protrudes about 2 mm. In this case, it is possible to reduce the possibility of breakage of the optical fiber and to reduce the influence of stray light circling around the raised skin tissue.

Embodiment 5 The measuring section 10 shown here is basically the same as that shown in Embodiment 3, but as shown in FIG. 7, above the optical fiber bundle 4 (at the time of measurement, the skin tissue side). ) Is provided with a support 14. In this case, it becomes easier to measure the tip of the raised skin tissue, and the possibility of measuring transmitted light of unwanted tissue such as subcutaneous tissue due to pinching of the skin tissue is reduced. In Examples 4 and 5, the end of the support 14 in contact with the living body surface tissue (skin tissue) was made of rubber, or the shape of the support 14 was made uneven so that the contact with the skin could be strengthened. Measurement becomes possible.

-Embodiment 6- The configuration other than the measurement unit 10 is the same as that of the first embodiment. As shown in FIG. 8, in the measuring section 10 of this embodiment, the measuring end of the optical fiber bundle 4 for receiving and emitting light is arranged via a groove D cut into a U-shaped cross section. The groove D cut in a U-shape has a width Dw of 2 mm and a depth Dt of 2 mm, and one measuring end of the optical fiber bundle 4 for light receiving and emitting is fixed at the uppermost position of the groove. The other measuring end is configured to be slidable on the optical axis in the horizontal direction, and serves as a protruding means for picking up the living epithelial tissue with the optical fiber bundle 4 for light receiving and emitting. In the sheet-like portion of the optical fiber bundle 4, a support 14 for protection and for guiding the movement in the optical axis direction is arranged below the sheet-like portion. The measurement is performed by pressing the living tissue 11 against the measuring unit 10. The living tissue 11 is gently pressed against the measuring unit 10 to gently lift the living tissue 11 as shown in FIG. 8A, and then the measuring end of the optical fiber bundle 4 as shown in FIG. Is slid to sandwich the living body surface tissue (skin tissue) 11 to make the light emitting / receiving interval appropriate. The biological surface layer tissue 11, which is preliminarily gently raised by a wide U-shaped groove, is further sandwiched between the measurement ends of the optical fiber bundle 4 to optimize the light emitting and receiving interval. Therefore, it is necessary to strongly press the tissue during measurement. And reliable measurement is possible.

Embodiment 7 The configuration other than the measuring unit 10 is the same as that of the embodiment 1. As shown in FIG. 9, the measuring section 10 of this embodiment has a sheet-like measuring end portion of the optical fiber bundle for light receiving and emitting 4 oppositely disposed via a groove D cut in a V-shape. The V-shaped groove D has a width Dw of 1.5 mm and a depth Dt of 1.5 mm, and is connected to a suction pump 18 for exhausting the groove D through an exhaust pipe 17. Measurement is for living tissue 11
Is lightly pressed against the measuring unit 10 and the pressure inside the groove D is lowered by the suction pump 18 so that the living body surface tissue 11 is raised. Since the living body surface tissue (skin tissue) can be reliably raised, it is not necessary to strongly press the tissue during measurement. .

Embodiment 8 As shown in FIG. 10, this embodiment is a combination of the suction pump 18 shown in Embodiment 7 and the slide structure shown in Embodiment 6. The groove D has a width Dw of 3 mm and a depth D
t is set to 2 mm, the living tissue 11 is gently pressed against the measurement unit 10 to gently lift the living tissue, and at the same time, the air pressure inside the groove D is lowered by the suction pump 18 so that the living surface tissue 11 is surely raised. The measurement end of the optical fiber bundle 4 is slid and the living body surface tissue (skin tissue) 1 is moved.
By interposing 1, the light receiving / emitting interval is optimized.

Embodiment 9 As shown in FIG. 11, a light source 1 is arranged on one side of a groove D cut in a U-shape through a slit 3 having a width of 0.2 mm. An end face of an optical fiber bundle 4 in which optical fiber wires having a cladding diameter of 200 μm are bundled in a sheet shape is disposed on the inner wall surface of the optical fiber bundle 4. The width Dw of the groove D is 2 mm, and the depth Dt is 2 mm. Light source 1 has a center wavelength of 1600 n
m, the half-width of the light emitting diode 22 is 160 nm,
Through the ball lens 21, the reflecting surface 20, and the slit 3, light is guided into the groove D into which the raised living body surface tissue 11 fits, and the light transmitted through the living body surface tissue 11 is transmitted to the optical fiber bundle 4. Lead. Since the light emitting diode 22 is used as the light source, the measuring unit 10 can be made compact, and the number of locations where the optical fiber bundle 4 is used can be reduced, so that the assembling is easy and the cost can be reduced. In the figure, reference numeral 23 denotes a heat sink. As in other embodiments, the light may be guided from the light source 1 such as a halogen lamp by the optical fiber bundle 4. In this case, since the slit 3 can be used, it is not necessary to process the end face of the optical fiber bundle 4 into a sheet.

Embodiment 10 In the embodiment 9 described above, the optical fiber bundle 4 is used on the light receiving side. Here, as shown in FIG.
The light transmitted through the living body surface tissue 11 is guided to the light receiving element unit 5 as a photodiode through the slit 3 ′ and the reflection surface 20 ′. As the light receiving unit 5, a unit in which three photodiodes 22 are arranged in parallel to the slit 3 'is used, and a unit in which the three photodiodes 22 are covered with interference filters having different wavelength characteristics is used. , So that the absorbance of three wavelengths can be measured at the same time. The interference filter has a transmission center wavelength of 1
Those having 540 nm, 1580 nm and 1685 nm were used. It is not limited to this wavelength, nor is the number of wavelengths used limited to three. In any case, the light receiving / emitting means can be integrated into the measuring unit 10 so as to be compact.

-Embodiment 11- As shown in FIG.
Embodiment 10 is different in that the light source 1 using the light emitting diode 22 and the light receiving unit 5 using the photodiode 25 are used.
The same as above, but with plate-like portions 33, 33 having slits 3
A displacement means 16 is provided for changing the width of the measuring end (slit 3 portion) on the circumference by opening and closing the opening. As the displacement means 16, a leaf spring whose end is fixed to the measuring unit 10 is used. Therefore, the opening and closing operation is performed so that the measuring end draws a circle around the vicinity of the fixed part.

The measurement is performed by pressing the living tissue against the measuring section 10. When the measuring unit 10 is in a non-weighted state, as shown in FIG. 13A, the measuring end interval (the interval between the slits 3 and 3) Dw
l is about 3 mm open, and when the living tissue 11 comes into contact with the measurement end at the time of measurement, it begins to pinch the skin tissue of the contact portion,
As shown in FIG. 13B, the entrapment ends when the living tissue 11 collides with the measurement unit main body. The near-infrared light emitted from the light-emitting diode 22 is reflected on the reflection surface 20 and is irradiated on the living body surface tissue 11 raised through the slit 3 on the light-emitting side. The light transmitted through the living body surface tissue 11 reaches the photodiode 25 through the slit 3 on the light receiving side and the reflection surface 20. The arriving light is converted into an electric signal, and the glucose concentration is calculated by a calibration formula in a personal computer (arithmetic unit). In this example, a calibration equation derived from multiple regression analysis was used.

Embodiment 12 As shown in FIG. 14, the measuring section 10 of this embodiment has a roller 26 penetrating an optical fiber bundle 4 having a sheet-like shape and an end portion of which is mirror-finished by a polishing machine. The rollers 26 on the light-emitting side and the light-receiving side normally make the light-receiving fiber bundle 4 and the light-emitting fiber bundle 4 parallel in the vertical direction, but contact the living tissue 11 and rotate the rollers 26 in the direction of the arrow. When this is done, the living body surface tissue 11 at the contact portion is lifted to sandwich the skin tissue 11 as shown in FIG. 14 (b), and at this point the optical axes of the light receiving and emitting optical fibers are almost coincident.

Embodiment 13 The measuring section 10 shown in FIG.
The optical fiber bundles 27 and 27 are the same as those shown in FIG. The same optical fiber bundle 27 as the optical fiber bundle 4 can be used as the optical fiber bundle 27. For example, 14 optical fiber strands each having a length of 1 cm and a cladding diameter of 200 μm are bundled in a sheet shape, and the ends are mirror-finished with a polishing machine. Finished products can be used. By making the optical fiber at the end of the light receiving and emitting means detachable in this way, even if the optical fiber at the tip that is likely to be damaged by measurement is damaged, it can be easily repaired by replacing the tip. Can be done.

The present invention is not limited to these embodiments. In addition, an example that can be preferably used for blood glucose measurement using the property that the correlation between glucose concentration in human skin tissue and glucose concentration in blood is high has been described, but it is needless to say that the present invention is not limited to this. .

[0044]

According to the present invention, light in a wavelength range having poor transmittance is used for raising a part of the surface tissue of a living body and performing spectroscopic analysis using light transmitted through the raised tissue. It also makes it possible to perform non-invasive analysis, and it is also possible to perform quantitative and qualitative analysis of chemical components or physical properties of living epithelial tissues such as skin tissues and mucous membranes in a transmission system with individual differences and measurement sites. Can be performed in a state in which the influence of is small. Also, a relatively ordinary light source such as a normal halogen lamp, a light emitting diode (LED), or a laser diode as a light receiving / emitting means, Si, Ge, or InGaAs is used.
In addition to being able to perform spectral analysis with a common light receiving element such as a photodiode manufactured by the company and simple light collecting means, it is easy to assemble a measurement portion that receives and emits light from a living tissue, thereby enabling low-cost analysis. In addition, by using transmitted light for analysis, it is easier to specify a tissue through which light is transmitted than when (diffuse) reflected light is used, and a simulation of the light transmission state can be easily performed. Became.

[Brief description of the drawings]

FIG. 1 shows an example of an embodiment of the present invention, in which (a)
(b) is a sectional view.

FIG. 2 is a schematic diagram showing an overall configuration of the above.

FIG. 3 is a perspective view of an optical fiber bundle used in the same.

FIG. 4 is a cross-sectional view showing another example.

5A and 5B show still another example, in which FIG. 5A is a plan view, FIG. 5B is a side view, and FIG. 5C is a sectional view.

FIG. 6 is a cross-sectional view of another example.

FIG. 7 is a sectional view of still another example.

FIG. 8 shows a different example, and (a) and (b) are cross-sectional views.

FIG. 9 shows another example, and (a) and (b) are cross-sectional views.

FIG. 10 shows still another example, in which (a) and (b) are cross-sectional views.

FIG. 11 is a cross-sectional view of another example.

FIG. 12 is a cross-sectional view of still another example.

FIG. 13 shows a different example, and (a) and (b) are cross-sectional views.

FIGS. 14A and 14B show still another example, and FIGS. 14A and 14B are cross-sectional views.

FIG. 15 is a sectional view of another example.

FIG. 16 is a cross-sectional view showing a skin tissue.

FIG. 17 is an explanatory diagram of a light transmission path called a banana shape.

[Explanation of symbols]

 4 Optical fiber bundle 10 Measuring unit 11 Living body surface tissue

Claims (15)

[Claims] 1. Analysis of the properties of the surface tissue of a living body, preferably skin tissue or mucosal tissue, more preferably the characteristic of dermal tissue, subcutaneous tissue or mucosal lamina propria or submucosa in skin tissue by absorption of light. Is a method for
Biological surface tissue characterized by performing a spectral analysis by raising and lowering a part of the surface tissue of a living body and performing a light emitting / receiving operation from a light emitting portion opposed to the light incident portion through the raised portion to a light incident portion. Analysis method. 2. The method according to claim 1, wherein a distance between the light emitting portion and the light incident portion is 5 mm or less, and preferably 2 mm or less. 3. The living body surface tissue according to claim 1, wherein the light emitting / receiving position by the light emitting / receiving means is within 5 mm, preferably within 2 mm, from the convex top end of the raised surface tissue. Analysis method. 4. The method for analyzing a surface tissue of a living body according to claim 1, wherein a part of the surface tissue of the living body is raised. 5. The living tissue according to claim 1, wherein a part of the living tissue is raised by a pressing pressure caused by abutting a measuring unit provided with a light emitting / receiving means on the surface tissue of the living body. The method for analyzing a living body surface tissue according to the above. 6. Analyzing the properties of the surface tissue of a living body, preferably the skin tissue or mucosal tissue, more preferably the dermal tissue, the subcutaneous tissue or the mucosal lamina propria or the submucosal layer in the subcutaneous tissue or mucosal tissue by light absorption. A device for raising a part of the surface tissue of a living body and guiding it between a light emitting part and a light incident part in a light emitting and receiving means. . 7. The living body surface tissue according to claim 6, wherein the means for raising a part of the living body surface tissue is a groove on the inner wall surface, the light emitting portion and the light incident portion facing each other. Analysis equipment. 8. The living body according to claim 6, wherein the means for raising a part of the surface tissue of the living body is a displacement means capable of displacing a light emitting portion and a light incident portion facing each other. Surface tissue analyzer. 9. The apparatus for analyzing a living body surface tissue according to claim 6, wherein the means for raising a part of the living body surface tissue is a roller. 10. The living body surface tissue analyzing apparatus according to claim 6, wherein the means for raising a part of the living body surface tissue is a reduced-pressure suction means. 11. The method according to claim 6, wherein at least one of the light emitting portion and the light incident portion is a slit, and the width of the slit is 1 mm or less, preferably 0.5 mm or less. The biological surface tissue analyzing apparatus according to the above item. 12. The living body surface tissue analyzing apparatus according to claim 6, wherein at least one of the light emitting portion and the light incident portion is an optical fiber or an optical fiber bundle. 13. The living body surface tissue analyzing apparatus according to claim 12, wherein the optical fiber bundle is formed by arranging a plurality of optical fiber wires in a sheet shape. 14. The living body surface tissue analyzing apparatus according to claim 13, wherein the sheet-like optical fiber bundle is provided with a support for maintaining this form. 15. The living body surface tissue analyzer according to claim 6, wherein the light emitting portion and the light incident portion are detachable.