JP4120684B2 - Blood component concentration analyzer by spectroscopic analysis - Google Patents

Description

The present invention relates to an apparatus for analyzing blood component concentrations by spectroscopic analysis.

  Spectroscopic analysis using 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 vibrations in the infrared region, and the harmonics of resonance of molecular vibrations in the near infrared region can be measured. Based on the analysis.

  Near-infrared spectroscopic methods for quantitative and qualitative analysis of substances using near-infrared light adjacent to the visible region among these wavelengths have recently been used in various fields including the agricultural field. Recently, it has attracted attention as a non-invasive and harmless analysis method in the field of living organisms. Near-infrared spectroscopic analysis is a technique in which light having a wavelength of 0.8 μm to 2.5 μm is irradiated onto a substance, and analysis is performed from the spectrum of transmitted or reflected light. This near-infrared spectroscopic method uses electromagnetic waves with low energy, so it can be applied to samples in various states such as solids, powders, fibers, liquids, and gases that do not damage the sample compared to infrared light. Since the absorption intensity of water is weakened by infrared light, it has an advantage that analysis in an aqueous solution is possible, and it is possible to non-invasively perform quantification and qualitative analysis of blood component concentration such as glucose.

  However, when using near-infrared light, the absorption signal is very weak compared to infrared light in order to deal with harmonics, and the band assignment is not clear. In the near-infrared spectroscopic analysis, a technique called “chemometrics” is used for quantification and qualification. This is a method of performing chemical analysis using multivariate analysis methods and statistical analysis methods, and has evolved with the development of computers. In recent near infrared spectroscopy, multivariate analysis methods such as principal component regression analysis or PLS regression analysis are used. Often used. Attempts have also been made to apply neural networks to analysis.

  A moisture meter is a conventional example using near infrared spectroscopy for chemical component analysis. Several types of moisture meters using near-infrared light are currently available on the market, but simple moisture determination in the early days has a neutral wavelength of 2.08 μm, which is not related to the absorbance at 1.93 μm of water absorption and the absorption of substances. Is carried out using a calibration curve obtained in advance by a single regression equation between the difference in absorbance (difference absorbance) and water. In actual measurement, the differential absorbance is measured, and the moisture content of the substance is measured by comparison with a calibration curve. However, since the moisture amount measurement is performed by irradiating the material surface with light and detecting the reflected light, there is no ability to selectively detect the moisture amount in the depth direction near the surface.

  Also, a method different from the spectroscopic method has been proposed. This is an attempt to determine the glucose concentration by spatially resolved measurement of multiple scattered light, as shown in JP-A-8-502912. Is measured at two light receiving and emitting intervals, and the glucose concentration is determined based on the dependence of the intensity on the light emitting and receiving intervals.

Unfortunately, at present, however, non-invasive quantitative qualitative analysis of blood component concentrations such as glucose has not yet been put into practical use. This is because the skin tissue in a living tissue is composed of an epidermis having a thickness of about 300 μm, a dermis tissue having a thickness of about 1 mm under the skin, and a sebaceous tissue having a large amount of fat cells in the lower layer. This is probably because it is assumed that the living tissue is homogeneous. In a biological tissue in which a complicated tissue structure is entangled, the concentration of a biological component such as glucose varies greatly depending on the tissue, and accurate quantification cannot be expected without taking this point into consideration.
Japanese National Patent Publication No. 8-502912

The present invention was invented in view of the conventional problems described above, and an object thereof is to provide an analyzer of the blood constituent concentration can be accurately quantified blood constituent concentration such glucose noninvasively Is.

The analyzer of the blood constituent concentration according to the present invention in order to solve the above problems, the blood constituent concentration of the biological and an analytical device for performing spectroscopic analysis of near-infrared light, in the range of 1,300~2,500nm A light-emitting optical fiber comprising a projection unit that projects near-infrared light having a wavelength onto the surface of a living body surface tissue, and a detection unit that detects near-infrared light from the surface tissue surface of the living body, one end of which is connected to a light-emitting means. The other end of the optical fiber is the projection unit, and the other end of the optical fiber for light reception whose one end is connected to the light receiving means is the detection unit. The spacer is interposed between the optical fiber for light emission and the optical fiber for light reception. The interval between the projection unit and the detection unit is determined by the interval at which the near infrared light introduced from the projection unit into the living tissue and detected by the detection unit selectively transmits the dermis part in the surface tissue of the living body or the dermis part. Selection And a calculation means for performing a quantitative analysis by using a correlation between the concentration of the blood component of the component for the purpose of quantification and the concentration in the dermis part. It has the feature in being.

In the skin tissue of the living body, the dermis part is highly correlated in terms of its concentration with respect to blood components, and near infrared light is selectively transmitted to the dermis part and selectively diffusely reflected by the dermis part. It is focused on the fact that it is possible. That is, as shown in FIG. 2, when the light emitting probe P and the light receiving probe R are arranged in parallel and face the measuring object 9, the light emitted from the light emitting probe P and observed by the light receiving probe R is so-called “banana shape”. It is confirmed experimentally and in a simulation using a numerical analysis method, and at this time, the depth direction of the measurement object 9 is adjusted by adjusting the distance between the light emitting probe P and the light receiving probe R. Focusing on the fact that the degree of light arrival at the surface can be changed, the distance between the projection unit that guides near-infrared light to the surface tissue surface of the living body and the detection unit that extracts near-infrared light from the surface tissue surface is 2 mm or less. Thus, near infrared light selectively transmitted through the dermis part or near infrared light selectively diffused and reflected by the dermis part is taken out and a near infrared light analysis is performed.

    In the light receiving and emitting intervals such as 3 mm and 5 mm shown in the embodiment of the publication, not only the signal of the dermis tissue but also the signal superposed with the signals of the muscle tissue and the fat tissue located in the lower layer is detected. Therefore, it is difficult to accurately measure the glucose concentration from a complex biological tissue even if a signal obtained by detecting two spatially separated near-infrared lights is used. Among them, the best glucose signal (that is, a glucose signal highly correlated with the blood glucose concentration) can be selectively extracted from a stable dermal tissue with little disturbance.

In addition, although it is practically difficult to provide the light emitting probe and the light receiving probe at the intervals as described above, the other end of the optical fiber for light emission, one end of which is connected to the light emitting means, is used as the projection unit, and the other end is used as the light receiving means. This problem can be solved by using the other end of the connected optical fiber for detection as a detection unit, and the projection unit and the detection unit are interposed by a spacer interposed between the optical fiber for light emission and the optical fiber for light reception. Therefore, it is possible to easily set the interval for selectively transmitting the dermis portion and selectively reflecting the dermis portion .

  An optical fiber having a wire diameter of 1 mm or less can be suitably used. An optical fiber having a diameter of several μm to several thousand μm (several mm) can be used, and among these, use of an optical fiber having a diameter of 70 μm to 1000 μm is particularly suitable. If what is used for the use which performs the quantitative analysis of the chemical component in a human dermis is described, as shown in FIG. 3, the human dermis 9b is the epidermis 9a about 300 micrometers thick, and the subcutaneous tissue 9c which consists of many fat cells. As shown in FIG. 1, an optical fiber having a wire diameter of 250 to 750 μm, for example, a bundle of optical fibers having a thickness of 500 μm is used for analysis of blood components in the dermis 9b. By producing a simple optical fiber and performing spectroscopic analysis, blood components in the dermis 9b can be analyzed. Since the path of light transmitted through the skin tissue varies depending on the physical properties of the tissue and the wavelength used for analysis, it is necessary to perform preliminary experiments and numerical simulations in advance to determine the wire diameter used for measurement. The obtained absorbance signal is numerically calculated by the calculation unit to calculate the target component concentration.

  Glucose can be raised as the target blood component. At this time, since a glucose signal highly correlated with blood glucose concentration can be obtained from the dermal tissue, quantitative analysis of glucose concentration should be performed with high accuracy. However, it is not limited to glucose.

A plurality of projection units for guiding near-infrared light to the surface tissue surface of the living body and detection units for extracting near-infrared light from the surface tissue surface are provided, and the minimum distance between the two points is 2 mm or less, preferably 1 mm or less. However, it is possible to selectively transmit the dermis part and selectively diffusely reflect the dermis part.

  In spectroscopic analysis using near-infrared light, near-infrared light having a wavelength in the range of 1,300 to 2,500 nm can be suitably used. A signal with a good S / N ratio cannot be obtained with light of less than 1,300 nm. Although it has excellent permeability in the living body, since the absorption signal is very small, it is difficult to quantify components such as glucose contained in trace amounts in the dermis tissue in measurement at the light receiving and emitting intervals set to 2 mm or less. This is because the wavelength of 1,300 to 2,500 nm is inferior in permeability in the living body, but the absorption signal is large, the S / N ratio is good, and the analysis accuracy is improved.

  Even within the above wavelength range, a preferable result is obtained by using at least one of near infrared light having a wavelength in the range of 1,400 to 1,800 nm or near infrared light having a wavelength in the range of 2,000 to 2,500 nm. Obtainable.

It is also preferable to use, as reference light, near-infrared light selectively transmitted through the epidermis part in the surface tissue of the living body or near-infrared light selectively diffused and reflected at the epidermis part. Since the absorption signal of the dermal tissue that is not affected by the epidermal tissue can be extracted, more accurate quantification can be performed. In this case, the light from the epidermis part can be detected by making the interval between the projection unit and the detection unit for measuring the reference light smaller than the interval for the spectroscopic analysis. The reference light is easily affected by the environment outside the living body, such as the epidermal tissue, especially the stratum corneum, and is mainly transmitted or diffusely reflected through the tissue where there are almost no capillaries. By using transmitted light or diffusely reflected light having a large contribution as the reference light, an absorption signal of the dermal tissue can be extracted, and more accurate quantification can be performed.

Also, by using an optical fiber, a light source with a relatively low light quantity such as a normal halogen lamp or light emitting diode without using special light receiving and emitting parts, or a normal light receiving such as a photodiode made of Si, Ge or InGaAs. Even when the element is used, a sufficient amount of light or light receiving sensitivity for analyzing the chemical composition in the vicinity of the surface of the substance can be obtained.

  In this case, when the reference light is used together, the interval between the reference light projection unit and the detection unit is set shorter than the single distance. For example, it is 0.5 mm or less, preferably 0.35 mm or less.

  The component concentration is calculated using a calibration curve or a calibration equation. A calibration curve or a calibration equation can be obtained in advance by analyzing absorption spectra in various states of an individual or a plurality of subjects. The analysis is a method of performing quantification and qualitative analysis using a multivariate analysis method or a statistical analysis method, and in the near-infrared spectroscopic analysis, a multivariate analysis method such as principal component regression analysis or PLS regression analysis is often performed. .

  In spectrum measurement, light from a light source such as a halogen lamp is split into light of an arbitrary wavelength using an optical filter such as an interference filter, or a single color light source such as a light emitting diode or laser diode is combined to obtain absorbance at multiple wavelengths. The light absorption spectrum of a predetermined wavelength is continuously obtained by using a diffraction grating or a Fourier transform method (FT-IR method) for light from a light source such as a halogen lamp as in a measurement method or a normal spectroscopic analysis method. It doesn't matter

In the present invention, the dermis portion in the skin tissue of a living body is highly correlated in terms of the concentration with respect to the blood component, and light that is selectively transmitted through the dermis portion or selectively diffusely reflected by the dermis portion. In order to perform spectroscopic analysis, it is possible to perform analysis with extremely high accuracy. Moreover, the other end of the light-emitting optical fiber whose one end is connected to the light-emitting means, the other end of the light-receiving optical fiber whose one end is connected to the light-receiving means, and the projection unit and the surface-layer structure that guide near-infrared light to the surface tissue of the living body. Since the detection unit for extracting near-infrared light from the surface is formed at the other end of the optical fiber for light reception, the projection unit and the detection unit are spaced at intervals of 2 mm or less to obtain light that is selectively diffusely reflected at the dermis. Can be realized without incurring physical problems, and a light source having a relatively low light quantity such as a normal halogen lamp or light emitting diode, Si, Ge, Even if a normal light receiving element such as an InGaAs photodiode is used, sufficient light quantity or light receiving sensitivity can be obtained for non-invasive analysis of blood component concentration. , Even select the interval between the projection portion and the detector since it is set by spacers interposed between the light-emitting optical fibers and light receiving optical fiber, in the dermal portion or to selectively transmits dermal portion It is possible to easily set the interval for reflecting light.

In addition, since the above-mentioned spacer is used, it is difficult to limit the diameter of the optical fiber to be used, and an appropriate optical fiber can be selected and used. In addition, when obtaining a reference, it is possible to obtain an optical fiber having the same diameter. It becomes.

Hereinafter, the present invention will be described with reference to an embodiment shown in the accompanying drawings. The one shown in FIG. 4 is for quantifying the glucose concentration in human skin tissue. A diffraction grating unit 2 containing a diffraction grating for spectrally separating the light from the light source, a stepping motor unit 3 for adjusting the spectral wavelength by controlling the rotation angle of the diffraction grating, and transmitting the light after spectroscopy to the object to be measured An optical fiber bundle 4 that transmits transmitted light to the light receiving unit 5 and an arithmetic unit 6 that performs numerical analysis based on a signal from the light receiving unit 5 and quantifies the glucose concentration.

  As shown in FIG. 6, the optical fiber bundle 4 is a bundle of two large-diameter fibers having a cladding diameter of 750 μm in contact with each other on one end B side serving as a measurement probe P. The cladding diameter is determined according to the thickness of the target dermis 9b tissue, and a 750 μm one is a suitable example. The end A of the light emitting optical fiber 4a of the optical fiber bundle 4 is connected to the diffraction grating unit 2, the end C of the light receiving optical fiber 4b is connected to the light receiving unit 5, and the end B is abutted at right angles to the skin to be measured. I do.

  If the distance between the light-emitting optical fiber 4a and the light-receiving optical fiber 4b, which are appropriately selected in this way, is specified, the transmitted light path (depth) is selected as shown in FIG. The dermis tissue 9b can be selectively transmitted (or selectively diffusely reflected by the dermis tissue 9b). Therefore, it is possible to easily analyze the blood component concentration in the dermal tissue 9b. Also, the optical fiber bundle 4 can be easily manufactured. If a combination of a pressure gauge and a pressing jig is used so that the pressing force to the skin of the end B is constant at the time of measurement, a highly accurate measurement can be performed.

  The light receiving unit 5 amplifies a light reception signal of an InGaAs photodiode having a light reception sensitivity range of 0.9 to 1.7 μm, and then AD converts the signal to transmit the signal to an arithmetic unit including a microcomputer. For quantitative determination of glucose concentration performed in the arithmetic unit, a multivariate analysis is performed using an absorption spectrum belonging to the near infrared region of 1.25 μm to 1.7 μm. This multivariate analysis uses a calibration curve (calibration formula) obtained by PLS (Partial Least Square) regression analysis. This calibration curve is obtained in advance from an experiment using the analyzer. That is, a calibration curve is obtained by performing PLS regression analysis with the absorption spectra measured from the skin tissues of a plurality of subjects as explanatory variables and the glucose concentration in the measured dermal cell fluid as a target variable.

  FIG. 5 shows another example. Here, light from a halogen lamp 1 of about 150 W provided with the reflecting mirror 10 is introduced into the light-emitting optical fiber 4 a through the lens 11, and light emitted from the light-receiving optical fiber 4 b is passed through the slit 20 to the flat field diffraction grating unit 2. The arrayed light receiving unit 5 receives the light guided and separated by the diffraction grating unit 2. In the figure, reference numeral 60 denotes an A / D conversion device arranged between the light receiving unit 5 and the arithmetic unit 6. For the light receiving unit 5, for example, an InGaAs photodiode having a light receiving sensitivity range of 0.9 to 2.1 μm is linearly arranged in 256 elements and cooled by a Peltier element. The arithmetic unit 6 uses the absorption spectrum belonging to the near-infrared region of 1.4 μm to 1.8 μm and quantifies the glucose concentration using a calibration equation (calibration curve) as in the above case.

  FIG. 7 shows another example of the optical fiber bundle 4. This shows an end B serving as a measurement probe P of the optical fiber bundle 4, and here, an optical fiber having a clad diameter of 750 μm bundled in a cage-like lattice is used, and a central optical fiber (indicated by a diagonal line in the figure). The light-emitting optical fiber 4a and the surrounding six optical fibers are light-receiving optical fibers 4b. By disposing the light-receiving optical fiber 4b around the light-emitting optical fiber 4a, more transmitted light attenuated / scattered during permeation of the skin tissue can be collected, so that highly accurate analysis is possible.

  FIG. 8 shows a bundle of about 70 optical fibers having a cladding diameter of 500 μm at the end B. The ratio of the number of light-emitting optical fibers (hatched in the figure) 4a and the number of light-receiving optical fibers 4b is set to about 1: 2, and the light-receiving optical fiber 4b is regularly surrounded by the light-receiving optical fiber 4b. It is a simple array. With such an optical fiber bundle 4, the amount of emitted light and the amount of received light can be determined by adjusting the number of optical fibers in accordance with the capabilities of the light source and the light receiving element, so that highly accurate analysis is possible.

  In the case shown in FIG. 9, when about 70 optical fibers having a clad diameter of 500 μm are randomly bundled at the end B, the ratio of the number of light emitting optical fibers (hatched in the figure) 4a and the number of light receiving optical fibers 4b is About 1: 3. In this case, even if bundled at random, the light receiving optical fiber 4b substantially surrounds the light emitting optical fiber 4a, and the performance almost equivalent to that shown in FIG. 7 can be obtained without performing the regular arrangement. . With this optical fiber bundle 4, the number of optical fibers can be adjusted according to the capabilities of the light source and the light receiving element, thereby enabling high-precision analysis and making the optical fiber bundle 4 easy.

  Here, when a large number of optical fibers are arranged regularly or randomly, the minimum distance between the light-emitting optical fiber 4a and the light-receiving optical fiber 4b is determined by adjacent ones, but various distances are generated. Become. However, anything other than the minimum interval may be substantially ignored. That is, as shown in FIG. 2B, with the light-emitting optical fiber 4a and the light-receiving optical fiber 4b in contact with each other, the end face of the light-receiving optical fiber 4a is brought into contact with the surface of the measuring object 9 at a right angle. However, if the light is sent to the surface of the measurement object 9 through the light emitting optical fiber 4a, the optical path to the adjacent light receiving optical fiber 4b, the optical path to the further away optical fiber 4b, and the farther light receiving light The light is incident on the light receiving optical fiber 4b through various optical paths such as the optical path C to the optical fiber 4b. Here, comparing the optical path lengths of the optical paths A, B, and C, when optical fibers having the same diameter are used for the light receiving and emitting optical fibers 4a and 4b, the optical paths B and C are considered to be almost twice or three times the optical path A. Good. Strictly speaking, the transmission of light in a material such as a living body that is optically opaque and highly scattered does not follow Lambert-Beer's law, but the amount of transmitted light decreases rapidly according to the optical path length, and the optical path length is doubled. Then, depending on the scattering state, it becomes 1/10 or less, and when the optical path length is tripled, it becomes about 1/10 or less. For this reason, the transmitted light condensed on the light receiving optical fiber 4b can be basically considered as the sum of the transmitted light from the adjacent light emitting optical fibers 4a. The light transmission path can be set to a required depth by the distance between the centers of the optical fibers for light reception 4b arranged in contact therewith.

  As shown in FIG. 10, an optical fiber having a cladding diameter of 250 .mu.m and nylon coating may be used to bundle about 50 fibers whose outer diameter is 500 .mu.m. Here, the ratio of the number of light-emitting optical fibers (hatched in the figure) 4a to the light-receiving optical fibers 4b is about 1: 2, and the light-receiving optical fiber 4b surrounds the light-emitting optical fibers 4a. Are arranged. If this optical fiber bundle 4 is used, high-precision analysis can be performed by adjusting the number of optical fibers according to the capabilities of the light source and the light receiving element, and the light receiving and emitting part of the optical fiber is limited to the central portion of the wire diameter. Therefore, the limitation of the optical path can be made sharper and analysis with high resolution becomes possible.

  The one shown in FIG. 11 is a further bundle of the optical fiber bundle shown in FIG. 7. When the bundle shown in FIG. 7 is taken as one unit, the bundle shown in FIG. Of course, the light-emitting optical fiber (hatched in the figure) 4a and the light-receiving optical fiber 4b are individually bundled at the opposite ends to form the ends A and C. If this optical fiber bundle 4 is used, highly accurate analysis can be performed by adjusting the number of optical fibers according to the capabilities of the light source and the light receiving element, and the optical fiber bundle 4 can be easily manufactured.

  FIG. 12 shows another example. Although the basic configuration is the same as that shown in FIG. 4, the optical fiber bundle 4 used here is a light-emitting optical fiber 4a having a cladding diameter of 500 μm at the end B as shown in FIG. 1) and two light receiving optical fibers 4b having clad diameters of 500 μm and 250 μm are bundled together.

  The other end A of the light emitting optical fiber 4 a is connected to the diffraction grating unit 2, and the other ends C and D of the two light receiving optical fibers 4 b and 4 b having different diameters are led to individual light receiving elements in the light receiving unit 5. . The light received by the light receiving optical fiber 4b having the smaller diameter can be used as the reference light. That is, as shown in FIG. 14, the transmitted light received by the 500 μm diameter light receiving optical fiber 4b is mainly transmitted through the dermis tissue 9b, and the transmitted light received by the 250 μm optical fiber 4b is mainly transmitted through the epidermis tissue 9a. Therefore, only the spectrum of the dermal tissue 9b can be extracted by using the difference spectrum. Of course, the optical fiber diameter is not limited to the above value, and the wire diameter is appropriately selected. In any case, the reference measurement indispensable in the spectroscopic analyzer can be performed with the same optical fiber bundle 4, and simultaneous measurement is possible by using two light receiving elements. Of course, such a configuration can also be applied to the optical fiber bundle 4 shown in FIGS.

  For example, in the optical fiber bundle 4 shown in FIG. 15, the end portion B is configured as a bundle of a plurality of optical fibers having cladding diameters of 500 μm and 250 μm, and several of the 500 μm diameter optical fibers are used as light emitting optical fibers (in the figure). 4a, and the rest of the 500 μm diameter optical fiber and the 250 μm optical fiber are used as the light receiving optical fiber 4b. The light-emitting optical fiber 4a and the light-receiving optical fiber 4b are regularly arranged so that the optical fiber can be used efficiently. If this optical fiber bundle 4 is used, high-precision analysis can be performed by adjusting the number of optical fibers according to the capabilities of the light source and the light receiving element. In the optical fiber bundle 4 shown in FIG. 16, two optical fibers with a cladding diameter of 500 μm and two optical fibers with a diameter of 250 μm are bundled as one unit, and this is configured as a bundle of seven units, and the cladding diameter in each unit Is a light emitting optical fiber 4a, and the remainder of the 500 μm diameter optical fiber and the 250 μm optical fiber are used as the light receiving optical fiber 4b. The light receiving optical fiber 4b is bundled separately at the opposite end according to the wire diameter to form an end C and an end D. If this optical fiber bundle 4 is used, it is possible to perform high-precision analysis by adjusting the number of optical fibers according to the capabilities of the light source and the light receiving element, and it is easy to manufacture the optical fiber bundle.

  17 and 18 show another example. The optical fiber bundle 4 used here uses optical fibers with cladding diameters of 500 μm and 250 μm as the light-emitting optical fiber 4 a and the light-receiving optical fiber 4 b, respectively. The light-emitting optical fiber 4a having a diameter of 500 μm is bundled with a light-receiving optical fiber 4b having a diameter of 500 μm, and the light-emitting optical fiber 4a having a diameter of 250 μm is bundled with a light-receiving optical fiber 4b having a diameter of 250 μm. The ends C and D of the bundle of light receiving optical fibers 4b and 4b for each diameter are connected to the light receiving unit 5.

  The light from the end C and the end D is guided to a light receiving element (for example, an InGaAs photodiode), and the light received by the optical fiber 4b having a small diameter is used as reference light, and the light received by the optical fiber 4b having a large diameter is used. Used as measurement light. The transmitted light received by the 500 μm diameter optical fiber 4b is mainly transmitted through the dermis, and the transmitted light received by the 250 μm optical fiber 4b is mainly transmitted through the skin layer. Therefore, only the spectrum of the dermis can be extracted by using the difference spectrum. Further, a bundle with an appropriate number of fibers may be used according to the light amount of the light source and the sensitivity of the light receiving unit.

  19 and 20, an optical fiber having a cladding diameter of 500 μm is used as a light emitting optical fiber 4a, and three optical fibers having cladding diameters of 500 μm, 250 μm, and 100 μm are used as a receiving optical fiber 4b. The optical fiber bundle 4 is configured by combining a plurality of units with one unit as a unit, and the light emitting optical fibers 4a are collectively connected to the diffraction unit 2 at the opposite end as the end A, and the light receiving fibers 4b of the respective diameters are combined. Are connected to the light receiving unit 5 as ends C, D, E together for each diameter.

  The light received by the optical fiber 4b having a cladding diameter of 100 μm is used as reference light, and the light received by the optical fibers 4b having a cladding diameter of 500 μm and 250 μm is used as measurement light. The transmitted light received by the 500 μm diameter optical fiber 4b is mainly transmitted through the central part of the dermis tissue 9b, and the transmitted light received by the 250 μm optical fiber 4b is transmitted mainly through the upper part of the dermal tissue 9b or the lower part of the epidermis layer 9a. The transmitted light received by the optical fiber 4b is mainly light transmitted through the center portion of the skin layer 9a. Therefore, by using these difference spectra, the glucose concentration distribution in the depth direction can be measured at a time. Further, since the measurement light and the reference light can be measured by the same measurement, the measurement time can be shortened. Here, although optical fibers having cladding diameters of 500 μm, 250 μm, and 100 μm are used, it is possible to perform component analysis at an arbitrary depth by appropriately selecting the wire diameter. Further, a bundle with an appropriate number of fibers may be used according to the light amount of the light source and the sensitivity of the light receiving unit.

  The optical fiber bundle 4 shown in FIG. 21 is a bundle of 50 light-emitting optical fibers 4a and light-receiving optical fibers 4b each having a clad diameter of 200 μm. Both optical fibers 4a and 4b are brought into contact with each other on one end B side serving as a probe. It is bundled in the state. That is, the four light emitting optical fibers 4a adjacent to each other are positioned at the lattice points of the rectangular lattice and the light receiving optical fiber 4b is positioned at the center point of the rectangular lattice points, and at the same time, the light receiving optical fibers 4b are adjacent to each other. Four of them are bundled in a state where the light emitting optical fiber 4a is positioned at the center point of the rectangular lattice point and the lattice point of the rectangular lattice. In this case, the center-to-center distance between the light-emitting optical fiber 4a and the light-receiving optical fiber 4b is the same value as the diameter of the optical fibers 4a and 4b at any position, in this case 200 μm, and the transmitted light path (depth) is specified. Therefore, component analysis in the dermis 9b can be facilitated. Further, if a combination of a pressure gauge and a pressing jig is used so that the pressing force to the skin of the end portion B is constant at the time of measurement, a highly accurate measurement can be performed.

  As shown in FIG. 22, a row in which the optical fibers for light emission 4a are arranged and a row in which the optical fibers for light reception 4b are arranged are shifted by a half pitch, or between the optical fibers for light emission 4a as shown in FIG. A light receiving optical fiber 4b having a smaller diameter than the light emitting optical fiber 4b may be provided (for example, the light emitting optical fiber 4a has a cladding diameter of 200 μm and the light receiving optical fiber 4b has a cladding diameter of 75 μm). In the former, each row is separated into a light-emitting optical fiber 4a and a light-receiving optical fiber 4b, so that they can be easily separated and manufactured. In the latter, the diameters of the two types of optical fibers 4a and 4b are different. It is easy to separate and easy to produce.

  In each of the above examples, the distance (center distance) between the light-emitting optical fiber 4a and the light-receiving optical fiber 4b is basically determined by the wire diameter (cladding diameter) of the optical fiber. The spacer 7 may be interposed between the optical fiber 4b and the spacer 7 to set the interval. In this case as well, it is a matter of course that the diameter of the optical fiber is an element that determines the interval.

  FIG. 24 shows an example in which the spacer 7 is used. When the light emitting optical fiber 4a and the light receiving optical fiber 4b are bundled at the end B, the diameters of the light emitting optical fiber 4a and the light receiving optical fiber 4b having the same diameter are shown. A square cross-section spacer 7 having sides of equal length is prepared, and the spacer 7 is disposed in close contact between the optical fibers 4a and 4b, and the four light-emitting optical fibers 4a adjacent to each other are lattice points of a rectangular lattice. In addition, the light receiving optical fiber 4b is positioned at the center point of the rectangular lattice point, and at the same time, the four adjacent light receiving optical fibers 4b are used as lattice points of the rectangular lattice, and the light emitting optical fiber 4a is disposed in the rectangular lattice point. They are bundled in a state where they are located at the center point of the points. On the other end side of each of the optical fibers 4a and 4b, as described above, an end portion A in which only the light emitting optical fibers 4a are bundled and an end portion C in which only the light receiving optical fibers 4b are bundled are formed.

  In this case, if optical fibers 4a and 4b having a cladding diameter of 200 μm are used, the distance between the centers of the light-emitting optical fiber 4a and the light-receiving optical fiber 4b is 280 μm at any position due to the interposition of the spacer 7, and transmission Since the optical path (depth) can be specified, component analysis in the dermal tissue 9b can be easily performed. Further, since only the light-emitting optical fiber 4a and the spacer 7 or only the light-receiving optical fiber 4b and the spacer 7 are separated, the two types of optical fibers 4a and 4b can be easily separated and easily produced.

  FIG. 25 shows another example. When bundling the light emitting optical fiber 4a and the light receiving optical fiber 4b at the end B, the square-shaped spacer 7a having sides having the same length as the diameter of the light emitting optical fiber 4a and the light receiving optical fiber 4b having the same diameter, A spacer 7b having a rectangular section having a thickness (short piece length) equal to the diameter of the optical fibers 4a and 4b is prepared, and a row in which the light-emitting optical fiber 4a and the light-receiving optical fiber 4b are arranged via the first spacer 7a, In this case, the light emitting optical fiber 4a and the light receiving optical fiber 4b are shifted by one pitch in the two rows sandwiching the spacer 7b. Four adjacent to the rectangular lattice point, and the light receiving optical fiber 4b as the central point of the rectangular lattice point. Simultaneously with the location, the grid points of a rectangular grid of four mutually adjacent light receiving optical fiber 4b, which bundled emission optical fiber 4a in a state to be located at the center point of the rectangular lattice points.

  In this case, when optical fibers 4a and 4b having a cladding diameter of 200 μm are used, the center-to-center distance between the light-emitting optical fiber 4a and the light-receiving optical fiber 4b is 400 μm at any position due to the interposition of the spacers 7a and 7b. Since the transmitted light path (depth) can be specified, component analysis in the depth direction near the surface can be easily performed.

  The optical fiber bundle 4 in which the light emitting optical fiber 4a and the light receiving optical fiber 4b are bundled in a lattice shape can be manufactured as follows. The optical fiber bundle 4 shown in FIG. 21 is provided with 50 light emitting optical fibers 4a having a clad diameter of 200 μm and a length of 40 cm, and 50 light receiving optical fibers 4b having a clad diameter of 200 μm and a length of 30 cm, and FIG. As shown in FIG. 5, the five light emitting optical fibers 4a and the five light receiving optical fibers 4b are alternately arranged on the plane and bonded to obtain a flat unit. After 10 sets of this flat unit are produced, as shown in FIG. 26 (b), the units are laminated and bonded to obtain what is shown in FIG. 26 (c). At this time, the two units arranged vertically are stacked with the front and back sides different. The obtained bundle of optical fibers 4a and 4b is put in a stainless steel tube 8 shown in FIG.

  On the other end side, the light-emitting optical fiber 4a and the light-receiving optical fiber 4b are separated and bundled, and are also put in a stainless steel tube and filled with an epoxy filler. The reason why the light-emitting optical fiber 4a and the light-receiving optical fiber 4b are different in length is to facilitate the separation, but it is not limited to the length, and may be separated by color coding, for example. The end faces of the end portions A, B, and C are finally polished by a polishing machine. The optical fiber bundle 4 shown in FIG. 22 can be manufactured by the same method.

  The optical fiber bundle 4 shown in FIG. 24 is provided with 25 light-emitting optical fibers 4a having a cladding diameter of 200 μm and a length of 40 cm, and 25 light-receiving optical fibers 4b having a cladding diameter of 200 μm and a length of 30 cm. Five units are prepared by alternately arranging and bonding the optical fibers 4a and the five spacers 7 on the plane, and five units are obtained by alternately arranging the five light receiving optical fibers 4b and the five spacers 7 on the plane. After the two types of units are alternately laminated and bonded, they are formed in a stainless steel tube 8 and filled with an epoxy-based filler 91. On the other end side, the light-emitting optical fiber 4a and the light-receiving optical fiber 4b are separated and bundled, and are also put in a stainless steel tube and filled with an epoxy filler. The end surfaces of the end portions A, B and C are finally polished by a polishing machine.

  As shown in FIG. 27 (a), a spacer 7 in which a plurality of spacers are connected at one end side is used, and a light-emitting optical fiber 4a is housed in a groove between the spacers 7 and a groove between the spacers 7. Alternatively, the optical fiber 4b for receiving light may be prepared, and these may be alternately stacked and bonded as shown in FIGS. 27 (b) (c). One end connecting the spacers 7 may be scraped off during final polishing.

  In the optical fiber bundle 4 shown in FIG. 25, 18 light-emitting optical fibers 4a having a clad diameter of 200 μm and a length of 40 cm are prepared, and 18 light-receiving optical fibers 4b having a clad diameter of 200 μm and a length of 30 cm are prepared. Six units are prepared by alternately arranging optical fibers 4a, three light receiving optical fibers 4b, and five spacers 7a on a plane and bonding the units and spacers 7b. It can be formed by filling the tube 8 with an epoxy filler 91. On the other end side, the light-emitting optical fiber 4a and the light-receiving optical fiber 4b are separated and bundled, and are also put in a stainless steel tube and filled with an epoxy filler. The end surfaces of the end portions A, B and C are finally polished by a polishing machine.

  As shown in FIG. 28, if an integrated spacer 7a and spacer 7b are used, the optical fibers 4a and 4b can be housed and assembled in the groove between the spacers 7a. It becomes easy. When the spacer 7 is used, the form is not limited to the above examples. For example, as shown in FIG. 29, a rectangular wave cross-section spacer 7 in which grooves are alternately formed on the front and back sides is prepared, and a plurality of units containing optical fibers 4a and 4b are formed in the respective grooves on the front and back sides. The units may be laminated and bonded. At this time, the light-emitting optical fiber 4a may be accommodated on one side of the spacer 7 and the light-receiving optical fiber 4b may be accommodated on the other side, and the distance between the centers of the optical fibers 4a and 4b can be freely set according to the thickness of the spacer 7. it can.

  FIG. 30 shows another example of the arrangement of the light emitting optical fiber 4 a and the light receiving optical fiber 4 b and the shape of the spacer 7. Here, the spacer 7 has a cylindrical shape, and the optical fibers 4b for light reception are arranged on the outer peripheral surface of the spacer 7 at substantially equal intervals, and the optical fibers 4a for light emission are arranged on the inner peripheral surface of the spacer 7 at substantially equal intervals. In the case shown in 30 (a), the light receiving optical fiber 4b and the light emitting optical fiber 4a are arranged at the same position in the circumferential direction. With this type in which the axial direction of both types of optical fibers 4a and 4b closely fixed to the peripheral surface of the spacer 7 is parallel, the optical fiber for light emission is at any distance between the centers of the optical fiber for light emission 4a and the optical fiber for light reception 4b. 4a, the radius of the light receiving optical fiber 4b, and the thickness of the spacer 7. If both types of optical fibers 4a and 4b have a cladding diameter of 200 .mu.m and a spacer 7 with a thickness of 100 .mu.m, the distance between the centers is 300 .mu.m. It becomes. Of course, as shown in FIG. 30 (b), the light emitting optical fiber 4a and the light receiving optical fiber 4b may be provided at positions shifted in the circumferential direction. In this case, the center-to-center distance is longer than the above value.

  FIG. 31 shows another example of the case where the above-described cylindrical spacer 7 is used. Two cylindrical spacers 7 and 7 having different diameters are prepared, and the light-emitting optical fiber 4a is provided on the outer peripheral surface of the spacer 7 having a small diameter. The light receiving optical fiber 4b is fixed to the outer peripheral surface of the spacer 7 having a large diameter, and the spacer 7 having a small diameter is fitted inside the spacer 7 having a large diameter. By aligning the difference between the inner diameter (radius) of the spacer 7 having a larger diameter and the outer diameter (radius) of the spacer 7 having a smaller diameter substantially equal to the diameter of the light-emitting optical fiber 4a, the alignment of the spacers 7 and 7 can be adjusted. It becomes easy. In this case, since the difficult work of fixing the optical fiber to the inner peripheral surface of the spacer 7 is not required, the manufacture is easy.

  The spacer 7 may be a sheet as shown in FIG. The light-emitting optical fiber 4a is fixed to one side of the sheet-like spacer 7 and the light-receiving optical fiber 4b is fixed to the other surface. In this case, the sheet-like spacer 7 can be bent into a form as shown in FIG. 30, or it can be appropriately formed by winding it in a spiral, making it into a wave shape, or folding it. Further, since the optical fibers 4a and 4b can be attached to the spacer 7 in a flat plate shape, the optical fibers 4a and 4b can be easily positioned and bonded and fixed.

  Although the thickness of the spacer 7 is a requirement for setting the distance between the centers of the light-emitting optical fiber 4a and the light-receiving optical fiber 4b, the spacer 7 includes a through hole 71 through which the optical fibers 4a and 4b can pass. It may be. As shown in FIG. 33, a plurality of through holes 71 are provided in the spacer 7, and the optical fibers 4 a and 4 b are respectively passed through the through holes 71, whereby the distance between the centers of the optical fibers 4 a and 4 b is set at the interval of the through holes 71. Is set. In the illustrated example, one light-emitting optical fiber 4a is arranged so as to be surrounded by a plurality of light-receiving optical fibers 4b. The arrangement includes the arrangement of the through-holes 71 and the through-holes 71 in which both types of optical fibers 4a and 4b are arranged. Various arrangements are possible depending on whether or not it is inserted.

  The spacer 7 provided with the through hole 71 can be used as a member for forming an end surface of the measurement probe P that contacts the living body. At this time, as shown in FIG. 34, the tips of the optical fibers 4a and 4b are used as spacers. When protruding slightly from 7, it is possible to eliminate the possibility that stray light is generated due to gaps between the optical fibers 4a and 4b and the skin tissue when the measurement probe P is applied to the skin tissue surface.

FIG. 35 shows a spacer in which the optical fibers 4a and 4b are arranged in a basket-like lattice so that the reference light receiving optical fiber 4b can be positioned in the vicinity of the light emitting optical fiber 4a .
In FIG. 36, a substrate on which minute light-emitting diodes 41a and light-receiving elements 41b are arranged is attached to the distal end surface of the measurement probe P, and these light-emitting diodes 41a and light-receiving elements 41b are placed on the surface tissue of the living body near infrared. This is a projection unit that guides light and a detection unit that extracts near-infrared light from the surface of the surface tissue. In FIG. 36 (b), the light emitting diodes 41a and the light receiving elements 41b each having a size of L2 (100 μm) are arranged at an L1 (200 μm) pitch, and L3 (100 μm) is disposed between the light emitting diodes 41a and the light receiving elements 41b. However, the present invention is not limited to this arrangement, and an arrangement similar to that using the optical fiber or a random arrangement can be adopted.

  One of the light emitting diode 41a and the light receiving element 41b may be replaced with an optical fiber. Although FIG. 37 shows the light-emitting optical fiber 4a surrounded by a plurality of light-receiving elements 41b, the light-receiving diode 41a may be surrounded by a plurality of light-receiving optical fibers 4b.

An example of the optical fiber bundle used for this invention is shown, (a) is a front view, (b) is an end view of one end side. (a) (b) is explanatory drawing of the permeation | transmission path | route of the light in skin tissue. It is explanatory drawing of the permeation | transmission path | route of the light with respect to a human skin tissue. It is a schematic explanatory drawing of an example of the analyzer of this invention. It is a schematic explanatory drawing of the other example same as the above. It is an end view of the end of the optical fiber bundle used for the same. It is an end view of the other example of an optical fiber bundle. It is an end elevation of other examples of an optical fiber bundle. FIG. 6 is an end view of another example of an optical fiber bundle. FIG. 6 is an end view of yet another example of an optical fiber bundle. FIG. 6 is an end view of a different example of an optical fiber bundle. It is a schematic explanatory drawing of another example. It is an end view of the end of the optical fiber bundle used for the same. It is explanatory drawing about reference light. It is an end view of the other example of an optical fiber bundle. It is an end elevation of other examples of an optical fiber bundle. It is a schematic explanatory drawing of another example. It is an end view of an example of the optical fiber bundle used for the same. It is a schematic explanatory drawing of a different example. It is an end view of an example of the optical fiber bundle used for the same. FIG. 6 is an end view of another example of an optical fiber bundle. FIG. 6 is an end view of yet another example of an optical fiber bundle. It is an end view of the other example of an optical fiber bundle. It is an end elevation of other examples of an optical fiber bundle. FIG. 6 is an end view of a different example of an optical fiber bundle. (a) (b) (c) is explanatory drawing of the manufacturing method of an optical fiber bundle. (a) (b) (c) is explanatory drawing of the manufacturing method of another optical fiber bundle. (a) (b) (c) is explanatory drawing of the manufacturing method of another optical fiber bundle. (a) (b) is explanatory drawing of the manufacturing method of a different optical fiber bundle. (a) and (b) are the end views of other examples of an optical fiber bundle, respectively. (a) is an end view of another example of the spacer of the optical fiber bundle, and (b) is an exploded perspective view of the same. It is a perspective view of another example of the spacer of an optical fiber bundle. (a) and (b) are perspective views of still another example of the spacer. It is a perspective view of the other example of an optical fiber bundle. It is a front view of the example from which a spacer differs. (a) is a front view of another example of the measurement probe, and (b) is an enlarged front view of the same. It is a front view of the other example of a measurement probe.

Explanation of symbols

4 Optical fiber bundle 4a Light emitting optical fiber 4b Light receiving optical fiber

Claims (2)

An analyzer that performs blood component concentration of a living body by spectroscopic analysis of near-infrared light, and projects a near-infrared light having a wavelength in the range of 1,300 to 2,500 nm on the surface tissue surface of the living body, A detecting unit for detecting near-infrared light from the surface tissue surface of a living body, and the other end of the optical fiber for light emission, one end of which is connected to the light emitting means, is used as the projection unit, and one end is connected to the light receiving means. The other end of the optical fiber is used as the detection unit, and the interval between the projection unit and the detection unit is introduced from the projection unit into the living tissue by a spacer interposed between the light-emitting optical fiber and the light-receiving optical fiber. The near-infrared light detected by the detection unit is set to a single distance of 2 mm or less, which is an interval that selectively transmits through the dermis part of the surface tissue of the living body or an area that selectively diffuses and reflects at the dermis part. Analyzer of the blood constituent concentration, characterized in that by using the correlation between the concentration in the in component concentration and the dermal portion blood components of interest and a calculation means for performing quantitative analysis. 2. The blood component concentration analyzer according to claim 1, wherein an interval between the projection unit and the detection unit shorter than the single distance is used as a reference .

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