JP2000131322A - Method and instrument for determining glucose concentration - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method and device by which the glucose concentration can be determined with accuracy by taking disturbing factors into consideration. SOLUTION: At the time of determining the glucose concentration in a bio- tissue or humor by utilizing the absorption of light in the near infrared domain of 1,300-1,900 nm, at least one wavelength or one wavelength region is selected from each of four wavelength ranges of 1,530-1,560 nm, 1,580-1,640 nm, 1,640-1,720 nm, and 1,720-1,750 nm and the glucose concentration is determined based on absorption signals obtained by using at least the four wavelength or wavelength regions.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a glucose concentration in a living tissue or a glucose concentration in a body fluid such as blood, serum, plasma, cell fluid, saliva, tears, sweat, urine, etc. for health care and treatment of diseases. The present invention relates to a quantification method and a quantification apparatus for measuring a concentration, and particularly to a biological tissue or the like, which can directly or directly substitute a glucose concentration (blood glucose level) in blood using a spectroscopic analysis technique in a near infrared region. The present invention relates to a quantitative method and a quantitative device for measuring a glucose concentration in a body fluid component.

[0002]

2. Description of the Related Art Near-infrared spectroscopy is used in various fields including agriculture, food and petrochemicals in recent years, since it does not require any special operation on a sample and can perform nondestructive and quick measurement. It has become.

[0003] Spectroscopic analysis in the near-infrared region is generally in comparison with spectroscopic analysis in the mid-infrared region.・ High ability to penetrate living organisms ・ It is often not necessary to prepare special samples for measurement, but on the other hand, analysis in the mid-infrared region captures absorption due to normal vibration of molecules. On the other hand, in the near-infrared region, overtones or combination sounds of the reference vibration observed due to the anharmonicity of molecular vibrations are captured, and the near-infrared region Absorption by a hydrogen atom involves CH group, OH group, N
Since it is generated by molecular vibration having a large anharmonicity such as the H group, the signal level is as small as about 1/100 as compared with the mid-infrared region. Has the disadvantage that the assignment of the absorption peak is often unclear because the signal of this molecular bond is captured. Due to this disadvantage, when performing quantitative or qualitative analysis in the near-infrared region, it is difficult to perform accurate analysis using an analysis method based on peak positions and peak heights as in the case of mid-infrared analysis.

In order to solve this problem, in recent years, a method of analyzing a measured spectrum using a statistical analysis method, for example, a multivariate analysis method such as linear multiple regression analysis (MLR), principal component regression analysis, or PLS regression analysis, A technique called so-called chemometrics is used. This method is an analysis method that has spread rapidly with the development of personal computers. By using a statistical method based on numerical analysis, it is possible to carry out quantitative and qualitative analysis for practical use even with an absorption signal with a small SN ratio in the near infrared region. Becomes

In this case, the analysis procedure is performed by irradiating the object to be measured with light containing a multi-wavelength component or monochromatic light, and detecting the reflected or transmitted light, as in other optical measurement techniques. When irradiating light containing a multi-wavelength component, it is necessary to perform a spectral operation before reaching the object to be measured or after being reflected or transmitted. As in the case of mid-infrared spectroscopy, an interference filter, a diffraction grating, and a Fourier transform method are used for the spectral operation. Absorption signals (spectrums) obtained as a function of wavelength are processed by statistical techniques to perform qualitative and quantitative analysis.

Here, in general, near-infrared spectroscopy analysis is performed by using visible light of 600 nm or more and less than 1000 nm or near-infrared wavelength of visible light, or between 1000 nm and less than 2500 nm. When analysis is performed using a wavelength near the mid-infrared region, the analysis can be roughly divided into two. This is because there is an excellent detection element called a silicon photodiode for detection below 1000 nm, and the spectrum observed in the near-infrared region is a harmonic of the absorption spectrum derived from the reference vibration observed in the infrared region or a combination thereof. Because the spectrum is a sound spectrum, the absorbance decreases logarithmically as the wavelength shifts from a wavelength closer to the mid-infrared to a wavelength closer to the visible light. That's why.

The property that the absorbance at a wavelength of 1000 nm or more is relatively large is very advantageous for quantitative or qualitative determination of a substance, but has a drawback of poor transmittance. In other words, when the analysis is performed at a wavelength of less than 1000 nm, it is possible to perform an analysis in which light is transmitted to the inside of an object to be measured due to excellent transmittance, whereas
When the analysis is performed at a wavelength of 000 nm or more, it often reaches only near the surface, depending on the characteristics and light intensity of the object to be measured. Generally, it is prepared in a sample and measured by transmitted light.

In any case, which wavelength is used for the qualitative or quantitative determination of a substance by near-infrared spectroscopy is determined by the characteristics of the measured object, the magnitude of the signal of the target quantitative substance, and the intensity of the light from the light source. The overall judgment is made in consideration of the characteristics of the light receiving element.

When analyzing glucose components in living tissues and body fluids such as humans and mammals, the characteristics of the sites and secretions used in the analysis are very important. In general, the body of an organism is composed of complex tissues, and is composed of epithelial tissues, supporting tissues composed of bones and connective tissues, muscle tissues, nerve tissues, and the like. The target for biological glucose analysis is intracellular fluid,
It is a component contained in body fluids such as interstitial fluid, blood, serum, plasma, saliva, tears, sweat, and urine. When measuring glucose directly from a living tissue, since the content of the glucose component differs depending on the tissue, selecting an appropriate site is indispensable for accurate measurement. In particular, fat tissue and bone tissue existing as supporting tissues have a low content of body fluid components, and a site containing many of these tissues is generally not suitable for analyzing glucose components in a living body.

Instead of directly measuring living tissue, tears,
Analyzes of secretions such as saliva, sweat, urine, and glucose components such as blood, serum, plasma, and cell fluid that are collected invasively can reduce the disturbance factor because conditions can be set more strictly than when directly measuring the living body In the direction.

On the basis of such a background, the quantification of the glucose concentration in a living body using near-infrared light has attracted much attention in recent years. This is because non-invasive quantification that does not require blood collection is possible. Among them, the following are typical examples.

US Pat. No. 4,655,225:
Non-Invasive Spectroscopic Measurement Method and Apparatus
At least one wavelength selected from 75, 1765, 2100, 2270 ± 15 nm, and no absorption or no absorption of glucose from 1000 nm to 2700
A technique for quantifying glucose from a reference wavelength selected from nm is disclosed, and 1100 nm is selected as the reference wavelength in the examples. This reference wavelength 110
0 nm is a wavelength belonging to the absorption region of the second harmonic, and
75, 1765, 2100, 2270 nm
Compared with the overtone or reference vibration absorption region, the magnitude of the signal is about 1/100 or less. Therefore, it can be said that the reference wavelength has no or no glucose absorption.

Conversely, this is the second or third harmonic.
This indicates that it is difficult to select a reference wavelength from a region other than a harmonic region such as an overtone. FIG. 1 shows the absorption spectra of distilled water, glucose, albumin, and cholesterol measured in the first overtone region and the second overtone region, respectively. There is no wavelength where there is no absorption by glucose, and there is only a place where there is relatively little absorption.In addition, it is impossible that the absorption at the above four wavelengths is only due to the glucose component, and other biological Considering that the absorption of the components is superimposed, it is considered practically impossible to determine the glucose concentration without considering the contribution of other biological components.

US Pat. No. 5,028,787:
Non-Invasive Measurement of Blood Sugar This U.S. Patent shows a technique for quantifying glucose in the range of 600 nm to 1100 nm;
An example in which glucose is quantified using two wavelengths of ± X nm is shown. Specifically, 945 nm and 1015 nm
(That is, X = 35) is shown. Since 980 nm, which has an important meaning here, is a wavelength indicating the absorption peak of the second harmonic of water, in this embodiment, glucose is quantified using two wavelengths selected with the absorption peak of water interposed. Will be. 945 nm and 101
It is shown that a good correlation with the glucose concentration is obtained as the reason for selecting 5 nm.

US Pat. No. 5,070,874:
Non-invasive determination of glucose concentration in a patient's body This U.S. patent discloses a method for non-invasive measurement of blood glucose by quantifying glucose from the nth derivative of a spectrum obtained by changing the wavelength in a narrow range around 1660 nm. Have been. Specifically, the absorbance lo measured at around 1660 nm
The second derivative of g1 / T is derived, and glucose is quantified using multivariate analysis. It can be considered that there is a characteristic absorption derived from glucose around 1660 nm. However, the quantitative analysis focusing on the absorption at 1660 nm derived from glucose is a quantitative analysis focusing on the absorption derived from glucose disclosed in our invention. In comparison, it can be estimated that the measurement accuracy is considerably poor. The reason is 1700nm
The absorption of the CH group observed in the above is a molecular bond that is universally present not only in glucose but also in other biological components.
Peaks are concentrated in the region near 00 nm, which makes it difficult to separate absorption derived from the CH group and absorption derived from glucose of the biological component other than glucose. In addition, the publication does not disclose the contribution of other biological components, and it is difficult to quantify the glucose concentration in this regard.

US Pat. No. 5,222,496: Near Infrared Glucose Sensor This US Pat.
It is disclosed to quantify glucose with reference light within nm. Specifically, from 1630 nm to 1660
An example is shown in which glucose is quantified from a reference wavelength selected in the range of nm and the absorption wavelength of glucose at 1600 nm. The reason for using a reference wavelength within the range of 1600 nm to 60 nm is that light having similar wavelengths has almost the same optical properties such as a refractive index, so that a signal with little influence of disturbance can be obtained. Also, the reason for selecting the absorption wavelength of glucose is U.S. Pat.
It shows that the peak of the spectrum in which glucose in the solid state was measured was present at 1600 nm as in the case of Japanese Patent No. 655,225. However, as in the conventional example, 1
In the vicinity of 600 nm, the absorption of the glucose component forms a broad absorption band rather than an absorption peak,
In some cases, it is considered that the glucose signal is hard to be clearly separated by reference light selected from within 30 nm. Also, this prior art does not disclose the contribution of other biological components, and in this respect, it is difficult to quantify the glucose concentration.

[0017]

As described above, the prior art generally determines the concentration of glucose in a living body by absorbing glucose with respect to reference light.
However, as described above, the absorption spectrum in the near-infrared region is generated by molecules that biological components basically have, such as OH group, NH group, and CH group. Because absorption is observed,
The absorption signal at a certain wavelength should be considered to be more or less superimposed with the absorption of various biological components.
For example, the absorption region derived from the NH group exists in the broad absorption region derived from the OH group of glucose, and the absorption derived from the OH group of glucose overlaps with the absorption of other biological components. Exists. Therefore, it can be said that quantification of glucose cannot be established without considering the effects of biological components other than glucose and the effects of disturbance components such as temperature, scattering, and optical path length.

According to the present invention, based on such knowledge, when quantifying the concentration of glucose in a biological component such as a biological tissue or a body fluid that changes every moment, the above-mentioned disturbance factors are taken into account to accurately determine the glucose concentration. It is an object of the present invention to provide a quantification method capable of performing quantitative analysis of a concentration and an apparatus therefor.

[0019]

SUMMARY OF THE INVENTION A method for quantifying glucose concentration according to the present invention is a method for quantifying glucose concentration in living tissue or body fluid by utilizing light absorption in the near infrared region from 1300 nm to 1900 nm. Fifteen
30 nm to 1560 nm wavelength range, 1580 nm to 1640 nm wavelength range, 1640 nm to 1720
at least one of each of four wavelength ranges consisting of a wavelength range of 1720 nm to 1750 nm.
It is characterized in that a wavelength or one wavelength region is selected and glucose is quantified based on an absorption signal obtained using at least four wavelengths or four wavelength regions.

Further, the glucose concentration quantifying device according to the present invention comprises a near-infrared light source, a detecting means for detecting near-infrared light,
Inducing means for introducing near-infrared light emitted from the near-infrared light source into living tissue or body fluid, and guiding the near-infrared light transmitted, diffusely reflected or scattered through the living tissue or body fluid to the detecting means, Computing means for computing the signal obtained by the means and converting it to glucose concentration,
The detection means includes a wavelength range of 1530 nm to 1560 nm, a wavelength range of 1580 nm to 1640 nm,
Detects an absorption signal obtained from at least four wavelengths or four wavelength regions by selecting at least one wavelength or one wavelength region from each of four wavelength ranges of 40 nm to 1720 nm and 1720 nm to 1750 nm. There is a characteristic in that there is.

The near-infrared light source has a wavelength range of 1530 nm to 1560 nm and a wavelength range of 1580 nm to 1640 nm.
m, a wavelength range from 1640 nm to 1720 nm, a wavelength range from 1720 nm to 1750 nm, or a part of the wavelength range may have light emission characteristics.
In this case, it is preferable that the detection unit receives light that is split into light having at least four central wavelengths.

As described above, when quantifying the glucose component in a living tissue or body fluid, it is necessary to grasp the state of the biological component in the living tissue or body fluid and the change in absorption of near-infrared light caused by the state. is there.

A description will now be given of the recognition of phenomena in the determination of glucose in a living body. Absorption in the near-infrared region is mainly due to CH, OH, and NH groups.
Although —N, CO, and C ＝ O groups or SH and PH groups are observed, the absorption of OH, CH, and NH groups in a living body may be considered. However, for hair, the SH group also has an important meaning.

The wavelength used for the qualitative or quantitative determination of a substance by near-infrared spectroscopy is determined by the characteristics of the object to be measured, the signal intensity of the target quantitative substance, the light intensity of the light source, Judgment will be made comprehensively taking into account the characteristics of the device, but when quantifying glucose, the absorption signal at a wavelength that has specific absorption compared to substances such as proteins, lipids, and water present in the living body It is self-evident that the above-described prior art is also based on the idea.However, the present inventors utilize the specific absorption of glucose, and use the disturbance superimposed on the glucose absorption spectrum. Accurate glucose quantification would not be possible without removing the effects of the components.

Therefore, at least one wavelength or one wavelength region is selected from a wavelength range of 1580 nm to 1640 nm as a specific absorption wavelength of glucose, and a wavelength range of 1530 nm to 1560 nm, 1640 nm is used as a wavelength for removing the influence of a superimposed disturbance component. From 1720
It has been found that it is effective to perform at least four wavelengths or four wavelengths in which at least one wavelength or one wavelength is selected from the wavelength range of 1720 nm to 1750 nm. That is, by measuring the glucose concentration using at least the four wavelengths or the four wavelength region, accurate quantification in consideration of the influence of disturbance in the living body becomes possible.

[0026]

BEST MODE FOR CARRYING OUT THE INVENTION The apparatus for quantifying glucose concentration according to the present invention will now be described. The apparatus for quantifying glucose concentration according to the present invention comprises a near-infrared light source, a detecting means for detecting near-infrared light, Inducing means for introducing near-infrared light emitted from an infrared light source into living tissue or body fluid, and guiding the near-infrared light transmitted, diffusely reflected or scattered to the living tissue or body fluid to the detecting means, and the detecting means. It comprises a calculating means for calculating the obtained signal and converting it into a glucose concentration. Here, at least 1
530 nm to 1560 nm wavelength range, 1580 nm
To 1640 nm wavelength range, 1640 nm to 172
At least one wavelength or one wavelength region is respectively selected from the wavelength range of 0 nm and the wavelength range of 1720 nm to 1750 nm, and the measurement is performed in at least four wavelengths or four wavelength regions. Then, the arithmetic means quantifies glucose by using a near-infrared light absorption signal using a calibration equation input in advance.

Although a halogen lamp is suitable as a near-infrared light source, in the present invention, glucose can be quantified in a relatively narrow wavelength range, and glucose can be quantified in at least four wavelengths. For this reason, light emitting diodes (LEDs) are also suitable. In the present technology, an InP (indium phosphide) -based light-emitting diode is suitable for the first overtone region. In some cases, depending on the characteristics of the light emitting diode, it is not necessary to use the spectral unit. In particular, since the half width can be set relatively large in the above-described wavelength or wavelength range in which the absorption of glucose molecules is measured, spectroscopic means such as an interference filter can be omitted.

When spectral means is required, various spectral means can be used as described above. However, when a relatively large half-value width is set, it is suitable to use an interference filter.

When the glucose concentration is determined by non-invasively measuring a living tissue as an inducing means, it is suitable to use an optical fiber. In particular, when quantification is performed in the first harmonic region, the degree of arrival of light in the search direction is controlled by the optical fiber interval, and the measurement accuracy can be improved by a method of quantifying the glucose concentration in the subcutaneous tissue at an arbitrary search. .

FIG. 2 shows an example of the optical fiber bundle 4 which can be suitably used as the guiding means. A plurality of light-emitting optical fibers and a plurality of light-receiving optical fibers are bundled on one end side, and at this time, the light-emitting fibers 1 are arranged in a cage-like lattice-like array surrounding six light-receiving fibers 2 on the bundled side. ing. An optical fiber to be used preferably has a diameter of 70 μm to 1000 μm.

This optical fiber bundle is used by abutting the end face on the one end side at a right angle to the surface of the object to be measured as shown in FIG. However, the angle is not limited to a right angle as long as the transmitted light path can be specified.

The light emitted from the light-emitting fiber 1 to the object to be measured is transmitted in various ways, such as an optical path A to an adjacent light-receiving fiber 2, an optical path B to a further distant light-receiving fiber 2, an optical path C to a further distant light-receiving fiber 2, and the like. The light passing through the appropriate optical path is incident on the light receiving fiber 2. Now, comparing the optical path lengths of the optical paths A, B, and C, in this example, since the optical fibers are arranged at the same interval, the optical paths B and C are almost twice as large as the optical path A and 3 times.
You can think of it as double. Strictly speaking, the transmission of light in a substance such as an organism which is optically opaque and scatters is Lambert-Beer.
Does not obey the law, but the amount of transmitted light sharply decreases in accordance with the optical path length.
When it is three times or less, it is further reduced to 1/10 or less. Therefore, the transmitted light focused on the light receiving fiber 2 can be basically considered to be the sum of the transmitted light from the adjacent light emitting fibers 1.

A specific example of a living tissue is a human dermis as shown in FIG. Human dermis is 100μ
The tissue has a thickness of about 1 mm sandwiched between the epidermis b having a thickness of about m and a subcutaneous tissue C having a large amount of fat cells. For the analysis of the chemical components in the dermis, the distance between light receiving and emitting is 250.
It is suitable to use a bundle of optical fibers of up to 750 μm. Since the path of light passing through the skin tissue differs from the physical properties of the tissue and the wavelength of the light used for analysis, preliminary experiments and numerical simulations must be performed in advance to determine the distance between optical fibers used for measurement and the wire diameter. preferable. The glucose concentration of the obtained light absorption signal is calculated by numerical calculation in the calculation unit.

Accurate measurement of glucose concentration in a living body, particularly, quantification of glucose concentration in a living tissue, requires grasping the state of glucose in the living body and the influence of disturbance components as an absorption signal in the near infrared region. Software, hardware that enables accurate measurement of absorption spectra with high reproducibility, selection of stable measurement sites from a medical point of view, etc., can be achieved only by combining many optimal factors. The above invention is an excellent technique for noninvasively measuring glucose concentration in a living body by near-infrared light.

Example 1 FIG. 5 shows a noninvasive blood glucose level quantifying apparatus in this example. Near-infrared light emitted from a halogen lamp 3 as a light source is condensed on an optical fiber bundle 4 as a guiding means, and the near-infrared light is guided to an object to be measured (skin tissue of a human forearm). The scattered light is guided to the flat field type diffraction grating unit 5 by the optical fiber bundle 4. The near-infrared light split by the diffraction grating unit 5 is applied to a light receiving element of an array type light receiving element unit 6 which is a detecting means, and is measured as a light receiving signal. The arithmetic unit 7 calculates a blood sugar level from the received light signal.

The optical fiber bundle 4 used in this embodiment
As shown in FIG. 2, optical fibers having a diameter of 200 μm are arranged in a kagome lattice (distance between light receiving and emitting 350 μm), and are composed of 25 light emitting fibers and 50 light receiving fibers. The spectrum measurement was performed by vertically protruding the measurement unit 10 (the end of the bundle) to the skin surface of the forearm. The measuring unit 10 uses a spring to contact the skin with a pressure of 470 gf / m ^2.
It is adjusted to be constant.

In this embodiment, the blood glucose concentration is quantified from the spectrum of the human forearm measured noninvasively. The experiment was performed using healthy male volunteers aged 25 years according to the following procedure.

After resting for 20 minutes, the subject takes 75 g of glucose by taking the partially hydrolyzed starch preparation Torayan G (manufactured by Shimizu Pharmaceutical Co., Ltd.). The blood glucose level was measured every ten minutes from the start of rest using fingertip blood using a simple blood glucose meter NovoAssist (manufactured by Novo Nordisk Pharma). The blood sugar level data every 10 minutes is interpolated to be blood sugar level data every 2 minutes, and a multivariate analysis is performed using this data as a target variable.

The measurement of the spectrum of the forearm was performed three times every two minutes for 104 minutes from the start to the end of the experiment to obtain a total of 159 spectra. In addition, the glucose concentration in the forearm skin tissue had a time delay having an individual difference with respect to the blood glucose concentration, and a time delay of 17 minutes was appropriate for this subject.

The calibration curve was prepared by using PLS regression analysis and multiple regression analysis with the blood glucose level data as the target variable and the spectrum measured 17 minutes later as the explanatory variable. The blood sugar level of the subject in this actual measurement varies from 89 mg / dl to 186 mg / dl.

FIG. 6 shows the actually measured absorption spectrum of the forearm skin tissue, and FIG. 7 shows the regression coefficients obtained by PLS regression analysis. PLS regression analysis from 1500 nm to 1760 nm
The cross-validation technique was used in the above wavelength range. It can be seen that the shape of this regression coefficient has a peak near 1600 nm and the blood glucose level is quantified from the absorption of glucose. The result obtained by this PLS regression analysis is the estimation of the number of principal components 4, and the correlation coefficient of the calibration curve is 0.963, the standard error SEP 8.9 mg / dl, the correlation coefficient of the calibration curve test is 0.957, the standard The error was 9.6 mg / dl of SEP.

The same data has a wavelength range of 1530 nm to 1560 nm, and a wavelength range of 1580 nm to 1640 nm.
1545 nm, 1620 nm, 1705 n from the four wavelength ranges of the wavelength range of nm, the wavelength range of 1640 nm to 1720 nm, and the wavelength range of 1720 nm to 1750 nm.
The glucose concentration was quantified using four wavelengths, m and 1735 nm. These four wavelengths correspond to the maximum value and the minimum value of the regression coefficient obtained by the PLS regression analysis. Multiple regression analysis (MLR) was used to estimate the glucose concentration. FIG. 8 shows the results obtained by performing multiple regression analysis. The results obtained by the four-wavelength multiple regression analysis obtained in the above experiment show a correlation coefficient of 0.955 for preparing a calibration curve and a standard error of SEP 9.2 m.
g / dl, the correlation coefficient of the calibration curve test was 0.952, and the standard error was SEP 9.5 mg / dl.

Example 2 The apparatus for quantifying glucose concentration in a living body in the present example is, as shown in FIG.
Near-infrared light irradiated from 4 is divided into an arbitrary center wavelength and a half-value width by an interference filter 15, and light condensed on an end face of the optical fiber bundle 4 by a lens 12 as a light condensing means is guided to an object to be measured. The absorption signal is measured by detecting the transmitted light of the object to be measured by the photodiode 16 as the detecting means, and the glucose concentration is calculated by the calculating means.

As shown in FIG. 9, four interference filters 15 are arranged on concentric circles of a disk. By rotating the motor 18 with a motor 18, a center wavelength and a half width corresponding to the characteristics of the interference filter can be obtained. is there. The detected absorption signal is converted into an absorbance, and the glucose concentration is calculated by a preset calibration curve.

The four types of interference filters 15 have a central wavelength of 1535 nm, a half width of 10 nm, and a central wavelength of 1620 nm.
The half width is 40 m at nm and the half width is 1 at the center wavelength of 1705 nm.
The one having a central wavelength of 1735 nm and a half width of 10 nm was used. The reason for setting these center wavelengths and half widths was based on the peak shape of the regression coefficient obtained in Example 1 in order to capture signals derived from glucose in the living body.

The measuring section 10 of the optical fiber bundle 4 is used by being vertically applied to an object to be measured. In the measuring section 10, the light-emitting fiber 1 and the light-receiving fiber 2 of the optical fiber are arranged in a kagome lattice, and are irradiated from the light-emitting fiber 1,
The near-infrared light transmitted through the living tissue is received by the light receiving fiber 2 and guided to the detector 16. The diameter of the optical fiber used for light emission and light reception is 200 μm, and the distance between the centers of the light reception and light emission fibers is 350 μm. As for the light emitting diode, a plurality of light emitting diodes having different center wavelengths may be used as a light source.

The calibration curve for calculating the glucose concentration is obtained by statistical analysis of the relationship between the true value of the glucose concentration obtained by another standard method and the absorbance according to the present invention using the user of the present invention or a plurality of persons as subjects. It is obtained by analyzing by The glucose concentration obtained by a standard method for analyzing the collected blood and the signal stored at the time of measurement are compared and converted into data, and a calibration curve is created by the analysis means built in the calculation means. A multiple regression analysis method is suitable for creating a calibration curve for individuals from absorption signals at several points as in this embodiment.

[0048]

As described above, in the present invention, the glucose concentration in the living body is taken into consideration in the wavelength range of 1580 nm to 1640 nm for measuring the absorption derived from glucose in the near infrared region, and the influence of disturbance superimposed on the glucose signal. At least 4 wavelengths selected from at least one wavelength range from 1530 nm to 1560 nm, 1640 nm to 1720 nm, and 1720 nm to 1750 nm.
Since glucose is quantified in the wavelength or four-wavelength region, not only absorption by glucose but also biological components as disturbance can be considered, and measurement accuracy can be improved.

If the above-mentioned wavelength region is selected in an adjacent region, glucose can be quantified by measuring in a relatively narrow wavelength region. For this reason, a light source such as a halogen lamp having emission characteristics in a wide wavelength range is used. Without this, it is possible to determine glucose in an element having a light emission characteristic at a relatively narrow wavelength such as a light emitting diode.

[Brief description of the drawings]

FIG. 1 is an absorption spectrum diagram of a biological material in a first overtone region.

FIGS. 2A and 2B show an optical fiber bundle used in the present invention, wherein FIG. 2A is a schematic diagram and FIG.

FIG. 3 is a conceptual diagram of an optical path of near-infrared light emitted from a fiber to a living tissue.

FIG. 4 is a conceptual diagram of human skin tissue.

FIG. 5 is a schematic view of an example of the device according to the present invention.

FIG. 6 is an absorption spectrum diagram obtained from a human forearm.

FIG. 7 is a graph showing regression coefficients for quantifying glucose concentration obtained by performing PLS regression analysis on an absorption spectrum obtained from a human forearm.

FIG. 8 is a graph showing actual measured values and estimated values of glucose concentration quantified by four wavelength absorption signals obtained from a human forearm.

FIG. 9 is a schematic view of another example of the device according to the present invention.

[Explanation of symbols]

 Reference Signs List 1 light emitting fiber 2 light receiving fiber 4 optical fiber bundle 5 diffraction grating unit 6 light receiving element unit 7 arithmetic unit 10 measuring unit

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Keisuke Shimizu 1048, Kazuma Kadoma, Kadoma, Osaka Pref.Matsushita Electric Works Co., Ltd. F term (reference) 2G045 AA13 AA16 AA25 CA25 CB03 CB07 CB11 CB12 DA31 FA25 FA29 GC10 GC11 JA07

Claims (3)

[Claims] 1. A method for determining glucose concentration in a living tissue or a body fluid by using light absorption in a near-infrared region from 1300 nm to 1900 nm, in which 1530 n
m to 1560 nm wavelength range, 1580 nm to 16
At least one wavelength or one wavelength region is selected from each of four wavelength ranges including a wavelength range of 40 nm, a wavelength range of 1640 nm to 1720 nm, and a wavelength range of 1720 nm to 1750 nm.
A method for quantifying glucose concentration, comprising quantifying glucose based on an absorption signal obtained using a wavelength or a four-wavelength region. 2. A near-infrared light source, detection means for detecting near-infrared light, and near-infrared light emitted from the near-infrared light source introduced into living tissue or body fluid, and transmitted or transmitted through the living tissue or body fluid. A guiding means for guiding the diffused or scattered near-infrared light to the detecting means, and a calculating means for calculating a signal obtained by the detecting means and converting the signal into a glucose concentration, wherein the detecting means is 1530 nm to 1560n.
m, 1580 nm to 1640 nm, 1640 1720 nm, 172
Glucose characterized in that at least one wavelength or one wavelength region is selected from each of four wavelength ranges from 0 nm to 1750 nm, and an absorption signal obtained from at least four wavelengths or four wavelength regions is detected. Concentration determination device. 3. The near-infrared light source has a wavelength of 1530 nm to 156 nm.
0 nm wavelength range, 1580 nm to 1640 nm wavelength range, 1640 nm to 1720 nm wavelength range, 1
3. The glucose according to claim 2, wherein the whole or a part of the wavelength range from 720 nm to 1750 nm has light emission characteristics, and the detection means receives light dispersed into light of at least four central wavelengths. Concentration determination device.