JP2008051826A - Method and apparatus for optically measuring biological material and chemical substance - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an apparatus for noninvasively or invasively, speedily, easily, and with high accuracy, measuring biological materials and chemical substances in biological tissues. <P>SOLUTION: Plastic is molded into a rod-like body having a circular or an elliptical cross section to form a housing. A battery 11, an arithmetic processing part 6, and a signal processing part 5 are adjacently arranged in the housing from one side along its longitudinal direction. A display part 7 is mounted on the upper part of the signal processing part 5. A lighting circuit part 8 is mounted adjacent, and a switch 15 for measurement is mounted adjacent. Two types of LEDs 1 or more, a lens system 9, and two types of light-receiving parts 4 or more are fixed adjacent, at intervals from each other in a cylinder made of a light metal, and the cylinder is arranged adjacent to the lighting circuit part 8. A finger inserting part is provided between the light-receiving parts 4 and a reflecting plate 13. The signal processing part 5 is arranged adjacent to the back of the reflecting plate 13. Each element of the apparatus is fixed by filling plastic in the noninvasive optical measuring apparatus of biological materials, and the like. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

The present invention relates to an optical measurement method and an optical measurement apparatus for biological substances and chemical substances contained in body fluids, cells and other biological tissues, and more particularly, blood, serum, cell fluid, saliva, It is contained in interstitial fluid, tears, sweat, urine, other body fluids, cells, blood cells, lymphocytes, and other living tissues, and includes an ultraviolet region (200 to 380 nm), a visible region (380 to 780 nm), and a near infrared region ( Biological substances and chemical substances having light absorption in any one of 780 to 2500 nm) and infrared region (2500 to 5000 nm) (in this specification, these substances are sometimes collectively referred to as “biological substances etc.”) And optical measurement methods and non-invasive or invasive optical measurement devices that perform rapid detection, qualitative and quantitative analysis using light from light emitting elements and diffraction gratings It relates.
In this specification, “light-emitting element” belongs to a semiconductor light-emitting element, and includes a light-emitting diode and a laser diode.

  According to the present invention, through qualitative and quantitative analysis of biological substances as described above, analytical information useful for diagnosis of dementia such as micro cancer, rheumatoid factor, Alzheimer, diabetes, hypertension, brain examination, etc. is provided. In addition, symptoms can be foreseen and diagnosed by using the measurement results, and can contribute to grasping the progress of the disease state.

  Conventionally, as a method for optical measurement of a biological substance, a qualitative and quantitative method used for noninvasive detection and diagnosis that has been developed has only been put to practical use for hemoglobin in blood ( For example, refer to JP 2002-107291 A).

In addition, even in measurement methods commonly used for invasive detection and diagnosis of blood components using blood or the like as a sample,
(1) There is a problem that the time required for diagnosis is long. There are many cases that require several tens of minutes or more than several tens of minutes even if they are short.
Also,
(2) In recent years, the number of diagnoses has been increased, and therefore a large amount of blood (for example, 2 to 3 vacuum glass tubes for 5 ml blood collection are required for normal diagnosis) has been collected. In addition to being painful, there is a risk of infection, so measures to prevent it are necessary. In addition, there arises a problem that a large amount of medical waste such as a blood collection device and a kit after diagnosis is produced.
further,
(3) Since there are many stages of diagnosis operations for biological substances in biological tissues and the operation is complicated, there are many methods that require skill, and as a result, many include difficulties in measurement accuracy. .
(4) The measurement methods for biological substances contained in biological tissues that have been conventionally employed in the circumstances as described above usually require a long time and are inevitably expensive.

  However, against this background, for example, Patent Document 1 (Japanese Patent Application Laid-Open No. 11-64218) discloses a concentration of a body fluid component in a biological tissue or cholesterol in a body fluid such as blood, cell fluid, saliva, etc. As a method for quantifying the concentration of components such as sex fat and albumin, a method using absorption of light derived from a CH group, an OH group and an NH group in the near infrared region over the wavelength range of 1480 to 1880 nm has been proposed. Although it uses the absorption spectrum of the substance to be measured, it still takes a long time and the operation is complicated, and it has not reached a stage where rapid detection, qualitative and quantitative determination is possible.

  Also, according to Patent Document 2 (Japanese Patent Laid-Open No. 5-176717), an optical measurement method for noninvasively measuring the glucose concentration in the human body using near infrared light having a wavelength of 380 to 1320 nm is proposed. Yes.

  However, as with the method described in Patent Document 1, rapid diagnosis is not solved.

  The above proposals all use near infrared light, and detect a wide range of biological substances including biological substances in the visible region and ultraviolet region contained in body fluids and other biological tissues, There is no disclosure and no suggestion of qualitative and quantitative analysis.

  Under such circumstances, the development of a rapid, simple and accurate optical measurement method for various biological substances as described above in body fluids or biological tissues, and capable of noninvasive measurement in addition to invasive measurement. It has been longing for.

Japanese Patent Laid-Open No. 11-64218 Japanese Patent Application Laid-Open No. 5-176717

  Therefore, in view of the circumstances as described above, the object of the present invention is to solve the above-mentioned problems, so that the ultraviolet region (200 to 380 nm), the visible region (380 to 780 nm), the near infrared region (780 to 2500 nm) and Qualitative analysis and quantitative analysis of biological materials having a light absorption band in any region of the infrared region (2500 to 5000 nm) can be quickly and easily performed, and the optical material capable of measuring the biological materials etc. in the field An optical measuring device capable of detecting biological materials, particularly for peripheral blood vessels and biological tissues in the human body, which can only be detected by a surgical invasive method. An object of the present invention is to provide an optical measuring device that can distinguish abnormalities in living cells, components, and blood that cannot be diagnosed.

  Therefore, the present inventor has made extensive studies to solve the above-mentioned problems, and as a result, it is possible to perform multivariate analysis by capturing and amplifying signals from light absorption of body fluids and trace amounts of biological substances in biological tissues. Furthermore, paying attention to the fact that it can be quantitatively achieved by eliminating and optimizing the signal of biological substances other than the desired biological substance, etc., and emitting light with an emission wavelength adapted to the light absorption wavelength region of the substance to be measured It has been found that such a problem can be easily achieved by using an element, and the present invention has been completed based on these findings.

That is, according to the present invention, an optical measurement method capable of detecting, qualitatively and quantitatively determining biological substances and chemical substances contained in body fluids, cells and other biological tissues,
An optical measurement method capable of detecting, qualifying and quantifying biological substances and chemical substances contained in body fluids, cells and other biological tissues,

1) For an object to be measured containing the biological substance and chemical substance having at least one light absorption band in any wavelength region including the ultraviolet region, visible region, near infrared region, and infrared region,
Irradiating the emitted light by using one or more light emitting elements that emit light having a wavelength suitable for a wavelength region to which the light absorption bands of the biological material and the chemical substance belong;
2) It includes at least a light receiving process in which light irradiated in the irradiation step and transmitted or reflected by the object to be measured is received by one or more light receiving elements and converted into an electrical signal. An optical measurement method for biological substances and chemical substances is provided.

Moreover, according to the present invention,
An optical measuring device capable of detecting, qualifying and quantifying biological substances and chemical substances contained in body fluids, cells and other biological tissues,

1) Selected in any wavelength region including ultraviolet region, visible region, near-infrared region and infrared region, so as to be suitable for at least one light absorption band of the biological substance or chemical substance A light emitting means for emitting light by one or more light emitting elements that emit light of a wavelength;
2) a light collecting means for collecting the light emitted from the light emitting means;
3) Light collecting / irradiating means for condensing and irradiating the light collected by the light collecting means on the object to be measured;
4) a light receiving means comprising one or more light receiving elements for receiving the light irradiated by the condensing / irradiating means and transmitted or reflected by the object to be measured;
5) Signal processing means for photoelectrically converting the output signal of the light receiving means;
6) A biological substance that detects, qualifies, or quantifies a biological substance by analyzing and calculating an absorbance spectrum by a cross-validation method and a partial least square method based on the detection signal photoelectrically converted by the signal processing means. An apparatus for noninvasive or invasive optical measurement of biological substances and chemical substances contained in body fluids, cells and other biological tissues, comprising at least an equivalent concentration calculating means and a display means for displaying the calculation results Provided.

  As described above, the present invention relates to an optical measurement method for biological substances contained in body fluids, cells and other biological tissues, and an optical measurement device configured to realize the optical measurement method. However, the following preferable embodiments 1) to 9) are included.

1) An optical measurement method for the biological material or the like in which the object to be measured is blood, urine, interstitial fluid, saliva, tears or sweat collected from a human body.
2) An optical measurement method for the biological material or the like, in which the measurement object is a cell, tissue, blood cell or lymphocyte collected from a human body.
3) The method for optically measuring a biological substance or the like, wherein the light emitting element is a combination of two or more light emitting diodes having the same wavelength.
4) Optical measurement of the biological material or the like in which the light-emitting element is a combination of two or more types of light-emitting diodes having an emission wavelength suitable for the light absorption band of the biological material and having different peak wavelengths. Method.
5) When measuring glucose concentration in blood, 1560 nm, 1570 n
m, 1580 nm, and 1590 nm, respectively. The optical measuring method of the said biological material etc. which use simultaneously the mutually different light emitting diode or laser diode which has each.
6) Optical measurement of the biological material or the like in which the object to be measured is a biological tissue containing a color reaction product conjugated to the color reaction product of the biological material by a second color reaction. Method.
7) The object to be measured is a peripheral blood vessel or tissue under the skin of a finger, arm, earlobe, lips or other body surface, and hemoglobins, serum albumin, cytochromes, flavins,
The noninvasive optical measurement apparatus for biological materials such as carotene, creatinine, bilirubin, cholesterol such as total cholesterol and free cholesterol, neutral fat, uric acid, triglyceride, phospholipid or microcancer tissue.
8) The noninvasive optical measurement apparatus for biological materials, etc., in which the object to be measured is a dyed product generated by a reaction with a color reagent, enzyme, antibody or the like.
9) The object to be measured is aspartate aminotransferase (GOT), alanine aminotransferase (GPT), glutamyl peptide transferase (γ-GTP), acid and alkaline phosphatase, lactate dehydrogenase, superoxide Reaction of dismutase, creatine phosphokinase, leucine aminopeptidase, cholinesterase, blood amylase, bisphenols, dioxins, polyvinyl chloride, phthalates, cocaine, morphine and narcotics with color reagents, enzymes or antibodies Invasive optical measurement apparatus for biological substances such as products and other disease test substances.

  As described above, the present invention provides a rapid, simple, and highly accurate optical measurement method for biological substances and chemical substances contained in body fluids, cells and other biological tissues. 1) The measurement time can be shortened to 1 second or less, (2) the minimum amount of sample is sufficient, (3) the detection reaction is simplified, (4) the cost can be extremely effectively reduced, (5) It has simplicity and (6) and produces effects such as enabling noninvasive measurement.

Hereinafter, the present invention will be described in detail.
Biological substances and chemical substances that are the targets of the optical measurement method according to the present invention are biological substances that are originally contained in body fluids, cells, and other biological tissues, or that are attached or invaded from the outside. There is no problem in measurement.

The body fluid is a collective term for various functionally different fluids contained in a living tissue, and is classified into an extracellular fluid and an intracellular fluid. In the present specification, specifically, blood, Serum, interstitial fluid, cell permeation fluid (gastrointestinal fluid, bladder fluid, secretory fluid in glandular tissue, etc.), saliva, tears, sweat, urine, etc. are included.
Moreover, the said biological tissue is used as what contains abnormal cells, such as a cancer cell, in addition to a normal cell.

In the optical measurement method according to the present invention, body fluids, cells and other biological tissues are used as objects to be measured, and biological substances and chemical substances contained in the objects to be measured are targets for detection, qualification and quantification. It is said.
Such optical measurement of a biological substance or the like can be performed mainly in the following four types.

  That is, the first form relates to noninvasive measurement performed from above the skin, and examples of biological materials that can be directly measured include the following. As shown in the table below, each biological substance can be measured by employing a wavelength that can be used for each measurement.

In non-invasive measurement of biological materials, etc., it is possible to target subcutaneous peripheral blood vessels as objects to be measured regardless of veins and arteries, such as fingers, arms, earlobe, lips, and other body surface tissues. Can be used.
Moreover, the following can be illustrated as chemical substances that enter and contain body fluids, cells, and other biological tissues, and that can be noninvasively measured.

等を挙げることができる。

Etc.

According to the noninvasive optical measurement method according to the present invention, the biological material can be measured even in a trace amount, and can be quantified to about nmol to μmol.
It should be noted that invasive measurement by collecting a sample of the biological material or the like can be performed quickly and with high accuracy. In addition, detection requiring a long time (for example, 10 to 60 minutes) can be performed in a short time (about 1 second or less) by gas crossgraphy such as a TNT chemical or dioxin.

  The second form relates to the measurement of biological substances contained in body fluids such as blood, urine, interstitial fluid, saliva, tears, sweat, etc. collected from the human body, and in particular, color reagents, enzymes or antibodies, etc. Examples of biological substances that can be detected, qualitatively determined, and quantified with respect to reaction products obtained by utilizing the reaction with the following can be exemplified.

Aspartate aminotransferase (GOT),
Alanine aminotransferase (GPT),
Glutamyl peptide transferase (γ-GTP),
Acid and alkaline phosphatases,
Lactate dehydrogenase,
Superoxide dismutase,
Creatine phosphokinase,
Leucine aminopeptidase,
Cholinesterase,
Blood amylase,
Triglyceride,
Phospholipids,
urea,
Bilirubin,
Examples include cancer cells and other color-diagnosis test substances.

  By using the color reaction product of the biological material as described above, even if the biological material itself cannot be optically measured in nature, the measurement can be performed, and the measurement accuracy can be improved. In addition, when the wavelength of the absorption band of the color reaction product is small and it is impossible to provide a light emitting device such as a light emitting diode having a peak wavelength suitable for the absorption band, the color reaction product is converted into a second color reaction. An optical measurement can be performed by providing a secondary color reaction product obtained by conjugation to.

Table 3 shows examples of the color reagent used for performing the color reaction.
In the color reaction, a color reaction product obtained by adding a color reagent to a biological substance (or chemical substance) is used as an object to be measured.

When an enzyme is used, at least one enzymatic action can be used for a product obtained by adding an enzyme to a biological substance or chemical substance, or for two or more reactions.
Furthermore, when an antibody is used, a color reaction reaction product obtained by adding the antibody to a biological substance or chemical substance or a color reaction by a combination of these reactions is used.

  The third form relates to measurement of biological substances contained in a part of a living body such as cells, tissues, blood cells, and lymphocytes collected from a human body, and is a color reagent, enzyme or antibody for abnormal tissues Reaction products such as, for example, products stained with a dye marker for micro cancer.

  Specifically, microscopic cancers that cannot be detected by biological diagnostic imaging equipment (such as MRI) are stained with dyes such as toluidine blue and FGG, or these dyes are selectively bound to antibodies. Enabling and non-invasively sensing its presence from the outside.

  Furthermore, as a fourth form, a chemical substance that has entered a living tissue from the outside and has an optical absorption activity from the ultraviolet region to the infrared region or an optical absorption activity by a color reaction is measured. For example, cocaine, morphine, dioxin, etc. are measured.

Next, a light-emitting element used in the optical measurement method for biological materials and the like according to the present invention will be described. A light emitting diode or a laser diode can be used as the light emitting element.
A light-emitting diode (hereinafter may be abbreviated as “LED”) is a semiconductor pn junction diode that emits light when an electric current is passed, and has a basic structure such as a homojunction, a single heterojunction, A double heterojunction can be mentioned. Conventionally, various LED crystal materials having emission wavelengths ranging from the infrared region, the visible region, and the ultraviolet region have been developed.

  The LED crystal material of the light-emitting diode suitable for the optical measurement method for biological substances, etc. according to the present invention is selected by controlling the peak wavelength by adjusting the composition ratio so as to cover the absorption band of biological substances, etc. can do. Among these, GaAs, GaP, GaN, InP, InN, and those whose wavelength is controlled by mixed crystals thereof, for example, InGaN, GaAsP, InGaP, GaAlInN, and the like can be mentioned. Specifically, GaInAs with an appropriate proportion of In added to GaAs and GaInAsP with P added to cover a region of wavelength 1000 nm or more, and a specific wavelength prepared by adjusting the composition. You can choose what you have. In addition, GaAs (peak wavelength: 900 nm), GaAlAs (660 to 850 nm) obtained by adding Al to GaAs, GaAsP (630 to 580 nm), GaP (700 nm), GaN (400 nm), and InGaN are used to cover a region of 1000 nm or less. (400 nm to 700) and the like can be exemplified.

  Among the crystalline materials, GaP (Zn—O) is particularly suitable for measuring hemoglobin, GaAlAs, etc. is suitable for cytochromes, and GaP (N), etc. is suitable for GOT and GPT. It is.

  The laser diode (LD) is a compound semiconductor provided with a pn junction and used as an active layer. In the optical measurement method of the present invention, the laser diode (LD) has a peak wavelength that can cover an absorption band of a biological substance, For example, it can be selected from various laser diodes such as GaAlAs and GaInAsP.

  In the irradiation step in the optical measurement method for biological substances and the like according to the present invention, a light emitting element having a peak wavelength that matches or matches the light absorption band of biological substances and the like is selected, and the emission to the object to be measured is performed. Although it irradiates light, it is important to employ | adopt the irradiation system which consists of the following structures as a more suitable form.

  That is, the first irradiation method uses two or more light emitting elements of the same wavelength region or the same type or different types simultaneously. For example, specifically, when measuring blood glucose, two or more LEDs having a peak wavelength of 1580 nm are simultaneously emitted to irradiate the object to be measured.

  The second irradiation method is a mode in which two or more types of light emitting elements having different continuous peak wavelengths are used at the same time so as to cover an absorption band of a biological material or the like. Specifically, in the measurement of blood glucose, a light-emitting diode or a laser diode having four types of peak wavelengths of 1560 nm, 1570 nm, 1580 nm, and 1590 nm is simultaneously used to irradiate the object to be measured.

  Further, the third irradiation method is a mode in which two or more types of light emitting elements having different discontinuous peak wavelengths are arranged and used simultaneously so as to cover an absorption band of a biological material or the like. . Specifically, in the measurement of blood glucose, a light emitting diode or a laser diode having discontinuous peak wavelengths of 1580 nm and 2140 nm is used at the same time.

  By adopting such an irradiation method, in particular, according to the first method, the intensity of the irradiation light can be increased and maintained, and according to the second and third systems, temperature drift can be avoided and measured. It is possible to suppress fluctuations in conditions, and with these effects, it is possible to achieve more stable and highly accurate measurement.

  In particular, near-infrared light such as temperature drift due to heat generation of the light-emitting element is suitable for preventing the shift of the peak wavelength due to temperature difference. For example, the absorption peak of glucose in the near-infrared region is suitable. One is at a wavelength of 1580 nm, but using light emitting diodes or laser diodes having three different peak wavelengths of 1560 nm, 1580 nm and 1590 nm is effective in avoiding temperature drift.

  Next, in the light receiving step in the optical measurement method according to the present invention, the light to be measured is irradiated by the light emitting step, and the light transmitted through or reflected by the object to be measured is received by the light receiving element, and an electric signal is transmitted. The signal is supplied to the next signal processing step. The light receiving element is preferably a conductive material composed of two or more kinds of semiconductors having different spectral sensitivity characteristics, and usually includes CdS, Si, GaAsS, InS, PbS, InSb, PbSe, Ge, etc. Then, CdS and CdSe are selected from Si and GaAs in the 900 nm region, GaInAs in the 1000 to 2000 nm region, and PbSe and PbS in the 2000 to 3000 nm region. In addition, when using a diode array as the light receiving means and measuring each wavelength simultaneously, it is possible to measure a plurality of wavelengths on the array, and it is also possible to compare by using noise removal at the same wavelength. .

  According to the optical measurement method of the present invention, the electrical signal output from the light receiving element is supplied to a signal processing step, the detection signal is supplied to a concentration calculation step of a biological substance, etc., and the absorption spectrum is analyzed and calculated. The measured value is calculated.

Next, an optical measurement apparatus for biological materials and the like according to the present invention will be described.
The optical measuring device comprises at least 1) a light emitting means, 2) a light collecting / irradiating means, 3) a light receiving means, 4) a signal processing means, 5) a biological substance concentration calculation means, and 6) a measured value display means. Specifically, it is configured as shown in FIG. 1, and will be described with reference to FIG.

1) The light emitting means 1 comprises a light emitting diode and a laser diode,
By sending a lighting start signal from the lighting circuit 8 to the LED 1 and passing a current, the light 1 ′
Release. The lighting circuit 8 is operated by a signal from the control circuit 9.
2) The condensing / irradiating means 2 is composed of a plano-convex lens and has a function of condensing the light 1 ′ emitted from the light emitting means 1 onto the sample 3. If the sample 3 is a blood sample, a glass cell is used.
3) The light receiving means 4 has a function of receiving the light transmitted through the sample 3 by a light receiving element, photoelectrically converting it, and outputting a signal, and transmits a change in the absorption density of the absorption maximum region of the biological material or the like to the signal processing means 5 To do.
4) The signal processing means 5 receives the output / signal of the light receiving means 4 and performs photoelectric conversion (A
/ D conversion) and input to the biological substance etc. concentration calculating means 6.
5) The biological substance equality calculating means 6 analyzes the absorption spectrum based on the detection signal photoelectrically converted by the signal processing means 5, and the absorption change is subjected to second-order differential processing. The concentration is calculated from multivariate analysis such as multiplication. The output signal is supplied to the display means 7 and displayed as a measured value.

A more suitable optical measuring device has the light emitting / irradiating / light receiving structure illustrated in FIG. 5, and the light emitting means 1 includes light emitting diodes or laser diodes having two or more different peak wavelengths. As shown, they are arranged in a row. In the figure, the light emitting means 1 has a light emitting diode having a peak wavelength that matches the maximum absorption band of a biological substance or the like at the center, and the figure shows two or more types of peak wavelengths that are continuously or discontinuously different from each other A light emitting diode is arranged.
The light receiving means 4 is formed by arranging two or more types of light receiving elements having different spectral sensitivity characteristics in a row as shown in FIG.

As a specific example of the non-invasive optical measurement apparatus according to the present invention, FIG. 6 illustrates an example using the light emission / irradiation / light reception system of FIG.
That is, a plastic housing is formed in a cylindrical housing having a length of 175 mm and a diameter of 25 mm, and each part of the device is embedded in the housing. 11, the calculation part 6 and the signal processing part 5 are arrange | positioned adjacently. A display unit 7 is disposed above the signal processing unit 5. A measurement switch 15 is arranged adjacent to the signal processing unit 5 and connected to the lighting circuit 8. An aluminum cylinder in which two or more kinds of LEDs 1, a lens system 9 and a light receiving element 4 are fixed at a predetermined interval is disposed adjacent to the lighting circuit 8. A finger insertion part is installed between the light receiving element 4 and the ceramic plate 13, and the signal processing device 5 is arranged adjacent to the ceramic plate 13.
After loading each part and device of these apparatuses, the periphery of each part and the space are filled with plastic and fixed. Such plastic filling can prevent disturbance factors from outside such as vibration and heat.

As a method of using the device configured as described above, when a finger is inserted into the finger insertion portion and the switch 15 is pressed, light emitted from the light emitting diodes 1 having two or more different wavelengths continuously travels along the optical path 14. Light collected by the condenser lens system 9, passes through the hole 44, passes through the finger inserted in front of the reflecting plate 13, and reflected light is received by the light receiving element 4, and its output is received by the signal processing unit 5. The photoelectric conversion is performed, and the concentration change calculation unit 6 calculates the absorption change by the absorption spectrum analysis, and the concentration is calculated by multivariate analysis such as a partial least square method.
FIG. 7 is an explanatory view showing a use state of the noninvasive optical measurement device according to the present invention. According to the figure, it is shown that the left finger is inserted into the finger insertion part, and the measured value is displayed on the display part on the right side of the apparatus.

  Next, the present invention will be described more specifically with reference to examples and comparative examples. However, the present invention is not limited to such examples.

Example 1
Commercially available glucose was dissolved in blood collected from a healthy person at a concentration of 0.1 to 1 mmol to prepare four kinds of measurement samples having different concentrations of 10 mg / ml to 50 mg / ml.
About each sample, the glucose color reaction 4-aminoantipyrine and the light absorbency in the phenol absorption wavelength of 505 nm were measured with "glucose CII test Wako" by Wako Pure Chemical Industries, Ltd., and it displayed on the horizontal axis shown in FIG. Using the commercially available infrared diode (L8254 manufactured by Hamamatsu Photonics) as a light source, the specific absorbance was measured for the same sample under the same conditions by the optical measurement method according to the present invention, and displayed on the vertical axis of the figure. The time required for the measurement was 5 to 10 minutes per sample in the conventional method using glucose CII “Test Wako” after sample preparation, whereas it was 1 second or less in the measurement method according to the present invention.
In addition, as shown in FIG. 2, the measurement result by the optical measurement method according to the present invention is almost the same as the measurement result by the glucose CII “Test Wako”, which is highly accurate and inferior to the practical product. I knew it was n’t there.

Example 2
Using a commercially available blue light emitting diode (blue LED NSPB500S manufactured by Nichia Corporation), the oxidation of reduced NAD in the measurement reaction of GOT (aspartate aminotransferase) is converted to reduced FAD using the action of dehydrogenase. As a result, GOT was quantified as an absorbance change near 450 nm. The measurement results are shown in FIG. The procedure is the same as in Example 1, but the high accuracy of the measurement method according to the present invention was proved when compared with the measured values by the displayed GOT UV “Test Wako” on the horizontal axis.

Example 3
Optical of FIG. 6 equipped with the light emission / irradiation / light reception structure shown in FIG. 5 in which two commercially available light emitting diodes having peak wavelengths of 1570 nm, 1580 nm and 2140 nm are arranged in parallel for 20 healthy people including mild diabetic patients. The glucose concentration was measured using a measuring device. In this case, a finger was inserted and fixed from the lower part of the apparatus.
Next, blood was collected from the same person at the same time, and the glucose concentration was measured using glucose CII “Test Wako”. The measurement results are shown on the horizontal axis of FIG.
The measurement device is operated by first pressing the measurement switch 15 and condensing the light emitted by simultaneously energizing the light emitting diodes 1 from the lighting circuit 8 with the combination lens system 9 and irradiating the finger with 6 pieces. The scattered light reflected from the peripheral blood vessels of the finger was captured by the light collecting element 4. The calculated value is shown on the vertical axis of FIG. From this result, temperature drift could be avoided and the correlation function was improved to 80% or more. For comparison, the correlation coefficient does not reach 50% when measured with only one type of light-emitting diode, and it can be seen that the measurement accuracy according to the present invention is remarkably high.

It is a block diagram which shows an example of a structure of the optical measuring device which concerns on this invention. FIG. 5 is a relationship diagram of measurement results of glucose using the measurement method according to the present invention and measurement results using a conventional “glucose CII test Wako”. It is a related figure of the measurement result by the measuring method which concerns on this invention about GOT (aspartate aminotransferase), and the measuring result by the measuring method using GOT-UV "Test Wako". FIG. 4 is a relationship diagram between a calculated value by multivariate analysis of blood glucose concentration measured by the noninvasive optical measurement device according to the present invention and a measurement result by “glucose CII test Wako”. It is explanatory drawing which shows one form of the light emission, irradiation, and light-receiving structure of the optical measuring device which concerns on this invention. It is explanatory drawing which shows one form of the internal structure of the noninvasive optical measuring device which concerns on this invention. It is explanatory drawing which shows one use condition of the noninvasive optical measuring device based on this invention of FIG.

Explanation of symbols

1. LED
2. Plano-convex lens Sample 4. Light receiving element 5. Signal processing device 6. Arithmetic unit 7. Display device 8. Lighting circuit
9. Lens system 10. Fingertip insertion part 11. Battery 12. Filled plastic13. Ceramic plate 14. Optical path 15. Measurement switch

Claims (2)

A non-invasive optical measurement device in which plastic is molded into a rod-shaped body having a circular or elliptical cross section and each element of the device is embedded in the housing,
A battery 11, an arithmetic processing unit 6, and a signal processing unit 5 are arranged adjacent to each other in the longitudinal direction from one side of the housing;
A display unit 7 is installed above the signal processing unit 5;
A lighting circuit unit 8 adjacent to the signal processing unit 5 and a measurement switch 15 adjacent to the lighting circuit unit 8;
A light metal cylinder in which two or more kinds of LEDs 1, a lens system 9, and two or more kinds of light receiving parts 4 are fixed at a predetermined interval is disposed adjacent to the lighting circuit part 8.
Providing a finger insertion part between the light receiving part 4 and the reflecting plate 13;
A signal processing device 5 is disposed adjacent to the back of the reflector 13;
The necessary connections between the elements;
Furthermore, the non-invasive optical measuring apparatus for biological substances and chemical substances, wherein each element of the apparatus is fixed by filling with plastic.   The non-invasive optical measurement apparatus according to claim 1, wherein the length of the housing is 170 to 220 mm, and the diameter when the cross section is circular or the long axis when the cross section is elliptical is 25 to 33 mm.

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