JP2014032145A - Concentration measuring device, and method for controlling the concentration measuring device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a new method for accurately measuring the concentration of a specific component in a test object containing a plurality of components.SOLUTION: In a concentration measuring device 1, first measurement light of a first wavelength and second measurement light of a second wavelength where absorbance of glucose substantially reaches an ignorable degree compared to absorbance of protein in a test object S are emitted to the test object S by a light source 10 that is an irradiation unit. Light transmitting through the test object S is received at a light receiving unit 50. An optical rotation calculation unit 120 calculates an optical rotation of the test object S in the first wavelength by the use of an output signal from the light receiving unit 50 in the case when the first measurement light is emitted. And, an absorbance calculation unit 130 calculates an absorbance of the test object S in the second wavelength by the use of an output signal from the light receiving unit 50 in the case when the second measurement light is emitted. Further, a concentration calculation unit 140 calculates the concentration of glucose by the use of the optical rotation calculated by the optical rotation calculation unit 120 and the absorbance calculated by the absorbance calculation unit 130.

Description

  The present invention relates to a concentration measuring device for measuring the concentration of a specific component in a subject.

  A method is known in which a component of a substance is known by measuring light transmitted through the substance. For example, when linearly polarized light passes through an optically active substance such as glucose, a phenomenon of optical rotation is known in which the plane of polarization rotates. In addition, a technique has been devised for measuring the concentration using the phenomenon of light absorption in which the absorption of light passing through the substance changes depending on the type and concentration of the substance (for example, Patent Documents 1 and 2).

JP 2004-81284 A JP 2004-113434 A

  Most of the conventional techniques for measuring the concentration non-invasively measure the concentration of a specific component in a subject by utilizing one of optical rotation and light absorption. However, with this technique, when measuring the concentration of a sample containing a plurality of types of components, it may be difficult to perform accurate measurement.

  This is because when the measurement is carried out on a specimen containing a plurality of types of components having similar optical rotation and absorption characteristics, the optical rotation and absorbance are each independently determined because the characteristics are similar. This is because it is difficult to separate each component.

  The present invention has been made in view of the above-described problems, and an object of the present invention is to propose a new method for correctly measuring the concentration of a specific component in a subject containing a plurality of components. .

  A first form for solving the above problem is a concentration measuring apparatus for measuring the concentration of the first component of a subject containing a first component and a second component having optical rotation and absorbance, A first measurement light having a first wavelength, and a second measurement light having a second wavelength at which the absorbance of the first component is substantially negligible compared to the absorbance of the second component in the subject. Using the output signal from the light receiving unit when the first measurement light is irradiated, the light receiving unit that receives the transmitted light that has passed through the subject, The object at the second wavelength using an optical rotation calculator for calculating the optical rotation of the object at one wavelength and an output signal from the light receiving part when the second measurement light is irradiated An absorbance calculation unit for calculating the absorbance of the optical rotation calculated by the optical rotation calculation unit, By using the absorbance calculated by serial absorbance calculation section, and a concentration calculator that calculates the concentration of the first component, the concentration measuring apparatus equipped with a.

  Further, as another embodiment, a method for controlling a concentration measuring apparatus that includes an irradiating unit that irradiates the subject with measurement light and a light receiving unit that receives the light transmitted through the subject, and measures the component concentration of the subject The analyte includes a first component and a second component having optical rotation and absorbance, and the first measurement light having the first wavelength and the absorbance associated with the second component in the subject. Compared to irradiating the irradiation unit with the second measurement light having the second wavelength at which the absorbance related to the first component is substantially negligible, and receiving the light when the first measurement light is irradiated. Calculating the optical rotation of the subject at the first wavelength using the output signal from the unit, and using the output signal from the light receiving unit when the second measurement light is irradiated, Calculating the absorbance of the analyte at a second wavelength; and the calculated optical rotation; By using the absorbance the calculated, and calculating the concentration of the first component, it is also possible to configure the control method comprising.

  According to the first embodiment, the absorbance of the first component can be substantially ignored by the irradiation unit compared to the first measurement light of the first wavelength and the absorbance of the second component in the subject. The subject is irradiated with the second measurement light having the second wavelength. The degree to which the absorbance is substantially negligible is, for example, based on the absorbance in terms of unit concentration of the first component and the second component and the assumed concentrations of the first component and the second component in the subject. It means that the absorbance of the first component is substantially negligible as compared to the absorbance of the second component in it. By irradiating the subject with the second measurement light having the second wavelength determined in this way, the first component and the second component can be separated.

  Specifically, the optical rotation of the subject at the first wavelength is calculated using an output signal from the light receiving unit when the first measurement light is irradiated. In addition, the absorbance of the subject at the second wavelength is calculated using the output signal from the light receiving unit when the second measurement light is irradiated. The optical rotation of the subject at the first wavelength is a value that mainly reflects the optical rotation of the first component and the second component. On the other hand, the absorbance of the subject at the second wavelength is a value that mainly reflects the absorbance of the second component. The optical rotation and absorbance can be converted to each other via the concentration. Therefore, the concentration of the first component can be calculated by using the optical rotation of the subject at the first wavelength and the absorbance of the subject at the second wavelength. That is, the concentration of the specific component in the subject can be accurately measured.

  More specifically, as a second mode, the concentration calculation unit in the concentration measurement apparatus of the first mode estimates the optical rotation related to the second component using the absorbance calculated by the absorbance calculation unit. The optical rotation of the first component using the second component optical rotation estimation unit, the optical rotation calculated by the optical rotation calculation unit, and the optical rotation estimated by the second component optical rotation estimation unit And a first component optical rotation estimator that estimates the concentration of the first component based on the optical rotation estimated by the first component optical rotation estimator. It is good.

  As described above, the absorbance of the subject at the second wavelength is a value that mainly reflects the absorbance of the second component. Therefore, the optical rotation related to the second component can be estimated by converting the absorbance calculated by the absorbance calculation unit into a concentration and converting it into the optical rotation. Further, the optical rotation of the subject at the first wavelength is a value mainly reflecting the optical rotation of the first component and the second component. Therefore, specifically, the optical rotation related to the first component is estimated by subtracting the optical rotation of the second component estimated by the second component optical rotation estimation unit from the optical rotation calculated by the optical rotation calculation unit. be able to. If the optical rotation related to the first component can be estimated, the concentration of the first component can be obtained.

  Further, as a third form, in the concentration measuring apparatus of the first or second form, the subject contains water, and the irradiation unit is compared with the absorbance related to the second component in the subject. The concentration measuring apparatus may be configured to irradiate the second wavelength with a wavelength at which the absorbance related to the first component and the absorbance related to water in the subject are substantially negligible.

  According to the third embodiment, the subject contains water, and the irradiation unit has the absorbance related to the first component in the subject and the absorbance related to water compared to the absorbance related to the second component in the subject. Is irradiated as the second wavelength. Thereby, it becomes possible to correctly calculate the concentration of the first component by eliminating the influence of light absorption.

  Further, as a fourth mode, in the concentration measuring apparatus according to any one of the first to third modes, a part of the irradiation light of the irradiation unit irradiated to the subject is contained in the subject. It further includes a reference light receiving unit that receives light via a reference body having a third component as a main component, and the absorbance calculation unit uses an output signal from the light receiving unit and an output signal from the reference light receiving unit. Thus, a concentration measuring device that calculates the absorbance at the second wavelength where the absorbance related to the third component is canceled may be configured.

  According to the fourth aspect, the reference body light receiving unit transmits a part of the irradiation light of the irradiation unit irradiated to the subject via the reference body mainly composed of the third component contained in the subject. Receive light. Then, the absorbance calculation unit calculates the absorbance at the second wavelength where the absorbance related to the third component is canceled, using the output signal from the light receiving unit and the output signal from the reference light receiving unit. Thereby, even when a component other than the first component and the second component (third component) is contained in the subject, it is possible to correctly calculate the concentration of the first component.

  Further, as a fifth mode, in the concentration measuring device according to the fourth mode, a concentration measuring device may be configured in which the third component is water.

  According to the fifth embodiment, coupled with the fourth embodiment, it is possible to eliminate the influence of water absorption even when water is contained in the subject.

  Further, as a sixth form, in the concentration measuring apparatus according to any one of the first to fifth forms, the subject is a living body, the first component is glucose, and the second component is a protein, The irradiation unit may constitute a concentration measurement apparatus that irradiates the subject with any wavelength of 400 nm to 900 nm as the first wavelength.

  According to the sixth embodiment, the subject is a living body, the first component is glucose, and the second component is protein. In this case, the irradiation unit calculates the optical rotation that reflects the optical rotation of glucose and protein by irradiating the subject with the first measurement light with the wavelength of any one of 400 nm to 900 nm as the first wavelength. Is possible.

  Moreover, as a seventh aspect, in the concentration measurement apparatus according to any one of the first to sixth aspects, the subject is a living body, the first component is glucose, and the second component is a protein, The irradiation unit may constitute a concentration measurement apparatus that irradiates the subject with any wavelength of 1600 nm to 1800 nm as the second wavelength.

  According to the seventh embodiment, the subject is a living body, the first component is glucose, and the second component is protein. In this case, the irradiation unit irradiates the subject with any one of wavelengths from 1600 nm to 1800 nm as the second wavelength, so that it is possible to calculate the absorbance that reflects the absorbance of the protein.

The block diagram which shows an example of a function structure of a density | concentration measuring apparatus. The figure which shows the wavelength dependence of the absorption coefficient in unit concentration conversion of each component. The flowchart which shows the flow of a density | concentration measurement process. The figure which shows the structural example of a 2nd optical apparatus. The flowchart which shows the flow of a 2nd density | concentration measurement process.

  Hereinafter, an example of a preferred embodiment of the present invention will be described with reference to the drawings. However, it is needless to say that embodiments to which the present invention is applicable are not limited to the embodiments described below.

1. 1. First embodiment 1-1. Configuration FIG. 1 is a block diagram illustrating an example of a functional configuration of a concentration measuring apparatus 1 according to the first embodiment. The concentration measuring apparatus 1 includes a first optical device 3A, a control unit 100, an operation unit 200, a display unit 300, a sound output unit 400, a communication unit 500, and a storage unit 600 as main components. Configured.

  The first optical device 3A includes a light source 10, a branching unit 20, a polarizing unit 30, an orthogonal separating unit 40, a light receiving unit 50, an amplification unit 60, a mirror 70, a second light receiving unit 80, and a second light receiving unit. And an amplifying unit 90.

  A subject S is disposed between the polarization unit 30 and the orthogonal separation unit 40. The subject S contains an optically active substance and can be an arbitrary sample such as a solid or liquid having optical transparency. In the present embodiment, the subject S will be described as a reagent containing glucose (first component), protein (second component), and water (third component) simulating the subcutaneous tissue of a living body. Among them, protein will be described as albumin and globulin, which are two types of plasma proteins that are contained in a large amount other than blood cell components in blood. This assumes a situation in which the glucose concentration in the interstitial fluid that has exuded from the blood into the body tissue is measured.

  The light source 10 is an irradiation unit configured to generate and emit measurement light having a plurality of wavelengths, and is configured as a multi-wavelength light source, for example. The light source 10 generates and emits measurement light having a wavelength designated by the irradiation control unit 110 under the control of the control unit 100.

  The branching unit 20 is a branching device that branches the measurement light emitted from the light source 10 into two light beams, a transmitted light beam and a reflected light beam, and has a beam splitter, for example. The transmitted light from the branching unit 20 enters the polarizing unit 30, and the reflected light is guided to the mirror 70.

  The polarizing unit 30 is a polarizing element (polarizer) that converts light emitted from the branching unit 20 into linearly polarized light. As the polarizing unit 30, for example, a Glan-Thompson prism, which is a kind of gran-type polarizer, can be applied.

  The orthogonal separation unit 40 is an optical element that separates the transmitted light having linearly polarized light transmitted through the subject S into orthogonal components, that is, polarized components different from each other by 90 degrees. For example, a Wollaston prism can be applied as the orthogonal separation unit 40.

  The light receiving unit 50 is an element that receives the light orthogonally separated by the orthogonal separation unit 40, and includes a photodetector such as a photodiode. The light receiving unit 50 includes a P-polarized light receiving unit 50A and an S-polarized light receiving unit 50B, and receives polarized components (P component and S component) orthogonally separated by the orthogonal separating unit 40. The light received by the light receiving unit 50 is photoelectrically converted, and a voltage value corresponding to the amount of received light is output to the amplifying unit 60. In the following description, the voltage photoelectrically converted by the P-polarized light receiving unit 50A is referred to as “P-polarized voltage”, and the voltage photoelectrically converted by the S-polarized light receiving unit 50B is referred to as “S-polarized voltage”. To do.

  The amplifying unit 60 is an arithmetic unit that amplifies the difference and sum of the received light levels in the light receiving unit 50, and includes an adder 61, a subtracter 63, an adding amplifier 65, and a subtracting amplifier 67. Is done. Outputs from the P-polarized light receiving unit 50A and the S-polarized light receiving unit 50B are added and subtracted by an adder 61 and a subtracter 63, respectively, and are amplified by an adding amplifier 65 and a subtracting amplifier 67, respectively.

  In the present embodiment, the amplification factor of the addition amplifier 65 is described as a first amplification factor “G1”, and the amplification factor of the subtraction amplifier 67 is described as a second amplification factor “G2”. The amplifying unit 60 outputs a voltage corresponding to the difference between the received light levels and a voltage corresponding to the sum of the received light levels to the control unit 100. In the following description, the voltage corresponding to the difference between the received light levels is referred to as “subtracted output voltage”, and the voltage corresponding to the sum of the received light levels is referred to as “added output voltage”.

The mirror 70 reflects one of the lights branched by the branching unit 20 and guides it to the second light receiving unit 80.
In the present embodiment, the light branched by the branching unit 20 is illustrated and described as being guided to the second light receiving unit 80 by the mirror 70, but instead, the light branched by the branching unit 20 is used. The optical path may be configured to guide the light to the second light receiving unit 80 using a light guide such as an optical fiber.

  The second light receiving unit 80 receives the measurement light reflected by the mirror 70. The light received by the second light receiving unit 80 is photoelectrically converted, and a voltage value corresponding to the amount of received light is output to the second amplifying unit 90.

  The second amplifying unit 90 is an amplifier that amplifies the voltage output from the second light receiving unit 80 with a predetermined amplification factor. In the present embodiment, the amplification factor of the second amplification unit 90 will be described as a third amplification factor “G3”.

  The light path from the branching unit 20 to the second amplifying unit 90 is an optical path designed for the purpose of simultaneously measuring the optical rotation and the absorbance, and is an optical path designed based on a so-called double beam method. .

  The control unit 100 is a control device that comprehensively controls each unit of the concentration measuring apparatus 1 and controls a microprocessor such as a CPU (Central Processing Unit) and a DSP (Digital Signal Processor), an ASIC (Application Specific Integrated Circuit), and the like. It is a kind of computer that has and is configured.

  The control unit 100 includes an irradiation control unit 110, an optical rotation calculation unit 120, an absorbance calculation unit 130, and a concentration calculation unit 140 as main functional units. However, these functional units are only described as one embodiment, and all the functional units are not necessarily essential components. Moreover, you may add a function part other than these as an essential component.

  The irradiation control unit 110 controls the irradiation of the measurement light to the subject S by the light source 10. Specifically, a control signal indicating the wavelength of the measurement light is output to the light source 10, and control is performed so that the measurement light having a desired wavelength is generated and emitted by the light source 10.

  The optical rotation calculation unit 120 calculates an output voltage (output signal) output from the amplification unit 60 when the subject S is irradiated with the first measurement light having the first wavelength in order to calculate the total optical rotation described later. Using this, the optical rotation of the subject S at the first wavelength is calculated.

  The absorbance calculation unit 130 outputs the output voltage (output from the amplification unit 60 and the second amplification unit 90 when the subject S is irradiated with the second measurement light having the second wavelength in order to calculate the protein absorbance described later. Output)), the absorbance of the subject S at the second wavelength is calculated.

  The concentration calculation unit 140 calculates the glucose concentration using the optical rotation calculated by the optical rotation calculation unit 120 and the absorbance calculated by the absorbance calculation unit 130. The concentration calculation unit 140 includes, as a functional unit, a protein optical rotation estimation unit 141 that estimates the optical rotation related to glucose using the absorbance calculated by the absorbance calculation unit 130. Further, the function unit includes a glucose optical rotation estimation unit 142 that estimates the optical rotation related to glucose using the optical rotation calculated by the optical rotation calculation unit 120 and the optical rotation estimated by the protein optical rotation estimation unit 141. Have as.

  The operation unit 200 is an input device that includes a button switch and the like, and outputs a signal of a pressed button to the control unit 100. By operating the operation unit 200, various instructions such as a glucose concentration measurement start instruction are input.

  The display unit 300 is configured to include an LCD (Liquid Crystal Display) or the like, and is a display device that performs various displays based on display signals input from the control unit 100. The display unit 300 displays information such as measured glucose concentration values.

  The sound output unit 400 is a sound output device that outputs various sounds based on a sound output signal input from the control unit 100. For example, notification sounds such as measurement start, measurement end, and error occurrence are output.

  The communication unit 500 is a communication device for transmitting / receiving information used inside the device to / from an external information processing device under the control of the control unit 100. As a communication method of the communication unit 500, a form in which a wired connection is made through a cable compliant with a predetermined communication standard, a form in which a connection is made through an intermediate device that is also used as a charger called a cradle, or short-range wireless communication is used. Various systems such as a wireless connection type can be applied.

  The storage unit 600 includes a storage device such as a ROM (Read Only Memory), a flash ROM, and a RAM (Random Access Memory). The storage unit 600 stores various programs, data, and the like for realizing various functions such as a system program of the concentration measuring apparatus 1, an optical rotation calculation function, and an absorbance calculation function. In addition, it has a work area for temporarily storing data being processed and results of various processes.

  The storage unit 600 stores a concentration measurement program 610 that is read by the control unit 100 and executed as a concentration measurement process (see FIG. 3). The concentration measurement process will be described later in detail using a flowchart.

  The storage unit 600 stores selected wavelength data 620, conversion data 630, total optical rotation 640, protein absorbance 650, and glucose concentration 660. These data will be described later.

1-2. Principle 1-2-1. Procedure for Measuring Glucose Concentration The concentration measuring apparatus 1 of the present embodiment measures the concentration of the first component of the subject S containing the first component and the second component having optical rotation and absorbance. In this embodiment, glucose concentration contained in the subject S is measured with glucose as the first component and protein as the second component. Rather than using either optical rotation or light absorbency alone, high-accuracy measurement of glucose concentration is realized by using both properties together.

  First, for the optical rotation, a first wavelength that is easy to transmit through the subject S and that shows a certain level of optical rotation of glucose and protein is selected. Then, the subject S is irradiated with the first measurement light having the first wavelength from the light source 10. In this case, the optical rotation calculation unit 120 calculates a value obtained by adding together the optical rotation of glucose and the optical rotation of protein as the optical rotation of the subject S at the first wavelength. The optical rotation calculated by the optical rotation calculation unit 120 is referred to as “total optical rotation”. That is, since the first wavelength can be said to be a wavelength used for calculating the total optical rotation, the first wavelength will be described as “total optical rotation calculation wavelength”. The inventor of the present application conducted experiments at various wavelengths and determined that it was appropriate to select the total optical rotation calculation wavelength from the wavelength range of 400 nm to 900 nm.

  Next, the second wavelength is selected for the absorbance such that the absorbance related to glucose is substantially negligible compared to the absorbance related to protein. The second wavelength here refers to the absorbance of glucose and protein in terms of unit concentration and the assumed concentration of glucose and protein in the specimen S, compared to the absorbance of the protein in the absorbance of the specimen. It means a wavelength at which the absorbance of glucose is substantially negligible. That is, the second wavelength means a wavelength at which protein appears predominantly compared to glucose in the phenomenon of light absorption on the subject S. Therefore, in the present embodiment, the second wavelength will be described as “protein absorption dominant wavelength”.

  According to experiments conducted by the inventors of the present application, the absolute values of albumin and globulin absorbances are relatively large compared to the absolute values of protein absorbances in the wavelength range of 1400 nm to 1500 nm and the wavelength range of 1600 nm to 1800 nm. I found it getting bigger. That is, it can be considered that these wavelength ranges are such that the absorbance related to glucose is substantially negligible compared to the absorbance related to protein.

  However, the problem here is that the subject S contains water as the third component. The light absorption of water is very large, and in addition, it has the property of being easily affected by temperature. Therefore, the light absorption of water is a major factor that lowers the measurement accuracy of the glucose concentration. Therefore, it is necessary to select the protein absorption dominant wavelength in consideration of the light absorption of water.

FIG. 2 is a graph showing the wavelength dependence of absorption coefficients (absorption coefficients) in terms of unit concentrations of glucose, protein and water. In FIG. 2, the horizontal axis represents wavelength (unit: nm), and the vertical axis represents absorption coefficient (unit: cm ⁻¹ ). The absorption coefficient on the vertical axis represents the absorption coefficient in terms of unit concentration (absorption coefficient normalized by concentration). The absorption coefficient of glucose is indicated by a solid line, the absorption coefficient of protein is indicated by a dotted line, and the absorption coefficient of water is indicated by a one-dot chain line.

  As can be seen from the graph, the absorption coefficient of water shows a maximum value at a wavelength in the vicinity of 1450 nm, and the absorption coefficient of water is larger than that of glucose or protein in the wavelength region in the vicinity. I understand that. For this reason, it is not appropriate to use a wavelength in this wavelength range. Therefore, paying attention to other wavelength regions, the protein absorption dominant wavelength is selected.

  It should be noted that the absorption spectrum in FIG. 2 represents an absorption spectrum in terms of unit concentration. When a living body is considered as a subject, the blood concentration of glucose is 80 to 100 [mg / dl] in a healthy person, whereas albumin, which is a kind of protein, is about 4 to 5 [g / dl]. The density has a difference of about 50 times. Therefore, it is necessary to select a protein absorption dominant wavelength in consideration of this concentration difference.

  Considering that the water absorption peak exists in the vicinity of 1460 nm or 2000 nm, the inventor of the present application preferably determines 1600 nm to 1800 nm, more preferably 1700 nm to 1800 nm, as judged from the absorption spectrum of FIG. It was judged that it was appropriate to select a protein absorption dominant wavelength from the wavelength range of.

  The sample S is irradiated with measurement light having a protein absorption dominant wavelength selected from the above wavelength range, and the absorbance is calculated using the amount of transmitted light and the amount of measurement light in that case. The absorbance calculated in this case is an absorbance in which the absorbance associated with the protein in the subject S is superior to the absorbance of glucose and water. Therefore, this absorbance is regarded as protein absorbance and used for calculation of glucose concentration. Specifically, the optical rotation related to the protein in the subject S (hereinafter referred to as “protein optical rotation”) is estimated using the absorbance calculated by the absorbance calculation unit.

但し、「Ａｂｓ」は吸光度算出部１３０によって算出された吸光度であり、「ε」はタンパク質のモル吸光係数である。また、「ｃ」はタンパク質の濃度であり、「ｌ」は被検体Ｓを測定光が透過する際の透過光路長である。 The estimation of the protein rotation can be performed by converting the absorbance calculated by the absorbance calculation unit 130 into a concentration and converting the concentration into an optical rotation. The conversion from absorbance to concentration can be performed, for example, according to the Lambert-Beer law given by the following equation (1).

However, “Abs” is the absorbance calculated by the absorbance calculator 130, and “ε” is the molar extinction coefficient of the protein. “C” is the protein concentration, and “l” is the transmitted light path length when the measurement light passes through the subject S.

  It is assumed that the Lambert-Beer law is not strictly established due to an error factor caused by the performance of the optical elements constituting the optical device. Therefore, a calibration curve indicating the relationship between the concentration and absorbance associated with the protein is obtained in advance, the data is stored in the storage unit 600, and conversion from absorbance to concentration is performed using the calibration curve data. Also good.

但し、［α］^t _λは温度ｔ、波長λでのタンパク質の比旋光度であり、「α」はタンパク質の旋光度である。 Subsequently, according to following Formula (2), the density | concentration of protein is converted into the optical rotation of protein.

Where [α] ^t _λ is the specific rotation of the protein at temperature t and wavelength λ, and “α” is the rotation of the protein.

  If the protein optical rotation is estimated as described above, the optical rotation related to glucose in the subject S (hereinafter referred to as “the optical rotation”) is calculated using the previously calculated total optical rotation and the estimated protein optical rotation. Called "glucose optical rotation"). The total optical rotation is the optical rotation obtained by adding together the optical rotation of glucose and the optical rotation of protein. Therefore, the glucose optical rotation can be estimated by subtracting the protein optical rotation from the total optical rotation.

  Finally, the glucose concentration in the subject S is estimated by converting the estimated glucose rotation into a concentration. The conversion from the optical rotation to the concentration in this case can be realized by applying Equation (2) as an equation relating to glucose.

  In order to realize the conversion from the absorbance to the optical rotation and the conversion from the optical rotation to the concentration, parameters such as the molar extinction coefficient and specific rotation of the component contained in the specimen S, and the absorption of each component Data such as a calibration curve may be stored in advance in the storage unit 600 as the conversion data 630.

1-2-2. Calculation Method of Optical Rotation The amount of transmitted light that has passed through the subject S is “E _a ² ”, the incident angle of linearly polarized light with respect to the orthogonal separating unit 40 is “θ ₀ ”, and the optical rotation by the subject S (optical rotation angle) Is “θ”. At this time, the electric field component of P-polarized light and the electric field component of S-polarized light are represented by “E _a × cos (θ + θ ₀ )” and “E _a × sin (θ + θ ₀ )”, respectively. Therefore, the P-polarized voltage and the S-polarized voltage are expressed by “E _a ² × cos ² (θ + θ ₀ )” and “E _a ² × sin ² (θ + θ ₀ )”, respectively.

At this time, by subtracting the S-polarized voltage from the P-polarized voltage, the subtracted voltage “Vs” can be obtained as in the following equation (3). Further, by adding the P-polarization voltage and the S-polarization voltage, the addition voltage “Va” can be obtained as in the following equation (4).

The amplifying unit 60 calculates the subtraction voltage “Vs” and the addition voltage “Va” expressed by the equations (3) and (4), and amplifies the calculation results. Since the amplification factor for the subtraction voltage “Vs” is the first amplification factor “G1” and the amplification factor for the addition voltage “Va” is the second amplification factor “G2”, the subtraction output voltage “V1” output from the amplifying unit 60. And the added output voltage “V2” are expressed by the following equations (5) and (6), respectively.

From the equations (5) and (6), the following equation (7) can be derived.

但し、「Ｇ１／Ｇ２＝Ｃ１」と置き換えた。 Therefore, from the formula (7), the optical rotation “θ” can be calculated as the following formula (8).

However, it was replaced with “G1 / G2 = C1”.

1-2-3. Method for calculating absorbance The amount of light received by the second light receiving unit 80 is defined as “E _b ² ”. At this time, the output voltage “V3” from the second amplifying unit 90 is given by the following equation (9).

但し、「Ｇ３／Ｇ２＝Ｃ２」と置き換えた。 In this case, the absorbance “Abs” can be calculated by the following equation (10) using the added output voltage “V2” and the output voltage “V3”.

However, it was replaced with “G3 / G2 = C2.”

1-2-4. Calibration of Optical Device In this embodiment, the optical device is calibrated so that the optical rotation and absorbance are correctly calculated.
The calculation of the optical rotation “θ” requires two parameter values “C1” and “θ ₀ ”. “C1” can be calculated using the design value of the first gain “G1” and the design value of the second gain “G2”. Further, “θ ₀ ” is mechanically set to a predetermined angle. However, in calculating the optical rotation expressed by a very small angle, the above parameter value determines whether the optical rotation is correctly calculated.

The design amplification factor of the amplifying unit 60 may include errors due to the accuracy of the elements used. It is conceivable that the measurement accuracy of the optical rotation decreases due to the error. Therefore, two or more types of substances whose optical rotation is known are measured, and the optical rotation is calculated using the voltage value output from the optical apparatus in this case. Then, the optical apparatus is calibrated based on the deviation between the calculated value of the optical rotation and the theoretical value of the optical rotation of the substance used as the measurement target. Since there are two “C1” and “θ ₀ ”, two unknowns can be obtained if two or more equations are established. The solution of the equation can be calculated using a known numerical calculation such as a least square method.

Similarly, the value of the parameter relating to the calculation of absorbance is obtained. Specifically, the ratio “C2” between the second gain “G2” and the third gain “G3”, and the ratio “E _a ² / E” between the light amounts “E _a ² ” and “E _b ² ”. The values of the two parameters “ _b ² ” are obtained. The amplification factors (design values) of the amplifying unit 60 and the second amplifying unit 90 may include errors due to the accuracy of the elements used as described above. In addition, fluctuations may occur in the amount of light received by the light receiving unit 50 and the second light receiving unit 80 due to the characteristics of the optical elements constituting the measurement light irradiation system and the light receiving system. These error factors are factors that reduce the accuracy of the absorbance calculation.

  Therefore, measurement is performed in a state where the subject S is not disposed (a state where there is no sample) or a state where a predetermined standard reagent is disposed, and in this case, the absorbance is calculated using the voltage value output from the optical device. Then, the optical apparatus is calibrated based on the deviation between the calculated absorbance value and the theoretical absorbance value of the standard reagent or the like.

1-3. Processing Flow FIG. 3 is a flowchart showing the flow of concentration measurement processing executed by the control unit 100 in accordance with the concentration measurement program 610 stored in the storage unit 600.

  First, the control unit 100 performs an initial calibration process (step A1). Specifically, as described above, the optical device is calibrated by obtaining the parameters for calculating the optical rotation and the parameters for calculating the absorbance.

  Next, the control unit 100 selects the total optical rotation calculation wavelength and the protein absorption dominant wavelength, and stores the selected wavelength data 620 in the storage unit 600 (step A3). The wavelength range for selecting these wavelengths is as described above.

  Next, the irradiation control unit 110 performs irradiation control of the measurement light having the total optical rotation calculation wavelength (step A5). Specifically, a control signal for generating and emitting measurement light having a combined optical rotation calculation wavelength is output to the light source 10 and control is performed so that the subject S is irradiated with the measurement light having the combined optical rotation calculation wavelength.

  Next, the optical rotation calculation unit 120 uses the parameter values calibrated in the initial calibration process and the addition output voltage and the subtraction output voltage output from the addition amplifier 65 and the subtraction amplifier 67 according to the equation (8). Is stored in the storage unit 600 as the combined optical rotation 640 (step A7).

  Thereafter, the irradiation control unit 110 performs emission control of the measurement light having the protein absorption dominant wavelength (Step A9). Specifically, a control signal for generating and emitting measurement light having a protein absorption dominant wavelength is output to the light source 10, and control is performed so that the measurement light having a protein absorption dominant wavelength is irradiated to the subject S.

  Next, the absorbance calculation unit 130 uses the parameter value calibrated in the initial calibration process, the addition output voltage output from the addition amplifier 65, and the output voltage output from the second amplification unit 90 to obtain equation (10). Then, the absorbance is calculated and stored in the storage unit 600 as the protein absorbance 650 (step A11).

  Next, the protein optical rotation estimation unit 141 uses the conversion data 630 stored in the storage unit 600 to estimate the protein optical rotation from the protein absorbance 650 (step A13). Then, the glucose optical rotation estimation unit 142 estimates the glucose optical rotation by subtracting the protein optical rotation from the total optical rotation (step A15).

  Thereafter, the concentration calculation unit 140 converts the glucose rotation into a concentration using the conversion data 630, and stores the conversion result in the storage unit 600 as the glucose concentration 660 (step A17). And the control part 100 complete | finishes a concentration measurement process, after performing the control which displays the calculated glucose concentration 660 on the display part 300 as a measurement result (step A19).

1-4. Action and Effect In the concentration measurement apparatus 1, the absorbance related to glucose is substantially ignored compared to the measurement light (first measurement light) of the total optical rotation calculation wavelength (first wavelength) and the absorbance related to the protein in the subject S. The measurement light (second measurement light) having a protein absorption dominant wavelength (second wavelength) to the extent possible is irradiated onto the subject S by the light source 10 (irradiation unit). The transmitted light that has passed through the subject S is received by the light receiving unit 50.

  The optical rotation calculation unit 120 calculates the optical rotation of the subject S at the first wavelength using the output signal from the light receiving unit 50 when the first measurement light is irradiated. In addition, the absorbance calculation unit 130 calculates the absorbance of the subject S at the second wavelength using the output signal from the light receiving unit 50 when the second measurement light is irradiated. Then, the concentration calculator 140 calculates the glucose concentration using the optical rotation calculated by the optical rotation calculator 120 and the absorbance calculated by the absorbance calculator 130.

  The optical rotation of the subject S at the first wavelength is calculated as a value mainly reflecting the optical rotation of glucose and protein. On the other hand, the second wavelength is a wavelength at which the absorbance related to glucose and the absorbance related to water are substantially negligible compared to the absorbance related to the protein in the subject S. The absorbance of the subject S is a value that mainly reflects the absorbance of the protein. The optical rotation and absorbance can be converted to each other via the concentration. Therefore, the glucose concentration can be correctly calculated by using the optical rotation of the subject S at the first wavelength and the absorbance of the subject S at the second wavelength.

2. Second Embodiment FIG. 4 is a diagram illustrating an example of a configuration of a second optical device 3B in the second embodiment. In the second optical device 3B, the reference body R is arranged between the mirror 70 and the second light receiving unit 80. In this case, the second light receiving unit 80 functions as a reference light receiving unit that receives part of the irradiation light from the light source irradiated to the subject via the reference body.

  In this embodiment, the reference body is water. The reason why the water is arranged as a reference body is to calculate the absorbance at the protein absorption dominant wavelength in which the absorbance related to water in the subject is canceled. By disposing water as the reference body R, transmitted light that has been absorbed by water is received by the second light receiving unit 80. In this case, when the absorbance is calculated according to the equation (10) using the output voltage “V3” from the second amplification unit 90, the absorbance of water is subtracted from the absorbance of the subject S, and the absorbance related to water is canceled. Absorbance at the absorption dominant wavelength is obtained. This measurement method is referred to as “differential measurement method”.

  However, the absorbance of water tends to change with temperature. Therefore, it is necessary to arrange the subject S and the reference body R in an environment where the temperature difference can be regarded as almost zero. For example, it is preferable that the components of the second optical device 3B other than the light source 10 are installed in a temperature-controlled room, or the temperature of the subject S and the reference body R is kept the same and constant by using a temperature control cell holder. is there. According to this configuration, since it is not necessary to consider the influence of water absorption, a wavelength different from the protein absorption dominant wavelength (second wavelength) exemplified in the first embodiment can be used for calculating the absorbance.

  Here, FIG. 2 will be referred to again. In the differential measurement method of the present embodiment, it is not necessary to consider the influence of water absorption, so it is only necessary to select a wavelength by paying attention only to the absorption characteristics of glucose and protein. Specifically, a wavelength at which the absorbance related to glucose is substantially negligible compared to the absorbance related to protein in the subject may be selected as the protein absorption dominant wavelength.

  For example, in the wavelength range of 1300 nm to 1450 nm, the absorbance of the protein is higher than the absorbance of glucose. Further, even in the wavelength range of 1700 nm to 1900 nm, the absorbance of the protein is higher than the absorbance of glucose. Therefore, for example, the absorbance may be calculated by selecting a protein absorption dominant wavelength from these wavelength ranges.

  Note that the principle and procedure for calculating the glucose concentration are as described in the first embodiment, and there is no difference except that water is disposed as the reference body S, and thus the description thereof is omitted.

3. Modifications Embodiments to which the present invention can be applied are not limited to the above-described embodiments, and can be changed as appropriate without departing from the spirit of the present invention. Hereinafter, modified examples will be described.

3-1. Application form The concentration measurement apparatus described in the above embodiment can be used by being incorporated in a measuring device such as a sugar measurement apparatus that measures the sugar content of fruits or a blood sugar level measurement apparatus that measures human blood sugar levels. It is.

  When applied to a sugar content measuring apparatus, for example, fruit juice may be measured by the procedure described in the above embodiment using the fruit juice as the subject S. In addition, when applied to a blood sugar level measuring device, a part having permeability such as a human earlobe, fingertip, or epidermis of a finger may be used as a measurement part, and the measurement light may be irradiated to the measurement part. . In this case, the living body is the subject.

3-2. Ingredients of specimen In the above embodiment, the first component is glucose and the second component is protein. However, these are only described as one example. As long as it is a component having optical rotation and light absorption, it is possible to measure the concentration of the first component in the same procedure as in the above embodiment, using any component as the first component and the second component.

  In the above-described embodiment, water has been described as an example of the third component contained in the subject. However, this is only an example. Even when the component other than water is the third component, it is possible to measure the concentration of the first component on the same principle as in the above embodiment.

3-3. Selection of Second Wavelength According to the absorption spectrum measured by the present inventor, in addition to the near-infrared wavelength region, there is a wavelength region in which the protein absorbance is larger than the glucose absorbance in the visible light wavelength region. Exists. Therefore, for example, the absorbance may be calculated by selecting the second wavelength from a wavelength range such as a wavelength range of 400 nm to 700 nm.

3-4. Spectral Analysis by Wavelength Sweep In the above embodiment, the case where the wavelength of the light source is discrete is assumed, and measurement light having a preselected wavelength is generated in the light source 10 and irradiated on the subject S. However, when the wavelength of the light source can be changed continuously, a wavelength sweep (wavelength sweep) is performed to store all the optical rotation and absorption spectrum data in the storage unit 600. It can be read out and used for density calculation.

  FIG. 5 is a flowchart showing the flow of the second concentration measurement process executed by the control unit 100 of the above embodiment in place of the concentration measurement process of FIG. 3 in this case. Note that the same steps as those in the concentration measurement process are denoted by the same reference numerals and description thereof is omitted.

  The control unit 100 starts wavelength sweeping of the light source 10 after step A3 (step B5). Specifically, the wavelength of the measurement light is continuously changed in a predetermined wavelength range (for example, 400 nm to 2000 nm). The control unit 100 performs spectral analysis of optical rotation and absorbance while performing wavelength sweep (step B7). By this spectral analysis, continuous spectral waveform data is obtained for each of the optical rotation and absorbance. Thereafter, the control unit 100 ends the wavelength sweep (step B9).

  Next, the control unit 100 reads the optical rotation corresponding to the total optical rotation calculation wavelength selected in step A3 from the optical rotation spectrum data obtained by the spectral analysis, and sets it as the total optical rotation (step B11). Moreover, the control part 100 reads the light absorbency corresponding to the protein light absorption dominant wavelength selected by step A3 from the data of the light absorbency spectrum obtained by the spectrum analysis, and makes it a protein light absorbency (step B13). The subsequent processing is the same as the concentration measurement processing.

3-5. Concentration calculation method In the above embodiment, one wavelength is selected as each of the total optical rotation calculation wavelength (first wavelength) and the protein absorption dominant wavelength (second wavelength), and the calculation of the total optical rotation and protein Absorbance was calculated. Then, the glucose concentration was calculated using one value for each of the total optical rotation and the protein absorbance. However, a plurality of wavelengths may be selected as the first wavelength and the second wavelength and used for calculating the glucose concentration.

  For example, in the graph of the absorption spectrum in terms of unit concentration in FIG. 2, a plurality of wavelengths having the same glucose ratio to the protein absorption coefficient are selected as protein absorption dominant wavelengths, and calculation is performed using the respective protein absorption dominant wavelengths. The measured glucose concentration may be used to determine the final measured glucose concentration. For example, statistical processing such as obtaining an average value of glucose concentration calculated using a plurality of protein absorption dominant wavelengths is performed, and a more reliable measurement value of glucose concentration is determined using a plurality of calculated glucose concentration values. It may be.

3-6. Calculation of optical rotation and absorbance In the above embodiment, the optical rotation and absorbance are calculated using the instantaneous values of the output voltages output from the amplifying unit 60 and the second amplifying unit 90. The optical rotation and absorbance may be calculated using the average value of the output voltages. Further, the step of calculating the optical rotation and absorbance using the instantaneous value of the output voltage is repeated to calculate a predetermined time or a predetermined number of optical rotations and absorbances, and these are averaged to calculate the optical rotation and absorbance. It is good.

3-7. Polarizing Optical Element In the above-described embodiment, the polarizing unit 30 has been described as having a Glan-Thompson prism, for example. However, it is needless to say that other polarizing optical elements may be used. . For example, it is good also as a structure which has the Grand Taylor prism which is the optical element for polarization | polarized-light of the same gran type.

  In the above embodiment, the orthogonal separation unit 40 is described as having a Wollaston prism, for example. However, the polarization optical element constituting the orthogonal separation unit 40 can be changed as appropriate. For example, it is good also as a structure which has the optical element for polarization | polarized-light which has orthogonal separation function, such as a grand laser prism and a lotion prism.

  DESCRIPTION OF SYMBOLS 1 Density measuring apparatus, 3A 1st optical apparatus, 3B 2nd optical apparatus, 10 Light source, 20 Branch part, 30 Polarization part, 40 Orthogonal separation part, 50 Light receiving part, 50A P polarized light receiving part, 50B S polarized light receiving part, 60 Amplifying unit, 61 adder, 63 subtractor, 65 adding amplifier, 67 subtracting amplifier, 70 mirror, 80 second light receiving unit, 90 second amplifying unit, 100 control unit, 200 operation unit, 300 display unit, 400 sound Output unit, 500 communication unit, 600 storage unit

Claims (8)

A concentration measuring device for measuring a concentration of the first component of a subject containing a first component and a second component having optical rotation and absorbance,
A first measurement light having a first wavelength, and a second measurement light having a second wavelength at which the absorbance of the first component is substantially negligible compared to the absorbance of the second component in the subject. An irradiation unit for irradiating the subject;
A light receiving unit that receives the transmitted light that has passed through the subject;
An optical rotation calculator that calculates an optical rotation of the subject at the first wavelength using an output signal from the light receiving unit when the first measurement light is irradiated;
An absorbance calculation unit that calculates an absorbance of the subject at the second wavelength, using an output signal from the light receiving unit when the second measurement light is irradiated;
A concentration calculator that calculates the concentration of the first component using the optical rotation calculated by the optical rotation calculator and the absorbance calculated by the absorbance calculator;
Concentration measuring device with The concentration calculator
A second component optical rotation estimation unit that estimates an optical rotation related to the second component using the absorbance calculated by the absorbance calculation unit;
A first component optical rotation estimation unit that estimates an optical rotation related to the first component using the optical rotation calculated by the optical rotation calculation unit and the optical rotation estimated by the second component optical rotation estimation unit. When,
And calculating the concentration of the first component based on the optical rotation estimated by the first component optical rotation estimation unit,
The concentration measuring apparatus according to claim 1. The subject contains water;
The irradiation unit has a wavelength at which the absorbance related to the first component in the subject and the absorbance related to water are substantially negligible compared to the absorbance related to the second component in the subject. Irradiate as the second wavelength,
The concentration measuring apparatus according to claim 1 or 2. A reference light receiving unit that receives a part of the irradiation light of the irradiation unit irradiated on the subject through a reference body mainly composed of a third component contained in the subject;
The absorbance calculation unit calculates an absorbance at the second wavelength in which the absorbance related to the third component is canceled using an output signal from the light receiving unit and an output signal from the reference light receiving unit.
The density | concentration measuring apparatus as described in any one of Claims 1-3. The third component is water;
The concentration measuring apparatus according to claim 4. The subject is a living body,
The first component is glucose;
The second component is a protein;
The irradiating unit irradiates the subject with any wavelength of 400 nm to 900 nm as the first wavelength.
The density | concentration measuring apparatus as described in any one of Claims 1-5. The subject is a living body,
The first component is glucose;
The second component is a protein;
The irradiation unit irradiates the subject with any one of wavelengths from 1600 nm to 1800 nm as the second wavelength.
The density | concentration measuring apparatus as described in any one of Claims 1-6. A method for controlling a concentration measuring apparatus comprising: an irradiating unit that irradiates a subject with measurement light; and a light receiving unit that receives light transmitted through the subject;
The subject includes a first component and a second component having optical rotation and absorbance,
A first measurement light having a first wavelength, and a second measurement light having a second wavelength at which the absorbance of the first component is substantially negligible compared to the absorbance of the second component in the subject. Irradiating the irradiation unit with
Calculating an optical rotation of the subject at the first wavelength using an output signal from the light receiving unit when the first measurement light is irradiated;
Calculating an absorbance of the subject at the second wavelength using an output signal from the light receiving unit when the second measurement light is irradiated;
Using the calculated optical rotation and the calculated absorbance to calculate the concentration of the first component;
Control method.

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