JP2005147896A - Method and apparatus for measuring concentration of mixed solution component - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a concentration measuring method, capable of noninvasively and accurately measuring the concentration of a plurality of biological components contained in a mixed solution. <P>SOLUTION: The absorption spectra of the mixed solution are measured in a process 1; the absorption spectra are shifted, in such a way that the absorbance within a prescribed wavelength region including wavelengths between 8.4-8.5 μm become zero in a process 2; wavelength regions λ1 and λ2 of the same number as that of the components are set in a measurement wavelength region, and absorbance area values S1 and S2, between the shifted absorbance spectra and the line of absorbance=0, are computed for each of the wavelength regions λ1 and λ2 in a process 3; correlation between the concentration of each component substance and absorbance is set for each substance to be measured in a process 4; and concentrations SA and SB of the components in the mixed solution are computed, on the basis of the absorbance area values S1 and S2 and the correlation of the process 4 in a process 5. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a concentration measuring method and a concentration measuring apparatus for measuring the concentration of each component in a mixed solution using infrared absorption.

  Conventionally, as a method of non-invasively measuring blood glucose levels without collecting blood, glucose is irradiated by irradiating a measurement site such as a patient's earlobe or finger and detecting the transmitted infrared light. There is a method of measuring the absorption of infrared light by, and estimating the blood glucose level from the result (see, for example, Patent Document 1).

Japanese Patent Laid-Open No. 2003-42948

  However, various methods have been proposed for determining the concentration of one component from a plurality of components contained in blood based on the measured degree of absorption of infrared light. However, the situation is still insufficient. Furthermore, no reliable method has been obtained for an analysis method for determining the concentration of each component from a mixed solution containing a plurality of components.

The invention of claim 1 irradiates a mixed solution containing a plurality of biological components as a measurement target substance with infrared light, detects absorbance by Fourier transform infrared spectroscopy, and includes a plurality of measurement target substances contained in the mixed solution Is a concentration measurement method for determining the concentration of an infrared ray by irradiating the mixed solution with infrared light, detecting transmitted infrared light in a measurement wavelength region from a wavelength of 7.5 μm to a wavelength of 10 μm transmitted through the mixed solution, and absorbance. A first step of acquiring a spectrum, a second step of correcting the absorbance spectrum so that the absorbance in a predetermined wavelength region including wavelengths from 8.4 μm to 8.5 μm is zero, and a measurement wavelength The third step of setting the same number of divided wavelength regions as the number of components of the substance to be measured in the region and calculating the absorbance area value between the corrected absorbance spectrum and the absorbance = 0 line for each divided wavelength region. When Measurement in a mixed solution based on the fourth step of setting the correlation between the concentration of the measurement target substance and the absorbance for each measurement target substance, and the correlation between the absorbance area value and each measurement target substance And a fifth step of calculating the concentration of the target substance.
According to a second aspect of the present invention, in the concentration measurement method according to the first aspect, the detected absorbance is corrected according to the temperature of the mixed solution.
The invention of claim 3 is the concentration measurement method according to claim 1 or 2, wherein the substance to be measured is a blood component in the living body, and is obtained by changing the blood flow volume at the measurement site instead of the absorbance spectrum. A concentration measurement method using a difference between absorbance spectra before and after the change.
The invention according to claim 4 determines the concentration of the plurality of measurement target substances contained in the mixed solution by irradiating the mixed solution containing a plurality of biological components as the measurement target substance with infrared light and detecting the amount of transmitted infrared light. A first step of setting the same number of divided wavelength regions as the number of components of a measurement target substance in a measurement wavelength region from a wavelength of 7.5 μm to a wavelength of 10 μm, and a transmitted infrared light amount related to the measurement target material The second step of setting the correlation between the absorbance and the absorbance for each measurement target substance and for each divided wavelength region, and the transmitted infrared light amount of the mixed solution in each divided wavelength region, respectively, Based on the third step of calculating the absorbance of the mixed solution in each divided wavelength region based on the ratio of the incident infrared light amount and the transmitted infrared light amount of the infrared light irradiated on the light source, and the absorbance and correlation of the mixed solution Measurement in mixed solution And a fourth step of calculating the concentration of the target substance.
According to a fifth aspect of the present invention, in the concentration measurement method according to the fourth aspect of the invention, the detected transmitted infrared light amount is corrected according to the temperature of the mixed solution.
The invention according to claim 6 is the concentration measurement method according to claim 4 or 5, wherein the substance to be measured is a blood component in a living body, and the blood flow volume at the measurement site is changed instead of the transmitted infrared light amount. A density measurement method using the difference in transmitted infrared light amount before and after the change obtained by the above.
A seventh aspect of the present invention is the concentration measuring apparatus using the concentration measuring method according to any one of the fourth to sixth aspects, wherein each of the divided wavelength regions includes a filter that transmits infrared light in the wavelength region, A filter switching mechanism for selectively disposing any one of a plurality of filters is provided in the optical path between the external light source and the irradiation target.

  ADVANTAGE OF THE INVENTION According to this invention, the density | concentration of the several biological component contained in a mixed solution can be measured noninvasively accurately.

  Hereinafter, the best mode for carrying out the present invention will be described with reference to the drawings. FIG. 1 is a conceptual diagram of an apparatus for measuring the component concentration of a mixed solution sample 1 using FTIR (Fourier transform infrared spectroscopy). The FTIR measuring apparatus performs analysis based on an infrared light irradiation unit 2 that irradiates the sample 1 with infrared light, a light receiving unit 3 that detects infrared light transmitted through the sample 1, and an output signal of the light receiving unit 3. And a processing unit 4.

  Infrared light 21 emitted from the infrared light source 20 enters the interferometer 22. As the interferometer 22, for example, a Michelson interferometer is used. The infrared light 21 is divided into two infrared lights 24 and 25 by the beam splitter 23 of the interferometer 22. The infrared light 24 transmitted through the beam splitter 23 is reflected by a moving mirror 26 provided in the interferometer 22 and then reflected by the beam splitter 23 toward the sample 1 on the right side of the drawing. The infrared light 25 reflected by the beam splitter 23 is reflected by the fixed mirror 27 and then passes through the beam splitter 23 in the direction of the sample 1.

  At this time, the infrared light 24 and 25 reflected by the movable mirror 26 and the fixed mirror 27 are combined by the beam splitter 23, and the interference light (interferogram) 28 corresponding to the phase difference between the infrared light 24 and 25 is combined. Become. The interference light 28 enters the sample 1 as measurement infrared light, and the infrared light 29 transmitted through the sample 1 is detected by the light receiving unit 3. The detection signal from the light receiving unit 3 is input to the calculation unit 40 of the analysis processing unit 4, and component concentration calculation as described later is performed in the calculation unit 40. The analysis processing unit 4 includes a storage unit 41 for storing data necessary for calculation, data after calculation, and a display unit 42 for displaying measurement data and calculation results.

  Note that the sample 1 to be measured is a mixed solution containing a plurality of substances, and in this embodiment, the main component of the mixed solution is a biological component such as glucose or lactic acid. Therefore, the measurement range of infrared light is set to a wavelength of 7.5 μm to 10 μm suitable for measurement of biological components.

  Next, the concentration measuring method according to the present invention will be described. FIG. 2 shows the absorbance spectrum SP1 of the glucose solution, the absorbance spectrum SP2 of the lactic acid solution, and the absorbance spectrum SP3 of the mixed solution of glucose and lactic acid. In the vicinity of the wavelength of 8.4 to 8.5 μm indicated by the symbol G, the absorbances of the three solutions are almost equal, and can be considered as an absorbance region that does not depend on the concentration of glucose or lactic acid.

  Therefore, in the present embodiment, the wavelength range of 8.4 to 8.5 μm is set as a reference wavelength, and the entire absorbance spectrum is shifted so that the absorbance at that time becomes zero. Then, concentration analysis is performed using the corrected absorbance spectrum. It was found that the absorbance spectrum after correction was the sum of the absorbance spectrum of the glucose solution and the absorbance spectrum of the lactic acid solution. That is, the peak absorbance appearing in the absorbance spectrum is proportional to the concentration of the substance in the solution. For example, the absorbance peak value at the concentration 2C that is twice the concentration C is twice as large as the absorbance peak value at the concentration C.

  In the present embodiment, each component concentration is analyzed based on these in the following procedure. Below, the case where the density | concentration of 2 components of the substances A and B, for example, the mixed solution of glucose and lactic acid is analyzed is demonstrated according to the procedure shown in FIG. First, as shown in Step 1, an absorbance spectrum as shown in FIG. 2 is obtained by FTIR measurement. In step 2, the absorbance spectrum is shifted so that the absorbance is zero with the wavelength around 8.4 to 8.5 μm as the reference wavelength. The spectrum curve L in FIG. 4 shows the absorbance spectrum after the shift.

  In step 3, predetermined wavelength regions λ1 and λ2 are set for the absorbance spectrum of the mixed solution (see FIG. 4), and the absorbance area values S1 and S2 in the respective wavelength regions λ1 and λ2 are calculated. The predetermined wavelength regions λ1 and λ2 are set in advance according to the target component for concentration measurement and stored in the storage unit 41. Here, the absorbance area value means an area value between the spectrum curve L and a straight line of absorbance 0 (horizontal axis). From the above, it is considered that these absorbance area values S1 and S2 are the sum of the absorbance due to the substance A and that due to the substance B.

  As described above, since the absorbance peak value increases in proportion to the concentration, the absorbance area value also increases in proportion to the concentration. Therefore, when the concentration of the substance A increases by a predetermined value (increased concentration ΔA), the increase amount of the absorbance area value in the wavelength region λ1 is A1, and the increase amount in the wavelength region λ2 is A2. FIG. 5A is a diagram showing the increments A1 and A2. At this time, when the amount of increase in concentration is twice the predetermined increase concentration ΔA, the absorbance area values become 2A1 and 2A2, which are twice each.

  Similarly, regarding the substance B, the amount of increase in the absorbance area value in the wavelength regions λ1 and λ2 with respect to the increased concentration ΔB is defined as B1 and B2. In step 4, these reference increase amounts A1, A2, B1, and B2 are set. For convenience of explaining the analysis procedure, the reference increase amounts A1, A2, B1, and B2 are set in step 4. However, in practice, the reference increase amounts A1, B2, B1, and B2 using the reference samples of the substances A and B are used. A2, B1, and B2 are measured, and a value obtained by the measurement is stored in advance in the storage unit 41 as a reference increase amount.

  FIG. 5B shows the increase amounts B1 and B2 of the absorbance area value of the substance B. Of course, the shape (absorption spectrum) is different from that of the substance A. In the example shown in FIGS. 5A and 5B, infrared light absorption by the substance A is greatly generated in the wavelength region λ2, while infrared light absorption by the material B is largely generated in the wavelength region λ1.

  Here, assuming that the concentration of the substance A in the mixed solution is SA and the concentration of the substance B is SB, the concentration SA is α times the increase concentration ΔA described above, and the concentration SB is β times the increase concentration ΔB. Suppose there was. That is, it is assumed that α = SA / ΔA and β = SB / ΔB. In that case, the absorbance spectrum pattern of FIG. 4 is an overlay of the pattern of FIG. 5A multiplied by α and the pattern of FIG. 5B multiplied by β.

Therefore, the following formula (1) is established for the absorbance area value S1 of the wavelength region λ1.
S1 = α · A1 + β · B1 (1)
Similarly, the following equation (2) holds for the absorbance area value in the wavelength region λ2.
S2 = α · A2 + β · B2 (2)
In step 5, by solving these simultaneous equations, α and β are obtained as in equations (3) and (4), and using these α and β, the concentrations SA and SB are calculated by the following equations (5) and (6). calculate.
α = (B2 · S1−B1 · S2) / (A1 · B2−A2 · B1) (3)
β = (A2, S1-A1, S2) / (B1, A2-B2, A1) (4)
SA = ΔA · α (5)
SB = ΔB · β (6)

When the components in the mixed solution are three components (A, B, and C), λ1, λ2, and λ3 are set for the three wavelength regions, and the increased concentrations ΔA, ΔB, and ΔC in the respective wavelength regions λ1 to λ3 are set. Find in advance. In this case, similarly to α and β described above, α1, α2 and α3 are given to the increased concentrations ΔA, ΔB and ΔC, and simultaneous equations consisting of the following equations (7) to (9) are established.
S1 = α1 · A1 + α2 · B1 + α3 · C1 (7)
S2 = α1 · A2 + α2 · B2 + α3 · C2 (8)
S3 = α1 · A3 + α2 · B3 + α3 · C3 (9)

Then, using the calculated α1, α2, and α3, the concentrations SA, SB, and SC of the components A, B, and C are calculated by the following equations (10) to (12). In the case of four or more components, the concentration of each component can be calculated in the same manner.
SA = ΔA · α1 (10)
SB = ΔB · α2 (11)
SC = ΔB · α3 (12)

  By the way, when the test object is blood in a living body, measurement by the ATR (total reflection measurement) method is common. In the ATR method, a prism as shown in FIG. 6A is used as an optical member. In the example shown in FIG. 6A, the measurement jig 5 is attached to the finger F, which is a measurement site, and infrared light measurement is performed. The prism 51 provided in the measurement jig 5 is disposed so as to be in close contact with the abdomen of the finger F. The prism 51 is a prism formed of a high refractive index material that transmits infrared rays.

  Infrared light (interference light) 28 is incident on the sample surface 51a of the prism 51 at an incident angle greater than the critical angle, and the infrared light totally reflected at the boundary between the prism 51 and the sample (finger F) is received by the light receiving unit. Lead to 3 and measure. FIG. 6B shows an enlarged boundary region between the finger F and the sample surface 51 a of the prism 51. In the boundary region, the infrared light 28 passes through the sample surface of the prism 51, passes through the very surface of the finger F, and then returns into the prism 51.

  The measuring jig 5 is provided with a temperature sensor 52 that measures the temperature of the finger F and a cuff 53 that applies a desired pressing force to the finger F by air pressure or the like. By changing the pressing force of the cuff 53, the blood flow rate of the blood flowing through the finger F can be changed. The thickness of human skin varies from person to person, and it is necessary to remove these error factors when measuring the degree of absorption of infrared light by blood.

  When the blood flow is intentionally changed by the cuff 53, the degree of absorption of infrared light also changes according to the change. Therefore, by analyzing this amount of change, the concentration of components (glucose and lactic acid) in the blood can be calculated without being affected by the thickness of the skin or the like. In this case, it is possible to obtain the same spectrum curve as in FIG. 4 described above by measuring the absorbance spectrum before and after the blood flow change and taking the difference between them. Since the calculation method of the concentration of each component based on the spectrum curve is the same as in the case of the measurement in FIG. 1, the description of the concentration calculation method is omitted.

  Moreover, the body temperature at the time of measuring the absorbance may be measured by the temperature sensor 52, and the absorbance spectrum may be corrected based on the measured body temperature. Since the degree to which infrared light is absorbed varies depending on the temperature of the measurement object, more accurate concentration measurement can be performed by correcting the measured absorbance based on body temperature. In this case, a calibration curve indicating how much the absorbance changes with temperature may be prepared in advance, and the absorbance spectrum may be calibrated according to the calibration curve.

  In the above-described embodiment, the concentration of each component is calculated based on absorbance measurement data using FTIR, but the present invention can also be applied to infrared light measurement other than FTIR measurement. For example, each concentration in the mixed solution can be calculated using an apparatus that measures the amount of transmitted infrared light as shown in FIG.

  In FIG. 7, the same parts as those in FIG. As in the apparatus of FIG. 1, the infrared light 21 emitted from the infrared light source 20 is divided into two infrared lights 24 and 25 by a branching element 68 that partially branches the beam. Here, the branch element 68 is set so as to reflect a part of the incident light and pass the remaining part. The infrared light 25 reflected by the branch element 68 is detected by the light receiving unit 64. The light receiving unit 64 outputs an output signal (output voltage) proportional to the amount of infrared light, and the output signal is amplified by the amplifier 65 and then input to the arithmetic unit 40 of the analysis processing unit 4.

  On the other hand, the infrared light 24 that has passed through the branch element 68 is incident on the sample 1. As for the infrared light 29 that has passed through the sample 1, only the infrared light in the predetermined wavelength region λ is transmitted by the band pass filter 60. The transmitted light from the band pass filter 60 passes through the light chopper 67 and is detected by the light receiving unit 61. The output signal of the light receiving unit 61 is amplified by the amplifier 62 and input to the lock-in amplifier 63. The lock-in amplifier 63 receives an on / off signal of a light chopper 67 that turns on and off infrared light incident on the light receiving unit 61 as a reference signal f.

  The lock-in amplifier 63 detects only a component equal to the reference signal frequency among various signals included in the measurement signal input from the light receiving unit 61 via the amplifier 62. Therefore, an unnecessary signal, for example, a noise signal detected as disturbance light is removed, and the S / N ratio can be improved, and a minute signal buried in the noise signal can also be measured. The output signal of the lock-in amplifier 63 is input to the calculation unit 40 as a measurement signal. The sample 1 is equipped with a temperature sensor 66 such as a thermocouple, and a detection signal from the temperature sensor 66 is input to the calculation unit 40.

<Single component analysis method>
First, a method for calculating the concentration of a single component will be described. In the above-described FTIR measurement, the frequency spectrum of absorbance can be directly measured. However, in the infrared light measurement apparatus of FIG. 7, the intensity of transmitted infrared light in the wavelength region λ defined by the bandpass filter 60 is measured by the light receiving unit 61. Detected. Therefore, one type of output voltage is measured for infrared light in the wavelength region λ.

  FIG. 8 is a diagram showing the output voltage Vu, and shows that the output voltage Vu is measured for infrared light in the wavelength region λ. When the unknown concentration of the single component contained in the sample 1 is Nu, the output voltage Vu is a voltage corresponding to the amount of infrared light transmitted in the wavelength region λ at the unknown concentration Nu, and the voltage Vu is transmitted through the wavelength region λ. This is called voltage.

  As described above, since a part of the light from the infrared light source 20 is reflected by the branch element 68 and the rest passes through the branch element 68, the voltage input from the amplifier 65 to the arithmetic unit 40 is This corresponds to a voltage value corresponding to the amount of infrared light incident on the sample 1. Therefore, this makes it possible to correct fluctuations in the amount of light output from the light source 20. Hereinafter, the voltage detected when passing through the reference pure water sample is V0, and this is called the incident output voltage. In other words, a pure water sample (no concentration) is incident on the sample 1 in advance, the amount of infrared light transmitted therethrough is measured, and a voltage value corresponding to the transmitted infrared light amount is stored in the storage unit 41 as data of the incident output voltage V0. Keep it.

A sample having a reference concentration Nk and a sample having a concentration Nh different from the reference concentration Nk by ΔN are prepared in advance, and the transmission output voltages Vk and Vh in the wavelength region λ of those samples are measured, and the obtained data is stored in the storage unit 41 (see FIG. 7). The concentration Nh is referred to as a change concentration. The absorbances Ak and Ah of the samples having the reference concentration Nk and the change concentration Nh are calculated by the equations (13) and (14) using the measured incident output voltage V0.
Ak = log (V0 / Vk) (13)
Ah = log (V0 / Vh) (14)

Further, the concentration of the sample 1 in the wavelength region λ is set as the unknown concentration Nu, and the absorbance Au of the unknown concentration Nu is also calculated by the equation (15) similarly to Ak and Ah.
Au = log (V0 / Vu) (15)

Then, as ΔA = Ah−Ak, Au can be expressed as the following formula (16). Since the values of Au, Ak, and ΔA can be calculated from the measured values, α can be obtained by solving equation (16). The unknown concentration Nu is calculated by substituting the calculated α into the following equation (17).
Au = Ak + αΔA (16)
Nu = Nk + αΔN (17)

  In addition, by measuring the temperature rise of the sample 1 and its vicinity by the temperature sensor 66, the relationship between the temperature change and the transmitted output voltage, that is, the relationship between the temperature change and the transmitted output voltage of the light receiving unit 61 can be detected. . Therefore, the accuracy of density calculation can be improved by correcting the transmission output voltage based on the temperature detected by the temperature sensor 66. Further, since the infrared light 25 branched by the branch element 68 is detected by the light receiving unit 64, the change in the output voltage due to the temporal variation of the infrared light source 20 can be captured and corrected.

  When the test object is blood in a living body, for example, measurement may be performed using a measurement jig 15 as shown in FIG. In the measurement jig 15, 115 is an infrared light source, 116 is a band pass filter, and 117 is a light receiving unit, which correspond to the infrared light source 20, the band pass filter 60 and the light receiving unit 61 in FIG. 7, respectively. Other configurations are the same as those of the measuring jig 5.

  In the case of infrared light measurement using the measurement jig 15, as in the case of FTIR measurement using the measurement jig 5, the measurement is performed by changing the blood flow with the cuff 53, thereby depending on the thickness of the skin. The error factor can be removed. Moreover, the body temperature at the time of measuring the absorbance may be measured by the temperature sensor 52, and the absorbance spectrum may be corrected based on the measured body temperature.

  Since the degree of absorption of infrared light varies depending on the thickness of the measurement target (finger F), the jig 15 is structured to sandwich the finger F up and down, and the thickness of the finger F is predetermined when worn. Clamp it to a thickness. As a result, variations in measured values due to the thickness of the measurement target can be reduced. In addition, regarding the incident output voltage V0 serving as a reference at this time, data is measured in advance regarding the combination of the infrared light source 115 and the band pass filter 116, and the data is stored in the storage unit 41 and used as needed.

《Analysis method of mixed components》
Next, the procedure of the analysis method when the sample 1 is a mixed solution in which three components A, B, and C are mixed will be described with reference to FIG.
[Step 1]
First, in the first step, three wavelength regions λ1, λ2, and λ3 are set corresponding to the number of components. For example, as the band-pass filter 60 in FIG. 7, a band-pass filter 60A1 in the transmission wavelength region λ1, a band-pass filter 60A2 in the transmission wavelength region λ2, and a band-pass filter 60A3 in the transmission wavelength region λ3 are prepared.

  Then, when measuring the transmission output voltage in the wavelength region λ1, the measurement is performed by inserting the band-pass filter 60A1 into each optical path. The same applies when measuring the transmission output voltages in the wavelength regions λ2 and λ3. As an example of a method for replacing the band-pass filters 60A1 to 60A3, the band-pass filters 60A1 to 60A3 are arranged in a rotary turret, and the filter is replaced by rotating the turret.

  Further, when measuring the concentrations of a plurality of components in the biometric jig 15 shown in FIG. 9A, a turret 118 as shown in FIG. The turret 118 is provided with three band-pass filters 119a, 119b, and 119c, and the turret 118 may be rotated so that band-pass filters corresponding to the wavelength regions λ1 to λ3 are disposed on the optical path. . Thus, by providing the turret 118 as a filter switching mechanism, the measurement work can be reduced.

[Step 2]
In the second step, for each component A, B, C, the relationship between the amount of transmitted infrared light and the absorbance is obtained. Here, since the transmitted output voltage output from the light receiving unit 61 is proportional to the received transmitted infrared light amount, the relationship between the transmitted output voltage and the absorbance is obtained. First, a sample having a reference concentration Nak including only the component A and a sample having a change concentration Nah are prepared. The transmission output voltages Vak1, Vak2, Vak3 and the transmission output voltages Vah1, Vah2, Vah3 in the wavelength regions λ1 to λ3 are respectively prepared. Measure. The change concentration Nah differs from the reference concentration Nak by ΔNa. The obtained data is stored in the storage unit 41. FIG. 11 is a diagram showing the transmission output voltages Vak1, Vak2, and Vak3 and the transmission output voltages Vah1, Vah2, and Vah3.

Further, the incident output voltages V01, V02, and V03 in the wavelength regions λ1 to λ3 are also measured. Using the measured transmission output voltages Vak1 to Vak3, Vah1 to Vah3 and the incident output voltages V01 to V03, the absorbances Aak1 to Aak3 and Aah1 to Aah3 are calculated according to the following formulas (18) to (23). Remember.
Aak1 = log (V01 / Vak1) (18)
Aak2 = log (V02 / Vak2) (19)
Aak3 = log (V03 / Vak3) (20)
Aah1 = log (V01 / Vah1) (21)
Aah2 = log (V02 / Vah2) (22)
Aah3 = log (V03 / Vah3) (23)

The same applies to the component B, and a sample having a reference concentration Nbk including only the component B and a sample having a change concentration Nbh having a concentration different from that by ΔNb are prepared. Output voltages Vbk1, Vbk2, and Vbk3 and transmitted output voltages Vbh1, Vbh2, and Vbh3 are measured, respectively. The obtained data is stored in the storage unit 41. Then, the absorbances Abk1 to Abk3 and Abh1 to Abh3 are calculated by the following equations (24) to (29) and stored in the storage unit 41.
Abk1 = log (V01 / Vbk1) (24)
Abk2 = log (V02 / Vbk2) (25)
Abk3 = log (V03 / Vbk3) (26)
Abh1 = log (V01 / Vbh1) (27)
Abh2 = log (V02 / Vbh2) (28)
Abh3 = log (V03 / Vbh3) (29)

For the component C, a sample having a reference concentration Nck including only the component C and a sample having a change concentration Nch having a concentration different by ΔNc are prepared, and the transmission output voltage Vck1 in the wavelength regions λ1 to λ3 is prepared for each sample. , Vck2, Vck3 and transmitted output voltages Vch1, Vch2, Vch3, respectively. The obtained data is stored in the storage unit 41. Then, the absorbances Ack1 to Ack3 and Ach1 to Ach3 are calculated by the following equations (24) to (29) and stored in the storage unit 41.
Ack1 = log (V01 / Vck1) (30)
Ack2 = log (V02 / Vck2) (31)
Ack3 = log (V03 / Vck3) (32)
Ach1 = log (V01 / Vch1) (33)
Ach2 = log (V02 / Vch2) (34)
Ach3 = log (V03 / Vch3) (35)

[Step 3]
In step 3, the transmission output voltage of the sample 1 in each wavelength region λ1, λ2, and λ3 is measured. As described above, since the transmitted output voltage is proportional to the amount of transmitted infrared light incident on the light receiving unit 61, the transmitted infrared light amount in each wavelength region λ1, λ2, λ3 is obtained by this measurement. Then, based on the obtained transmission output voltage, the absorbance of the sample 1 in each wavelength region λ1, λ2, λ3 is calculated.

  First, when the transmission output voltage is measured for the sample 1 using the bandpass filters 60A1 and 60B1, the transmission output voltage Vd1 of the sample 1 in the wavelength region λ1 is obtained. Similarly, the transmission output voltage Vd2 in the wavelength region λ2 is obtained when the bandpass filters 60A2 and 60B2 are used, and the transmission output voltage Vd3 in the wavelength region λ3 is obtained when the bandpass filters 60A3 and 60B3 are used. FIG. 12 is a diagram illustrating the transmission output voltages Vd1 to Vd3 in the wavelength regions λ1 to λ3 of the sample 1.

From the transmission output voltages Vd1 to Vd3 and the incident output voltages V01 to V03, the absorbances Ad1, Ad2, and Ad3 of the sample 1 in the wavelength regions λ1 to λ3 are calculated by the following equations (36) to (38). In the expressions (36) to (38), V01 / Vdh1 and the like represent the ratio of the incident infrared light amount and the transmitted infrared light amount,
Adh1 = log (V01 / Vdh1) (36)
Adh2 = log (V02 / Vdh2) (37)
Adh3 = log (V03 / Vdh3) (38)

[Step 4]
In step 4, the concentrations of components A, B, and C contained in the sample 1, that is, unknown concentrations Na, Nb, and Nc are calculated based on the calculated absorbances.

First, the absorbances Ad1 to Ad3 of the sample 1 (mixed solution) in each wavelength region λ1 to λ3 can be considered to be the sum of contributions to the absorbance due to the respective a to c, and thus are obtained for the respective components A to C. The following data (39) to (41) can be expressed using the obtained data. In each equation, ΔAmn (where m = a, b, c, n = 1, 2, 3) is a value calculated by ΔAmn = Amhn−Amkn.
Adh1 = (Aak1 + αΔAa1) + (Abk1 + βΔAb1)
+ (Ack1 + γΔAc1) (39)
Adh2 = (Aak2 + αΔAa2) + (Abk2 + βΔAb2)
+ (Ack2 + γΔAc2) (40)
Adh3 = (Aak3 + αΔAa3) + (Abk3 + βΔAb3)
+ (Ack3 + γΔAc3) (41)

Α, β, and γ can be obtained by solving the simultaneous equations of the equations (39) to (41). And each unknown density | concentration Na-Nc is computable by following Formula (42)-(44) by using computed (alpha), (beta), and (gamma).
However, ΔNa = Nah−Nak, ΔNb = Nbh−Nbk, and ΔNc = Nch−Nck.
Na = Nak + αΔNa (42)
Nb = Nbk + βΔNb (42)
Nc = Nck + γΔNc (42)

  Further, when the number of components is 4 or more, the unknown concentration of each component can be calculated by the same method by setting the number of divisions of the wavelength region to 4 or more correspondingly. In the embodiment described above, the density is measured by detecting the amount of transmitted light. However, the present invention can also be applied to the case where the density is measured by detecting the amount of reflected light. In addition, the present invention is not limited to the above embodiment as long as the characteristics of the present invention are not impaired.

It is a conceptual diagram of the apparatus which measures the component density | concentration of the mixed solution sample 1 using FTIR. It is a figure which shows absorbance spectrum SP1, SP2 and SP3. It is a figure which shows the density | concentration analysis procedure in FTIR measurement. It is a figure which shows the light absorbency spectrum after a shift. It is a figure explaining the light-absorbency area value corresponding to a density | concentration increase, (a) is related with the substance A, (b) is related with the substance B. It is a figure explaining the biological measurement by ATR method, (a) is sectional drawing of the measurement jig | tool 5, (b) is a figure explaining reflection of the infrared light 28 in a boundary. It is a figure which shows schematic structure of an infrared-light measuring apparatus. It is a figure explaining a permeation | transmission output voltage. It is a figure explaining the measurement jig | tool 15, (a) is sectional drawing of the measurement jig | tool 15, (b) is a figure which shows the turret 118. FIG. It is a figure which shows the density | concentration analysis procedure at the time of using an infrared-light measuring apparatus. It is a figure which shows the transmission output voltage Vak1, Vak2, Vak3 and the transmission output voltage Vah1, Vah2, Vah3. FIG. 6 is a diagram showing transmitted output voltages Vd1 to Vd3 in the wavelength regions λ1 to λ3 of the sample 1.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Sample 2 Infrared light irradiation part 3,61,64 Light-receiving part 4 Analysis processing part 5,15 Measuring jig 20,115 Infrared light source 40 Calculation part 41 Memory | storage part 51 Prism 52,66 Temperature sensor 53 Cuff 60,116, 119a, 119b, 119c Band pass filter 118 Turret λ, λ1, λ2, λ3 Wavelength region

Claims (7)

Irradiating a mixed solution containing a plurality of biological components as a measurement target substance with infrared light, and detecting the absorbance by Fourier transform infrared spectroscopy to determine the concentration of the plurality of measurement target substances contained in the mixed solution A concentration measuring method comprising:
A first step of irradiating the mixed solution with infrared light, detecting transmitted infrared light in a measurement wavelength region from a wavelength of 7.5 μm to a wavelength of 10 μm transmitted through the mixed solution, and acquiring an absorbance spectrum;
A second step of correcting the absorbance spectrum so that the absorbance in a predetermined wavelength region including a wavelength from a wavelength of 8.4 μm to a wavelength of 8.5 μm is zero;
The same number of divided wavelength regions as the number of components of the measurement target substance are set in the measurement wavelength region, and the absorbance area value between the corrected absorbance spectrum and the absorbance = 0 line is set for each of the divided wavelength regions. A third step of calculating;
A fourth step of setting a correlation between the concentration of the measurement target substance and the absorbance for each measurement target substance;
And a fifth step of calculating a concentration of the measurement target substance in the mixed solution based on the absorbance area value and the correlation set for each measurement target substance. . The concentration measurement method according to claim 1,
A concentration measuring method, wherein the detected absorbance is corrected according to the temperature of the mixed solution. The concentration measuring method according to claim 1 or 2,
The measurement target substance is a blood component in a living body, and instead of the absorbance spectrum, a difference between absorbance spectra before and after the change obtained by changing the blood flow at the measurement site is used. . A concentration measurement method in which a mixed solution containing a plurality of biological components as a measurement target substance is irradiated with infrared light, a transmitted infrared light amount is detected, and the concentration of the plurality of measurement target substances contained in the mixed solution is determined. There,
A first step of setting the same number of divided wavelength regions as the number of components of the measurement target substance in a measurement wavelength region from a wavelength of 7.5 μm to a wavelength of 10 μm;
A second step of setting a correlation between the amount of transmitted infrared light and absorbance of the measurement target substance for each measurement target substance and for each divided wavelength region;
Each of the divided wavelength regions is acquired based on the ratio of the incident infrared light amount of the infrared light irradiated to the mixed solution and the transmitted infrared light amount, respectively, in each of the divided wavelength regions. A third step of calculating the absorbance of the mixed solution in
A concentration measuring method comprising: a fourth step of calculating a concentration of the measurement target substance in the mixed solution based on the absorbance of the mixed solution and the correlation. The concentration measurement method according to claim 4,
The concentration measuring method, wherein the detected transmitted infrared light amount is corrected according to the temperature of the mixed solution. In the concentration measuring method according to claim 4 or 5,
The measurement target substance is a blood component in a living body, and instead of the transmitted infrared light amount, a difference between the transmitted infrared light amount before and after the change obtained by changing the blood flow volume at the measurement site is used. Concentration measurement method. In the density | concentration measuring apparatus using the density | concentration measuring method in any one of Claims 4-6,
Each of the divided wavelength regions includes a filter that transmits infrared light in the wavelength region, and selectively selects one of the plurality of filters in the optical path between the infrared light source and the irradiation target. A concentration measuring apparatus comprising a filter switching mechanism to be disposed.

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