JPH0843301A - Method and device for measuring absorbance, component concentration or specific gravity of liquid sample - Google Patents

Abstract

PURPOSE:To easily measure component concentration and specific gravity with high accuracy. CONSTITUTION:Measuring luminous flux is made incident on a triangular cell 2 containing a liquid sample, and transmitted light is received by a linear sensor 3 to detect both transmitted light intensity and a luminous flux position. A refractive index is calculated based on the detection position by the linear sensor 3 by a refractive index calculation part 30. Absorbance depending upon component concentration, in which influence of a transmission factor change in the triangular cell 2 is corrected, is calculated by an absorbance calculation part 31 by using the transmitted light intensity and the refractive index of the sample calculated by the refractive index calculation part 30. Multivariate analysis calculation is conducted by a component concentration calculation part 32 to calculate concentration of each component, based on the absorbance depending upon the component concentration at a plurality of measuring wavelength calculated by the absorbance calculation part 31. Specific gravity is calculated by 2 specific gravity calculation part 33 based on the concentration of each component calculated by the component concentration calculation part 32. In a urine specific gravity calculation part 35, already known data indicating relationship between a refractive index of urine and its specific gravity is used, the refractive index of urine sample obtained by the refractive index calculation part 30 is applied to the data to find the specific gravity of the urine sample, and an increasing quantity of urine specific gravity corresponding to concentration of glucose and protein in the component concentration calculated by the component concentration calculation part 32 is corrected.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for measuring the absorbance, component concentration or specific gravity of various liquid samples including urine and blood, and a measuring device therefor.

[0002]

Lambert-Beer's law is used for measuring absorbance. The absorption equation of the Lambert-Beer law in an ideal state is expressed by the following equation (1). log {Io (λ) / I (λ)} = ε (λ) × C × L (1) Io (λ): incident light intensity on the cell I (λ): intensity of the measurement light transmitted through the cell ε (λ): Extinction coefficient of component (depending on wavelength) C: Concentration of component in solution L: Cell length From formula (1), if concentration C of solution and optical path length L do not change during wavelength scanning. , Io and I can be measured to obtain a spectrum in a form proportional to the absorption coefficient peculiar to the substance.

The specific gravity of urine is an index showing the concentration of total solutes dissolved in urine, and is determined by the amount of urine regulated by the kidney and the amount of solute finally excreted in urine. The urine specific gravity is roughly divided into the following five methods. Gravimetric method: Calculate the specific gravity of urine from the weight ratio of pure water and the same volume of urine at the same temperature and pressure. Ultrasonic method: Determine the specific gravity of urine by measuring the difference in ultrasonic velocity due to the difference in solution density. Test strip method: Determine urine specific gravity by measuring ionic strength. Droplet drop method: Determine the specific gravity from the precipitation rate of urine dropped in a solvent that does not mix with water, such as oil. Refractive index method: Refractive index is one of optical properties and has a deep correlation with the purity of liquid and the concentration of solution. In addition, the refractive index of a solution can be precisely measured. In particular, since the refractive index of urine is almost proportional to the specific gravity of urine, the urine refractive index is used in correspondence with the refractive index using the Japanese Society for Clinical Pathology nomograms of FIGS. 2 and 3 created in 1979 by the Japanese Society for Clinical Pathology Standardization Committee. Calculate the specific gravity. In this case, the refractive index is measured using a refractometer.

In the routine inspection, the refractive index method and the test strip method are often used. Since the test paper used in the test paper method has a blue-green to yellow-green color tone depending on the hydrogen ion concentration, the urine specific gravity is 1.
It is shown in seven steps of 0.005 width in the range of 000 to 1.030. The test strip method has the advantage that it is less susceptible to proteins and sugars. However, the accuracy of the specific gravity presentation is 0.001 in the refractive index method, while it is 0.0 in the test strip method.
05 width and coarse. Further, while the test strip method is a measurement method that is performed by visual judgment, the refractive index method is easy to construct a measurement device, and automatic measurement can be performed at high speed and with high accuracy.

[0005] By improving the variation among manufacturers by the refractive index method and by compensating for the difference between the gravimetric method based on the change in the composition ratio of solute components, a unified standard in Japan has been made. Therefore, the following two items were examined. (1) The main solutes present in urine are sodium chloride, urea, etc., which act depending on the physiological or pathological state to affect the specific gravity of urine. (2) Under pathological conditions, an increase in the concentration of proteins and sugars and the administration of drugs have a greater effect on changes in the specific gravity of urine.

Considering these points, the influence of glucose and protein on the specific gravity of urine is as follows: (1) The specific gravity of glucose is increased by 1% and the specific gravity of urine is increased by 0.004. The specific gravity is supposed to be corrected by increasing 0.003. Therefore, the measurement of urine specific gravity by the refractive index method is performed in combination with a general-purpose test strip method for measuring proteins and sugars in urine, and the specific gravity obtained using a refractometer is measured with a test strip. It is corrected according to the sugar and protein concentrations obtained by using.

A method for determining the urine specific gravity by using the relationship between the urea concentration and the urine specific gravity has also been proposed (Japanese Patent Laid-Open No. 5-18084).
No. 6 publication). In the proposed method, the urea concentration is measured by using a urea concentration measuring color tester that shows the urea concentration in urine as a color change, such as a urine test strip, and the result is previously calculated. The urine specific gravity is calculated by fitting it to a standard color chart showing the relationship between the urea concentration and the urine specific gravity. The standard color chart showing the relationship between color development based on urea concentration and urine specific gravity is
The relationship between the urea concentration and the specific gravity of urine is: Specific gravity of urine = Concentration of urea (mg / dl) x 1.43 x 10 ^-5 +
It is based on what is shown in 1.008, and the urine specific gravity range normally measured between 1.000 and 1.030 is 7 in 0.005 steps.
It is created by equally dividing the color tone of the urea concentration measuring color test paper showing the urea concentration with respect to the center value of each range.

[0008]

When a cell such as glass is used as a container for a sample in absorption measurement,
Light is reflected at the cell-air interface and the cell-solution interface, and the transmitted light intensity is affected. The reflection between the cell and the air is related only to the refractive index of the air and the cell and not to the concentration of the solution. However, the reflection at the cell-solution interface is related to the refractive index of the solution and changes with different solution concentrations. for that reason,
It is necessary to correct the effect of refraction on the transmitted light intensity via the change in transmittance.

Therefore, considering that the transmitted light intensity changes due to the change in transmittance due to refraction, the transmitted light intensity I is
From the Lambert-Bear absorption equation, it is expressed as the following equation (2). I = Iot (no, nc, n) exp (-ΣαiCiL) (2) αi: absorption coefficient of i component in solution (dependent on wavelength) Ci: i component concentration in solution t (no, nc, n) : Transmittance no; refractive index of air n; refractive index of solution (dependent on wavelength) nc; refractive index of cell In other words, since the refractive index differs between the atmosphere, the cell and the solution, the transmittance t depends on the wavelength. As a result of the change, the transmitted light intensity I changes, which affects the absorbance. As a result, an error resulting from the change in transmittance is introduced into the measurement result of the component concentration.

Various methods for correcting the incident light intensity Io have been devised. For example, (1) a reference substance such as water is put in the same cell for measurement, and (2) a part of light source light is monitored without passing through the cell. Not up to.

Further, the influence of the change in transmittance due to refraction on the intensity of transmitted light becomes relatively small when the cell length L is increased, and the accuracy of absorption measurement can be improved. But,
When the cell length is increased, the intensity of transmitted light becomes smaller and the S / N ratio becomes worse when a highly scattering substance or the like is measured.
In the conventional refractive index method for obtaining the specific gravity of urine, since the refractive index and the component concentration are measured by different means, an expensive device is required, and there is a problem that the measurement labor and complexity are added.

It is impossible to obtain the resolution shown in the nomogram of the Japanese Society for Clinical Pathology by the method of the above-mentioned reference that uses the relationship between the urea concentration and the urine specific gravity. Can only be used for screening. Therefore, if an abnormal value appears, it is necessary to re-measure with another method. In addition, since the same or similar color that appears in the color tester is visually determined for the coloration state that appears by measuring the urea concentration, the individual differences of the measurers are included.

The first object of the present invention can also be applied to a highly scattering substance, and without compensating the cell length, it compensates for an error caused by a difference in refractive index between air, a cell and a substance to be measured, and absorbs light. The object is to provide a simple method and device for measuring. A second object of the present invention is to provide a method and apparatus for determining the component concentration based on its absorbance. A third object of the present invention is to provide a method and an apparatus for calculating not only urine samples but also solution samples in general, the component concentration based on the absorbance and further calculating the specific gravity using the concentration. A fourth object of the present invention is to measure the refractive index and the component concentration of a urine sample at the same time with a single measuring device, determine the specific gravity of urine from the relationship between the refractive index and the specific gravity, and determine the protein that is a correction factor for the specific gravity of urine. It is an object of the present invention to provide a method and a device for easily performing highly accurate and precise urine specific gravity measurement by also performing correction based on the concentration value of sugar.

[0014]

According to the absorbance measuring method of the present invention, a liquid sample is accommodated in a triangular cell whose exit surface is inclined with respect to the incident surface of the measuring light beam, and the measuring light beam is directed in a direction perpendicular to the incident surface. The measurement light flux emitted from the output surface is received by a linear sensor that can detect both the intensity and position of the light, and the transmitted light intensity is detected for each of the multiple measurement wavelengths of the measurement light flux. The refractive index of the sample is calculated from the position of the measurement light beam on the sensor, and the transmitted light intensity is obtained through the change in the transmittance in the triangular cell using the calculated refractive index, the known atmospheric refractive index, and the known cell refractive index. Absorbance is calculated by correcting the effect on

The component concentration measuring method according to the present invention uses the absorbance for each measurement wavelength obtained by the above method,
A multivariate analysis calculation is performed to calculate the concentration of each component. In the method of measuring the specific gravity of a liquid sample according to the present invention, the density of each component calculated by the above method is added to calculate the density, and the specific gravity is calculated based on the density. The urine specific gravity measuring method according to the present invention uses known data showing the relationship between the refractive index and the specific gravity of urine, and applies the refractive index of the urine sample obtained by the above method to the data to determine the specific gravity of the urine sample. The urine specific gravity increase corresponding to the glucose and protein concentrations of the component concentrations obtained and calculated by the above method is corrected.

An apparatus for implementing the method of the present invention is shown in FIG. Reference numeral 2 denotes a triangular cell that contains a liquid sample and has an exit surface inclined with respect to an incident surface of the measurement light beam.
Is combined with a measurement optical system in which the measurement optical path is set so as to be incident in a direction perpendicular to the incident surface of. Reference numeral 3 denotes a linear sensor which is provided at a position for receiving the measurement light flux emitted from the emission surface of the triangular cell 2 and which can detect both the intensity and the position of the light. Reference numeral 30 denotes a refractive index calculation unit, which is used when the liquid having a known refractive index is put into the triangular cell 2 for measurement.
The linear sensor 3 receives the light emitted from the triangular cell 2 when a sample with an unknown refractive index is put into the triangular cell 2 for measurement with reference to the detection position when the light emitted from the linear sensor 3 is received. The variable position amount of the detected position at that time is detected, and the refractive index of the sample corresponding to the variable position amount is calculated by a calibration curve or calculation. Reference numeral 31 denotes an absorbance calculator, which is the transmitted light intensity when the light emitted from the triangular cell 2 is received by the linear sensor 3, the refractive index of the atmosphere and the refractive index of the cell, and the sample of the sample calculated by the refractive index calculator 30. The refractive index is used to calculate the absorbance depending on the component concentration in which the influence of the transmittance change in the triangular cell 2 is corrected. 32 is a component concentration calculation unit,
Each component concentration is calculated by performing a multivariate analysis calculation based on the absorbances that are calculated by the absorbance calculation unit 31 and that depend on the component concentrations at a plurality of measurement wavelengths. Reference numeral 33 denotes a specific gravity calculating unit, which adds the component concentrations calculated by the component concentration calculating unit 32 to calculate the density and calculates the specific gravity based on the density. Reference numeral 35 denotes a urine specific gravity calculation unit, which uses known data showing the relationship between the refractive index and specific gravity of urine, and applies the refractive index of the urine sample obtained by the refractive index calculation unit 30 to the data to obtain the urine sample The specific gravity is calculated, and the increase in urine specific gravity corresponding to the glucose and protein concentrations in the component concentration calculated by the component concentration calculating unit 32 is corrected. 34 is a recorder or CR for outputting the absorbance, the component concentration, the specific gravity of the liquid sample, or the specific gravity of the urine sample calculated in each part.
An output unit such as T.

The triangular cell according to the present invention is not limited to one having a triangular outer shape, but a pair of glass surfaces through which a light beam used for measurement passes are not parallel to each other, and the pair of glass surfaces intersect directly or on an extension line. If That is, a cell whose output surface is inclined with respect to the incident surface of the measurement light beam is called a triangular cell.

[0018]

The operation of the refractive index calculator 30 and the absorbance calculator 31 will be described. Refractive Index and Absorbance Calculation The theoretical formula considering the effect of refractive index on transmittance is given by the formula (2)
However, here, the transmittance I is calculated from the equation (2).
o / I is transformed as follows. Io / I = (1 / t) exp (ΣαiCiL) (3)

The absorbance A is obtained from the equation (3) as follows. A = log (Io / I) = log {(1 / t) exp (ΣαiCiL)} = − logt + ΣαiCiL = An + Ac (4) Ac: Absorbance dependent on component concentration Ci An: Absorbance affected by reflection

From equation (4), the absorbance Ac depending on the component concentration Ci can be obtained as follows. Ac = A-An (5) The absorbance A can be obtained from the equation (4) using the measured values of Io and I. I is the peak position of the waveform captured by the linear sensor 3 after passing through the cell 2 as shown in FIG. 4 in which the transmitted light intensity and the refractive index n of the solution are simultaneously measured using the triangular cell 2. Calculated from the output value. Io is a value peculiar to the apparatus and is measured at the time of setting the optical system. t
Are each interface 1, 2 ,, of the cell 2 shown schematically in FIG.
From the transmittances at 3 and 4, t = t ₁ t ₂ t ₃ t ₄ (6) t ₁ : the transmittance at the interface 1 t ₂ : the transmittance at the interface 2 t ₃ : the transmittance at the interface 3 t ₄ : It is the transmittance at interface 4. The transmittance at the interface between air and cell 2 is t
₁ = t ₄ , and t ₂ = t ₃ at the transmittance at the interface between the cell 2 and the solution 2a. Therefore, using the Fresnel equation, t ₁ = t ₄ = 4n ₀ nc / (n ₀ + nc) ² (7) t ₂ = t ₃ = 4n ₀ n / (nc + n) ² (8) From the equation (7) and the equation (8), the equation (6) is t = 256n ₀ ⁴ n ² nc ² / (n ₀ + nc) ⁴ (nc + n) ⁴ (9)

In the equation (9), the refractive index n _{0 of} air is 1
Using the known value determined by the material as the refractive index nc of the cell and the value measured from the device shown in FIG. 4 as the refractive index n of the solution, t can be calculated,
The absorbance An can be calculated by An = −logt using the calculated value t.

Here, the principle of measuring the refractive index n of the solution using the apparatus of FIG. 4 will be described. The refractive index calculation unit 30 does not directly obtain the absolute value of the refractive index, but in FIG. 4, the irradiation position on the light receiving surface of the linear sensor 3 of the optical axis when the reference substance (for example, water) is measured, and the urine sample. The difference between the optical axis and the irradiation position on the light-receiving surface of the linear sensor 3 (this is defined as a variable position amount) is measured and converted into a refractive index.

In FIG. 4, the measurement light that has entered the entrance surface of the triangular cell 2 at a right angle is refracted, emitted to the air layer, and enters the linear sensor 3. The refraction relationship between the cell 2, the solution and the air is as follows: θ ₁ : incident angle from solution to cell interface θ ₂ : refraction angle from solution side cell interface to cell layer θ ₃ : exit angle from cell layer to air layer n ₀ : refractive index of air nc: refractive index of cell n: refractive index of solution (depending on wavelength), n · sin θ ₁ = nc · sin θ ₂ (10) nc · sin θ ₂ = n ₀ · sin θ ₃ ( 11) becomes. From the equations (10) and (11), n · sin θ ₁ = n ₀ · sin θ ₃ and the refractive index n of the solution is n = n ₀ · sin θ ₃ / sin θ ₁ (12). Expression (12) is modified as follows because sin θ ₁ = sin α. n = n ₀ · sin θ ₃ / sin α (13) Since the refractive index n ₀ = 1 of air and α is the apex angle of the triangular cell 2, the refractive index n of the solution is calculated by measuring the refractive angle θ _3. Can be found at.

Here, instead of measuring the refraction angle θ ₃ , the displacement amount D of the measurement light flux due to the change in the refractive index (for example, the change between water and the sample solution) is measured, and it is Calculate the refractive index based on it. The amount of displacement D is the peak position of the waveform detected by the linear sensor 3, and the peak position D ₀ of the waveform when the reference substance (for example, water) is measured is used as a reference to measure the waveform of the sample solution. It is determined by measuring the distance D to the peak position. If the emission angle θ ₃ from the cell layer to the air layer changes by dθ ₃ between when the reference substance is measured and when the sample solution is measured,
The variable position amount D is D = M · dθ ₃ . M is the distance from the light emitting point of the triangular cell to the linear sensor 3. On the other hand, from equation (13), since it is _{dn = (n 0 · cosθ 3} / sinα) · dθ 3, become the two equations _{dn = D · n 0 · cosθ} 3 / M · sinα (14). Here, cos θ ₃ is a value peculiar to the apparatus and is measured at the time of setting the optical system. According to the equation (14), the difference dn between the refractive index n of the sample solution and the refractive index ns of the reference substance is the displacement amount D.
Is proportional to Since n = ns + dn, the refractive index n of the sample solution can be obtained only by calculation from the measurement of the displacement amount D by using the equation (14).

A practical method for obtaining the refractive index with high accuracy is to use a calibration curve. In the calibration curve method, a sample having a specific gravity range (for example, 1.000 to 1.050) is used, and for each sample, data of the displacement amount D measured by the method of the present invention and a refractometer are separately used. A calibration curve formula is derived from the obtained refractive index data. In measuring the sample solution, the displacement amount value D
Is measured and the refractive index n is calculated using a calibration curve.

According to the present invention, the measured absorbance A and the calculated An are used to calculate Ac (= A-An) by the equation (5), whereby the refraction changes to the transmitted light intensity through the change in the transmittance. The influence given can be corrected, and the component concentration Ci
It is possible to accurately obtain the absorbance Ac depending on

Calculation of Component Concentration The operation of the component concentration calculating unit 32 for calculating the component concentration based on the absorbance Ac depending on the component concentration will be described. (4)
From the formula, the absorbance Ac depending on the component concentration is Ac = ΣαiCiL, and the unknown variable is Ci (i = 1, 2, ... K; K is the number of components), so the absorbance at K independent wavelengths is The concentration of each component can be calculated by measuring and solving the simultaneous equations. The concentration can be obtained with higher accuracy by performing data analysis using a multivariate regression analysis method such as a principal component regression analysis method (PCR method) or a partial least squares method (PLS method).

In the multivariate regression analysis method, since regression analysis can be performed using a large amount of absorbance information at one time, quantitative analysis can be performed with higher accuracy than single regression analysis. The multiple regression analysis is most frequently used, but a large number of samples are required, and when the correlation between the absorbance values at each wavelength is high, the accuracy of the quantitative analysis becomes very low. On the other hand, the principal component regression analysis method, which is a multivariate regression analysis method, can aggregate the multi-wavelength absorbance information into principal components that are uncorrelated with each other, and can also eliminate unnecessary noise data, thus achieving high quantification. Analytical accuracy can be obtained. Further, since the partial least squares method can also use the data of the sample concentration when extracting the main component, it is possible to obtain a high quantitative analysis accuracy as in the principal component regression analysis method.

For example, for each sample component to be measured, the absolute value of the correlation coefficient between the concentration of the single component aqueous solution in the visible or near infrared wavelength region and the absorbance is 0.5 or more,
Preferably, a wavelength of 0.9 or more is selected as a measurement wavelength peculiar to the component, the sample solution is irradiated with visible light or near infrared light, and each of the plurality of components to be measured is selected under the above conditions. By measuring the absorbance at different measurement wavelengths, a plurality of sample components can be simultaneously quantitatively analyzed by the multivariate regression analysis method. The correlation coefficient Rj between the absorbance A and the concentration at the wavelength λj is given by the following equation.

[0030]

[Equation 1]

In the above equation, Aij is the absorbance of the component at the wavelength λj in the i-th sample, and Ci is the concentration of the component in the i-th sample. When the sample is a urine sample, the measurement wavelength of each urinary component should be a wavelength range that strongly absorbs water, and has a high transmittance for water.
000-5280 cm ^-1 or 4980-4000 cm ^-1
Select from the wavenumber region of.

The preferred measurement wavelength of each urinary component is represented by wave number, and is 11380-9720 for glucose.
cm ^-1, 9430~9400cm ^-1, 9340~932
0cm ^-1, 9260~6560cm ^-1, 6510~55
40cm ^-1, 5530~5280cm ^-1, 4980~4
850cm ^-1, 4830~4480cm ^-1, 4440~
Select from 4330cm ^-1 or 4300~4010cm ^-1, relative to the hemoglobin 25000~7250cm
^-1 , 7220-6430 cm ^-1 , 6190-5690c
m ^-1 , 5660-5280 cm ^-1 or 4900-408
It is selected from 0 cm ^-1 and for albumin 7280-
6350 cm ^-1 , 5910-5880 cm ^-1 , 5790
~ 5740 cm ^-1 , 5630-5300 cm ^-1 , 490
0-4720 cm ^-1 , 4670-4280 cm ^-1 or 4
230-4070 cm ^-1 , selected from lithium acetoacetate 8490-6360 cm ^-1 , 6040-5
610 cm ^-1 , 5430-5300 cm ^-1 , 4900-
4760 cm ^-1 , 4680-4510 cm ^-1 or 447
It is selected from ⁰ to 4320 cm ^-1 , and 7270 to 6520 cm ^-1 and 6430 to 5290 c for ascorbic acid.
m ^-1 , 4950-4860 cm ^-1 or 4810-409
Select from 0 cm ^-1 and 9370 for creatinine
~ 5870 cm ^-1 , 5810-5280 cm ^-1 , 498
0-4730 cm ^-1 , 4690-4320 cm ^-1 or 4
Selected from 290 to 4090 cm ^-1, and 7640 to 5280 cm ^-1 or 4980 to 40 for sodium chloride
Choose from 80 cm ^-1 and 8 for sodium nitrite
It is selected from 680 to 5300 cm ^-1 , 4980 to 4210 cm ^-1 or 4160 to 4100 cm ^-1 .

Specific gravity calculation The operation of the specific gravity calculator 33 will be described. The specific gravity calculating unit 33 calculates the specific gravity from all the component concentrations in the sample solution obtained by the component concentration calculating unit 32. The density ρ is defined by ρ = m / V (15) m: weight of all components, V: volume of sample solution. When the weight of each component is mi, the volume concentration Ci of each component is Ci = mi / V (16). Since m = Σmi, the formula (15) and the formula (1
From 6), ρ = m / V = Σmi / V = ΣCi (17) The specific gravity can be calculated from the density calculated by the equation (17) and the density of water (constant number), and the specific gravity can be calculated from the component concentration without measuring the weight of the component. This method of calculating the specific gravity of the sample solution by calculation can, of course, be applied to a urine sample, but can also be generally applied to other solution samples.

A method of calculating the refractive index of the urine sample by the refractive index calculating unit 30 and calculating the specific gravity of urine by the specific gravity calculating unit 35 when the urine specific gravity measurement sample is the urine sample will be described. This method alone is unique to urine samples and cannot be applied to solution samples other than urine.

The specific gravity calculating unit 35 uses the refractive index obtained by the refractive index calculating unit 30 to calculate the specific gravity from the nomograms shown in FIGS. 2 and 3, for example. Specific gravity range is 1.035
For the range exceeding, the specific gravity is calculated using a nomogram other than those shown in FIGS. Further, the absorbance calculation unit 31 and the component concentration calculation unit 32 use the glucose and protein concentrations among the component concentrations calculated by correcting the influence of refraction on the transmitted light intensity through the change in transmittance, and the glucose ... … The specific gravity of urine increased by 0.004 per concentration of 1% protein .... Based on the fact that the specific gravity of urine increased by 0.003 per concentration of 1%, the specific gravity values obtained from the nomograms of FIGS. 2 and 3 are corrected.

That is, by simultaneously measuring the refractive index and the absorbance, the concentrations of glucose and protein, which are the correction factors of the specific gravity, are obtained from the measurement of the absorbance, and the urine specific gravity is corrected on the basis of the obtained concentrations to obtain a single method and It becomes possible to perform simple and precise urine specific gravity measurement with a single device.

[0037]

FIG. 6 shows a first embodiment. The light source 1 is a light source capable of selectively emitting measurement light beams of a plurality of wavelengths, and is, for example, a laser diode array, a variable wavelength laser, or a combination of a light source that generates multiple wavelengths and a spectroscope. The light source and the cell 2 are arranged so that the measurement light beam from the light source 1 is incident on the entrance surface of the triangular cell 2 at a right angle. The measurement light beam that has passed through the cell 2 and is refracted is received by the linear sensor 3. The linear sensor 3 is capable of converting both the intensity and position of incident light into an electric signal and outputting the electric signal. As such a linear sensor, a photodiode array or a CCD sensor can be used. Data processing unit 4
Includes a storage medium 9 such as an input / output port 10 for separating an electric signal from the linear sensor 3 into a signal for each wavelength, and A / D converting the signal into a digital signal, a CPU 6, a ROM 7, a RAM 8, and a magnetic storage device. I'm out. Reference numeral 5 is a recorder as an output unit. The refractive index calculation unit 30, the absorbance calculation unit 31, the component concentration calculation unit 32, and the specific gravity calculation unit 3 in FIG.
3, 35 are realized by the data processing unit 4.

FIG. 7 shows a second embodiment. The light source 1a is a light source that simultaneously generates a plurality of wavelengths, such as a halogen lamp. The measurement light after passing through the cell 2 is spectroscopic device 11
The light is received by the linear sensor 3 after passing through. The spectroscopic device 11 is not a diffraction grating, but is a filter rotor that includes a plurality of interference filters and performs spectral separation by switching filters on the optical path. In FIG. 6, the incident light of the measurement light beam has a selected wavelength, whereas in FIG. 7, the incident light includes a plurality of wavelengths, and the transmitted light is spectrally separated to select the wavelength. There is. The configuration of the data processing unit 4 is the same as that of FIG.

FIG. 8 shows the data processing unit 4 in FIGS. 6 and 7 more specifically. The input / output port 10 in FIGS. 6 and 7 is an amplifier 1 that amplifies the output of the sensor 3.
2. A / D converter 13 for converting into a digital signal, input port 14, input data buffer 15, input port 22,
Output port 23, sensor control unit 19, I / O control unit 20
And a light source controller 21. The data processing unit 4 further includes a display unit 16, an operation unit 17, and an external input / output interface 18.

The flow of the process for obtaining the component concentration will be described with reference to the flowchart of FIG. 9 using the embodiment of FIG. 6 or 7. When the power supply of the data processing unit 4 is turned on, the power supply of the entire control unit is turned on, the microcomputer portion in the data processing unit 4 is initialized, and the CPU 6 and the RAM 8 are initialized. After the microcomputer operation becomes possible, the initial value data regarding the measurement and the device operation is read from the storage medium 9 and written in the RAM 8. Initialization work of the device is performed based on this data, and an instruction to start measurement is awaited.

The sample is injected into the triangular cell 2 and set in a predetermined place. When the start button is pressed, the measurement operation starts. The measurement light beam from the light source 1 or 1a is incident perpendicularly on the incident surface of the triangular cell 2, and the measurement light transmitted through the triangular cell 2 is received by the linear sensor 3. The linear sensor 3 converts an optical signal into an electric signal. Data processing unit 4
Then, the electric signal from the linear sensor 3 for one measurement wavelength is A / D converted and taken in as a digital signal. The transmitted light intensity I and the displacement amount D are detected from the electric signal from the linear sensor 3.

The measurement light is switched to the next measurement wavelength. In the embodiment of FIG. 6, the switching of the measurement wavelength is performed by the lighting LD in the light source 1.
This is performed by switching the elements, switching the wavelength of the variable wavelength laser, or scanning the spectroscope. In the embodiment of FIG.
This is done by switching the filter at. The electric signal from the linear sensor 3 at the switched measurement wavelength is similarly A / D converted and captured. In this way, the intensity I and the displacement amount D of the light transmitted through the cell 2 are detected and captured for each measurement wavelength.

When the acquisition of the electric signal from the linear sensor 3 at the predetermined wavelength is completed, the refractive index is obtained from the displacement amount D, and the transmitted light intensity is corrected using this refractive index to obtain the absorbance. Using the absorbances at a plurality of measurement wavelengths, multivariate analysis calculation is performed to obtain the component concentration. The result is output to the recorder 5 or the like. Finally, the power of the data processing unit device is turned off to end the measurement.

The operation of obtaining the specific gravity from the concentration of each component will be described with reference to the flowchart of FIG. 10 using the embodiment of FIG. 6 or 7. The procedure from turning on the power of the data processing unit to setting the sample, starting the measurement, and completing the data acquisition is the same as in FIG. In FIG. 10, the refractive index is obtained, the transmitted light intensity is corrected using the refractive index to obtain the absorbance, and the component concentration is obtained from the absorbance by a multivariate analysis calculation. For not only urine samples but also general solution samples, when the concentration of each component is obtained, the density is obtained by the sum of the concentrations of all the components, and the specific gravity of the sample is obtained.

The operation of obtaining the specific gravity of urine when measuring urine as a sample will be described with reference to the flowchart of FIG. 11 using the embodiment of FIG. 6 or 7. In this case as well, the power supply of the data processing unit is turned on, the sample is set, the wavelength of the light source is switched, and the electric signal from the linear sensor 3 at each wavelength is converted into a digital value and fetched as shown in FIG. 9 and FIG. This is the same as the operation of 10.

In FIG. 11, the refractive index is calculated, the transmitted light intensity is corrected, and the absorbance is calculated. Based on this, the sugar and protein concentrations are calculated by a multivariate analysis calculation. On the other hand, known data showing the relationship between the refractive index and the specific gravity is used, and the refractive index obtained by the measurement is applied to it to obtain the specific gravity value of the urine sample. On the other hand, the specific gravity value is corrected based on the sugar and protein concentrations obtained by the multivariate analysis calculation, and the result is output.

[0047]

According to the present invention, by using the triangular cell and the linear sensor, the transmitted light intensity of the measuring light transmitted through the cell and the position of the transmitted light on the linear sensor are detected to obtain the transmitted light intensity. It becomes possible to measure the refractive index of the liquid sample at the same time, whereby the influence of refraction on the intensity of transmitted light through the change in transmittance can be corrected and the absorbance can be measured with high accuracy. Moreover, since the transmitted light intensity and the refractive index can be measured simultaneously by one measuring device, the device configuration is simple and the operation is simple. Further, in the present invention, since the absorbance of the liquid sample can be accurately measured for each measurement wavelength as described above, the concentration of each component can be calculated with high accuracy by the multivariate analysis calculation. In the present invention, not only the urine sample but also the general liquid sample can accurately determine the concentration of each component, so that by adding them, the density can be calculated, and thus the specific gravity can be determined. When the present invention is applied to the method for measuring the specific gravity of a urine sample, since the refractive index and the component concentration of the urine sample can be measured at the same time, the specific gravity is calculated using known data from the refractive index, and its specific gravity value, By performing correction based on the sugar and protein concentrations obtained at the same time, the specific gravity of urine can be accurately and easily obtained with a single measuring device.

[Brief description of drawings]

FIG. 1 is a block diagram showing an apparatus of the present invention.

FIG. 2 is a nomogram table advocated by the Japanese Society of Clinical Pathology showing standard criteria for refractive index and urine specific gravity.

FIG. 3 is a graph of the same nomogram.

4A and 4B are diagrams illustrating the principle of simultaneously measuring transmitted light intensity and refractive index using a triangular cell in the present invention, FIG. 4A is a plan view showing a cell and a linear sensor, and FIG. 4B is a linear sensor. It is a figure which shows the cell transmitted light intensity which a linear sensor receives.

FIG. 5 is a cross-sectional view of a cell schematically showing transmission of light irradiated on the cell at each interface.

FIG. 6 is a schematic block diagram showing the overall configuration of an embodiment.

FIG. 7 is a schematic block diagram showing the overall configuration of another embodiment.

FIG. 8 is a block diagram illustrating a data processing unit according to an embodiment.

FIG. 9 is a flowchart showing an operation for obtaining a component concentration.

FIG. 10 is a flowchart showing an operation for obtaining a specific gravity value from a component concentration.

FIG. 11 is a flowchart showing an operation for obtaining a specific gravity value of a urine sample.

[Explanation of symbols]

 2 triangular cell 3 linear sensor 30 refractive index calculation unit 31 absorbance calculation unit 32 component concentration calculation unit 33 specific gravity calculation unit 35 urine specific gravity calculation unit

─────────────────────────────────────────────────── ───

[Procedure amendment]

[Submission date] July 28, 1995

[Procedure Amendment 1]

[Document name to be amended] Statement

[Name of item to be corrected] Figure 2

[Correction method] Change

[Correction content]

FIG. 2 is a nomogram chart advocated by the Japanese Society of Clinical Pathology showing standard criteria for refractive index and urine specific gravity.

Claims (8)

[Claims] 1. A measurement light beam, in which a liquid sample is housed in a triangular cell whose emission surface is inclined with respect to the incident surface of the measurement light beam, the measurement light beam is made incident in a direction perpendicular to the incidence surface, and is emitted from the emission surface. Is received by a linear sensor that can detect both the intensity and position of the light, the transmitted light intensity is detected for each of the multiple measurement wavelengths of the measurement light beam, and the refractive index of the sample is measured from the position of the measurement light beam on the linear sensor. Is calculated, and the calculated refractive index, known atmospheric refractive index, and known cell refractive index are used to correct the influence on the transmitted light intensity through the change in transmittance in the triangular cell, and the absorbance is characterized by Measuring method. 2. A measurement light flux, in which a liquid sample is housed in a triangular cell whose emission surface is inclined with respect to the incidence surface of the measurement light flux, the measurement light flux is made incident in a direction perpendicular to the incidence surface, and which is emitted from the emission surface. Is received by a linear sensor that can detect both the intensity and position of the light, the transmitted light intensity is detected for each of the multiple measurement wavelengths of the measurement light beam, and the refractive index of the sample is measured from the position of the measurement light beam on the linear sensor. The calculated refractive index, the known atmospheric refractive index and the known cell refractive index are used to correct the effect on the transmitted light intensity via the transmittance change in the triangular cell for each measurement wavelength. A method for measuring the component concentration of a liquid sample, which calculates the absorbance and performs multivariate analysis calculation to calculate the concentration of each component. 3. A measurement light flux, in which a liquid sample is housed in a triangular cell whose emission surface is inclined with respect to the incident surface of the measurement light flux, the measurement light flux is incident in a direction perpendicular to the incidence surface, and the measurement light flux is emitted from the emission surface. Is received by a linear sensor that can detect both the intensity and position of the light, the transmitted light intensity is detected for each of the multiple measurement wavelengths of the measurement light beam, and the refractive index of the sample is measured from the position of the measurement light beam on the linear sensor. The calculated refractive index, the known atmospheric refractive index and the known cell refractive index are used to correct the effect on the transmitted light intensity via the transmittance change in the triangular cell for each measurement wavelength. A liquid sample characterized by calculating the absorbance, performing multivariate analysis calculation to calculate the concentration of each component, adding the calculated concentration of each component to calculate the density, and then calculating the specific gravity based on it. Specific gravity measurement method. 4. The liquid solution is urine, and the liquid sample is housed in a triangular cell whose output surface is inclined with respect to the incident surface of the measurement light beam, and the measurement light beam is made incident in a direction perpendicular to the incident surface. The measurement light flux emitted from the exit surface is received by a linear sensor that can detect both the intensity and position of the light, the transmitted light intensity is detected for each of the multiple measurement wavelengths of the measurement light flux, and the measurement is performed on the linear sensor. The refractive index of the sample is calculated from the position of the light beam, and the calculated refractive index, known atmospheric refractive index, and known cell refractive index are used to correct the effect on the transmitted light intensity through the change in transmittance in the triangular cell. Then calculate the absorbance for each measurement wavelength, calculate the concentration of each component by performing a multivariate analysis calculation, using known data showing the relationship between the refractive index and specific gravity of urine,
The sample refractive index obtained above is applied to the data to obtain the specific gravity of the urine sample, and the increase in urine specific gravity corresponding to the glucose and protein concentrations of the component concentrations calculated above is corrected. Urine specific gravity measurement method. 5. A triangular cell (2) for accommodating a liquid sample, the exit surface of which is inclined with respect to the incident surface of the measuring light beam, and the measuring light beam so as to enter in a direction perpendicular to the incident surface of the triangular cell (2). A measurement optical system having a measurement optical path set in, a linear sensor (3) provided at a position for receiving the measurement light flux emitted from the emission surface of the triangular cell (2), and capable of detecting both the intensity and the position of the light; The triangular cell (2) is based on the detection position when the light emitted from the triangular cell (2) when the liquid having a known refractive index is put into the cell (2) and measured is received by the linear sensor (3). The variable amount of the detection position when the light emitted from the triangular cell (2) when the sample having an unknown refractive index is put into the measurement is received by the linear sensor (3) is detected, and the variable amount is detected. The refractive index of the corresponding sample is calculated using a calibration curve or calculation. Light output from the folding rate calculation unit (30) and the triangular cell (2) is input to the linear sensor (3).
Influence of the transmittance change in the triangular cell (2) by using the transmitted light intensity when received by the device, the atmospheric refractive index and the cell refractive index, and the sample refractive index calculated by the refractive index calculation unit (30) An absorbance measuring device comprising: an absorbance calculating unit (31) for calculating the absorbance depending on the corrected component concentration. 6. A triangular cell (2) containing a liquid sample and having an exit surface inclined with respect to the incident surface of the measuring light beam, and a measuring light beam incident on the incident surface of the triangular cell (2) in a direction perpendicular thereto. A measurement optical system having a measurement optical path set in, a linear sensor (3) provided at a position for receiving the measurement light flux emitted from the emission surface of the triangular cell (2), and capable of detecting both the intensity and the position of the light; The triangular cell (2) is based on the detection position when the light emitted from the triangular cell (2) when the liquid having a known refractive index is put into the cell (2) and measured is received by the linear sensor (3). The variable amount of the detection position when the light emitted from the triangular cell (2) when the sample having an unknown refractive index is put into the measurement is received by the linear sensor (3) is detected, and the variable amount is detected. The refractive index of the corresponding sample is calculated using a calibration curve or calculation. Light output from the folding rate calculation unit (30) and the triangular cell (2) is input to the linear sensor (3).
Influence of the transmittance change in the triangular cell (2) by using the transmitted light intensity when received by the device, the atmospheric refractive index and the cell refractive index, and the sample refractive index calculated by the refractive index calculation unit (30) A multivariate analysis calculation is performed based on the absorbance calculation unit (31) that calculates the absorbance that depends on the component concentration corrected for and the absorbance that is calculated by the absorbance calculation unit (31) that depends on the component concentrations at multiple measurement wavelengths. And a component concentration calculation unit (32) for calculating each component concentration.
A component concentration measuring device comprising: 7. A triangular cell (2) for accommodating a liquid sample, the exit surface of which is inclined with respect to the incident surface of the measuring light beam, and the measuring light beam so as to enter in a direction perpendicular to the incident surface of the triangular cell (2). A measurement optical system having a measurement optical path set in, a linear sensor (3) provided at a position for receiving the measurement light flux emitted from the emission surface of the triangular cell (2), and capable of detecting both the intensity and the position of the light; The triangular cell (2) is based on the detection position when the light emitted from the triangular cell (2) when the liquid having a known refractive index is put into the cell (2) and measured is received by the linear sensor (3). The variable amount of the detection position when the light emitted from the triangular cell (2) when the sample having an unknown refractive index is put into the measurement is received by the linear sensor (3) is detected, and the variable amount is detected. The refractive index of the corresponding sample is calculated using a calibration curve or calculation. Light output from the folding rate calculation unit (30) and the triangular cell (2) is input to the linear sensor (3).
Influence of the transmittance change in the triangular cell (2) by using the transmitted light intensity when received by the device, the atmospheric refractive index and the cell refractive index, and the sample refractive index calculated by the refractive index calculation unit (30) A multivariate analysis calculation is performed based on the absorbance calculation unit (31) that calculates the absorbance that depends on the component concentration corrected for and the absorbance that is calculated by the absorbance calculation unit (31) that depends on the component concentrations at multiple measurement wavelengths. The specific gravity for calculating the density by adding each component concentration calculated by the component concentration calculating unit (32) which calculates the component concentration and the component concentration calculating unit (32). A specific gravity measuring device comprising: a calculator (33). 8. A triangular cell (2) containing a liquid sample and having an exit surface inclined with respect to the incident surface of the measuring light beam, and a measuring light beam so as to enter in a direction perpendicular to the incident surface of the triangular cell (2). A measurement optical system having a measurement optical path set in, a linear sensor (3) provided at a position for receiving the measurement light flux emitted from the emission surface of the triangular cell (2), and capable of detecting both the intensity and the position of the light; The triangular cell (2) is based on the detection position when the light emitted from the triangular cell (2) when the liquid having a known refractive index is put into the cell (2) and measured is received by the linear sensor (3). The variable amount of the detection position when the light emitted from the triangular cell (2) when the sample having an unknown refractive index is put into the measurement is received by the linear sensor (3) is detected, and the variable amount is detected. The refractive index of the corresponding sample is calculated using a calibration curve or calculation. Light output from the folding rate calculation unit (30) and the triangular cell (2) is input to the linear sensor (3).
Influence of the transmittance change in the triangular cell (2) by using the transmitted light intensity when received by the device, the atmospheric refractive index and the cell refractive index, and the sample refractive index calculated by the refractive index calculation unit (30) A multivariate analysis calculation is performed based on the absorbance calculation unit (31) that calculates the absorbance that depends on the component concentration corrected for and the absorbance that is calculated by the absorbance calculation unit (31) that depends on the component concentrations at multiple measurement wavelengths. Using the component concentration calculation unit (32) that calculates the concentration of each component and known data indicating the relationship between the refractive index and specific gravity of urine,
The specific refractive index of the urine sample is calculated by applying the sample refractive index obtained by the refractive index calculation unit (30) to the data, and the specific concentration of glucose and protein in the component concentrations calculated by the component concentration calculation unit (32) is calculated. A urine specific gravity measuring device comprising: a urine specific gravity calculating section (35) for correcting a corresponding increase in urine specific gravity.