Standard solution, automatic analysis device, and method for adjusting light intensity of light source thereof

Abstract

The present invention provides a standard solution, an automatic analyzer, and a method for adjusting the light intensity of a light source thereof. As a standard solution for evaluating a scattered light measuring optical system assembled in the automatic analyzer, a standard solution containing an insoluble carrier at a concentration with a transmittance in the range of 10% to 50% is used, and the light intensity of the light source is adjusted so that the output of a scattered light detector becomes a predetermined value.

Description

[0001] This application is a divisional application of an invention patent application with an international application date of November 28, 2016, an international application number of PCT / JP2016 / 085133, a priority date of January 22, 2016, an application number of 2016800789147, and an invention name of "Automatic analyzer and standard solution for evaluating the scattered light measurement optical system thereof". Technical Field

[0002] The present invention relates to an automatic analyzer for analyzing the amount of components contained in a sample such as blood or urine, a standard solution for evaluating a scattered light measurement optical system of the automatic analyzer, and an adjustment method for the automatic analyzer using the standard solution for evaluating a scattered light measurement optical system. Background Art

[0003] An automatic analyzer is widely used. The automatic analyzer irradiates a reaction solution containing a mixture of a specimen such as serum or urine and a reagent with light from a light source, calculates the absorbance based on changes in the amount of transmitted light at a specific wavelength, and quantifies the concentration of the substance being measured according to the Lambert-Beer law (Patent Document 1).

[0004] As the reaction measured by the automatic analyzer, there are mainly two types of color development reaction based on the reaction of substrate and enzyme, and immunoagglutination reaction of antigen and antibody. The analysis using the former reaction is called biochemical analysis, and has enzymes, lipids, nitrogen compounds, etc. as inspection items. The analysis using the latter reaction is called immunoassay, and among the inspection items, there are trace proteins (CRP), tumor markers, hormones, blood drugs, etc. Among the inspection items of immunoassay, there are inspection items requiring high sensitivity detection in low concentration areas, and inspection items that are very important for clinical diagnosis. In these inspection items, latex immunoturbidimetry, etc., which uses latex particles that sensitize (bind) antibodies on the surface as sensitizers, is used. In the latex immunoturbidimetry, the latex particles contained in the reagent are agglomerated with each other via the measured substance in the specimen to generate agglomerates.

[0005] The reaction solution in which the specimen and the reagent are mixed on the automatic analyzer is irradiated with light, and the change in the amount of transmitted light that is not scattered and transmitted is measured to quantify the concentration of the substance to be measured in the specimen. The higher the concentration of the substance to be measured, the greater the change in the amount of light. In recent years, the demand for the measurement of immunoassay projects has increased, and the performance in immunoassay projects has been required to be improved. Therefore, the following method is used: instead of using the change in the amount of light of the transmitted light, the change in the amount of light of the scattered light that is easy to capture a larger change in the amount of light is used to quantify the concentration with high sensitivity (Patent Document 2).

[0006] Prior Art Literature

[0007] Patent Literature

[0008] Patent Document 1: US Patent 4,451,433

[0009] Patent Document 2: Japanese Patent No. 5318206

[0010] Problems to be solved by the invention

[0011] In an automatic analyzer, a plurality of monomers are arranged on a circumference, and the specimen is reacted with a reagent in each monomer to quantify the concentration of a substance to be measured in the specimen. Before measuring a substance to be measured with an unknown concentration, a substance to be measured with a known concentration is measured in advance, and a calibration curve is prepared to investigate the relationship between the concentration of the substance to be measured and the change in the amount of light. Thus, even if there is a deviation in the amount of scattered light between devices, the concentration of the substance to be measured in the specimen can be accurately quantified. However, in order to manage the device status and detect abnormalities, it is desired that the same scatterer in any device or monomer shows the same amount of scattered light. For example, in Japanese Patent Gazette No. 2014-119425, the amount of scattered light is corrected according to each monomer.

[0012] However, no suitable scatterer for evaluating the deviation is known on the automatic analyzer. As commercially available scatterers, there are solid scatterers using milky white diffusion plates, crystallized glass, and Teflon (registered trademark) system materials. Since they are solid, there is a problem that it is difficult to set them to the reaction liquid position using the usual analysis operation on the automatic analyzer. In addition, there is a problem that the deviation of each individual solid scatterer is large. Therefore, a liquid scatterer is desired.

[0013] Turbidity standard solutions used in turbidity meters and the like are liquid scatterers, so they are easy to set at the reaction solution position where the usual analysis operation is used, which is useful in this respect. However, for example, when the turbidity meter standard solution is 100 degrees, it is mixed with relatively large particles with particle sizes of 0.5μm, 1.0μm, 2.0μm, 5.0μm, 10.0μm, etc., and there are the following problems: particles with a particle size of about 0.3μm used as latex reagents for automatic analyzers are not mixed; particles precipitate when left for a long time; reagents on automatic analyzers are usually stored in a refrigerator, and when dispensed into a monomer, the temperature is raised by a constant temperature bath (constant at 37°C), causing dissolved oxygen to foam, which easily generates bubbles on the wall surface of the monomer. As such, there is no known scatterer (standard solution) for evaluating the optical system of a light scattering photometer for measuring changes in light quantity caused by the reaction of latex reagents for automatic analyzers. Summary of the invention

[0014] Solution

[0015] In the present invention, as a standard solution for evaluating the scattered light measurement optical system of an automatic analyzer having a light source, a monomer containing a reaction solution, and a detector for detecting light irradiated from the light source to the monomer and scattered by the reaction solution in the monomer, a standard solution containing an insoluble carrier at a concentration in the range of 10% to 50% is used when dispensed into the monomer, and the scattering angle of the light scattered by the standard solution in the monomer is 20° or 30°. The standard solution more preferably contains the insoluble carrier at a concentration in the range of 18% to 40% when dispensed into the monomer, and further preferably contains the insoluble carrier at a concentration in the range of 22.4% to 31.6% when dispensed into the monomer. The optical path length of the monomer can be, for example, 5 mm, and the insoluble carrier can be latex particles with a particle size of 250 to 350 nm.

[0016] Effects of the Invention

[0017] According to the present invention, the entire scattered light measurement optical system including the light source and the detector can be evaluated while reducing the influence of the error in the concentration of the standard solution. Thus, a scattered light measurement device with high reliability can be provided to the clinical field.

[0018] The other problems, structures, and effects than those described above will become clear from the following description of the embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 : is a schematic diagram showing a structural example of a light scattering photometer.

[0020] Figure 2 This is a graph showing experimental results indicating the absorbance dependence of the scattered light amount of a latex solution.

[0021] Figure 3 This is a diagram illustrating the trend of the absorbance dependence of the scattered light amount.

[0022] Figure 4 It is a graph showing the relationship between the transmittance of a solution and the absorbance of the solution at each optical path length.

[0023] Figure 5 This is a comparison diagram of the experimental results and the calculated results of the absorbance dependence of the scattered light amount of the latex solution.

[0024] Figure 6 This is a graph showing the relationship between the absorbance and transmittance of a solution when measured as a single body with an optical path length of 5 mm.

[0025] Figure 7 This is a schematic diagram showing an example of the overall configuration of an automatic analyzer.

[0026] Figure 8 It is a schematic diagram showing a configuration example of an absorbance measuring unit.

[0027] Fig. 9 It is a schematic diagram showing a configuration example of a scattered light measuring unit.

[0028] Fig.10 This is a graph showing data obtained by measuring a turbidity standard solution using an absorptiophotometer.

[0029] Fig.11 This is a diagram showing data obtained by measuring a turbidity standard solution using a scattering photometer.

[0030] Fig.12 This is a graph showing the absorbance dependence of scattered light of a commercially available latex reagent on the fluctuation.

[0031] Fig.13 This is a diagram showing the results of measuring a standard solution for optical system evaluation using an absorbance measuring unit.

[0032] Fig.14 This is a diagram showing the results of measuring a standard solution for optical system evaluation using a scattered light measuring unit.

[0033] Fig.15 1 is a schematic diagram showing an example of an LED light amount adjustment screen for adjusting the light amount.

[0034] Fig.16 It is a graph showing the evaluation results of the variation in the measured values ​​between the devices.

[0035] Fig.17 This is a diagram showing the relationship between the particle size of latex particles and the output of a scattered light receiver.

[0036] Description of reference numerals:

[0037] 2. Sample cup;

[0038] 3. Sample tray;

[0039] 5. Reagent bottles;

[0040] 6 Reagent tray;

[0041] 8 monomers;

[0042] 9 reaction plate;

[0043] 13. Absorbance measurement unit;

[0044] 16 scattered light measurement unit;

[0045] 26 Data processing department. DETAILED DESCRIPTION

[0046] Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings.

[0047] Figure 1 Schematic diagram showing a structural example of a light scattering photometer for measuring the amount of scattered light. Light 42 from a light source 41 for measuring scattered light is irradiated onto a solution 7 in a monomer 8 whose temperature is adjusted by a constant temperature fluid 15. Transmitted light 44 is received by a transmitted light receiver 46, and scattered light 43 in a 20° direction is received by a scattered light receiver 45.

[0048] Figure 2 This is a diagram showing the experimental results obtained by using a latex solution in solution 7 and measuring the amount of scattered light while changing the concentration. For the monomer 8 placed in solution 7, a monomer with an optical path length of 5 mm was used. However, in this specification, all the absorbances of the solution are converted to the absorbance when measured with an optical path length of 10 mm. For example, even if the transmittance of a certain solution is 10% in a monomer with an optical path length of 5 mm, the absorbance of the solution is expressed as 2.0 abs because it is converted when measured with an optical path length of 10 mm. The latex particles contained in the latex solution used particles with particle sizes of 100 nm, 200 nm, 300 nm, and 400 nm. According to Figure 2 It can be seen that the amount of scattered light is maximum at around 1.15 abs regardless of the particle size, and at this time, even if the concentration (absorbance) of the particles changes, the amount of scattered light does not change much.

[0049] Figure 3 This is an explanatory diagram showing the method of considering the particle concentration dependence of the scattered light amount. The generated scattered light (ideal scattered light intensity) increases in proportion to the number of particles (absorbance), but the scattered light is further scattered by other particles, and only the part with the solution transmittance passes through and is received by the light receiver. When the ideal scattered light intensity measured by the scattered light receiver in a certain direction is set to I ideal When the transmittance of the solution is set to T, the received scattered light Is(θ) is expressed by Formula 1.

[0050] Formula 1

[0051] Is(θ)=I ideal ·T

[0052] Here, multiple scattering is not considered, and only the case of scattered light after receiving only one scattering is considered. When the number density per unit volume of particles in the solution is n, the volume of the solution measured by irradiation with irradiation light is V, the efficiency of scattering in the θ direction relative to the energy of light received by one particle is i(θ), the light receiving efficiency (solid angle part) of scattered light is Er, and the irradiation light amount irradiated to the reaction solution is I0, I ideal It is expressed by formula 2.

[0053] Formula 2

[0054] I ideal =n·i(θ)·V·Er·I0

[0055] On the other hand, when the optical path length in the solution to the scattered light receiver is represented by Ls and the absorbance of the solution is represented by A, the transmittance T is represented by the following formula 3.

[0056] Formula 3

[0057]

[0058] According to Formula 2 and Formula 3, Formula 1 can be expressed as Formula 4.

[0059] Formula 4

[0060]

[0061] When the equation 4 is differentiated to obtain the absorbance A1 of the solution where the slope is 0 and the amount of scattered light is maximum, A1 is expressed by equation 5.

[0062] Formula 5

[0063]

[0064] According to Formula 5, if the influence of multiple scattering is not considered, for example, in the case of an optical path length of 5 mm, the amount of scattered light is calculated to be the maximum at an absorbance of 0.8686 abs. The optical path length in the solution to the scattered light receiver has an angle with respect to the straight light, and is therefore slightly longer than the optical path length (the optical path length of a single body), but this is ignored here and is assumed to be the same as the optical path length of a single body. In addition, in the above calculation, the absorbance of the solution where the amount of scattered light is the maximum is calculated, but when the absorbance is considered in terms of transmittance, it can be calculated as 1 / e (≈transmittance 36.8%).

[0065] Figure 4 This is a graph showing the relationship between the transmittance (%) of the monomer at each optical path length of 10mm, 5mm, and 3mm and the absorbance of the solution (converted to an optical path length of 10mm). The absorbance of the solution with a transmittance of 36.8% depends on the optical path length through the solution. Therefore, if the optical path length of the monomer changes, the absorbance of the solution that is the maximum changes, but the calculation result that is the maximum at a transmittance of 36.8% does not change. For example, even if the angle of reception of the scattered light is not 20° but 90°, as long as the optical path length through the solution is 5mm, the trend that the amount of scattered light becomes the maximum at 0.8686abs is the same.

[0066] Figure 5 Yes Figure 2A graph comparing the experimental results and the calculated results for a median particle size of 300 nm. The vertical axis is normalized so that the scattered light amounts of the experimental results (actual measurements) and the calculated results match in the plot of dilution series No. 1.

[0067] Figure 5 The difference between the experimental results and the calculated results is believed to be due to the influence of multiple scattering. The peak position is 1.15 abs compared to the calculated value of 0.8686 abs, which is about 1.3 times different when set as absorbance. Figure 2 and Figure 5 It can be seen from the actual measurement that the peak value is around 1.15 abs, that is, in the range of 1.0 to 1.3 abs, regardless of the latex particle size. Figure 2 It is known that the scattered light amount has almost no concentration dependence when it is about 0.8 to 1.5 abs, and has little concentration dependence at high concentrations. Therefore, in practice, it is considered that it has little concentration dependence when it is about 0.6 to 2.0 abs and can be used.

[0068] Figure 6 This is a graph showing the relationship between the absorbance and transmittance of a solution in a monomer having an optical path length of 5 mm. The absorbance was measured using a monomer having an optical path length of 5 mm, and the absorbance converted to an optical path length of 10 mm is shown. Figure 6 It can be seen that when the above-mentioned absorbance is converted into transmittance, it can actually be measured within the range of transmittance 10% to 50%. In order to achieve good accuracy, it can be measured at a transmittance of 18% to 40%. In order to achieve further high accuracy, by measuring at a solution concentration ranging from a transmittance of 22.4% to a transmittance of 31.6%, the concentration dependence of the scattered light amount is small, and stable measurement can be achieved.

[0069] Next, a specific example of an automatic analyzer that measures scattered light of a solution and quantifies the concentration of a substance to be measured in a sample based on its temporal change will be described. Figure 7 It is a schematic diagram showing an example of the overall configuration of the automatic analyzer according to this embodiment.

[0070] The automatic analysis device of this embodiment has three types of disks: a sample disk 3, a reagent disk 6, and a reaction disk 9; dispensing mechanisms 10 and 11 for moving samples and reagents between these disks; a control circuit 23 for controlling the dispensing mechanisms 10 and 11; an absorbance measurement circuit 24 for measuring the absorbance of the reaction liquid; a scattered light measurement circuit 25 for measuring the scattered light from the reaction liquid; a data processing unit 26 for processing the data measured by each measurement circuit; an input unit 27 and an output unit 28 as interfaces with the data processing unit 26; and a scattering light source driving circuit 29 capable of adjusting the light amount of the scattered light source. It should be noted that the data processing unit 26 has a data storage unit 2601 and an analysis unit 2602. The data storage unit 2601 stores control data, measurement data, data for data analysis, analysis result data, etc. The input unit 27 and the output unit 28 input and output data to and from the data storage unit 2601. Figure 7 In the example shown in FIG. 1 , the input unit 27 is a keyboard, but may be another input device such as a touch panel or a keypad.

[0071] A plurality of sample cups 2, which are containers for storing samples 1, are arranged on the circumference of the sample disk 3. The sample 1 is, for example, blood. A plurality of reagent bottles 5, which are containers for storing reagents 4, are arranged on the circumference of the reagent disk 6. A plurality of reaction liquids 7, which are mixtures of the sample 1 and the reagent 4, are arranged on the circumference of the reaction disk 9. The sample dispensing mechanism 10 is a mechanism used when a certain amount of sample 1 is moved from the sample cup 2 to the monomer 8. The sample dispensing mechanism 10 includes: for example, a nozzle for ejecting or sucking a solution; a robot for positioning and transporting the nozzle to a specified position; and a pump for ejecting or sucking a solution from the nozzle. The reagent dispensing mechanism 11 is a mechanism used when a certain amount of reagent 4 is moved from the reagent bottle 5 to the monomer 8. The reagent dispensing mechanism 11 also includes: for example, a nozzle for ejecting or sucking a solution; a robot for positioning and transporting the nozzle to a specified position; and a pump for ejecting or sucking a solution from the nozzle to the nozzle. The stirring section 12 is a mechanism section for stirring the sample 1 and the reagent 4 in the monomer 8 to mix them. The cleaning section 14 is a mechanism section for discharging the reaction solution 7 from the monomer 8 after the analysis process is completed and then cleaning the monomer 8. In the monomer 8 after the cleaning is completed, the next sample 1 is dispensed from the sample dispensing mechanism 10 again, and the new reagent 4 is dispensed from the reagent dispensing mechanism 11 for other reaction processes. In the reaction disk 9, the monomer 8 is immersed in the constant temperature fluid 15 in the constant temperature bath whose temperature and flow rate are controlled. Therefore, the temperature of the monomer 8 and the reaction solution 7 in the monomer 8 is kept constant even when the reaction disk 9 is moved. In the case of this embodiment, water is used as the constant temperature fluid 15, and its temperature is adjusted to 37±0.1°C by the control circuit 23. Of course, the medium and temperature used as the constant temperature fluid 15 are examples. The absorbance measuring section 13 and the scattered light measuring section 16 are arranged on a part of the circumference of the reaction disk 9. The absorbance measuring section 13 is also called an absorptiophotometer, and the scattered light measuring section 16 is also called a scattered light photometer.

[0072] Figure 8 1 is a schematic diagram showing a configuration example of the absorbance measuring unit 13 . Figure 8 The absorbance measuring unit 13 shown has the following structure: light emitted from a halogen lamp light source 31 is irradiated to the monomer 8, and the light 32 that has passed through the monomer 8 is split by a diffraction grating 33 and received by a photodiode array 34. As an example, the wavelength of the light received by the photodiode array 34 is 340nm, 405nm, 450nm, 480nm, 505nm, 546nm, 570nm, 600nm, 660nm, 700nm, 750nm, and 800nm. The light receiving signals of these light receivers are sent to the data storage unit 2601 of the data processing unit 26 through the absorbance measuring circuit 24. Here, the absorbance measuring circuit 24 obtains the light receiving signals of each wavelength domain every constant period and outputs the obtained light quantity value to the data processing unit 26.

[0073] Fig. 9 1 is a schematic diagram showing a structural example of the scattered light measuring unit 16. In the case of the present embodiment, the light source 41 uses, for example, an LED light source unit. The irradiation light 42 emitted from the LED light source unit is irradiated to the monomer 8 located on its optical path, and the transmitted light 44 that has passed through the monomer 8 is received by the transmitted light receiver 46. As for the wavelength of the irradiation light, for example, a wavelength of 700 nm is used. In the present embodiment, the LED light source unit is used as the light source 41, but a laser light source, a xenon lamp, a halogen lamp, etc. may also be used.

[0074] In the scattered light measuring section 16, the scattered light receiver 45a receives the scattered light 43a in the direction separated by an angle of 20° in the air with respect to the optical axis of the irradiated light 42 or the transmitted light 44. In addition, in the scattered light measuring section 16, the scattered light receiver 45b receives the scattered light 43b in the direction separated by an angle of 30° in the air with respect to the optical axis of the irradiated light 42 or the transmitted light 44. The scattered light receivers 45a and 45b are composed of, for example, photodiodes. The light receiving signals of these scattered light receivers 45a and 45b are sent to the data storage section 2601 of the data processing section 26 through the scattered light measuring circuit 25. The scattered light measuring circuit 25 obtains two light receiving signals with different light receiving angles for each constant period, and outputs the obtained light quantity value to the data processing section 26.

[0075] The scattered light receivers 45a and 45b are arranged in a plane substantially perpendicular to the moving direction of the cell 8 caused by the rotation of the reaction disk 9. Here, the reference position of the light receiving angle (the starting point of scattering) is set to the center of the optical path of the light passing through the cell 8.

[0076] Fig. 9 In the embodiment, the case where scattered light receivers 45a and 45b are arranged in a manner corresponding to the light receiving angles of 20° and 30° respectively is described, but it can also be configured to be a linear array of a single body that holds multiple light receivers inside, and receive scattered light at multiple angles at one time. By using a linear array, the options for light receiving angles can be widened. In addition, it is also possible to configure an optical system such as an optical fiber and a lens instead of configuring a light receiver, and guide light to a scattered light receiver arranged at another position. In addition, there can also be one scattered light receiver.

[0077] The quantitative determination of the concentration of the substance to be measured contained in the specimen (sample) 1 is performed by the following steps. First, the control circuit 23 drives the cleaning unit 14 to clean the monomer 8. Next, the control circuit 23 drives the sample dispensing mechanism 10 to dispense a certain amount of the sample 1 in the sample cup 2 into the monomer 8. Next, the control circuit 23 drives the reagent dispensing mechanism 11 to dispense a certain amount of the reagent 4 in the reagent bottle 5 into the monomer 8. When dispensing each solution, the control circuit 23 drives the sample disk 3, the reagent disk 6, and the reaction disk 9 to rotate using the corresponding driving units. At this time, the sample cup 2, the reagent bottle 5, and the monomer 8 are positioned at the specified dispensing position according to the driving timing of the corresponding dispensing mechanism. Next, the control circuit 23 controls the stirring unit 12 to stir the sample 1 and the reagent 4 dispensed into the monomer 8 to generate the reaction solution 7. Through the rotation of the reaction disk 9, the monomer 8 containing the reaction solution 7 passes through the measurement position configured with the absorbance measurement unit 13 and the measurement position configured with the scattered light measurement unit 16. When the monomer 8 passes through the measurement position, the transmitted light or scattered light from the reaction solution 7 in the monomer 8 is measured by the corresponding absorbance measurement unit 13 or scattered light measurement unit 16. In the case of this embodiment, each measurement time is about 10 minutes. The measurement data measured by the absorbance measurement unit 13 and the scattered light measurement unit 16 are output to the data storage unit 2601 in sequence and accumulated as reaction process data.

[0078] During the accumulation of the reaction process data, the reagent dispensing mechanism 11 dispenses additional reagent 4 into the monomer 8 as needed, and the stirring unit 12 stirs the monomer 8, and further measures a certain time. Thus, the reaction process data acquired at a certain time interval is stored in the data storage unit 2601.

[0079] The concentration quantitative value is calculated based on the reaction process data at a certain scattering angle of the scattered light receiver 45a or 45b selected in advance by the user and stored in the data storage unit 2601. The scattered light receiver at which scattering angle is used is specified for each measurement item.

[0080] Fig.10 This is a diagram showing data obtained by using a 100-degree turbidity standard solution as a sample, setting the reagent in an automatic analyzer, and measuring the absorbance measurement unit 13 at the monomer position through the analysis operation on the device. The composition of the 100-degree turbidity standard solution is a mixture of particles with particle sizes of 0.5 μm, 1.0 μm, 2.0 μm, 5.0 μm, and 10.0 μm, and the absorbance of the solution is about 0.22 abs. It should be noted that the transmittance of this solution in a monomer with an optical path length of 5 mm is 77.6%. Fig.10 The photometric points shown on the horizontal axis represent the order in which the reaction process data were measured, and the time from the 1st point to the 34th point is about 10 minutes. Fig.10The vertical axis represents the absorbance measured by the absorbance measurement circuit 24. Fig.11 3 is a diagram showing the results of measuring the same solution using the scattered light measuring unit 16 . Fig.11 The vertical axis represents the amount of scattered light measured by the scattered light measuring circuit 25 .

[0081] Fig.10 , Fig.11 In the experiment, 20 cells were repeatedly measured, but in one measurement, the measured value drifted as time passed. This is believed to be caused by the growth of bubbles attached to the cell wall, which increased the amount of scattered light. Fig.11 As a result of the scattered light measurement, when the fluctuation of the measured value is calculated as the value obtained by dividing the standard deviation (N) of the measured data of the photometric points 20 to 34 by the average value (B), N / B is 0.17%. The lower the noise ratio (N / B) in the reaction process, the more accurate the photometry can be, and the higher the reproducibility, so it is preferred.

[0082] In the automatic analyzer of this embodiment, physiological saline was used as a sample and mixed with a commercially available latex reagent, and the noise ratio N / B (%) of the reaction process data after light measurement by the scattered light measuring unit 16 was calculated without reacting them. Fig.12 This is a graph showing data plotted with absorbance as the horizontal axis. Fig.12 It can be seen that the larger the base absorbance, i.e., the absorbance before the reaction, the lower the N / B. It can be seen that if the absorbance is around 0.6abs to 2.0abs, the N / B is below 0.04%, the fluctuation of the measured value is small, and the photometry can be performed with high accuracy. These suggest that the fixed noise component is reduced as the concentration increases, and the concentration dependence of the scattered light amount is small. Figure 2 In the vicinity of the peak position of the scattered light in the image, the influence of the concentration unevenness of particles in the measurement volume caused by convection etc. is small, and it is considered that the fluctuation of the measurement value becomes the smallest.

[0083] In this regard, as a standard solution for evaluating the scattered light measurement optical system of the automatic analyzer, in this embodiment, a latex solution with an absorbance of 1.13abs containing latex particles with a particle size of 300nm as an insoluble carrier is used. In the solvent for dispersing latex particles with a specific gravity of 1.05 as an insoluble carrier, a glycerol aqueous solution containing 20% ​​by weight of glycerol with a specific gravity of 1.26 is used as a solution for specific gravity adjustment. The solution for specific gravity adjustment is used to make the specific gravity of the solvent for dispersing the insoluble carrier roughly consistent with the specific gravity of the insoluble carrier. By making the specific gravity of the solvent roughly consistent with the specific gravity of the insoluble carrier, for example, within ±25%, the precipitation of the insoluble carrier in the standard solution can be prevented. Specifically, even if an aqueous solution containing 15 to 25% by weight of glycerol is used as a solvent for dispersing the latex particles, the specific gravity can be roughly consistent with the raw material of the latex particles, that is, polystyrene, and the effect of inhibiting the precipitation of the latex particles can be obtained. In addition, 0.5% Triton X-100 is mixed as a surfactant. By mixing the surfactant in the standard solution, the wettability of the monomer wall surface can be improved, the change in light intensity caused by the growth of bubbles after the solution is dispensed into the monomer can be suppressed, and stable scattered light photometry can be achieved.

[0084] Fig.13 : is a diagram showing the result obtained by dispensing the standard solution for evaluating the scattered light measurement optical system into the monomer 8 and measuring it with the absorbance measurement unit 13. Fig.14 This is a diagram showing the results obtained by dispensing a standard solution for evaluating the scattered light measuring optical system into the monomer 8 and measuring it with the scattered light measuring unit 16. In all of these cases, a surfactant is mixed in the standard solution, so bubbles do not adhere to the monomer wall surface and grow, and no drift is found in the measured values. In addition, it can be seen that the N / B calculated based on the measurement data of the photometric points 20 to 34 is suppressed to a low of 0.03%. It can be seen that when the standard solution of this embodiment is used, there is no influence of uneven concentration of insoluble carrier particles, and the optical system can be evaluated with high precision. It should be noted that in Fig.13 and Fig.14 The output fluctuations observed at the first few measurement points are the output fluctuations caused by dispensing and stirring.

[0085] The concentration of the insoluble carrier such as latex particles contained in the standard solution may be such that the absorbance is 0.6 to 2.0 abs or the transmittance is 10% to 50% when dispensed into the monomer, more preferably the absorbance is 0.8 to 1.5 abs or the transmittance is 18% to 40%, and further preferably the absorbance is 1.0 to 1.3 abs or the transmittance is 22.4% to 31.6%. In addition, the particle size of the latex particles is preferably 250 to 350 nm.

[0086] Fig.15 28. The automatic analysis device of this embodiment has a light source light intensity adjustment mode in addition to the normal analysis mode. When the adjustment mode is selected, the LED light intensity adjustment screen is displayed. Fig.15 The LED light intensity adjustment screen is shown.

[0087] In the light source intensity adjustment mode, a standard solution for evaluating the scattered light measurement optical system is dispensed into a monomer of the reaction solution containing the automatic analyzer, that is, a standard solution containing an insoluble carrier is dispensed so that the absorbance becomes 0.6 to 2.0 abs or the transmittance becomes 10% to 50% when dispensed into the monomer, and light is irradiated from a light source to the monomer into which the standard solution is dispensed, and a scattered light detector is used to detect light scattered by the standard solution in the monomer, so that the light intensity of the light source is adjusted in such a way that the output of the scattered light detector becomes a predetermined value.

[0088] In the LED light quantity adjustment screen of the present embodiment, the value obtained by adding the light quantity received by the transmitted light photoreceiver 46 and the scattered light photoreceivers 45a and 45b of the scattered light measuring unit 16 to the basic count (the value when the light quantity is 0) 6667, which is a fixed value on the circuit. Here, when the evaluation latex solution with a particle size of 300nm and a concentration of 1.13abs is measured, the LED drive current value of the scattered light source driving circuit 29 is adjusted so that the output value of the ADC circuit at a scattering angle of 20° becomes 14000±100. The adjustment of the LED drive current value can be realized automatically from the device screen on the software, and in this case, there is an advantage of easy change.

[0089] Fig.161 is a diagram showing the values ​​of scattered light at scattering angles of 20° and 30° before and after the light intensity adjustment of the light source in three automatic analyzers of the same structure as the automatic analyzer used in this embodiment. Before the light intensity adjustment of the light source, the deviation rate ((MAX-MIN) / MIN×100(%)) has a deviation of about 18%, but the deviation rate can be suppressed to about 6% by adjusting the light intensity. In the light intensity adjustment, a 20° scattered light receiver is used to adjust the output value to less than ±2%. Since there is a sensitivity deviation in the receivers set according to each light receiving angle, although they are not completely consistent, the light intensity deviation can be reduced. In this way, by using the standard solution of this embodiment to adjust the light intensity of the LED used as the light source when the automatic analyzer is shipped or the light source is replaced, the difference between the devices when shipped or the light source is replaced can be reduced.

[0090] In addition, in the above embodiment, latex particles with a particle size of 300nm were used as insoluble carriers, but as long as particles with a particle size of 250nm to 350nm are used, the particle size will be consistent with the latex reagent measured on the automatic analyzer, and the amount of scattered light will also be consistent, so it is preferred.

[0091] It should be noted that if the difference in scattered light amount due to the difference in particle size is measured in advance and the relationship between the particle size and the scattered light amount is understood, even the difference between batches of latex particles with slightly different particle sizes can be corrected. Fig.17 This is a diagram showing the relationship between the particle size of latex particles and the ADC output value of the signal from the scattered light receiver. If the LED drive current is changed to make the ADC output value consistent with 14385 when the particle size of the latex particles is 310nm, it can also be known that when the particle size is 300nm, the ADC output value is consistent with 14000. In addition, in this embodiment, the LED drive current is adjusted to eliminate the difference between the devices, but the difference between the devices can also be eliminated by correcting the amplification factor of the circuit, etc.

[0092] It should be noted that the present invention is not limited to the above-mentioned embodiments, and includes various modified examples. For example, the above-mentioned embodiments are detailed descriptions for the purpose of easily understanding the present invention, and are not limited to having all the structures described. In addition, a part of the structure of a certain embodiment may be replaced with the structure of another embodiment, and a structure of another embodiment may be added to the structure of a certain embodiment. In addition, for a part of the structure of each embodiment, other structures may be added, deleted, or replaced.

Claims

1. A method for adjusting the light intensity of a light source of an automatic analyzer, the automatic analyzer comprising the light source, a cell containing a reaction solution, and a detector for detecting light irradiated from the light source to the cell and scattered by the reaction solution in the cell, wherein: The method for adjusting the light intensity of the light source of the automatic analysis device comprises the following steps: Dispensing a standard solution into the monomer, the standard solution being a standard solution for evaluating the scattered light measuring optical system of the automatic analyzer, the standard solution containing an insoluble carrier at a concentration such that the transmittance of light of a wavelength of 700 nm irradiated from the light source to the monomer when the standard solution is dispensed into the monomer is in the range of 10% to 50% when the optical path length of the monomer is 3 mm, 5 mm, or 10 mm, and the scattering angle of light scattered by the standard solution in the monomer is 20° or 30°; irradiating light from the light source to the monomer into which the standard solution is dispensed, and detecting light scattered by the standard solution in the monomer by the detector; as well as The light intensity of the light source is adjusted so that the output of the detector becomes a predetermined value.

2. The method for adjusting the light intensity of a light source of an automatic analysis device according to claim 1, wherein: The insoluble carrier used is a standard solution of latex particles with a particle size of 250 to 350 nm.

3. The method for adjusting the light intensity of a light source of an automatic analysis device according to claim 1, wherein: The solvent used is a standard solution of a glycerol aqueous solution containing 15 to 25% by weight of glycerol.

4. The method for adjusting the light intensity of a light source of an automatic analysis device according to claim 1, wherein: Use a standard solution containing a surfactant.

5. An automatic analysis device comprising: A sample tray, which is provided with a sample cup for receiving the sample; A reagent tray, which is provided with reagent bottles for containing reagents; A reaction disk, which is a single unit for accommodating a reaction solution containing a mixture of a sample and a reagent; a sample dispensing mechanism for dispensing the sample from the sample cup to the monomer; a reagent dispensing mechanism for dispensing reagent from the reagent bottle into the monomer; light source; as well as a scattered light detector for measuring the amount of scattered light of the light irradiated from the light source to the reaction solution in the monomer, in, The automatic analysis device has an adjustment mode, In the adjustment mode, a standard solution containing an insoluble carrier at a concentration in which the transmittance of light of a wavelength of 700 nm irradiated from the light source to the monomer is in the range of 10% to 50% when the optical path length of the monomer is 3 mm, 5 mm, or 10 mm is contained in the monomer instead of the reaction solution, and the light intensity of the light source is adjusted so that the output of the scattered light detector becomes a predetermined value.

6. The automatic analysis device according to claim 5, wherein: The solvent of the standard solution is a glycerol aqueous solution containing 15-25% by weight of glycerol, the standard solution contains a surfactant, and the insoluble carrier is latex particles with a particle size of 250-350 nm.

7. The automatic analysis device according to claim 5, wherein: The light source is an LED, and the light quantity of the light source is adjusted by adjusting the driving current of the LED.

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