Automatic analyzer

Abstract

To solve the problem in which: conventionally, a high concentration specimen falling outside a quantification range in a light scattering detection method needs reinspection, which requires long measurement time.SOLUTION: An automatic analyzer acquires a second light quantity value from a light scattering photometer for a first reaction liquid of a specimen, a first reagent, and a second reagent, determines whether quantitative analysis based on the second light quantity value can be conducted on the basis of the second light quantity value at a predetermined first photometric point, when determining that the quantitative analysis based on the second light quantity cannot be conducted, acquires a first light quantity value from an absorptiometer for a second reaction liquid of the specimen, first reagent, and second reagent, and conducts quantitative analysis based on the first light quantity value. The fluid volume ratio between the first reagent and the second reagent in the first reaction liquid is different from the fluid volume ratio between the first reagent and the second reagent in the second reaction liquid.SELECTED DRAWING: Figure 8

Description

[Technical Field]

[0001] The present invention relates to an automatic analyzer for clinical testing. [Background technology]

[0002] Automated analyzers for clinical testing detect the concentration of target components in biological samples (hereinafter referred to as "samples") such as blood or urine using optical measurement. Specifically, the turbidity change that occurs when light is irradiated onto a reaction solution containing a mixture of the sample and a reagent corresponding to the test item is measured. Next, the measured turbidity change over a certain period of time or the amount of change in the measured value is extracted and compared with a calibration curve prepared in advance for each test item to quantify the concentration of the target component in the sample. If the sample falls outside the measurable and quantifiable range (hereinafter sometimes referred to as the "quantitative range"), the sample volume is changed and retested (hereinafter sometimes referred to as "retest" or "remeasurement"). For example, if the result is below the quantitation range, a retest with an increased sample volume is performed, and if the result is above the quantitation range, a retest with a reduced sample volume is performed.

[0003] While many methods for measuring target components use absorptiometry, which measures the amount of light transmitted through a reaction solution, in recent years, methods using light scattering detection, which allows for more sensitive measurement than absorptiometry, have been reported. These two detection methods have different characteristics, such as different quantification ranges. Taking advantage of the difference in the quantification ranges of these two photometers, an automated analyzer has been developed that incorporates two types of photometers in a single device to expand the dynamic range of measurement (Patent Document 1). Achieving a wide dynamic range reduces the number of samples that fall outside the quantification range, which ultimately leads to a reduction in the rate of retests with different sample amounts.

[0004] Furthermore, a method for shortening the time required to obtain quantitative results while performing retests with reduced or increased amounts is disclosed in Patent Document 2. Patent Document 2 discloses an apparatus that compares the measurement value during measurement of a reaction liquid in which a sample and a reagent are mixed with a preset threshold value, and if the measurement value exceeds the threshold value, starts a retest with a changed sample amount without waiting for the results of the initial measurement. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Laid-Open No. 2014-6160 [Patent Document 2] Japanese Patent Application Publication No. 4-249744 Summary of the Invention [Problem to be solved by the invention]

[0006] Light scattering detection is specialized for highly sensitive measurements and does not have a wide quantitative range. For this reason, for high-concentration samples that fall outside the quantitative range due to the high concentration of the component being measured, a retest with a reduced sample volume has traditionally been performed. This means that it takes the time of two tests, an initial test and a retest, to obtain quantitative results. Furthermore, although it is possible to expand the quantitative range by combining it with absorptiometry, which is suitable for measuring high-concentration samples, different concentration ranges of reagents are required for each detection method, so different reagents are required for each detection method.

[0007] Furthermore, in recent years, the amount of sample used for one measurement has been reduced due to the high sensitivity of reagents, etc. In this case, if a retest is performed using an even smaller amount of sample than was originally a small amount, even a slight variation in dispensing accuracy will have a greater impact on the test results, and there is a risk of reducing the accuracy of the quantitative results. [Means for solving the problem]

[0008] An automatic analyzer according to one embodiment of the present invention comprises a reaction disk having cells arranged on a circumference, each cell containing a reaction solution of a sample and a reagent; a sample dispensing mechanism for dispensing samples into the cells on the reaction disk; a reagent dispensing mechanism for dispensing reagents into the cells on the reaction disk; an absorption photometer for measuring light irradiated from a first light source and transmitted through the reaction solution contained in the cells on the reaction disk; a scattering photometer for measuring light irradiated from a second light source and scattered from the reaction solution contained in the cells on the reaction disk; a control circuit for driving the reaction disk, the sample dispensing mechanism, and the reagent dispensing mechanism; and a data processing unit for executing a sample measurement program and controlling the control circuit in accordance with the sample measurement program. The data processing unit acquires a second light intensity value from the scattering photometer for a first reaction solution of the sample dispensed by the sample dispensing mechanism and the first and second reagents dispensed by the reagent dispensing mechanism, and determines whether quantitative analysis based on the second light intensity value is possible based on the second light intensity value at a predetermined first photometric point.If it determines that quantitative analysis based on the second light intensity value is not possible, it acquires a first light intensity value from the absorption photometer for a second reaction solution of the sample dispensed by the sample dispensing mechanism and the first and second reagents dispensed by the reagent dispensing mechanism, and performs quantitative analysis based on the first light intensity value, and the liquid volume ratio of the first reagent to the second reagent in the first reaction solution is different from the liquid volume ratio of the first reagent to the second reagent in the second reaction solution. [Effects of the Invention]

[0009] The time required to obtain results can be shortened even in the case of a highly concentrated sample. Problems, configurations, and effects other than those described above will become apparent from the following description of the embodiments. [Brief explanation of the drawings]

[0010] [Figure 1] 10 is an example of a flow of an analysis operation in the first embodiment. [Figure 2] FIG. 1 is a schematic diagram comparing the reaction process and the time required to obtain the results between the conventional method and Example 1. [Figure 3] 1 is a schematic diagram illustrating the overall configuration of an automatic analyzer. [Figure 4]10 is an example of a setting screen for application parameters according to the first embodiment. [Figure 5] FIG. 10 is a diagram illustrating an example of the relationship between photometry points and light amounts. [Figure 6] 1 is an example of a calibration curve for scattered light measurement. [Figure 7] 1 is an example of a calibration curve for absorbance measurement. [Figure 8] 10 is an example of a flow of an analysis operation in the second embodiment. [Figure 9] 1 shows an example of the reaction process and the time required to obtain the results of Example 2. [Figure 10] 10 is an example of a setting screen for application parameters according to the second embodiment. [Figure 11] FIG. 10 is a diagram illustrating an example of the relationship between photometry points and light amounts. DETAILED DESCRIPTION OF THE INVENTION

[0011] Hereinafter, an embodiment of the present invention will be described with reference to the drawings. [Example]

[0012] In Example 1, for items measured by the light scattering detection method, the measured light intensity value is compared with a preset threshold light intensity during measurement, and if it is determined to be out of range, latex test solution is added to the reaction solution and measurement is continued by the absorptiometry method.

[0013] In conventional latex immunoturbidimetry, a sample is mixed by adding a first reagent (buffer solution) and a second reagent (latex reagent solution) once each. The order of addition is, for example, sample, buffer solution, and latex reagent solution. The change in turbidity of the reaction solution that occurs after the addition of the latex reagent solution is optically measured to quantify the concentration of the component to be measured in the sample. In this case, for example, if the sample falls outside the upper limit of the quantification range, the amount of sample added is reduced and retesting is performed. In Example 1, in items primarily using light scattering detection, if the sample falls outside the upper limit of the quantification range, the concentration is quantified in a single measurement without retesting.

[0014] FIG. 1 shows an example of the analytical operation flow of Example 1. First, scattered light measurement of a reaction solution in which a sample, a buffer solution, and a latex reagent solution have each been dispensed once is initiated (S101). The sample, buffer solution, and latex reagent solution constituting the reaction solution can be dispensed in any order, as long as the buffer solution is not dispensed last, e.g., sample, buffer solution, and latex reagent solution. The measured light intensity is compared with a preset threshold light intensity during measurement to determine whether the measurement is over range (S102). If the measurement is determined to be over range, latex reagent solution is added to the reaction solution, the detector is switched from the scattering photometer to the absorptiometer, and measurement is continued (S106). After the measurement is completed (S107), the concentration quantified based on the measurement results from the absorptiometer is output (S108). On the other hand, if the range-over determination (S102) determines that the measurement is within range, measurement is continued without switching detectors or adding any reagent to the reaction solution (S103). After the measurement is completed (S104), the concentration quantified based on the measurement result of the scattering photometer is output (S105).

[0015] In the operation of step S106, the operation may be switched to measurement using only the absorptiometer, or measurement using the scattering photometer may be continued in addition to measurement using the absorptiometer. Furthermore, at the start of measurement (S101), measurement using the scattering photometer may be performed in parallel with measurement using the absorptiometer. In this case, the operation of step S104 prioritizes output of the results from the scattering photometer, and the operation of step S108 prioritizes output of the results from the absorptiometer.

[0016] Figure 2 is a schematic diagram comparing the reaction process and the time required to obtain results between the conventional method and Example 1. The horizontal axis of the reaction process represents the photometry point (elapsed time), and the vertical axis represents the light intensity. Reaction processes 201 and 203 are reaction processes in which the light intensity plateaus after adding the latex reagent solution due to the high concentration of the component to be measured, exceeding the measurement range during measurement. For this reason, in conventional methods 1 and 2, retests are conducted with reduced sample amounts, as shown in reaction processes 202 and 204, respectively.

[0017] In Conventional Method 1, after the measurement of the initial test (reaction process 201) is completed, a retest (reaction process 202) using a reduced sample volume is initiated. In this case, if the measurement time per test is 10 minutes, for example, a total of 20 minutes is required to obtain the final quantitative results. In Conventional Method 2, the concentration of the component to be measured is calculated from the light intensity during the measurement after the addition of the latex reagent in the initial test (reaction process 203), and is compared with a preset threshold value. If the calculated value exceeds the threshold value, a retest (reaction process 204) is initiated. In this case, if the measurement time per test is 10 minutes and the retest is initiated 7 minutes into the initial test, for example, a total of 17 minutes is required to obtain the final quantitative results. Compared to Conventional Method 1, this reduces the time required to obtain the quantitative results by 3 minutes.

[0018] In contrast, in Example 1, as shown in Figure 1, the light intensity value during measurement after adding the latex reagent is compared with a preset threshold light intensity. If the result is determined to be overrange, additional latex reagent is added to the reaction solution, the detector is switched from the scattering photometer to the absorption photometer, and measurement is continued to quantify the concentration. Reaction process 205 is an example of the reaction process in Example 1, where an overrange determination is made and measurement is continued after switching the detector. The reaction process up to the second addition of the latex reagent is represented by data measured with the scattered light clock (●), and the reaction process after the second addition of the latex reagent is represented by data measured with the absorption photometer (▲). Adding the second latex reagent adjusts the reagent concentration to a concentration suitable for absorption spectrophotometry, and then switching to the absorption photometer, which has a wider quantification range than the scattering photometer, enables concentration quantification in a single measurement without the need for retesting. Thus, Example 1 significantly reduces the time required to obtain quantitative results compared to conventional methods.

[0019] (Automatic analyzer) 3 shows the overall schematic configuration of the automatic analyzer 100, and the basic operation of the device will be described. Note that this is an example and is not limited to the following example.

[0020] The automatic analyzer 100 is generally configured to have three types of disks: a sample disk 103, a reagent disk 106, and a reaction disk 109; a sample dispensing mechanism 110 and a reagent dispensing mechanism 111 that move samples and reagents between these disks; a drive unit 117 that drives the three types of disks and the dispensing mechanism; a control circuit 118 that controls the drive unit; an absorbance measurement circuit 119 that measures the absorbance of the reaction liquid; a scattered light measurement circuit 120 that measures scattered light from the reaction liquid; a data processing unit 121 that processes data measured by each measurement circuit; an operation unit 122 that interfaces with the data processing unit 121; a printer 123 that prints and outputs information; and a communication interface 124 that connects to a network or the like.

[0021] A plurality of sample cups 102, which are containers for holding specimens 101, are arranged on the circumference of specimen disk 103. The specimens 101 include blood, urine, cerebrospinal fluid, standard solutions, etc. A plurality of reagent bottles 105, which are containers for holding reagents 104, are arranged on the circumference of reagent disk 106. The reagents include a first reagent (buffer solution) and a second reagent (latex test solution). A plurality of cells 108, which are containers for holding reaction solutions 107 obtained by mixing specimens 101 and reagents 104, are arranged on the circumference of reaction disk 109. Each disk is rotated by a motor included in drive unit 117, and this motor is controlled by control circuit 118.

[0022] The specimen dispensing mechanism 110 is a mechanism used to transfer a fixed amount of specimen 101 from a sample cup 102 placed on a specimen disk 103 that rotates clockwise and counterclockwise to a cell 108. The specimen dispensing mechanism 110 is composed of, for example, a nozzle that dispenses or aspirates the specimen 101, a robot that moves the nozzle to a predetermined position, and a pump that dispenses or aspirates the specimen 101 from the nozzle. The robot and the pump correspond to a driving unit 117.

[0023] The reagent dispensing mechanism 111 is a mechanism used to transfer a fixed amount of reagent 104 from reagent bottles 105 arranged on a reagent disk 106 that rotates clockwise and counterclockwise to cells 108. The reagent dispensing mechanism 111 is composed of, for example, a nozzle that dispenses or aspirates the reagent 104, a robot that moves the nozzle to a predetermined position, and a pump that dispenses or aspirates the reagent 104 from or into the nozzle. The robot and pump correspond to a driving unit 117.

[0024] The cell 108 is immersed in a constant temperature fluid 112 in a constant temperature bath in which the temperature and flow rate are controlled on the reaction disk 109. Therefore, the temperature of the cell 108 and the reaction solution 107 therein is maintained at a constant temperature even while the cell 108 moves with the rotation of the reaction disk 109. In this embodiment, water is used as the constant temperature fluid 112, and its temperature is adjusted to 37±0.1°C by the control circuit 118. Of course, the medium and temperature used as the constant temperature fluid 112 are merely examples.

[0025] The stirring mechanism 113 is a mechanism that stirs and mixes the specimen 101 and the reagent 104 in the cell 108. The stirring mechanism 113 is composed of, for example, a stirring rod that stirs the mixture of the specimen 101 and the reagent 104, a robot that moves the stirring rod to a predetermined position, and a motor that rotates the stirring rod. The robot and the motor correspond to the drive unit 117.

[0026] The cleaning mechanism 114 is a mechanism that aspirates the reaction liquid 107 from the cell 108 after the analysis process has been completed, and cleans the empty cell 108. The cleaning mechanism 114 is composed of, for example, a nozzle that aspirates the reaction liquid 107 after the analysis has been completed, a nozzle that dispenses cleaning water into the cell 108 after the reaction liquid 107 has been aspirated, a nozzle that aspirates the cleaning water, and a mechanism for moving the nozzle. This mechanism is included in the drive unit 117. After the cleaning process is completed, the next sample 101 is dispensed into the cell 108 from the specimen dispensing mechanism 110, and new reagent 104 is dispensed from the reagent dispensing mechanism 111, and the cell 108 is used for a new analysis process.

[0027] An absorbance measuring unit 115 and a scattered light measuring unit 116 are arranged on a part of the circumference of the reaction disk 109 .

[0028] The absorbance measurement unit 115 includes a light source and a transmitted light receiver, which are arranged to sandwich the cell 108 on the reaction disk 109. For example, the light source may be a halogen lamp, and the cell 108 is irradiated with light emitted from the light source. The light transmitted through the reaction solution 107 contained in the cell 108 is dispersed by a diffraction grating and received by a photodiode array. The wavelengths received by the photodiode array are 340 nm, 405 nm, 450 nm, 480 nm, 505 nm, 546 nm, 570 nm, 600 nm, 660 nm, 700 nm, 750 nm, and 800 nm. Light reception signals from these receivers are transmitted to a memory unit 121a of a data processing unit 121 via an absorbance measurement circuit 119. The absorbance measurement circuit 119 acquires light reception signals for each wavelength range at regular intervals and outputs the acquired light intensity values to the data processing unit 121. The absorbance measurement unit 115 and the absorbance measurement circuit 119 are collectively referred to as an absorptiometer.

[0029] The scattered light measurement unit 116 includes a light source, a transmitted light receiver, and a scattered light receiver, and the light source, transmitted light receiver, and scattered light receiver are arranged to sandwich the cell 108 on the reaction disk 109. For example, the light source is an LED, and light emitted from the light source is irradiated onto the cell 108. The light transmitted through the reaction solution 107 contained in the cell 108 is received by the transmitted light receiver, and the light scattered by the reaction solution 107 is received by the scattered light receiver. The wavelength of the irradiated light is, for example, 700 nm. In scattered light measurement, it is preferable to use irradiated light with a wavelength of 600 nm to 800 nm, which is visible light, as it is less susceptible to the influence of impurities contained in the sample (chyle, hemolysis, jaundice). In addition to an LED, a laser light source, a xenon lamp, a halogen lamp, or the like may be used as the light source. For example, a photodiode is used as the light receiver. The transmitted light and light reception signals from the scattered light receiver are transmitted to the memory unit 121a of the data processing unit 121 via the scattered light measurement circuit 120. The scattered light measurement circuit 120 also acquires light reception signals at regular intervals and outputs the acquired light intensity values to the data processing unit 121. The scattered light receiver is disposed, for example, in a plane that is approximately perpendicular to the direction of movement of the cell 108 due to the rotation of the reaction disk 109. In this case, a line sensor may be used as the receiver, and a configuration may be adopted in which scattered light from multiple angles is received at once. The use of a line sensor can expand the range of light reception angles. Furthermore, instead of directly arranging the receiver, an optical system such as a fiber or lens may be disposed to guide light to a scattered light receiver disposed in a separate location. The scattered light measurement unit 116 and the scattered light measurement circuit 120 are collectively referred to as a scattered light photometer.

[0030] The reaction disk 109 is rotated a fixed amount in one cycle. The absorptiometer and scattered light meter measure the cell 108 passing through the absorbance measurement unit 115 and scattered light measurement unit 116, respectively, so the time interval between photometry points at which the absorptiometer measures the reaction solution 107 in the cell 108 and the time interval between photometry points at which the scattered light meter measures the reaction solution in the cell 108 are the time it takes for the reaction disk 109 to make one rotation, which is a fixed time.

[0031] The data processing unit 121 includes a memory unit 121a and an analysis unit 121b. The memory unit 121a stores a control program, a measurement program, a data analysis program, calibration curve data, measurement data, analysis results, and the like. The measurement program is, for example, a measurement program for data used to generate a calibration curve and a sample measurement program. The sample measurement program includes a program for comparing the light intensity during measurement with a threshold light intensity, as shown in FIG. 1, to determine the next action. When an analysis request is input to the data processing unit 121 via the operation unit 122 or the communication interface 124, the corresponding measurement program is executed and the control program operates. The control program operates the control circuit, which in turn operates the drive unit, thereby influencing each mechanism and performing the analysis. The measurement data output to the data processing unit 121 via the absorbance measurement circuit 119 and the scattered light measurement circuit 120 is stored in the memory unit 121a and read out to the analysis unit 121b together with the data analysis program. The data analysis program is, for example, a calibration curve generation program, a program for quantifying sample concentration using the calibration curve, and a program for determining errors in the calibration curve and sample measurement results. The analysis results and other data obtained by analysis according to the data analysis program are returned to and stored in the storage unit 121a. The analysis results and error information stored in the storage unit 121a are displayed on the display unit 122a of the operation unit 122, and, if necessary, are printed out by the printer 123. The data processing unit 121 is realized by, for example, a processor such as a CPU.

[0032] The operation unit 122 includes a display unit 122a and, as input units, a keyboard 122b and a mouse 122c. In addition to using the keyboard 122b, input may be made by touching the screen of the display unit 122a, or by selecting an item displayed on the screen of the display unit 122a with the mouse 122c.

[0033] The communication interface 124 is connected to, for example, a network within a hospital, and communicates with a hospital information system (HIS) and a laboratory information system (LIS).

[0034] (Analysis operation) First, the parameters required for the analysis are set. Figure 4 shows an example of an application parameter setting screen for Example 1. First, on the analysis item setting screen 501, the item to be quantified, the sample volume, the analysis request method, whether or not to perform R3 addition during analysis, and the output unit are input. In this Example, since light scattering analysis is the main target, an example is shown in which "light scattering analysis" is selected for "analysis request method." In "Perform R3 addition during analysis," by selecting whether or not to perform reagent R3 addition, it is possible to select whether to perform measurement according to Example 1 or the conventional method. Here, an example is shown in which "Perform R3 addition during analysis" is selected as "Yes."

[0035] Next, the parameters required for measurements with the scattering photometer and absorptiometer are entered. The parameter screen 502 for scattering photometer measurements includes the analysis method, photometric point used for calculation, reagent dispensed amount, light receiving angle, and quantitative range, as well as the check measurement point and threshold light intensity. The check measurement point and threshold light intensity may be displayed on the application parameter setting screen as shown in Figure 4 and treated as parameters that can be set by the user, or they may not be displayed on the setting screen and default values for each item may be stored in the measurement program, etc. The parameter screen 503 for absorptiometer measurements includes the analysis method, photometric point used for calculation, wavelength, R3 dispensed amount, and quantitative range.

[0036] Here, the reagents are represented as R1, R2, and R3, and are dispensed in ascending order of numbers. R1 indicates the dispensing of the buffer solution, and R2 and R3 indicate the dispensing of the latex test solution. The numerical values of R1 and R2 in the measurement parameters of the absorptiometer are the same as the numerical values of R1 and R2 in the measurement parameters of the scattering photometer. This is because in the measurement method of Example 1, the reagents dispensed during measurement are used as they are for light scattering analysis (see reaction process 205 in Figure 2).

[0037] Examples of analytical methods include one-point analysis, two-point rate analysis, and two-point end analysis. Figure 4 shows an example where two-point end analysis is selected. With two-point end analysis, the change in light intensity between two photometric points is used to quantify the concentration. The two photometric points are specified in the photometric point input field shown in Figure 4. The numerical values in the quantification range are the concentration values of the component to be measured, and indicate the lower and upper limits of the quantification range.

[0038] Among the parameters for scattered light measurement, the check measurement point and threshold light intensity are information used in the range over determination (S102) in Figure 1. The check measurement point and threshold light intensity may be set by the user, automatically calculated within the device using the measurement value of the standard solution, or provided by the reagent manufacturer. The measurement value (light intensity) of the highest concentration standard solution in scattered light measurement may also be used as the threshold light intensity. If set by the user, it is recommended to provide an input field on the application parameter setting screen. In other cases, it is not necessarily necessary to display an input field on the application parameter setting screen. The check measurement point is equal to or greater than the point after R2 is dispensed and equal to or less than the point before R3 is dispensed.

[0039] An example of the relationship between photometric points and light intensity when R2 is dispensed up to R3 is shown in Figure 5. Figure 5 shows an example where R2 is dispensed between photometric points 5 and 6, and R3 is dispensed between photometric points 16 and 17. The light intensity up to R3 dispensing is the scattered light intensity (●) measured by the scattered light clock, and the light intensity after R3 dispensing is the absorbance (▲) measured by the absorptiometer. In the example of Figure 5, the "photometric points for check execution" are set between photometric points 6 and 16.

[0040] After setting the parameters required for analysis, calibration is performed. In calibration, a standard solution with a known analyte concentration is measured to obtain a calibration curve showing the relationship between the concentration of the component to be measured and the light intensity. In this embodiment, two calibration curves are prepared. One is a calibration curve obtained when a reaction solution containing a mixture of the analyte, R1, and R2 is measured using a scattering photometer, and is used when measurement using the light scattering detection method is completed (step S105 in FIG. 1). This calibration curve is used as the scattered light measurement calibration curve, an example of which is shown in FIG. 6. The other is a calibration curve obtained when a reaction solution containing a mixture of the analyte, R1, R2, and R3 is measured using an absorptiometer, and is used when measurement is completed after switching from light scattering detection to absorptiometry (step S108 in FIG. 1). This calibration curve is used as the absorbance measurement calibration curve, and an example of which is shown in FIG. 7.

[0041] The horizontal axis in Figures 6 and 7 represents the concentration of the component to be measured, and the vertical axis represents the light intensity calculated according to the analysis method and photometric points set in the application parameters. For example, when using the application parameters in Figure 4, the analysis method for the scattered light meter is the two-point end method, and the photometric points are 7 and 22. Therefore, the scattered light meter measurement shows the light change (change in scattered light intensity) at photometric points 7 and 22. The analysis method for the absorption photometer is the two-point end method, and the photometric points are 19 and 34. Therefore, the light change (change in absorbance) at photometric points 19 and 34. For example, the effective range of the scattered light measurement calibration curve (Figure 6) is a concentration range of 500 ng / mL or less, and the effective range of the absorbance measurement calibration curve (Figure 7) is a concentration range of 400 to 1000 ng / mL. Although there is a concentration range where the effective ranges overlap (in this example, the range from 400 to 500 ng / mL), which calibration curve to use should be determined according to the flowchart in Figure 1, and the calibration curve derived from the photometer used should be used.

[0042] After calibration, a sample of unknown concentration is measured. The measurement operation flow is as shown in Figure 1. Specifically, for example, a sample of unknown concentration, a buffer solution (R1), and a latex test solution (R2) are dispensed into cell 108, and scattered light measurement is initiated (S101). The dispensed amounts of the sample, R1, and R2 are the amounts set as parameters for the scattered light meter among the application parameters. When the light intensity at the "check measurement point" is acquired, the light intensity at the check measurement point is compared with the "threshold light intensity" during measurement to determine whether it is within range (S102). The check measurement point and threshold light intensity are default values or values set on the application parameter setting screen and stored in the measurement program, etc. If it is determined to be within range, scattered light measurement continues (S103). After measurement is completed (S104), the light intensity is calculated from the acquired reaction process according to the "analysis method" and "photometric point" set as parameters for the scattered light meter among the application parameters. This light intensity is compared with the light intensity on the scattered light measurement calibration curve to quantify and output the concentration (S105). For example, in accordance with the application parameters of the scattered light meter in Figure 4, the analysis method is the two-point end analysis method and the photometric points are 7 and 22, so the amount of scattered light change between these photometric points is calculated and compared with the amount of scattered light change on the scattered light measurement calibration curve (Figure 6) to quantify the concentration.

[0043] On the other hand, if the range is exceeded in the range over determination (S102), latex test solution is added (R3 is dispensed), the detector is switched from the scattering photometer to the absorptiometer, and measurement continues (S106). The amount of R3 dispensed at this time is the amount set as a parameter for the absorptiometer among the application parameters. After measurement is completed (S107), the light intensity is calculated from the acquired reaction process according to the "analysis method" and "photometric point" set as a parameter for the absorptiometer among the application parameters. This light intensity is compared with the light intensity on the calibration curve for absorptiometry (Figure 7) to quantify the concentration and output it (S108).

[0044] In Example 1, an example was shown in which the light intensity during measurement was compared with a preset threshold light intensity to determine whether the range is exceeded, but determinations other than those using light intensity may also be used. For example, the light intensity after a certain time has elapsed may be estimated from the light intensity at an arbitrary photometric point, and the estimated light intensity may be compared with a separately set threshold light intensity. Alternatively, the analyte concentration may be estimated from the light intensity at an arbitrary photometric point or the estimated light intensity after a certain time has elapsed, and compared with a separately set threshold concentration. Alternatively, the slope of the reaction process between arbitrary photometric points after the addition of R2 may be compared with a separately set threshold slope to determine whether the range is exceeded. [Example]

[0045] In Example 2, for items measured by light scattering detection, the measured light intensity value is compared with a preset threshold light intensity during measurement, and if it is determined to be out of range, the liquid volume ratio of the reagent is changed so that the reagent concentration is suitable for absorptiometry, and re-measurement is started using absorptiometry before the initial measurement is completed.

[0046] FIG. 8 shows an example of the analytical operation flow of Example 2. First, scattered light measurement of a reaction solution in which a sample, a buffer solution, and a latex reagent solution have each been dispensed once is initiated (S301). The sample, buffer solution, and latex reagent solution that make up the reaction solution can be dispensed in any order, as long as the buffer solution is not dispensed last, e.g., sample, buffer solution, and latex reagent solution. The measured light intensity is compared with a preset threshold light intensity during measurement to determine whether it is overrange (S302). If it is determined to be overrange, the liquid volume ratio of the buffer solution to the latex reagent solution is changed, and absorbance measurement is initiated with a reagent concentration appropriate for absorptiometry before the initial measurement is completed (S306). After the measurement is completed (S307), the quantified concentration is output based on the measurement results from the absorptiometer (S308). On the other hand, if the overrange determination (S302) determines that the value is within range, the scattering light meter measurement continues (S303). After the measurement is completed (S304), the concentration quantified based on the measurement results of the scattering photometer is output (S305).

[0047] The timing of dispensing the buffer solution and the latex test solution at the start of measurement (S301) can be in two cases, out of the dispensing timings R1, R2, and R3 described in Example 1: the buffer solution may be dispensed at R1 and the latex test solution at R2, or the buffer solution may be dispensed at R1 and the latex test solution at R3.

[0048] Figure 9 is a schematic diagram of the reaction process and the time required to obtain results in Example 2. The horizontal axis of the reaction process represents the photometry point (elapsed time), and the vertical axis represents the light intensity. Reaction process 401 shows the scattered light measurement reaction process in which the light intensity exceeded the measurement range during measurement after adding the latex reagent due to the high concentration of the analyte. Reaction process 402 shows an example in which the sample volume is the same as the initial test, but the ratio of the buffer solution to the latex reagent solution is changed from the initial test, and absorbance measurement is performed at a reagent concentration suitable for absorptiometry. In this case, for example, if the measurement time per test is 10 minutes and a retest is started 7 minutes into the initial test, a total of 17 minutes is required to obtain the final quantitative result. The time required to obtain the quantitative result is the same as that of Conventional Method 2 in Example 1 (see Figure 2). However, the method of Example 2 changes the reagent concentration and uses a detector appropriate for the quantitative range, which makes it more likely that the quantitative range can be expanded compared to a retest using only a change in sample volume.

[0049] The configuration of the automatic analyzer that realizes the second embodiment is the same as that of the first embodiment (FIG. 3), so a duplicated description will be avoided here.

[0050] (Analysis operation) First, the parameters required for the analysis are set. FIG. 10 shows an example of an application parameter setting screen for Example 2. First, on an analysis item setting screen 601, the item to be quantified, the analysis request method, whether or not to change the photometer during retesting, whether or not to perform retesting during measurement, and the output unit are input. In this Example, since items that mainly involve light scattering analysis are targeted, an example is shown in which "light scattering analysis" is selected for "analysis request method." By selecting whether or not to "change the photometer during retesting" and whether or not to "perform retesting during measurement," it is possible to select whether to perform measurement according to Example 2 or the conventional method. FIG. 10 shows an example in which "change the photometer during retesting" is selected as "OK" and "perform retesting during measurement" is selected as "OK" (measurement according to Example 2 is selected).

[0051] Next, the parameters required for measurements using the scattering photometer and absorptiometer are entered. The parameter screen 602 for measurements using the scattering photometer includes the analysis method, photometric point used for calculation, sample volume, reagent dispensed volume, light receiving angle, and quantification range, as well as the check measurement point and threshold light intensity. The check measurement point and threshold light intensity may be displayed on the application parameter setting screen as shown in Figure 10 and treated as parameters that can be set by the user, or they may not be displayed on the setting screen and default values for each item may be stored in the measurement program, etc. The parameter screen 603 for measurements using the absorptiometer includes the analysis method, photometric point used for calculation, wavelength, sample volume, reagent dispensed volume, and quantification range.

[0052] Here, the reagents are represented as R1, R2, and R3, and they are dispensed in ascending order of numbers. R1 indicates the dispensing of the buffer solution, and R2 and R3 indicate the dispensing of the latex test solution. Here, an example is shown in which the buffer solution is dispensed at the timing of R1, and the latex test solution is dispensed at the timing of R3. R2 being zero means that nothing is dispensed at the dispensing timing of R2. It is also possible to set R3 to zero and set the dispensing amount of the latex test solution to R2.

[0053] The values of R1, R2, or R3 in the measurement parameters of the absorption photometer differ from those of the scattering photometer. The preferred concentration of latex reagent in the reaction solution differs between the absorption photometer and the scattering photometer, with a higher concentration being preferable for the absorption photometer. Therefore, it is desirable that the amount of R1 (buffer solution) in the measurement parameters of the absorption photometer be smaller than the R1 in the measurement parameter of the scattering photometer, and that the amount of R2 or R3 (latex reagent) in the measurement parameters of the absorption photometer be larger than the R2 or R3 in the measurement parameter of the scattering photometer. Furthermore, it is desirable to set the total amount of R1, R2, or R3 to be equal for each photometer. However, even if the total amount differs between the photometers, this is not a problem because calibration is performed for each photometer. The sample volume may be the same or different for each photometer. Even if the sample volume differs, this is not a problem because calibration is performed for each photometer according to the measurement conditions.

[0054] The analytical method, photometric points, and quantitative range are explained in the same manner as in Example 1, so a duplicate explanation will be avoided here.

[0055] Among the parameters for scattered light measurement, the check measurement point and threshold light intensity are information used in the range over determination (S302) in Figure 8. The check measurement point and threshold light intensity may be set by the user, may be automatically calculated within the device using the measurement value of the standard solution, or may be provided by the reagent manufacturer. The measurement value (light intensity) of the highest concentration standard solution in scattered light measurement may also be used as the threshold light intensity. If set by the user, it is recommended that an input field be provided on the application parameter setting screen. In other cases, it is not necessarily necessary to display an input field on the application parameter setting screen. The check measurement point is above the point after R2 or R3 dispensing.

[0056] Figure 11 shows an example of the relationship between the photometric point and the amount of light (scattered light intensity) when R1 and R3 are dispensed in scattered light measurement. Figure 11 shows an example where R3 is dispensed between photometric points 16 and 17. In this case, the "check photometric point" is set to a value greater than or equal to 17 and less than or equal to the measurement end photometric point (34 in Figure 11). In this example, the closer the check photometric point is to 17, the sooner the range over determination can be made, and the earlier the timing for starting retesting will be.

[0057] After setting the parameters required for analysis, calibration is performed. In calibration, a standard solution with a known sample concentration is measured to obtain a calibration curve showing the relationship between the concentration of the component to be measured and the light intensity. In Example 2, two calibration curves are also prepared. One is a scattered light measurement calibration curve when measured with a scattering photometer, and the other is an absorbance measurement calibration curve when measured with an absorption photometer. The light intensity on the vertical axis of the calibration curve is the light intensity calculated according to the analysis method and photometric points set in the application parameters. It can be obtained by performing scattering photometer measurements and absorbance photometer measurements independently according to the application parameters set for each photometer.

[0058] After calibration, a sample of unknown concentration is measured. The operational flow for measurement is as shown in Figure 8. Specifically, for example, a sample of unknown concentration, a buffer solution (R1), and a latex test solution (R3) are dispensed into cell 108, and scattered light measurement begins (S301). The dispensed amounts of the sample, R1, and R3 are the amounts set as parameters for the scattered light meter among the application parameters. When the light intensity at the "check measurement point" is acquired, the light intensity at the check measurement point is compared with the "threshold light intensity" during measurement to determine whether it is within range (S302). The check measurement point and threshold light intensity are default values or values set on the application parameter setting screen and stored in the measurement program, etc. If it is determined to be within range, scattered light measurement continues (S303). After measurement is completed (S304), the light intensity is calculated from the acquired reaction process according to the "analysis method" and "photometric point" set as parameters for the scattered light meter among the application parameters. This light amount is compared with the light amount on the scattered light measurement calibration curve to quantify the concentration and output it (S305). For example, in accordance with the application parameters of the scattered light meter in Figure 10, the analysis method is the two-point end analysis method and the photometric points are 20 and 32, so the amount of scattered light change between these photometric points is calculated and compared with the amount of scattered light change on the scattered light measurement calibration curve to quantify the concentration.

[0059] On the other hand, if the range is exceeded in the range over determination (S302), a new sample of unknown concentration, buffer solution (R1), and latex reagent (R3) are dispensed into a new cell 108, and measurement is restarted with the absorptiometer (S306). The dispensed amounts of the sample, R1, and R3 are the amounts set as parameters for the absorptiometer among the application parameters. This measurement is started before the scattered light measurement is completed. After the measurement is completed (S307), the light intensity is calculated from the acquired reaction process according to the "analysis method" and "photometric point" set as parameters for the absorptiometer among the application parameters. This light intensity is compared with the light intensity of the calibration curve for absorptiometry, and the concentration is quantified and output (S308).

[0060] This embodiment is characterized in that absorbance measurement is started at a reagent concentration suitable for absorptiometry before the initial test is completed. This not only shortens the time required to obtain quantitative results, but also has the effect of expanding the quantitative range by using a detector appropriate for the quantitative range.

[0061] In Example 2, an example was shown in which the light intensity during measurement was compared with a preset threshold light intensity to determine whether the range is exceeded. However, determinations other than those using light intensity may also be used. For example, the light intensity after a certain time has elapsed may be estimated from the light intensity at an arbitrary photometric point, and the estimated light intensity may be compared with a separately set threshold light intensity. Alternatively, the analyte concentration may be estimated from the light intensity at an arbitrary photometric point or the estimated light intensity after a certain time has elapsed, and compared with a separately set threshold concentration. Alternatively, the slope of the reaction process between arbitrary photometric points after the addition of R2 or R3 may be compared with a separately set threshold slope to determine whether the range is exceeded.

[0062] The present invention is not limited to the above-described first and second embodiments, but includes various modifications. In this embodiment, a latex immunoturbidimetric test is used as an example, in which a latex test solution sensitized with an antibody or antigen is mixed with a standard solution or specimen containing the target component (antigen or antibody), and the latex agglutination reaction resulting from the antigen-antibody reaction is measured using a scattering photometer or an absorptiometer. However, the present invention is not limited to latex immunoturbidimetric tests. For example, a system may be used in which an insoluble carrier (silica particles, magnetic particles, metal colloid, etc.) sensitized with an antibody or antigen is mixed with a standard solution or specimen containing the target component (antigen or antibody), and the agglutination reaction of particles resulting from the antigen-antibody reaction is measured using a scattering photometer or an absorptiometer. Furthermore, the target component to be quantified may be its activity value rather than its concentration.

[0063] The above-described embodiments have been described in detail to clearly explain the present invention, and are not necessarily limited to those including all of the described configurations. It is possible to replace part of the configuration of one embodiment with the configuration of another embodiment, and it is also possible to add the configuration of another embodiment to the configuration of one embodiment. Furthermore, it is possible to add, delete, or replace part of the configuration of each embodiment with the same configuration or other configurations. [Explanation of symbols]

[0064] 100: automatic analyzer, 101: specimen, 102: sample cup, 103: specimen disk, 104: reagent, 105: reagent bottle, 106: reagent disk, 107: reaction liquid, 108: cell, 109: reaction disk, 110: specimen dispensing mechanism, 111: reagent dispensing mechanism, 112: constant temperature fluid, 113: stirring mechanism, 114: cleaning mechanism, 115: absorbance measuring unit, 116: scattered light measuring unit, 117: driving unit, 118: control circuit, 119 : absorbance measurement circuit, 120: scattered light measurement circuit, 121: data processing unit, 121a: memory unit, 121b: analysis unit, 122: operation unit, 122a: display unit, 122b: keyboard, 122c: mouse, 123: printer, 124: communication interface, 201, 202, 203, 204, 205, 401, 402: reaction process, 501, 601: analysis item setting screen, 502, 503, 602, 603: parameter screen.

Claims

1. a reaction disk on which cells containing reaction solutions of samples and reagents are arranged on the circumference; a sample dispensing mechanism that dispenses a sample into a cell on the reaction disk; a reagent dispensing mechanism that dispenses reagents into cells on the reaction disk; an absorptiometer that measures light that is irradiated from a first light source and that has passed through the reaction solution contained in the cell on the reaction disk; a scattering photometer that measures light that is irradiated from a second light source and scattered by the reaction solution contained in the cell on the reaction disk; a control circuit that drives the reaction disk, the sample dispensing mechanism, and the reagent dispensing mechanism; and a data processing unit that executes a sample measurement program and controls the control circuit in accordance with the sample measurement program, the data processing unit acquires a second light quantity value from the scattering photometer for a first reaction solution of the specimen dispensed by the specimen dispensing mechanism and the first and second reagents dispensed by the reagent dispensing mechanism, and determines whether or not quantitative analysis based on the second light quantity value is possible based on the second light quantity value at a predetermined first photometric point; if it determines that quantitative analysis based on the second light quantity value is not possible, acquires a first light quantity value from the absorptiometer for a second reaction solution of the specimen dispensed by the specimen dispensing mechanism and the first and second reagents dispensed by the reagent dispensing mechanism, and performs quantitative analysis based on the first light quantity value; An automated analyzer, wherein a liquid volume ratio between the first reagent and the second reagent in the first reaction liquid is different from a liquid volume ratio between the first reagent and the second reagent in the second reaction liquid.

2. In claim 1, When the data processing unit determines that quantitative analysis based on the second light quantity value is possible, the automatic analyzer performs quantitative analysis on the first reaction solution based on the second light quantity value.

3. In claim 2, the data processing unit holds a first calibration curve for quantitative analysis based on the first light quantity value and a second calibration curve for quantitative analysis based on the second light quantity value; the first calibration curve is a calibration curve created based on the first light quantity value acquired according to a measurement condition when it is determined that quantitative analysis based on the second light quantity value in the sample measurement program is not possible for standard solutions of different concentrations, The second calibration curve is a calibration curve created based on the second light intensity value obtained according to the measurement conditions when quantitative analysis based on the second light intensity value in the sample measurement program is determined to be possible for standard solutions of different concentrations.

4. In claim 1, the first reagent is a buffer solution, and the second reagent is a latex reagent; An automated analyzer, wherein the concentration of the latex reagent in the second reaction solution is higher than the concentration of the latex reagent in the first reaction solution.

5. In claim 1, a display unit that displays a parameter setting screen for setting measurement conditions in the sample measurement program; The parameter setting screen has a selection section for selecting whether or not to perform quantitative analysis based on the first light quantity value of the second reaction liquid.

Images