Automated analysis apparatus and specimen analysis method

Abstract

To overcome disadvantage in a conventional light scattering detection method that a high-concentration specimen outside a quantitative range requires retesting and a long measurement time.SOLUTION: A first light quantity value from an absorption photometer and a second light quantity value are obtained from a scattering photometer for a reaction solution of a specimen and a reagent, it is determined whether or not a quantitative analysis is possible based on the second light quantity value at a predetermined first photometry point, and the reagent is additionally dispensed into the reaction solution when it is determined that the quantitative analysis is not possible based on the second light intensity value and the quantitative analysis based on the first light intensity value of at the photometric point is performed after the additional dispensing.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to an automatic analyzer for clinical tests and a specimen analysis method.

Background Art

[0002] In an automatic analyzer for clinical tests, the concentration of a measurement target component contained in a biological sample such as blood or urine (hereinafter referred to as a specimen) is detected based on optical measurement. Specifically, first, the turbidity change that occurs when light is irradiated onto a reaction solution obtained by mixing a specimen and a reagent corresponding to a test item is measured. Next, among the measured turbidity changes, a measured value or a change amount of the measured value over a certain period of time is extracted, and the concentration of the measurement target component in the specimen is quantified by comparing it with a calibration curve prepared in advance for each test item. At this time, for a specimen outside the measurable and quantifiable range (hereinafter sometimes referred to as the "quantification range"), the specimen amount is changed and re-examination (hereinafter sometimes referred to as "re-examination" or "re-measurement") is performed. For example, when the specimen amount is below the quantification range, an increased amount re-examination with an increased specimen amount is performed, and when the specimen amount exceeds the quantification range, a decreased amount re-examination with a decreased specimen amount is performed.

[0003] As a method for measuring the measurement target component, many use the absorptiometry that measures the transmitted light amount of the reaction solution. In recent years, a method using a light scattering detection method that can measure with higher sensitivity than absorptiometry has been reported. These two detection methods have differences in characteristics. For example, there is a difference in the quantification range. Therefore, an automatic analyzer has been developed that utilizes the difference in the quantification range between these two photometers and mounts two types of photometers on one device to expand the dynamic range of measurement (Patent Document 1). The realization of a wide dynamic range leads to a reduction in the number of specimens deviating from the quantification range, and as a result, leads to a reduction in the re-examination rate with a changed specimen amount.

[0004] In addition, Patent Document 2 discloses a method for shortening the time required to obtain a quantification result, although it performs a reduction re-examination or an increase re-examination. In Patent Document 2, a device is disclosed that compares a measured value during the measurement of a reaction solution in which a sample and a reagent are mixed with a preset threshold value, and when the threshold value is exceeded, starts a re-examination in which the sample amount is changed without waiting for the result of the first measurement.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0006] The light scattering detection method is specialized for highly sensitive measurement and the quantification range is not wide. For this reason, a high-concentration sample that is outside the quantification range due to the high concentration of the component to be measured has conventionally been subjected to a reduction re-examination in which the sample amount is reduced. For this reason, it takes the time for two measurements, the first measurement and the re-examination, to obtain a quantification result. Also, although it is possible to expand the quantification range by using it in combination with the absorption photometry method, which is suitable for measuring high-concentration samples, since the concentration ranges of the reagents suitable for each detection method are different, reagents are required for each detection method.

[0007] In recent years, due to the high sensitivity of reagents and the like, the amount of sample used for one measurement has been reduced. In this case, if a reduction re-examination is performed on a sample that is originally small in amount by further reducing the sample amount, the influence of slight variations in dispensing accuracy on the test result also becomes large, and there is a risk of degrading the accuracy of the quantification result.

Means for Solving the Problems

[0008] An automatic analyzer according to an embodiment of the present invention includes a reaction disk on which cells for accommodating a reaction solution of a sample and a reagent are arranged on a circumference, a sample dispensing mechanism for dispensing a sample into the cells on the reaction disk, a reagent dispensing mechanism for dispensing a reagent into the cells on the reaction disk, an absorptiometer for measuring light transmitted through the reaction solution accommodated in the cells on the reaction disk irradiated from a first light source, a nephelometer for measuring light scattered by the reaction solution accommodated in the cells on the reaction disk irradiated from a second light source, 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 according to the sample measurement program. The data processing unit acquires a first light quantity value from the absorptiometer and a second light quantity value from the nephelometer for a reaction solution of a sample dispensed by the sample dispensing mechanism and a reagent dispensed by the reagent dispensing mechanism, determines whether quantitative analysis based on the second light quantity value is possible based on the second light quantity value at a predetermined first measurement point, and when it is determined that the quantitative analysis based on the second light quantity value is not possible, additionally dispenses a reagent into the reaction solution by the reagent dispensing mechanism and performs quantitative analysis based on the first light quantity value at the measurement point after the additional dispensing.

Advantages of the Invention

[0009] Even in the case of a high-concentration sample, the time until result acquisition can be shortened. Problems, configurations, and effects other than those described above will be clarified by the description of the following embodiments.

Brief Description of the Drawings

[0010]

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

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

[0013] Conventionally, in latex immunoturbidimetry, a specimen is mixed with a first reagent (buffer solution) and a second reagent (latex reagent solution) by adding each reagent once. The order of addition is, for example, specimen, 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 specimen. At this time, for example, if the specimen falls outside the upper limit of the quantification range, the amount of specimen added is reduced and retesting is performed. In Example 1, in items mainly using light scattering detection, if the specimen falls outside the upper limit of the quantification range, the concentration is quantified by a single measurement without retesting.

[0014] FIG. 1 shows an example of the flow of the analysis operation of Example 1. First, the measurement of the scattered light of the reaction solution in which the specimen, the buffer solution, and the latex test solution are each dispensed once is started (S101). The dispensing order of the specimen, the buffer solution, and the latex test solution that make up the reaction solution only needs to be such that the buffer solution is not dispensed last. For example, the order is the specimen, the buffer solution, and the latex test solution. The measured light quantity is compared with a preset threshold light quantity during the measurement, and a range-over determination is performed (S102). When it is determined that there is a range-over, a latex test solution is added to the reaction solution, the detector is switched from the scattered light photometer to the absorption photometer, and the measurement is continued (S106). After the measurement is completed (S107), the concentration quantified based on the measurement result of the absorption photometer is output (S108). On the other hand, in the range-over determination (S102), when it is determined that it is within the range, the measurement is continued without switching the detector and without adding anything to the reaction solution (S103). After the measurement is completed (S104), the concentration quantified based on the measurement result of the scattered light photometer is output (S105).

[0015] In the operation of step S106, it may be switched to measurement only with the absorption photometer, or the measurement with the scattered light photometer may also be continued in combination with the measurement with the absorption photometer. Also, at the time of starting the measurement (S101), not only the measurement with the scattered light photometer but also the measurement with the absorption photometer may be performed in parallel. In this case, in the operation of step S104, the result of the scattered light photometer may be preferentially output, and in the operation of step S108, the result of the absorption photometer may be preferentially output.

[0016] FIG. 2 is a schematic diagram comparing the reaction process and the required time until the result is obtained between the conventional method and Example 1. The horizontal axis of the reaction process represents the photometric point (elapsed time), and the vertical axis represents the light quantity. The reaction processes 201 and 203 are reaction processes in which the light quantity levels off after exceeding the measurement range during the measurement after the addition of the latex test solution because the concentration of the component to be measured is high. For this reason, in the conventional methods 1 and 2, re-tests with reduced sample amounts, shown as reaction processes 202 and 204 respectively, are performed.

[0017] In the conventional method 1, after the measurement of the first inspection (reaction process 201) is completed, a re-inspection (reaction process 202) with a reduced sample amount is started. In this case, for example, if the measurement time per time is 10 minutes, a total of 20 minutes is required to obtain the final quantitative result. In the conventional method 2, the concentration of the component to be measured is calculated from the light amount during the measurement after the addition of the latex test solution in the first inspection (reaction process 203), and when it exceeds a preset threshold value compared with the preset threshold value, a re-inspection (reaction process 204) is started. In this case, for example, if the measurement time per time is 10 minutes and the re-inspection is started at the 7th minute of the first inspection, a total of 17 minutes is required to obtain the final quantitative result. Compared with the conventional method 1, the time can be shortened by 3 minutes until the quantitative result is obtained.

[0018] On the other hand, in Example 1, as shown in FIG. 1, the light amount value during the measurement after the addition of the latex test solution is compared with a preset threshold light amount, and when it corresponds to a range over determination, a latex test solution is added to the reaction solution, the detector is switched from a scattered light photometer to an absorption photometer, and the measurement is continued to quantify the concentration. The reaction process 205 is an example of the reaction process of Example 1, and is an example of the reaction process when it is determined that there is a range over and the measurement is continued after switching the detector. The reaction process until the second addition of the latex test solution is the data (●) measured by the scattered light clock, and the reaction process after the second addition of the latex test solution is the data (▲) measured by the absorption photometer. By making the reagent concentration suitable for the absorption photometry method by adding the latex test solution for the second time and switching to the measurement with an absorption photometer having a wider quantitative range than the measurement with the scattered light photometer, it is possible to quantify the concentration in a single measurement time without re-inspection. Thus, in Example 1, the time until the acquisition of the quantitative result can be greatly shortened compared with the conventional method.

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

[0020] The automatic analyzer 100 generally comprises three types of disks, namely a specimen disk 103, a reagent disk 106, and a reaction disk 109, a specimen dispensing mechanism 110 and a reagent dispensing mechanism 111 for moving specimens and reagents between these disks, a drive unit 117 for driving the three types of disks and the dispensing mechanisms, a control circuit 118 for controlling the drive unit, an absorbance measurement circuit 119 for measuring the absorbance of the reaction solution, a scattered light measurement circuit 120 for measuring the scattered light from the reaction solution, a data processing unit 121 for processing the data measured by each measurement circuit, an operation unit 122 which is an interface with the data processing unit 121, a printer 123 for printing and outputting information, and a communication interface 124 for connecting to a network or the like.

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

[0022] The specimen dispensing mechanism 110 is a mechanism used when moving a fixed amount of the specimen 101 from the sample cup 102 arranged on the specimen disk 103, which rotates clockwise and counterclockwise, to the cell 108. The specimen dispensing mechanism 110 is composed of, for example, a nozzle for discharging or sucking the specimen 101, a robot for moving the nozzle to a predetermined position, and a pump for discharging the specimen 101 from the nozzle or sucking it into the nozzle. This robot and pump correspond to the drive unit 117.

[0023] The reagent dispensing mechanism 111 is a mechanism used when moving a fixed amount of reagent 104 from a reagent bottle 105 placed on a reagent disk 106 that rotates clockwise and counterclockwise to a cell 108. The reagent dispensing mechanism 111 is composed of, for example, a nozzle that discharges or aspirates the reagent 104, a robot that moves the nozzle to a predetermined position, and a pump that discharges the reagent 104 from the nozzle or aspirates it into the nozzle. This robot and pump correspond to the drive unit 117.

[0024] The cell 108 is immersed in a thermostatic fluid 112 in a thermostatic bath where the temperature and flow rate are controlled on a reaction disk 109. For this reason, the temperature of the cell 108 and the reaction solution 107 therein is maintained at a constant temperature even during movement accompanying the rotation of the reaction disk 109. In the case of this embodiment, water is used as the thermostatic fluid 112, and its temperature is adjusted to 37 ± 0.1 °C by a control circuit 118. Of course, the medium and temperature used as the thermostatic fluid 112 are just 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 mixed solution 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. This robot and motor correspond to the drive unit 117.

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

[0027] A part of the circumference of the reaction disk 109 is provided with an absorbance measurement unit 115 and a scattered light measurement unit 116.

[0028] The absorbance measurement unit 115 has a light source and a transmitted-light photoreceptor, and the light source and the transmitted-light photoreceptor are arranged so as to sandwich the cell 108 on the reaction disk 109. For example, the light source is a halogen lamp, the light emitted from the light source irradiates the cell 108, the light transmitted through the reaction solution 107 contained in the cell 108 is spectroscopically analyzed by a diffraction grating, and the light is 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. The light reception signals from these photoreceptors are transmitted to the storage unit 121a of the data processing unit 121 through the absorbance measurement circuit 119. Here, the absorbance measurement circuit 119 acquires the light reception signals in each wavelength range at regular intervals and outputs the acquired light quantity 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 photoreceptor, and a scattered light photoreceptor, and the light source, the transmitted light photoreceptor, and the scattered light photoreceptor are arranged so as to sandwich the cell 108 on the reaction disk 109. For example, the light source is an LED, the light emitted from the light source irradiates the cell 108, the light transmitted through the reaction solution 107 accommodated in the cell 108 is received by the transmitted light photoreceptor, and the light scattered by the reaction solution 107 is received by the scattered light photoreceptor. For the wavelength of the irradiation light, for example, 700 nm is used. In scattered light measurement, it is less susceptible to the influence of contaminants (cloudiness, hemolysis, jaundice) contained in the specimen, and it is preferable to use irradiation light with a wavelength of 600 nm to 800 nm, which is visible light. In addition to an LED, the light source may be a laser light source, a xenon lamp, a halogen lamp, or the like. For example, a photodiode is used as the photoreceptor. The light reception signals from the transmitted light and scattered light photoreceptors are transmitted through the scattered light measurement circuit 120 to the storage unit 121a of the data processing unit 121. The scattered light measurement circuit 120 also acquires the light reception signal at regular intervals and outputs the acquired light quantity value to the data processing unit 121. The scattered light photoreceptor is arranged, for example, in a plane that is substantially perpendicular to the moving direction of the cell 108 due to the rotation of the reaction disk 109. At this time, a line sensor may be used as the photoreceptor, and a configuration in which scattered light at a plurality of angles is received at once may be adopted. By using a line sensor, the options for the light reception angle can be expanded. Also, instead of directly arranging the photoreceptor, an optical system such as a fiber or a lens may be arranged to guide the light to the scattered light photoreceptor arranged at another position. The scattered light measurement unit 116 and the scattered light measurement circuit 120 are collectively referred to as a scattered light photometer.

[0030] The rotation amount of the reaction disk 109 that is rotationally driven in one cycle is set to a fixed amount. Since the absorption photometer and the scattered light photometer respectively perform measurements on the cell 108 passing through the absorbance measurement unit 115 and the scattered light measurement unit 116, the time interval between the photometric points at which the absorption photometer measures the reaction solution 107 in the cell 108 and the time interval between the photometric points at which the scattered light photometer 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 storage unit 121a and an analysis unit 121b. The storage unit 121a stores a control program, a measurement program, a data analysis program, calibration curve data, measurement data, analysis results, etc. The measurement program is, for example, a measurement program for calibration curve generation data or a specimen measurement program. The specimen measurement program includes a program that compares the light quantity during measurement as shown in FIG. 1 with a threshold light quantity and determines the next operation. 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 drives the control circuit, and the control circuit drives the driving unit, so that an analysis is performed on each mechanism. 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 storage 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 the specimen concentration using the calibration curve, a program for determining an error with respect to the calibration curve and the specimen measurement result, etc. The analysis results analyzed according to the data analysis program are returned to and held 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 printed out by the printer 123 if necessary. The data processing unit 121 is realized by a processor such as a CPU, for example.

[0032] The operation unit 122 includes a display unit 122a, a keyboard 122b as an input unit, and a mouse 122c. In addition to input by the keyboard 122b, input may be performed by touching the screen of the display unit 122a, or input may be performed by selecting what is 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 HIS (Hospital Information System) and a LIS (Laboratory Information System).

[0034] (Analysis operation) First, set the parameters required for the analysis. FIG. 4 shows an example of the application parameter setting screen of Example 1. First, from the analysis item setting screen 501, enter the item to be quantified, the sample volume, the analysis request method, whether to perform R3 addition during analysis, and the output unit. In this example, since the item mainly targeted is light scattering analysis, an example is shown where "light scattering analysis" is selected for the "analysis request method". For "performing R3 addition during analysis", by selecting whether to perform reagent R3 addition, it is possible to select measurement according to Example 1 or measurement according to the conventional method. Here, an example is shown where "performing R3 addition during analysis" is selected as "yes".

[0035] Next, enter the parameters required for measurement with a scattering photometer and an absorption photometer. The parameter screen 502 for measurement with a scattering photometer includes an analysis method, photometric points used for calculation, reagent dispensing volume, light receiving angle, quantification range, in addition to the photometric points for check implementation and the threshold light quantity. The photometric points for check implementation and the threshold light quantity may be treated as parameters that can be set by the user and are displayed on the application parameter setting screen as shown in FIG. 4, or may be stored in a measurement program or the like with a specified value for each item without being displayed on the setting screen. The parameter screen 503 for measurement with an absorption photometer includes an analysis method, photometric points used for calculation, wavelength, dispensing volume of R3, and quantification range.

[0036] Here, the reagents are expressed as R1, R2, and R3, and it is assumed that they are dispensed in ascending order of the numbers. R1 is a buffer solution, and the dispensing of R2 and R3 indicates latex test solutions. The numerical values of R1 and R2 in the measurement parameters of the absorption photometer 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 reagent dispensed during measurement is directly used as light scattering analysis (see the reaction process 205 shown in FIG. 2).

[0037] As analysis methods, for example, there are 1-point analysis method, 2-point rate analysis method, 2-point end analysis method, etc. Fig. 4 shows an example in which the 2-point end analysis method is selected. In the 2-point end analysis method, the amount of changing light between two photometric points is used for the quantification of concentration. The two photometric points are specified in the input field of the photometric points shown in Fig. 4. The numerical values in the quantification range are the concentration values of the component to be measured, indicating the lower limit value and the upper limit value of the quantification range.

[0038] Among the parameters in the measurement of the scattering photometer, the photometric point for check execution and the threshold light amount are the information used in the range over determination (S102) of Fig. 1. The photometric point for check execution and the threshold light amount may be set by the user, automatically calculated in the device using the measurement values of the standard solution, or provided by the reagent manufacturer. Also, the measurement value (light amount) of the standard solution with the highest concentration in the scattered light measurement may be used as the threshold light amount as it is. In the case of user setting, it is advisable to provide an input field on the setting screen of the application parameters. In other cases, it is not necessarily required to display the input field on the setting screen of the application parameters. The photometric point for check execution should be equal to or greater than the point after R2 dispensing and equal to or less than the point before R3 dispensing.

[0039] Here, Fig. 5 shows an example of the relationship between the photometric point and the light amount when up to R3 dispensing is carried out. Fig. 5 is an example in which R2 is dispensed between photometric points 5 and 6, and R3 is dispensed between photometric points 16 and 17. The light amount up to R3 dispensing is the scattered light intensity (●) measured by the scattered light clock, and the light amount after R3 dispensing means the absorbance (▲) measured by the absorption photometer. In the case of the example in Fig. 5, the "photometric point for check execution" will be set between photometric points 6 to 16.

[0040] After setting the parameters necessary for the 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 amount of light. In the case of this embodiment, two calibration curves are prepared. One is the calibration curve when the reaction solution obtained by mixing the specimen, R1, and R2 is measured with a nephelometer, and it is used when the measurement is completed by the light scattering detection method (step S105 in FIG. 1). This calibration curve is referred to as the calibration curve for nephelometric measurement, and an example is shown in FIG. 6. The other is the calibration curve when the reaction solution obtained by mixing the specimen, R1, R2, and R3 is measured with an absorptiometer, and it is used when the measurement is completed after switching from the light scattering detection method to the absorptiometric method (step S108 in FIG. 1). This calibration curve is referred to as the calibration curve for absorptiometric measurement, and an example is shown in FIG. 7.

[0041] The horizontal axes in FIGS. 6 and 7 represent the concentration of the component to be measured, and the vertical axes represent the amount of light calculated according to the analysis method and photometric points set for each application parameter. For example, when following the application parameters in FIG. 4, since the analysis method of the nephelometer is the two-point endpoint analysis method and the photometric points are 7 and 22, the amount of light change (change in scattered light intensity) at photometric points 7 and 22 is obtained in the measurement with the nephelometer. Since the analysis method of the absorptiometer is the two-point endpoint analysis method and the photometric points are 19 and 34, the amount of light change (change in absorbance) at photometric points 19 and 34 is obtained in the measurement with the absorptiometer. In the calibration curve for nephelometric measurement (FIG. 6), for example, the calibration curve in the range where the concentration is 500 ng / mL or less is defined as the effective range, and in the calibration curve for absorptiometric measurement (FIG. 7), for example, the calibration curve in the range where the concentration is 400 to 1000 ng / mL is defined as the effective range. Although there is a concentration region where the effective ranges overlap (in this example, the range from 400 to 500 ng / mL), which calibration curve to use shall follow the flowchart in FIG. 1, and the calibration curve derived from the used photometer shall be used.

[0042] After calibration, a sample with an unknown concentration is measured. The operation flow during measurement is as shown in FIG. 1. Specifically, for example, a sample with an unknown concentration, a buffer solution (R1), and a latex test solution (R2) are dispensed into cell 108 to start scattered light measurement (S101). The dispensing amounts of the sample, R1, and R2 at this time are the amounts set as parameters of the scattered light photometer among the application parameters. When the light amount at the "measurement point for check execution" is acquired, the light amount at the "measurement point for check execution" is compared with the "threshold light amount" during measurement to perform a range-over determination (S102). The measurement point for check execution and the threshold light amount are stored in a measurement program or the like as specified values or values set from the setting screen of the application parameters. If it is determined that it is within the range, the scattered light measurement is continued (S103). After the measurement is completed (S104), from the acquired reaction process, the light amount is calculated according to the "analysis method" and "measurement point" set as parameters of the scattered light photometer among the application parameters. This light amount is compared with the light amount of the calibration curve for scattered light measurement to quantify and output the concentration (S105). For example, when following the application parameters of the scattered light photometer in FIG. 4, since the analysis method is the two-point endpoint analysis method and the measurement points are 7 and 22, the change amount of the scattered light between these measurement points is calculated and compared with the change amount of the scattered light of the calibration curve for scattered light measurement (FIG. 6) to quantify the concentration.

[0043] On the other hand, if it is determined that there is a range-over in the range-over determination (S102), a latex test solution is added (R3 dispensing), the detector is switched from the scattered light photometer to the absorption photometer, and the measurement is continued (S106). The dispensing amount of R3 at this time is the amount set as a parameter of the absorption photometer among the application parameters. After the measurement is completed (S107), from the acquired reaction process, the light amount is calculated according to the "analysis method" and "measurement point" set as parameters of the absorption photometer among the application parameters. This light amount is compared with the light amount of the calibration curve for absorption measurement (FIG. 7) to quantify and output the concentration (S108).

[0044] In Example 1, an example of performing a range-over determination by comparing the light amount during measurement with a preset threshold light amount was shown, but it may be other than the determination using the light amount. For example, the light amount after a certain period of time may be estimated from the light amount at an arbitrary photometric point, and the estimated light amount may be compared with a separately set threshold light amount. Further, the analyte concentration may be estimated from the light amount at an arbitrary photometric point or the estimated light amount after a certain period of time, and compared with a separately set threshold concentration. Also, 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 perform a range-over determination.

Example

[0045] In Example 2, regarding the items measured by the light scattering detection method, the measured light amount value is compared with a preset threshold light amount during measurement. When it corresponds to a range-over determination, the liquid volume ratio of the reagent is changed so that the reagent concentration suitable for the absorptiometry is obtained, and re-measurement is started by absorptiometry before the measurement of the first test is completed.

[0046] Fig. 8 shows an example of the flow of the analysis operation of Example 2. First, the measurement of the scattered light of the reaction solution obtained by dispensing the sample, the buffer solution, and the latex test solution one by one is started (S301). The dispensing order of the sample, the buffer solution, and the latex test solution constituting the reaction solution only needs to be such that the buffer solution is not dispensed last. For example, the order is sample, buffer solution, and latex test solution. The measured light amount is compared with a preset threshold light amount during measurement, and a range-over determination is performed (S302). When it is determined that it is out of range, the liquid volume ratio of the buffer solution and the latex test solution is changed, and absorbance measurement is started at a reagent concentration suitable for absorptiometry before the measurement of the first test is completed (S306). After the measurement is completed (S307), the concentration quantified based on the measurement result of the absorptiometer is output (S308). On the other hand, in the range-over determination (S302), when it is determined that it is within the range, the measurement by the scattered light photometer is continued (S303). After the measurement is completed (S304), the concentration quantified based on the measurement result of the scattered light photometer is output (S305).

[0047] At the time of measurement start (S301), there are two possible cases for the dispensing timings of the buffer solution and the latex test solution: when the buffer solution is dispensed at the timing of R1 and the latex test solution is dispensed at the timing of R2 among the dispensing timings of R1, R2, and R3 described in Example 1, and when the buffer solution is dispensed at the timing of R1 and the latex test solution is dispensed at the timing of R3.

[0048] Figure 9 is a schematic diagram of the reaction process and the required time until the results of Example 2 are obtained. The horizontal axis of the reaction process represents the photometric point (elapsed time), and the vertical axis represents the light quantity. The reaction process 401 is the reaction process of scattered light measurement in which the light quantity levels off beyond the measurement range during the measurement after the addition of the latex test solution because the concentration of the component to be measured is high. The reaction process 402 shows an example in which the sample amount is the same as that in the initial test, the liquid volume ratio of the buffer solution and the latex test solution is changed from the initial test, and absorbance measurement is performed at a reagent concentration suitable for the absorbance photometry method. In this case, for example, if the measurement time per time is 10 minutes and the re-test is started at the 7th minute of the initial test, a total of 17 minutes are required to obtain the final quantitative result. The time required to obtain the quantitative result is the same as that of the conventional method 2 of Example 1 (see Figure 2). However, in the case of the method of Example 2, since the reagent concentration is changed and a detector corresponding to the quantitative range is used, there is a high possibility that the quantitative range can be expanded compared to the re-test by only changing the sample amount.

[0049] Since the configuration of the automatic analyzer for realizing Example 2 is the same as that of Example 1 (Figure 3), the description is avoided here to prevent duplication.

[0050] (Analysis operation) First, set the parameters required for the analysis. FIG. 10 shows an example of the setting screen for the application parameters of Example 2. First, from the analysis item setting screen 601, input the item to be quantified, the analysis request method, whether the photometer can be changed during re-examination, whether re-examination is to be performed during measurement, and the output unit. In this example, since the items mainly for light scattering analysis are targeted, an example is shown where "light scattering analysis" is selected for the "analysis request method". By selecting whether "the photometer can be changed during re-examination" and whether "re-examination is to be performed during measurement", it is possible to select whether to perform the measurement according to Example 2 or the conventional method. In FIG. 10, an example (selecting the measurement according to Example 2) is shown where "the photometer can be changed during re-examination" is selected as "yes" and "re-examination is to be performed during measurement" is selected as "yes".

[0051] Next, input the parameters required for measurement with the scattering photometer and the absorption photometer. The parameter screen 602 for measurement with the scattering photometer includes, in addition to the analysis method, the photometric points used for calculation, the sample volume, the reagent dispensing volume, the light receiving angle, the quantification range, the photometric points for check implementation, and the threshold light quantity. The photometric points for check implementation and the threshold light quantity may be treated as parameters that can be set by the user and are displayed on the application parameter setting screen as shown in FIG. 10, or may be stored in the measurement program, etc. for each item with specified values without being displayed on the setting screen. The parameter screen 603 for measurement with the absorption photometer includes the analysis method, the photometric points used for calculation, the wavelength, the sample volume, the reagent dispensing volume, and the quantification range.

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

[0053] The numerical values of R1 and R2 or R3 in the measurement parameters of the absorptiometer are different from those of the nephelometer. The suitable concentration of the latex test solution in the reaction solution is different between the absorptiometer and the nephelometer, and a higher concentration is desirable for the absorptiometer. For this reason, the amount of R1 (buffer solution) in the measurement parameters of the absorptiometer is desirably made smaller than that of R1 in the measurement parameters of the nephelometer, and the amount of R2 or R3 (latex test solution) in the measurement parameters of the absorptiometer is desirably made larger than that of R2 or R3 in the measurement parameters of the nephelometer. Also, at this time, it is desirable to set the total amount of R1 and R2 or R3 to be equal between the photometers, but even if the total amounts are different between the photometers, it is not a problem because calibration is performed for each photometer. The amount of the test sample may be the same or different for each photometer. Even when the amounts of the test samples are different, it is not a problem because calibration according to the measurement conditions is performed for each photometer.

[0054] Since the explanations of the analysis method, photometric points, and quantitative range are the same as those in Example 1, duplication of the explanations is avoided here.

[0055] Among the parameters in the measurement by the nephelometer, the photometric point for check implementation and the threshold light amount are the information used in the range-over determination (S302) in FIG. 8. The photometric point for check implementation and the threshold light amount may be set by the user, may be automatically calculated in the apparatus using the measured values of the standard solution, or may be provided by the reagent manufacturer. Also, the measured value (light amount) of the standard solution with the highest concentration in the nephelometric measurement may be used as the threshold light amount as it is. In the case of user setting, it is advisable to provide an input field on the setting screen for the application parameters. In other cases, it is not always necessary to display the input field on the setting screen for the application parameters. The photometric point for check implementation is at or above the point after the dispensing of R2 or R3.

[0056] Here, an example of the relationship between the photometric points and the light quantity (scattered light intensity) when dispensing R1 and R3 in scattered light measurement is shown in FIG. 11. FIG. 11 is an example where R3 is dispensed between photometric points 16 and 17. In this case, the "measurement execution photometric point" is set to a value that is 17 or more and less than or equal to the measurement end photometric point (34 in FIG. 11). In the case of this example, the closer the measurement execution photometric point is to 17, the earlier the range over determination can be performed, and the earlier the re-check start timing becomes.

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

[0058] After calibration, a sample with an unknown concentration is measured. The operation flow during measurement is as shown in FIG. 8. Specifically, for example, a sample with an unknown concentration, a buffer solution (R1), and a latex solution (R3) are dispensed into cell 108 to start scattered light measurement (S301). The dispensed amounts of the sample, R1, and R3 at this time are the amounts set as parameters of the scattered light photometer among the application parameters. When the light amount at the "measurement point for check execution" is acquired, the light amount at the "measurement point for check execution" is compared with the "threshold light amount" during measurement to perform a range-over determination (S302). The "measurement point for check execution" and the "threshold light amount" are stored in a measurement program or the like as specified values or values set from the setting screen of the application parameters. If it is determined that the value is within the range, the scattered light measurement is continued (S303). After the measurement is completed (S304), from the acquired reaction process, the light amount is calculated according to the "analysis method" and "measurement point" set as parameters of the scattered light photometer among the application parameters. This light amount is compared with the light amount of the calibration curve for scattered light measurement to quantify and output the concentration (S305). For example, when following the application parameters of the scattered light photometer in FIG. 10, since the analysis method is the two-point endpoint analysis method and the measurement points are 20 and 32, the change amount of the scattered light between these measurement points is calculated, and the concentration is quantified by comparing it with the change amount of the scattered light of the calibration curve for scattered light measurement.

[0059] On the other hand, if it is determined that there is a range-over in the range-over determination (S302), a new sample with an unknown concentration, a buffer solution (R1), and a latex solution (R3) are newly dispensed into a new cell 108 to start re-measurement with an absorption photometer (S306). The dispensed amounts of the sample, R1, and R3 at this time are the amounts set as parameters of the absorption photometer among the application parameters. This measurement is started before the scattered light measurement is completed. After the measurement is completed (S307), from the acquired reaction process, the light amount is calculated according to the "analysis method" and "measurement point" set as parameters of the absorption photometer among the application parameters. This light amount is compared with the light amount of the calibration curve for absorption measurement to quantify and output the concentration (S308).

[0060] In this embodiment, it is characterized in that absorbance measurement is started at a reagent concentration suitable for the absorbance photometry method before the initial inspection is completed. In addition to shortening the time until a quantitative result is obtained, expanding the quantitative range by using a detector according to the quantitative range is effective.

[0061] In Example 2, an example was shown in which a range-over determination was performed by comparing the light quantity during measurement with a preset threshold light quantity. However, other than the determination using the light quantity may be used. For example, the light quantity after a certain period of time may be estimated from the light quantity at an arbitrary photometric point, and the estimated light quantity may be compared with a separately set threshold light quantity. Further, the analyte concentration may be estimated from the light quantity at an arbitrary photometric point or the estimated light quantity after a certain period of time, and compared with a separately set threshold concentration. Further, 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 perform a range-over determination.

[0062] The present invention is not limited to the above-described Examples 1 and 2, and includes various modifications. In this embodiment, taking the latex immunoturbidimetry item as an example, a latex test solution in which an antibody or an antigen is sensitized is mixed with a standard solution or a sample containing a measurement target component (antigen or antibody), and the latex aggregation reaction caused by the antigen-antibody reaction is measured by a nephelometer or an absorbance photometer. However, the present invention is not limited to the latex immunoturbidimetry item. For example, a system in which an insoluble carrier (such as silica particles, magnetic particles, metal colloids, etc.) in which an antibody or an antigen is sensitized is mixed with a standard solution or a sample containing a measurement target component (antigen or antibody), and the aggregation reaction of the particles caused by the antigen-antibody reaction is measured with a nephelometer or an absorbance photometer may be used. Further, the measurement target component to be quantified may be an activity value instead of a concentration.

[0063] The above-described embodiments have been described in detail for easy understanding of the present invention, and are not necessarily limited to those having all the configurations described. It is possible to replace a 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. Further, for a part of the configuration of each embodiment, it is possible to add, delete, or replace the same configuration or another configuration.

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 solution, 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 measurement unit, 116: Scattered light measurement unit, 117: Driving unit, 118: Control circuit, 119: Absorbance measurement circuit, 120: Scattered light measurement circuit, 121: Data processing unit, 121a: Storage 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 in which cells for accommodating a reaction solution of a specimen and a reagent are arranged on a circumference, a specimen dispensing mechanism for dispensing a specimen into the cells on the reaction disk, a reagent dispensing mechanism for dispensing a reagent into the cells on the reaction disk, an absorptiometer that measures light irradiated from a first light source and transmitted through the reaction solution accommodated in the cells on the reaction disk, a nephelometer that measures light irradiated from a second light source and scattered by the reaction solution accommodated in the cells on the reaction disk, a control circuit for driving the reaction disk, the specimen dispensing mechanism, and the reagent dispensing mechanism, a data processing unit that executes a specimen measurement program and controls the control circuit according to the specimen measurement program, and has, The data processing unit acquires a first light quantity value from the absorptiometer and a second light quantity value from the nephelometer for a reaction solution of a specimen dispensed by the specimen dispensing mechanism and a reagent dispensed by the reagent dispensing mechanism, and based on the second light quantity value at a predetermined first photometric point, determines whether quantitative analysis based on the second light quantity value is possible. When it is determined that quantitative analysis based on the second light quantity value is not possible, the reagent is additionally dispensed into the reaction solution by the reagent dispensing mechanism, and quantitative analysis is performed based on the first light quantity value at the photometric point after the additional dispensing. An automatic analyzer.

2. In Claim 1, When the data processing unit determines that quantitative analysis based on the second light quantity value is possible, an automatic analyzer that performs quantitative analysis based on the second light quantity value at photometric points before and after the first photometric point.

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 obtained according to the measurement conditions when it is determined that quantitative analysis based on the second light quantity value in the specimen measurement program is not possible for standard solutions with different concentrations, The second calibration curve is a calibration curve created based on the second light quantity value obtained according to the measurement conditions when it is determined that quantitative analysis based on the second light quantity value in the specimen measurement program is possible for standard solutions with different concentrations. An automatic analyzer.

4. In Claim 1, The data processing unit is an automatic analyzer that determines whether to perform quantitative analysis based on the second light quantity value when the second light quantity value at the first photometry point exceeds a preset threshold light quantity.

5. In claim 4, the data processing unit sets the threshold light quantity based on the second light quantity value obtained according to the measurement conditions when it is determined that quantitative analysis based on the second light quantity value in the specimen measurement program for the standard solution is possible. An automatic analyzer.

6. In claim 1, in the absorptiometer, the first light source and the transmitted light receiver are arranged so as to sandwich a cell on the reaction disk, in the nephelometer, the second light source and the scattered light receiver are arranged so as to sandwich a cell on the reaction disk, The time interval between photometry points at which the absorptiometer measures the light transmitted through the reaction solution, or the time interval between photometry points at which the nephelometer measures the light scattered by the reaction solution, is the time for one rotation of the reaction disk that is rotationally driven. An automatic analyzer.

7. In claim 1, it has a display unit that displays a parameter setting screen for setting measurement conditions in the specimen measurement program, the parameter setting screen has a selection unit for selecting whether to perform additional dispensing of the reagent into the reaction solution. An automatic analyzer.

8. A reaction disk in which cells for accommodating a reaction solution of a specimen and a reagent are arranged on the circumference, a specimen dispensing mechanism for dispensing a specimen into a cell on the reaction disk, a reagent dispensing mechanism for dispensing a reagent into a cell on the reaction disk, an absorptiometer that measures light irradiated from a first light source and transmitted through the reaction solution accommodated in the cell on the reaction disk, a nephelometer that measures light irradiated from a second light source and scattered by the reaction solution accommodated in the cell on the reaction disk, a control circuit that drives the reaction disk, the specimen dispensing mechanism, and the reagent dispensing mechanism, and a data processing unit that executes a specimen measurement program and controls the control circuit according to the specimen measurement program. A specimen analysis method using an automatic analyzer, the specimen dispensing mechanism dispenses a specimen into a cell on the reaction disk, the reagent dispensing mechanism dispenses a reagent into the cell, the data processing unit acquires at least a second light quantity value from the nephelometer for the reaction solution of the specimen and the reagent, The data processing unit determines the feasibility of quantitative analysis based on the second light quantity value at a predetermined first photometric point, when the data processing unit determines that the quantitative analysis based on the second light quantity value is not feasible, the reagent dispensing mechanism additionally dispenses the reagent into the cell, and the data processing unit acquires at least the first light quantity value from the absorptiometer for the reaction solution to which the reagent has been added, and performs quantitative analysis based on the first light quantity value at the photometric point after the additional dispensing. A specimen analysis method.

9. In claim 8, when the data processing unit determines that the quantitative analysis based on the second light quantity value is feasible, the data processing unit performs quantitative analysis based on the second light quantity value at the photometric points before and after the first photometric point. A specimen analysis method.

10. In claim 8, 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 obtained according to the measurement conditions when it is determined that the quantitative analysis based on the second light quantity value in the specimen measurement program is not feasible for standard solutions with different concentrations, and the second calibration curve is a calibration curve created based on the second light quantity value obtained according to the measurement conditions when it is determined that the quantitative analysis based on the second light quantity value in the specimen measurement program is feasible for standard solutions with different concentrations. A specimen analysis method.

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