Calibration curve generation method, automatic analysis device, calibration curve generation program

Abstract

This application relates to a method for generating calibration curves. The object of this invention is to ensure the accuracy of calibration curves and reduce the cumbersome process of generating calibration curves in analytical procedures using two or more standard solutions (two concentrations). In the calibration curve generation method of this invention, a mixed reaction solution containing one standard solution of the analyte at a concentration other than zero and a reagent reacting with the analyte is irradiated with light. The turbidity change of the mixed reaction solution over time is measured, thereby obtaining reaction process data. Multiple light intensity data at multiple different times are extracted from a fitted line obtained by supplementing the discrete portions of the reaction process data. These multiple different times are converted into multiple concentrations of the analyte, thereby generating the calibration curve (Figure 1) representing the relationship between the multiple light intensity data and the multiple concentrations.

Description

Technical Field

[0001] This invention relates to a technique for generating calibration curves used to quantify the concentration of a substance being measured contained in a sample. Background Technology

[0002] An automated analytical device is used to quantify proteins, hormones, viruses, and other substances contained in biological samples such as blood and urine. In this device, the reagent corresponding to the test item is mixed with the sample. The device captures the turbidity change (changes in transmitted and scattered light) of the reaction solution when the mixture is irradiated with light. The absorbance, scattered light intensity, or their changes over a certain period are compared with a pre-prepared calibration curve for each test item to quantify the concentration of the analyte in the sample.

[0003] In automated analytical devices, calibration curves represent the relationship between the concentration or activity of the analyte and absorbance, scattered light intensity, or their variations, generated through a correction (calibration) process. Calibration is necessary to eliminate inter-device and batch-to-batch variations in reagents, especially when new devices or reagents are introduced, or when reagent batches are changed.

[0004] The samples used to generate calibration curves are standard solutions containing known concentrations of the analyte. The number of standard solutions varies depending on the test item and reagent manufacturer; some test items use multiple standard solutions containing the analyte at known concentrations. In calibration, these standard solutions are first mixed with the reagent corresponding to the test item, and the turbidity change (changes in transmitted and scattered light) of the reaction solution after irradiation with light is recorded as reaction process data. Next, absorbance, scattered light intensity, or their changes over a certain time period are extracted from the reaction process data of each standard solution. The extracted data are plotted against the concentration of the analyte in each standard solution to obtain the relationship between the concentration of the analyte and the extracted data, thus generating the calibration curve. The number of times each standard solution is measured (the number of times reaction process data is obtained) during calibration curve generation varies depending on the apparatus. In apparatuses that obtain multiple reaction process data for each standard solution, the average or median value of the extracted data over a certain time period is used.

[0005] Thus, to obtain a calibration curve, multiple standard solutions need to be prepared and data for calibration curve generation needs to be acquired. These tasks are generally performed before the measurement of samples with unknown concentrations of the analyte begins. Therefore, when there are multiple calibration items, time is required from the start of the measurement of samples with unknown concentrations of the analyte. Therefore, to alleviate the burden of generating calibration curves, techniques have been developed to simplify calibration curve generation and reduce the number of generation steps.

[0006] Patent Document 1 discloses a method for automatically diluting a standard solution of one concentration to generate a calibration curve with multiple concentrations. Patent Document 2 discloses an apparatus that controls the analytical conditions in the same way each time and quantifies the concentration of the substance to be measured based on pre-stored calibration curve data.

[0007] Existing technical documents

[0008] Patent documents

[0009] Patent Document 1: Japanese Patent Application Publication No. 2001-249137

[0010] Patent Document 2: Japanese Patent Application Publication No. 2008-175722 Summary of the Invention

[0011] The problem that the invention aims to solve

[0012] The number of standard solutions used to generate a calibration curve depends on the test item, but in most cases it is six or more (six concentrations). The number of times each standard solution is measured during a single calibration curve generation varies depending on the apparatus, reagents, and test item; some apparatuses generate calibration curves based on data from multiple measurements. For test items with a large number of standard solutions and numerous measurements of each standard solution during calibration curve generation, the amount of reagents consumed to generate the calibration curve increases. Furthermore, when there are multiple test items requiring calibration, multiple different standard solutions are prepared for each test item, making the process complex. Consequently, time is required to generate calibration curves for all items, and the waiting time before starting measurements on samples with unknown concentrations of the analyte becomes longer.

[0013] In Patent Document 1, multiple standard solutions are prepared by diluting one standard solution, so in reality only one standard solution is used. In Patent Document 2, the same calibration curve is repeatedly used with identical analytical conditions each time, making it difficult to reduce the number of standard solutions used to prepare a single calibration curve. Therefore, in existing methods for simplifying calibration curve generation as described in Patent Documents 1 and 2, it is considered difficult to fully reflect the data obtained from multiple standard solutions on the calibration curve, and it is also difficult to reduce the cumbersome process of preparing the calibration curve.

[0014] The present invention was made in view of the above-mentioned problems, and its purpose is to ensure the accuracy of the calibration curve and reduce the cumbersome process of generating the calibration curve in analytical procedures that use two or more standard solutions (two concentrations) to generate the calibration curve.

[0015] Methods for solving problems

[0016] In the calibration curve generation method of the present invention, a mixed reaction solution containing a standard solution of a substance to be measured at a concentration other than zero and a reagent that reacts with the substance to be measured is irradiated with light, and the turbidity change of the mixed reaction solution over time is measured to obtain reaction process data. Multiple light intensity data at multiple different times are extracted from a fitted line obtained by supplementing the discrete part of the reaction process data, and the multiple different times are converted into multiple concentrations of the substance to be measured, thereby generating the calibration curve representing the relationship between the multiple light intensity data and the multiple concentrations.

[0017] That is, in existing methods, multiple sets of standard solutions with known concentrations are measured to obtain reaction process data for each standard solution, and the light intensity data extracted from these reaction process data is used to generate a calibration curve. However, in this invention, the characteristic is that multiple light intensity data equivalent to multi-point calibration data can be extracted from the fitted line of the reaction process data of a single standard solution with any concentration other than zero to generate a calibration curve.

[0018] Invention Effects

[0019] According to the calibration curve generation method of the present invention, in inspection items requiring calibration, a calibration curve equivalent to multi-point calibration is derived from the reaction process data obtained by measuring one standard solution. Therefore, compared with existing methods that generate calibration curves by measuring multiple standard solutions of known concentrations, the consumption of reagents can be suppressed. Furthermore, compared with existing methods, the number of standard solutions prepared can be reduced, thus eliminating the tediousness of preparation. Other issues, structures, and effects will become clear from the following description of embodiments. Attached Figure Description

[0020] [ Figure 1 [ ] is a flowchart illustrating the calibration curve generation steps in Implementation Method 1.

[0021] [ Figure 2 [Illustration of the overall structure of the automatic analysis device 100 in Embodiment 1]

[0022] [ Figure 3 This represents an example of a settings screen used to set calibration information.

[0023] [ Figure 4 [This represents an example of reaction process data obtained through absorbance measurement.]

[0024] [ Figure 5 This is an example of reaction process data obtained by measuring the absorbance of six standard solutions with known concentrations C'1 to C'6.

[0025] [ Figure 6 This section shows an example of a calibration curve when the data in Table 1 is plotted and approximated using a polyline.

[0026] [ Figure 7 This section shows an example of the reaction process data and fitted line after data processing of standard solution 6.

[0027] [ Figure 8 [] indicates the fitted line after data processing of standard solution 6 and the photometric point corresponding to the absorbance change data used to generate the calibration curve.

[0028] [ Figure 9 This section represents an example of reaction process data and fitted lines after data processing of standard solution N.

[0029] [ Figure 10 The figure represents the fitted line after data processing of standard solution N and the absorbance change corresponding to the measurement points: P1~PN: ΔA1~ΔAN (output information).

[0030] [ Figure 11 [] represents an example of a calibration curve generated in Implementation 1 when the calibration curve type is a polyline.

[0031] [ Figure 12 This indicates an example of inputting the calculated metering point into the metering point field in the calibration settings screen.

[0032] [ Figure 13 The line represents the fitted line of the reaction process data after processing the data representing the reaction between reagent (batch C) and standard solution 6 (batch D).

[0033] [ Figure 14 The line represents the fitted curve after data processing for standard solution 6 (batch D) and is equivalent to... Figure 12 The change in absorbance at the measurement point shown (output information).

[0034] [ Figure 15 The symbol ] represents the generated calibration curve.

[0035] [ Figure 16 ] indicates the calibration curve generated by the method of Implementation 1. Figure 15 Examples of calibration curves that coincide with those generated by existing methods.

[0036] [ Figure 17 This indicates an example of inputting the calculated metering point into the metering point field in the calibration settings screen.

[0037] [ Figure 18 The line represents the fitted data of the reaction process data representing the reaction between reagent (batch G) and standard solution 3 (batch H).

[0038] [ Figure 19 The line represents the fitted curve after data processing for standard solution 3 (batch H), equivalent to... Figure 17 The change in the intensity of scattered light at the measurement point shown (output information).

[0039] [ Figure 20 The symbol ] represents the generated calibration curve.

[0040] [ Figure 21 ] indicates the calibration curve generated by the method of Implementation 1. Figure 20 Examples of calibration curves that coincide with those generated by existing methods.

[0041] [ Figure 22 [This represents an example of a calibration information setting screen in Implementation Method 2.]

[0042] [ Figure 23 The figure represents the fitted line after data processing of standard solution N and the absorbance change corresponding to the measurement points: P2~PN: ΔA2~ΔAN (output information).

[0043] [ Figure 24 [] indicates the reaction process data obtained by measuring the reaction process of standard solution 1 with zero concentration of the analyte.

[0044] [ Figure 25 [] represents an example of the calibration curve generated in Implementation Method 2. Detailed Implementation

[0045] <Implementation Method 1>

[0046] The inventors of this application have discovered that in latex immunoturbidimetry, a test requiring calibration, the reaction process data obtained by measuring a standard solution of a concentration (CN) other than zero for the analyte reflects the reaction of a standard solution with a lower concentration. Specifically, the following insight is gained: in the reaction process data obtained by measuring a standard solution of concentration CN, the measured or calculated value at second X after the start of the reaction is equivalent to the measured or calculated value at second Y (Y≥X) of a standard solution of concentration CM (CM≤CN). Based on this insight, the inventors of this application believe that by using only the reaction process data obtained by measuring a single standard solution of a concentration other than zero for the analyte, extracting multiple data points (measured or calculated values) at different reaction times from this reaction process data, and plotting them in relation to multiple concentrations of the analyte, and approximating these plots using arbitrary mathematical formulas, a calibration curve equivalent to the calibration curve generated by existing methods using reaction process data obtained from measuring multiple concentrations of standard solutions can be generated.

[0047] In Embodiment 1 of the present invention, the following situation is described: for inspection items where the number of standard solutions is N (N≥2) or more, a calibration curve is generated based on the reaction process data obtained by measuring only the standard solution N with the highest concentration of the analyte corresponding to the item.

[0048] Figure 1This is a flowchart illustrating the calibration curve generation steps in Embodiment 1. A new calibration curve is generated when a new device or reagent is introduced, or when the reagent batch is changed. Using standard solution N, which has the highest concentration of the analyte among the standard solutions used in this test item, reaction process data is measured. After data processing of the obtained reaction process data based on the calculation point of this item, a fitted line is derived. In the "Measuring Point-Concentration Conversion Data," which represents the relationship between the concentration of the analyte in standard solutions 1 to N (separately set independently of the measurement of standard solution N) and reaction time (measuring point), the measuring point information is first applied to the fitted line, thereby determining the point corresponding to the calibration data of standard solutions 1 to N based on the fitted line. At this moment, multiple light quantity data (absorbance, scattered light intensity, or their changes) corresponding to multiple measuring points are obtained. Next, the multiple measuring point information is converted into the concentration information of the analyte according to the aforementioned "Measuring Point-Concentration Conversion Data," thereby generating a calibration curve representing the relationship between the light quantity data and the concentration of the analyte. The aforementioned "measuring point-concentration conversion data" establishes a correspondence between the measuring point information and the concentration information of the analyte corresponding to the standard solution group. This measuring point information is required to extract the photometric data corresponding to the calibration data of the standard solution group (1-N) from the reaction process data of standard solution N. Here, when standard solutions 1-N are treated as a group, they are labeled as a standard solution group, and "determination of the standard solution group" refers to "determination of standard solutions 1-N". The details of the above steps will be described later.

[0049] Currently, range calibration exists as a calibration method that uses measurement data from a standard solution of any known concentration other than zero concentration. Range calibration involves updating only the K-value (K-factor) corresponding to the slope in the existing calibration curve using data from a standard solution of any known concentration other than zero concentration. However, range calibration has the problem that it cannot be applied to updating calibration curve information for nonlinear systems (e.g., spline functions) generated in multi-point calibrations with multiple calibration factors. In this embodiment 1, data for generating calibration curves equivalent to multi-point calibration is extracted from the reaction process data of a standard solution of any known concentration other than zero concentration, and the relationship between the aforementioned data and concentration is obtained to generate a calibration curve. Therefore, it is also possible to address calibration curves for spline functions, which are a problem with range calibration.

[0050] The reaction process data in Embodiment 1 are measured, for example, using an automated analytical apparatus. "Metering point-concentration conversion data," which represents the relationship between the concentration of the analyte and the reaction time (measuring point), can be provided, for example, by the manufacturer of the reagents and standard solutions. If the automated analytical apparatus contains calibration curve data generated by existing methods and reaction process data of the most concentrated standard solution used in generating the calibration curve, this data can also be used for calculations within the apparatus. Alternatively, information stored in an external storage medium can be read and used. When provided by the manufacturer, it is envisioned that the data be provided in combination of reagent batches and standard solution batches, or in individual reagent batches, or in individual standard solution batches.

[0051] <Implementation Method 1: Structure of the Automatic Analysis Device>

[0052] Figure 2 This is a schematic diagram illustrating the overall structure of the automatic analysis device 100 according to Embodiment 1. (Using...) Figure 2 The basic operation of the device is explained, but it is not limited to the following examples.

[0053] The automatic analysis device 100 generally consists of three types of disks: a sample disk 103, a reagent disk 106, and a reaction disk 109; dispensing mechanisms 110 and 111 that move the sample and reagent between these disks; a drive unit 117 that drives the three disks and the dispensing mechanisms; a control circuit 118 that controls the drive unit; an absorbance measuring circuit 119 that measures the absorbance of the reaction solution; a scattered light measuring circuit 120 that measures the scattered light from the reaction solution; a data processing unit 121 that processes the data measured by each measuring 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.

[0054] Multiple sample cups 102, serving as containers for samples 101, are arranged on the circumference of the sample tray 103. Samples 101 may be blood, urine, bone marrow fluid, standard solutions, etc. Multiple reagent bottles 105, serving as containers for reagents 104, are arranged on the circumference of the reagent tray 106. Multiple containers, or units 108, for mixing reaction solution 107, formed by mixing samples 101 and reagents 104, are arranged on the circumference of the reaction tray 109. Each tray rotates via a motor included in the drive unit 117, which is controlled by a control circuit 118.

[0055] The sample dispensing mechanism 110 is used to move the sample 101 from the sample cup 102, which is disposed on a sample tray 103 that rotates clockwise and counterclockwise, towards the unit 108 by a certain amount. The sample dispensing mechanism 110 consists, for example, a nozzle that ejects or draws the sample 101, a robot that moves the nozzle to a predetermined position, and a pump that ejects or draws the sample 101 from or into the nozzle. The robot and the pump correspond to the drive unit 117.

[0056] The reagent dispensing mechanism 111 is used to move the reagent 104 from the reagent bottle 105, which is arranged on a reagent tray 106 that rotates clockwise and counterclockwise, to the unit 108 by a certain amount. The reagent dispensing mechanism 111 consists, for example, a nozzle that sprays or draws out the reagent 104, a robot that moves the nozzle to a predetermined position, and a pump that sprays out or draws out the reagent 104 from the nozzle. The robot and the pump correspond to the drive unit 117.

[0057] Unit 108 is immersed in a thermostatic fluid 112 within a thermostatic bath where the temperature and flow rate are controlled, within a reaction dish 109. Therefore, the temperature of unit 108 and the reaction liquid 107 therein remains constant as they move with the rotation of the reaction dish 109. In this embodiment, water is used as the thermostatic 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 thermostatic fluid 112 are just one example.

[0058] The stirring mechanism 113 is a mechanism for stirring and mixing sample 101 and reagent 104 within unit 108. The stirring mechanism 113 consists, for example, a stirring rod for stirring sample 101 and reagent 104, a robot for moving the stirring rod to a predetermined position, and a motor for rotating the stirring rod. The robot and motor correspond to drive unit 117.

[0059] The cleaning mechanism 114 is a mechanism that draws the reaction liquid 107 from the unit 108 after the analysis process is completed, and cleans the empty unit 108. The cleaning mechanism 114 is, for example, composed of a nozzle for drawing the reaction liquid 107 after analysis, a nozzle for spraying cleaning water into the unit 108 after the reaction liquid 107 has been drawn, a nozzle for drawing the cleaning water, and a mechanism for moving the nozzle. This mechanism is included in the drive unit 117. After cleaning, the next sample 101 is dispensed again from the sample dispensing mechanism 110, and new reagent 104 is dispensed from the reagent dispensing mechanism 111 for a new analysis process.

[0060] An absorbance measuring unit 115 and a scattered light measuring unit 116 are arranged on a portion of the circumference of the reaction disk 109. The absorbance measuring unit 115 and the scattered light measuring unit 116 are not necessarily required; either one or both can be installed.

[0061] The absorbance measuring unit 115 includes a light source and a light receiver. For example, the light source is a halogen lamp. Light emitted from the light source is directed to the unit 108. A diffraction grating is used to separate the light transmitted through the reaction liquid 107 contained in the unit 108, and a photodiode array is used for light reception. The wavelengths of the light received by the photodiode array are 340nm, 405nm, 450nm, 480nm, 505nm, 546nm, 570nm, 600nm, 660nm, 700nm, 750nm, and 800nm. The light received signals from these receivers are transmitted to the storage unit 121a of the data processing unit 121 via the absorbance measuring circuit 119. Here, the absorbance measuring circuit 119 acquires the light received signals for each wavelength region at regular intervals and outputs the acquired light intensity values ​​to the data processing unit 121.

[0062] The scattered light measurement unit 116 includes a light source, a transmitted light receiver, and a scattered light receiver. For example, the light source is an LED. Light emitted from the light source is irradiated onto the unit 108. Light that passes through the reaction liquid 107 contained in the unit 108 is received by the transmitted light receiver, and light scattered by the reaction liquid 107 is received by the scattered light receiver. The wavelength of the irradiated light is, for example, 700 nm. In the scattered light measurement, considering that it is less susceptible to the influence of impurities (chyle, hemolysis, jaundice) contained in the sample and is visible light, it is preferable to use irradiated light with a wavelength of 600 nm to 800 nm. In addition to LEDs, laser light sources, xenon lamps, halogen lamps, etc., can also be used as the light source. The receiver is, for example, a photodiode. The light received signals from the transmitted light and scattered light receivers are transmitted through the scattered light measurement circuit 120 and sent to the storage unit 121a of the data processing unit 121. The scattered light measurement circuit 120 also acquires the light received signal at regular intervals and outputs the acquired light quantity value to the data processing unit 121. The light-scattering receiver is, for example, positioned in a plane substantially perpendicular to the direction of movement of the unit 108 caused by the rotation of the reaction disk 109. Alternatively, a linear array of multiple units can be internally configured to receive scattered light from multiple angles simultaneously. Using a linear array expands the range of light-receiving angles. Alternatively, instead of a receiver, an optical system such as an optical fiber or lens can be used to guide the light to a light-scattering receiver positioned elsewhere.

[0063] The data processing unit 121 consists of a storage unit 121a and an analysis unit 121b. The storage unit 121a stores control programs, measurement programs, data analysis programs, calibration curve data, measurement data, and analysis results. Measurement programs include, for example, calibration curve generation data generation programs and sample measurement programs. 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 activates the control circuit, which in turn activates the drive unit, thereby performing action analysis on each mechanism. 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 along with the data analysis program. Data analysis programs include, for example, calibration curve generation programs, programs for quantifying the concentration of samples with unknown concentrations of the analyte using calibration curves, and programs for judging errors in calibration curves and sample measurement results. The analysis results, analysis conditions, and data generated during the analysis, as determined by the data analysis program, are returned to and stored in the storage unit 121a. The analysis results and error messages stored in the storage unit 121a are displayed on the display unit 122a of the operation unit 122, and can be printed out by the printer 123 if necessary. The data processing unit 121 is implemented, for example, by a processor such as a CPU.

[0064] The operation unit 122 consists of a display unit 122a, a keyboard 122b and a mouse 122c, which serve as input units. In addition to the keyboard 122b, input can also be performed by touching the screen of the display unit 122a, and input can also be performed by using the mouse 122c to select the screen displayed on the display unit 122a.

[0065] Communication interface 124, for example, connects to the hospital's network and communicates with HIS (Hospital Information System) and LIS (Laboratory Information System).

[0066] <Implementation Method 1: Obtaining Reaction Process Data for Calibration Curve Generation>

[0067] In this embodiment 1, the acquisition of reaction process data used to generate calibration curves will be explained.

[0068] Figure 3This example shows a setup screen used to set calibration information. First, for the inspection items requiring calibration, the calibration information and analysis parameters are set. The setup screen has fields for inputting the following: the batch number of the standard solution, the concentration of the standard solution N used, the position number of the sample cup 102 containing the standard solution N when placed on the sample tray 103, the number of calibration curve data points, the concentration at which the calibration curve was generated corresponding to the number of data points, and the photometric point information, etc. Figure 3 In this diagram, the batch number of the standard solution is set as AAA, the concentration of the standard solution as Y, the placement location of the standard solution as 10, the number of calibration curve data points as N, the concentration as C1 to CN, and the photometric point information as P1 to PN. The significance of concentration and photometric points will be described later. Analytical parameters include sample and reagent dispensing volumes, and calculation points used in data processing. Information other than the placement location of the standard solution is provided by the manufacturer of the reagents and standard solutions. Preferably, the placement location of the standard solution can be arbitrarily set by the operator.

[0069] Calibration information and analysis parameters can be input from the operation unit 122, read into the storage unit 121a via a storage medium such as a CD-ROM, or read through the communication interface 124. Alternatively, if the information has already been stored in the storage unit 121a, it can be retrieved. The concentration and photometric point, which are part of the calibration information, correspond to photometric point-concentration conversion data. If the storage unit 121a contains calibration curve data generated by existing methods and reaction process data of the highest concentration standard solution used in generating the calibration curve, the concentration and photometric point can also reflect the values ​​calculated by the analysis unit 121b using this data and the concentration information of the standard solution N. An example of the calculation method is described later in <Embodiment 1: Setting of Photometric Point-Concentration Conversion Data>. Figure 3 The example shown is a setting screen that displays specific concentration and metering point information, but it could also be a setting screen that does not display these parameters. The set information is stored in the storage unit 121a and read by the parsing unit 121b for use in generating the calibration curve.

[0070] Next, the reagent bottle for this project is placed on reagent tray 106, and the standard solution N is placed on sample tray 103. Then, a calibration request is input via operation unit 122 or communication interface 124. The input is transmitted to data processing unit 121, which executes the measurement program for generating calibration curve data stored in storage unit 121a, and controls the program to operate. The control program activates the control circuit, which in turn activates the drive unit, thereby performing action analysis on each mechanism. Specific analysis actions are described below. Here, an example is given of a project containing a first reagent and a second reagent, but the present invention is not limited to projects containing a first reagent and a second reagent.

[0071] First, the cleaning mechanism 114 operates to clean the unit 108. Next, the sample dispensing mechanism 110 operates to dispense a certain amount of sample 101 (equivalent to standard solution N) from sample cup 102 into the unit 108. The reagent dispensing mechanism 111 operates, dispensing a certain amount of reagent 104 from reagent bottle 105 into the unit 108 containing the sample 101, forming a reaction solution 107, which is a mixture of sample 101 and reagent 104. During the dispensing of sample 101 and reagent 104, the control circuit 118 activates the drive unit 117, causing the sample tray 103, reagent tray 106, and reaction tray 109 to rotate. At this time, the sample cup 102, reagent bottle 105, and unit 108, arranged on each tray, rotate to and position themselves at the designated dispensing positions according to the timing of the operation of the sample dispensing mechanism 110 and reagent dispensing mechanism 111.

[0072] Next, the stirring mechanism 113 operates to stir the reaction liquid 107 within the unit 108. Due to the rotation of the reaction disk 109, the unit 108 containing the reaction liquid 107 passes through the absorbance measuring unit 115 and the scattered light measuring unit 116. Each time the light passes through these measuring units, the transmitted or scattered light signals from the reaction liquid 107 are transmitted to the storage unit 121a of the data processing unit 121 via the absorbance measuring circuit 119 and the scattered light measuring circuit 120, respectively. This data is accumulated as reaction process data.

[0073] Approximately 5 minutes after the initial sample 101 is dispensed, the second reagent 104 is added by the reagent dispensing mechanism 111 into the unit 108 containing the reaction solution 107. The solution is stirred by the stirring mechanism 113 and, as the reaction disk 109 rotates for a certain period (approximately 5 minutes), passes through the absorbance measuring unit 115 and the scattered light measuring unit 116 respectively. The transmitted or scattered light signals from the reaction solution 107 obtained each time the solution passes through each measuring unit are sent to the storage unit 121a of the data processing unit 121 via the absorbance measuring circuit 119 and the scattered light measuring circuit 120, respectively, resulting in a total of approximately 10 minutes of reaction process data.

[0074] Figure 4 This example illustrates reaction process data obtained through absorbance measurement. The horizontal axis represents the measurement points, indicating the order in which the reaction process data was measured. The vertical axis represents the absorbance data measured by the absorbance measurement circuit 119. In this example, absorbance data is acquired at approximately 18-second intervals. Measurement points 1-16 are absorbance data obtained from the reaction solution of the sample and the first reagent, while measurement points 17-34 are absorbance data obtained from the reaction solution of the sample, the first reagent, and the second reagent. In the case where the reaction process data is scattered light intensity data measured by the scattered light measurement circuit 120, Figure 4The vertical axis represents the intensity of scattered light. The reaction process data of the obtained standard solution N is stored in the storage unit 121a and read out by the analysis unit 121b for use in generating the calibration curve. When multiple reaction process data are obtained, the average data obtained can be used as the data for generating the calibration curve, or any one of them can be selected.

[0075] <Implementation Method 1: Setting Data for Metering Point-Concentration Conversion>

[0076] Next, the setting of the "measuring point-concentration conversion data," which represents the relationship between reaction time and the concentration of the analyte, will be explained. Reaction time can be interchanged with measuring point. Here, it is assumed that the horizontal axis of the reaction process data is output as measuring points, and the reaction time is represented as measuring points. Here, an example of deriving the measuring point-concentration conversion data using calibration curve data generated by existing methods and reaction process data of the highest concentration standard solution used in the generation of that calibration curve will be described, but this is not limited to the following derivation example.

[0077] The data processing method for generating calibration curves in existing methods is known, and this method needs to be applied. Therefore, the generation of calibration curves according to existing methods will be recorded first. First, reaction process data for multiple standard solution groups with known concentrations C′1 to C′N (N≥2) will be obtained. For specific illustration, N will be set to 6.

[0078] Figure 5 This is an example of reaction process data for absorbance determination of six standard solution groups with known concentrations C'1 to C'6. Here, assuming the calculation points set by the analytical parameters are, for example, (18, 30) (calculation point 18 corresponds to the start point of the calculation, and 30 corresponds to the end point), the absorbance change ΔA'1 to ΔA'6 over a certain time interval between these points is calculated. Calculation points are specified for each test item. The calculated absorbance change (ΔA'1 to ΔA'6) is plotted against the concentrations (C'1 to C'6) of each analyte in the standard solution group, and the relationship between these data is used as a calibration curve. Table 1 shows the data used to generate the calibration curve obtained by existing methods.

[0079] [Table 1]

[0080] Table 1. Data for generating calibration curves obtained using existing methods.

[0081] standard solution 1 2 3 4 5 6 concentration C’1 C’2 C’3 C’4 C’5 C’6 Change in absorbance ΔA'1 ΔA'2 ΔA'3 ΔA'4 ΔA'5 ΔA'6

[0082] Figure 6 This example shows a calibration curve when the data in Table 1 is plotted and approximated using a polyline. This calibration curve is equivalent to a calibration curve generated using existing methods.

[0083] Next, the reaction process data for the highest concentration standard solution 6, C'6, is processed. First, the measured values ​​are processed using the calculation points used in the data extraction for calibration curve generation. For example, zero-point adjustment is performed. In this example, the change in absorbance at measurement point 18 (A'18) is used as the data for calibration curve generation; therefore, A'18 is also subtracted from all measured values ​​in the reaction process data for standard solution C'6. The processed reaction process data is then fitted to derive a fitting function to supplement the discrete measured data. The fitting function can be, for example, a polynomial function or an exponential function.

[0084] Figure 7 This example shows the reaction process data and fitted line after data processing of standard solution 6.

[0085] Figure 8 Table 2 shows the fitted line after data processing of standard solution 6 and the measurement points (P1 to P6) corresponding to the absorbance change data (ΔA'1 to ΔA'6) obtained by the existing method for generating the calibration curve. Substituting the absorbance change data (ΔA'1 to ΔA'6) obtained by the existing method in Table 1 into the fitted equation, the measurement points (P1 to P6) corresponding to the absorbance change (ΔA'1 to ΔA'6) of each standard solution are calculated. Table 2 shows the relationship between the change data (ΔA'1 to ΔA'6) obtained by the existing method for generating the calibration curve and the measurement points (P1 to P6) required when extracting these data only from the reaction process data of standard solution 6.

[0086] [Table 2]

[0087] Table 2 shows the relationship between the change data obtained by the existing method for generating the calibration curve and the number of measurement points required when extracting the change data only from the reaction process data of standard solution 6.

[0088] Change in absorbance ΔA'1 ΔA'2 ΔA'3 ΔA'4 ΔA'5 ΔA'6 Metering point P1 P2 P3 P4 P5 P6

[0089] In Tables 1 and 2, the data on the change in absorbance (ΔA'1~ΔA'6) are the same. Therefore, as shown in Table 3, the relationship between the concentration of the measured substance and the measurement point can be derived.

[0090] [Table 3]

[0091] Table 3 Relationship between the concentration of the measured substance and the measurement point

[0092] concentration C’1 C’2 C’3 C’4 C’5 C’6 Metering point P1 P2 P3 P4 P5 P6

[0093] The setting of the "measuring point-concentration conversion data" is not accomplished by deriving the information in Table 3. It is necessary to re-evaluate the concentrations (C'1 to C'6) of the analytes in Table 3 based on the concentration (C6) of the standard solution 6 reused when generating the calibration curve. The calibration curve needs to be regenerated, especially whenever the reagent batch changes. The standard solution 6 is reused when generating the calibration curve, but the concentration (C6) of the analytes in this standard solution 6 corresponds to the concentration (C'6) of the analytes in the standard solution group used in the export of Table 3. However, sometimes their concentrations are different (e.g., in the case of different standard solution batches). To prevent such a situation, the concentrations (C'1 to C'6) of the standard solution group (standard solutions 1 to 6) shown in Table 3 are corrected by using the concentration (C6) of the standard solution 6 reused when generating the calibration curve, thus completing the final setting of the "measuring point-concentration conversion data". Here, an example of using the following formula (1) to correct the concentration is shown.

[0094] CM=CN×(C′M÷C′N)…Equation (1)

[0095] CM is the concentration of the analyte at the Mth (1≤M≤N) data point of the calibration curve generated in this invention; CN is the concentration of standard solution N (N≥2); C'M is the concentration of standard solution M in the standard solution group used in the derivation of the relationship table between the concentration of the analyte and the measurement point (Table 3); and C'N is the concentration of standard solution N in the standard solution group used in the derivation of the relationship table between the concentration of the analyte and the measurement point (Table 3).

[0096] As illustrated in the example above, the concentration of the substance being measured (CM) and the reaction time (measuring point) (PM) are derived. Here, the derived information is referred to as "measuring point-concentration conversion data." For ease of understanding, the "measuring point-concentration conversion data" are presented in Table 4 with N=6 as an example.

[0097] [Table 4]

[0098] Table 4 Data for Metering Point-Concentration Conversion

[0099] concentration C1 C2 C3 C4 C5 C6 Metering point P1 P2 P3 P4 P5 P6

[0100] The "Data for Metering Point-Concentration Conversion" in Table 4 is equivalent to Figure 3The information includes the concentration and measurement point. The measurement point information can be derived from a combination of standard solution batches and reagent batches, or it can be obtained by averaging measurement point data derived from various batch combinations. This "measurement point-concentration conversion data" can also be provided by the manufacturer of the reagents and standard solutions according to a combination of reagent and standard solution batches, or according to individual reagent batches, or according to individual standard solution batches. Furthermore, as described above, if the storage unit 121a contains the information necessary for deriving this information, the necessary information and calculation program can be read out to the analysis unit 121b, calculated by the analysis unit 121b, and then returned to the storage unit 121a for retrieval as needed. Alternatively, information stored in an external storage medium can also be read for use.

[0101] In this illustrative example, the change in reaction process data over a certain period of time is used as the calibration curve data generated by existing methods. However, it can be any other than the change; it could be the absorbance or scattered light intensity at a certain measurement point, or the average of data from points before and after a specified measurement point (these are equivalent to setting the calculation point to 1). In this case, processing of the reaction process data of standard solution 6 is not necessary; the original data can be used, or the average of data before and after the calculation point can be used. Furthermore, in the generation of calibration curve data in existing methods, similar to this illustrative example, even when calculating the change in reaction process data over a certain period of time, simple subtraction between calculation points is not required; instead, the average of data from points before and after the calculation point can be subtracted. In this case, the same calculation process can be performed on the reaction process data of standard solution 6 obtained for generating the calibration curve. In addition, the reassessment of concentration is not limited to the conversion formula of equation (1); polynomial functions, exponential functions, etc., can also be used. The data processing method is determined for each inspection item.

[0102] The inventors of this application have discovered that the reaction process data of standard solution 6, which has the highest concentration of the measured substance among standard solutions 1-6, includes the reaction process data of other standard solutions 1-5. That is, it can be seen that in the fitted line obtained by supplementing the discrete portion of the reaction process data of standard solution 6, the light intensity data at measurement points P1-P6 shown in Table 4 are equivalent to the light intensity data (absorbance changes ΔA'1-ΔA'6 in the above description) used to generate the calibration curve calculated using existing methods based on the reaction process data of each standard solution group (standard solutions 1-6).

[0103] Therefore, in this embodiment 1, by temporarily applying the optical quantity data obtained from the standard solution group (standard solutions 1 to 6) using existing methods to the fitting line of the reaction process data of standard solution 6, photometric point information equivalent to the multi-point calibration data of existing methods is derived from the fitting line of the reaction process data of standard solution 6. Figure 8 Furthermore, these photometric point information are correlated with information equivalent to the concentrations of the analytes contained in the standard solution sets (standard solutions 1-6) (Table 4). Here, the relationship between this correlated photometric point information and the concentration of the analytes is referred to as "photometric point-concentration conversion data". In this invention, by using only the "photometric point-concentration conversion data" and the reaction process data of standard solution 6 obtained in the modified reagent batch, a calibration curve equivalent to the calibration curve generated using the standard solution sets (all of standard solutions 1-6) is achieved.

[0104] Here, the method for generating the calibration curve in this invention is briefly described. More detailed steps and specific examples will be described later in <Embodiment 1: Generation of Calibration Curve>.

[0105] In this invention, firstly, for the fitted line of the reaction process data of standard solution 6 obtained only from the modified reagent batch, multiple light quantity data (absorbance, scattered light intensity, or their changes) are extracted using the photometer point information in the "photometer point-concentration conversion data". At this point, multiple light quantity data corresponding to multiple photometer points are obtained. Next, the photometer point information is converted into the concentration information of the analyte according to the "photometer point-concentration conversion data", thereby establishing a correlation between the extracted light quantity data and the concentration of the analyte. A calibration curve is generated by obtaining the relationship between the concentration of the analyte and the extracted light quantity data. In this way, even if recalibration is required, it is not necessary to obtain the reaction process data of the standard solution group (a group of standard solutions with multiple concentrations) as in existing methods. Only the "photometer point-concentration conversion data" and the reaction process data of standard solution 6 obtained from the modified reagent batch are used, while achieving a calibration curve equivalent to the case of using the standard solution group (all of standard solutions 1 to 6). The details of the steps and specific examples are described later.

[0106] <Implementation Method 1: Generation of Calibration Curve>

[0107] The steps for generating a calibration curve using the set "measuring point-concentration conversion data" are explained. The calibration information stored in storage unit 121a ( Figure 3The data includes the calculation points and calibration curve type of the analytical parameters, the reaction process data of standard solution N (standard solution 6 in the above example) (data obtained in <Empirical Implementation 1: Acquisition of Reaction Process Data for Calibration Curve Generation>, here set as absorbance data), and the calibration curve generation program is called by the analysis unit 121b. "Data for Metering Point-Concentration Conversion" is equivalent to calibration information. Figure 3 The information includes the concentration and measurement point. The execution content of the calibration curve generation program is as follows.

[0108] First, the reaction process data of standard solution N is processed according to the information of the calculation points. The calculation points are determined by the inspection items. The preferred processing method is the same as the method used to process the reaction process data of a standard solution with a known concentration C'N in the setting of the photometric point-concentration conversion data. For example, here, taking the processing method used in <Embodiment 1: Setting of Photometric Point-Concentration Conversion Data> as an example, the calculation points are set to the two points (18, 30), and the absorbance of photometric point 18: A18 is used as a reference, and A18 is subtracted from all the measured values. The reaction process data after data processing is fitted, and a fitting formula is derived to supplement the discrete measurement data.

[0109] Figure 9 This example shows the reaction process data and fitted line after data processing of standard solution N. The fitted function is, for example, a polynomial function, an exponential function, etc. It is preferable to use a function of the same type as the fitted function used in setting the measurement point-concentration conversion data. This will be determined by calibration information ( Figure 3 Substitute the set photometer point information (P1~PN) into the obtained fitting formula to calculate (output) the data of absorbance change (ΔA1~ΔAN).

[0110] Figure 10 The fitted line after data processing of standard solution N and the absorbance changes corresponding to the measurement points: P1 to PN: ΔA1 to ΔAN (output information). Here, the output absorbance changes: ΔA1 to ΔAN are equivalent to the photometric data obtained from the reaction process data when measuring the standard solution group (standard solutions 1 to N) in the calibration curve generation based on the existing method. Next, based on the measurement point-concentration conversion data, the measurement points: P1 to PN are converted into the concentration information of the analyte. Figure 3 The concentration information (C1~CN) is used to establish a correlation between the concentrations (C1~CN) and the absorbance changes (ΔA1~ΔAN). The absorbance changes (ΔA1~ΔAN) are plotted relative to the concentrations (C1~CN), and the calibration factor is calculated by approximating the calibration curve type (linear, piecewise linear, spline, etc.) specified by the analytical parameter information, thus generating a calibration curve.

[0111] Figure 11This example shows the calibration curve generated in Implementation 1 when the calibration curve type is a piecewise linear curve. The horizontal axis represents the concentration of the analyte, and the vertical axis represents the absorbance change data: ΔA. The calibration factor is an approximation of the absorbance, scattered light intensity, or their changes at calibration points (calibration curve points), the slope of the calibration curve, etc. The calibration factor and its calculation method vary depending on the type of calibration curve (linear, piecewise linear, spline, etc.). The generated calibration curve, processed reaction process data, etc., are stored in the storage unit 121a. When a sample with an unknown concentration of the analyte is measured, the calibration curve information is retrieved by the analysis unit 121b for quantifying the concentration of the analyte.

[0112] Here, the processing of reaction process data for standard solution N was described with two calculation points, but there is also a case where there is only one calculation point. In the case of one calculation point, the data from that point can be used directly, or the average of the data before and after that point can be used. Alternatively, in the case of two calculation points, the subtraction operation may not be based on the measurement data from the starting point (equivalent to point 18 in the above description). For example, the subtraction operation can be based on the average of the data from multiple points before and after the starting point. In this case, the average of the data from multiple points before and after the point being subtracted can also be used in the data of the point being subtracted.

[0113] <Implementation Method 1: Generation of Calibration Curve and Calculation of Calibration Factor Example 1>

[0114] The following describes specific testing items and examples of generating calibration curves using commercially available reagents and standard solutions, following the instructions in Embodiment 1. For absorbance measurement, FDP (fibrinogen / fibrinogen degradation products) is selected; for scattered light measurement, high-sensitivity CRP (C-reactive protein) is selected. Examples of calibration curve generation are described below. Both are latex immunoturbidimetric tests, but this invention is not limited to latex immunoturbidimetric tests.

[0115] First, let's introduce the FDP project. First, we'll set up the data for the photometric point-concentration conversion. Here, following the derived example described above, we need to generate calibration curve data using existing methods. This data was obtained using the following reagents and standard solutions.

[0116] • Reagent: Batch A

[0117] • Standard solution group: Batch B, concentration of 6 points.

[0118] • Concentrations of standard solutions (batch B): Standard solution 1 - 0.0 μg / mL, Standard solution 2 - 7.6 μg / mL, Standard solution 3 - 15.0 μg / mL, Standard solution 4 - 29.0 μg / mL, Standard solution 5 - 61.0 μg / mL, Standard solution 6 - 121.0 μg / mL.

[0119] First, the reagent (batch A) was reacted with the standard solution group (batch B), and the reaction process data of the standard solution groups (standard solutions 1-6) were obtained respectively. Using two calculation points (19, 34), the absorbance change between these points was calculated. Here, the data from the previous point was also used; the average absorbance of points 18 and 19 was subtracted from the average absorbance of points 33 and 34 to obtain the absorbance change. Next, the reaction process data of standard solution 6 in the standard solution group (batch B) was processed using equation (2). X represents points 18-34.

[0120] The data at point X = (the average absorbance of points X and (X-1)) - (the average absorbance of points 18 and 19) ... Equation (2)

[0121] The processed reaction process data are fitted using an exponential function. At this point, the fitting is differentiated between before and after the 24-point measurement point, using measurement point 24 as the boundary. The calculated absorbance changes of the standard solution groups are substituted into the obtained fitting formula to calculate the measurement points. Here, the data before and after 24 points are fitted separately, but it is not always necessary to divide the data for fitting; it is preferable to fit when the fitted line best matches the processed reaction process data.

[0122] Figure 12 This is an example of inputting the calculated metering point into the metering point field in the calibration settings screen.

[0123] Next, the concentration information is set. The reagents and standard solutions used to obtain the reaction process data used in generating the calibration curve are described below. The batches of reagents and standard solutions used here are different from those used in setting the data for the photometric point-concentration conversion.

[0124] • Reagent: Batch C

[0125] • Standard solution: Batch D, concentration 6 points, only standard solution 6 is used.

[0126] • Concentration of standard solution (batch D): Standard solution 6 - 121.0 μg / mL (for reference, the concentrations of other standard solutions are recorded: Standard solution 1 - 0.0 μg / mL, Standard solution 2 - 7.3 μg / mL, Standard solution 3 - 15.2 μg / mL, Standard solution 4 - 29.0 μg / mL, Standard solution 5 - 61.0 μg / mL)

[0127] Here, the concentration is calculated using equation (1). The calculated concentration of the substance being measured is as follows: Figure 12 The concentration column in the calibration setting example shown is illustrated here. The concentration of the analyte in standard solution 6 of the standard solution group (batch B) (121.0 μg / mL) is the same as the concentration of the analyte in standard solution 6 (batch D) (121.0 μg / mL). Therefore, the result of converting the concentration using equation (1) is the same as the concentration of the analyte in the standard solution group. However, when the concentrations of the analyte in standard solution 6 of batch B and batch D are different, it is necessary to convert the concentration of the analyte used in generating the calibration curve to the value corresponding to standard solutions 1 to 6 of the standard solution group (batch B) according to equation (1). This conversion is also performed in Example 2 described later.

[0128] Finally, a calibration curve is generated. The reaction process data obtained by reacting the reagent (batch C) with the standard solution 6 (batch D) is processed using equation (2) and fitted with an exponential function to obtain the fitting equation. At this time, the fitting is distinguished between points before and after the photometric point 24, with the photometric point 24 as the boundary. Since the fitting conditions used when setting the photometric point-concentration conversion data are preferred, the fitting is performed under the same conditions.

[0129] Figure 13 The fitted line represents the processed data representing the reaction process data of reagent (batch C) and standard solution 6 (batch D).

[0130] Figure 14 This represents the fitted line and equivalent data of standard solution 6 (batch D) after data processing. Figure 12 The change in absorbance at the metering point is shown (output information). Figure 12 Substitute the measurement points into the fitting formula to calculate the absorbance change corresponding to each calibration curve point.

[0131] Table 5, in addition to the calibration curve points and concentrations, also indicates... Figure 14 The measurement point and absorbance change (output information).

[0132] [Table 5]

[0133] Table 5. Relationship between calibration curve points, concentration, measurement points, and absorbance changes.

[0134] Calibration curve points 1 2 3 4 5 6 Concentration (μg / mL) 0.0 7.6 15.0 29.0 61.0 121.0 Metering point 19.1 19.6 20.1 21.2 23.8 34.0 Change in absorbance 18 153 292 563 1050 2035

[0135] Figure 15This represents the generated calibration curve. The calibration curve is generated by plotting the absorbance change relative to the concentration using a broken line approximation. In this example, the calibration curve type is a broken line, and the calibration factors include, for example, the absorbance change at each calibration curve point and the slope of each concentration interval. The absorbance change at each calibration curve point is shown in Table 5. The slopes of each concentration interval are as follows: When the FDP concentration is above 0.0 μg / mL and below 7.6 μg / mL, the slope is (153-18) / (7.6-0.0)≈17.8; when the FDP concentration is above 7.6 μg / mL and below 15.0 μg / mL, the slope is (292-153) / (15.0-7.6)≈18.8; when the FDP concentration is above 15.0 μg / mL and below 29.0 μg / mL... The slope is (563-292) / (29.0-15.0)≈19.4. When the FDP concentration is above 29.0 μg / mL and below 61.0 μg / mL, the slope is (1050-563) / (61.0-29.0)≈15.2. When the FDP concentration is above 61.0 μg / mL, the slope is (2035-1050) / (121.0-61.0)≈16.4.

[0136] Figure 16 This indicates the calibration curve generated by the method of Embodiment 1. Figure 15 Examples of calibration curves that coincide with those generated by existing methods. A calibration curve generated by existing methods refers to a curve obtained by processing standard solutions 1-6 (batch D) as a standard solution group, using reaction process data obtained from reacting with reagent (batch C), subtracting the average absorbance at points 18 and 19 from the average absorbance at points 33 and 34, and plotting the absorbance change relative to the concentrations of standard solutions 1-6 (batch D) (standard solution 1 - 0.0 μg / mL, standard solution 2 - 7.3 μg / mL, standard solution 3 - 15.2 μg / mL, standard solution 4 - 29.0 μg / mL, standard solution 5 - 61.0 μg / mL, standard solution 6 - 121.0 μg / mL), and approximating it with a broken line. Based on... Figure 16 The calibration curve generated by the method of this embodiment 1 is roughly the same as the calibration curve generated by the existing method.

[0137] Furthermore, here, standard solutions 1-6 of batch D are considered as samples of unknown concentration, and are reacted with reagent (batch C). The reaction process data is measured and compared with the calibration curve data generated by the method of Embodiment 1. Figure 15The concentrations of standard solutions 1–6 (batch D) were quantified by comparison. Specifically, the absorbance changes obtained by subtracting the average absorbance values ​​at points 18 and 19 from the average absorbance values ​​at points 33 and 34 in the reaction process data of standard solutions 1–6 (batch D) were compared with the calibration curve data to quantify the concentrations of the analytes in standard solutions 1–6. Table 6 shows the results and accuracy.

[0138] [Table 6]

[0139] Table 6 shows the results and accuracy of quantifying the concentrations of the analytes in standard solutions 1–6 (batch D) using calibration curve data generated by the method of Embodiment 1.

[0140]

[0141] The accuracy obtained was confirmed to be within 85% to 115% of the expected value. Here, the expected value is equivalent to a known concentration.

[0142] <Implementation Method 1: Generation of Calibration Curve and Calculation of Calibration Factor Example 2>

[0143] Next, we will introduce the high-sensitivity CRP project. First, we will set the data for the photometric point-concentration conversion. Here, since we are following the derived example described above, we need to generate calibration curve data using existing methods. This data was obtained using the following reagents and standard solutions.

[0144] • Reagent: Batch E

[0145] • Standard solution group: Batch F, concentration of 3 points.

[0146] • Concentration of standard solution group (batch F): Standard solution 1 0.0 mg / dL, Standard solution 2 0.2 mg / dL, Standard solution 3 1.0 mg / dL.

[0147] First, the reagent (batch E) was reacted with the standard solution group (batch F), and the reaction process data of the standard solution groups (standard solutions 1-3) were obtained respectively. Using two calculation points (20, 34), the change in scattered light intensity between these points was calculated. Here, the data of the previous point for each point was also used, and the average of the scattered light intensity at points 19 and 20 was subtracted from the average of the scattered light intensity at points 33 and 34 to obtain the change in scattered light intensity. Next, the reaction process data of standard solution 3 in the standard solution group (batch F) was processed using equation (3). X represents points 18-34.

[0148] The data at point X = (the average of the scattered light intensities at points X and (X-1)) - (the average of the scattered light intensities at points 19 and 20) ... Equation (3)

[0149] The processed reaction process data are fitted using an exponential function. At this point, the fitting is differentiated between before and after point 21, using the measurement point 21 as the boundary. The calculated changes in the intensity of scattered light from the standard solution group are substituted into the obtained fitting formula to calculate the measurement point. Here, the data before and after point 21 are fitted separately, but it is not always necessary to divide the data for fitting; it is preferable to fit when the fitted line best matches the processed reaction process data.

[0150] Figure 17 This is an example of inputting the calculated metering point into the metering point field in the calibration settings screen.

[0151] Next, the concentration information is set. The reagents and standard solutions used to obtain the reaction process data used in generating the calibration curve are described below. The batches of reagents and standard solutions used here are different from those used in setting the data for the photometric point-concentration conversion.

[0152] • Reagent: Batch G

[0153] • Standard solution: Batch H, concentration 3 points, only standard solution 3 is used.

[0154] • Concentration of standard solution (batch H): Standard solution 3 - 1.0 mg / dL (for reference, the concentrations of other standard solutions are recorded. Standard solution 1 - 0.0 mg / dL, Standard solution 2 - 0.2 mg / dL)

[0155] Here, the concentration is calculated using equation (1). The derived concentration information of the measured substance is as follows: Figure 17 The concentration column is shown in the example calibration settings screen.

[0156] Finally, a calibration curve is generated. The reaction process data obtained by reacting the reagent (batch G) with the standard solution 3 (batch H) is processed using equation (3) and fitted with an exponential function to obtain the fitting equation. At this time, the fitting is distinguished between before and after the photometric point 21, with the photometric point 21 as the boundary. Since the fitting conditions used when setting the photometric point-concentration conversion data are preferred, the fitting is performed under the same conditions.

[0157] Figure 18 The fitted line represents the processed data representing the reaction process data of reagent (batch G) and standard solution 3 (batch H).

[0158] Figure 19 This represents the fitted line and equivalent to the data processing of standard solution 3 (batch H). Figure 17 The change in scattered light intensity at the measurement point is shown (output information). Figure 17 Substitute the photometer points into the fitting formula to calculate the change in scattered light intensity corresponding to each calibration curve point.

[0159] Table 7, in addition to the calibration curve points and concentrations, also indicates... Figure 19 The measurement point and the change in the intensity of scattered light (output information).

[0160] [Table 7]

[0161] Table 7 shows the relationship between calibration curve points, concentration, photometric points, and changes in scattered light intensity.

[0162] Calibration curve points 1 2 3 Concentration (mg / dL) 0.0 0.2 1.0 Metering point 20.2 22.4 34.2 Change in scattered light intensity 4 538 1553

[0163] Figure 20 This represents the generated calibration curve. The change in scattered light intensity relative to the concentration is plotted, and the calibration curve is generated using a broken line approximation. In this example, the calibration curve type is a broken line, and the calibration factors include, for example, the change in scattered light intensity at each calibration curve point and the slope of each concentration interval. The change in scattered light intensity at each calibration curve point is shown in Table 7. The slopes of each concentration interval are as follows: When the CRP concentration is above 0.0 mg / dL and below 0.2 mg / dL, the slope is (538-4) / (0.2-0.0) = 2670.0; when the CRP concentration is above 0.2 mg / dL, the slope is (1553-538) / (1.0-0.2) ≈ 1268.8.

[0164] Figure 21 This indicates the calibration curve generated by the method of Embodiment 1. Figure 20 Examples of calibration curves that coincide with those generated by existing methods. Calibration curves generated by existing methods refer to those obtained by treating standard solutions 1-3 (batch H) as a standard solution group, using reaction process data obtained from reactions with reagent (batch G), and plotting the change in scattered light intensity (obtained by subtracting the average of scattered light intensities at points 19 and 20 from the average of scattered light intensities at points 33 and 34) relative to the concentrations of standard solutions 1-3 (batch H) (standard solution 1 - 0.0 μg / mL, standard solution 2 - 0.2 mg / dL, standard solution 3 - 1.0 μg / mL) using a broken line approximation. Based on... Figure 21 The calibration curve generated by the method of this embodiment 1 is roughly the same as the calibration curve generated by the existing method.

[0165] Furthermore, here, standard solutions 1-3 of batch H are considered as samples of unknown concentration, and are reacted with reagent (batch G). The reaction process data is measured and compared with the calibration curve data generated by the method of Embodiment 1. Figure 20The concentrations of standard solutions 1–3 (batch H) were quantified by comparison. Specifically, in the reaction process data of standard solutions 1–3 (batch H), the change in scattered light intensity obtained by subtracting the average scattered light intensity at points 19 and 20 from the average scattered light intensity at points 33 and 34 was compared with the calibration curve data to quantify the concentration of the analyte in standard solutions 1–3. Table 8 shows the results and accuracy.

[0166] [Table 8]

[0167] Table 8 shows the results and accuracy of quantifying the concentration of the analyte in standard solutions 1-3 (batch H) using calibration curve data generated by the method of Embodiment 1.

[0168] sample Standard solution 1 Standard solution 2 Standard solution 3 ①The concentration is known [mg / dL] 0.0 0.2 1.0 ② Quantitative results [mg / dL] 0.00 0.21 1.00 Accuracy (②÷①×100%) - 102.8％ 100.5％

[0169] The accuracy obtained was confirmed to be within 90–110% of the expected value. Here, the expected value is equivalent to a known concentration.

[0170] This document describes an example of calculating a calibration factor for a piecewise linear calibration curve, but the calculation method is not limited to this. Furthermore, the calibration factor and its calculation method vary depending on the type of calibration curve (linear, piecewise linear, spline, etc.).

[0171] <Implementation Method 1: Summary>

[0172] The automatic analysis apparatus 100 of this embodiment determines the point in the reaction process data of standard solution N that corresponds to the photometric point shown in the "photometric point-concentration conversion data" by applying "photometric point-concentration conversion data" to the reaction process data obtained by measuring the reaction process of standard solution N. This photometric point information is information needed to extract photometric data equivalent to calibration data obtained from previous measurements of standard solution groups (standard solutions 1 to N) solely from the reaction process data of standard solution N, and is information set separately and independently from the measurement of standard solution N. Furthermore, this photometric point information is associated with information on the concentration of the analyte corresponding to the standard solution group. The determined point consists of a photometric point and photometric data. Based on the "photometric point-concentration conversion data," the photometric point information in the determined point is converted into the concentration of the analyte, thereby generating a calibration curve representing the relationship between the photometric data and the concentration of the analyte. Thus, although only standard solution N is actually measured, calibration data for standard solutions 1 to N can be obtained. Therefore, a calibration curve equivalent to that generated using the standard solution group (all of the standard solutions 1 to N) can be obtained by measuring only the standard solution N.

[0173] The above embodiments have described the calibration curve generation method in the case of using the standard solution N with the highest concentration of the analyte. However, it is not necessarily required to use the standard solution N. It is also possible to use only the standard solution (N−n) (n is an integer, 0 < n < N) having a concentration sufficient to extrapolate the reaction of the highest concentration of the analyte contained in the standard solution N, and generate a calibration curve by the same method as described above. In this case, only the standard solution (N−n) is actually measured, and a calibration curve incorporating the calibration data of the standard solutions 1 to N can be generated. Therefore, it is possible to obtain a calibration curve equivalent to the calibration curve generated by using the set of standard solutions (all of the standard solutions 1 to N) by measuring only the standard solution (N−n).

[0174] When the batch of the set of standard solutions used by the automatic analyzer 100 of the first embodiment for obtaining the data for converting the measurement point to the concentration is different from the batch of the standard solution for obtaining the reaction process data for generating the calibration curve, the calibration curve is generated after correcting the difference in the concentration of the analyte between the batches according to formula (1). Thus, if the measurement point information is temporarily obtained, it is not necessary to specify the batch of the standard solution used for obtaining the reaction process data for generating the calibration curve and the concentration of the analyte contained in the standard solution. That is, it is possible to generate a calibration curve by measuring only one standard solution (standard solution N or standard solution (N−n)) of a batch different from the batch of the set of standard solutions used for obtaining the data for converting the measurement point to the concentration.

[0175] In the first embodiment, the data for converting the measurement point to the concentration can be obtained by actually measuring the set of standard solutions (standard solutions 1 to N) using the automatic analyzer 100, or by reading out the previously obtained data for converting the measurement point to the concentration. The data for converting the measurement point to the concentration is not limited to the method of reading from the storage device attached to the automatic analyzer, and can also be obtained using a communication unit such as the Internet. In addition, it can also be input via an input screen exemplified in Figure 12 etc. Thus, the data for converting the measurement point to the concentration can be obtained in various ways according to the operating conditions of the automatic analyzer 100 and the like.

[0176] <Embodiment 2>

[0177] In Embodiment 2 of the present invention, the following situation will be described: In test items where the number of standard solutions is N (N≥3) or more, in addition to measuring the standard solution N with the highest concentration, a standard solution 1 with a zero concentration that does not contain the analyte is also measured. A calibration curve is generated using data corresponding to calibration curve points 2 to N extracted from the reaction process data of standard solution N using the same method as in Embodiment 1, and data of calibration curve point 1 extracted from the reaction process data of standard solution 1. The difference from Embodiment 1 is that not only is the reaction process data of the standard solution N with the highest concentration actually measured, but also the data of standard solution 1 with a zero concentration of the analyte is actually measured. In this Embodiment 2, the effects of non-specific reactions unrelated to the analyte that occur can be accurately reflected in the calibration curve.

[0178] Until now, calibration using two standard solutions—a zero-concentration standard solution and a standard solution of any known concentration other than zero—has been a two-point calibration. In two-point calibration, the data from the two standard solutions are used to update the calibration factors (reagent blank value and K value) in the existing calibration curve. Specifically, the zero-concentration standard solution is used to correct the reagent blank value (blank absorbance, blank scattered light intensity, or both), and the K value (K factor) is updated using a standard solution of any known concentration other than zero. The invention according to Embodiment 2 uses multi-point data corresponding to calibration curve points 2 to N extracted from the reaction process data of the aforementioned standard solution N and data from calibration curve point 1 extracted from the reaction process data of the aforementioned standard solution 1 to generate a new calibration curve, which is an application of two-point calibration.

[0179] The structure of the automatic analysis device and the setting of the photometric point-concentration conversion data are the same as in Embodiment 1. Therefore, to avoid repeating the description, the description is omitted here, and only the structural parts that are different from Embodiment 1 are described.

[0180] <Implementation Method 2: Obtaining Reaction Process Data for Calibration Curve Generation>

[0181] The acquisition of reaction process data used in generating the calibration curve in Embodiment 2 will be explained. First, calibration information and analysis parameters are set for the inspection items that require calibration.

[0182] Figure 22 This is an example of a screen showing the calibration information settings in Embodiment 2. The calibration information includes the batch number of the standard solution, the concentrations of standard solution 1 and standard solution N used, the position number of the sample cup 102 containing standard solution 1 and standard solution N when placed on the sample tray 103, the number of calibration curve data points, the concentration at which the calibration curve for the data points was generated, and photometric point information, etc. Figure 22In the table, the batch number of the standard solution is set as: BBB, the concentration of standard solution 1 is: 0, the concentration of standard solution N is: Z, the installation position of standard solution 1 is: 13, the installation position of standard solution N is: 14, the number of calibration curve data points is: N, the concentration is: C1~CN, and the photometric point information is: P2~PN (the photometric point corresponding to C1 cannot be entered or displayed).

[0183] The reason for setting the photometric point corresponding to C1 to be uninputable and undisplayable is as follows. Standard solution 1 typically uses a standard solution with a concentration of zero for the substance being measured ( Figure 22 (As in the case of inputting the concentration of the standard solution). In this case, standard solution 1 typically does not react with the reagent, and no change over time is observed in the reaction process data. However, in reality, a slight reaction sometimes results in a change in light intensity. Therefore, in this embodiment 2, for standard solution 1, light intensity data for generating the calibration curve is obtained through actual measurement. Therefore, the data for generating the calibration curve of standard solution 1 is calculated using the calculation points specified by the analytical parameters. Thus, for C1, the photometric point information that is not required in the reaction process data of standard solution N is set to be uninputable.

[0184] The analytical parameters include information such as sample and reagent dispensing volumes, and calculation points used in data processing. Information other than the placement location of the standard solution is provided, for example, by the manufacturer supplying the reagents and standard solutions. Preferably, the placement location of the standard solution can be arbitrarily set by the operator. Calibration information and analytical parameters can be input from the operation unit 122, read into the storage unit 121a via a storage medium such as a CD-ROM, or read through the communication interface 124. Alternatively, if the information has been previously stored in the storage unit 121a, it can be retrieved. The concentration and photometric point, which are part of the calibration information, correspond to photometric point-concentration conversion data. If the storage unit 121a contains calibration curve data generated by existing methods and reaction process data of the standard solution with the highest concentration used in generating the calibration curve, the concentration and photometric point can also reflect the values ​​calculated by the analysis unit 121b using this data and the concentration information of the standard solution N. An example of the calculation method is described in Embodiment 1. Figure 22 The example shown is a setting screen that displays specific concentration and metering point information, but it could also be a setting screen that does not display these parameters. The set information is stored in the storage unit 121a and read by the parsing unit 121b for use in generating the calibration curve.

[0185] Next, the reagent bottle for this project is placed on the reagent tray 106, and standard solution 1 and standard solution N are placed on the sample tray 103. Then, a calibration request is input via the operation unit 122 or the communication interface 124. The input is transmitted to the data processing unit 121, which executes the measurement program for generating calibration curve data stored in the storage unit 121a, and controls the program to operate. The control program activates the control circuit, which in turn activates the drive unit, thereby performing action analysis on each mechanism. The specific analysis operations are the same as in Embodiment 1, so descriptions are omitted here. The reaction process data of standard solution 1 and standard solution N are stored in the storage unit 121a and read by the analysis unit 121b for use in generating the calibration curve. Here, when multiple reaction process data are obtained from each standard solution, the average data obtained can be used as input information when generating the calibration curve, or any one of them can be selected as input information.

[0186] <Implementation Method 2: Generation of Calibration Curve>

[0187] The generation of the calibration curve in Embodiment 2 will be explained. The calibration information, the calculation points of the analytical parameters, the calibration curve type, the reaction process data of standard solution 1 and standard solution N (here, absorbance data), stored in the storage unit 121a, and the calibration curve generation program are called by the parsing unit 121b. The execution content of the calibration curve generation program is as follows.

[0188] First, the reaction process data of standard solution N is processed according to the information of the calculation points. The calculation points are determined by the inspection items. The preferred processing method is the same as the method used to process the reaction process data of a standard solution with a known concentration C'N in the setting of the photometric point-concentration conversion data. For example, here, the calculation points are set to (18, 30), and A18 is subtracted from all measured values ​​based on the absorbance of photometric point 18: A18. The processed reaction process data is then fitted to derive a fitting function to supplement the discrete measured data. The fitting function is, for example, a polynomial function, an exponential function, etc. It is preferable to use a function of the same type as the fitting function used in the setting of the photometric point-concentration conversion data. The calibration information ( Figure 22 Substitute the set photometer point information (P2~PN) into the obtained fitting formula, and calculate the absorbance change data (ΔA2~ΔAN) as the output information.

[0189] Figure 23 The fitted line after data processing of standard solution N and the absorbance change corresponding to the measurement points: P2~PN: ΔA2~ΔAN (output information).

[0190] Figure 24 This represents the reaction process data for standard solution 1, where the analyte was measured at zero concentration. Next... Figure 23 , data is extracted from the reaction process data of Standard Solution 1 according to the operation points. The operation points are uniquely specified for each test item, so in the above example, the two points (18, 30) are used. Calculate the change in absorbance ΔA1 within a certain time between these points (= absorbance at the 30th point ﹣ absorbance at the 18th point).

[0191] Data on the change in absorbance is plotted against the concentration, and the calibration factor is calculated by approximating it with a mathematical formula of the calibration curve type (linear, broken line, spline, etc.) specified by the analysis parameter information, and a calibration curve is generated. The calibration factor is the coefficient information of an approximate formula such as the absorbance, scattered light intensity, or their change data, and the slope of the calibration curve at the calibration points (calibration curve points). The calibration factor and its calculation method vary according to the type of calibration curve (linear, broken line, spline, etc.).

[0192] Figure 25 An example of the calibration curve generated in Embodiment 2 is shown. The generated calibration curve, processed reaction process data, etc. are stored in the storage unit 121a. When measuring a sample with an unknown concentration of the analyte, the information of the calibration curve is retrieved by the analysis unit 121b and used for the quantification of the concentration of the analyte.

[0193] Here, in the processing of the reaction process data of Standard Solution N, the case where the operation points are two points is described, but there is also a case where the operation points are one point. In the case of one point, the data of this point can be directly used, or the average value of the data before and after this point can be used. In addition, in the case where the operation points are two points, the processing content may not be subtraction based on the measurement data of the operation start point (corresponding to point 18 in the above), for example, subtraction can also be performed based on the average value of multiple points before and after the operation start point. At this time, in the data of the subtraction target point, the average value of multiple points before and after this point can also be used. In addition, when extracting data from the reaction process data of Standard Solution 1 according to the operation points, not only the above calculation examples, but various calculation formulas can also be used in the same way as in the case of Standard Solution N according to the number of operation points.

[0194] The above embodiment describes the calibration curve generation method in the case of using Standard Solution N with the highest concentration of the analyte and Standard Solution 1 with zero concentration of the analyte, but a standard solution (N - n) (n is an integer, 0 < n < N) with a concentration capable of extrapolating the reaction of the highest concentration of the analyte contained in Standard Solution N can be used instead of Standard Solution N, and a calibration curve can be generated by the same method as above.

[0195] <Embodiment 3>

[0196] In Embodiment 3 of the present invention, the procedure for generating calibration curves as described in Embodiments 1 and 2 will be explained, where a calibration curve is generated using a tool independent of the automatic analysis device. The basic procedure will be described below, but the method is not limited to the examples below.

[0197] The program includes, for example, a step of setting the photometric point-concentration conversion data (step (1)), a step of extracting the photometric data for generating the calibration curve from the reaction process data of standard solution N based on the photometric point set in step (1) (step (2)), a step of converting the photometric point information used during data extraction into the concentration information of the substance being measured and associating the concentration information with the extracted data (step (3)), and a step of plotting the extracted data relative to the concentration of the substance being measured and approximating the plot with a specified mathematical formula to generate the calibration curve (step (4)). The specific processing content in step (1) is the same as that described in <Embodiment 1: Setting the photometric point-concentration conversion data>, so repeated explanation is avoided here. The specific processing content in steps (2) to (4) is also the same as that described in <Embodiment 1: Generating the calibration curve>, so explanation is omitted. In this program, for example, step (2) can also be the step of extracting the photometric data for generating the calibration curve from the reaction process data of standard solution 1 and standard solution N, as in Embodiment 2.

[0198] The program in this embodiment 3 is mounted on an analytical tool or similar device independent of the automatic analyzer 100. The information used in the program includes calibration curve information (calibration data) generated by existing methods, the calculation points used when generating the calibration curve, the concentration of the standard solution, reaction process data, concentration information of standard solution N and standard solution 1 measured after reagent batch change, and reaction process data. This information may also be data already stored in the analytical tool on which the program is mounted. Alternatively, this information can be input from the operation unit of the analytical tool, or read into the analytical tool via an external storage medium or communication interface. Alternatively, information obtained from an automatic analyzer connected to the analytical tool can be read from the automatic analyzer and used in the analytical tool, or information obtained from an automatic analyzer not connected to the analytical tool can be read into the analytical tool via an external storage medium, the Internet, or the like.

[0199] According to the procedure of Embodiment 3, in an automated analysis device without the calibration curve generation unit of this invention, by connecting the analysis tool equipped with the procedure of Embodiment 3 to the device, the calibration curve generated by the analysis tool is sent to the device, and the calibration curve generated by the method of this invention can also be used in the device. Alternatively, the calibration curve generated by the analysis tool can be stored in the storage unit within the analysis tool without sending it to the device. The reaction process data of a sample with an unknown concentration of the analyte, as determined by the device, can be read into the analysis tool, and the concentration of the analyte can be quantified using the calibration curve data within the analysis tool. In this case, the quantitative result of the concentration of the analyte can be sent to the device and displayed on the device, or it can be sent to the intra-hospital network via a communication interface connected to the device, or it can be sent directly from the analysis tool to the intra-hospital network. Here, the connection between the analysis tool and the device is not necessary; the concentration of a sample with an unknown concentration of the analyte can also be quantified using the calibration curve generated in this invention by exchanging necessary information via an external storage medium, the Internet, etc.

[0200] <Implementation Method 4>

[0201] In Embodiment 4 of the present invention, an automatic analysis device 100 and an analysis tool equipped with the following functions will be described: The calibration curves generated in Embodiments 1 to 3 are compared with calibration curve data already stored in the automatic analysis device 100 or an analysis tool equipped with a calibration curve generation program; error checking is performed; if the error checking settings are met, errors in the generated calibration curve are reported; and a selection is made as to whether to use the calibration curve. Here, the calibration curve data already stored in the automatic analysis device or the analysis tool equipped with a calibration curve generation program refers to calibration curve data generated by conventional methods, the previous data of the calibration curve generated by the method of the present invention, etc.

[0202] The structure of the automatic analysis device is as described in Embodiment 1, therefore, the focus here is on the implementation of error checking, error reporting, and the selection function for whether to use the calibration curve in the automatic analysis device. When a calibration curve is generated in the analysis unit 121b using the method of the present invention, error determination information stored in the storage unit 121a is read out to the analysis unit 121b and compared with the generated calibration curve data to check for errors. As part of the error checking, for example, the coefficient information in the mathematical formula of the calibration curve, such as the calibration factor, is compared with the stored calibration curve data and the calibration curve data of the present invention to calculate the degree of deviation. If the deviation exceeds a pre-set threshold, an error is reported. The result of the error checking is sent to the storage unit 121a along with the generated calibration curve information. In the case of error information, the error information, the calibration curve data, and a confirmation request regarding whether to use the calibration curve are sent from the storage unit 121a to the intra-agency network for display. Preferably, this display can be selected by the user to be shown or not shown. The user can choose whether to use the service by touching the screen of display unit 122a, or by using mouse 122c to select the screen displayed on display unit 122a. Alternatively, the information selected on the intranet can be sent to storage unit 121a via communication interface 124.

[0203] Next, the implementation of error checking, error reporting, and selection of the calibration curve used in the analysis tool equipped with the calibration curve generation program will be explained. This function can be incorporated into the calibration curve generation program described in Embodiment 3 as step (5), or the analysis unit in the analysis tool can have an error determination function.

[0204] When the calibration curve generation program described in Embodiment 3 is incorporated as step (5), for example, after generating the calibration curve in steps (1) to (4), as step (5), the calibration curve checking program operates. The calibration curve data for comparison stored in the storage unit of the analysis tool is read into the program and compared with the generated calibration curve data to check for errors. The content of the error check is as described above. The result of the error check is sent to the storage unit of the analysis tool along with the generated calibration curve information. If there is an error message, the error message, calibration curve data, and a confirmation request for whether to use the calibration curve are displayed on the display unit of the analysis tool. This display can preferably be selected by the user to be displayed or not displayed. Alternatively, the confirmation request and other information can be sent to the storage unit 121a of the automatic analysis device connected to the analysis tool and displayed via the display unit 122a or the communication interface 124 to the intra-institutional network, etc. The selection result of whether the calibration curve can be used is sent to the storage unit of the analysis tool. If "use" is selected, the calibration curve generated in Embodiments 1 to 3 is used.

[0205] When the analysis unit within the analysis tool has an error detection function, for example, after generating a calibration curve using a calibration curve generation program, the stored comparison calibration curve data is read from the storage unit to the analysis unit, and the information in these calibration curves is compared to check for errors. The error check is performed as described above. The result of the error check is sent to the storage unit within the analysis tool. If an error message is present, the error message, calibration curve data, and a confirmation request regarding whether to use the calibration curve are displayed on the display unit of the analysis tool. Preferably, this display can be selected by the user. Alternatively, the confirmation request and other information can be sent to the storage unit 121a of the automatic analysis device connected to the analysis tool, and displayed via the display unit 122a or the communication interface 124 to an intra-institutional network. The selection result regarding whether the calibration curve can be used is sent to the storage unit within the analysis tool; if "use" is selected, the calibration curve generated in embodiments 1 to 3 is used.

[0206] Here, we explain the function of choosing whether to use the calibration curve when an error is reported in the generated calibration curve data. However, if "do not use" is selected, we can also add a function that allows us to select the calibration curve to use.

[0207] <Implementation Method 5>

[0208] In Embodiment 5 of the present invention, a case is described in which a sample in which the substance to be measured has an unknown concentration is measured and its concentration is quantified using a calibration curve generated in Embodiments 1 to 3 or a calibration curve generated in Embodiments 1 to 3 and selected in Embodiment 4.

[0209] First, the acquisition of reaction process data for a sample containing an unknown concentration of the analyte will be described. The reagent bottle for this project is placed on reagent tray 106, and the sample is placed on sample tray 103. Then, a sample measurement request is input via operation unit 122 or communication interface 124. The input is transmitted to data processing unit 121, which executes the sample measurement program stored in storage unit 121a, controlling the program's operation. The control program activates the control circuit, which in turn activates the drive unit, thereby performing action analysis on each mechanism. The specific analysis actions are the same as described in <Embodiment 1: Acquisition of Reaction Process Data for Calibration Curve Generation>, therefore, descriptions are omitted here. The acquired reaction process data is stored in storage unit 121a.

[0210] Next, the quantification of the concentration of the analyte is explained. The reaction process data, calibration curve data, and data analysis program are read from the storage unit 121a to the analysis unit 121b. From the reaction process data of the sample with an unknown concentration of the analyte, absorbance, scattered light intensity, or their changes are extracted based on the calculation points specified for each measurement item. The extracted data is compared with the light intensity data of the calibration curve to quantify the concentration of the analyte in the sample. The extracted data, the quantified concentration information, error information, etc., are stored in the storage unit 121a and displayed on the display unit 122a of the operation unit 122. Furthermore, as needed, in addition to printing via the printer 123, the data can be transmitted to the hospital's network via the communication interface 124. Here, an example is described of quantifying the concentration of the analyte in a sample using the analysis unit 121b in an automatic analysis device. However, the obtained reaction process data can also be read into other tools equipped with a calibration curve generation program like that in Embodiment 3, and the calibration curve data and sample measurement data can be compared in the tool to quantify the concentration of the analyte in the sample.

[0211] <Regarding variations of the present invention>

[0212] This invention is not limited to the embodiments described above, and includes various modifications. The embodiments described above are given in detail for the purpose of easily understanding and illustrating the invention, and are not limited to having all the described configurations. A portion of the configuration of one embodiment can be replaced with the configuration of another embodiment, and the configuration of another embodiment can be added to the configuration of one embodiment. In addition, for a portion of the configuration of each embodiment, the same configuration or other configurations can be added, deleted, or replaced.

[0213] In the above embodiments, taking the latex immunoturbidimetric assay as an example, it was explained that a latex reagent sensitized with antibodies or antigens was mixed with a standard solution containing the substance to be measured (antigen or antibody) or a sample from a living organism, and the latex agglutination reaction caused by the antigen-antibody reaction was measured by light absorption or light scattering. However, the test items measured in this invention are not limited to the latex immunoturbidimetric assay. For example, it could also be a system in which an insoluble carrier sensitized with antibodies or antigens (silica particles, magnetic particles, metal colloids, etc.) is mixed with a standard solution containing the substance to be measured (antigen or antibody) or a sample from a living organism, and the agglutination reaction of particles caused by the antigen-antibody reaction is measured by light absorption or light scattering.

[0214] In other words, as long as the reaction process data obtained by measuring the standard solution N (N≥2) with the highest concentration of the analyte in two or more (two concentration levels) standard solutions contains the reactions in the standard solutions with lower concentrations than the standard solution N, and the calibration curve generated based on the reaction process data of the standard solution N and the data for converting measurement points to concentrations is approximate to the calibration curve generated using the set of standard solutions (standard solutions 1 to N) (the difference between the two is within the threshold, and no error as described in Embodiment 4 occurs), then, in addition to the samples, test items, and standard solutions described in the above embodiments, the calibration curve generation method of the present invention can be applied.

[0215] In addition, it is not necessarily required to use the standard solution N. Even when using a standard solution (N−n) (n is an integer, 0 < n < N) with a concentration sufficient to extrapolate the reaction of the highest concentration of the analyte contained in the standard solution N to replace the standard solution N, as long as the reaction process data of the standard solution (N−n) contains the reactions in the standard solutions with lower concentrations than the standard solution (N−n), and furthermore, the reaction of the standard solution N can be extrapolated using this reaction process data, and the calibration curve generated based on the reaction process data of the standard solution (N−n) and the data for converting measurement points to concentrations is approximate to the calibration curve generated using the set of standard solutions (standard solutions 1 to N), the calibration curve generation method of the present invention can be applied to samples, test items, and standard solutions other than those described in the above embodiments.

[0216] Symbol Explanation

[0217] 100: Automatic analyzer, 101: Sample, 102: Sample cup, 103: Sample tray, 104: Reagent, 105: Reagent bottle, 106: Reagent tray, 107: Reaction solution, 108: Unit, 109: Reaction tray, 110: Sample 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.

Claims

1. A calibration curve generation method characterized by, A calibration curve is generated in an automated analytical device that quantifies the concentration of the analyte contained in a sample. During the generation of a single calibration curve, the calibration curve generation method has the following characteristics: The step of determining the reaction process of the analyte within the single standard solution by irradiating light with a mixture containing only one standard solution of non-zero concentration and a reagent that reacts with the analyte. The step of extracting calibration data from a line obtained by fitting reaction process data representing the reaction process of the analyte in the one standard solution, wherein the calibration data consists of multiple light intensity data at multiple different times, and The step of generating the calibration curve representing the relationship between the concentration and the light intensity data by converting the multiple different times into multiple concentrations of the substance being measured.

2. The calibration curve generation method according to claim 1, characterized by, The step of converting the multiple different times into multiple concentrations of the substance being measured includes: The step of generating photometric point-concentration conversion data, wherein the photometric point-concentration conversion data represents the relationship between photometric points from which multiple photometric data are extracted from the fitted line and the concentration of the substance being measured, wherein the multiple photometric data are photometric data equivalent to calibration data of a standard solution group consisting of multiple known concentrations, and The step of converting the time to the concentration using the generated photometric point-concentration conversion data.

3. The calibration curve generation method according to claim 2, characterized in that, The concentration of the single standard solution corresponds to the concentration of the most concentrated standard solution in the standard solution group.

4. The calibration curve generation method according to claim 2, characterized in that, The concentration of the one standard solution corresponds to the concentration of the standard solution other than the highest concentration in the standard solution group. The calibration data of the highest concentration standard solution is generated by extrapolating the reaction process data of the one standard solution.

5. The calibration curve generation method according to claim 2, characterized in that, The concentration of the one standard solution corresponds to the concentration of any standard solution in the standard solution group. If they differ, the concentration of the one standard solution used when generating the calibration curve is used to correct the concentrations of all standard solutions in the standard solution group.

6. The calibration curve generation method according to claim 2, characterized in that, In the step of converting the multiple different times into multiple concentrations of the substance being measured, the additionally obtained photometric point-concentration conversion data is read out to the automatic analysis device for use.

7. The calibration curve generation method according to claim 6, characterized in that, The data used for photometric point-concentration conversion is stored in an external storage medium.

8. The calibration curve generation method according to claim 2, characterized in that, In the step of converting the multiple different times into multiple concentrations of the substance being measured, the photometric point-concentration conversion data input on the user interface is used.

9. The calibration curve generation method according to claim 2, characterized in that, For the light intensity data of the plurality of light intensity data that are equivalent to the standard solution with zero concentration of the substance being measured, the light intensity data are obtained by actual measurement of the standard solution with zero concentration.

10. The calibration curve generation method according to claim 1, characterized in that, The calibration curve is generated using a tool independent of the automated analysis device.

11. The calibration curve generation method according to claim 1, characterized in that, have: The generated calibration curve is compared with previously obtained calibration curve data, and an error checking step is performed. If the error exceeds the threshold set in the error check, an error is reported for the generated calibration curve, and a screen is displayed showing whether to use it.

12. An automatic analysis device, characterized in that, have: A light irradiation unit that irradiates light onto a unit containing a mixture of a sample and reagents of unknown concentration. The measuring unit measures the light from the mixture, and The analysis unit, when generating a calibration curve, (1) measures the reaction process of the substance in the one standard solution by irradiating light onto a mixture containing only one standard solution with a non-zero concentration of the substance to be measured and a reagent that reacts with the substance; (2) extracts multiple light intensity data, i.e., calibration data, at multiple different times from a line obtained by fitting the reaction process data representing the reaction process of the substance in the one standard solution; and (3) uses a calibration curve representing the relationship between the concentration and the light intensity data generated by converting the multiple different times into multiple concentrations of the substance, and the light intensity data obtained from the reaction process data in the analysis unit to quantify the concentration of the sample.

13. The automatic analysis device according to claim 12, characterized in that, The calibration curve is stored in the storage unit of the automatic analysis device and read out by the analysis unit for quantifying the concentration of the analyte in the sample.

14. A computer program product for generating calibration curves, which causes a computer to perform a process for generating calibration curves in an automated analysis device that quantifies the concentration of a analyte contained in a sample, characterized in that the computer performs the following steps: The step of measuring the reaction process of the analyte within the single standard solution during calibration curve generation is to irradiate a mixture containing only one standard solution of non-zero concentration of the analyte and a reagent that reacts with the analyte. The step of extracting calibration data from a line obtained by fitting reaction process data, wherein the reaction process data represents the reaction process of the analyte in one standard solution, and the calibration data consists of multiple photometric data at multiple different times; and The step of generating the calibration curve representing the relationship between the concentration and the light intensity data by converting the multiple different times into multiple concentrations of the substance being measured.

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