Information processing device and information processing method

Abstract

In the present invention, a control device 4 is connected to a sensor module in which a plurality of electrochemical sensors are integrated, the electrochemical sensors measuring values pertaining to the concentrations of predetermined components in an inspection well and in a correction well. During calibration, the control device 4 acquires values measured by the electrochemical sensors in the inspection well and in the correction well, and during actual measurement, which is performed after the calibration, acquires values measured by the electrochemical sensors in the inspection well and in the correction well. The control device 4 generates a calibration curve at the time of the actual measurement on the basis of the values measured in the inspection well and the correction well during calibration and the values measured in the correction well during the actual measurement. The control device 4 derives the concentrations of said components in the inspection well during the actual measurement, on the basis of the values measured in the inspection well at the time of the actual measurement and the calibration curve at the time of the actual measurement.

Description

[Technical Field]

[0001] The present disclosure relates to data processing technology, and more particularly to an information processing device and an information processing method. [Background technology]

[0002] Electrochemical sensors are sometimes used to measure the state of chemical reactions such as glucose metabolism. Electrochemical sensors are characterized by their sensitivity changing over time due to the influence of the measurement environment and storage environment. Therefore, a correction coefficient is calculated in advance to reflect the change in sensitivity over time, and a calibration curve showing the relationship between the measurement value of a predetermined physical quantity obtained by the electrochemical sensor and the concentration of a predetermined component is corrected using the correction coefficient (see, for example, Patent Document 1). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Publication No. Hei 7-110333 Summary of the Invention [Problem to be solved by the invention]

[0004] The degree of change in sensitivity of electrochemical sensors varies depending on the environment, and preparing correction coefficients in advance to suit various environments requires extensive testing.

[0005] The present disclosure has been made in view of these problems, and one object of the present disclosure is to provide a technique for improving the accuracy of long-term measurements using electrochemical sensors. [Means for solving the problem]

[0006] In order to solve the above problem, an information processing device of one embodiment of the present disclosure is a device connected to a sensor module in which multiple electrochemical sensors that measure values ​​related to the concentration of a specified component in each of a test well and a correction well are integrated, and is equipped with a sensor value acquisition unit that acquires values ​​measured by the electrochemical sensors in each of the test wells and the correction wells during calibration when the concentration of the component in the test well is known, and acquires values ​​measured by the electrochemical sensors in each of the test wells and the correction wells during actual measurement after calibration when the concentration of the component in the test well is unknown; a calibration curve generation unit that generates a calibration curve for the actual measurement showing the relationship between the measurement value by the electrochemical sensor and the concentration of the component based on the values ​​measured in each of the test wells and the correction wells during calibration and the value measured in the correction well during the actual measurement; and a concentration derivation unit that derives the concentration of the component in the test well during the actual measurement based on the value measured in the test well during the actual measurement and the calibration curve for the actual measurement.

[0007] Another aspect of the present disclosure is also an information processing device, which is connected to a sensor module integrally configured with a plurality of electrochemical sensors that measure values ​​related to the concentrations of predetermined components in test wells and correction wells, and includes a sensor value acquisition unit that acquires values ​​measured by the electrochemical sensors in the test wells and correction wells during calibration when the concentrations of the components in the test wells are known, and acquires values ​​measured by the electrochemical sensors in the test wells and correction wells during actual measurement after calibration when the concentrations of the components in the test wells are unknown; The apparatus is equipped with a calibration curve generation unit that generates an initial calibration curve showing the relationship between the measurement value by the electrochemical sensor and the concentration of a component based on the value measured in the test well, a correction coefficient derivation unit that derives a correction coefficient related to the change in sensitivity of the electrochemical sensor over time from the time of calibration to the time of the main measurement based on the value measured in the correction well during calibration and the value measured in the correction well during the main measurement, and a concentration derivation unit that derives the concentration of the component in the test well during the main measurement based on the value measured in the test well during the main measurement corrected based on the correction coefficient and the initial calibration curve.

[0008] Yet another aspect of the present disclosure is an information processing method, in which an apparatus connected to a sensor module integrally configured with multiple electrochemical sensors that measure values ​​related to the concentrations of predetermined components in test wells and correction wells executes the following steps: acquiring values ​​measured by the electrochemical sensors in each of the test wells and the correction wells during calibration when the concentrations of the components in the test wells are known, acquiring values ​​measured by the electrochemical sensors in each of the test wells and the correction wells during actual measurement after the calibration when the concentrations of the components in the test wells are unknown, generating a calibration curve for the actual measurement that indicates the relationship between the values ​​measured by the electrochemical sensors and the concentrations of the components based on the values ​​measured in the test wells and the correction wells during calibration and the values ​​measured in the correction wells during the actual measurement, and deriving the concentrations of the components in the test wells during the actual measurement based on the values ​​measured in the test wells during the actual measurement and the calibration curve for the actual measurement.

[0009] Yet another aspect of the present disclosure is also an information processing method. This method involves a device connected to a sensor module that integrates multiple electrochemical sensors that measure values ​​related to the concentration of a predetermined component in each of a test well and a correction well. The device acquires values ​​measured by the electrochemical sensors in each of the test wells and the correction wells during calibration, when the concentration of the component in the test well is known, and acquires values ​​measured by the electrochemical sensors in each of the test wells and the correction wells during actual measurement, after calibration, when the concentration of the component in the test well is unknown. The device also performs the following steps: generating an initial calibration curve that shows the relationship between the measurement value by the electrochemical sensor and the concentration of the component based on the values ​​measured in the test wells during calibration; deriving a correction coefficient related to the change in sensitivity of the electrochemical sensor over time from calibration to actual measurement, based on the values ​​measured in the correction wells during calibration and the values ​​measured in the correction wells during actual measurement; and deriving the concentration of the component in the test well during actual measurement, based on values ​​obtained by correcting the values ​​measured in the test wells during actual measurement based on the correction coefficients and the initial calibration curve.

[0010] Any combination of the above components, or any conversion of the expression of the present disclosure between a system, a computer program, a recording medium on which a computer program is recorded, etc., is also valid as an aspect of the present disclosure. [Effects of the Invention]

[0011] The techniques disclosed herein can improve the accuracy of measurements over long periods of time using electrochemical sensors. [Brief explanation of the drawings]

[0012] [Figure 1] FIG. 1 is a diagram showing a measurement procedure using an electrochemical sensor. [Figure 2] FIG. 10 is a diagram showing an example of a calibration curve. [Figure 3]FIG. 10 is a diagram showing examples of conditions that affect the change in sensitivity of an electrochemical sensor over time, and examples of explanatory variables corresponding to each condition. [Figure 4] FIG. 1 is a diagram illustrating a configuration of an analysis system according to a first embodiment. [Figure 5] FIG. 5 is a diagram showing the appearance of the detector in FIG. 4. [Figure 6] FIG. 6 is a diagram showing details of the adapter unit of FIG. 5. [Figure 7] FIG. 6 is a diagram showing an example of the settings of the well plate in FIG. 5. [Figure 8] FIG. 2 is a block diagram showing functional blocks of the control device of the first embodiment. [Figure 9] FIG. 10 is a diagram showing an example of a blank information input screen. [Figure 10] FIG. 10 is a diagram illustrating an example of a blank placement screen. [Figure 11] FIG. 10 is a diagram illustrating an example of a group information input screen. [Figure 12] FIG. 10 is a diagram illustrating an example of a group arrangement screen. [Figure 13] FIG. 10 is a diagram showing an example of measurement results used to generate an initial calibration curve. [Figure 14] FIG. 10 is a diagram showing an example of an initial calibration curve. [Figure 15] FIG. 10 is a diagram showing an example of measurement results used to generate a calibration curve during actual measurement. [Figure 16] FIG. 10 is a diagram showing an example of a calibration curve during actual measurement. [Figure 17] FIG. 10 is a diagram showing an example of measurement results using a plurality of blanks REF and a plurality of blanks BKG. [Figure 18] FIG. 10 is a diagram showing an example of measurement results used to derive a correction coefficient. [Figure 19] FIG. 10 is a diagram showing an example of a calibration curve during actual measurement. [Figure 20] FIG. 10 is a block diagram showing functional blocks of a control device according to a third embodiment. [Figure 21] FIG. 10 is a diagram showing an example of deriving a glucose concentration from a sensor measurement value. [Figure 22] FIG. 10 is a diagram showing an example of a time series change in glucose response value. [Figure 23] FIG. 1 is a diagram showing an example of time-series changes in lactate response values. DETAILED DESCRIPTION OF THE INVENTION

[0013] The present disclosure will be described below with reference to preferred embodiments and drawings. The embodiments are illustrative and do not limit the present disclosure, and all features and combinations thereof described in the embodiments are not necessarily essential to the present disclosure. The same or equivalent components, parts, and processes shown in each drawing are designated by the same reference numerals, and redundant descriptions will be omitted where appropriate. The scale and shape of each part shown in each drawing are set for convenience to facilitate explanation and should not be interpreted as limiting unless otherwise specified. Furthermore, when terms such as "first" and "second" are used in this specification or claims, unless otherwise specified, these terms do not indicate any order or importance, but are intended to distinguish one configuration from another. Furthermore, some components that are not important for explaining the embodiments are omitted from each drawing.

[0014] First, an overview of the embodiment will be described. An electrochemical sensor (hereinafter referred to as an "electrochemical sensor") is sometimes used to measure the state of a chemical reaction such as glucose metabolism. FIG. 1 shows the procedure for measurement using an electrochemical sensor. The horizontal axis of FIG. 1 indicates the passage of time, and the vertical axis of FIG. 1 indicates the response value, which is the value measured by the electrochemical sensor. The response value of the electrochemical sensor is a current value corresponding to the concentration of a predetermined component (e.g., glucose, etc.).

[0015] Calibration is the process of determining the relationship between the known concentration of a specific component and the response value measured by an electrochemical sensor. Conventionally, the response value after stabilization is measured in each of the first calibration (Calibration A) and the second calibration (Calibration B). Then, after Calibration B, a main measurement is performed in which the concentration of the specific component is measured multiple times. In this measurement, the concentration of the specific component is unknown, and the concentration of the component is measured multiple times using a calibration curve based on the response values ​​measured in Calibrations A and B.

[0016] FIG. 2 shows an example of a calibration curve. A calibration curve is a graph showing the relationship between the response value measured by an electrochemical sensor and the concentration of a specific component. For example, the measurement result of calibration A (x smp,CalibA , y smp,calibA ) and the measurement result of calibration B (x smp,CalibB , y smp,calibB ) and create a graph connecting them as the calibration curve 100.

[0017] Electrochemical sensors have the characteristic that their sensitivity changes over time due to the influence of the measurement environment and storage environment. Conventionally, a method has been used in which conditions that affect the sensitivity change over time of an electrochemical sensor are identified in advance, a correction coefficient over time is obtained for each condition in advance, and the correction coefficient is used to reflect the change in sensitivity of the sensor. In the example of Figure 2, a predetermined correction coefficient is used to move the calibration curve 100 over time, for example, gradually making the slope of the calibration curve 100 gentler.

[0018] The following equation 1 shows an example of a regression equation for determining the correction coefficient Y as a response variable. Y = a1× X1+ a2× X2+ a3× X3+ + a i × X i + b...(Formula 1) X1, X2, . . ., X i are the conditions that affect the change in sensitivity of the electrochemical sensor over time, and are explanatory variables for the correction coefficient Y. a1, a2,..., ai is the weight of each explanatory variable.

[0019] Figure 3 shows examples of conditions that affect the change in sensitivity of an electrochemical sensor over time, and examples of explanatory variables corresponding to each condition. The conditions and explanatory variables are diverse, and a huge amount of testing is required to determine appropriate explanatory variables, weights, and correction coefficients for each environment. It is also difficult to obtain correction coefficients that reflect the influence of unknown (or unexpected) environments. Furthermore, the weights a of each condition i To know this, information on the history of the measurement and storage environments is required, but it is not always easy to obtain such information. Furthermore, as shown in Figure 1, in the past, the accuracy of concentration measurement could be reduced due to a drop in the response value until the temperature became stable immediately after the start of the experiment, or fluctuations in the response value caused by temperature changes due to opening and closing the door of the incubator 3, etc.

[0020] Therefore, in each embodiment of the present disclosure, a multiwell plate is provided with wells for sensitivity correction, and a calibration curve is sequentially generated or updated to reflect sensitivity changes in parallel with the actual measurement. Alternatively, a correction coefficient is sequentially derived to reflect sensitivity changes in parallel with the actual measurement. This improves the accuracy of long-term measurements using an electrochemical sensor.

[0021] First Embodiment 4 shows the configuration of the analysis system 1 of the first embodiment. The analysis system 1 includes an incubator 3 and a control device 4. A detector 2 is installed inside the incubator 3. The detector 2 detects the measurement results obtained by the electrochemical sensor.

[0022] The control device 4 is an information processing device that analyzes the measurement results obtained by the electrochemical sensor. The control device 4 is connected to the detector 2 via an electric cable 5, and is connected to a sensor module 14 (described below) via the detector 2. An electric signal indicating the measurement results obtained by the electrochemical sensor of the sensor module 14 is sent from the detector 2 to the control device 4 via the electric cable 5.

[0023] FIG. 5 shows the appearance of the detector 2 in FIG. 4. An adapter unit 10 is housed inside the detector 2. FIG. 6 shows the details of the adapter unit 10 in FIG. 5. The adapter unit 10 is configured by stacking a sensor module 14 on top of a well plate 12. The well plate 12 is a multi-well plate containing 24 wells. The sensor module 14 is a component integrally configured with 24 electrochemical sensors (hereinafter referred to as "sensors 16") that measure the concentrations of components in the 24 wells.

[0024] Each sensor 16 is immersed in the culture solution in the well and is used to measure the components contained in the culture solution. For example, the sensor 16 can be used to measure the concentration of a culture component such as glucose, or to measure the concentration of a metabolite such as lactic acid excreted from a culture of cells or the like.

[0025] The measurement principle of the sensor 16 will now be explained. In the well, an enzyme reacts specifically with glucose and lactic acid, oxidizing the glucose and lactic acid and generating electrons. The sensor 16 quantifies and measures the electrons in the well as a current value. The glucose concentration (or lactic acid concentration) in the well can be determined based on the current value measured by the sensor 16 and a calibration curve that defines the relationship between the current value measured by the sensor 16 and the glucose concentration (or lactic acid concentration).

[0026] As shown in FIG. 6, the sensor 16 of the first embodiment is a three-electrode type sensor, and has a structure in which a working electrode 18, a counter electrode 22, and a reference electrode 20 are provided at the tip of, for example, a long and narrow substrate. The sensor 16 also has two working electrodes 18. In this case, each working electrode 18 can measure the concentration of a different component (e.g., glucose and lactic acid). The number of working electrodes 18 may be one. Alternatively, the sensor 16 may be a two-electrode type having only a working electrode 18 and a counter electrode 22.

[0027] FIG. 7 shows an example of the configuration of the well plate 12 of FIG. 5. As mentioned above, the well plate 12 of the first embodiment includes 24 wells 102. In the well plate 12, groups of wells 102 are provided for each combination of the type of cell to be cultured and the type of culture medium. Group 1 in FIG. 7 is a group of cell A and culture medium A (glucose concentration Xa [mM], lactate concentration Ya [mM]). Group 2 is a group of cell A and culture medium B (glucose concentration Xb [mM], lactate concentration Yb [mM]). Group 3 is a group of cell B and culture medium B (glucose concentration Xb [mM], lactate concentration Yb [mM]). Xa and Xb may be different values, and Ya and Yb may be different values. The wells 102 in each group may also be referred to as test wells and hereinafter as "sample wells." Cell A may be, for example, Jurkat cells, and cell B may be, for example, NB4 cells.

[0028] The well plate 12 also has wells 102 containing only culture medium without cells (hereinafter also referred to as "blanks" or "blank wells"). Blanks can also be considered as correction wells, that is, wells for obtaining correction data to reflect changes in sensitivity of the electrochemical sensor. Blanks are provided for each type of culture medium. Blank A in Figure 7 corresponds to culture medium A and corresponds to group 1. Blank B corresponds to culture medium B and corresponds to groups 2 and 3. Each of blanks A and blank B includes a background well (hereinafter referred to as "BKG") and a reference well (hereinafter referred to as "REF").

[0029] The BKG of blank A is without cells and medium A (glucose concentration 0 [mM], lactate concentration 0 [mM]). The REF of blank A is without cells and medium A (glucose concentration X [mM], lactate concentration Y [mM]). The BKG of blank B is without cells and medium B (glucose concentration 0 [mM], lactate concentration 0 [mM]). The REF of blank B is without cells and medium B (glucose concentration X [mM], lactate concentration Y [mM]). The glucose concentration and lactate concentration of the REF of each blank may be determined to appropriate values ​​based on the experimenter's knowledge or experiments using the analysis system 1. In the first embodiment, as a suitable example of the glucose concentration of the REF, the same glucose concentration as that of the corresponding sample well is set.

[0030] Figure 8 is a block diagram showing the functional blocks of the control device 4 in Figure 4. Each block shown in the block diagram of the present disclosure can be realized in hardware terms by elements and mechanical devices such as a computer CPU and memory, and in software terms by a computer program, etc., but here, functional blocks realized by the cooperation of these elements are depicted. Those skilled in the art will understand that these functional blocks can be realized in various ways by combining hardware and software.

[0031] The control device 4 includes a data processing unit 30, a storage unit 32, a display unit 34, and a communication unit 36. The data processing unit 30 executes data processing related to the control of the experiment and data processing related to the analysis of the measurement results by the sensor module 14. The storage unit 32 stores data that is referenced or updated by the data processing unit 30.

[0032] The display unit 34 displays various information. The display unit 34 includes a touch panel and also functions as an input unit through which a user (experimenter) inputs operations. The communication unit 36 ​​communicates with external devices according to a predetermined communication protocol. The data processing unit 30 is connected to the detector 2 (sensor module 14) via the communication unit 36.

[0033] The memory unit 32 includes an experimental condition memory unit 40 and an experimental result memory unit 42. The experimental condition memory unit 40 stores data on experimental conditions set by the user. The experimental result memory unit 42 stores data on experimental results in the analysis system 1. The experimental result data stores the concentration of a predetermined component in each well of the well plate 12 based on the measurement results using the electrochemical sensor. In the first embodiment, the component whose concentration is measured is glucose, but the technology of the first embodiment can also be applied to cases where the concentration of another component whose concentration can be measured using an electrochemical sensor is the measurement target. The other component may be, for example, lactic acid or glutamine.

[0034] The data processing unit 30 includes an operation reception unit 44, an experiment condition setting screen generation unit 46, a display control unit 48, an experiment control unit 50, a sensor value acquisition unit 52, a calibration curve generation unit 54, a concentration derivation unit 58, and an analysis unit 60. The functions of at least some of these multiple functional blocks may be implemented in a computer program (hereinafter also referred to as an "experiment support program"). The experiment support program may be installed in the storage of the control device 4 via a recording medium or a network. The processor (CPU, etc.) of the control device 4 may perform the functions of the multiple functional blocks by reading the experiment support program from the storage to main memory and executing it.

[0035] The operation receiving unit 44 receives operations input by the user to the display unit 34. The experimental condition setting screen generating unit 46 generates data for a screen (hereinafter also referred to as the "experimental condition setting screen") on which the user sets experimental conditions for the analysis system 1. The display control unit 48 displays the experimental condition setting screen generated by the experimental condition setting screen generating unit 46 on the display unit 34. The experiment control unit 50 proceeds with an experiment in the analysis system 1, including cell culture in the well plate 12, in accordance with the experimental conditions stored in the experimental condition storage unit 40.

[0036] During calibration when the glucose concentration in the sample well is known, the sensor value acquiring unit 52 acquires from the detector 2 the current values ​​measured by the sensor 16 in each of the sample wells and the blank wells corresponding to the sample wells. Furthermore, during actual measurement after calibration when the glucose concentration in the sample well is unknown, the sensor value acquiring unit 52 acquires from the detector 2 the current values ​​measured by the sensor 16 in each of the sample wells and the blank wells corresponding to the sample wells.

[0037] The calibration curve generating unit 54 generates a calibration curve for the actual measurement based on the values ​​measured in the sample well and the blank well during calibration and the value measured in the blank well during the actual measurement. The calibration curve generating unit 54 includes a correction value deriving unit 56. As will be described in detail later, the correction value deriving unit 56 derives a correction value based on the change in sensitivity of the sensor 16 over time in order to generate the calibration curve for the actual measurement.

[0038] The concentration derivation unit 58 derives the glucose concentration in the sample well during the main measurement based on the calibration curve during the main measurement generated by the calibration curve generation unit 54 and the value measured in the sample well during the main measurement. The concentration derivation unit 58 stores the experiment result data including the glucose concentration in the sample well during the main measurement in the experiment result storage unit 42.

[0039] The analysis unit 60 generates data for the analysis screen using the experimental result data stored in the experimental result storage unit 42. For example, the analysis unit 60 may generate an analysis screen including a concentration transition graph with time on the horizontal axis and glucose concentration on the vertical axis. The concentration transition graph may be a graph showing the time series transition of glucose concentration for each well, or may be a graph showing the time series transition of average glucose concentration for each group.

[0040] The operation of the analysis system 1 configured as above will now be described. The user starts the experiment support program on the control device 4. The experiment condition setting screen generation unit 46 of the control device 4 generates data for the experiment condition setting screen, and the display control unit 48 of the control device 4 displays the experiment condition setting screen on the display unit 34. The experiment condition setting screen of the first embodiment includes a blank information input screen 110, a blank placement screen 112, a group information input screen 114, and a group placement screen 116, which transition in this order.

[0041] 9 shows an example of a blank information input screen 110. The blank information input screen 110 is a screen for inputting information about a blank well (blank A in FIG. 9). The user inputs the glucose concentration and lactate concentration of a reference blank well into the blank information input screen 110.

[0042] 10 shows an example of a blank placement screen 112. The blank placement screen 112 is a screen for placing blank wells in wells in the well plate 12. In FIG. 10, on the blank placement screen 112, the user places each of BKG and REF of blank A in at least one of the 24 wells in the well plate 12.

[0043] 11 shows an example of a group information input screen 114. The group information input screen 114 is a screen for inputting information about a group well (group 1 in FIG. 11). The user sets a blank (blank A in FIG. 11) to be used for temporal correction in area 130. The user also sets the glucose concentration and lactate concentration of the solution to be used in calibration A, which is the first calibration, and the glucose concentration and lactate concentration of the solution to be used in calibration B, which is the second calibration, in area 132.

[0044] 12 shows an example of the group arrangement screen 116. The group arrangement screen 116 is a screen for arranging sample wells of each group in wells in the well plate 12. In FIG. 12, on the group arrangement screen 116, the user arranges the sample wells of group 1 in at least one of the 24 wells in the well plate 12. As shown in FIG. 7, the user can arrange multiple groups (e.g., groups 1 to 3) in the well plate 12, and can also arrange multiple blanks (e.g., blanks A and B) in the well plate 12.

[0045] The operation reception unit 44 of the control device 4 receives the experimental conditions input by the user on the experimental condition setting screens (including the blank information input screen 110, blank arrangement screen 112, group information input screen 114, and group arrangement screen 116). The experimental condition storage unit 40 of the control device 4 stores the experimental conditions input on the experimental condition setting screens.

[0046] The experiment control unit 50 of the control device 4 executes an automatic culture process in the well plate 12 in cooperation with a pump unit (not shown) and the like, in accordance with the experimental conditions stored in the experimental condition storage unit 40. The automatic culture process may include automatic culture medium replacement for each well of the well plate 12. In the automatic culture process of the first embodiment, calibration A (20 hours or more), calibration B (20 hours or more), and main measurement (approximately 10 days) are executed in this order. The automatic culture process may be realized using known technology.

[0047] During each of the periods for calibration A, calibration B, and main measurement, each sensor 16 of the sensor module 14 measures a current value periodically (at one-minute intervals in the first embodiment). The detector 2 sequentially transmits the current values ​​measured by each sensor 16 of the sensor module 14 to the control device 4. The sensor value acquisition unit 52 of the control device 4 acquires the current values ​​(response values) measured by each sensor 16 of the sensor module 14 and transmitted from the detector 2. The calibration curve generation unit 54 of the control device 4 generates an initial calibration curve based on the current values ​​measured in the sample wells during calibration A and calibration B.

[0048] FIG. 13 shows an example of measurement results used to generate an initial calibration curve. In FIG. 13, the measurement results of the blank REF, the sample well, and the blank BKG are shown in descending order of response value. This also applies to subsequent figures showing measurement results. In the first embodiment, the correction value derivation unit 56 of the calibration curve generation unit 54 derives a correction value (the third point in FIG. 13) obtained by correcting the value measured in the sample well during calibration A based on the current value measured in the blank well during calibration A and the current value measured in the blank well during calibration B, so as to reflect the change in sensitivity of the sensor 16 over time from calibration A to calibration B.

[0049] Specifically, the correction value derivation unit 56 calculates the correction value y^ according to Equation 2. smp,CalibA is derived.

number

[0050] FIG. 14 shows an example of an initial calibration curve. The calibration curve generating unit 54 generates an initial calibration curve 120 based on the current value measured in the sample well during calibration B (the second point in FIG. 13) and the correction value derived according to Equation 2 (the third point in FIG. 13). In the first embodiment, the calibration curve generating unit 54 further generates an initial calibration curve 120 based on the current value measured in the blank BKG during calibration B (the first point (0, y blk BKG,CalibB )) to generate the initial calibration curve 120. For example, the calibration curve generating unit 54 may use a known curve fitting to derive, as the initial calibration curve 120, an approximation curve for the current value measured in the blank BKG during calibration B (the first point in FIG. 13 ), the current value measured in the sample well during calibration B (the second point in FIG. 13 ), and the correction value derived according to Equation 2 (the third point in FIG. 13 ).

[0051] As a modified example, a configuration without a blank BKG may be used. In this case, the calibration curve generating unit 54 may derive, as the initial calibration curve 120, an approximation curve for a predetermined value (e.g., the origin (0 nA, 0 mM)), the current value measured in the sample well during calibration B (the second point in FIG. 13), and the correction value derived according to Equation 2 (the third point in FIG. 13).

[0052] In FIG. 14, a graph of a quadratic function (y = ax 2 + bx + c). The initial calibration curve may be a linear function, or a cubic or higher order function. The same applies to calibration curves other than the initial calibration curve.

[0053] As a variant, the calibration curve generating unit 54 may generate the initial calibration curve 120 based on a pair of current values ​​and glucose concentrations measured in the sample wells during calibration A, and a pair of current values ​​and glucose concentrations measured in the sample wells during calibration B, as described in relation to Figures 1 and 2.

[0054] When the current values ​​measured in the sample well and the blank well during the main measurement are acquired by the sensor value acquiring unit 52, the calibration curve generating unit 54 generates a calibration curve during the main measurement (hereinafter also referred to as the "main measurement calibration curve"). In other words, the calibration curve generating unit 54 generates a new main measurement calibration curve for determining the glucose concentration at the time of the current measurement each time the main measurement result is acquired. As described above, in the first embodiment, the main measurement result is acquired at one-minute intervals. Therefore, the calibration curve generating unit 54 updates the main measurement calibration curve at one-minute intervals.

[0055] 15 shows an example of measurement results used to generate a calibration curve during the actual measurement. The correction value derivation unit 56 of the calibration curve generation unit 54 derives a first correction value (the third point in FIG. 15) that is a value obtained by correcting the value measured in the sample well during calibration A so as to reflect changes in the sensitivity of the sensor 16 over time from calibration A to the actual measurement, based on the value measured in the blank well during calibration and the value measured in the blank well during the actual measurement.

[0056] In the first embodiment, when deriving the first correction value, the correction value derivation unit 56 uses the value measured in the blank well during calibration A and the value measured in the blank well during the main measurement. That is, based on the value measured in the blank well during calibration A and the value measured in the blank well during the main measurement, the correction value derivation unit 56 derives the first correction value by correcting the value measured in the sample well during calibration A so as to reflect the change in sensitivity of the sensor 16 over time from calibration A to the main measurement.

[0057] Specifically, the correction value derivation unit 56 calculates the first correction value y^ according to Equation 3. smp,CalibA is derived.

number

[0058] In addition, the correction value derivation unit 56 derives a second correction value (the second point in Figure 15), which is a value obtained by correcting the value measured in the sample well during calibration B based on the value measured in the blank well during calibration and the value measured in the blank well during the actual measurement to reflect the change in sensitivity of the sensor 16 over time from calibration B to the actual measurement.

[0059] In the first embodiment, the correction value derivation unit 56 derives a second correction value by correcting the value measured in the sample well during calibration B based on the value measured in the blank well during calibration B and the value measured in the blank well during the actual measurement, to reflect the change in sensitivity of the sensor 16 over time from calibration B to the actual measurement.

[0060] Specifically, the correction value derivation unit 56 calculates the second correction value y^ according to Equation 4. smp,CalibB is derived.

number

[0061] FIG. 16 shows an example of a calibration curve during actual measurement. The calibration curve generating unit 54 generates a calibration curve 122 during actual measurement based on the first and second correction values ​​derived by the correction value deriving unit 56. In the first embodiment, the calibration curve generating unit 54 further generates a current value measured in the blank BKG during actual measurement (the first point (0, y in FIG. 15 )). blk BKG,i 15)) to generate the calibration curve 122 during the main measurement. For example, the calibration curve generating unit 54 may use a known curve fitting to derive the calibration curve 122 during the main measurement as an approximation curve for the current value measured in the blank BKG during the main measurement (the first point in FIG. 15), the first correction value (the third point in FIG. 15), and the second correction value (the second point in FIG. 15).

[0062] The concentration deriving unit 58 of the control device 4 derives the glucose concentration of the sample well during the main measurement based on the current value measured in the sample well during the main measurement, which is acquired by the sensor value acquiring unit 52, and the main measurement calibration curve generated by the calibration curve generating unit 54 when the measurement results were acquired. The concentration deriving unit 58 stores the experimental results, including sets of the current value, glucose concentration, and time (measurement time) measured in the sample well, as data for each of calibration A, calibration B, and the main measurement, in the experimental result storage unit 42. That is, the concentration deriving unit 58 stores the experimental results, including information indicating the time-series transition of the glucose concentration in the sample well, in the experimental result storage unit 42.

[0063] In addition, for the blank well, the concentration deriving unit 58 records the current value ratio to the current value after stabilization of calibration B. Specifically, the current value of the blank REF after stabilization of calibration B is calculated as A(= y blk REF ,CalibB ) and the blank REF current value during this measurement is B(= y blk REF ,Meas ), the density deriving unit 58 records B / A as the current value ratio of the blank REF. Also, the current value of the blank BKG after the calibration B has been stabilized is C(= ​​y blk BKG ,CalibB ), and the current value of the blank BKG during this measurement is D(= y blk BKG ,Meas), the concentration deriving unit 58 records D / C as the current value ratio of the blank BKG. The concentration deriving unit 58 stores the current value ratios of the blank REF and the blank BKG in the experiment result storage unit 42. Note that outliers of blank wells, which will be described later, may be determined using the current value ratios.

[0064] The analysis unit 60 of the control device 4 generates data for an analysis screen based on the experiment result data stored in the experiment result storage unit 42 in response to a user operation input to the display unit 34. The display control unit 48 of the control device 4 causes the display unit 34 to display the data for the analysis screen.

[0065] In the analysis system 1 of the first embodiment, the blank wells (BKG and REF) are set in the same medium as the sample wells, and therefore have the same components and temperature effects as the sample wells. Furthermore, because multiple sensors 16 (electrochemical sensors) are integrated into the sensor module 14, the multiple sensors 16 share the same manufacturing lot, storage environment, and measurement environment. In the analysis system 1 of the first embodiment, the calibration curve is sequentially updated to reflect changes in the sensitivity of the sensor 16 over time based on the behavior of the blank wells over time. This improves the accuracy of measurements over long periods using electrochemical sensors. For example, it can absorb the decrease in response value until the temperature adjusts immediately after the start of an experiment, the fluctuation in response value due to temperature changes caused by opening and closing the incubator door, and the deterioration in sensitivity of the electrochemical sensor. Furthermore, it eliminates the need for prior verification of correction coefficients or acquisition of explanatory variable values.

[0066] Furthermore, in the analysis system 1 of the first embodiment, the actual measurement calibration curve 122 is generated based on a first correction value obtained by correcting the value measured in the sample well during calibration A to reflect the change in sensitivity of the sensor 16 over time from calibration A to the actual measurement, and a second correction value obtained by correcting the value measured in the sample well during calibration B to reflect the change in sensitivity of the sensor 16 over time from calibration B to the actual measurement. This makes it possible to improve the measurement accuracy during the actual measurement using the actual measurement calibration curve 122 that reflects the change in sensitivity of the electrochemical sensor. Furthermore, by deriving the first correction value based on the value measured in the blank well during calibration A and the value measured in the blank well during the actual measurement, it is possible to obtain the actual measurement calibration curve 122 that accurately reflects the change in sensitivity since calibration A.

[0067] The present disclosure has been described above based on the first embodiment. The first embodiment is merely an example, and it will be understood by those skilled in the art that various modifications are possible to the combination of each component or each treatment process of the first embodiment, and that such modifications are also within the scope of the present disclosure.

[0068] A modified example of the first embodiment will be described. When deriving the first correction value, the correction value derivation unit 56 may use the value measured in the blank well during calibration B and the value measured in the blank well during the main measurement. That is, the correction value derivation unit 56 may derive the first correction value by correcting the value measured in the sample well during calibration A so as to reflect the change in sensitivity of the sensor 16 over time from calibration A to the main measurement, based on the value measured in the blank well during calibration B and the value measured in the blank well during the main measurement. Specifically, the denominator of Equation 3 may be changed to (y blk REF,CalibA -y blk BKG,CalibA ) to (y blk REF,CalibB -y blk BKG,CalibB ) may be changed to

[0069] Some electrochemical sensors have unstable measurement values ​​until a certain amount of time has passed since the start of the experiment. Therefore, by deriving the first correction value using the value measured in the blank well during calibration B, when the measurement value of the electrochemical sensor is relatively stable, as in this modified example, it is possible to suppress a decrease in the accuracy of the first correction value even when using an electrochemical sensor whose measurement value becomes unstable until a certain amount of time has passed since the start of the experiment, and to obtain an actual measurement calibration curve 122 that accurately reflects the change in sensitivity since calibration A.

[0070] Another modified example of the first embodiment will be described. If the value measured in the blank well is an outlier, the calibration curve generating unit 54 of the control device 4 may exclude the value measured in the blank well to generate the calibration curve 122 for the actual measurement. An outlier can also be said to be a value that deviates from the normal range. Whether the value measured in the blank well is an outlier may be determined by the user, or may be determined autonomously by the control device 4 based on predetermined reference data.

[0071] For example, after the entire period of this measurement is completed, the analysis unit 60 may generate data for an analysis screen including a screen element (e.g., a GUI object) that allows the user to designate the sensor 16 in each well of the well plate 12 as the sensor 16 that measured an outlier (hereinafter also referred to as an "outlier sensor"). The user may look at the concentration transition graph displayed on the analysis screen and designate the sensor 16 of the sample well whose concentration or current value is an abnormal value as the outlier sensor.

[0072] Furthermore, the analysis unit 60 may generate data for an analysis screen including a graph showing the time series transition of the current value ratio of the blank REF stored in the experiment result storage unit 42 and a graph showing the time series transition of the current value ratio of the BKG stored in the experiment result storage unit 42. The user may check the transition of the current value ratio of the blank REF displayed on the analysis screen and designate the sensor 16 of the blank REF as an outlier sensor. The user may check the transition of the current value ratio of the blank BKG displayed on the analysis screen and designate the sensor 16 of the blank BKG as an outlier sensor.

[0073] The control device 4 may further include an outlier detection unit (not shown). The outlier detection unit may detect, as an outlier sensor, a sensor 16 in which a current value measured deviates from a predetermined normal range, among the sensors 16 in each well of the well plate 12. Alternatively, the outlier detection unit may detect, as an outlier sensor, a sensor 16 in which a concentration derived based on a measured current value deviates from a predetermined normal range, among the sensors 16 in each well of the well plate 12.

[0074] Furthermore, the outlier detection unit may detect the blank REF sensor 16 as an outlier sensor if the current value ratio of the blank REF stored in the experiment result storage unit 42 deviates from a predetermined normal range. Furthermore, the outlier detection unit may detect the blank BKG sensor 16 as an outlier sensor if the current value ratio of the blank BKG stored in the experiment result storage unit 42 deviates from a predetermined normal range. Hereinafter, when simply referring to an outlier sensor, this includes an outlier sensor designated by the user on the analysis screen and an outlier sensor detected by the outlier detection unit.

[0075] If the outlier sensor is the sensor 16 that measures the sample well, the analysis unit 60 may exclude information based on the measurement value of the outlier sensor (for example, a graph showing the time series change in glucose concentration) from being displayed on the analysis screen. In other words, the analysis unit 60 may hide information based on the measurement value of the outlier sensor on the analysis screen.

[0076] On the other hand, if the outlier sensor is the sensor 16 that measures a blank well, the calibration curve generating unit 54 may recalculate the initial calibration curve 120 and the main measurement calibration curve 122. The concentration deriving unit 58 may use the recalculated main measurement calibration curve 122 to re-derive the glucose concentration in the sample well at each time point during the main measurement period.

[0077] A processing example will be described in which the outlier sensor is the sensor 16 that measures a blank well. When the sensor 16 that measures a blank BKG is an outlier sensor, the calibration curve generating unit 54 may set the current value measured by the blank BKG to 0 and recalculate the initial calibration curve 120 and the calibration curve 122 during main measurement.

[0078] If the sensor 16 measuring the blank REF is an outlier sensor, the calibration curve generating unit 54 may change its processing depending on whether one or more valid sensors 16 measuring the blank REF remain, excluding the outlier sensor. If one or more valid sensors 16 measuring the blank REF remain, the calibration curve generating unit 54 may exclude the measurement value of the outlier sensor and recalculate the initial calibration curve 120 and the calibration curve 122 during the actual measurement using the measurement value of the valid sensor 16 measuring the blank REF. Note that if multiple valid sensors 16 measuring the blank REF remain, the calibration curve generating unit 54 may recalculate the initial calibration curve 120 and the calibration curve 122 during the actual measurement using the average values ​​of the measurement values ​​of the multiple valid sensors 16.

[0079] If the valid sensor 16 measuring the blank REF becomes 0, the temporal correction process may be stopped. For example, the calibration curve generating unit 54 may stop generating the calibration curve 122 during the actual measurement. The calibration curve generating unit 54 may also generate an initial calibration curve 120 based on a pair of the current value and glucose concentration measured in the sample well during calibration A and a pair of the current value and glucose concentration measured in the sample well during calibration B. The concentration deriving unit 58 may use the initial calibration curve 120 to derive the glucose concentration during the actual measurement.

[0080] According to this modified example, after the entire measurement period is completed or during the measurement, a sensor in which an abnormality is detected can be set as an outlier sensor and the concentration can be recalculated, thereby further improving the accuracy of the concentration measurement.

[0081] The following describes the process when multiple blank wells corresponding to one sample group are provided. Figure 17 shows an example of measurement results for multiple blank wells. As an example, Figure 17 shows measurement results for three blank REFs and measurement results for two blank BKGs. When multiple blank REFs and / or multiple blank BKGs corresponding to one group are provided as in Figure 17, the correction value derivation unit 56 derives the average value of the values ​​calculated for each blank as the correction value or correction coefficient.

[0082] Below, we will explain a specific example of deriving correction values ​​or correction coefficients when multiple blanks REF and / or multiple blanks BKG are provided corresponding to one group. Here, we will assume that the number of blanks REF is n and the number of blanks BKG is m.

[0083] The correction value derivation unit 56 of the calibration curve generation unit 54 calculates the correction value y^ used to generate the initial calibration curve. smp,CalibA is derived according to Equation 2'.

number

[0084] The correction value derivation unit 56 also calculates the first correction value y^ used to generate the calibration curve during the actual measurement. smp,CalibA is derived according to Equation 3'.

number

[0085] The correction value derivation unit 56 also calculates the second correction value y^ used to generate the calibration curve during the actual measurement. smp,CalibBis derived according to Equation 4'.

number

[0086] Second Embodiment The second embodiment will be described focusing on the differences from the first embodiment, and a description of the commonalities will be omitted. The features of the second embodiment can, of course, be arbitrarily combined with the features of the other embodiments and modifications. In the second embodiment, the initial calibration curve is updated sequentially to reflect the change in sensitivity of the sensor 16 over time.

[0087] The configuration of the analysis system 1 of the second embodiment is the same as the configuration of the analysis system 1 of the first embodiment shown in Fig. 4. Furthermore, the functional blocks of the control device 4 of the second embodiment are the same as the functional blocks of the control device 4 of the first embodiment shown in Fig. 8.

[0088] The correction value derivation unit 56 of the calibration curve generation unit 54 of the control device 4 derives a correction coefficient for the change in sensitivity of the sensor 16 over time from the time of calibration to the time of the actual measurement, based on the value measured in the blank well during calibration and the value measured in the blank well during the actual measurement.

[0089] 18 shows an example of measurement results used to derive the correction coefficient. In the second embodiment, the correction value derivation unit 56 derives the sensitivity of the sensor 16 at the end of calibration B (hereinafter also referred to as "initial sensitivity") based on the measurement values ​​of the blank REF and blank BKG. In addition, the correction value derivation unit 56 derives the sensitivity of the sensor 16 at an arbitrary time t i The sensitivity of the sensor 16 (hereinafter referred to as "t i (also called "time sensitivity").

[0090] Specifically, the correction value derivation unit 56 calculates the correction coefficient k corr,i is derived.

number

[0091] As a modified example, a blank BKG may not be set in the well plate 12. In this case, the correction value derivation unit 56 calculates the correction coefficient k based on the ratio of the measurement values ​​of the blank REF. corr,i Specifically, the denominator on the right side of Equation 5 can be calculated by y blk REF,CalibB The numerator on the right side is y blk REF,i It may also be possible to use the following.

[0092] 19 shows an example of the calibration curve during the actual measurement. The calibration curve generating unit 54 calculates the correction coefficient k corr,i By correcting the initial calibration curve 120 based on i In FIG. 19, the initial calibration curve 120 is an example of a quadratic function, and the calibration curve generating unit 54 adds a correction coefficient k corr,i The calibration curve 122 for the actual measurement is generated by multiplying the y-intercept by the time t i Alternatively, when a blank BKG is not set, the origin (0 nA, 0 mM) may be used.

[0093] Thereafter, as in the first embodiment, the concentration deriving unit 58 of the control device 4 derives the glucose concentration in the sample well during the main measurement using the main measurement calibration curve 122. Note that the correction value deriving unit 56 calculates a new t i The time sensitivity is derived and a new correction coefficient k corr,i The calibration curve generating unit 54 derives a new correction coefficient k corr,i Each time a new calibration curve 122 is derived, a new calibration curve 122 is generated.

[0094] The analysis system 1 of the second embodiment also achieves the same effects as the analysis system 1 of the first embodiment. For example, the analysis system 1 of the second embodiment can improve the accuracy of long-term measurements using an electrochemical sensor. Furthermore, there is no need to verify correction coefficients or the like in advance or to obtain values ​​of explanatory variables.

[0095] Furthermore, in the analysis system 1 of the second embodiment, the initial calibration curve 120 is successively updated to reflect changes in sensitivity of the sensor 16 over time, thereby generating the calibration curve 122 during actual measurement. However, in the analysis system 1 of the second embodiment, as in the first embodiment, the initial calibration curve 120 is generated using a corrected value to reflect changes in sensitivity of the sensor 16 over time from calibration A to calibration B. This can improve the accuracy of the initial calibration curve 120, and can also improve the accuracy of the calibration curve 122 during actual measurement, which is based on the initial calibration curve 120.

[0096] The present disclosure has been described above based on the second embodiment. The second embodiment is merely an example, and it will be understood by those skilled in the art that various modifications are possible in the combination of each component or each treatment process of the second embodiment, and that such modifications are also within the scope of the present disclosure.

[0097] A modification of the second embodiment will be described. When a value measured in a blank well is an outlier, the calibration curve generating unit 54 of the control device 4 may exclude the value measured in the blank well to generate the calibration curve 122 during the main measurement. The difference from the modification of the first embodiment is that when recalculating the calibration curve 122 during the main measurement, the correction value deriving unit 56 excludes the measurement result from the outlier sensor and calculates the correction coefficient k corr,i The calibration curve generating unit 54 recalculates the correction coefficient k corr,i The calibration curve 122 is recalculated using the above formula.

[0098] The above-described process when multiple blank wells corresponding to one sample group are provided can also be applied to the second embodiment. Specifically, the correction value derivation unit 56 of the calibration curve generation unit 54 calculates the correction value y^ used to generate the initial calibration curve.smp,CalibA is derived according to the above equation 2'.

[0099] Furthermore, the correction value derivation unit 56 calculates the correction coefficient k corr,i is derived.

number

[0100] <Third embodiment> The third embodiment will be described focusing on the differences from the first embodiment, and a description of the commonalities will be omitted. The features of the third embodiment can, of course, be combined with the features of the other embodiments and modifications. In the third embodiment, the measurement value of the sensor 16 is corrected using the same correction coefficient as in the second embodiment to reflect the change in sensitivity of the sensor 16 over time.

[0101] The configuration of the analysis system 1 of the third embodiment is the same as the configuration of the analysis system 1 of the first embodiment shown in Fig. 4. Fig. 20 is a block diagram showing the functional blocks of the control device 4 of the third embodiment. The control device 4 of the third embodiment further includes a correction coefficient derivation unit 62 in addition to the functional blocks included in the control device 4 of the first embodiment.

[0102] The correction coefficient derivation unit 62 of the control device 4 derives a correction coefficient for the change in sensitivity of the sensor 16 over time from the time of calibration to the time of the actual measurement, based on the value measured in the blank well during calibration and the value measured in the blank well during the actual measurement. Specifically, the correction coefficient derivation unit 62 calculates the correction coefficient k corr,i is derived.

[0103] The concentration deriving unit 58 of the control device 4 calculates the initial calibration curve 120 generated by the calibration curve generating unit 54 described in the first embodiment and the value measured in the sample well during the actual measurement using a correction coefficient k corr,iThe glucose concentration in the sample well during the actual measurement is calculated based on the value corrected based on the above.

[0104] The correction coefficient derivation unit 62 calculates a new correction coefficient k corr,i Each time the result of the main measurement is acquired, the concentration derivation unit 58 calculates the measured value of the result of the main measurement as a new correction coefficient k corr,i The corrected value is applied to the initial calibration curve 120 to derive the glucose concentration.

[0105] 21 shows an example of deriving the glucose concentration from the measurement value of the sensor 16. The concentration deriving unit 58 calculates the current value y measured by the sensor 16 in the sample well during the actual measurement. smp,i is the correction coefficient k corr,i By dividing by , the corrected value of the current value (y smp,i / k corr,i This correction value can also be said to be the current value obtained when the sensor 16 is at the initial sensitivity. The concentration deriving unit 58 obtains the correction value (y smp,i / k corr,i The concentration corresponding to this is calculated as the glucose concentration in the sample well during the measurement.

[0106] The analysis system 1 of the third embodiment also achieves the same effects as the analysis system 1 of the first embodiment. For example, the analysis system 1 of the third embodiment can improve the accuracy of long-term measurements using an electrochemical sensor. For example, in the example of FIG. 21, the glucose concentration can be determined with high accuracy by eliminating the influence of deterioration in sensitivity of the sensor 16 over time. Furthermore, there is no need to verify correction coefficients or the like in advance, or to obtain values ​​of explanatory variables.

[0107] Furthermore, in the analysis system 1 of the third embodiment, the component concentrations are derived by applying the corrected value of the current value measured by the sensor 16 to the initial calibration curve 120, but in the analysis system 1 of the third embodiment, as in the first embodiment, the initial calibration curve 120 is generated using a corrected value that reflects a change in sensitivity of the sensor 16 over time from calibration A to calibration B. This can improve the accuracy of the initial calibration curve 120, and can also improve the accuracy of the component concentrations derived using the initial calibration curve 120.

[0108] The present disclosure has been described above based on the third embodiment. The third embodiment is merely an example, and it will be understood by those skilled in the art that various modifications are possible in the combination of each component or each treatment process of the third embodiment, and that such modifications are also within the scope of the present disclosure.

[0109] A modification of the third embodiment will be described. When a value measured in a blank well is an outlier, the correction coefficient derivation unit 62 of the control device 4 excludes the value measured in the blank well and calculates the correction coefficient k corr,i As in the modified example of the first embodiment, whether the value measured in the blank well is an outlier may be determined by the user or may be determined autonomously by the control device 4 based on predetermined reference data.

[0110] The differences from the modified example of the first embodiment will be described below. When the sensor 16 measuring the blank BKG is an outlier sensor, the calibration curve generating unit 54 may recalculate the initial calibration curve 120 by setting the current value measured by the blank BKG to 0. The correction coefficient deriving unit 62 may calculate the correction coefficient k corr,i may be derived.

[0111] If the sensor 16 that measures the blank REF is an outlier sensor and one or more valid sensors 16 that measure the blank REF remain, the calibration curve generating unit 54 may exclude the measurement value of the outlier sensor and recalculate the initial calibration curve 120 using the measurement value of the valid sensor 16 that measures the blank REF. Similarly, the correction coefficient derivation unit 62 may exclude the measurement value of the outlier sensor and recalculate the initial calibration curve 120 using the measurement value of the valid sensor 16 that measures the blank REF. corr,i may be derived.

[0112] If the sensor 16 that measures the blank REF is an outlier sensor and the valid sensor 16 that measures the blank REF is 0, the correction coefficient derivation unit 62 calculates the correction coefficient k corr,i Alternatively, the calibration curve generating unit 54 may stop the derivation of the initial calibration curve 120 based on the pair of the current value and glucose concentration measured in the sample well during calibration A and the pair of the current value and glucose concentration measured in the sample well during calibration B. The concentration derivation unit 58 may use the initial calibration curve 120 to derive the glucose concentration during the main measurement.

[0113] According to this modified example, after the entire measurement period is completed or during the measurement, a sensor in which an abnormality is detected can be set as an outlier sensor and the concentration can be recalculated, thereby further improving the accuracy of the concentration measurement.

[0114] The above-described process when multiple blank wells corresponding to one sample group are provided can also be applied to the third embodiment. Specifically, the correction value derivation unit 56 of the calibration curve generation unit 54 calculates the correction value y^ used to generate the initial calibration curve. smp,CalibA The correction value derivation unit 56 derives the correction coefficient k corr,i is derived.

[0115] Another modified example will be described. This modified example is applicable to any of the above-described first to third embodiments. In both calibration A and calibration B, the sample well and the blank well (blank REF in this modified example) may contain solutions with the same component concentrations. For example, the solution contained in the sample well and the solution contained in the blank REF may have the same glucose concentration and the same lactate concentration. The solution may be a medium capable of culturing cultures such as cells.

[0116] FIG. 22 shows an example of the time series progression of the glucose response value. The glucose response value is a current value related to the glucose concentration in a solution. The solid line graph shows the progression of the glucose response value measured in the sample well, and the dashed line graph shows the progression of the glucose response value measured in the blank REF. During calibration A and calibration B, neither the sample well nor the blank REF contains a culture medium, such as cells. Therefore, the progression of the glucose response value measured in the sample well and the progression of the glucose response value measured in the blank REF are approximately the same.

[0117] In the example of Figure 22, during this measurement, the glucose concentrations in the sample well and blank REF are the same as during calibration B. Because the blank REF does not contain a culture of cells or the like, the glucose response value corresponding to the glucose concentration is basically constant. On the other hand, because the sample well contains a culture of cells or the like, the glucose response value corresponding to the glucose concentration decreases over time.

[0118] FIG. 23 shows an example of the time series progression of the lactate response value. The lactate response value is a current value related to the lactate concentration in a solution. The solid line graph shows the progression of the lactate response value measured in the sample well, and the dashed line graph shows the progression of the lactate response value measured in the blank REF. During calibration A and calibration B, neither the sample well nor the blank REF contains a culture of cells or the like, so the progression of the lactate response value measured in the sample well and the progression of the lactate response value measured in the blank REF are substantially identical.

[0119] During this measurement, the lactate concentration in the blank REF is the same as during calibration B. On the other hand, the lactate concentration in the sample well is set lower than during calibration B. Because the blank REF does not contain any cultured material such as cells, the lactate response value corresponding to the lactate concentration is basically constant. On the other hand, because the sample well contains cultured material such as cells, the lactate response value corresponding to the lactate concentration increases over time.

[0120] In each of the above-described embodiments, the calibration curve and correction coefficient are updated to reflect the change in sensitivity of the sensor 16 over time based on the behavior of the blank well over time. In this modification, the sensor 16 in the sample well and the sensor 16 in the blank REF are exposed to the same environment during calibration, thereby further improving the detection accuracy of the component concentration in the sample well during actual measurement. Furthermore, according to this modification, the sample well and the blank REF contain solutions with the same component concentration during calibration, reducing the number of solutions that the user needs to adjust and reducing the user's effort. Furthermore, according to this modification, when multiple blank REFs are provided, if an abnormality is detected in a sample well during calibration, the well used for the blank REF can be easily switched to the sample well.

[0121] In this modified example, during calibration, the sample well and the blank REF contain solutions with the same component concentrations, but this "same component concentration" may include a deviation in concentration within a predetermined allowable range.

[0122] Some or all of the functions provided in the control device 4 in the first to third embodiments described above may be provided in the detector 2. Furthermore, the functions provided in the control device 4 in the first to third embodiments described above may be distributed and implemented in multiple devices. The multiple devices may include the control device 4, the detector 2, and a server on the cloud.

[0123] Any combination of the above-described embodiments and modifications is also useful as an embodiment of the present disclosure. A new embodiment resulting from a combination combines the effects of the combined embodiments and modifications. It will also be understood by those skilled in the art that the functions to be performed by each component recited in the claims can be realized by each component shown in the embodiments and modifications, either individually or in combination.

[0124] The embodiment may be specified by the items described below. [Item 1] A device (4) connected to a sensor module (14) integrally configured with a plurality of electrochemical sensors (16) for measuring values ​​relating to the concentration of a predetermined component in each of a test well (102) and a correction well (102), a sensor value acquisition unit (52) that acquires values ​​measured by the electrochemical sensor (16) in each of the test well (102) and the correction well (102) during calibration when the concentration of the component in the test well (102) is known, and acquires values ​​measured by the electrochemical sensor (16) in each of the test well (102) and the correction well (102) during actual measurement after the calibration when the concentration of the component in the test well (102) is unknown; a calibration curve generating unit (54) that generates a calibration curve for the actual measurement that indicates the relationship between the measured value by the electrochemical sensor (16) and the concentration of the component based on the values ​​measured in the test well (102) and the correction well (102) during the calibration and the value measured in the correction well (102) during the actual measurement; a concentration deriving unit (58) that derives the concentration of the component in the test well (102) during the main measurement based on the value measured in the test well (102) during the main measurement and a calibration curve during the main measurement; An information processing device (4) comprising: [Item 2] the calibration curve generating unit (54) generates an initial calibration curve based on values ​​measured in the test wells (102) during the calibration; the calibration curve generating unit (54) derives a correction coefficient for a change in sensitivity of the electrochemical sensor (16) over time from the time of the calibration to the time of the main measurement, based on the value measured in the correction well (102) during the calibration and the value measured in the correction well (102) during the main measurement; the calibration curve generating unit (54) corrects the initial calibration curve based on the correction coefficient to generate a calibration curve for the main measurement. The information processing device (4) according to item 1. [Item 3] the calibration curve generating unit (54) derives a value obtained by correcting the value measured in the test well (102) during the first calibration based on the value measured in the correction well (102) during the first calibration and the value measured in the correction well (102) during the second calibration so as to reflect a change in sensitivity of the electrochemical sensor (16) over time from the first calibration to the second calibration; the calibration curve generating unit (54) generates the initial calibration curve based on the values ​​measured in the test wells (102) during the second calibration and the corrected values; The information processing device (4) according to item 2. [Item 4] the calibration curve generating unit (54) derives a first correction value, which is a value obtained by correcting the value measured in the test well (102) during the first calibration so as to reflect a change in sensitivity of the electrochemical sensor (16) over time from the first calibration to the main measurement, based on the value measured in the correction well (102) during calibration and the value measured in the correction well (102) during the main measurement; the calibration curve generating unit (54) derives a second correction value, which is a value obtained by correcting the value measured in the test well (102) during the second calibration based on the value measured in the correction well (102) during calibration and the value measured in the correction well (102) during the main measurement, so as to reflect a change in sensitivity of the electrochemical sensor (16) over time from the second calibration to the main measurement; the calibration curve generating unit (54) generates a calibration curve for the main measurement based on the first correction value and the second correction value. The information processing device (4) according to item 1. [Item 5] the calibration curve generating unit (54) uses a value measured in the correction well (102) during the second calibration and a value measured in the correction well (102) during the main measurement when deriving the first correction value; When deriving the second correction value, the calibration curve generating unit (54) uses a value measured in the correction well (102) during the second calibration and a value measured in the correction well (102) during the main measurement. Item 4. An information processing device (4) according to item 4. [Item 6] the calibration curve generating unit (54) uses a value measured in the correction well (102) during the first calibration and a value measured in the correction well (102) during the main measurement when deriving the first correction value; When deriving the second correction value, the calibration curve generating unit (54) uses a value measured in the correction well (102) during the second calibration and a value measured in the correction well (102) during the main measurement. Item 4. An information processing device (4) according to item 4. [Item 7] When the value measured in the correction well (102) is an outlier, the calibration curve generating unit (54) excludes the value measured in the correction well (102) and generates the calibration curve for the main measurement. 7. An information processing device (4) according to any one of items 1 to 6. [Item 8] A device (4) connected to a sensor module integrally configured with a plurality of electrochemical sensors (16) for measuring values ​​relating to the concentration of a predetermined component in each of a test well (102) and a correction well (102), a sensor value acquisition unit (52) that acquires values ​​measured by the electrochemical sensor (16) in each of the test well (102) and the correction well (102) during calibration when the concentration of the component in the test well (102) is known, and acquires values ​​measured by the electrochemical sensor (16) in each of the test well (102) and the correction well (102) during actual measurement after the calibration when the concentration of the component in the test well (102) is unknown; a calibration curve generating unit (54) that generates an initial calibration curve showing the relationship between the measurement value obtained by the electrochemical sensor (16) and the concentration of the component based on the value measured in the test well (102) during the calibration; a correction coefficient derivation unit (62) that derives a correction coefficient related to a change in sensitivity of the electrochemical sensor (16) over time from the time of the calibration to the time of the main measurement, based on a value measured in the correction well (102) during the calibration and a value measured in the correction well (102) during the main measurement; a concentration deriving unit (58) that derives the concentration of the component in the test well (102) during the main measurement based on a value obtained by correcting the value measured in the test well (102) during the main measurement using the correction coefficient and the initial calibration curve; An information processing device (4) comprising: [Item 9] the calibration curve generating unit (54) derives a value obtained by correcting the value measured in the test well (102) during the first calibration based on the value measured in the correction well (102) during the first calibration and the value measured in the correction well (102) during the second calibration so as to reflect a change in sensitivity of the electrochemical sensor (16) over time from the first calibration to the second calibration; the calibration curve generating unit (54) generates the initial calibration curve based on the values ​​measured in the test wells (102) during the second calibration and the corrected values; Item 8. The information processing device (4) according to item 8. [Item 10] When a value measured in the correction well (102) is an outlier, the correction coefficient derivation unit (62) excludes the value measured in the correction well (102) and derives the correction coefficient. 10. The information processing device (4) according to item 8 or 9. [Item 11] During the calibration, the test well (102) and the correction well (102) contain solutions with the same component concentrations. Item 10. The information processing device (4) according to item 1 or 8. [Item 12] The device (4) is connected to a sensor module (14) that is integrally configured with a plurality of electrochemical sensors (16) that measure values ​​related to the concentration of a predetermined component in each of the test wells (102) and the correction wells (102), acquiring values ​​measured by the electrochemical sensor (16) in each of the test well (102) and the correction well (102) during calibration when the concentration of the component in the test well (102) is known, and acquiring values ​​measured by the electrochemical sensor (16) in each of the test well (102) and the correction well (102) during actual measurement after the calibration when the concentration of the component in the test well (102) is unknown; generating a calibration curve for the actual measurement that indicates the relationship between the measurement value obtained by the electrochemical sensor (16) and the concentration of the component based on the values ​​measured in the test well (102) and the correction well (102) during the calibration and the value measured in the correction well (102) during the actual measurement; deriving the concentration of the component in the test well (102) during the main measurement based on the value measured in the test well (102) during the main measurement and the calibration curve during the main measurement; An information processing method that performs the above. [Item 13] a sensor module (16) integrally configured with a plurality of electrochemical sensors (16) for measuring values ​​relating to the concentration of a predetermined component in each of a test well (102) and a correction well (102), and connected to the device; acquiring values ​​measured by the electrochemical sensor (16) in each of the test well (102) and the correction well (102) during calibration when the concentration of the component in the test well (102) is known, and acquiring values ​​measured by the electrochemical sensor (16) in each of the test well (102) and the correction well (102) during actual measurement after the calibration when the concentration of the component in the test well (102) is unknown; generating an initial calibration curve showing the relationship between the measurement value by the electrochemical sensor (16) and the concentration of the component based on the values ​​measured in the test well (102) during the calibration; deriving a correction coefficient for a change in sensitivity of the electrochemical sensor (16) over time from the time of the calibration to the time of the main measurement, based on the value measured in the correction well (102) during the calibration and the value measured in the correction well (102) during the main measurement; a step of deriving the concentration of the component in the test well (102) during the main measurement based on a value obtained by correcting the value measured in the test well (102) during the main measurement using the correction coefficient and the initial calibration curve; An information processing method that performs the above. [Industrial Applicability]

[0125] The technology of the present disclosure can be used in information processing devices, analysis systems, and the like. [Explanation of symbols]

[0126] 1 Analysis system, 2 Detector, 3 Incubator, 4 Control device, 14 Sensor module, 16 Sensor, 52 Sensor value acquisition unit, 54 Calibration curve generation unit, 56 Correction value derivation unit, 58 Concentration derivation unit, 62 Correction coefficient derivation unit, 102 Well.

Claims

1. An apparatus connected to a sensor module in which a plurality of electrochemical sensors are integrally configured to measure values ​​relating to the concentration of a predetermined component in each of a test well and a correction well, a sensor value acquisition unit that acquires values ​​measured by the electrochemical sensor in each of the test wells and the correction wells during calibration when the concentrations of the components in the test wells are known, and acquires values ​​measured by the electrochemical sensor in each of the test wells and the correction wells during actual measurement after the calibration when the concentrations of the components in the test wells are unknown; a calibration curve generating unit that generates a calibration curve for the actual measurement that indicates the relationship between the measured value by the electrochemical sensor and the concentration of the component based on the values ​​measured in the test well and the correction well during the calibration and the value measured in the correction well during the actual measurement; a concentration deriving unit that derives the concentration of the component in the test well during the main measurement based on the value measured in the test well during the main measurement and a calibration curve during the main measurement; An information processing device comprising:

2. the calibration curve generating unit generates an initial calibration curve based on values ​​measured in the test wells during the calibration; the calibration curve generating unit derives a correction coefficient for a change in sensitivity of the electrochemical sensor over time from the time of the calibration to the time of the main measurement, based on the value measured in the correction well during the calibration and the value measured in the correction well during the main measurement; the calibration curve generating unit corrects the initial calibration curve based on the correction coefficient to generate a calibration curve for the main measurement. The information processing device according to claim 1 .

3. the calibration curve generating unit derives a value obtained by correcting the value measured in the test well during the first calibration based on the value measured in the correction well during the first calibration and the value measured in the correction well during the second calibration so as to reflect a change in sensitivity of the electrochemical sensor over time from the first calibration to the second calibration; the calibration curve generating unit generates the initial calibration curve based on the values ​​measured in the test wells during the second calibration and the corrected values. The information processing device according to claim 2 .

4. the calibration curve generating unit derives a first correction value, which is a value obtained by correcting the value measured in the test well during a first calibration based on the value measured in the correction well during calibration and the value measured in the correction well during the main measurement, so as to reflect a change in sensitivity of the electrochemical sensor over time from the first calibration to the main measurement; the calibration curve generating unit derives a second correction value, which is a value obtained by correcting the value measured in the test well during a second calibration based on the value measured in the correction well during calibration and the value measured in the correction well during the main measurement, so as to reflect a change in sensitivity of the electrochemical sensor over time from the second calibration to the main measurement; the calibration curve generating unit generates a calibration curve for the main measurement based on the first correction value and the second correction value. The information processing device according to claim 1 .

5. the calibration curve generating unit uses a value measured in the correction well during the second calibration and a value measured in the correction well during the main measurement when deriving the first correction value; When deriving the second correction value, the calibration curve generating unit uses a value measured in the correction well during the second calibration and a value measured in the correction well during the main measurement. The information processing device according to claim 4 .

6. the calibration curve generating unit uses a value measured in the correction well during the first calibration and a value measured in the correction well during the main measurement when deriving the first correction value; When deriving the second correction value, the calibration curve generating unit uses a value measured in the correction well during the second calibration and a value measured in the correction well during the main measurement. The information processing device according to claim 4 .

7. When the value measured in the correction well is an outlier, the calibration curve generating unit excludes the value measured in the correction well and generates the calibration curve for the main measurement.

7. The information processing device according to claim 1.

8. An apparatus connected to a sensor module in which a plurality of electrochemical sensors are integrally configured to measure values ​​relating to the concentration of a predetermined component in each of a test well and a correction well, a sensor value acquisition unit that acquires values ​​measured by the electrochemical sensor in each of the test wells and the correction wells during calibration when the concentrations of the components in the test wells are known, and acquires values ​​measured by the electrochemical sensor in each of the test wells and the correction wells during actual measurement after the calibration when the concentrations of the components in the test wells are unknown; a calibration curve generating unit that generates an initial calibration curve showing the relationship between the measurement value by the electrochemical sensor and the concentration of the component based on the value measured in the test well during the calibration; a correction coefficient derivation unit that derives a correction coefficient related to a change in sensitivity of the electrochemical sensor over time from the time of the calibration to the time of the main measurement, based on the value measured in the correction well during the calibration and the value measured in the correction well during the main measurement; a concentration derivation unit that derives the concentration of the component in the test well during the main measurement based on a value obtained by correcting the value measured in the test well during the main measurement using the correction coefficient and the initial calibration curve; An information processing device comprising:

9. the calibration curve generating unit derives a value obtained by correcting the value measured in the test well during the first calibration based on the value measured in the correction well during the first calibration and the value measured in the correction well during the second calibration so as to reflect a change in sensitivity of the electrochemical sensor over time from the first calibration to the second calibration; the calibration curve generating unit generates the initial calibration curve based on the values ​​measured in the test wells during the second calibration and the corrected values. The information processing device according to claim 8 .

10. When a value measured in the correction well is an outlier, the correction coefficient derivation unit excludes the value measured in the correction well and derives the correction coefficient.

10. The information processing device according to claim 8.

11. During the calibration, the test well and the correction well contain solutions having the same component concentrations.

9. The information processing device according to claim 1 or 8.

12. a device connected to a sensor module integrally configured with a plurality of electrochemical sensors for measuring values ​​relating to the concentrations of predetermined components in each of a test well and a correction well; a step of acquiring values ​​measured by the electrochemical sensor in each of the test wells and the correction wells during calibration when the concentration of the component in the test well is known, and acquiring values ​​measured by the electrochemical sensor in each of the test wells and the correction wells during actual measurement after the calibration when the concentration of the component in the test well is unknown; generating a calibration curve for the actual measurement that indicates the relationship between the measured value by the electrochemical sensor and the concentration of the component based on the values ​​measured in the test well and the correction well during the calibration and the value measured in the correction well during the actual measurement; deriving the concentration of the component in the test well during the main measurement based on the value measured in the test well during the main measurement and the calibration curve during the main measurement; An information processing method that performs the above.

13. a device connected to a sensor module integrally configured with a plurality of electrochemical sensors for measuring values ​​relating to the concentrations of predetermined components in each of a test well and a correction well; a step of acquiring values ​​measured by the electrochemical sensor in each of the test wells and the correction wells during calibration when the concentration of the component in the test well is known, and acquiring values ​​measured by the electrochemical sensor in each of the test wells and the correction wells during actual measurement after the calibration when the concentration of the component in the test well is unknown; generating an initial calibration curve showing the relationship between the measurement value by the electrochemical sensor and the concentration of the component based on the values ​​measured in the test well during the calibration; a step of deriving a correction coefficient for a change in sensitivity of the electrochemical sensor over time from the time of the calibration to the time of the main measurement, based on the value measured in the correction well during the calibration and the value measured in the correction well during the main measurement; a step of deriving the concentration of the component in the test well during the main measurement based on a value obtained by correcting the value measured in the test well during the main measurement using the correction coefficient and the initial calibration curve; An information processing method that performs the above.

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