Measurement method and measurement device

Abstract

To provide a measurement method and a measurement device for measuring a measurement object in blood, in which a correct measured value is obtained even when the blood is additionally adhered to a biosensor.SOLUTION: A measurement method comprises: a first detection step in which, using a biosensor that includes a flow path in which blood including a measurement object is introduced, an upstream electrode pair which is formed inside of the flow path and in which a reagent that reacts with the measurement object is placed on one electrode, and a downstream electrode pair which is formed downstream of the upstream electrode pair in the flow path, a first introduction of the blood up to the upstream electrode pair is detected with the upstream electrode pair; a second detection step in which a second introduction of the blood up to the downstream electrode pair is detected with the downstream electrode pair; a time measurement step in which a time difference from a temporal reference point at which the first introduction is detected to a temporal reference point at which the second introduction is detected is measured; and a measurement step in which, after detecting the second introduction, a measured value associated with the measurement object is acquired using any two electrodes of the electrodes of the upstream electrode pair and the downstream electrode pair on the basis of the time difference measured in the time measurement step.SELECTED DRAWING: Figure 4

Description

[Technical Field]

[0001] The present invention relates to a measurement method and a measurement device for measuring a measurement target in blood. [Background technology]

[0002] In biosensors with a flow path that guides a deposited liquid sample to a measurement electrode by capillary action, it is necessary to detect whether the flow path is sufficiently filled with the sample. Therefore, such detection is usually performed using an electrode located at the most downstream position in the flow path. Many biosensors have an electrode for detecting the sample at the most downstream position in the flow path, and this electrode is often used as the working electrode for detecting the sample, while the electrode for measuring the target substance, such as glucose, also serves as the counter electrode.

[0003] Patent Document 1 listed below discloses a microchip that collects droplets by capillary action, which is equipped with an injection port having an injection width larger than the droplet and a recess in a protruding portion that protrudes from a main body portion to which the microchip is attached, and a capillary cavity that communicates with the injection port and is connected to a holding chamber that holds the collected fluid, and the capillary cavity that communicates with the injection port is configured so that the side of the protruding portion is also open and exposed to the outside air.

[0004] The following Patent Document 2 discloses a configuration for a bioinformation measuring device that measures blood glucose levels, in which, in order to improve measurement accuracy, different voltage values ​​are applied from a voltage application unit between a first input terminal and a second input terminal at a first time and a second time, thereby capturing a number of different factors that affect the variation in bioinformation measurement as changes in current value, calculating a bioinformation correction value from this change in current value, and correcting the measured bioinformation measurement value using the bioinformation correction value. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Laid-Open No. 2008-157708 [Patent Document 2] WO2013 / 183215 Summary of the Invention [Problem to be solved by the invention]

[0006] An embodiment of the present disclosure aims to obtain accurate measurement values ​​even when additional blood is deposited on the biosensor in a measurement method and measurement device that measures a measurement target in blood using a biosensor. [Means for solving the problem]

[0007] One aspect of the present disclosure is a measurement method for measuring a measurement value of a analyte using a biosensor having a flow path into which blood containing the analyte is introduced, an upstream electrode pair formed in the flow path and having a reagent that reacts with the analyte placed on at least one electrode, and a downstream electrode pair formed downstream of the upstream electrode pair in the flow path. This measurement method includes a first detection step of detecting a first introduction of blood to the upstream electrode pair using the upstream electrode pair, a second detection step of detecting a second introduction of blood to the downstream electrode pair using the downstream electrode pair, a time measurement step of measuring the time difference from a temporal reference point at which the first introduction is detected to a temporal reference point at which the second introduction is detected, and a measurement step of, after detecting the second introduction, obtaining a measurement value related to the analyte based on the time difference measured in the time measurement step using two electrodes, the electrode of the upstream electrode pair on which the reagent is placed and an electrode provided in the flow path. [Effects of the Invention]

[0008] According to an embodiment of the present disclosure, in a measurement method and measurement device that uses a biosensor to measure a measurement target in blood, it is possible to obtain an accurate measurement value even if additional blood is deposited on the biosensor. [Brief explanation of the drawings]

[0009] [Figure 1] 1 is a perspective view showing the appearance of a measuring device according to an embodiment. [Figure 2] FIG. 1 is a schematic diagram showing a general configuration of a biosensor. [Figure 3] FIG. 2 is a block diagram showing the functions of the measurement device. [Figure 4] 1 is a flowchart illustrating an example of a measurement method according to an embodiment. [Figure 5] 1 is a graph showing the relationship between pulse voltage application and the corresponding response current. [Figure 6] 10 is a graph showing the relationship between the time difference between additional drops and the deviation of glucose values. [Figure 7] FIG. 10 is a schematic diagram showing a schematic configuration of a modified example of a biosensor. DETAILED DESCRIPTION OF THE INVENTION

[0010] The following describes a measurement method and a measurement device according to an embodiment of the present disclosure. In the following description, the "upstream side" and the "downstream side" are defined along the direction in which blood deposited on the biosensor flows through the flow path.

[0011] (1)Measurement method The measurement method according to this embodiment is a method for measuring a measurement value of the analyte using a biosensor having a flow path into which blood containing the analyte is introduced, an upstream electrode pair formed in the flow path and having a reagent that reacts with the analyte placed on at least one electrode, and a downstream electrode pair formed downstream of the upstream electrode pair in the flow path. This measurement method includes a first detection step of detecting a first introduction of blood to the upstream electrode pair using the upstream electrode pair, a second detection step of detecting a second introduction of blood to the downstream electrode pair using the downstream electrode pair, a time measurement step of measuring the time difference from a temporal reference point at which the first introduction is detected to a temporal reference point at which the second introduction is detected, and a measurement step of, after detecting the second introduction, obtaining a measurement value related to the analyte based on the time difference measured in the time measurement step using two electrodes, the electrode of the upstream electrode pair on which the reagent is placed and the electrode provided in the flow path.

[0012] The measurement object refers to a chemical component contained in blood, such as glucose (blood sugar) or lactate (lactic acid). The upstream electrode pair is a pair of electrodes located upstream of the flow path, with a reagent placed on at least one of the electrodes. The upstream electrode pair may be entirely covered with the reagent, but it is preferable that the reagent be placed only on the downstream electrode of the upstream electrode pair. The reagent is a chemical substance that reacts with the measurement object, and may include, for example, an enzyme and a mediator. The downstream electrode pair is a pair of electrodes located downstream of the upstream electrode pair. Here, the upstream electrode pair and the downstream electrode pair may share some electrodes, but it is preferable that they each be composed of separate electrodes. The downstream electrode pair may also be placed with a reagent, or may be continuous with the reagent placed on the upstream electrode pair.

[0013] When electrical conduction occurs between the upstream electrode pair via the blood deposited in the flow path, a first introduction is detected, which means that blood has been introduced up to this upstream electrode pair. In addition, a time reference point at which the first introduction is detected is also obtained. The process of detecting this first introduction is the first detection process.

[0014] This first detection step preferably includes the steps of applying a pulse voltage between the upstream electrode pair, measuring the peak value of the response current corresponding to the applied pulse voltage, and determining whether the measured peak value exceeds a predetermined current threshold. If the measured peak value exceeds the predetermined threshold a predetermined number of times or more, detecting the first introduction is detected. Specifically, measuring the peak value of the response current using a pulse wave generated by a pulse voltage can obtain a higher value than when a DC voltage of the same value is applied. For example, the frequency of the pulse wave is preferably 1 to 2000 Hz (with a period of 0.5 ms to 1 s), the potential difference from the base to the peak of the pulse wave is preferably 50 to 1000 mV, and the rise time of the pulse wave from the base to the peak is preferably 30 μs or less. By keeping this time below 30 μs, the peak value of the response signal can be generated with high accuracy. While the predetermined number of times may be one, it is preferably multiple times, even three times, to avoid erroneous determination due to accidentally high peak values ​​obtained due to noise components such as static electricity. The time reference point at which the introduction of blood in this first detection step is detected may be the point at which the measured peak value is detected, or the point at which a predetermined current threshold is exceeded.Furthermore, if detection is performed multiple times, this time reference point may be the point at which the peak value in the last measurement is detected, or the point at which a predetermined current threshold is exceeded.

[0015] Next, electrical conduction between the downstream electrode pair via blood causes a second introduction, which means that blood has been introduced up to the downstream electrode pair, to be detected. The process of detecting this second introduction is the second detection process. One of the downstream electrode pair is preferably provided at the most downstream position of the flow path, and in that case, once it is detected that blood has been introduced up to the downstream electrode pair, it can be assumed that the entire flow path is filled with blood.

[0016] This second detection step preferably includes the steps of applying a voltage between the downstream electrode pair, measuring a response current value corresponding to the applied voltage, and determining whether the measured response current value exceeds a predetermined current threshold, and detecting a second introduction if so. As with the first introduction, a time reference point at which the second introduction is detected is also obtained. The voltage applied in the second detection step may be a DC voltage, and the time reference point at which the introduction of blood is detected may be the time when the measured response current value exceeds the predetermined current threshold, or the time when the highest response current value is detected.

[0017] In the time measurement step, the time difference between the detection of the first introduction and the detection of the second introduction is measured. Specifically, the time difference is calculated from the time reference point at which the introduction of blood is detected in the second detection step to the time reference point at which the introduction of blood is detected in the first detection step. Note that each time reference point may be stored as a time, and the difference between them may be used as the time difference, or the time difference may be calculated by counting the time from the time reference point in the first detection step to the time reference point in the second detection step.

[0018] Then, after the second introduction is detected, a measurement step is performed in which a measurement value related to the measurement target in the blood is obtained using two electrodes of the upstream electrode pair, at least one of which includes the electrode on which the reagent is placed. The other electrode of these two electrodes is preferably one of the electrodes of the upstream electrode pair or the downstream electrode pair, and more preferably the electrode located upstream of the downstream electrode pair. However, the other electrode may be an electrode other than the upstream electrode pair or the downstream electrode pair, for example, an electrode formed between the downstream electrode of the upstream electrode pair and the upstream electrode of the downstream electrode pair. In this measurement step, a measurement value is obtained based on the time difference measured in the time measurement step.

[0019] Here, by the time the first introduction is detected, the sample has reached the upstream electrode pair, including the electrode on which the reagent is placed. If the time difference until the second introduction is detected is longer than a normal value (e.g., less than 0.5 seconds), it can be assumed that blood has been deposited twice into the flow path, i.e., that additional blood has been deposited. If the time difference until the second introduction is detected is longer than a predetermined value (e.g., 5 seconds), which is longer than the normal value, much of the reagent that would be involved in the reaction with the analyte on the electrode dissolves, and the second blood drop sweeps the reagent downstream from the position where it was deposited. As a result, when measuring the measured value of the analyte, the amount of reagent that would be involved in the reaction with the analyte on the electrode is reduced (depleted) compared to when the time difference is extremely short (i.e., when a sufficient amount of blood is deposited in one drop). As a result, the amount of analyte reacting with the reagent on the electrode is reduced (depleted), resulting in a decrease in the amount of analyte, and consequently a decrease in the response current value. On the other hand, if the time difference until the detection of the second introduction is longer than the normal value but shorter than the predetermined value (e.g., 0.5 to 5 seconds), the reagent on the electrode dissolves somewhat during the first application, but the amount washed downstream is small. However, compared to a normal case in which a sufficient amount of blood is applied in one application (e.g., a normal time difference of less than 0.5 seconds), the reagent dissolves during the time between the first and second application, and the reaction between the analyte and the reagent progresses. Therefore, when voltage is applied to obtain a measurement value, the reaction between the analyte and the reagent is in a more advanced state than normal. In other words, the response current value measured is one in which the reaction rate is faster, and as a result, the reaction is enhanced and the response current value becomes higher.

[0020] Therefore, in the measurement step, it is desirable to first perform a preliminary measurement step using the two electrodes to acquire parameters related to the analyte, and then perform a correction step to acquire a measured value by correcting these parameters based on the time difference. The parameter here may be, for example, a response current value obtained by applying a voltage between the electrodes, or a tentative concentration of the analyte obtained by applying this response current value to a calibration curve obtained from response current values ​​measured in blood containing a known concentration of the analyte. In this embodiment, the measured value may be a response current value obtained by applying a voltage between the electrodes and corresponding to the true concentration, or a true concentration of the analyte obtained by applying this response current value to a calibration curve obtained from response current values ​​previously measured in blood containing a known concentration of the analyte.

[0021] In the correction step, the parameter is corrected based on the time difference by referring to correction information for correcting the parameter in response to the time difference to obtain the measured value. This correction information is calculation information that, when the time difference is longer than the normal value and less than a predetermined value, reduces the value of the obtained parameter by discounting the parameter value that was increased due to the enhanced reaction at the electrode, thereby estimating the true concentration value. Furthermore, when the time difference is equal to or greater than a predetermined value, this correction information is calculation information that increases the value of the obtained parameter by increasing the parameter value that was discounted due to the decreased reaction at the electrode, thereby estimating the true concentration value. However, if the time difference exceeds a limit value (e.g., longer than 10 seconds), an error message may be displayed and no value may be estimated. Here, the correction information may be a correction coefficient, as described below, or a calibration curve or comparison table based on measured values ​​obtained by measuring blood containing a known concentration of the analyte.

[0022] The normal value may be set as the average or median of the time differences (elapsed time) between the reference time points for the first and second introductions when a sufficient amount of blood is flowed through the flow path of the biosensor for multiple blood types. Alternatively, the normal value may be set as a very short time difference, in which the effect of dissolution of the reagent in the blood described above does not substantially appear in the parameters.

[0023] The predetermined value can be determined, for example, by calculating the ratio of a parameter obtained when multiple blood samples are applied at various time differences to a parameter obtained when the time difference is normal, and then setting the inflection point at which the calculation result changes from a value higher than 100% to a value lower than 100%, i.e., the time difference at which the value becomes 100%, as the predetermined value. Note that the predetermined value is a threshold value for the time difference, and therefore can be referred to as a time threshold value.

[0024] Here, the correction method in the correction step can be, for example, to measure parameters in advance when multiple samples are applied with various time differences. Correction coefficients calculated from the rate of deviation of the parameter from the parameter measured when the time difference is zero are obtained for various time differences and compiled into a data table, and the parameters obtained in the preliminary measurement step are multiplied by the correction coefficients corresponding to the measured time differences. Note that a time difference of zero may refer to a time difference of a normal value.

[0025] For example, the parameter when the time difference is zero is P0, and the parameter when the time difference is t (seconds) is P t When this is the case, the deviation X (%) can be calculated using the following formula (1).

[0026] X=(P0-P t ) / P0×100 (1)

[0027] For example, if t is less than a predetermined value, the deviation X will be a positive value, and if t is equal to or greater than the predetermined value, the deviation X will be a negative value. From the deviation X, the correction coefficient C can be calculated using the following formula (2).

[0028] C = 100 / (100 + X) (2)

[0029] That is, when t is less than a predetermined value, deviation X is a positive value, so correction coefficient C is less than 1, and the numerical value of the parameter multiplied by this coefficient decreases. On the other hand, when t is equal to or greater than a predetermined value, deviation X is a negative value, so correction coefficient C is greater than 1, and the numerical value of the parameter multiplied by this coefficient increases.

[0030] Here, if the time difference value obtained when measuring an actual blood sample does not correspond to a value in the data table, the correction coefficient C can be calculated by linear interpolation using the values ​​of the correction coefficient C corresponding to the time differences located before and after the measured time difference value in the data table.

[0031] The method of correcting parameters based on correction coefficients is just one example. Parameters may be measured in advance when multiple samples are spotted at various time lags, and the parameters may be corrected by referring to correction information for calculating correction values ​​for the parameters, such as a calibration curve or comparison table calculated from the rate of deviation from the parameters measured when the time lag is zero.

[0032] In the measurement step, it is also possible to select measurement conditions based on the time difference after detecting the second introduction without correcting the parameters as described above, and obtain a measurement value based on the selected measurement conditions. Specifically, methods for changing the measurement conditions include changing the voltage applied between the electrodes or changing the timing for measuring the response current value. For example, when the time difference is less than the predetermined value, the voltage applied between the electrodes can be weakened compared to when the time difference is zero, thereby reducing the obtained response current value, and when the time difference is equal to or greater than the predetermined value, the voltage applied can be increased compared to when the time difference is zero, thereby increasing the response current value. In this case, the applied voltage value is, for example, when the voltage applied when the time difference is zero is E0, the voltage value E applied when the time difference is t is t can be calculated using the correction coefficient C according to the following formula (3).

[0033] E t =E0×C (3)

[0034] And the voltage value E t A voltage of 100 kJ / cm is applied between the electrodes, and the response current value obtained is applied to a predetermined calibration curve, thereby obtaining a measurement value for the object to be measured.

[0035] The measurement may be corrected based on a measurement value of another item other than the object to be measured, obtained using any two electrodes formed in the flow path of the biosensor, including the electrodes of the upstream electrode pair and the downstream electrode pair. An example of such another item is hematocrit. For example, the deviation X may be measured using blood having various hematocrit values, a data table of correction coefficients C may be created in advance for each hematocrit value, and the data table corresponding to the hematocrit value measured in the measurement step may be selected to perform correction based on the hematocrit value. If a data table corresponding to the actually measured hematocrit value is not available, the value may be corrected by linear interpolation using data tables corresponding to hematocrit values ​​before and after the measured hematocrit value.

[0036] (2) Measuring equipment An embodiment of a measuring device for carrying out the above-described measuring method will be described below. FIG. 1 is a perspective view showing the appearance of measuring device 1 according to this embodiment. In this embodiment, measuring device 1 is a portable blood glucose meter, as an example. In FIG. 1, measuring device 1 is a portable blood glucose meter, and a biosensor 2 configured to be detachable from measuring device 1 is provided. This biosensor 2 is formed with a blood supply port 2d as an inlet for flow path 2a (described below) so that a patient's blood as a sample can be introduced into flow path 2a, and an air hole 2e for discharging air from flow path 2a due to the introduction of blood, and is configured to have the function of detecting blood glucose levels (glucose levels) in the blood. Measuring device 1 shown in FIG. 1 can be used, for example, as a blood glucose meter, such as a portable blood glucose monitor or a self-monitoring blood glucose meter.

[0037] The measuring device 1 also includes a main body 1a, which has an insertion port 1b for inserting a strip-shaped biosensor 2. The main body 1a also includes a control unit 100, which is configured, for example, by a microprocessor and controls each part of the measuring device 1. As shown in FIG. 3, the main body 1a also includes a voltage applicator 50 that supplies a predetermined voltage signal to the biosensor 2 and receives a voltage signal indicating the measurement result from the biosensor 2 and performs A / D conversion on the voltage signal, a measuring device 60 that generates measurement data indicating the measurement value, and a recording unit (not shown) that records the measurement data obtained by the measuring unit. The measurement data obtained by the measuring device 60 is recorded in the recording unit in association with the measurement time, patient ID, etc.

[0038] The main body 1a is also provided with a display screen 1c for displaying measurement data and a connector 1d for data communication with external devices. This connector 1d is configured to transmit and receive data such as measurement data, measurement time, and patient ID to and from external devices such as mobile devices such as smartphones and personal computers. That is, the measurement device 1 is configured to transfer measurement data and measurement time to external devices via the connector 1d, and to receive patient IDs and the like from external devices and associate them with measurement data and the like.

[0039] In addition to the above description, the measuring device 60 may be provided at the end of the biosensor 2, and measurement data may be generated on the biosensor 2 side. Also, the main body 1a of the measuring device 1 may be provided with a user interface including an input unit such as buttons or a touch panel for a user such as a patient to input data. Also, the display screen 1c, recording unit, etc. may not be provided on the main body 1a, but may be provided on an external device connectable to the main body 1a.

[0040] FIG. 2 is a schematic diagram of a biosensor 2 used in the measurement device 1 of this embodiment. In the figure, the upper side is the upstream side, and the lower side is the downstream side. In the biosensor 2, an electrode layer formed of, for example, a metal material such as gold (Au) or a carbon material such as carbon is formed on a substrate formed of, for example, synthetic resin (plastic). A spacer (not shown) having a rectangular cutout as the covering region 2b is layered on the electrode layer, and a synthetic resin cover (not shown) having an air hole 2e formed thereon is further layered on top of that. The layering of the substrate, spacer, and cover forms a space having a blood supply port 2d formed by the cutout in the spacer, and this space becomes the flow path 2a. The air hole 2e is formed near the downstream end of the flow path 2a.

[0041] In this embodiment, the electrode layer includes five electrodes: a first working electrode 11 and a first counter electrode 12 as a first electrode pair 10, a second working electrode 21 and a second counter electrode 22 as a second electrode pair 20, and a blood detection electrode 30. These five electrodes are exposed in a rectangular shape parallel to each other in the longitudinal and transverse directions of the biosensor 2 within the flow path 2a. The first electrode pair 10, the second electrode pair 20, and the blood detection electrode 30 exposed in the flow path 2a come into contact with the introduced blood and function as a measurement region. Note that adjacent electrodes are insulated from each other. For example, when the electrode layer is formed from a metal material formed by physical vapor deposition, the electrodes are insulated from each other by drawing a predetermined electrode pattern with a laser beam (trimming). In addition, when the electrode layer is formed using a carbon material, the electrodes are formed at a predetermined interval. The electrode layer in this embodiment is formed from a nickel-vanadium alloy.

[0042] Each electrode extends along the longitudinal direction of biosensor 2 and is bent widthwise at its upstream end. This bent portion is positioned parallel to the width direction in the following order from the upstream side: second working electrode 21, second counter electrode 22, first working electrode 11, first counter electrode 12, and blood detection electrode 30. Each electrode is covered with the cover (not shown) in covering region 2b from the upstream end to the vicinity of the downstream end of biosensor 2, but the downstream end portion is uncovered and exposed, forming connector region 2c for insertion into insertion port 1b of main body 1a. In connector region 2c, lead portion 11a of first working electrode 11, lead portion 12a of first counter electrode 12, lead portion 21a of second working electrode 21, lead portion 22a of second counter electrode 22, and lead portion 30a of blood detection electrode 30 each form an exposed contact point.

[0043] In the widthwise center of the upstream portion of the biosensor 2, a gap is formed between each electrode and a cover (not shown). As described above, this gap is the capillary-shaped flow path 2a through which blood containing the analyte is introduced and flows. Furthermore, a non-conductive region 45, which is the gap between the second counter electrode 22 (the second electrode counting from the upstream side) and the first working electrode 11 (the third electrode), is wider than the gaps between the other electrodes. This non-conductive region 45 is formed by drawing a rectangular pattern on the electrode layer with laser light, thereby isolating it from the other electrodes. Furthermore, a reagent 40 is placed on the first working electrode 11. The region in which this reagent 40 is placed extends to the middle of the first counter electrode 12 on the downstream side and to the middle of the non-conductive region 45 on the upstream side, but does not extend to the second counter electrode 22. In other words, because the first working electrode 11 and the second counter electrode 22 are separated by the non-conductive region 45, contact between the reagent 40 placed on the first working electrode 11 and the second counter electrode 22 is prevented. When blood is deposited on the blood supply port 2d of the biosensor 2, capillary force causes the blood to flow downstream through the flow path 2a, passing through the second working electrode 21, the second counter electrode 22, the first working electrode 11, the first counter electrode 12, and the blood detection electrode 30 in this order. When the blood reaches the first working electrode 11, the reagent 40 placed on the first working electrode 11 is dissolved by the blood.

[0044] 3 is a block diagram showing the functions of the measurement device 1 of this embodiment. As described above, the measurement device 1 of this embodiment includes a biosensor 2 having a first electrode pair 10 consisting of a first working electrode 11 and a first counter electrode 12 for measuring a analyte in blood, a second electrode pair 20 formed upstream of the first electrode pair 10 and consisting of a second working electrode 21 and a second counter electrode 22, a blood detection electrode 30 formed downstream of the first electrode pair 10, and a reagent 40 placed in contact with at least the first working electrode 11 and reacting with the analyte. The second counter electrode 22 and the first working electrode 11 form an upstream electrode pair 15, and the first counter electrode 12 and the blood detection electrode 30 downstream form a downstream electrode pair 25. As described above, the reagent 40 is placed on the first working electrode 11, which is one of the electrodes constituting the upstream electrode pair 15.

[0045] Lead portions 11a, 12a, 21a, 22a, and 30a of the electrodes of biosensor 2 are connected in parallel to a voltage applicator 50 (described later) and ground via a connection circuit 200. Connection circuit 200 is provided with a first working electrode switch 211 between voltage applicator 50 and lead portion 11a, a first counter electrode switch 212 between voltage applicator 50 and lead portion 12a, a second working electrode switch 221 between voltage applicator 50 and lead portion 21a, a second counter electrode switch 222 between voltage applicator 50 and lead portion 22a, and a blood detection electrode switch 230 between voltage applicator 50 and lead portion 30a.

[0046] Furthermore, the leads 11a, 12a, 21a, 22a, and 30a of the electrodes are branched from the corresponding switches 211, 212, 221, 222, and 230, and are connected in parallel to the ground. A first working electrode ground switch 311, a first counter electrode ground switch 312, a second working electrode ground switch 321, a second counter electrode ground switch 322, and a blood detection electrode ground switch 330 are provided in a connection circuit 200 between each branch point and the ground. Each switch is an electronic switch, and is turned on and off by the control unit 100, as described below.

[0047] The measuring device 1 includes a voltage applicator 50 equipped with a power supply. The voltage applicator 50 can be connected to each electrode via a connection circuit 200. The voltage applicator 50 also includes a current / voltage conversion circuit 51 that converts the current flowing between the electrodes into a voltage and outputs it, and an A / D conversion circuit 52 that converts the voltage value from the current / voltage conversion circuit 51 into a pulse. By using the control unit 100 to turn on the desired switch corresponding to the electrode to be used and variably controlling the voltage applied between each electrode at ground, the voltage applicator 50 can apply a voltage between the electrodes and obtain the value of the response current flowing between the electrodes.

[0048] The measuring device 1 further includes a control unit 100, which is a central control device that executes a predetermined program. The control unit 100 acquires parameters corresponding to first information about the measurement object (e.g., glucose level) and second information about a measurement item other than the measurement object (e.g., hematocrit level) based on pulses from the A / D conversion circuit 52 of the voltage applicator 50, and further corrects the parameters. The control unit 100 also includes a measuring device 60 (referred to as a backup measuring device 61 when acquiring the first information, as an auxiliary measuring device 62 when acquiring the second information, and as a corrector 63 when correcting the parameters), an introduction detector 65 (referred to as a first detector 66 when detecting the first introduction, and as a second detector 67 when detecting the second introduction) that detects the first introduction and the second introduction, and a time measuring device 70 that measures the time difference between the detection of the first introduction and the detection of the second introduction.

[0049] The measuring device 1 further includes an error indicator 90 that displays an error when the time difference measured by the time measuring device 70 is equal to or greater than a limit value.

[0050] Each detection step and each measurement step will be described below with reference to Table 1 below, which shows the open / closed state of each switch.

[0051] [Table 1]

[0052] The first detection step described in (1) uses an upstream electrode pair 15 consisting of a second counter electrode 22 and a first working electrode 11. In the first detection step, the control unit 100 first controls the second counter electrode switch 222 and the first working electrode ground switch 311 to a connected state (CLOSE) and the other switches to a disconnected state (OPEN) (see Table 1). Next, the voltage applicator 50 applies a steady voltage (e.g., 200 mV) between the second counter electrode 22 and the first working electrode 11. At this time, the control unit 100 controls the second counter electrode switch 222 to open and close at a predetermined cycle, thereby periodically applying a pulse voltage between these electrodes. When blood is introduced up to the first working electrode 11, the measuring device 60 can measure the peak value of the response current corresponding to the applied pulse voltage. The introduction detector 65 (first detector 66) determines whether the peak value of the response current measured by the measuring device 60 exceeds a predetermined current threshold, and if so, detects the first introduction.

[0053] In the above-described embodiment, the second counter electrode 22 is used as the working electrode. When the amount of blood deposited on the biosensor 2 is insufficient, a relatively large amount of blood is present on the upstream electrode, but the amount of blood is small on the downstream electrode. Therefore, by using the upstream second counter electrode 22 as the working electrode, a current flow is more likely to occur, thereby improving the accuracy of detecting a blood shortage.

[0054] On the other hand, when the first working electrode 11 located downstream is used as the working electrode, it can be used in common with the first working electrode 11 in the preliminary measurement step described below. This simplifies the configuration of the electrical circuit. In this case, it is necessary to control the first working electrode switch 211 and the second counter electrode ground switch 322 so that they are connected.

[0055] In FIG. 3, the second counter electrode 22 located downstream of the second electrode pair 20 is shown as part of the upstream electrode pair 15. However, if the second working electrode 21 is located downstream, the second working electrode 21 becomes part of the upstream electrode pair 15. In FIG. 3, the first working electrode 11 located upstream of the first electrode pair 10 is shown as part of the upstream electrode pair 15. However, if the first counter electrode 12 is located upstream and a reagent 40 is also placed on the first counter electrode 12, the first counter electrode 12 becomes part of the upstream electrode pair 15. The voltage value of the applied pulse voltage is preferably set in the range of 50 to 1000 mV, for example, and more preferably in the range of 100 to 600 mV. The peak value of the response current is preferably set to, for example, 0.3 μA or more, and more preferably 0.7 μA or more.

[0056] The second detection step described in (1) uses a downstream electrode pair 25 consisting of a first counter electrode 12 and a blood detection electrode 30. In the second detection step, the control unit 100 first connects the first counter electrode switch 212 and the blood detection electrode ground switch 330, and controls the other switches to be disconnected (see Table 1). Next, the voltage applicator 50 applies a steady voltage (e.g., 200 mV) between the first counter electrode 12 and the blood detection electrode 30. The control unit 100 then maintains the first counter electrode switch 212 in a constantly connected state, thereby periodically applying a DC voltage between these electrodes. When blood is introduced up to the blood detection electrode 30, the measuring device 60 measures the peak value of the response current corresponding to the applied DC voltage. The introduction detector 65 (second detector 67) determines whether the peak value of the response current measured by the measuring device 60 exceeds a predetermined current threshold, and if so, detects the second introduction.

[0057] In this embodiment, the first counter electrode 12 located downstream of the first electrode pair 10 is considered to be part of the downstream electrode pair 25. However, the first working electrode 11 located upstream may also be part of the downstream electrode pair 25. The voltage value of the applied DC voltage is preferably set, for example, in the range of 50 to 1000 mV, more preferably in the range of 100 to 600 mV. The peak value of the response current is preferably set, for example, to 0.1 μA or more, more preferably 0.15 μA or more. Although a DC voltage is applied in this embodiment, a pulse voltage can also be applied by the control unit 100 controlling the first counter electrode switch 212 to open and close at a predetermined cycle. In this case, the measuring device 60 may measure the peak value of the response current value in response to the pulse voltage or the current value after a predetermined time has elapsed since the initial response, and the introduction detector 65 (second detector 67) may determine whether this current value exceeds a predetermined current threshold value to detect the second introduction.

[0058] The time measuring device 70 performs the time measuring step described in (1) above. The time measuring device 70 measures the time difference from the time reference point at which the first introduction detected by the introduction detector 65 is detected to the time reference point at which the second introduction is detected. The time measuring device 70 can be implemented by a central processing unit (CPU) that executes a predetermined program in the control unit 100 of the measurement device.

[0059] In the preliminary measurement step described in (1) above, the first electrode pair 10, i.e., the first working electrode 11 and the first counter electrode 12, are used. In the preliminary measurement step, first, the control unit 100 controls the first working electrode switch 211 and the first counter electrode ground switch 312 to be connected, and the other switches to be disconnected (see Table 1). Next, when the voltage applicator 50 applies a DC voltage (e.g., 200 mV) to the first electrode pair 10, the measuring device 60 (preliminary measuring device 61) measures a response current value as first information corresponding to the applied DC voltage. The voltage value of the applied DC voltage is desirably set, for example, in the range of 100 to 1000 mV, more preferably in the range of 200 to 500 mV.

[0060] The response current value measured by the preliminary measuring device 61 may be used as the first information as it is, or may be converted into the concentration of the object to be measured by referring to a calibration curve or comparison table prepared in advance using response current values ​​measured for an object to be measured at a known concentration, and the converted value may be used as the first information.

[0061] In addition, in the auxiliary measurement step of measuring the second information, the second electrode pair 20, i.e., the second working electrode 21 and the second counter electrode 22, are used. In the auxiliary measurement step, first, either before or after measuring the first information, the control unit 100 controls the second working electrode switch 221 and the second counter electrode ground switch 322 to be in a connected state and the other switches to be in a disconnected state (see Table 1). Next, when the voltage applicator 50 applies a DC voltage (e.g., 3.5 V) to the second electrode pair 20, the measuring device 60 (auxiliary measuring device 62) measures a response current value as the second information corresponding to the applied DC voltage. The voltage value of the applied DC voltage is desirably set, for example, in the range of 2 to 20 V, more preferably in the range of 3 to 10 V.

[0062] The response current value measured by auxiliary measuring device 62 may be used as the second information as is. Alternatively, the second information may be a value converted into a numerical value of a measurement item (e.g., hematocrit value) by referring to a calibration curve or comparison table prepared in advance using response current values ​​measured with other blood for which the measurement item of auxiliary measuring device 62 is known.

[0063] The corrector 63 performs the correction step described in (1) above. That is, the corrector 63 corrects the first information as a parameter based on the time difference measured by the time measuring device 70 and the second information, and calculates the concentration of the object to be measured as a measurement value. This corrector 63 can be implemented by a central processing unit (CPU) that executes a predetermined program in the control unit of the measuring device. The correction of the parameters in the corrector 63 is the same as that described in the correction step in (1) above.

[0064] The error indicator 90 is realized as a device that displays an error message or emits an audio warning sound when the time difference measured by the time measuring device 70 exceeds a predetermined value. For example, the display screen 1c of the measuring device 1 in Figure 1 can be used as the error indicator 90 to display an error message.

[0065] (3) Measurement example An example of the measurement method of this embodiment will be described below with reference to the flowchart in Fig. 4. In this example, a glucose value is measured as the first information, and a hematocrit value is measured as the second information. Note that the glucose value obtained as the first information is a value affected by the hematocrit value in the blood, and therefore needs to be corrected based on the hematocrit value obtained as the second information.

[0066] 2 is formed by providing each electrode on a substrate having a width of 6 mm and a length of 30 mm, for example. The width of the flow channel 2a is 2 mm and the length is 4 mm, for example.

[0067] First, an example of the composition of the reagent 40 placed on the first working electrode 11 is as follows. Hexaammineruthenium (III) chloride: 38.9% by mass 1-Methoxy PES (Dojindo Laboratories): 0.2% by mass SN Deformer 1315 (San Nopco): 0.1% by mass 0.6M phosphate buffer (pH7.0): 8.8% by mass CHAPS (Dojindo Chemical Research Institute): 4.0% by mass Glycine: 4.0% by mass Distilled water: 44.0% by mass

[0068] 0.1 mg of reagent 40 with this composition is applied to a region 3 mm wide and 1 mm long, centered on the first working electrode 11. This region is adjusted to cover approximately the middle of the first counter electrode 12 on the downstream side and approximately the middle of the non-conductive region 45 on the upstream side. In addition, 4.1 units of glucose dehydrogenase (AMANO8, Amano Enzyme) are applied to the region where reagent 40 has been applied.

[0069] This biosensor 2 is attached to the connector 1d of the main body 1a of the measuring device 1. Then, in the first detection step shown in S100 of FIG. 4, the control unit 100 first controls the second counter electrode switch 222 and the first working electrode ground switch 311 to be connected and the other switches to be disconnected (see Table 1). Next, the voltage applicator 50 applies a steady voltage of 200 mV between the upstream electrode pair 15 (the second counter electrode 22 and the first working electrode 11). Next, blood is deposited in the flow path 2a, and when the blood fills the space above the second counter electrode 22 and the first working electrode 11, the measuring device 60 measures a current equal to or greater than 0.7 μA, which is the threshold current. This detects that the electrodes are electrically connected. After detecting a current of 0.7 μA or more for the first time, the control unit 100 controls the second counter electrode switch 222 to open and close at a predetermined cycle of 2.5 ms, thereby changing the voltage application method so that a pulse voltage is applied between the electrodes in which a voltage of 500 mV is applied for 2.5 ms and then stopped for 2.5 ms.

[0070] FIG. 5 is a graph showing the relationship between voltage application and current. When an initial steady voltage or a second or subsequent pulse voltage is applied as shown in the upper graph, a current having a peak indicating a transient response is generated as shown in the lower graph. In step S110, the introduction detector 65 (first detector 66) determines whether the peak value of this peak current has exceeded the threshold current of 0.7 μA a predetermined number of times, specifically, three times. The voltage application is repeated until a peak value exceeding the threshold is detected three times. Note that the initial voltage application method may not be a steady voltage of 200 mV, but may be a pulse voltage (AC voltage) in which a voltage of 500 mV is applied for 2.5 ms and then stopped for 2.5 ms, as in the second and subsequent applications.

[0071] As shown in FIG. 5, the first peak value tends to be lower than subsequent peak values. This is thought to be because, at the time the current having the first peak is generated, blood has not yet reached the entire surface of the first working electrode 11, and the reagent has not yet been completely dissolved by the blood. Therefore, it is preferable that the current threshold value for the first peak value (first current threshold value) be higher than the current threshold value for subsequent peak values ​​(second current threshold value). The current threshold value for the first peak value can be, for example, 0.2 to 0.5 μA, and more preferably 0.35 μA.

[0072] When a peak value equal to or greater than the threshold is detected three times in step S110, indicating that the first introduction has occurred, the control unit 100 first controls the first counter electrode switch 212 and the blood detection electrode ground switch 330 to connect, and the other switches to disconnect (see Table 1) in the second detection step shown in S120. The voltage applicator 50 then applies a continuous voltage of 200 mV between the downstream electrode pair 25 (first counter electrode 12 and blood detection electrode 30). The measuring device 60 then detects a current peak similar to that shown in FIG. 5. In step S130, the introduction detector 65 (second detector 67) determines whether this peak value has been detected to be equal to or greater than the threshold current of 0.15 μA for a predetermined time, specifically 15 msec. If this detection is not detected, the time measuring device 70 determines whether an upper limit time, specifically 10 seconds, has elapsed since the first introduction was detected in the time measurement step shown in S140. If the upper limit time has not elapsed, the voltage application is repeated at step S120. On the other hand, if it is determined that the upper limit time has elapsed, an error process is performed by the error indicator 90 at step S160, and subsequent processes are stopped.

[0073] On the other hand, if a peak value equal to or greater than the threshold current continues for 15 msec or more at the stage shown in S130 and a second introduction is detected, in the time measurement step shown in S150, the timer 70 acquires the time difference from the detection of the first introduction to the detection of the second introduction. That is, it measures the time difference from the time reference point when the first introduction is detected to the time reference point when the second introduction is detected.

[0074] Next, in a preliminary measurement step shown in S170, the first information is measured by measuring device 60 (auxiliary measuring device 61). At the same time, in an auxiliary measurement step, the second information is measured by measuring device 60 (auxiliary measuring device 62).

[0075] In measuring the first information, first, the control unit 100 controls the first working electrode switch 211 and the first counter electrode ground switch 312 to be connected, and the other switches to be disconnected (see Table 1). Next, the voltage applicator 50 applies a voltage of 200 mV to the first electrode pair 10 for 4.5 seconds, and the measuring device 60 (auxiliary measuring device 61) measures the first information as a response current value associated with the voltage applicator 50. In measuring the second information, first, the control unit 100 controls the second working electrode switch 221 and the second counter electrode ground switch 322 to be connected, and the other switches to be disconnected (see Table 1). Next, the voltage applicator 50 applies a voltage of 3.5 V to the second electrode pair 20 for 1 second, and the measuring device 60 (auxiliary measuring device 62) measures the second information as a response current value associated with the voltage applicator 50. Furthermore, the response current value of the first information is applied to a predetermined calibration curve to calculate the glucose value as a parameter.

[0076] Then, in the correction step shown in S180, corrector 63 obtains a correction coefficient from the hematocrit value and time difference of the second information. Fig. 6 shows an example of an actual measurement of the relationship between the time difference from the first detection to the second detection, that is, the time difference from the time reference point when the first introduction is detected to the time reference point when the second introduction is detected, and the deviation. FIG. 6 shows a graph plotting the deviation (%) of the response current (i.e., glucose measurement value) measured after a drop of blood with a constant glucose level and known hematocrit values ​​of 10%, 42%, and 55% was applied to biosensor 2 in an amount sufficient to fill the upstream electrode pair for first detection but not the downstream electrode pair for second detection. The drop was then applied 1.5, 5, 10, and 20 seconds later to fill the entire flow path. The deviation (%) of the response current (i.e., glucose measurement value) measured after the drop of blood was compared with the response current (i.e., glucose measurement value) measured without the drop of blood (i.e., the entire flow path was filled with a single drop of blood) was plotted against the time difference. Each plot is the average value for 45 blood samples. The deviation (%) was calculated using Equation (1). The plot for a time difference of 0.5 seconds shows the time difference without the drop of blood. In other words, the deviation (%) at 0.5 seconds is the response current value when no additional spotting is performed, and based on equation (1), P0-P t= 0, X in equation (1) also becomes 0, and the correction coefficient C in equation (2) becomes 1. As a result, for all hematocrit values, a positive deviation peak was observed at a time lag of 1.5 seconds. The deviation remained positive for up to 5 seconds, with the correction coefficient C falling below 1.0. However, after 5 seconds, as the time lag increased, the deviation became negative and the correction coefficient C rose to 1 or greater. Furthermore, the absolute value of the deviation increased with increasing hematocrit value. This is thought to be because the higher the hematocrit value, the higher the viscosity, making it difficult for the dissolved reagent to diffuse after the first application. Additionally, the high viscosity of the reagent reduces the diffusion area of ​​the reagent that reacts with the glucose to be measured, which is thought to be why even slight changes in the diffusion state of the reagent near the electrode surface are reflected in the measured current. Furthermore, since it was thought that if the time difference exceeded 10 seconds, the degree of discrepancy would increase and effective correction would not be possible, it was decided that the time difference for the follow-up spotting would be allowed up to 10 seconds.

[0077] The correction coefficients calculated from the deviations in FIG. 6 using the formula (2) are shown in Table 2 below.

[0078] [Table 2]

[0079] In the correction process, at the step shown in S180, a correction coefficient calculated based on the hematocrit value and time difference as shown in Table 2 is obtained for the glucose value as a parameter calculated from the first information. Correction coefficients corresponding to hematocrit values ​​and time differences not listed in the table can be calculated by linearly interpolating the values ​​in the table. Then, at the step shown in S190, the glucose value as a parameter is multiplied by this correction coefficient to calculate the glucose value as a measured value. Note that because the deviation is zero up to a time difference of 0.5 seconds, correction of the glucose value as a parameter is not necessary.

[0080] In the above measurement example, if the time difference is less than 0.5 seconds, no correction based on the time difference is made (the parameter value is left unchanged), if it is 0.5 seconds or more but less than 5 seconds, a correction is made to decrease the parameter value, and if the time difference is 5 seconds or more but less than 10 seconds, a correction is made to increase the parameter value. However, the time set as the predetermined value and the value of the correction coefficient can be adjusted appropriately for each biosensor depending on the characteristics of the reagent in the biosensor used (viscosity, enzyme activity, etc.), various conditions of the biosensor including the distance between the upstream electrode pair and the downstream electrode pair and the length and width of the flow path, the detection method for the first and second introductions, or the method for measuring the measured value of the analyte. However, the tendency of the deviation to be positive when the time difference is less than the predetermined value and negative when it is greater than the predetermined value depends on the degree of dissolution of the reagent and the degree of reaction between the reagent and the analyte, so the same tendency can be observed regardless of the type of biosensor used.

[0081] Furthermore, in the above measurement examples, a biosensor 2 is used that has five electrodes in flow path 2a: first working electrode 11 and first counter electrode 12 as first electrode pair 10, second working electrode 21 and second counter electrode 22 as second electrode pair 20, and blood detection electrode 30. However, the present invention can be applied to any biosensor 2 that has upstream electrode pair 15, on which reagent 40 that reacts with the analyte is placed, and downstream electrode pair 25 formed downstream of upstream electrode pair 15 in flow path 2a. Modified examples 1 and 2 are shown below as modified biosensors.

[0082] (4) Variation 1 The biosensor 2 of the first modification has a configuration similar to that of the biosensor 2 shown in Figures 2 and 3 in the configuration of (2) above, but does not include the blood detection electrode 30. That is, the biosensor 2 is provided with only four electrodes, namely, the first electrode pair 10 and the second electrode pair 20. The second counter electrode 22 of the second electrode pair 20 and the first working electrode 11 of the first electrode pair 10 form the upstream electrode pair 15, as in the configuration of (2) above. However, the first electrode pair 10 is used as the downstream electrode pair 25, which is different from the configuration of (2) above. Even with this configuration, measurements similar to the measurement example of (3) above are possible.

[0083] (5) Variation 2 The biosensor 2 of the second modification has a schematic configuration as shown in Fig. 7. That is, from the upstream side of the flow path 2a, only three electrodes are provided: a second counter electrode 22 for measuring hematocrit values, and a first electrode pair 10 (a first working electrode 11 and a first counter electrode 12). Even with this configuration, by configuring the two upstream electrodes, i.e., the second counter electrode 22 and the first working electrode 11, as an upstream electrode pair 15, and the two downstream electrodes, i.e., the first working electrode 11 and the first counter electrode 12, as a downstream electrode pair 25, it is possible to perform measurements similar to the measurement example (3) above. [Industrial Applicability]

[0084] The present invention can be used as a portable blood glucose measurement meter or blood glucose self-measurement meter that uses a biosensor, and can also be used as a measurement device that can measure items other than blood glucose. [Explanation of symbols]

[0085] 1 Measuring device 1a Main body 1b Insertion port 1c display screen 1d connector 2 Biosensor 2a Flow path 2b Covered area 2c Connector area 2d Blood supply port 2e Air vent 10 first electrode pair 11 first working electrode 11a lead portion 12 First counter electrode 12a Lead section 15 Upstream electrode pair 20 second electrode pair 21 second working electrode 21a lead portion 22 Second counter electrode 22a Lead section 25 downstream electrode pair 30 Blood detection electrode 30a Lead part 40 Reagents 45 Non-conductive area 50 Voltage applicator 51 Current / voltage conversion circuit 52 A / D conversion circuit 60 Measuring instrument 61 Spare measuring instrument 62 Auxiliary measuring instrument 63 Corrector 65 Introduction detector 66 First detector 67 Second detector 70 Time measuring device 90 Error indicator 100 control section 200 Connection Circuit 211 First working electrode switch 212 First counter electrode switch 221 Second working electrode switch 222 Second counter electrode switch 230 Blood detection electrode switch 311 Ground switch for first working electrode 312 Ground switch for first counter electrode 321 Ground switch for second working electrode 322 Ground switch for second counter electrode 330 Ground switch for blood detection electrode

Claims

1. a flow path into which blood containing a measurement object is introduced; an upstream electrode pair formed in the flow path, at least one of which has a reagent placed thereon that reacts with the object to be measured; a downstream electrode pair formed downstream of the upstream electrode pair in the flow channel; A measurement method for measuring a measurement value of a measurement object using a biosensor having a first detection step of detecting a first introduction of blood to the upstream electrode pair using the upstream electrode pair; a second detection step of detecting a second introduction of blood to the downstream electrode pair using the downstream electrode pair; a time measurement step of measuring a time difference from a time reference point at which the first introduction is detected to a time reference point at which the second introduction is detected; a measuring step of, after detecting the second introduction, acquiring the measurement value related to the measurement object based on the time difference measured in the time measuring step, using two electrodes of the upstream electrode pair, that is, the electrode on which the reagent is placed and the electrode provided in the flow path; the measurement step includes a preliminary measurement step of acquiring a parameter related to the object to be measured using the two electrodes, and a correction step of correcting the parameter based on the time difference to acquire the measurement value, the correction step refers to correction information for correcting and calculating the parameters in accordance with the time difference, corrects the parameters based on the time difference, and acquires the measurement values; The correction information is calculation information that decreases the value of the parameter when the time difference is longer than a normal value and less than a predetermined value, and increases the value of the parameter when the time difference is equal to or greater than the predetermined value.

2. The measurement method according to claim 1 , wherein the measurement step acquires the measured value using the two electrodes under measurement conditions based on the time difference.

3. 3. The measurement method according to claim 1, wherein the electrode other than the electrode on which the reagent is placed, of the two electrodes, is one of the electrodes constituting the upstream electrode pair and the downstream electrode pair.

4. The measurement method according to claim 1 , wherein the upstream electrode pair and the downstream electrode pair are each composed of separate electrodes.

5. a flow path into which blood containing a measurement object is introduced; an upstream electrode pair formed in the flow path, at least one of which has a reagent placed thereon that reacts with the object to be measured; a downstream electrode pair formed downstream of the upstream electrode pair in the flow channel; a biosensor having a first detector for detecting a first introduction of blood to the upstream electrode pair at the upstream electrode pair; a second detector for detecting a second introduction of blood to the downstream electrode pair at the downstream electrode pair; a time measuring device that measures the time difference between the detection of the first introduction and the detection of the second introduction; a measuring device that, after detecting the second introduction, acquires a measurement value related to the object to be measured based on the time difference measured by the time measuring device, using two electrodes, that is, the electrode of the upstream electrode pair on which the reagent is placed and another electrode provided in the flow path; the measuring device includes a spare measuring device that acquires a parameter related to the object to be measured using the two electrodes, and a corrector that corrects the parameter based on the time difference to acquire the measurement value; the corrector refers to correction information for performing a correction calculation on the parameter in response to the time difference, corrects the parameter based on the time difference, and acquires the measurement value; The correction information is calculation information that decreases the value of the parameter when the time difference is longer than the normal value and less than a predetermined value, and increases the value of the parameter when the time difference is equal to or greater than the predetermined value.

6. The measurement device according to claim 5 , wherein the measurement instrument obtains the measurement value using the two electrodes under measurement conditions based on the time difference.

7. The measuring device according to claim 5 or 6, wherein the other electrode of the two electrodes is one of the electrodes constituting the upstream electrode pair and the downstream electrode pair.

8. 8. The measuring device according to claim 5, wherein the upstream electrode pair and the downstream electrode pair are each composed of separate electrodes.

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