JP6895876B2 - Measuring method and measuring device to measure hematocrit value in blood - Google Patents

Description

The present invention relates to a measuring method and a measuring device for measuring a hematocrit value in blood.

Various techniques have been proposed as techniques for measuring the hematocrit value in blood. Patent Document 1 proposes a technique in which the resistance value of the electrode of a biosensor is measured in advance and the measured value of the hematocrit value is corrected by using the measurement result of the resistance value. Patent Document 2 proposes a technique for measuring a hematocrit value by applying a pulse wave to an electrode of a biosensor. Patent Document 3 describes a technique for measuring a hematoclit value using the ratio of the impedance of blood when a low frequency AC voltage of 5 kHz or less is applied to the impedance of blood when a high frequency AC voltage of 20 MHz or more is applied. It is disclosed.

Japanese Unexamined Patent Publication No. 2015-114153 Japanese Patent No. 6158133 Special Fair 5-18382 Gazette

Since the biosensor used for measuring the hematocrit value in blood is disposable for hygiene management because blood adheres to it, it is required to manufacture it as cheaply as possible. In addition, many biosensor products are small in size, which is smaller than the size of a fingertip. Since micro products are manufactured where there is a demand for low cost, manufacturing errors are likely to occur in the resistance value of the electrodes and the flow path through which blood flows, which each biosensor has. The above-mentioned manufacturing error may cause the desired accuracy of the hematocrit value measured by the biosensor to not be obtained.

One aspect of the disclosed technique is to suppress the influence of the manufacturing error of the biosensor on the measurement accuracy of the hematocrit value.

One aspect of the disclosed technique is exemplified by measuring methods for measuring hematocrit values in blood, such as: In this measurement method, the first step of applying AC signals of different frequencies to the electrode pairs with which blood is in contact, and the second step of acquiring the response values from the electrode pairs for each of the AC signals of different frequencies. And the value related to the relative relationship between the AC signal and the response value for each of the AC signals having different frequencies, and the rate of change of the value related to the relative relationship with respect to the frequency in the range of the different frequencies. It includes a third step of calculating and a fourth step of calculating the hematocrit value in the blood based on the rate of change. The disclosed technology can also be grasped as a measuring device.

The disclosed technique can suppress the influence of the manufacturing error of the biosensor on the measurement accuracy of the hematocrit value.

FIG. 1 is a diagram showing an example of a measurement system according to an embodiment. FIG. 2 is a perspective view showing an example of a biosensor. FIG. 3 is a diagram showing an example inside the housing of the measuring device. FIG. 4 is a diagram showing an example of calibration curve data. FIG. 5 is a diagram showing an example of a processing flow of the measurement system according to the embodiment. FIG. 6 is a graph illustrating the relationship between the frequency of the AC voltage applied to the electrode pair in contact with blood and the admittance value calculated using the biosensor and the measuring device. FIG. 7 is a graph illustrating the slope of the graph illustrated in FIG. 6 at each frequency. FIG. 8 is an example of a diagram illustrating the deviation between the hematocrit value and the true value converted by the calibration curve data. FIG. 9 is an example of a diagram illustrated in FIG. 8 enlarged from a frequency of 500 kHz to 1 MHz. FIG. 10 is a diagram showing an example of the coefficient of variation of the hematocrit value calculated based on the slope illustrated in FIG. 7 and the calibration curve at each frequency.

Hereinafter, embodiments will be described. The configurations of the embodiments shown below are examples, and the disclosed technology is not limited to the configurations of the embodiments.

(Measurement method for measuring hematocrit value in blood)
The measuring method for measuring the hematocrit value in blood according to this embodiment is
The first step of applying AC signals of different frequencies to the electrode pair with which blood is in contact, and
The second step of acquiring the response value from the electrode pair for each of the AC signals of different frequencies, and
A third value for calculating the relative relationship between the AC signal and the response value for each of the AC signals having different frequencies, and calculating the rate of change of the value related to the relative relationship with respect to the frequency in the range of the different frequencies. Process and
A fourth step of calculating the hematocrit value in the blood based on the rate of change is included.

(First step)
The AC signal is, for example, an AC voltage or an AC current. When an AC voltage is used as an example of an AC signal, a sinusoidal AC voltage is preferable. However, the AC voltage is not limited to a sine wave, and may be, for example, a triangular wave or a square wave AC voltage. Even when an AC current is used as an example of an AC signal, various waveforms can be obtained as in the case of an AC voltage. The electrode pair used in the above measuring method includes at least an working electrode and a counter electrode, and the electrode pair does not contain a reagent. The cell membrane of red blood cells, which make up the majority of blood components, consists of two layers, the electrical properties of which resemble capacitors. When the frequency of the AC voltage applied to the blood is 50 kHz or less, the red blood cells are regarded as an insulator, and when the frequency exceeds 100 kHz, the capacitive current begins to flow through the cell membrane of the red blood cells, and the impedance of the cell membrane is almost negligible at 20 MHz or more. Further, it is described in Patent Document 3 (Japanese Patent Publication No. 5-18362) that the impedance of blood is significantly reduced at 100 kHz to 10 MHz. As a result of diligent research, the inventor has found that the hematocrit value can be measured by utilizing the change in impedance (or admittance). Furthermore, it was confirmed that the hematocrit value can be measured for AC signals of any frequency if there is a change in impedance with respect to AC signals at different frequencies. Therefore, in the method for measuring the hematocrit value in blood according to the embodiment, the frequency of the AC signal applied to the electrode pair with which the blood is in contact is not limited, but it is preferable to use a frequency having a large change in impedance. The range of frequencies where the change in impedance is large is, for example, the range from the frequency at which the capacitive current begins to flow through the cell membrane of blood cells contained in blood to the frequency at which the change in the flow of the capacitive current becomes a certain range. .. The AC signal applied to the blood in the first step will be described in detail later, but is preferably an AC signal having a frequency between 400 kHz and 3 MHz, and more preferably an AC signal having a frequency between 600 kHz and 2 MHz. is there. Further, when applying the AC signal, an AC signal having a frequency of at least two selected points may be applied, or an AC signal may be applied while continuously changing the frequency in a predetermined range.

(Second step)
In the second step, the response values from the electrode pairs are acquired for each of the AC signals of different frequencies applied in the first step. As for the response value, for example, when the AC signal is an AC voltage, the current value is the response value, and when the AC signal is an AC current, the voltage value is the response value. However, the response value is not limited to these. The response value may be a value that can be obtained from the electrode pair as a response to the applied AC signal. When an AC signal is applied while continuously changing the frequency in the first step, the frequency at which the response value is acquired is determined, and the response value at the determined frequency is acquired. The frequency at which the response value is acquired may be a predetermined frequency, or may be determined from the tendency of the response value with respect to the actually acquired AC signal.

(Third step)
In the third step, a value related to the relative relationship between the AC signal and the response value is calculated for each of the AC signals having different frequencies. The value related to the relative relationship is, for example, an impedance value or an admittance value when the AC signal is an AC voltage and the response value is the current value flowing through the blood. Since the impedance value and the admittance value are inversely related to each other, it is easy to calculate the other by calculating one of them.

Further, in the third step, the rate of change of the value related to the relative relationship with respect to the frequency in different frequency ranges is calculated. For example, when the frequencies of the AC voltage applied in the first step are two different frequencies, the rate of change is calculated by dividing the difference between the calculated values related to the relative relationship by the difference between the two different frequencies. To. Further, for example, when the frequencies of the AC voltage applied in the first step are three different frequencies (F1, F2, and F3 from the highest frequency), the values related to the relative relationship with respect to F1 and F2. The difference between the value related to the relative relationship is divided by the difference between F1 and F2 to calculate the first value, and the difference between the value related to the relative relationship for F2 and the value related to the relative relationship for F3 is F2 and F3. The second value divided by the difference between the first value and the second value may be calculated, and the rate of change may be calculated as the average value of the first value and the second value. When an AC signal is applied while continuously changing the frequency in the first step, the same processing may be performed for the set of the response value for the frequency determined in the second step and the frequency determined. Further, for example, as another example in the case where the AC signal is applied while continuously changing the frequency in the first step, the value related to the relative relationship is taken on one coordinate axis and the frequency of the AC voltage is taken on the other coordinate axis. On the two-dimensional coordinates, the frequency of the AC voltage and the value related to the relative relationship with respect to the frequency are recorded as points on the two-dimensional coordinates, and an approximate curve passing through the recorded points is determined. The differential value at the predetermined coordinates on the determined approximate curve may be calculated as the rate of change. Here, there is no limitation on the approximation method for determining the approximation curve. The approximation method may be, for example, a first-order approximation or a quadratic approximation. Further, the predetermined coordinates may be, for example, points on the determined approximate curve, and one coordinate may be a coordinate corresponding to one frequency selected from the applied different frequencies.

(4th step)
In the fourth step, the hematocrit value in blood is calculated based on the calculated rate of change. In the calculation, for example, the hematocrit value is calculated based on the correspondence between the rate of change and the hematocrit value. The correspondence is, for example, a calibration curve that associates the rate of change with the hematocrit value, a function that outputs the hematocrit value when the rate of change is input, and the like. In biosensors, as described above, individual differences may occur for each product due to manufacturing errors and the like. However, in the present embodiment, by calculating the rate of change between the measured relative values, the influence of the error can be suppressed and the decrease in the measurement accuracy of the hematocrit value in blood can be suppressed.

The measuring method for measuring the hematocrit value in blood and the measuring device for executing the measuring method will be described in more detail with reference to the following drawings. In the following, a case of measuring the hematocrit value in blood using a biosensor will be described.

FIG. 1 is a diagram showing an example of the measurement system 1 according to the embodiment. The measuring system 1 includes a measuring device 30 and a biosensor 40. The measuring system 1 measures the hematocrit value in the blood spotted on the biosensor 40. The measuring device 30 includes a housing 31, a plurality of operation buttons 32, a display panel 33, and a sensor insertion port 34.

As shown in FIG. 1, the housing 31 of the measuring device 30 is provided with an operation button 32 and a display panel 33. The operation button 32 is used for performing various settings (setting of measurement conditions, input of a user's ID, etc.) and operations such as start and end of measurement. The operation button 32 may be a contact type touch panel. The display panel 33 displays the measurement result and the error, and also displays the operation procedure, the operation status, and the like at the time of setting. The display panel 33 is, for example, a liquid crystal display device, a plasma display panel, a CRT, an electroluminescence panel, or the like. The operation buttons 32 and the display panel 33 may be integrated by arranging the contact type touch panel on the display panel 33 in an overlapping manner.

The biosensor 40 includes a pair of electrodes with which the blood to be measured comes into contact. FIG. 2 is a perspective view showing an example of the biosensor 40. The biosensor 40 is formed by laminating a substrate 41, a spacer 42, and a cover 43 in the height direction. The electrode pair 44 formed on the upper surface of the substrate 41 includes an working electrode 44a and a counter electrode 44b in measuring the hematocrit value. Each of the working electrode 44a and the counter electrode 44b is conductive and is arranged at a predetermined distance. In the following description, the expression "electrode" is used when two or more electrodes (such as the working electrode 44a and the counter electrode 44b) forming the electrode pair 44 are not particularly distinguished. The material of the electrode is not particularly limited as long as it is a conductive material, but for example, a metal material such as gold (Au), platinum (Pt), silver (Ag) and palladium (Pd), or graphite or carbon nanotube. , Graphene, mesoporous carbon and other carbon materials typified by carbon. The electrodes are formed on, for example, an insulating substrate 41, and preferably, each electrode forming the electrode pair 44 (such as the working electrode 44a and the counter electrode 44b) is formed on the same substrate 41. The insulating substrate 41, spacer 42 and cover 43 are made of various resins (plastics) such as thermoplastic resins such as polyetherimide (PEI), polyethylene terephthalate (PET) and polyethylene (PE), polyimide resins and epoxy resins. ), Made of insulating materials such as glass, ceramics and paper. The size, thickness, and position of the working electrode 44a, the counter electrode 44b, and the substrate 41 can be appropriately set. The electrodes can be formed on the substrate 41 by, for example, screen printing using carbon ink. One end of the electrode is arranged so as to sandwich the blood in the flow path 46 between them, and the other end is exposed on the substrate 41 so as to be electrically connected to the measuring device 30. In biosensors, reagents such as enzymes and mediators capable of reacting with components may be used for electrode pairs in order to detect components contained in blood (for example, glucose, lactic acid, ascorbic acid, acetaminophen, etc.). The electrode pair 44 of the biosensor 40 according to the present embodiment does not use such a reagent. The electrode pair 44 including the working electrode 44a and the counter electrode 44b is an example of an “electrode pair”.

The flow path 46 is formed by an insulating substrate 41, a spacer 42, and a cover 43, and a collection port 45 on which blood is spotted is provided at one end thereof. The cover 43 is provided with an exhaust port 47 for exhausting the gas inside the flow path 46 to the outside. The blood sprinkled on the collection port 45 moves in the flow path 46 toward the exhaust port 47 by utilizing the capillary phenomenon. The blood flowing toward the exhaust port 47 comes into contact with the electrode pair 44 in the flow path 46.

FIG. 3 is a diagram showing an example of the inside of the housing 31 of the measuring device 30, and shows a state in which the biosensor 40 is inserted into the sensor insertion port 34 of the measuring device 30. In FIG. 3, the working pole 44a and the counter pole 44b of the biosensor 40 are shown in a simplified manner. Inside the housing 31, a connection unit 101, an application unit 102, an acquisition unit 103, a control unit 104, a storage unit 107, and an output unit 108 are provided. The connection portion 101 has a number of connection terminals 101a and 101b corresponding to the electrodes of the electrode pair 44 so that the biosensor 40 can be electrically connected to the electrode pair 44.

The application unit 102 generates AC signals having different frequencies, and applies the generated AC signals to the electrode pair 44 of the biosensor 40 connected to the connection unit 101. The application unit 102 may generate an AC voltage or an AC current as an AC signal. The waveform of the AC signal generated by the application unit 102 is preferably a sine wave, but is not limited to the sine wave. The application unit 102 may select at least two frequencies and apply an AC signal of the selected frequency, or may apply the AC signal while continuously changing the frequency in a predetermined range.

The acquisition unit 103 acquires the response value to the AC signals of different frequencies applied to the electrode pair 44 of the biosensor 40 by the application unit 102. For example, when the application unit 102 applies an AC voltage to the electrode pair 44, a current is applied between the working electrode 44a of the electrode pair 44 and the counter electrode 44b of the electrode pair 44 through the blood in contact with the electrode pair 44. Flows. Then, the acquisition unit 103 can acquire the response current value, which is the response value to the AC voltage, via the connection terminal 101b of the connection unit 101 connected to the counter electrode 44b. Here, when at least two frequencies are selected and the application unit 102 applies the AC signal of the selected frequency, the acquisition unit 103 acquires the response value for the AC signal of each of the selected frequencies. When the application unit 102 applies an AC signal while continuously changing the frequency, the frequency at which the response value is acquired is determined, and the acquisition unit 103 acquires the response value for the AC signal at the determined frequency. As the frequency for acquiring the response value, for example, a predetermined frequency may be stored in the storage unit 107 in advance, and the acquisition unit 103 may acquire the response value for the predetermined frequency stored in the storage unit 107. Further, for example, the frequency at which the response value is acquired may be determined by the acquisition unit 103 from the tendency of the response value with respect to the acquired AC signal.

The control unit 104 controls the AC voltage applied by the application unit 102, calculates the hematocrit value in blood using the response current value acquired by the acquisition unit 103, and the like. The control unit 104 is, for example, an arithmetic processing unit exemplified by a central processing unit (CPU). C
The PU is also called a microprocessor unit (MPU) or a processor. The CPU is not limited to a single processor, and may have a multiprocessor configuration.

The storage unit 107 includes an auxiliary storage device such as a Random Access Memory (RAM), a Read Only Memory (ROM), and a hard disk. The storage unit 107 stores a program executed by the control unit 104, calibration curve data for calculating the hematocrit value in blood, and information used for various measurements. FIG. 4 is a diagram showing an example of the calibration curve data. Since the rate of change and the hematocrit value (hematocrit conversion value) are associated with each other in the calibration curve data, the control unit 104 hematocrits based on the rate of change. The value can be calculated. The calibration curve data stored in the storage unit 107 is an example, and the correspondence between the rate of change and the hematocrit value in blood may be stored in the storage unit 107. The correspondence stored in the storage unit 107 may be, for example, a function that outputs a hematocrit value when the rate of change is input. Further, the storage unit 107 stores information necessary for various measurements in addition to the calibration curve data, and is used by the first calculation unit 105, the second calculation unit 106, and the like.

By executing the program stored in the storage unit 107, the control unit 104 executes the processing as the first calculation unit 105 and the second calculation unit 106, and controls the AC signal applied by the application unit 102. Or something. The first calculation unit 105 calculates a value related to the relative relationship between the AC signal of the frequency applied by the application unit 102 and the response value acquired by the acquisition unit 103 for each of the different frequencies, and is relative in a range of different frequencies. Calculate the rate of change of the value related to the relationship with respect to the frequency. For example, when the application unit 102 applies an AC voltage as an AC signal, the acquisition unit 103 calculates an impedance value and an admittance value as values related to the relative relationship. The second calculation unit 106 calculates the hematocrit value in blood based on the rate of change calculated by the first calculation unit 105 and the calibration curve data stored in the storage unit 107. The output unit 108 outputs various information including the hematocrit value in blood calculated by the control unit 104 to be displayed on the display panel 33.

FIG. 5 is a diagram showing an example of a processing flow of the measurement system 1 according to the embodiment. As a preparation before the start of the processing flow of FIG. 5, the biosensor 40 in a state where the blood to be measured is in contact with the electrode pair 44 is inserted into the sensor insertion port 34 of the measuring device 30. In the following processing flow, a case where an AC voltage is applied as an AC signal will be described. Hereinafter, an example of the processing flow of the measurement system 1 will be described with reference to FIG.

In S1, the application unit 102 applies an AC voltage of a different frequency to the electrode pair 44 of the biosensor 40. In the present embodiment, the application unit 102 applies, for example, an AC voltage of 855 kHz and an AC voltage of 845 kHz to the electrode pair 44 as AC voltages of different frequencies. The step S1 is an example of the "first step".

In S2, the acquisition unit 103 acquires the response current value for the AC voltage of 855 kHz and the response current value for the AC voltage of 845 kHz. The step S2 is an example of the "second step".

In S3, the first calculation unit 105 determines the admittance value and 845 kHz when an AC voltage of 855 kHz is applied based on the AC voltage applied by the application unit 102 in S1 and the response current value acquired by the acquisition unit 103 in S2. The admittance value when the AC voltage of is applied is calculated.

In S4, the first calculation unit 105 calculates the rate of change in the admittance value with respect to the frequency based on the difference in the frequency of the AC voltage applied in S1 and the difference in the admittance value calculated in S3. In calculating the rate of change, for example, the first calculation unit 105 determines the difference between the admittance value when the AC voltage of 855 kHz calculated in S3 is applied and the admittance value when the AC voltage of 845 kHz is applied. The rate of change is calculated by dividing the difference between the calculated admittance values by 10 kHz, which is the difference between 855 kHz and 845 kHz. The steps S3 and S4 are an example of a "third step". The frequency of 855 kHz is an example of the "first frequency", and the frequency of 845 kHz is an example of the "second frequency".

In S5, the second calculation unit 106 calculates the hematocrit value based on the rate of change of the admittance value with respect to the frequency calculated in S4 and the calibration curve data stored in the storage unit 107. The step S5 is an example of the "fourth step".

Here, the principle of the measurement method according to the embodiment will be described. FIG. 6 is a graph illustrating the relationship between the frequency of the AC voltage applied to the electrode pair 44 in contact with blood and the admittance value calculated using the biosensor 40 and the measuring device 30. In FIG. 6, the vertical axis represents the admittance value, and the horizontal axis represents the frequency of the applied AC voltage. The horizontal axis of FIG. 6 is represented by a logarithm. In the measurement according to FIG. 6, the applied voltage is 0.2 V _pp . In the measurement according to FIG. 6, the frequency of the AC voltage is changed in the range of 10 kHz to 5 MHz, and the impedance value is measured. The admittance value illustrated in FIG. 6 is calculated based on the average value of the impedance values measured five times. The blood to be measured has a hematocrit value of 10% (graph A in FIG. 6), a hematocrit value of 42% (graph B in FIG. 6), and a hematocrit value of 65% (graph C in FIG. 6). ). The hematocrit value of the blood to be measured is measured in advance by centrifuging the blood with a centrifuge.

FIG. 7 is a graph illustrating the slope of the graph illustrated in FIG. 6 at each frequency. In FIG. 7, in the graph illustrated in FIG. 6, the slope is calculated and graphed for each frequency of 10 kHz. In FIG. 7, the vertical axis shows the slope and the horizontal axis shows the frequency of the applied AC voltage. The horizontal axis of FIG. 7 is represented by a logarithm as in FIG. Graph A, graph B, and graph C in FIG. 7 correspond to graph A, graph B, and graph C in FIG. 6, respectively. As can be understood with reference to FIG. 7, in the frequency band around 850 kHz, there is less variation in the slope with respect to the frequency in each of the graphs A, B, and C than in the other frequency bands, and the graphs A, B, and C are also separated from each other. ing. The frequency band around 850 kHz is considered to be a frequency band in which the hematocrit value can be calculated with higher accuracy than other frequency bands by the slope of the graph.

Based on the correspondence between the slope illustrated in FIG. 7 and the hematocrit value, a calibration curve for calculating the hematocrit value from the slope at each frequency is determined. The calibration curve is, for example, as shown in FIG. 4 described above, in which the slope and the hematocrit value are associated with each other. FIG. 8 is an example of a diagram illustrating the deviation between the hematocrit value converted by the calibration curve and the true value. FIG. 9 is an example of a diagram illustrated in FIG. 8 enlarged from a frequency of 500 kHz to 1 MHz. The true values in FIGS. 8 and 9 are, for example, values measured by centrifuging blood with a centrifuge. In FIGS. 8 and 9, the vertical axis indicates the magnitude of deviation from the true value, and the horizontal axis indicates the frequency of the applied AC voltage. With reference to FIGS. 8 and 9, it can be seen that in the frequency band from 500 kHz to 1 MHz around 850 kHz, the deviation from the true value is smaller than in the other frequency bands.

FIG. 10 is a diagram showing an example of the coefficient of variation of the hematocrit value calculated based on the slope illustrated in FIG. 7 and the calibration curve at each frequency. In FIG. 10, the coefficient of variation is exemplified for each of blood having a hematocrit value of 10%, blood having a hematocrit value of 42%, and blood having a hematocrit value of 65%. In order to preferably calculate the hematocrit value, the coefficient of variation is preferably 10% or less, and more preferably 5% or less. From this, the frequency of the AC voltage used when calculating the hematocrit value is preferably 400 kHz to 3 MHz, and more preferably 600 kHz to 2 MHz. Based on the above principle, in the processing flow illustrated in FIG. 5 of the present embodiment, 855 kHz and 845 kHz are selected as the two different frequencies, but the frequency value, the number of measurements, and the number of measurements are based on the above principle. The difference in frequency between the values may be appropriately selected. It can be said that selecting the frequency according to the above principle determines the frequency at which the response current value is acquired from the tendency of the response current value with respect to the AC voltage.

<Effect of embodiment>
In the biosensor 40, as described above, individual differences are likely to occur for each product in the resistance values of the working electrode 44a and the counter electrode 44b, the height h of the flow path 46, and the like due to manufacturing errors and the like. In the present embodiment, the resistance value of the working electrode 44a and the counter electrode 44b and the height h of the flow path are calculated by calculating the rate of change between the measured impedance values (or admittance values) affected by the manufacturing error or the like. The effect of the error is suppressed. Therefore, even if the biosensor 40 has a manufacturing error in the resistance value of the working electrode 44a and the counter electrode 44b, the height h of the flow path 46, etc., the influence of the error is suppressed and the measurement accuracy of the hematocrit value in blood is lowered. Can be suppressed. Further, since the influence of the error of the resistance values of the working pole 44a and the counter electrode 44b is suppressed, the step of measuring the resistance values of the working pole 44a and the counter electrode 44b in advance and the step of correcting the hematocrit value based on the measured resistance values. Can be omitted. As a result, in the present embodiment, the influence of the above-mentioned manufacturing error on the measurement accuracy of the hematocrit value on the biosensor can be suppressed by a simple configuration.

In the method for measuring the hematocrit value according to the present embodiment, even if the measurement has a low hematocrit value (for example, about 10%) in which the influence of the error on the resistance values of the working electrode 44a and the counter electrode 44b becomes large, the measurement is about the same as the phase measurement. Measurement accuracy is realized. Further, since the hematocrit value measuring method according to the present embodiment does not require high-speed sampling, it can be realized by a system that is cheaper than the hematocrit value measuring method using phase measurement that requires high-speed sampling.

The method for measuring the hematocrit value according to the present embodiment includes a low hematocrit value because the measurement accuracy is higher at a low hematocrit value when compared with the technique according to Patent Document 2 for measuring the hematocrit value using a pulse wave. High measurement accuracy can be achieved for blood with various hematocrit values.

Since the method for measuring the hematocrit value according to the present embodiment does not need to use a high frequency of 20 MHz or more as in the technique according to Patent Document 3, it can be realized by an apparatus cheaper than the technique according to Patent Document 3.

1 ... Measuring system 30 ... Measuring device 31 ... Housing 32 ... Operation button 33 ... Display panel 34 ... Sensor insertion port 40 ... Biosensor 41 ... Board 42.・ ・ Spacer 43 ・ ・ ・ Cover 44 ・ ・ ・ Electrode pair 44a ・ ・ ・ Working electrode 44b ・ ・ ・ Counter electrode 45 ・ ・ ・ Collection port 46 ・ ・ ・ Flow path 101 ・ ・ ・ Connection part 102 ・ ・ ・ Application part 103・ ・ ・ Acquisition unit 104 ・ ・ ・ Control unit 105 ・ ・ ・ First calculation unit 106 ・ ・ ・ Second calculation unit 107 ・ ・ ・ Storage unit 108 ・ ・ ・ Output unit

Claims (9)

The first step of applying AC signals of different frequencies to the electrode pair with which blood is in contact, and
The second step of acquiring the response value from the electrode pair for each of the AC signals of different frequencies, and
A third value for calculating the relative relationship between the AC signal and the response value for each of the AC signals having different frequencies, and calculating the rate of change of the value related to the relative relationship with respect to the frequency in the range of the different frequencies. Process and
Includes a fourth step of calculating the hematocrit value in the blood based on the rate of change.
A measuring method for measuring the hematocrit value in blood. The electrode pair does not contain reagents,
The measuring method according to claim 1. In the third step, the relative relationship is the ratio of the AC signal to the response value.
The rate of change by dividing the difference between the value of the ratio corresponding to the first frequency and the value of the ratio corresponding to the second frequency by the difference between the first frequency and the second frequency. To calculate,
The measuring method according to claim 1 or 2. In the fourth step, the hematocrit value in the blood is calculated based on the calibration curve in which the rate of change and the hematocrit value are associated with each other.
The measuring method according to any one of claims 1 to 3. The AC signal is an AC voltage, and the response value is a current value flowing through the blood due to the AC voltage.
The measuring method according to any one of claims 1 to 4. The different frequencies are selected from the frequency at which the capacitive current begins to flow through the cell membrane of the blood cells contained in the blood to the frequency at which the change in the flow of the capacitive current falls within a certain range.
The measuring method for measuring the hematocrit value according to any one of claims 1 to 5. The different frequencies are selected from between 400 kHz and 3 MHz.
The measuring method according to any one of claims 1 to 6. The different frequencies are selected from between 600 kHz and 2 MHz.
The measuring method according to claim 7. A connection with a biosensor, including a pair of electrodes that come into contact with blood,
An application unit that applies AC signals of different frequencies to the electrode pair connected to the connection unit, and an application unit.
An acquisition unit that acquires a response value from the electrode pair for each of the AC signals of different frequencies, and
A first calculation unit that calculates a value related to the relative relationship between the AC signal and the response value for each of the different frequencies, and calculates the rate of change of the value related to the relative relationship with respect to the frequency in the range of the different frequencies. When,
A second calculation unit for calculating the hematocrit value in the blood based on the rate of change is provided.
measuring device.

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