WO2010061629A1 - センサチップ、バイオセンサシステム、生体試料の温度測定方法、血液試料の温度測定方法、血液試料中の分析物の濃度測定方法 - Google Patents
センサチップ、バイオセンサシステム、生体試料の温度測定方法、血液試料の温度測定方法、血液試料中の分析物の濃度測定方法 Download PDFInfo
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- WO2010061629A1 WO2010061629A1 PCT/JP2009/006435 JP2009006435W WO2010061629A1 WO 2010061629 A1 WO2010061629 A1 WO 2010061629A1 JP 2009006435 W JP2009006435 W JP 2009006435W WO 2010061629 A1 WO2010061629 A1 WO 2010061629A1
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- temperature
- data
- concentration
- blood sample
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- QYGJLXSNKWVKMQ-IENPIDJESA-N CC[C@H](C1)C=C(C)C1(C)N Chemical compound CC[C@H](C1)C=C(C)C1(C)N QYGJLXSNKWVKMQ-IENPIDJESA-N 0.000 description 1
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
- G01N27/3271—Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood
- G01N27/3274—Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/28—Electrolytic cell components
- G01N27/30—Electrodes, e.g. test electrodes; Half-cells
- G01N27/327—Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01K—MEASURING TEMPERATURE; MEASURING QUANTITY OF HEAT; THERMALLY-SENSITIVE ELEMENTS NOT OTHERWISE PROVIDED FOR
- G01K1/00—Details of thermometers not specially adapted for particular types of thermometer
- G01K1/16—Special arrangements for conducting heat from the object to the sensitive element
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01K—MEASURING TEMPERATURE; MEASURING QUANTITY OF HEAT; THERMALLY-SENSITIVE ELEMENTS NOT OTHERWISE PROVIDED FOR
- G01K7/00—Measuring temperature based on the use of electric or magnetic elements directly sensitive to heat ; Power supply therefor, e.g. using thermoelectric elements
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/416—Systems
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/49—Blood
Definitions
- the present invention relates to a sensor chip, a biosensor system, a temperature measurement method for a biological sample, a temperature measurement method for a blood sample, and a concentration measurement method for an analyte in the blood sample.
- a portable biosensor system including a measuring instrument having a calculation unit and a sensor chip detachably attached to the measuring instrument in order to measure an analyte concentration in a blood sample, for example, a blood glucose concentration (blood glucose level). It is used.
- concentration of the analyte is calculated by an electrochemical method or an optical method based on the amount of an oxidant or a reductant generated by an enzyme cycling reaction via an oxidoreductase using the analyte as a substrate.
- the rate of the enzyme cycling reaction depends on the temperature at which the reaction proceeds (reaction temperature). For this reason, it is desirable to correct the concentration of the analyte based on the reaction temperature.
- the reaction temperature is measured by, for example, a temperature sensor arranged in a measuring instrument (Patent Document 1).
- a temperature sensor arranged in a measuring instrument
- the measured reaction temperature does not accurately reflect the temperature of the blood sample. For this reason, errors may occur in the measurement of the analyte concentration.
- Patent Documents 2 to 4 disclose biosensor systems aimed at improving reaction temperature measurement accuracy.
- the biosensor systems of Patent Documents 2 and 3 have a heat conducting member in the vicinity of the blood sample holding part of the sensor chip, and the temperature of the blood sample transmitted through the heat conducting member is arranged in a measuring instrument. Detected by a temperature sensor.
- the heat conducting member does not contact the blood sample.
- a temperature sensor and a heat conduction member are arranged in a mounting portion of a measuring instrument for attaching a sensor chip, and the temperature of the blood sample is transmitted to the temperature sensor via the heat conduction member. .
- the measured reaction temperature is the temperature of the blood sample. Does not reflect accurately.
- a sensor chip is a sensor chip that measures the temperature of a biological sample, and has at least a working electrode and a counter electrode to measure the temperature of the biological sample, and a DC voltage is applied. And a capillary for introducing a biological sample to the temperature electrode. The working electrode and / or the counter electrode of the temperature electrode are arranged so as to contact the biological sample introduced into the capillary. The DC voltage is set so that the influence of the hematocrit on the temperature measurement result is reduced when the DC voltage is applied.
- the sensor chip according to the second aspect of the present invention is the sensor chip according to the first aspect, wherein the amount of the biological sample taken in the capillary is 5 ⁇ L or less, and the application time of the DC voltage at the temperature electrode is 15 seconds or less. is there.
- the sensor chip according to the third aspect of the present invention is the sensor chip according to the first or second aspect, and the predetermined DC voltage is a range in which the solvent of the biological sample is electrolyzed.
- the sensor chip according to the fourth aspect of the present invention is a sensor chip according to any one of the first to third aspects and is disposable.
- a sensor chip is a sensor chip that measures the concentration of an analyte in a blood sample, and is disposed so as to contact the blood sample, and at least acts to measure the temperature of the blood sample.
- a temperature electrode having an electrode and a counter electrode; and a concentration measuring unit used for measuring an item related to the concentration of the analyte in the blood sample.
- the sensor chip according to the sixth aspect of the present invention is the sensor chip according to the fifth aspect, and the concentration measuring unit is an analysis electrode including at least a working electrode and a counter electrode.
- the sensor chip according to the seventh aspect of the present invention is the sensor chip according to the sixth aspect, and the temperature electrode and the analysis electrode are provided separately.
- a sensor chip according to an eighth aspect of the present invention is the sensor chip according to the sixth or seventh aspect, wherein a sample introduction port, a capillary for introducing a blood sample from the sample introduction port to the temperature electrode and the analysis electrode, Is further provided.
- the temperature electrode is disposed closer to the sample introduction port than the analysis electrode.
- a sensor chip according to a ninth aspect of the present invention is the sensor chip according to any one of the fifth to eighth aspects, wherein the temperature electrode is not in contact with at least one of the oxidoreductase and the electron mediator. Has been placed.
- a sensor chip according to a tenth aspect of the present invention is the sensor chip according to any one of the fifth to ninth aspects, wherein the concentration measuring unit further includes a reaction reagent that causes an oxidation-reduction reaction, and a temperature electrode Is arranged so as not to come into contact with a reaction reagent that causes a redox reaction.
- the sensor chip according to the eleventh aspect of the present invention is the sensor chip according to any one of the fifth to ninth aspects, and is disposed so as not to contact any reagent.
- the sensor chip according to the twelfth aspect of the present invention is the sensor chip according to the sixth aspect, wherein the working electrode of the temperature electrode is common to at least either the working electrode or the counter electrode of the analysis electrode.
- the sensor chip according to the thirteenth aspect of the present invention is the sensor chip according to the sixth aspect, wherein the counter electrode of the temperature electrode is common to at least either the working electrode or the counter electrode of the analysis electrode.
- a sensor chip according to a fourteenth aspect of the present invention is the sensor chip according to any one of the sixth to eighth aspects, wherein the concentration measuring unit has one or more electrodes other than the working electrode and the counter electrode. In addition, at least one of the electrodes of the concentration measuring unit other than the working electrode and the counter electrode is common to at least one of the working electrode and the counter electrode of the temperature electrode.
- the electrode included in the concentration measuring unit may also serve as at least one of the working electrode and the counter electrode of the temperature electrode.
- the sensor chip of the twelfth and thirteenth aspects may include a plurality of working electrodes and / or a plurality of counter electrodes as analysis electrodes. At least one of the plurality of working electrodes and / or counter electrodes can also serve as the working electrode and / or counter electrode of the temperature electrode.
- Electrodes other than the working electrode and the counter electrode in the fourteenth aspect As an example of electrodes other than the working electrode and the counter electrode in the fourteenth aspect, -Electrodes for measuring hematocrit, -Electrodes for measuring the concentration or amount of reducing substances, -A sensing electrode that detects the introduction of blood, -Other measurement electrodes provided in addition to electrodes for measuring glucose concentration, hematocrit, or concentration or amount of reducing substance.
- the sensor chip according to the fifteenth aspect of the present invention is the sensor chip according to the sixth aspect, wherein the area of the working electrode in the temperature electrode is the same as or smaller than the area of the counter electrode in the temperature electrode.
- the sensor chip according to the sixteenth aspect of the present invention is the sensor chip according to any one of the fifth to fifteenth aspects, and the item relating to the concentration of the analyte includes at least hematocrit.
- a sensor chip according to a seventeenth aspect of the present invention is the sensor chip according to any one of the fifth to sixteenth aspects, wherein the item relating to the concentration of the analyte includes at least the amount or concentration of the reducing substance. It is.
- a biological sample temperature measurement method is a temperature measurement method for measuring a temperature of a biological sample in a sensor chip including a temperature electrode formed from a working electrode and a counter electrode, and a capillary.
- the first voltage is set so that the influence of the hematocrit on the temperature measurement result is reduced when the first voltage is applied to the temperature electrode.
- This method makes it possible to measure the temperature of a biological sample independent of the hematocrit value in the biological sample. As a result, the accuracy of temperature measurement of the biological sample can be increased, and the accuracy of various corrections using the temperature of the biological sample can be increased.
- a temperature measurement method is the temperature measurement method according to the eighteenth aspect, in which a DC voltage value is measured and stored in advance so that the influence of hematocrit on the temperature measurement result is reduced.
- the adjustment step is a step of adjusting to the first voltage based on the stored DC voltage.
- the biological sample temperature measurement method according to the twentieth aspect of the present invention is the biological sample temperature measurement method according to the eighteenth or nineteenth aspect, wherein the uptake amount of the biological sample in the uptake step is 5 ⁇ L or less, The application time of the DC voltage in the application step is 15 seconds or less.
- a blood sample temperature measuring method is a method for measuring the temperature of a blood sample used in a sensor chip having a temperature electrode formed of a working electrode and a counter electrode, Applying a voltage to the temperature electrode brought into contact with the sample; obtaining data a related to the temperature of the blood sample based on the magnitude of the current flowing in the blood sample by applying the voltage; calculating a temperature t of the blood sample based on a.
- the temperature t of the blood sample is calculated based on the data a related to the temperature of the blood sample that can be acquired by applying a voltage to the temperature electrode brought into contact with the blood sample.
- the method for measuring the concentration of an analyte in a blood sample is based on the magnitude of the current flowing in the blood sample by applying a voltage to a pair of electrodes in contact with the blood sample.
- the data a obtained by directly measuring the temperature of the blood sample is obtained without going through the resin plate or the heat conducting member, and the data a related to the temperature of the blood sample and the concentration of the analyte are obtained. Based on data b, the analyte concentration in the blood sample is determined.
- a method for measuring the concentration of an analyte in a blood sample according to a twenty-third aspect of the present invention is a method for measuring the concentration of an analyte in a blood sample according to the twenty-second aspect, wherein the concentration measuring step is based on data a. a step of correcting b.
- the method for measuring the concentration of an analyte in a blood sample according to the twenty-fourth aspect of the present invention is a method for measuring the concentration of an analyte in a blood sample according to the twenty-second aspect, wherein the concentration measuring step is based on the data b.
- the method for measuring the concentration of an analyte in a blood sample according to the twenty-fifth aspect of the present invention is a method for measuring the concentration of an analyte in a blood sample according to the twenty-second aspect, wherein the concentration measuring step is based on the data a.
- a method for measuring the concentration of an analyte in a blood sample according to a twenty-sixth aspect of the present invention is a method for measuring the concentration of an analyte in a blood sample according to the twenty-second aspect, wherein the concentration measuring step is based on data a.
- a method for measuring the concentration of an analyte in a blood sample according to a twenty-seventh aspect of the present invention is a method for measuring the concentration of an analyte in a blood sample according to any one of the twenty-second to twenty-sixth aspects, wherein the data a
- the step of acquiring is performed before the step of acquiring the data b.
- An analyte concentration measurement method in a blood sample according to a twenty-eighth aspect of the present invention is an analyte concentration measurement method in a blood sample according to the twenty-second aspect, wherein the concentration measurement step is performed after blood b is acquired.
- a method for measuring the concentration of an analyte in a blood sample according to the twenty-ninth aspect of the present invention is a method for measuring the concentration of an analyte in a blood sample according to the twenty-second aspect, wherein the concentration measuring step is based on data a.
- a step of calculating the temperature t of the blood sample a step of calculating the concentration x of the analyte of the blood sample based on the data b, a step of measuring the ambient temperature t1 around the blood sample, the temperature t and the ambient temperature
- the temperature t of the blood sample is calculated based on the data a
- the concentration x of the analyte of the blood sample is calculated based on the data b
- the ambient temperature t1 around the blood sample is further measured. Then, the difference between the temperature t and the environmental temperature t1 is compared with the temperature threshold Z and corrected as follows.
- the concentration x is corrected based on the temperature t.
- the concentration x is corrected based on the temperature t1. Since the concentration x can be corrected using a suitable temperature, the measurement accuracy of the analyte concentration in the blood sample can be improved.
- a method for measuring the concentration of an analyte in a blood sample according to the thirtieth aspect of the present invention is a method for measuring the concentration of an analyte in a blood sample according to any one of the twenty-second to twenty-ninth aspects, comprising:
- the data a related to the temperature a includes the temperature
- the data b related to the concentration of the analyte includes the glucose concentration.
- temperature is included as an item of data acquired as data a
- glucose concentration is included as an item of data acquired as data b.
- the analyte concentration measuring method in the blood sample according to the thirty-first aspect of the present invention is the analyte concentration measuring method in the blood sample according to the thirty-first aspect, wherein the data b relating to the analyte concentration includes Hematocrit is included.
- hematocrit is included as an item of data acquired as data b.
- a method for measuring the concentration of an analyte in a blood sample according to the thirty-second aspect of the present invention is a method for measuring the concentration of an analyte in a blood sample according to the thirty or thirty-first aspect, wherein the data relates to the concentration of the analyte.
- b contains the amount or concentration of the reducing substance.
- the amount or concentration of reducing substance is included as an item of data acquired as data b.
- a method for measuring the concentration of an analyte in a blood sample according to the thirty-third aspect of the present invention is a method for measuring the concentration of an analyte in a blood sample according to any one of the thirty-third to thirty-second aspects, wherein the data a And at least two items of data included in data b are measured simultaneously.
- two or more items are measured simultaneously.
- the glucose concentration and the amount or concentration of the reducing substance are simultaneously measured.
- a method for measuring the concentration of an analyte in a blood sample according to a thirty-fourth aspect of the present invention is a method for measuring the concentration of an analyte in a blood sample according to any one of the thirty-second to thirty-second aspects, wherein the data a And measurement of data included in data b are performed independently.
- a method for measuring the concentration of an analyte in a blood sample according to the thirty-fifth aspect of the present invention is a method for measuring the concentration of an analyte in a blood sample according to any one of the thirtieth to thirty-second aspects, wherein the data a
- the measurement of data included in data b is performed in the order of temperature, glucose concentration and amount or concentration of reducing substance, and hematocrit.
- the order of data measurement is specified. This makes it possible to obtain advantageous effects in terms of speed, accuracy, and burden on the electrodes.
- a method for measuring the concentration of an analyte in a blood sample according to a thirty-sixth aspect of the present invention is a method for measuring the concentration of an analyte in a blood sample according to any one of the thirtieth to thirty-fifth aspects, wherein the data a And measurement of data included in data b is performed via independent electrodes.
- the measurement is performed via independent electrodes.
- a biosensor system includes the sensor chip according to any one of the first to seventeenth aspects, and a measuring instrument including a control circuit that applies a voltage to a temperature electrode of the sensor chip.
- a biosensor system for measuring the concentration of an analyte in a blood sample based on a voltage application unit for applying a voltage to the temperature electrode according to a control circuit, and a magnitude of a current flowing through the temperature electrode brought into contact with the blood sample Based on the magnitude of the current flowing in the blood sample due to the reaction involving the temperature measurement unit that acquires the data a related to the temperature of the blood sample and the oxidoreductase that uses the analyte in the blood sample as a substrate,
- An analyte measurement unit that acquires data b related to the concentration of the analyte and a concentration determination unit that determines the analyte concentration in the blood sample based on the data a and data b are provided.
- the concentration determination unit determines the analyte concentration in the blood sample.
- a biosensor system is the biosensor system according to the thirty-seventh aspect, wherein the concentration determination unit includes a first analyte correction unit that corrects the data b based on the data a. It is out.
- the first analyte correction unit performs the concentration of the analyte in the blood sample.
- the data b related to is corrected.
- a biosensor system is the biosensor system according to the thirty-seventh aspect, wherein the concentration determination unit includes a calculation unit that calculates the concentration x of the analyte of the blood sample based on the data b. And a second analyte correction unit for correcting the concentration x based on the data a.
- the analyte correction unit calculates the analyte concentration x of the blood sample based on the data b
- the data acquired by the second analyte correction unit directly measuring the temperature of the blood sample.
- the density x is corrected based on a.
- a biosensor system is the biosensor system according to the thirty-seventh aspect, wherein the concentration determining unit calculates a temperature t of the blood sample based on the data a, and the temperature t And a third analyte correction unit for correcting the data b.
- the third analyte correction unit performs the data based on the temperature t. b is corrected.
- a biosensor system is the biosensor system according to the thirty-seventh aspect, in which the concentration determining unit calculates a temperature t of the blood sample based on the data a, and data b And a fourth analyte correction unit that corrects the concentration x based on the temperature t.
- the calculation unit calculates the analyte concentration x of the blood sample based on the temperature t.
- the analyte correction unit 4 corrects the concentration x based on the temperature t.
- a biosensor system is the biosensor system according to any one of the thirty-seventh to forty-first aspects, wherein the analysis is performed after acquiring the data a related to the temperature of the sample by the temperature measurement unit. Data b related to the concentration of the analyte is acquired by the object measuring unit.
- a biosensor system is the biosensor system according to the thirty-seventh aspect, in which the concentration determining unit determines the magnitude of the current flowing through the temperature electrode brought into contact with the blood sample after acquiring the data b. Based on the data, the temperature measuring unit that acquires data c related to the temperature of the blood sample, the data a and the data c to calculate data d related to the temperature of the blood sample, and the data d And a calculation unit that calculates the concentration x of the analyte corrected according to the temperature of the blood sample.
- the data c related to the temperature of the blood sample is acquired once again by the same acquisition method as that of the data a, and the calculation unit calculates the data a and the data c and relates to the temperature of the blood sample.
- the data d to be obtained is obtained.
- the calculation unit corrects the density x based on the data d.
- a biosensor system is the biosensor system according to the thirty-seventh aspect, wherein the concentration determining unit is configured to calculate a temperature t of the blood sample based on the data a, and the data Based on b, the concentration calculation unit for calculating the concentration x of the analyte of the blood sample, the environmental temperature measurement unit for measuring the environmental temperature t1 around the blood sample, and the difference between the temperature t and the environmental temperature t1 is expressed as a temperature threshold value. If the comparison unit comparing with Z and
- the temperature t of the blood sample is calculated based on the data a
- the concentration x of the analyte of the blood sample is calculated based on the data b
- the ambient temperature t1 around the blood sample is further measured. Then, the difference between the temperature t and the environmental temperature t1 is compared with the temperature threshold Z and corrected as follows.
- the concentration x is corrected based on the temperature t.
- the concentration x is corrected based on the temperature t1. Since the concentration x can be corrected using a suitable temperature, the measurement accuracy of the analyte concentration in the blood sample can be improved.
- a biosensor system is the biosensor system according to any one of the 37th to 44th aspects, wherein the data a relating to the temperature of the blood sample includes the temperature.
- the data b related to the concentration of the analyte includes the glucose concentration.
- temperature is included as an item of data acquired as data a
- glucose concentration is included as an item of data acquired as data b.
- the biosensor system according to the forty-sixth aspect of the present invention is the biosensor system according to the forty-fifth aspect, and the data b related to the concentration of the analyte contains hematocrit.
- hematocrit is included as an item of data acquired as data b.
- a biosensor system according to a 47th aspect of the present invention is the biosensor system according to the 45th or 46th aspect, wherein the data b relating to the concentration of the analyte contains the amount or concentration of the reducing substance. .
- the amount or concentration of the reducing substance is included as an item of data acquired as data b.
- a biosensor system is the biosensor system according to any one of the 45th to 47th aspects, wherein at least two items of data included in data a and data b are provided. And a sequence control unit for controlling the control circuit so as to measure simultaneously.
- the sequence control unit controls the control circuit so as to measure two or more items at the same time.
- the sequence control unit controls the control circuit so as to simultaneously acquire the glucose concentration and the amount or concentration of the reducing substance.
- a biosensor system according to a 49th aspect of the present invention is the biosensor system according to any one of the 45th to 47th aspects, wherein measurement of data included in the data a and the data b is independently performed.
- a sequence control unit for controlling the control circuit is further provided.
- the sequence control unit controls the control circuit so as to measure one by one instead of measuring two or more items at the same time.
- the order which each item acquires may be arbitrary.
- the biosensor system according to the 50th aspect of the present invention is the biosensor system according to any one of the 45th to 47th aspects, wherein the measurement of data contained in the data a and the data b is performed by measuring the temperature, glucose A sequence control unit is further provided for controlling the control circuit so that the control is performed in the order of the concentration and the amount or concentration of the reducing substance, and hematocrit.
- the order of data measurement is specified. This makes it possible to obtain advantageous effects in terms of speed, accuracy, and burden on the electrodes.
- a biosensor system is the biosensor system according to any one of the 45th to 50th aspects, wherein the measurement of data included in the data a and the data b is performed using independent electrodes. And an electrode selection unit for controlling the control circuit so as to perform the operation.
- the electrode selection unit controls the control circuit so as to be performed via independent electrodes.
- the occurrence of measurement errors due to the temperature of the use environment is suppressed, It is possible to improve the measurement accuracy of the analyte concentration.
- FIG. 1 is a perspective view of a biosensor system according to an embodiment of the present invention.
- 1 is an exploded perspective view of a biosensor chip according to an embodiment of the present invention.
- 1 is a perspective plan view of a biosensor chip according to an embodiment of the present invention.
- the circuit block diagram in the biosensor system which concerns on one Embodiment of this invention.
- the flowchart which shows the measuring method of the analyte concentration in the blood sample in the biosensor system which concerns on one Embodiment of this invention.
- (b) is a flowchart which shows the measuring method of the analyte density
- FIG. 1 is an exploded perspective view of a sensor chip according to an embodiment of the present invention.
- 1 is a perspective plan view of a sensor chip according to an embodiment of the present invention.
- (A), (b), and (c) are the current characteristic graphs corresponding to FIG. 8 in Example 1.
- FIG. 8 The current characteristic graph obtained with respect to predetermined temperature in Example 1.
- FIG. 8 The current characteristic graph obtained with respect to predetermined temperature in Example 1.
- (A), (b), and (c) are the current characteristic graphs obtained with respect to a predetermined applied voltage and a predetermined hematocrit value when the temperature in Example 7 is 4 degrees.
- (A), (b), and (c) are the current characteristic graphs obtained with respect to a predetermined applied voltage and a predetermined hematocrit value when the temperature in Example 7 is 13 degrees.
- (A), (b), and (c) are the current characteristic graphs obtained with respect to a predetermined applied voltage and a predetermined hematocrit value when the temperature in Example 7 is 21 degrees.
- (A), (b), and (c) are the current characteristic graphs obtained with respect to a predetermined applied voltage and a predetermined hematocrit value when the temperature in Example 7 is 30 degrees.
- FIG. 20 is a perspective view showing the distance between electrodes of a sensor chip in Example 11.
- (A) to (d) are graphs showing response current values according to distance between electrodes and hematocrit when the blood sample is 11 ° C. in Example 11.
- FIG. (A) to (d) are graphs showing response current values according to distance between electrodes and hematocrit when the blood sample is 21 ° C. in Example 11.
- FIG. (A) to (d) are graphs showing response current values by distance between electrodes and by hematocrit when the blood sample is 30 ° C. in Example 11.
- FIG. (A) And (b) is a perspective view which shows the sensor chip in Example 12.
- FIG. (A) And (b) is a graph which shows the response current value according to the electrode shape according to the blood sample in 11th Embodiment and hematocrit in Example 12.
- FIG. (A) And (b) is a graph which shows the response current value according to electrode shape according to Example 12, and hematocrit in the blood sample in Example 12.
- FIG. (A) And (b) is a graph which shows the response current value according to electrode shape according to Example 12, and hematocrit according to the blood sample in Example 12.
- FIG. (A) And (b) is a graph which shows the response current value according to electrode shape according to Example 12, and hematocrit according to the blood sample in Example 12.
- FIG. (A) And (b) is a perspective view which shows the sensor chip in Example 13.
- FIG. (A) to (d) are graphs showing response current values for each lead width and hematocrit when the blood sample is 30 ° C. in Example 13.
- FIG. (A) And (b) is a graph which shows the response current value according to capillary height and hematocrit at 11 degreeC in the blood sample in Example 14.
- FIG. (A) And (b) is a graph which shows the response current value according to capillary height and hematocrit when the blood sample is 21 ° C. in Example 14.
- (A) And (b) is a graph which shows the response current value according to capillary height according to Example 14 according to capillary height and hematocrit in 30 degreeC.
- (A) And (b) is a graph which shows the response current value according to palladium resistance in the blood sample in Example 15 at 4 degreeC.
- (A) And (b) is a graph which shows the response current value according to palladium resistance in the blood sample in Example 15 at 13 degreeC.
- (A) And (b) is a graph which shows the response current value according to palladium resistance in the blood sample in Example 15 in 21 degreeC.
- (A) And (b) is a graph which shows the response current value according to palladium resistance in the blood sample in Example 15 at 30 degreeC.
- (A) And (b) is a graph which shows the response current value according to palladium resistance in the blood sample in Example 15 in 38 degreeC.
- the blood sample shows the response current value according to glucose concentration at 24 ° C.
- the blood sample shows the response current value according to ascorbic acid concentration in 24 degreeC.
- the graph which shows the response electric current value according to temperature at the time of introduce
- the perspective view which shows the upper direction of the sensor chip in Example 19, and a lower direction.
- Example 20 in the environment of 24 degreeC, the graph which shows the response electric current value when not pinching the case where the front-end
- FIG. 23 is an explanatory diagram showing a measurement sequence in Example 21.
- (A) is a graph showing the response current value of glucose measured in Example 21, and
- (b) is a graph showing the response current value of temperature and Hct measured in Example 21.
- (A) is a graph which shows the response current value of the temperature measurement in Example 21,
- (b) is a graph which shows the response current value according to temperature at the time of measuring temperature in Example 21.
- FIG. 25 is an explanatory diagram showing another measurement sequence in Example 21.
- (A) And (b) is a flowchart which shows the measuring method of the analyte concentration in the blood sample in the biosensor system which concerns on the modification 1 of this invention.
- (A) And (b) is a flowchart which shows the measuring method of the analyte concentration in the blood sample in the biosensor system which concerns on the modification 1 of this invention.
- (A) And (b) is a circuit block diagram in the biosensor system which concerns on the modification 1 of this invention.
- (A) And (b) is a circuit block diagram in the biosensor system which concerns on the modification 1 of this invention.
- the circuit block diagram in the biosensor system which concerns on the modification 2 of this invention The circuit block diagram in the biosensor system which concerns on one Embodiment of this invention.
- the biosensor system acquires the temperature of an analyte from a blood sample by a measurement unit arranged on a sensor chip.
- FIG. 1 is a diagram for explaining an example of a biosensor system according to the present invention.
- the biosensor system 100 includes a rectangular parallelepiped measuring device 101 and a sensor chip 200.
- a mounting port 102 that is a rectangular hole is formed on the side wall surface of the measuring instrument 101.
- the sensor chip 200 is connected to the measuring instrument 101 while being detachably attached to the mounting opening 102.
- a display unit 103 for displaying the measurement result is disposed at a substantially central portion of one main surface of the measuring instrument 101.
- FIG. 2 is an exploded perspective view of the sensor chip 200
- FIG. 3 is a plan view thereof.
- the sensor chip 200 is formed on the insulating substrate 201 through the spacer 202 in which the rectangular cutout portion 204 is formed, and leaving one end of the insulating substrate 201 (the right end in FIG. 2).
- a cover 203 is disposed.
- the members 201, 202, and 203 are integrated by, for example, adhesion or heat welding.
- the notch 204 of the spacer 202 functions as the capillary 40 that holds the blood sample after the integration of the members.
- the capillary 40 has a long shape along the long side of the sensor chip 200, and communicates with the outside at one end of the spacer 202 (the left end in FIGS. 2 and 3). In other words, the capillary 40 communicates with the blood sample introduction port 17 that opens to the outside of the sensor chip 200.
- the cover 203 has the exhaust port 16 near the end of the capillary 40 opposite to the blood sample introduction port 17 side. Thereby, the blood sample is easily sucked into the capillary 40 from the blood sample introduction port 17 by capillary action.
- electrodes (voltage application units) 11, 12, 13, 14, and 15 are arranged so that each part (portions 31, 32, 33, 34, and 35) faces the capillary 40. Yes.
- the part 31 of the electrode 11 and the part 32 of the electrode 12 are arranged at positions closer to the blood sample introduction port 17 than the part 33 of the electrode 13 and the part 34 of the electrode 14.
- the reaction reagent layer 20 is formed so as to cover the entire portion 33 of the electrode 13 and partially cover the portion 34 of the electrode 14 and the portion 35 of the electrode 15.
- the reaction reagent layer 20 contains an oxidoreductase having an analyte in a blood sample as a substrate and an electron mediator.
- the reaction reagent layer 20 is formed at a position away from the part 31 of the electrode 11 and the part 32 of the electrode 12.
- no reaction reagent containing an oxidoreductase or electron mediator is disposed on the part 31 of the electrode 11 and the part 32 of the electrode 12, and more preferably, no reaction reagent is disposed.
- the portion 33 of the electrode 13 and the portion 34 of the electrode 14 are arranged closer to the blood sample inlet 17 than the portion 31 of the electrode 11 and the portion 32 of the electrode 12, the blood sample
- the reaction reagent layer 20 on the portion 33 of the electrode 13 and the portion 34 of the electrode 14 is flowed to reach the portion 33 of the electrode 13 and the portion 34 of the electrode 14. It can happen. Therefore, such an arrangement should be avoided.
- the sensor chip 200 has a measurement unit 41 (measurement unit A).
- the measuring part A is constituted by an electrode system (temperature electrode) constituted by the part 31 of the electrode 11 and the part 32 of the electrode 12 and a part of the capillary 40 that accommodates the part 31 and the part 32.
- the sensor chip 200 has a measurement unit 42 (measurement unit B).
- the measurement part B includes an electrode system (analysis electrode) constituted by the part 33 of the electrode 13 and the part 34 of the electrode 14 and a part of the capillary 40 that accommodates the reaction reagent layer 20 and the part 33 and part 34. Composed.
- the electrode 11 functions as a working electrode and the electrode 12 functions as a counter electrode.
- the electrode 13 functions as a working electrode and the electrode 14 functions as a counter electrode.
- the measurement unit A (temperature measurement unit) acquires data a related to the temperature of the blood sample based on the amount of current flowing through the temperature electrode.
- the substance that electrochemically reacts on the temperature electrode is mainly a component in the blood sample, may be water, or may be a blood cell component such as red blood cells and white blood cells.
- Measurement unit B obtains data b related to the concentration of the analyte in the blood sample based on the amount of current flowing between the analysis electrodes.
- Substances that electrochemically react on the analysis electrode are mainly electron mediators that have exchanged electrons with an oxidoreductase.
- the data b acquired by the measurement unit B is corrected based on temperature using the data a.
- the concentration of the analyte is calculated using the corrected data b.
- Both or one of the portion 33 of the electrode 13 and the portion 34 of the electrode 14 can serve as both or one of the portion 31 of the electrode 11 and the portion 32 of the electrode 12. However, these electrodes are preferably provided separately.
- the portion 35 of the electrode 15 is disposed in the vicinity of the end on the back side of the capillary 40, in other words, in the vicinity of the end opposite to the end communicating with the outside.
- a voltage may be applied between the electrode 14 and the electrode 15 instead of the electrode 13.
- Electrodes 11, 12, 13, 14, and 15 are connected to leads (not shown), respectively.
- One end of the lead is exposed to the outside of the sensor chip 200 at the end of the insulating substrate 201 not covered with the spacer 202 and the cover 203 so that a voltage can be applied between the electrodes.
- Analytes in blood samples include substances other than blood cells, such as glucose, albumin, lactic acid, bilirubin, and cholesterol.
- the oxidoreductase one using the target analyte as a substrate is used.
- the oxidoreductase include glucose oxidase, glucose dehydrogenase, lactate oxidase, lactate dehydrogenase, bilirubin oxidase and cholesterol oxidase.
- Examples of the amount of oxidoreductase in the reaction reagent layer include 0.01 to 100 units (U), preferably 0.05 to 10 U, more preferably 0.1 to 5 U.
- the reaction reagent layer 20 includes an electron mediator having a function of transferring electrons generated by the enzyme reaction to the electrode, such as potassium ferricyanide, p-benzoquinone, p-benzoquinone derivative, oxidized phenazine methosulfate, methylene blue, ferricinium, and ferricinium derivative. It is desirable to contain.
- the reaction reagent layer 20 may contain a water-soluble polymer compound in order to improve the moldability of the reaction reagent layer.
- water-soluble polymer compound examples include carboxymethyl cellulose and salts thereof, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, ethyl hydroxyethyl cellulose, carboxyethyl cellulose and salts thereof, polyamino acids such as polyvinyl alcohol, polyvinyl pyrrolidone and polylysine, polystyrene sulfonic acid and Examples thereof include at least one selected from salts thereof, gelatin and derivatives thereof, polyacrylic acid and salts thereof, polymethacrylic acid and salts thereof, starch and derivatives thereof, maleic anhydride polymer and salts thereof, agarose gel and derivatives thereof Is done.
- the insulating substrate 201, spacer 202 and cover 203 are made of a resin such as polyethylene terephthalate, polycarbonate, polyimide, polyethylene, polypropylene, polystyrene, polyvinyl chloride, polyoxymethylene, monomer cast nylon, polybutylene terephthalate, methacrylic resin and ABS resin. Further, glass is exemplified.
- the electrodes 11, 12, 13, 14, and 15 are made of a known conductive material such as palladium, platinum, gold, silver, titanium, copper, nickel, and carbon.
- FIG. 4 is a diagram illustrating an example of a circuit configuration for measuring an analyte concentration in a blood sample in the biosensor system 100.
- the measuring instrument 101 includes a control circuit 300 that applies a voltage between at least two electrodes 11, 12, 13, 14, and 15 in the sensor chip 200, and a display unit 400 that displays a measurement result. .
- the control circuit 300 includes five connectors 301a, 301b, 301c, 301d, and 301e, a switching circuit 302, a current / voltage conversion circuit 303, an analog / digital (A / D) conversion circuit 304, and a reference voltage source 305. And a calculation unit 306.
- the control circuit 300 can switch the potential applied to the electrode through the switching circuit 302 so that one electrode can be used as a positive electrode or a negative electrode.
- the calculation unit (concentration determination unit) 306 has a known central processing unit (CPU) and a conversion table for determining the analyte concentration in the blood sample based on the data a and data b.
- the calculation unit 306 corrects the analyte concentration by referring to a conversion table in which a correction coefficient based on the environmental temperature is described. More specifically, after the analyte concentration is provisionally calculated with reference to the provisional measurement conversion table, the calculation unit 306 corrects the analyte concentration by referring to the temperature correction conversion table.
- the measurement of the analyte concentration in the blood sample using the biosensor system 100 is performed as follows, for example, as shown in FIG. First, in response to a command from the CPU of the calculation unit 306, the electrode 13 is connected to the current / voltage conversion circuit 303 via the connector 301b, and the electrode 15 is connected to the reference voltage source 305 via the connector 301c.
- a constant voltage is applied between both electrodes in accordance with a command from the CPU (step S1).
- the voltage is, for example, 0.01 to 2.0 V, preferably 0.1 to 1.0 V, more preferably 0.2 to 0.5 V when the electrode 15 is represented as a positive electrode and the electrode 13 is represented as a negative electrode. It is.
- This voltage is applied after the sensor chip is inserted into the measuring instrument 101 until the blood sample is introduced to the back of the capillary 40.
- a current flows between the electrode 15 and the electrode 13.
- the CPU detects that the capillary 40 is filled with the blood sample by identifying the amount of increase in current per unit time at that time.
- the current value is converted into a voltage value by the current / voltage conversion circuit 303, converted into a digital value by the A / D conversion circuit 304, and then input to the CPU.
- the CPU detects that the blood sample has been introduced to the back of the capillary based on this digital value.
- the analyte in the blood sample and the enzyme and the enzyme and the electron mediator are reacted in the range of 0 to 60 seconds, preferably 0 to 15 seconds, more preferably 0 to 5 seconds. .
- step S2 the data a is acquired as follows (step S2).
- the voltage switching circuit 302 is operated by a command from the CPU, the electrode 11 is connected to the current / voltage conversion circuit 303 via the connector 301a, and the electrode 12 is connected to the reference voltage source 305 via the connector 301e. . Subsequently, a constant voltage is applied between both electrodes in the measurement unit A according to a command from the CPU.
- the voltage is 0.1 to 5.0 V, preferably 1.0 to 3.0 V, more preferably 1.V when the electrode 11 is represented as a positive electrode and the electrode 12 is represented as a negative electrode. 5 to 2.5V.
- the voltage application time is in the range of 0.1 to 30 seconds, preferably 0.5 to 10 seconds, more preferably 1 to 5 seconds.
- the amount of current flowing between the electrodes due to the application of the voltage is converted into a voltage value by the current / voltage conversion circuit 303 when a signal instructing acquisition of the data a is given from the control circuit to the measurement unit A. Thereafter, it is converted into a digital value by the A / D conversion circuit 304 and input to the CPU, and stored as data a in the memory of the arithmetic unit 306.
- step S3 the data b is acquired as follows (step S3).
- the switching circuit 302 is operated by a command from the CPU, the electrode 13 is connected to the current / voltage conversion circuit 303 via the connector 301b, and the electrode 14 is connected to the reference voltage source 305 via the connector 301d. Thereafter, a measurement sequence in the measurement unit B is input according to a command from the CPU.
- the voltage is 0.05 to 1.0 V, preferably 0.1 to 0.8 V, more preferably 0.2 to 0.2 V when the electrode 13 is represented as a positive electrode and the electrode 14 is represented as a negative electrode. 0.6V.
- the voltage application time is in the range of 0.1 to 30 seconds, preferably 0.1 to 15 seconds, and more preferably 0.1 to 5 seconds.
- the amount of current flowing between the electrodes due to the application of the voltage is converted into a voltage value by the current / voltage conversion circuit 303 when a signal instructing acquisition of the data b is given from the control circuit to the measurement unit B. Thereafter, it is converted into a digital value by the A / D conversion circuit 304 and input to the CPU, and is stored in the memory of the arithmetic unit 306 as data b.
- the control circuit instructs the acquisition of the data b within a range of 0.5 seconds to less than 5 seconds from the time when the blood sample is introduced into the capillary 40 of the sensor chip. It is preferable to supply the signal to be measured to the measurement unit B.
- the data b may be acquired before the data a. However, since it takes a sufficient time for the dissolution of the reagent, the enzyme reaction, the reaction between the electron mediator and the enzyme, etc. until the data b is obtained, the data b is preferably obtained later.
- data b and data a may be acquired at the same time. However, in this case, since voltages are applied to two sets of electrode systems simultaneously in one solution system, the respective currents interfere with each other. There are cases where they meet each other. Therefore, it is preferable that the acquisition of data a and the acquisition of data b are performed separately.
- step S101 the biosensor system 100 applies a constant voltage between both electrodes (step S101), acquires data a related to the temperature of the blood sample (step S102), and then the concentration of the analyte in the blood sample. Is obtained (step S103), and thereafter, data c related to the temperature of the blood sample is obtained again (step S104).
- the calculation unit 306 obtains the data d by performing an operation such as averaging the data a and the data c (step S105), corrects the temperature of the data b using the data d, and sets the concentration of the analyte. Calculate (step S106). At this time, the calculation unit (concentration determination unit) 306 (see FIG. 4) in the biosensor system 100, as shown in FIG. 6B, obtains the current flowing through the temperature electrode brought into contact with the blood sample after acquiring the data b.
- a temperature measurement unit 307 that acquires data c related to the temperature of the blood sample based on the size; a calculation unit 308 that calculates data a and data c to obtain data d related to the temperature of the blood sample; And a concentration calculation unit 309 that calculates the concentration x of the analyte corrected according to the temperature of the blood sample based on the data d.
- the calculation unit 306 refers to the conversion table and determines the analyte concentration in the blood sample based on the data a and the data b (step S4). Then, the determined analyte concentration is displayed on the display unit 400 as an image. If a temperature conversion table is prepared for the data a, the calculation unit 306 can calculate the temperature in the blood sample, and can display the temperature on the display unit 400 as an image. The calculation program for the determination is appropriately designed according to the data structure of the conversion table. When numerical data that completely matches the data a and the data b is not described in the conversion table, the calculation unit 306 calculates a known linear interpolation method from the data described in the conversion table and approximates the data a and the data b. The analyte concentration can be determined by using it.
- the electrode 11 and the electrode 12 may be used as an electrode for temperature measurement and an electrode for other analysis applications.
- Other analytical applications include, for example, measurement of hematocrit in blood samples, or reducing substances such as ascorbic acid, uric acid, bilirubin, acetaminophen, etc. that may affect data b with substances in blood samples It is a measurement of.
- a method using the electrode 11 or the electrode 12 as a working electrode (positive electrode) and the electrode 13 or the electrode 14 as a counter electrode (negative electrode) is known.
- the voltage between the temperature electrodes in the measuring section A can be influenced by the configuration of the sensor chip, such as the electrode area and the electrode material, so it is necessary to determine the optimum applied voltage in advance.
- the amount of current obtained when a voltage deviating from the optimum value is applied can depend on the hematocrit value (Hct value) in the blood sample.
- the Hct value means a numerical value indicating the proportion of the volume of blood cell components in the blood.
- FIG. 8 shows changes in the amount of current when the optimum voltage value is Vm, the voltage value higher than the optimum voltage value is Vh, and the voltage value Vl lower than the optimum voltage value (Vl ⁇ Vm ⁇ Vh).
- the amount of current increases as the Hct value increases.
- the voltage value higher than the optimum voltage value is Vh
- the current amount increases as the Hct value decreases.
- the optimum voltage value Vm as shown in FIG. 8B, a constant current amount is shown regardless of the Hct value.
- Vm is 0.1 to 5.0 V, preferably 1.0 to 3.0 V, and more preferably 1.5 to 2.5 V.
- the amount of current flowing between the temperature electrodes in the measurement unit A depends on the electrode area. A larger amount of current can be obtained regardless of whether the area of the portion 31 of the electrode 11 (working electrode) or the area of the portion 32 of the electrode 12 (counter electrode) is large.
- the area of the portion 32 on the counter electrode side is wide. Specifically, the range of the ratio of the area on the working electrode side / the area on the counter electrode side is preferably 1 to 0.25.
- the biosensor system of this embodiment can measure the analyte concentration with high accuracy even when the temperature of the environment in which the sensor is used changes rapidly. For this reason, the environmental temperature measurement part represented by the thermistor does not need to be installed in a measuring device.
- an environmental temperature measurement unit 315 may be provided in the measuring instrument.
- the number of environmental temperature measurement units 315 provided may be only one, but may be two or more. When two or more environmental temperature measurement units 315 are provided, each environmental temperature measurement unit 315 monitors the accuracy of each other, thereby ensuring a more accurate measurement result of the environmental temperature.
- the temperature correction obtained by comparing the temperature data obtained from the measurement unit A of the sensor and the temperature data obtained from the thermistor provided in the measuring instrument can also be performed by monitoring each temperature change to obtain the optimum temperature. It can also be selected and used for temperature correction.
- a method of correcting the temperature with reference to the difference between the temperature of the measuring unit A and the temperature of the thermistor, a method of acquiring a plurality of temperature differences, and selecting an optimum temperature correction value can be executed. Of course, it is also possible to execute a method that utilizes data on average values rather than temperature differences.
- the calculation unit 306 compares the temperature t acquired by the measurement unit A with the temperature t1 (step S43) acquired by the environmental temperature measurement unit 315 of the measuring instrument, and the difference between the two. Only when this occurs, the temperature t acquired by the measurement unit A is adopted. That is, as shown in FIG. 7A, the calculation unit 306 calculates the temperature t based on the data a (step S41). The calculator 306 calculates the density x based on the data b (step S42). The environmental temperature measurement unit 315 measures the environmental temperature t1 (step S43).
- the calculation unit 306 employs the temperature t1 (step S45). This is because the environmental temperature measurement unit 315 has high measurement accuracy. If there is a difference between the external environment temperature and the blood sample temperature due to a rapid change in temperature or the like, the environment temperature measurement unit 315 of the measuring instrument cannot cope with this difference. Therefore, the temperature t acquired by the measurement unit A is employed (step S46). More specifically, the temperature threshold value Z is set in advance. The computing unit 306 compares the value of
- the range of the temperature threshold Z is determined in consideration of the accuracy of the environmental temperature measuring unit of the measuring instrument and the accuracy of the measuring unit A of the sensor chip, and is 0.01 to 5.0 ° C., preferably 0.1 to 2
- the range is 0.0 ° C., more preferably 0.2 to 1.0 ° C.
- the calculation unit (concentration determination unit) 306 (see FIGS. 4 and 52) in the biosensor system 100 includes a temperature calculation unit 310 and a concentration calculation unit 311 as shown in FIG. 7B.
- the temperature calculation unit 310 calculates the temperature t of the blood sample based on the data a.
- the concentration calculation unit 311 calculates the analyte concentration x of the blood sample based on the data b.
- the measuring instrument includes an environmental temperature measurement unit 312, a comparison unit 313, and a correction unit 314.
- the environmental temperature measurement unit 312 measures the environmental temperature t1 around the blood sample.
- the comparison unit 313 compares the difference between the temperature t and the environmental temperature t1 with the temperature threshold Z.
- the correction unit 314 corrects the density x based on the temperature t when
- Example 1 The sensor chip 210 shown in FIGS. 9 and 10 was produced.
- the capillary was designed to have a width of 1.2 mm, a length (depth) of 4.0 mm, and a height of 0.15 mm.
- Polyethylene terephthalate was used as the insulating substrate. After palladium is vapor-deposited insulating substrate, the area is 0.12 mm 2 parts 31 of the electrodes 11, such that the area of the portion 32 of the electrode 12 is 0.48 mm 2, by a slit in the palladium layer with a laser Each electrode was formed.
- Three types of blood samples having Hct values of 25%, 45% and 65% were prepared.
- the temperature of the blood sample was 23 ° C.
- These blood samples were introduced into the capillaries of separate sensor chips.
- a voltage of 2.0 V, 2.2 V, or 2.4 V was applied between both electrodes (temperature electrodes).
- a current (response current) flowing between the working electrode and the counter electrode with voltage application was measured.
- Example 2 Using the sensor chip having the structure described in Example 1, a blood sample having an Hct value of 45% and a temperature of 23 ° C. was introduced into the capillary of the sensor chip. Thereafter, using the electrode 11 as a working electrode (positive electrode) and the electrode 12 as a counter electrode (negative electrode), a response current was measured when a voltage of 2.2 V was applied between both electrodes (temperature electrodes). The current value 3 seconds after the start of voltage application is shown in Table 1 below. The current value in Example 2 was 1.88 ⁇ A.
- Example 3 Area 0.24 mm 2 of the portion 31 of the sensor chip electrodes 11, the area of the portion 32 of the electrode 12 so that a 0.48 mm 2, to form an electrode. Other conditions were the same as those of the sensor chip described in Example 2.
- the current value 3 seconds after the start of voltage application is shown in Table 1 below.
- the current value in Example 3 was 2.47 ⁇ A. Compared with Example 2, the current value increased by 32%.
- the area of the working electrode of the sensor chip in the third embodiment is twice that in the second embodiment.
- Example 4 Area 0.48 mm 2 of the portion 31 of the sensor chip electrodes 11, the area of the portion 32 of the electrode 12 so that a 0.48 mm 2, to form an electrode. Other conditions were the same as those of the sensor chip described in Example 2.
- the current value 3 seconds after the start of voltage application is shown in Table 1 above.
- the current value in Example 4 was 3.13 ⁇ A, and the current value increased by 67% compared to Example 2.
- the area of the working electrode of the sensor chip in the fourth embodiment is four times that in the second embodiment and twice that in the third embodiment. That is, it was found that the current value increases as the working electrode area increases.
- Example 5 The electrodes were formed such that the area of the portion 31 of the electrode 11 of the sensor chip was 0.12 mm 2 and the area of the portion 32 of the electrode 12 was 0.96 mm 2 . Other conditions were the same as in Example 2.
- the current value 3 seconds after the start of voltage application is shown in Table 1 above.
- the current value in Example 5 was 3.08 ⁇ A.
- the area of the counter electrode of the sensor chip in Example 5 was twice that in Example 2. That is, it has been found that the current value increases as the area of the counter electrode increases. Further, as compared with Example 3, the increase rate of the current ground was only 32% under the condition that the area of the working electrode was doubled. Therefore, it is considered that a higher response value can be obtained by increasing the counter electrode area than the working electrode.
- Example 6 Area 0.24 mm 2 of the portion 31 of the sensor chip electrodes 11, the area of the portion 32 of the electrode 12 so that a 0.96 mm 2, to form an electrode. Other conditions were the same as in Example 2.
- the current value 3 seconds after the start of voltage application is shown in Table 1 above.
- the current value in Example 6 was 3.65 ⁇ A, and the current value increased by 94% compared to Example 2.
- the area of the working electrode and the counter electrode of the sensor chip in Example 6 is twice as compared with that in Example 2. That is, it was found that when the ratio of the electrode area is the same, the current value increases in proportion to the increase in the electrode area.
- Example 7 The sensor chip described in Example 1 was prepared. 15 kinds of Hct values of 25%, 45% and 65% are combined with 5 kinds of temperatures of 4 ° C, 13 ° C, 21 ° C, 30 ° C and 38 ° C, respectively. A blood sample was prepared.
- each blood sample described above was introduced into the capillary of the sensor chip. Then, using the electrode 11 as a working electrode (positive electrode) and the electrode 12 as a counter electrode (negative electrode), voltages of 2.1 V, 2.15 V, and 2.2 V were applied between both electrodes (temperature electrodes), and the response at that time The current was measured.
- 13 to 17 are graphs showing the response current for each temperature condition and applied voltage condition.
- the temperature conditions and applied voltage conditions in each graph are as follows.
- the optimum applied voltage condition using the response current in the high temperature region as a guide.
- the optimum applied voltage determined as described above in Example 7 is 2.15V.
- the current value after 3 seconds when a blood sample having an Hct value of 45% and a temperature of 21 ° C. was introduced was 1.93 ⁇ A.
- Example 8 Area 0.20 mm 2 of the portion 31 of the sensor chip electrodes 11, the area of the portion 32 of the electrode 12 so that a 0.40 mm 2, to form an electrode.
- Other sensor chips were configured in the same manner as in Example 1.
- the optimum applied voltage of Example 8 determined based on the response current in the high temperature region was 2.1V.
- the current value after 3 seconds when a blood sample having an Hct value of 45% and a temperature of 21 ° C. was introduced was 1.69 ⁇ A.
- Example 9 The area of the portion 31 of the sensor chip electrodes 11 0.30 mm 2, the area of the portion 32 of the electrode 12 an electrode was formed such that 0.30 mm 2. Other sensor chips were configured in the same manner as in Example 1.
- Example 7 the optimum applied voltage was determined based on the response current in the high temperature region.
- the optimum applied voltage of Example 9 was 2.05V.
- the current value after 3 seconds when a blood sample having an Hct value of 45% and a temperature of 21 ° C. was introduced was 1.48 ⁇ A. From the results of Examples 7, 8 and 9, it was found that when the electrode area is different, the optimum applied voltage is different and the magnitude of the response current is also changed. It was also found that a larger response current can be obtained with a larger counter electrode area under the same condition of the sum of the working electrode area and the counter electrode area.
- Example 10 A sensor chip having the configuration of FIGS. 2 and 3 was produced.
- the capillary was designed to have a width of 1.2 mm, a length (depth) of 4.0 mm, and a height of 0.15 mm.
- Polyethylene terephthalate was used as the insulating substrate, and palladium was evaporated on the insulating substrate. Thereafter, the area of the portion 31 of the electrode 11 is 0.30 mm 2, such that the area of the portion 32 of the electrode 12 is 0.48 mm 2, by a slit in the laser palladium layer to form a respective electrode.
- the reaction reagent layer was formed as follows. An aqueous solution containing glucose dehydrogenase, potassium ferricyanide (manufactured by Kanto Chemical Co., Inc.), taurine (manufactured by Nacalai Tesque), and glucose dehydrogenase was prepared. The concentration of glucose dehydrogenase was adjusted to a concentration of 2.0 U / sensor. A reagent solution was obtained by further dissolving potassium ferricyanide in a concentration of 1.7% by mass and taurine in a concentration of 1.0% by mass in this aqueous solution. This reagent solution was applied onto a polyethylene terephthalate substrate and then dried in an atmosphere of 45% humidity and 21 ° C.
- the Hct values of the blood samples were 25%, 45% and 65%, and the glucose concentrations were 40 mg / dl, 80 mg / dl, 200 mg / dl, 400 mg / dl and 600 mg / dl.
- the temperature of the blood sample was 4 ° C, 13 ° C, 22 ° C, 30 ° C, 39 ° C.
- the applied voltage and application time between the electrodes were set as follows. From immediately after blood sample introduction to 3 seconds later, 2.075 V was applied between both electrodes (temperature electrode) of electrode 11 (positive electrode) and electrode 12 (negative electrode). From 3 seconds to 5 seconds later, 0.25 V was applied between both electrodes (analytical electrodes) of the electrode 13 (positive electrode) and the electrode 14 (negative electrode). The measurement was completed in 5 seconds after the blood sample was introduced.
- the response current value after 3 seconds between the temperature electrodes is shown in Table 3 and the graph of FIG.
- the response current value after 3 seconds did not depend on the Hct value and depended on the temperature.
- the response current value after 3 seconds can be converted into the temperature of the blood sample.
- the response current value after 5 seconds between the analysis electrodes is shown in Table 4 below.
- the response current value after 5 seconds increased with increasing glucose concentration at each temperature, and also increased with increasing temperature at each glucose concentration. If the temperature is known, the response current value after 5 seconds can be converted to the glucose concentration of the blood sample by using the table shown in Table 4 below as the conversion table for the glucose concentration.
- Example 11 Four types of sensor chips having the configurations of FIGS. 9 and 10 were prepared. In these first to fourth types of sensor chips, the interelectrode distances in FIG. 19 were 100 ⁇ m, 300 ⁇ m, 500 ⁇ m, and 700 ⁇ m, respectively.
- 20 (a) to 20 (d) show the response current values by the distance between electrodes and hematocrit when the blood sample is 11 ° C.
- FIGS. 21 (a) to 21 (d) show the distance by electrode distance when the blood sample is 21 ° C.
- FIG. 22A to 22D show response current values by hematocrit, and blood current response values by electrode distance and hematocrit at 30 ° C.
- the first type of sensor chip had the configuration of FIGS. 9, 10, and 23 (a).
- the area of the electrode 11 part (working electrode) 31 is 0.24 mm 2
- the area of the electrode 12 part (counter electrode) 32 is 0.96 mm 2
- the inter-electrode distance was 300 [mu] m.
- the second type of sensor chip had the configuration shown in FIG.
- the area of the electrode 11 portion (working electrode) 31 in FIG. 23B was 0.24 mm 2
- the electrode 12 portion (counter electrode) 32 was divided into two locations.
- the area of the two parts of the part 32 was 0.48 mm 2
- the total value of the part 32 as the electrode 12 part was 0.96 mm 2 .
- the distance between the electrodes was 300 ⁇ m.
- FIGS. 24A and 24B show response current values according to electrode shape and hematocrit when the blood sample is 11 ° C.
- FIGS. 25A and 25B show electrode current shapes and hematocrit when the blood sample is 21 ° C.
- FIG. 26A and FIG. 26B show response current values according to electrode shape and hematocrit when the blood sample is 30 ° C.
- Example 13 Four types of sensor chips having different lead widths of the counter electrode 12 were prepared. Each type of sensor chip had the configuration shown in FIG. 2, FIG. 3, and FIG. In each type of sensor chip, the area of the electrode 11 portion (working electrode) 31 was 0.30 mm 2 , the area of the electrode 12 portion (counter electrode) 32 was 0.30 mm 2 , and the distance between the electrodes was 100 ⁇ m. In the first to fourth types of sensor chips, the lead widths of the counter electrode 12 shown in FIG. 27B were 0.5 mm, 1.0 mm, 1.5 mm, and 2.0 mm, respectively.
- the Hct values of the first to third blood samples were 25%, 45%, and 65%, respectively.
- the temperature of each type of blood sample was 23 ° C. (room temperature).
- Example 14 Two types of sensor chips were prepared.
- the first and second types of sensor chips have the configuration shown in FIGS. 9 and 10.
- the area of the electrode 11 portion (working electrode) 31 was 0.12 mm 2
- the area of the electrode 12 portion (counter electrode) 32 was 0.48 mm 2
- the distance between the electrodes was 300 ⁇ m.
- the thickness (capillary height) of the spacer 202 shown in FIG. 29 was 0.15 mm and 0.09 mm, respectively.
- . 30 (a) and 30 (b) show the response current values according to capillary height and hematocrit when the blood sample is 11 ° C.
- FIGS. 31 (a) and 31 (b) show the capillary height when the blood sample is 21 ° C.
- FIG. 32A and FIG. 32B show response current values by capillary height and hematocrit when the blood sample is 30 ° C., respectively.
- Example 15 Two types of sensor chips were prepared. Each type of sensor chip had the structure shown in FIGS. In each type of sensor chip, the area of the electrode 11 portion (working electrode) 31 was 0.12 mm 2 , the area of the electrode 12 portion (counter electrode) 32 was 0.48 mm 2 , and the distance between the electrodes was 100 ⁇ m. In the first and second types of sensor chips, the low surface efficiency of the palladium vapor deposition substrate was 115 ⁇ / ⁇ and 60 ⁇ / ⁇ , respectively.
- FIGS. 33 to 37 (a) and (b) show the response current value for each palladium resistance when the blood sample is 4 ° C.
- FIGS. 34 (a) and (b) show the response current value for each palladium resistance when the blood sample is 13 ° C.
- 35 (a) and 35 (b) show the response current value according to palladium resistance when the blood sample is 21 ° C.
- FIGS. 36 (a) and 36 (b) show the response according to palladium resistance when the blood sample is 30 ° C.
- FIG. 37 (a) and (b) show the current value, and the response current value according to palladium resistance when the blood sample is 38 ° C., respectively.
- Example 16 A sensor chip having the configuration of FIGS. 9 and 10 was prepared.
- the area of the electrode 11 portion (working electrode) 31 was 0.12 mm 2
- the area of the electrode 12 portion (counter electrode) 32 was 0.48 mm 2
- the distance between the electrodes was 100 ⁇ m.
- Three types of blood samples were prepared by adding a glucose concentrate to blood having an Hct value of 45% and a temperature of 24 ° C.
- the glucose concentrations of the first to third types of blood samples were 0 mg / dL, 205 mg / dL, and 640 mg / dL, respectively.
- the above-described blood sample was introduced into the capillaries in each of the above-described sensor chips. Thereafter, a voltage of 2.15 V was applied between both electrodes (temperature electrodes), and the response current in each case was measured.
- Example 17 formed so that the electrode 11 part (working electrode) area 31 is 0.12 mm 2 as shown in FIG. 10, the area of the electrode 12 part (counter electrode) 32 is 0.48 mm 2, the distance between electrodes becomes 100 ⁇ m A prepared sensor chip is prepared.
- 3 types of blood samples having different ascorbic acid concentrations were prepared by adding an ascorbic acid concentrate to blood having an Hct value of 45% and a temperature of 24 ° C.
- the glucose concentrations of the first to third blood samples were 0 mg / dL, 10 mg / dL, and 20 mg / dL, respectively.
- the above-described blood sample was introduced into the capillaries in each of the above-described sensor chips. Thereafter, a voltage of 2.15 V was applied between both electrodes (temperature electrodes), and the response current in each case was measured.
- FIG. 39 shows the response current value for each ascorbic acid concentration in the blood sample at 24 ° C. According to the graph, even when the ascorbic acid concentration changed, no significant difference was observed in the response current value. From the results of Example 17, it was found that the response current was hardly affected by the ascorbic acid concentration. That is, in this example, the measurement accuracy of the blood glucose level was not affected by the concentration of ascorbic acid, which is a reducing substance in blood. Therefore, it was found that the sensor chip of this example can be used as a blood glucose level sensor without any problem.
- Example 18 A sensor chip having the configuration of FIGS. 9 and 10 was prepared.
- the area of the electrode 11 portion (working electrode) 31 was 0.12 mm 2
- the area of the electrode 12 portion (counter electrode) 32 was 0.48 mm 2
- the distance between the electrodes was 100 ⁇ m.
- the Hct value was 45% and the temperature was 4 ° C.
- the Hct value was 45% and the temperature was 42 ° C.
- the blood sample described above was introduced into the capillaries of the sensor chips described above one minute after being transferred to a 24 ° C. environment. Thereafter, a voltage of 2.15 V was applied between both electrodes (temperature electrodes), and the response current in each case was measured.
- a dotted line in FIG. 40 indicates a response current when blood at 24 ° C. is introduced in an environment at 24 ° C. (hereinafter referred to as “normal introduction”).
- the solid line in FIG. 40 shows the response current when the 4 ° C. blood sample was introduced 1 minute after being transferred to the 24 ° C. environment (hereinafter referred to as “4 ° C. introduction”).
- the broken line in FIG. 40 indicates the response current when the 42 ° C. blood sample is introduced 1 minute after being transferred to the 24 ° C. environment (hereinafter referred to as “42 ° C. introduction”).
- the temperature indicated by introduction at 4 ° C is lower than the temperature indicated by normal introduction, and the temperature indicated by introduction at 42 ° C is higher than the temperature indicated by normal introduction. It was. And with the progress of the measurement time, the temperature difference between 42 ° C. introduction, 4 ° C. introduction, and 42 ° C. introduction disappeared. As described above, the temperature difference disappears with the passage of time of measurement because the blood sample at 4 ° C. or 42 ° C. was brought into the environment at 24 ° C. This is probably because the temperature has shifted to 24 ° C., which is the temperature of the chip.
- the sensor chip is disposed so as to come into contact with the blood sample, and includes a temperature electrode that measures the temperature of the blood sample. Therefore, by using this sensor chip, it is possible to obtain the temperature of the blood sample in consideration of changes over time, and to correct the glucose concentration and the like using this. That is, the accuracy of various corrections can be improved.
- Example 19 A sensor chip having the configuration of FIGS. 9 and 10 was prepared.
- the area of the electrode 11 portion (working electrode) 31 was 0.12 mm 2
- the area of the electrode 12 portion (counter electrode) 32 was 0.48 mm 2
- the distance between the electrodes was 100 ⁇ m.
- a blood sample was prepared.
- the Hct value was 45%.
- about 3 ⁇ L of blood was dropped in advance on the sensor chip.
- blood was dripped onto the top of the cover 203. This dripping of blood is hereinafter referred to as “over”.
- the blood sample described above was introduced into the capillary 204 of each sensor chip in an environment at 24 ° C. Thereafter, a voltage of 2.15 V was applied between both electrodes (temperature electrodes), and the response current in each case was measured.
- the broken line in FIG. 42 indicates that blood has been dropped in advance in a 24 ° C. environment
- the solid line in FIG. 42 indicates that blood has been previously dropped in a 24 ° C. environment.
- the dotted line in FIG. 42 indicates the response current when blood is not dripped in both the upper and lower directions (hereinafter referred to as normal introduction) in the environment of 24 ° C.
- the response current value in the upper and lower directions was lower than in the normal introduction. This is considered to be caused by the fact that the upper and lower blood adhering excessively outside the range of the capillary 204 lowers the temperature of the blood sample in the capillary 204 due to the heat of vaporization.
- the influence of heat of vaporization as shown in FIG. 42 can be accurately grasped.
- the sensor chip is disposed so as to come into contact with the blood sample, and includes a temperature electrode that measures the temperature of the blood sample. Therefore, it is possible to obtain the temperature of the blood sample in consideration of the effect of heat of vaporization, and to correct the glucose concentration and the like using this. For this reason, it is possible to improve the accuracy of various corrections.
- Example 20 formed so that the electrode 11 part (working electrode) area 31 is 0.12 mm 2 as shown in FIG. 10, the area of the electrode 12 part (counter electrode) 32 is 0.48 mm 2, the distance between electrodes becomes 100 ⁇ m
- a prepared sensor chip is prepared.
- blood whose Hct value is set to 45% is prepared.
- the blood sample described above was introduced in an environment of 24 ° C., then a voltage of 2.15 V was applied between both electrodes (temperature electrodes), and the response current in each case was measured.
- the solid line in FIG. 43 indicates that the tip of the sensor chip is pinched with a finger for 5 seconds in an environment of 24 ° C.
- the solid line in FIG. I s a response current when the signal is not held for 5 seconds (hereinafter referred to as normal introduction).
- the response current value was higher than that during normal introduction. This is considered to be because when the sensor tip is pinched with a finger, the temperature of the fingertip is transmitted to the blood sample via the sensor tip.
- an error due to the fingertip temperature as shown in FIG. 43 can be grasped.
- the sensor chip of the present invention is disposed so as to be in contact with the blood sample and includes a temperature electrode for measuring the temperature of the blood sample, the temperature of the blood sample can be obtained in consideration of the influence of the fingertip temperature. This can be used to correct the glucose concentration and the like. For this reason, it is possible to improve the accuracy of various corrections.
- Example 21 Figure 2 and the electrode 11 portions as shown in FIG. 3 (working electrode) area 31 is 0.30 mm 2, the electrode 12 part (counter electrode) 32 area of 0.48 mm 2, formed as the inter-electrode distance is 100 ⁇ m
- the sensor chip described in Example 10 was prepared. Moreover, each blood with a glucose concentration of 209 mg / dL, Hct values of 25, 45%, 65% and a temperature of 22 ° C. is prepared.
- a predetermined voltage was applied between predetermined electrodes in the order shown in FIG. That is, a voltage of 2075 mV is applied between the electrode 11 and the electrode 12 (between the electrodes 11-12 shown in FIG. 44) from 0 second to 3.0 seconds, and from the electrode 13 to the electrode 13 from 3.0 seconds to 5.0 seconds. A voltage of 250 mV is applied between the electrodes 14 (between the electrodes 13 and 14 shown in FIG. 44), and between the electrodes 11 and 13 (the electrode 11- shown in FIG. 44) from 5.1 seconds to 5.5 seconds. A voltage of 2500 mV was applied between (13). And the response current at this time was measured.
- each item of glucose, temperature, and Hct can be measured in order. Further, the order of measurement of glucose, temperature, and Hct is not limited to the case described above, but can be arbitrarily rearranged. For example, the order of temperature, Hct, glucose, etc. may be used.
- the items of glucose, temperature, Hct, and reducing substance may be measured. That is, as shown in FIG. 47, between electrode 11 and electrode 12 (between electrodes 11-12 shown in FIG. 47) from 0 second to 3.0 seconds, between electrode 12 and electrode from 3 seconds to 4.95 seconds. 14 (between the electrodes 12-14 shown in FIG. 47) and between the electrodes 13 and 14 (between the electrodes 13-14 shown in FIG. 47) almost simultaneously (3 to 5.0 seconds). In addition, a voltage may be applied between the electrode 11 and the electrode 13 (between the electrodes 11-13 shown in FIG. 47) from 5.1 seconds to 5.5 seconds. Even in this case, a response current corresponding to each condition can be obtained.
- Step S4 concentration determination step
- Step S101 to S106 concentration determination step
- the concentration determination step S4 may include a step 141 for correcting the data b based on the data a as shown in FIG.
- the calculation unit (concentration determination unit) 306 in the biosensor system 100 performs the first analyte correction that corrects the data b based on the data a, as shown in FIG. Part 321 is included.
- the concentration x of the analyte of the blood sample is calculated based on the data b, and the concentration x is corrected based on the data a.
- Step S242 may be included.
- the calculation unit (concentration determination unit) 306 (see FIG. 4) in the biosensor system 100 calculates the analyte concentration x of the blood sample based on the data b, as shown in FIG. 50 (b).
- a concentration calculation unit 331 and a second analyte correction unit 332 that corrects the concentration x based on the data a may be included.
- the concentration determination step S4 includes a step S341 for calculating the temperature t of the blood sample based on the data a, and a step S342 for correcting the data b based on the temperature t. May be included.
- the calculation unit (concentration determination unit) 306 in the biosensor system 100 calculates a temperature t of the blood sample based on the data a as shown in FIG. 341 and a third analyte correction unit 342 that corrects the data b based on the temperature t.
- the concentration determination step S4 includes step S441 for calculating the temperature t of the blood sample based on the data a, and the concentration x of the analyte in the blood sample based on the data b. May be included, and step S443 for correcting the density x based on the temperature t.
- the calculation unit (concentration determination unit) 306 in the biosensor system 100 calculates a temperature t of the blood sample based on the data a as shown in FIG. 351, a concentration calculation unit 352 that calculates the analyte concentration x of the blood sample based on the data b, and a fourth analyte correction unit 353 that corrects the concentration x based on the temperature t. .
- the control circuit 300 in the above embodiment may further include a sequence control unit 501 and an electrode selection unit 502, as shown in FIG.
- the sequence control unit 501 may control the control circuit 300 to measure at least two items simultaneously when measuring temperature, glucose, hematocrit, and reducing substance.
- the sequence control unit 501 may control the control circuit 300 so that the temperature, glucose, hematocrit, and reducing substance are measured independently. At this time, the order of measuring each item can be arbitrarily set.
- the sequence control unit 501 may control the control circuit 300 so that the temperature, the glucose concentration, the reducing substance, and the hematocrit are performed in this order when measuring the temperature, glucose, hematocrit, and reducing substance.
- the electrode selection unit 502 may control the control circuit 300 to perform the measurement via an independent electrode when measuring the temperature, glucose, hematocrit, and reducing substance.
- the present invention has great utility value in each field where high accuracy of measurement is required to suppress the occurrence of measurement error due to the temperature at which the measurement is performed in the measurement of the analytical concentration in a blood sample. Have.
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Abstract
Description
これにより、生体試料におけるヘマトクリット値に依存しない生体試料の温度測定が可能となる。この結果、生体試料の温度測定の精度を高めることが可能となると共に、生体試料の温度を利用した各種補正についての精度も高めることが可能となる。
第12及び第13観点のセンサチップは、分析電極として複数の作用極及び/又は複数の対極を備えていてもよい。この複数の作用極及び/又は対極のうちの少なくとも1つが、温度電極の作用極及び/又は対極を兼ねることができる。
‐ヘマトクリット測定用電極、
‐還元物質の濃度又は量の測定用電極、
‐血液の導入を検知する検知極、
‐グルコース濃度、ヘマトクリット、又は還元物質の濃度若しくは量の測定用の電極以外に設けられた他の測定用の電極が挙げられる。
これにより、正確に取得された血液試料の温度に関連するデータaに基づいて、血液試料の温度tを算出することができるので、使用環境の温度に起因する測定誤差の発生を抑制することが可能となる。
|t-t1|<Zを満たす場合、温度t1に基づいて濃度xを補正
これにより、外部温度環境に応じた適正な温度を用いて濃度xを補正することができるので、血液試料中の分析物濃度の測定精度を向上することが可能となる。
|t-t1|<Zを満たす場合、温度t1に基づいて濃度xを補正
これにより、外部温度環境に応じた適正な温度を用いて濃度xを補正することができるので、血液試料中の分析物濃度の測定精度を向上することが可能となる。
測定部A(温度測定部)は、温度電極に流れる電流の量に基づいて、血液試料の温度に関連するデータaを取得する。温度電極上で電気化学反応する物質は、主に血液試料中の成分であり、水であってもよく、赤血球および白血球などの血球成分であってもよい。
図4は、バイオセンサシステム100における、血液試料中の分析物濃度を測定するための回路構成の一例を示す図である。測定器101は、センサチップ200における電極11、12、13、14、15のうち少なくとも2つの電極間に電圧を印加する制御回路300と、測定結果を表示する表示部400とを有している。
まず、演算部306のCPUの指令により、電極13がコネクタ301bを介して電流/電圧変換回路303に接続され、電極15がコネクタ301cを介して基準電圧源305に接続される。
温度の急激な変化などによって、外部環境温度と血液試料温度とに差が生じた場合は、測定器の環境温度測定部315は、この差に対応することができない。そこで、測定部Aで取得される温度tが採用される(ステップS46)。より具体的には、温度閾値Zが予め設定される。演算部306は、|t-t1|の値と温度閾値Zとを比較する(ステップS44)。そして、演算部306は、|t-t1|の値が温度閾値Z以上の場合には、温度tに基づいて濃度xを補正し(ステップS45)、温度閾値Zより小さい場合には、環境温度t1に基づいて濃度xを補正する(ステップS46)。
以下、実施例により、本発明をさらに詳細に説明する。
図9および図10に示すセンサチップ210を作製した。キャピラリを、幅1.2mm、長さ(奥行き)4.0mm、高さ0.15mmになるように設計した。絶縁基板としては、ポリエチレンテレフタレートを用いた。絶縁基板にパラジウムを蒸着させた後、電極11の部分31の面積が0.12mm2、電極12の部分32の面積が0.48mm2となるように、レーザーでパラジウム層にスリットを入れることで、各電極を形成した。
印加電圧が2.0Vである場合は、図11(a)に示すように、Hct値が高いほど応答電流が大きかった。この結果は、図8(a)に対応する。
図11(c)に示すように、印加電圧が2.4Vであった場合は、Hct値が低いほど応答電流が大きかった。この結果は、図8(c)に対応する。
実施例1に記載の構成のセンサチップを用い、Hct値45%、温度23℃の血液試料をセンサチップのキャピラリに導入した。その後、電極11を作用極(正極)、電極12を対極(負極)として用い、2.2Vの電圧を両電極(温度電極)間に印加したときの応答電流を測定した。電圧印加開始から3秒後の電流値を以下の表1に示す。実施例2における電流値は、1.88μAであった。
センサチップの電極11の部分31の面積が0.24mm2、電極12の部分32の面積が0.48mm2となるように、電極を形成した。他の条件は、実施例2に記載のセンサチップと同様とした。電圧印加開始から3秒後の電流値を以下の上記表1に示す。実施例3における電流値は、2.47μAとなり、実施例2と比較すると、電流値は32%増加する結果であった。実施例3におけるセンサチップの作用極の面積は、実施例2の場合と比較して2倍である。
センサチップの電極11の部分31の面積が0.48mm2、電極12の部分32の面積が0.48mm2となるように、電極を形成した。他の条件は、実施例2に記載のセンサチップと同様とした。電圧印加開始から3秒後の電流値を上記表1に示す。実施例4における電流値は、3.13μAとなり、実施例2と比較すると電流値は67%増加する結果となった。実施例4におけるセンサチップの作用極の面積は、実施例2の場合と比較して4倍、また、実施例3の場合と比較して2倍である。すなわち、作用極の面積増加に伴い電流値が増加することがわかった。
センサチップの電極11の部分31の面積が0.12mm2、電極12の部分32の面積が0.96mm2となるように、電極を形成した。他の条件は、実施例2と同様とした。電圧印加開始から3秒後の電流値を上記表1に示す。実施例5における電流値は、3.08μAであり、実施例2と比較すると、電流値は65%増加した。実施例5におけるセンサチップの対極の面積は、実施例2の場合と比較して2倍であった。すなわち、対極の面積増加に伴い電流値が増加することがわかった。また、実施例3と比較すると、作用極の面積が2倍である条件では、電流地の増加率は32%に留まっていた。よって、作用極よりも対極の面積を増加させたほうが、より高い応答値が得られると考えられる。
センサチップの電極11の部分31の面積が0.24mm2、電極12の部分32の面積が0.96mm2となるように、電極を形成した。他の条件は、実施例2と同様とした。電圧印加開始から3秒後の電流値を上記表1に示す。実施例6における電流値は3.65μAであり、実施例2と比較すると、電流値は94%増加した。実施例6におけるセンサチップの作用極および対極の面積は、実施例2の場合と比較してともに2倍である。すなわち、電極面積の比率が同じ場合には、電極面積の増加に比例して、電流値も増加することがわかった。
実施例1に記載のセンサチップを準備した。Hct値が25%、45%、および65%の3通りのHct値と、4℃、13℃、21℃、30℃、および38℃の5通りの温度と、をそれぞれ組み合わせて、15種類の血液試料を準備した。
(温度条件)
図13(a)、(b)、(c):4℃
図14(a)、(b)、(c):13℃
図15(a)、(b)、(c):21℃
図16(a)、(b)、(c):30℃
図17(a)、(b)、(c):38℃
(印加電圧条件)
図13(a)、図14(a)、図15(a)、図16(a)、図17(a):2100mV
図13(b)、図14(b)、図15(b)、図16(b)、図17(b):2150mV
図13(c)、図14(c)、図15(c)、図16(c)、図17(c):2200mV
ここで、応答電流が小さい4℃および13℃の低温条件では、いずれの印加電圧条件においても同様に、Hct値に依存しない応答電流を示した。
センサチップの電極11の部分31の面積が0.20mm2、電極12の部分32の面積が0.40mm2となるように、電極を形成した。他のセンサチップの構成は、実施例1と同様にした。実施例7で示したように、高温領域での応答電流を目安にして決定した実施例8の最適印加電圧は2.1Vであった。このとき、上記表2に示すように、Hct値45%、温度21℃の血液試料を導入したときの3秒後の電流値は1.69μAであった。
センサチップの電極11の部分31の面積を0.30mm2、電極12の部分32の面積を0.30mm2となるように電極を形成した。他のセンサチップの構成は、実施例1と同様にした。
図2および図3の構成を有するセンサチップを作製した。キャピラリを、幅1.2mm、長さ(奥行き)4.0mm、高さ0.15mmになるように設計した。絶縁基板として、ポリエチレンテレフタレートを用い、絶縁基板にパラジウムを蒸着させた。その後、電極11の部分31の面積が0.30mm2、電極12の部分32の面積が0.48mm2となるように、パラジウム層にレーザーでスリットを入れることで、各電極を形成した。
図9および図10の構成を有する4種類のセンサチップを準備した。これらの第1~第4種類のセンサチップにおいて、図19の電極間距離は、それぞれ、100μm、300μm、500μm、700μmであった。
次に、上述したそれぞれのセンサチップにおけるキャピラリに、上述したそれぞれの血液試料を導入した後、両電極(温度電極)間に2.2Vの電圧を印加し、それぞれの場合における応答電流を測定した。
電極形状が異なる2種類のセンサチップを準備した。
第1種類のセンサチップは、図9,図10,および図23(a)の構成を有した。第1種類のセンサチップにおいて、電極11部分(作用極)31の面積は0.24mm2、電極12部分(対極)32の面積は0.96mm2、電極間距離は300μmであった。
次に、上述したそれぞれのセンサチップにおけるキャピラリに、上述したそれぞれの血液試料を導入した後、両電極(温度電極)間に2.2Vの電圧を印加し、それぞれの場合における応答電流を測定した。
対極12のリード幅の異なる4種類のセンサチップを準備した。各種類のセンサチップは、図2、図3、及び図27(a)に示される構成を有した。各種類のセンサチップにおいて、電極11部分(作用極)31の面積は0.30mm2、電極12部分(対極)32の面積が0.30mm2、電極間距離は100μmであった。第1~第4種類のセンサチップにおいて、図27(b)に示す対極12のリード幅は、それぞれ、0.5mm、1.0mm、1.5mm、2.0mmであった。
上記グラフによれば、ヘマトクリットが異なっても、応答電流には変化がほとんど見られなかった。また、リード幅が変化しても応答電流値に有意差が見られない結果となった。実施例13の結果により、応答電流は、リード幅(抵抗)の影響をほとんど受けないことが分かった。
2種類のセンサチップを準備した。第1および第2種類のセンサチップは、図9および図10に示される構成を有した。第1および第2種類のセンサチップにおいて、電極11部分(作用極)31の面積は0.12mm2、電極12部分(対極)32の面積は0.48mm2、電極間距離は300μmであった。第1種類および第2種類のセンサチップにおいて、図29に示すスペーサー202の厚さ(キャピラリ高さ)は、それぞれ、0.15mmおよび0.09mmであった。
次に、上述したそれぞれのセンサチップにおけるキャピラリに、上述したそれぞれの血液試料を導入した後、両電極(温度電極)間に2.2Vの電圧を印加し、それぞれの場合における応答電流を測定した。
2種類のセンサチップを準備した。各種類のセンサチップは、図9および図10の構造を有した。各種類のセンサチップにおいて、電極11部分(作用極)31の面積が0.12mm2、電極12部分(対極)32の面積が0.48mm2、電極間距離が100μmであった。第1種類及び第2種類のセンサチップにおいて、パラジウム蒸着基板の表面低効率は、それぞれ115Ω/□および60Ω/□であった。
次に、上述したそれぞれのセンサチップにおけるキャピラリに、上述したそれぞれの血液試料を導入した後、両電極(温度電極)間に2.15Vの電圧を印加し、それぞれの場合における応答電流を測定した。
図9および図10の構成を有するセンサチップを準備した。センサチップにおいて、電極11部分(作用極)31の面積は0.12mm2、電極12部分(対極)32の面積は0.48mm2、電極間距離は100μmであった。
上記グラフによれば、グルコース濃度が変化しても、応答電流値に有意差が見られなかった。実施例16の結果により、応答電流は、グルコース濃度の影響をほとんど受けないことが分かった。この結果、血糖値センサ(グルコースセンサ)に本発明を適用した場合であっても、グルコース濃度によって測定精度が左右されることがないので、問題なく使用できることが分かった。
図9、図10に示すような電極11部分(作用極)31の面積が0.12mm2、電極12部分(対極)32の面積が0.48mm2、電極間距離が100μmとなるように形成されたセンサチップを準備する。
上記グラフによれば、アスコルビン酸濃度が変化しても、応答電流値に有意差が見られなかった。実施例17の結果により、応答電流は、アスコルビン酸濃度の影響をほとんど受けないことが分かった。つまり、本実施例において、血液中の還元物質であるアスコルビン酸の濃度によって、血糖値の測定精度は左右されなかった。よって、本実施例のセンサチップは、血糖値センサとして問題なく使用できることが分かった。
図9および図10の構成を有するセンサチップを準備した。センサチップにおいて、電極11部分(作用極)31の面積は0.12mm2、電極12部分(対極)32の面積は0.48mm2、電極間距離は100μmであった。
また、センサチップは、血液試料に接触するように配置され、血液試料の温度を測定する温度電極を備えている。よって、このセンサチップを用いると、経時的変化が考慮された血液試料の温度を得ることができ、これを用いてグルコース濃度等を補正することができる。すなわち、各種補正の精度を向上させることが可能となる。
図9および図10の構成を有するセンサチップを準備した。このセンサチップにおいて、電極11部分(作用極)31の面積は0.12mm2、電極12部分(対極)32の面積は0.48mm2、電極間距離は100μmであった。
図41に示すように、センサチップに、予め約3μLの血液を滴下した。このとき、血液は、カバー203の上部に滴下された。血液をこのように滴下することを、以下、“上回り”と示す。
また、センサチップは、血液試料に接触するように配置され、血液試料の温度を測定する温度電極を備えている。よって、気化熱の影響を考慮した血液試料の温度を得ることができ、これを用いてグルコース濃度等を補正することができる。このため、各種補正の精度を向上させることが可能となる。
図9、図10に示すような電極11部分(作用極)31の面積が0.12mm2、電極12部分(対極)32の面積が0.48mm2、電極間距離が100μmとなるように形成されたセンサチップを準備する。また、Hct値が45%に設定された血液を準備する。
また、本発明のセンサチップは、血液試料に接触するように配置され、血液試料の温度を測定する温度電極を備えているので、指先温度の影響を考慮した血液試料の温度を得ることができ、これを用いてグルコース濃度等を補正することができる。このため、各種補正の精度を向上させることが可能となる。
図2および図3に示すような電極11部分(作用極)31の面積が0.30mm2、電極12部分(対極)32の面積が0.48mm2、電極間距離が100μmとなるように形成された、実施例10に記載のセンサチップを準備する。また、グルコース濃度が209mg/dL、Hct値が25、45%、65%、温度が22℃に設定されたそれぞれの血液を準備する。
また、グルコース、温度、Hctの計測の順番は、上記に示した場合だけでなく、任意に並べ変えることも可能である。例えば、温度、Hct、グルコース等の順番であってもよい。
上記他の実施形態においては、図6(a)に示すように、ステップS4における血液試料中の分析濃度を決定するステップ(濃度決定ステップ)が、ステップS101~ステップS106を含んでいる例を挙げて説明した。しかし、本発明はこれに限定されるものではない。
上記実施形態における制御回路300は、図52に示すように、シーケンス制御部501と、電極選択部502とをさらに備えていてもよい。
16 排気口
17 血液試料導入口
20 反応試薬層
31 キャピラリに面する電極11の一部分
32 キャピラリに面する電極12の一部分
33 キャピラリに面する電極13の一部分
34 キャピラリに面する電極14の一部分
35 キャピラリに面する電極15の一部分
40 キャピラリ
41 測定部A(温度測定部)
42 測定部B(分析物測定部)
100 バイオセンサシステム
101 測定器
102 装着口
103 表示部
200 センサチップ
201 絶縁基板
202 スペーサー
203 カバー
204 切欠部
210 センサチップ
300 制御回路
301a、301b、301c、301d、301e コネクタ
302 切換回路
303 電流/電圧変換回路
304 アナログ/デジタル(A/D)変換回路
305 基準電圧源
306 演算部(濃度決定部)
307 温度測定部
308 演算部
309 濃度算出部
310 温度算出部
311 濃度算出部
312 環境温度測定部
313 比較部
314 補正部
315 環境温度測定部
321 第1の分析物補正部
331 濃度算出部
332 第2の分析物補正部
341 温度算出部
342 第3の分析物補正部
351 温度算出部
352 濃度算出部
353 第4の分析物補正部
400 表示部
501 シーケンス制御部
502 電極選択部
S ステップ
Claims (51)
- 生体試料の温度を測定するセンサチップであって、
前記生体試料の温度を測定するために少なくとも作用極と対極とを有しており、直流電圧が印加される温度電極と、
前記生体試料を前記温度電極まで導入するキャピラリと、
を備え、
前記温度電極の作用極及び/または対極は、前記キャピラリに導入された前記生体試料と接触するように配置され、
前記直流電圧は、前記直流電圧の印加時にヘマトクリットが温度の測定結果に与える影響が小さくなるように設定されている、センサチップ。 - 前記キャピラリにおける前記生体試料の取込量は5μL以下であり、
前記温度電極における前記直流電圧の印加時間は15秒以下である、
請求項1に記載のセンサチップ。 - 前記直流電圧は、前記生体試料の溶媒が電気分解される範囲である、
請求項1または2に記載のセンサチップ。 - 使い捨てである、請求項1から3のいずれか1項に記載のセンサチップ。
- 血液試料中の分析物の濃度を測定するセンサチップであって、
前記血液試料に接触するように配置され、前記血液試料の温度を測定するために少なくとも作用極と対極とを有する温度電極と、
前記血液試料の分析物の濃度に関する項目の測定に用いられる濃度測定部と
を備えるセンサチップ。 - 前記濃度測定部は、少なくとも作用極と対極とを備える分析電極である、
請求項5に記載のセンサチップ。 - 前記温度電極と前記分析電極とは、別に設けられている、
請求項6に記載のセンサチップ。 - 試料導入口と、
前記試料導入口から前記温度電極及び分析電極まで血液試料を導入するキャピラリと、
をさらに備え、
前記温度電極は、前記分析電極よりも前記試料導入口に近い位置に配置されている、
請求項6または7に記載のセンサチップ。 - 前記濃度測定部は、酸化還元酵素および電子メディエータをさらに備え、
前記温度電極は、前記酸化還元酵素および電子メディエータの少なくとも1つと接しないように配置されている、
請求項5から8のいずれか1項に記載のセンサチップ。 - 前記濃度測定部は、酸化還元反応を起こす反応試薬をさらに備え、
前記温度電極は、前記反応試薬と接しないように配置されている、
請求項5から9のいずれか1項に記載のセンサチップ。 - 前記濃度測定部は、試薬をさらに備え、
前記温度電極は、如何なる試薬とも接しないように配置されている、
請求項5から9のいずれか1項に記載のセンサチップ。 - 前記温度電極の作用極は、少なくとも前記分析電極の作用極または対極のいずれかと共通である、
請求項6に記載のセンサチップ。 - 前記温度電極の対極は、少なくとも前記分析電極の作用極または対極のいずれかと共通である、
請求項6に記載のセンサチップ。 - 前記濃度測定部は、前記作用極及び前記対極以外の1以上の電極を有しており、
前記作用極及び前記対極以外の前記濃度測定部の前記電極のうちの少なくとも1つが、前記温度電極の作用極及び対極のうちの少なくとも1つと共通である、
請求項6から8のいずれか1項に記載のセンサチップ。 - 前記温度電極における作用極の面積は、前記温度電極における対極の面積と同じか、それより小さい、
請求項6に記載のセンサチップ。 - 前記分析物の濃度に関する項目には、少なくともヘマトクリットが含まれている、
請求項5から15のいずれか1項に記載のセンサチップ。 - 前記分析物の濃度に関する項目には、少なくとも還元物質の量または濃度が含まれている、
請求項5から16のいずれか1項に記載のセンサチップ。 - 作用極と対極とから形成される温度電極と、キャピラリと、を備えているセンサチップにおいて、前記生体試料の温度を測定する温度測定方法であって、
前記キャピラリにより、前記生体試料を前記温度電極まで導入する導入ステップと、
前記温度電極に直流電圧を印加する印加ステップと、
前記印加ステップにおいて印加される前記直流電圧を、第1電圧に調整する調整ステップと、
を備え、
前記第1電圧は、前記温度電極への前記第1電圧の印加時にヘマトクリットが温度の測定結果に与える影響が小さくなるように設定されている、
生体試料の温度測定方法。 - ヘマトクリットが温度の測定結果に与える影響が小さくなるような直流電圧の値を予め測定および記憶しておき、
前記調整ステップは、前記記憶された直流電圧に基づいて前記第1電圧に調整する、
請求項18に記載の生体試料の温度測定方法。 - 前記取込ステップにおける前記生体試料の取込量は5μL以下であり、
前記印加ステップにおける直流電圧の印加時間は15秒以下である、
請求項18または19に記載の生体試料の温度測定方法。 - 作用極と対極とから形成されている温度電極を備えたセンサチップで使用される血液試料の温度を測定する方法であって、
前記血液試料に接触させた前記温度電極に電圧を印加するステップと、
前記電圧を印加することによって前記血液試料中に流れる電流の大きさに基づいて、前記血液試料の温度に関連するデータaを取得するステップと、
前記データaに基づいて、前記血液試料の温度tを算出するステップと、
を備えている、血液試料の温度測定方法。 - 前記血液試料に接触させた一対の電極に電圧を印加することによって前記血液試料中に流れる電流の大きさに基づいて、前記血液試料の温度に関連するデータaを取得するステップと、
前記血液試料中の分析物を基質とする酸化還元酵素が関与する反応によって前記血液試料中に流れる電流の大きさに基づいて、前記分析物の濃度に関連するデータbを取得するステップと、
前記データaおよび前記データbに基づいて、血液試料中の分析物濃度を決定する濃度測定ステップと、
を備えている、血液試料中の分析物の濃度測定方法。 - 前記濃度測定ステップは、前記データaに基づいて前記データbを補正するステップを含んでいる、
請求項22に記載の血液試料中の分析物の濃度測定方法。 - 前記濃度測定ステップは、
前記データbに基づいて、前記血液試料の前記分析物の濃度xを算出するステップと、
前記データaに基づいて、前記濃度xを補正するステップと、
を含んでいる、請求項22に記載の血液試料中の分析物の濃度測定方法。 - 前記濃度測定ステップは、
前記データaに基づいて、前記血液試料の温度tを算出するステップと、
前記温度tに基づいて、データbを補正するステップと、
を含んでいる、請求項22に記載の血液試料中の分析物の濃度測定方法。 - 前記濃度測定ステップは、
前記データaに基づいて、前記血液試料の温度tを算出するステップと、
前記データbに基づいて、前記血液試料の前記分析物の濃度xを算出するステップと、
前記温度tに基づいて、前記濃度xを補正するステップと、
を含んでいる、請求項22に記載の血液試料中の分析物の濃度測定方法。 - 前記データaを取得するステップは、前記データbを取得するステップよりも先に行う、
請求項22から26のいずれか1項に記載の血液試料中の分析物の濃度測定方法。 - 前記濃度測定ステップは、
前記データb取得後に、前記血液試料に接触させた前記一対の電極に前記所定の電圧を印加することによって前記血液試料中に流れる電流の大きさに基づいて、前記血液試料の温度に関連するデータcを取得するステップと、
前記データaと前記データcとを演算することによって前記血液試料の温度に関連するデータdを求めるステップと、
前記データdに基づいて、前記データbを補正するステップと、
を含んでいる、請求項22に記載の血液試料中の分析物の濃度測定方法。 - 前記濃度測定ステップは、
前記データaに基づいて、前記血液試料の温度tを算出するステップと、
前記データbに基づいて、前記血液試料の前記分析物の濃度xを算出するステップと、
前記血液試料の周囲の環境温度t1を測定するステップと、
前記温度tと前記環境温度t1との差分を温度閾値Zと比較するステップと、
|t-t1|≧Zを満たす場合、前記温度tに基づいて前記濃度xを補正し、|t-t1|<Zを満たす場合、前記温度t1に基づいて前記濃度xを補正するステップと、
を含んでいる、請求項22に記載の血液試料中の分析物の濃度測定方法。 - 前記血液試料の温度に関連するデータaには温度が含まれており、
前記分析物の濃度に関連するデータbにはグルコース濃度が含まれている、
請求項22から29のいずれか1項に記載の血液試料中の分析物の濃度測定方法。 - 前記分析物の濃度に関連するデータbにはヘマトクリットが含まれている、
請求項30に記載の血液試料中の分析物の濃度測定方法。 - 前記分析物の濃度に関連するデータbには還元物質量または濃度が含まれている、
請求項30または31に記載の血液試料中の分析物の濃度測定方法。 - 前記データaおよび前記データbに含まれるデータのうち、少なくとも2つの項目を同時に測定する、
請求項30から32のいずれか1項に記載の血液試料中の分析物の濃度測定方法。 - 前記データaおよび前記データbに含まれるデータの測定は、それぞれ独立して行われる、
請求項30から32のいずれか1項に記載の血液試料中の分析物の濃度測定方法。 - 前記データaおよび前記データbに含まれるデータの測定は、前記温度、前記グルコース濃度および前記還元物質の量もしくは濃度、前記ヘマトクリットの順番で行われる、
請求項30から32のいずれか1項に記載の血液試料中の分析物の濃度測定方法。 - 前記データaおよび前記データbに含まれるデータの測定は、独立した電極を介して行われる、
請求項30から35のいずれか1項に記載の血液試料中の分析物の濃度測定方法。 - 温度電極を有する請求項1から請求項17のいずれか1項に記載のセンサチップと、前記センサチップの前記温度電極に電圧を印加する制御回路を含む測定器とを有する、血液試料中の分析物の濃度を測定するバイオセンサシステムであって、
前記制御回路に従って前記温度電極に電圧を印加する電圧印加部と、
前記血液試料に接触させた前記温度電極に流れる電流の大きさに基づいて、前記血液試料の温度に関連するデータaを取得する温度測定部と、
前記血液試料中の分析物を基質とする酸化還元酵素が関与する反応によって前記血液試料中に流れる電流の大きさに基づいて、前記分析物の濃度に関連するデータbを取得する分析物測定部と、
前記データaおよび前記データbに基づいて、血液試料中の分析物濃度を決定する濃度決定部と、
を備えている、バイオセンサシステム。 - 前記濃度決定部は、前記データaに基づいて、前記データbを補正する第1の分析物補正部を含んでいる、
請求項37に記載のバイオセンサシステム。 - 前記濃度決定部は、
前記データbに基づいて、前記血液試料の前記分析物の濃度xを算出する算出部と、
前記データaに基づいて、前記濃度xを補正する第2の分析物補正部と、
を含んでいる、請求項37に記載のバイオセンサシステム。 - 前記濃度決定部は、
前記データaに基づいて、前記血液試料の温度tを算出する算出部と、
前記温度tに基づいて、前記データbを補正する第3の分析物補正部と、
を含んでいる、請求項37に記載のバイオセンサシステム。 - 前記濃度決定部は、
前記データaに基づいて、前記血液試料の温度tを算出する算出部と、
前記データbに基づいて、前記血液試料の前記分析物の濃度xを算出する算出部と、
前記温度tに基づいて、前記濃度xを補正する第4の分析物補正部と、
を含んでいる、請求項37に記載のバイオセンサシステム。 - 前記温度測定部により試料の温度に関連する前記データa取得後に、前記分析物測定部により前記分析物の濃度に関連するデータbを取得する、
請求項37から41のいずれか1項に記載のバイオセンサシステム。 - 前記濃度決定部は、
前記データb取得後に、前記血液試料に接触させた前記温度電極に流れる電流の大きさに基づいて、前記血液試料の温度に関連するデータcを取得する温度測定部と、
前記データaと前記データcとを演算し、前記血液試料の温度に関連するデータdを求める演算部と、
前記データdに基づいて、前記血液試料の温度に応じて補正された前記分析物の濃度xを算出する算出部と、
を含んでいる、請求項37に記載のバイオセンサシステム。 - 前記濃度決定部は、
前記データaに基づいて、前記血液試料の温度tを算出する温度算出部と、
前記データbに基づいて、前記血液試料の前記分析物の濃度xを算出する濃度算出部と、
前記血液試料の周囲の環境温度t1を測定する環境温度測定部と、
前記温度tと前記環境温度t1との差分を温度閾値Zと比較する比較部と、
|t-t1|≧Zを満たす場合、前記温度tに基づいて前記濃度xを補正し、|t-t1|<Zを満たす場合、前記環境温度t1に基づいて前記濃度xを補正する補正部と、
を含んでいる、請求項37に記載のバイオセンサシステム。 - 前記血液試料の温度に関連するデータaには温度が含まれており、
前記分析物の濃度に関連するデータbにはグルコース濃度が含まれている、
請求項37から44のいずれか1項に記載のバイオセンサシステム。 - 前記分析物の濃度に関連するデータbにはヘマトクリットが含まれている、
請求項45に記載のバイオセンサシステム。 - 前記分析物の濃度に関連するデータbには還元物質の量または濃度が含まれている、
請求項45または46に記載のバイオセンサシステム。 - 前記データaおよび前記データbに含まれるデータのうち、少なくとも2つの項目を同時に測定するように前記制御回路を制御するシーケンス制御部をさらに備えている、
請求項45から47のいずれか1項に記載のバイオセンサシステム。 - 前記データaおよび前記データbに含まれるデータの測定をそれぞれ独立して行うように前記制御回路を制御するシーケンス制御部をさらに備えている、
請求項45から47のいずれか1項に記載のバイオセンサシステム。 - 前記データaおよび前記データbに含まれるデータの測定は、前記温度、前記グルコース濃度および前記還元物質の量または濃度、前記ヘマトクリットの順番で行うように前記制御回路を制御するシーケンス制御部をさらに備えている、
請求項45から47のいずれか1項に記載のバイオセンサシステム。 - 前記データaおよび前記データbに含まれるデータの測定は独立した電極を介して行うように前記制御回路を制御する電極選択部をさらに備えている、
請求項45から50のいずれか1項に記載のバイオセンサシステム。
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Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013157263A1 (ja) * | 2012-04-19 | 2013-10-24 | パナソニック株式会社 | 生体情報測定装置とそれを用いた生体情報測定方法 |
WO2013168390A1 (ja) * | 2012-05-07 | 2013-11-14 | パナソニック株式会社 | 生体情報測定装置とそれを用いた生体情報測定方法 |
WO2014091682A1 (ja) * | 2012-12-12 | 2014-06-19 | パナソニックヘルスケア株式会社 | 血液成分の測定装置、血液成分の測定方法、及び、バイオセンサ |
WO2014174815A1 (ja) * | 2013-04-26 | 2014-10-30 | パナソニックヘルスケア株式会社 | 液体試料測定装置、液体試料測定方法、及び、バイオセンサ |
WO2015004900A1 (ja) * | 2013-07-08 | 2015-01-15 | パナソニックヘルスケア株式会社 | 血液成分の測定装置、血液成分の測定方法 |
JP2015503743A (ja) * | 2011-12-29 | 2015-02-02 | ライフスキャン・スコットランド・リミテッド | 分析物を含有する試料の検知された物理的特性及び導出されたバイオセンサのパラメータに基づく、電気化学的試験ストリップにおける正確な分析物測定 |
US9664639B2 (en) | 2009-01-30 | 2017-05-30 | Panasonic Healthcare Holdings Co., Ltd. | Method for measuring temperature of biological sample, measuring device, and biosensor system |
JP2019168363A (ja) * | 2018-03-23 | 2019-10-03 | アークレイ株式会社 | 測定方法、及び測定装置 |
US11644434B2 (en) | 2015-05-15 | 2023-05-09 | Ascensia Diabetes Care Holdings Ag | Biosensor system analyte measurement |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101346441B1 (ko) * | 2008-11-28 | 2014-01-02 | 파나소닉 주식회사 | 센서 칩, 바이오센서 시스템, 생체 시료의 온도 측정 방법, 혈액 시료의 온도 측정 방법, 혈액 시료 중의 분석물의 농도 측정 방법 |
CA2837127C (en) * | 2011-05-24 | 2019-09-17 | Ingeny PCR B.V. | System for and method of changing temperatures of substances |
WO2013065248A1 (ja) | 2011-11-01 | 2013-05-10 | パナソニック株式会社 | 生体試料測定装置 |
US20150132855A1 (en) * | 2013-11-11 | 2015-05-14 | Qualcomm Incorporated | Interface for disposable sensors |
US20160187291A1 (en) * | 2014-12-31 | 2016-06-30 | Nipro Diagnostics, Inc. | Glucose test strip with interference correction |
WO2018222005A1 (ko) * | 2017-06-02 | 2018-12-06 | 주식회사 비바이오 | 센서 스트립 및 이를 이용한 생체 물질 측정 장치 |
WO2019181436A1 (ja) | 2018-03-19 | 2019-09-26 | Phcホールディングス株式会社 | 血液中の血液成分の量を測定する方法 |
KR102095959B1 (ko) * | 2018-07-11 | 2020-04-01 | 주식회사 아이센스 | 인공지능 딥러닝 학습을 이용한 생체측정물 농도 측정방법 |
CN109884150B (zh) * | 2019-03-08 | 2021-05-14 | 武汉璟泓科技股份有限公司 | 一种红细胞积压校正方法及存储介质 |
CN113853514A (zh) | 2019-05-21 | 2021-12-28 | 安晟信医疗科技控股公司 | 用于分析物生物传感器中的热敏电阻感测的补偿系统及方法 |
KR102401133B1 (ko) * | 2019-08-30 | 2022-05-25 | 주식회사 비바이오 | 혈당 측정 장치 및 방법 |
DE102022107214A1 (de) * | 2022-03-28 | 2023-09-28 | Senslab - Gesellschaft Zur Entwicklung Und Herstellung Bioelektrochemischer Sensoren Mbh | Verfahren und Sensor zur Bestimmung einer plasmabezogenen Analytkonzentration in Vollblut |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH09250996A (ja) * | 1996-03-14 | 1997-09-22 | Daikin Ind Ltd | 濃度測定方法およびその装置 |
JP2001235444A (ja) | 1999-12-23 | 2001-08-31 | Roche Diagnostics Corp | 熱伝導性センサー |
JP2003062812A (ja) | 2001-08-29 | 2003-03-05 | Takashige Shinohara | 木板連結パネル |
JP2003156469A (ja) | 2001-11-22 | 2003-05-30 | Matsushita Electric Ind Co Ltd | バイオセンサ、バイオセンサ用測定装置及び基質の定量方法 |
JP2007033458A (ja) * | 2006-10-03 | 2007-02-08 | Matsushita Electric Ind Co Ltd | バイオセンサ、バイオセンサ用測定装置及び基質の定量方法 |
JP2007524818A (ja) * | 2003-06-20 | 2007-08-30 | エフ ホフマン−ラ ロッシュ アクチェン ゲゼルシャフト | 多段の電気的機能性をもったバイオセンサー |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3231534A1 (de) | 1982-08-25 | 1984-03-01 | Endress Hauser Gmbh Co | Taupunktmessgeraet |
US5264103A (en) * | 1991-10-18 | 1993-11-23 | Matsushita Electric Industrial Co., Ltd. | Biosensor and a method for measuring a concentration of a substrate in a sample |
US7407811B2 (en) | 1997-12-22 | 2008-08-05 | Roche Diagnostics Operations, Inc. | System and method for analyte measurement using AC excitation |
CN100346158C (zh) | 2000-11-30 | 2007-10-31 | 松下电器产业株式会社 | 基质的定量方法 |
JP4639465B2 (ja) | 2000-11-30 | 2011-02-23 | パナソニック株式会社 | バイオセンサ |
US20080125751A1 (en) * | 2002-01-14 | 2008-05-29 | Edwards Lifesciences Corporation | Temperature compensation for enzyme electrodes |
EP1467201B1 (en) | 2002-01-18 | 2018-10-31 | ARKRAY, Inc. | Analyzer having temperature sensor |
EP1467206A1 (en) | 2003-04-08 | 2004-10-13 | Roche Diagnostics GmbH | Biosensor system |
EP2579031B1 (en) | 2003-12-04 | 2017-09-27 | Panasonic Healthcare Holdings Co., Ltd. | Biosensor for measuring blood component and hematocrit. |
JP4136979B2 (ja) | 2004-03-18 | 2008-08-20 | 農工大ティー・エル・オー株式会社 | カード型標的物質検出装置 |
CN2772044Y (zh) * | 2004-11-18 | 2006-04-12 | 比亚迪股份有限公司 | 一种锂离子二次电池 |
JPWO2006132250A1 (ja) | 2005-06-06 | 2009-01-08 | 日機装株式会社 | バイオセンサ及びバイオセンサセル |
US20090018404A1 (en) | 2007-07-12 | 2009-01-15 | Cardiac Pacemakers, Inc. | Cardiovascular Autonomic Neuropathy Testing Utilizing an Implantable Medical Device |
US8603768B2 (en) * | 2008-01-17 | 2013-12-10 | Lifescan, Inc. | System and method for measuring an analyte in a sample |
JP5487467B2 (ja) * | 2008-06-16 | 2014-05-07 | パナソニックヘルスケア株式会社 | 分析対象物の測定方法、バイオセンサおよび測定器 |
KR101346441B1 (ko) * | 2008-11-28 | 2014-01-02 | 파나소닉 주식회사 | 센서 칩, 바이오센서 시스템, 생체 시료의 온도 측정 방법, 혈액 시료의 온도 측정 방법, 혈액 시료 중의 분석물의 농도 측정 방법 |
-
2009
- 2009-11-27 KR KR1020117011411A patent/KR101346441B1/ko active IP Right Grant
- 2009-11-27 EP EP09828879.8A patent/EP2372356B1/en active Active
- 2009-11-27 WO PCT/JP2009/006435 patent/WO2010061629A1/ja active Application Filing
- 2009-11-27 CA CA2742149A patent/CA2742149C/en active Active
- 2009-11-27 US US13/127,585 patent/US8721851B2/en active Active
- 2009-11-27 JP JP2010540389A patent/JP5092021B2/ja active Active
- 2009-11-27 EP EP17197312.6A patent/EP3301439A1/en active Pending
- 2009-11-27 CN CN2009801445103A patent/CN102209893B/zh active Active
-
2012
- 2012-06-13 JP JP2012133918A patent/JP5270780B2/ja active Active
- 2012-09-14 JP JP2012202521A patent/JP5358014B2/ja active Active
-
2014
- 2014-03-31 US US14/230,221 patent/US9658182B2/en active Active
-
2017
- 2017-04-18 US US15/490,009 patent/US10690620B2/en active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH09250996A (ja) * | 1996-03-14 | 1997-09-22 | Daikin Ind Ltd | 濃度測定方法およびその装置 |
JP2001235444A (ja) | 1999-12-23 | 2001-08-31 | Roche Diagnostics Corp | 熱伝導性センサー |
JP2003042995A (ja) | 1999-12-23 | 2003-02-13 | Roche Diagnostics Corp | 熱伝導性センサー |
JP2003062812A (ja) | 2001-08-29 | 2003-03-05 | Takashige Shinohara | 木板連結パネル |
JP2003156469A (ja) | 2001-11-22 | 2003-05-30 | Matsushita Electric Ind Co Ltd | バイオセンサ、バイオセンサ用測定装置及び基質の定量方法 |
JP2007524818A (ja) * | 2003-06-20 | 2007-08-30 | エフ ホフマン−ラ ロッシュ アクチェン ゲゼルシャフト | 多段の電気的機能性をもったバイオセンサー |
JP2007033458A (ja) * | 2006-10-03 | 2007-02-08 | Matsushita Electric Ind Co Ltd | バイオセンサ、バイオセンサ用測定装置及び基質の定量方法 |
Cited By (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10520461B2 (en) | 2009-01-30 | 2019-12-31 | Phc Holdings Corporation | Method for measuring temperature of biological sample, measuring device, and biosensor system |
US9874537B2 (en) | 2009-01-30 | 2018-01-23 | Panasonic Healthcare Holdings Co., Ltd. | Method for measuring temperature of biological sample, measuring device, and biosensor system |
US9664639B2 (en) | 2009-01-30 | 2017-05-30 | Panasonic Healthcare Holdings Co., Ltd. | Method for measuring temperature of biological sample, measuring device, and biosensor system |
JP2015503743A (ja) * | 2011-12-29 | 2015-02-02 | ライフスキャン・スコットランド・リミテッド | 分析物を含有する試料の検知された物理的特性及び導出されたバイオセンサのパラメータに基づく、電気化学的試験ストリップにおける正確な分析物測定 |
US9903831B2 (en) | 2011-12-29 | 2018-02-27 | Lifescan Scotland Limited | Accurate analyte measurements for electrochemical test strip based on sensed physical characteristic(s) of the sample containing the analyte and derived biosensor parameters |
JPWO2013157263A1 (ja) * | 2012-04-19 | 2015-12-21 | パナソニックヘルスケアホールディングス株式会社 | 生体情報測定装置とそれを用いた生体情報測定方法 |
WO2013157263A1 (ja) * | 2012-04-19 | 2013-10-24 | パナソニック株式会社 | 生体情報測定装置とそれを用いた生体情報測定方法 |
US9625442B2 (en) | 2012-04-19 | 2017-04-18 | Panasonic Healthcare Holdings Co., Ltd. | Biological information measurement device, and biological information measurement method using same |
US10012610B2 (en) | 2012-04-19 | 2018-07-03 | Phc Holdings Corporation | Biological information measurement device, and biological information measurement method using same |
US9804115B2 (en) | 2012-04-19 | 2017-10-31 | Panasonic Healthcare Holdings Co., Ltd. | Biological information measurement device, and biological information measurement method using same |
JPWO2013168390A1 (ja) * | 2012-05-07 | 2016-01-07 | パナソニックヘルスケアホールディングス株式会社 | 生体情報測定装置とそれを用いた生体情報測定方法 |
WO2013168390A1 (ja) * | 2012-05-07 | 2013-11-14 | パナソニック株式会社 | 生体情報測定装置とそれを用いた生体情報測定方法 |
US9629577B2 (en) | 2012-05-07 | 2017-04-25 | Panasonic Healthcare Holdings Co., Ltd. | Biological information measurement device and biological information measurement method using same |
JP5801479B2 (ja) * | 2012-05-07 | 2015-10-28 | パナソニックヘルスケアホールディングス株式会社 | 生体情報測定装置とそれを用いた生体情報測定方法 |
WO2014091682A1 (ja) * | 2012-12-12 | 2014-06-19 | パナソニックヘルスケア株式会社 | 血液成分の測定装置、血液成分の測定方法、及び、バイオセンサ |
JPWO2014091682A1 (ja) * | 2012-12-12 | 2017-01-05 | パナソニックヘルスケアホールディングス株式会社 | 血液成分の測定装置、血液成分の測定方法、及び、バイオセンサ |
US10509005B2 (en) | 2012-12-12 | 2019-12-17 | Phc Holdings Corporation | Blood component measuring device, method for measuring blood component, and bio-sensor |
US9816957B2 (en) | 2012-12-12 | 2017-11-14 | Panasonic Healthcare Holdings Co., Ltd. | Blood component measuring device, method for measuring blood component, and bio-sensor |
US10317360B2 (en) | 2013-04-26 | 2019-06-11 | Phc Holdings Corporation | Liquid sample measurement device, liquid sample measurement method, and biosensor |
WO2014174815A1 (ja) * | 2013-04-26 | 2014-10-30 | パナソニックヘルスケア株式会社 | 液体試料測定装置、液体試料測定方法、及び、バイオセンサ |
JPWO2014174815A1 (ja) * | 2013-04-26 | 2017-02-23 | パナソニックヘルスケアホールディングス株式会社 | 液体試料測定装置、液体試料測定方法、及び、バイオセンサ |
US11268926B2 (en) | 2013-04-26 | 2022-03-08 | Phc Holdings Corporation | Liquid sample measurement device, liquid sample measurement method, and biosensor |
US9738916B2 (en) | 2013-07-08 | 2017-08-22 | Panasonic Healthcare Holdings Co., Ltd. | Blood component measurement device and blood component measurement method |
WO2015004900A1 (ja) * | 2013-07-08 | 2015-01-15 | パナソニックヘルスケア株式会社 | 血液成分の測定装置、血液成分の測定方法 |
US10344312B2 (en) | 2013-07-08 | 2019-07-09 | Phc Holdings Corporation | Blood component measurement device and blood component measurement method |
JPWO2015004900A1 (ja) * | 2013-07-08 | 2017-03-02 | パナソニックヘルスケアホールディングス株式会社 | 血液成分の測定装置、血液成分の測定方法 |
US11644434B2 (en) | 2015-05-15 | 2023-05-09 | Ascensia Diabetes Care Holdings Ag | Biosensor system analyte measurement |
JP2019168363A (ja) * | 2018-03-23 | 2019-10-03 | アークレイ株式会社 | 測定方法、及び測定装置 |
JP6997659B2 (ja) | 2018-03-23 | 2022-01-17 | アークレイ株式会社 | 測定方法、及び測定装置 |
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US20140209482A1 (en) | 2014-07-31 |
JP5270780B2 (ja) | 2013-08-21 |
EP2372356A4 (en) | 2013-05-29 |
KR20110074776A (ko) | 2011-07-01 |
JP5358014B2 (ja) | 2013-12-04 |
US20110203942A1 (en) | 2011-08-25 |
EP2372356A1 (en) | 2011-10-05 |
JP2012168203A (ja) | 2012-09-06 |
CN102209893B (zh) | 2013-06-26 |
US20170254773A1 (en) | 2017-09-07 |
JP2013029516A (ja) | 2013-02-07 |
US8721851B2 (en) | 2014-05-13 |
EP2372356B1 (en) | 2018-01-10 |
US10690620B2 (en) | 2020-06-23 |
CA2742149A1 (en) | 2010-06-03 |
CA2742149C (en) | 2016-07-05 |
JPWO2010061629A1 (ja) | 2012-04-26 |
KR101346441B1 (ko) | 2014-01-02 |
EP3301439A1 (en) | 2018-04-04 |
JP5092021B2 (ja) | 2012-12-05 |
CN102209893A (zh) | 2011-10-05 |
US9658182B2 (en) | 2017-05-23 |
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