WO2011081211A1 - Measuring device having a biosensor - Google Patents

Measuring device having a biosensor Download PDF

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Publication number
WO2011081211A1
WO2011081211A1 PCT/JP2010/073829 JP2010073829W WO2011081211A1 WO 2011081211 A1 WO2011081211 A1 WO 2011081211A1 JP 2010073829 W JP2010073829 W JP 2010073829W WO 2011081211 A1 WO2011081211 A1 WO 2011081211A1
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WO
WIPO (PCT)
Prior art keywords
electrode
temperature
biosensor
sample
blood
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PCT/JP2010/073829
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French (fr)
Japanese (ja)
Inventor
滋 関根
勝也 白崎
満洋 森田
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ニプロ株式会社
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Publication of WO2011081211A1 publication Critical patent/WO2011081211A1/en

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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
    • G01N27/3272—Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/001—Enzyme electrodes
    • C12Q1/005—Enzyme electrodes involving specific analytes or enzymes
    • C12Q1/006—Enzyme electrodes involving specific analytes or enzymes for glucose

Definitions

  • the present invention relates to a measuring apparatus in which a biosensor having a first electrode on which an enzyme is immobilized and a second electrode corresponding to the first electrode is detachably provided on the apparatus body.
  • Insulin is known as a drug that controls blood glucose levels and is administered to diabetic patients as a therapeutic agent for diabetes.
  • the need to administer insulin is determined based on the blood glucose level of the diabetic patient. For this reason, it is important for a diabetic patient to grasp a blood glucose level.
  • the blood glucose level is the glucose concentration in the blood.
  • a simple blood glucose measuring device has been developed for the purpose of allowing a diabetic patient to easily measure his blood glucose level.
  • the biosensor has an electrode on which an enzyme that reacts with blood sugar is fixed.
  • Glucose oxidase hereinafter sometimes abbreviated as “GOD”
  • GDH glucose dehydrogenase
  • a biosensor an electrode on which an enzyme is immobilized is called a working electrode, and an electrode that supplies electrons into a sample is called a counter electrode.
  • the working electrode When blood, which is a sample, is introduced into the biosensor and the working electrode GOD reacts with glucose in the blood, glucose is decomposed into gluconic acid and hydrogen peroxide, and the hydrogen peroxide is decomposed into water and electrons. The electrons generated in this way are transmitted to the working electrode. On the other hand, electrons are supplied from the counter electrode into the blood. In this way, a current flows between the working electrode and the counter electrode due to the reaction between GOD and glucose. Then, based on the flowing current value, the glucose concentration in the blood, that is, the blood glucose level is calculated. In addition, a substance that transmits electrons may be fixed to the working electrode. This material is referred to as an electron mediator. Examples of the electron mediator include organic compounds such as potassium ferricyanide, hexaammineruthenium and quinone derivatives, or organic-metal complexes.
  • the electron mediator include organic compounds such as potassium ferricyanide, hexaammineruthenium and quinone derivatives, or
  • the temperature affects the measured value.
  • the temperature characteristics of the resistance for converting the current flowing through the biosensor into voltage, the temperature dependence of the reaction rate of the enzyme, the temperature dependence of the diffusion rate of the mediator, etc. have been pointed out.
  • a configuration is known in which a temperature sensor is provided in a measurement device to which a biosensor is attached and the glucose measurement value is corrected based on the measurement value of the temperature sensor.
  • Patent Documents 5 to 7 Further, a configuration is known in which a part where blood is introduced in a biosensor is brought into contact with a part of a measuring apparatus, and a temperature sensor is used for the part of the contact (Patent Document 8).
  • Patent Document 9 and 10 the structure which provides a heat conductive layer in a biosensor and measures the temperature of the blood introduced into the biosensor through the heat conductive layer is known (patent documents 9 and 10).
  • a configuration is known in which a biosensor is separately provided with an electrode pair that causes a redox reaction for substances other than glucose, and the measured glucose value is corrected based on the current value obtained by the redox reaction. Yes (Patent Document 11).
  • the blood introduction location of the biosensor is arranged so as to overlap a part of the measurement device. There is a need. If it does so, there exists a possibility that the operation
  • the present invention has been made in view of the above-described circumstances, and an object thereof is to provide means capable of accurately and quickly measuring the temperature of a biosensor.
  • the present invention relates to a measuring apparatus having a biosensor that can be attached to and detached from the apparatus main body.
  • the biosensor includes a first electrode on which an enzyme that reacts with a substance to be detected in a sample is fixed, a second electrode electrically corresponding to the first electrode, a third electrode for detecting temperature, It comprises.
  • the apparatus main body includes a quantification means for quantifying the substance to be detected in the sample based on a current flowing between the first electrode and the second electrode as a result of the enzyme reacting with the substance to be detected.
  • the biosensor is for electrochemically detecting a substance to be detected in a biological sample.
  • biological samples include mainly liquids such as blood, saliva, and urine.
  • the substance to be detected include blood glucose, cortisol, cholesterol, neutral fat, hemoglobin, bilirubin, and trace metals such as copper, zinc and iron.
  • the biological sample is brought into contact with the electrode of the biosensor, the biological sample and the enzyme are mixed, and the substance to be detected causes an enzyme reaction.
  • a substance to be detected can be detected electrically by the charge generated in the course of the enzyme reaction flowing to the electrode.
  • the enzyme immobilized on the first electrode is not particularly limited as long as it reacts with the detected substance or the reaction product for electrical detection of the aforementioned detected substance.
  • the detected substance is blood. If it is medium glucose, glucose oxidase or glucose dehydrogenase is mentioned.
  • a mediator may be further fixed to the first electrode.
  • the mediator refers to a substance that transmits electrons generated in the above-described enzymatic reaction process.
  • Examples of mediators used for GOD and GDH include organic compounds such as potassium ferricyanide, hexaammineruthenium and quinone derivatives, or organic-metal complexes.
  • the third electrode is made of a material whose resistance value varies with temperature. If the resistance value and temperature coefficient of the material at the reference temperature are known, the temperature of the third electrode can be calculated from the resistance value measured at the third electrode. In order to accurately calculate the temperature, it is preferable that the temperature coefficient shows a certain large value. Examples of such materials include zinc, aluminum, antimony, gold, silver, copper, and nickel.
  • Biosensor can be attached to the device body.
  • the attachment detection means detects that the biosensor is attached.
  • the pair of connection terminals of the apparatus main body are in electrical contact with the third electrode.
  • a control means operates a temperature calculating means.
  • the temperature calculation means calculates the temperature of the third electrode based on the resistance value between the connection terminals.
  • the correcting means corrects the quantitative value of the substance to be detected determined by the quantitative means based on the temperature of the third electrode.
  • the second electrode may also serve as the third electrode.
  • the biosensor since the biosensor is provided with the third electrode and the temperature is calculated based on the resistance value of the third electrode, the temperature of the biosensor is measured accurately and quickly, and the temperature is measured in the apparatus main body. Based on this, the quantitative value can be corrected.
  • FIG. 1 is a perspective view showing an appearance of a blood glucose measurement device 10 according to an embodiment of the present invention.
  • FIG. 2 is an exploded perspective view of the biosensor 11.
  • FIG. 3 is a block diagram showing an internal configuration of the blood glucose measurement device 10.
  • the blood glucose measurement device 10 includes a biosensor 11 and a device body 12.
  • the biosensor 11 and the apparatus main body 12 are electrically connected by inserting the biosensor 11 into the connection portion 13 of the apparatus main body 12.
  • the biosensor 11 is replaced for each blood glucose measurement.
  • This biosensor 11 corresponds to the biosensor in the present invention.
  • the blood glucose measurement device 10 corresponds to the measurement device according to the present invention.
  • the apparatus main body 12 is an electronic apparatus in which an electronic component is accommodated in a housing 50.
  • a liquid crystal display 51 and operation keys 52, 53, and 54 are disposed on the front side of the housing 50.
  • the operation keys 52, 53, and 54 are for generating corresponding commands based on user operations.
  • the liquid crystal display 51 displays the state of the apparatus main body 12, measurement results, error display, and the like.
  • the liquid crystal display 51 corresponds to display means in the present invention.
  • the internal structure of the apparatus main body 12 will be described later.
  • the biosensor 11 has an elongated sheet shape.
  • the biosensor 11 is attached to the apparatus main body 12 by inserting one end of the biosensor 11 in the longitudinal direction 101 into the connection portion 13 of the apparatus main body 12.
  • the attached biosensor 11 protrudes from the apparatus main body 12 in the longitudinal direction 101. Further, when the biosensor 11 is pulled out in the longitudinal direction 101, the biosensor 11 is removed from the apparatus main body 10.
  • the side inserted into the connecting portion 13 corresponds to the second end in the present invention, and the opposite side corresponds to the first end in the present invention.
  • the front and back of the biosensor 11 are relative, any of them may be front or back.
  • the side that appears in FIG. 1 is referred to as the front, and the side that does not appear in FIG. 1 is referred to as the back. That is, the biosensor 11 has a sheet shape in which the first surface 21 and the second surface 22 are front and back surfaces.
  • the biosensor 11 mainly includes a first substrate 23, a counter electrode 24, a temperature detection electrode 42, a spacer 25, a working electrode 26, a sample detection electrode 27, and a second substrate 28.
  • the first substrate 23, the counter electrode 24 and the temperature detection electrode 42, the spacer 25, the working electrode 26 and the sample detection electrode 27, and the second substrate 28 are stacked in this order, and are elongated in the longitudinal direction 101.
  • a sheet-shaped biosensor 11 is configured.
  • the first substrate 23 is a sheet having substantially the same shape as the biosensor 11 in plan view.
  • the first substrate 23 is made of an electrically insulating material.
  • the electrically insulating material include polyesters such as polyethylene terephthalate (PET) and polymethyl methacrylate (PMMA), fluororesin, polycarbonate, and glass.
  • One surface of the first substrate 23 constitutes the first surface 21.
  • a counter electrode 24 and a temperature detection electrode 42 are provided on the surface 32 opposite to the first surface 21.
  • one end side in the longitudinal direction 101 inserted into the connection portion 13 of the apparatus main body 12 is a narrow portion 29 having a narrow width along the direction 102 orthogonal to the longitudinal direction 101.
  • a pair of colored portions 30 and 31 are formed at both ends in the direction 102.
  • the colored portions 30 and 31 are color-coded with the first surface 21.
  • the coloring portions 30 and 31 are for facilitating visual recognition of the position of a sample introduction port 41 to be described later. Therefore, the coloring portions 30 and 31 are arranged immediately above the sample introduction port 41.
  • the counter electrode 24 is provided on the surface 32 of the first substrate 23 opposite to the first surface 21.
  • the counter electrode 24 occupies about one half of the direction 102 on the surface 32 of the first substrate 23.
  • Examples of the counter electrode 24 include silver / silver chloride, gold, palladium, and platinum.
  • the counter electrode 24 is laminated on the surface 32 with respect to the first substrate 23 by a method such as a screen printing method, an ink jet method, sputtering, vacuum deposition, sol-gel method, cluster beam deposition, or PLD.
  • a portion corresponding to the narrow portion 29 of the first substrate 23 is a connection terminal 33 inserted into the connection portion 13 of the apparatus main body 12.
  • the counter electrode 24 corresponds to the second electrode in the present invention.
  • the temperature detection electrode 42 is provided on the surface 32 of the first substrate 23 opposite to the first surface 21.
  • the temperature detection electrode 42 is disposed so as not to overlap the counter electrode 24 on the surface 32 of the first substrate 23.
  • the temperature detection electrode 42 has a resistance value and a temperature coefficient at a reference temperature unique to the material.
  • the resistance value at the reference temperature is known as a resistance value at 20 ° C., for example.
  • the temperature coefficient is known as a resistance value that changes every time the temperature increases by 1 ° C.
  • Examples of the temperature detection electrode 42 include zinc, aluminum, antimony, gold, silver, copper, and nickel.
  • the temperature detection electrode 42 is laminated on the surface 32 with respect to the first substrate 23 by a method such as a screen printing method, an inkjet method, sputtering, vacuum deposition, sol-gel method, cluster beam deposition, or PLD.
  • the temperature detection electrode 42 corresponds to the third electrode in the present invention.
  • the temperature detection electrode 42 is a U-shape in which two portions that are electrically independently extended from the narrow portion 29 along the longitudinal direction 101 are electrically connected at a portion 45 at a position corresponding to the space 40. It has a shape. In the space 40, a portion including a part 45 of the temperature detection electrode 42 is disposed. The portions corresponding to the narrow portion 29 of the temperature detection electrode 42 are two electrically independent end portions, and these end portions are connection terminals 46 and 47 inserted into the connection portion 13 of the apparatus main body 12. is there.
  • the second substrate 28 is a sheet having substantially the same shape as the biosensor 11 in plan view.
  • the second substrate 28 is made of an electrically insulating material.
  • the electrically insulating material include polyesters such as polyethylene terephthalate (PET) and polymethyl methacrylate (PMMA), fluororesin, polycarbonate, and glass.
  • One surface of the second substrate 28 constitutes the second surface 22.
  • a working electrode 26 and a sample detection electrode 27 are provided on a surface 34 opposite to the second surface 22.
  • a narrow portion 35 having a narrow width along the direction 102.
  • the second surface 22 of the second substrate 28 is formed with colored portions similar to the colored portions 30 and 31.
  • the working electrode 26 is provided on a surface 34 of the second substrate 28 opposite to the second surface 22.
  • the working electrode 26 occupies most of the second substrate 28 other than the periphery of the surface 34, but a recessed portion 36 is formed so that the width in the direction 102 becomes narrow at a position corresponding to a space 40 described later. ing.
  • Examples of the material of the working electrode 26 include carbon. Since carbon is used for the working electrode 26, the resistance value of the first electrode 23 employing silver / silver chloride, gold, palladium, platinum or the like is lower than the resistance value of the working electrode 26 made of carbon. Electrons are easily supplied to 40 blood.
  • the working electrode 26 corresponds to the first electrode in the present invention.
  • connection terminal 37 inserted into the connection portion 13 of the apparatus main body 12. None of the spacer 25, the counter electrode 24, the temperature detection electrode 42, or the first substrate 23 is opposed to the connection terminal 37 and is exposed to the outside of the biosensor 11. Since the working electrode 26 is formed on the surface 34 side of the second substrate 28, the connection terminal 37 is exposed only on the first surface 21 side of the biosensor 11.
  • a GOD and a mediator are fixed to a region 38 corresponding to the space 40.
  • a mediator the compound containing transition metals, such as ruthenium, osmium, molybdenum, tungsten, iron, cobalt, is mentioned, for example.
  • the GOD and the mediator are fixed by applying a liquid containing the GOD and the mediator to the working electrode 26 and drying it.
  • sample detection electrode 27 As shown in FIG. 2, the sample detection electrode 27 is provided on the surface 34 of the second substrate 28 opposite to the second surface 22.
  • the sample detection electrode 27 is elongated in the longitudinal direction 101 on the surface 34 of the second substrate 28 and is bent so that one end thereof enters the recess 36 of the working electrode 26.
  • Examples of the material of the sample detection electrode 27 include silver / silver chloride, gold, palladium, and platinum.
  • the sample detection electrode 27 is an electrode for detecting whether blood is introduced into the space 40.
  • the part corresponding to the narrow part 35 of the second substrate 28 is a connection terminal 39 inserted into the connection part 13 of the apparatus main body 12. None of the spacer 25, the counter electrode 24, the temperature detection electrode 42, or the first substrate 23 is opposed to the connection terminal 39, and is exposed to the outside of the biosensor 11. Since the sample detection electrode 27 is formed on the surface 34 side of the second substrate 28, the connection terminal 39 is exposed only on the first surface 21 side of the biosensor 11.
  • the spacer 25 is a sheet having substantially the same shape as the biosensor 11 in plan view.
  • a double-sided tape having electrical insulation is preferably used.
  • the spacer 25 has a space 40 extending in the direction 102 at a position corresponding to the coloring portions 30 and 31. That is, the spacer 25 is composed of two sheets separated by the space 40 with respect to the longitudinal direction 101.
  • the space 40 forms a sample space corresponding to the thickness of the spacer 25 between the counter electrode 24 and the temperature detection electrode 42 and the working electrode 26 and the sample detection electrode 27. That is, the space 40 becomes the sample space.
  • a part of the counter electrode 24, a part 45 of the temperature detection electrode 42, a part of the working electrode 26, and a part of the sample detection electrode 27 are exposed.
  • the counter electrode 24 and the temperature detection electrode 42, the working electrode 26 and the sample detection electrode 27 are opposed to each other in the space 40 while being separated in the thickness direction of the biosensor 11.
  • the space 40 is opened at the end of the biosensor 11, and this opening serves as the sample introduction port 41.
  • the space 40 is also opened at a position facing the sample introduction port 41.
  • connection portion 13 of the apparatus main body 12 is provided with five connection terminals 61 to 65.
  • the connection terminals 61 to 65 correspond to the connection terminal 33 of the counter electrode 24, the connection terminals 46 and 47 of the temperature detection electrode 42, the connection terminal 37 of the working electrode 26, and the connection terminal 39 of the sample detection electrode 27.
  • the two connection terminals 62 and 63 are electrically connected to the connection terminals 46 and 47 of the temperature detection electrode 42, respectively.
  • the connection terminals 62 and 63 correspond to a pair of connection terminals in the present invention.
  • the apparatus main body 12 is provided with a control unit 70.
  • the control unit 70 is an arithmetic unit configured by a CPU for performing various calculations, a ROM for storing various programs, a RAM for temporarily storing data for various calculations, a bus for transmitting data, and the like.
  • a blood glucose determination unit 71, a sample detection unit 72, a temperature calculation unit 73, a correction unit 74, a liquid crystal display 51, and operation keys 51, 52, and 53 are connected to the control unit 70 so as to be able to transmit and receive electrical signals.
  • the control unit 70 controls each operation of the blood glucose determination unit 71, the sample detection unit 72, the temperature calculation unit 73, the correction unit 74, and the liquid crystal display 51.
  • the control unit 70 corresponds to the control means in the present invention.
  • the blood glucose determination unit 71 calculates a blood glucose level based on the current value flowing between the counter electrode 24 and the working electrode 26 of the biosensor 11, and the current flowing between the counter electrode 24 and the working electrode 26 is calculated. It has a circuit that converts it into a voltage, shapes an electrical signal represented by the voltage, and converts it into a digital signal expressed numerically. Moreover, it has a program which calculates a blood glucose level based on the electric current value which flowed between the counter electrode 24 and the working electrode 26. This program may be stored in the control unit 70. An electrical signal indicating the calculated blood glucose level is stored in the RAM of the control unit 70.
  • the blood sugar quantification unit 71 corresponds to the quantification means in the present invention.
  • the sample detector 72 determines whether a sample has been introduced into the space 40 based on the current value flowing between the counter electrode 24 and the sample detection electrode 27.
  • the control unit 70 requests the blood glucose determination unit 71 to calculate the blood glucose level and the temperature calculation unit 73 to calculate the temperature on the condition that the sample detection unit 72 determines that there is a sample.
  • the temperature calculation unit 73 calculates a temperature based on a resistance value generated between the connection terminals 46 and 47 of the temperature detection electrode 42 and the connection terminals 62 and 63 connected thereto.
  • the temperature calculation unit 73 stores a resistance value and a temperature coefficient at a reference temperature unique to the material of the temperature detection electrode 42, and a resistance value generated between the connection terminals 62 and 63 and a resistance value at the reference temperature are stored.
  • the temperature of the temperature detection electrode 42 is calculated by dividing the difference by the temperature coefficient.
  • An electric signal indicating the calculated temperature is stored in the RAM of the control unit 70.
  • the resistance value and the temperature coefficient at the reference temperature specific to the material of the temperature detection electrode 42 may be stored in the control unit 70.
  • the temperature calculation unit 73 corresponds to the temperature calculation means in the present invention.
  • the correction unit 74 performs temperature correction of the blood glucose level based on each electrical signal indicating the blood glucose level and temperature stored in the RAM of the control unit 70.
  • the correction unit 74 has a table indicating the relationship between the temperature and the correction coefficient.
  • the correction unit 74 selects a correction coefficient corresponding to the temperature stored in the RAM of the control unit 70, and calculates the corrected blood sugar level by multiplying the blood sugar level stored in the RAM by the correction coefficient.
  • An electrical signal indicating the corrected blood glucose level is stored in the RAM of the control unit 70.
  • the correction unit 74 corresponds to the correction unit in the present invention.
  • connection terminals 61 to 65, the connection terminal 33 of the counter electrode 24, the connection terminals 46 and 47 of the temperature detection electrode 42, the connection terminal 37 of the working electrode 26, and the connection terminal 39 of the sample detection electrode 27 are electrically connected. Connected to.
  • the control unit 70 When the biosensor 11 is connected to the apparatus main body 12, a current can flow between the connection terminals 62 and 63 of the apparatus main body 12 via the temperature detection electrode 42.
  • the control unit 70 When the power of the apparatus main body 12 is turned on, the control unit 70 periodically applies a weak potential between the connection terminals 62 and 63, and detects a current flowing between the connection terminals 62 and 63, thereby detecting the biosensor. 11 is attached.
  • the mounting detection means in the present invention is realized.
  • the control unit 70 causes the temperature calculation unit 72 to apply a predetermined potential and current to the temperature detection electrode 42 and measure the resistance value of the temperature detection electrode 42 on the condition that the biosensor 11 has been mounted.
  • the resistance value of the temperature detection electrode 42 is measured as a resistance value with respect to a current flowing from the connection terminal 46 through the part 45 to the connection terminal 47 or a current flowing from the connection terminal 47 through the part 45 to the connection terminal 46.
  • the temperature calculation unit 72 calculates the temperature of the temperature detection electrode 42 based on the resistance value of the temperature detection electrode 42 and the resistance value and temperature coefficient at the reference temperature. An electric signal indicating the calculated temperature is stored in the RAM of the control unit 70.
  • Measured person collects his own blood.
  • the blood can be collected by the person himself / herself using, for example, a lancet. This blood corresponds to the sample in the present invention.
  • the collected blood is introduced into the space 40 from the sample inlet 41 of the biosensor 11 as a sample.
  • the blood is guided to the space 40 by capillary action.
  • a current is generated between the counter electrode 24 and the sample detection electrode 27, and the sample detection unit 72 determines that there is a sample based on this current.
  • the blood introduced into the space 40 is held between the counter electrode 24 and the working electrode 26 and causes an electrochemical reaction.
  • This electrochemical reaction generates a current that correlates with the blood glucose level between the counter electrode 24 and the working electrode 26.
  • the control unit 70 causes the blood glucose determination unit 71 to calculate the blood glucose level based on the current flowing between the counter electrode 24 and the working electrode 26 on the condition that the sample detection unit 72 determines that there is a sample. Note that when blood is introduced into the space 40, the blood contacts the part 45 of the temperature detection electrode 42.
  • the temperature calculation unit 72 measures the resistance value of the temperature detection electrode 42 as soon as the biosensor 11 is attached to the apparatus main body 12, and this measurement ends until the sample detection unit 72 determines that there is a sample. However, the control unit 70 does not apply the potential and current to the connection terminals 62 and 63 on condition that the sample detection unit 72 determines that there is a sample.
  • the control unit 70 causes the correction unit 74 to perform temperature correction of the blood glucose level on the obtained blood glucose level based on the already measured temperature. Then, the controller 70 displays the obtained corrected blood glucose level on the liquid crystal display 51.
  • the temperature detection electrode 42 is provided in the biosensor 11, and the temperature calculation unit 72 calculates the temperature of the temperature detection electrode 42 based on the resistance value of the temperature detection electrode 42. Can be measured accurately and quickly to correct the blood glucose level based on the temperature.
  • the counter electrode 24 and the working electrode 26 are opposed to each other with the space 40 interposed therebetween, and even if an elongated sheet shape is used as a whole, the loss due to heat conduction in the temperature detection electrode 42.
  • the temperature of the biosensor 11 is measured without being affected by the above.
  • the space 40 and the sample introduction port 41 are arranged on the side opposite to the side connected to the connection portion 13 of the apparatus main body 12, blood is introduced at the distal end side of the biosensor 11 protruding from the apparatus main body 12. This facilitates introduction of blood into the space 40 and facilitates the attachment of blood to the apparatus main body 12.
  • the enzyme contained in the reagent is GOD, but it goes without saying that the enzyme in the present invention is not limited to GOD.
  • GDH may be included in the reagent as an enzyme instead of GOD.
  • the configuration of the biosensor 11 shown in the present embodiment is only one aspect of the configuration of the biosensor according to the present invention. Therefore, instead of the three-dimensional type in which the counter electrode 24 and the working electrode 26 are opposed to each other via the spacer 25 like the biosensor 11, the bio-type is a planar type in which the working electrode and the counter electrode are arranged on the same substrate. A sensor may be realized.
  • the biosensor according to the present invention is not limited to the portable blood glucose measurement device like the blood glucose measurement device 10. Therefore, when a biosensor is used for measuring other components in blood, it can also be used in an embodiment in which a reagent containing an enzyme necessary for the measurement is fixed to the electrode.
  • the sample is not limited to blood, and may be a biological sample such as urine or saliva, or an aqueous solution containing a substance to be detected.
  • the temperature detection electrode 42 is provided independently of the working electrode 24, the counter electrode 26, and the sample detection electrode 27 in the biosensor 11, but the temperature detection electrode 42 is provided as the counter electrode 26 or the sample detection electrode 27. May also be served.
  • two connection terminals are connected to the connection terminal 37 of the counter electrode 26 that also serves as the temperature detection electrode 42 or the connection terminal 39 of the sample detection electrode 27 in the connection part 13 of the apparatus body 12. Since no enzyme or mediator is fixed to the counter electrode 26 or the sample detection electrode 27, even if a potential or current is applied through the two connection terminals of the connection unit 13 before blood is introduced into the biosensor 11, There is no electrical effect on the enzyme or mediator. Thereby, size reduction and cost reduction of the biosensor 11 and the apparatus main body 12 are implement
  • a mode is shown in which the control unit 70 detects that the biosensor 11 is attached to the apparatus main body 12 based on a change in current between the connection terminals 62 and 63.
  • the control unit 70 detects that the biosensor 11 is attached to the apparatus main body 12 based on a change in current between the connection terminals 62 and 63.
  • a configuration may be adopted in which the biosensor 11 is mechanically detected by providing the connection portion 13 with a mechanical switch that can be pressed by the biosensor 11.
  • a configuration in which the biosensor 11 is optically detected by providing a photo interrupter that is shielded by the sensor 11 may be employed.

Abstract

Disclosed is a measuring device that has a biosensor that can be removed from a main device. The biosensor is provided with: a first electrode; a second electrode; and a third electrode for measuring a temperature. The main device is provided with: a quantity measurement means that measures the quantity of a target substance in a sample on the basis of a current that flows between the first electrode and the second electrode as a result of oxygen reacting with the target substance; a pair of connection terminals that electrically connect to the third electrode; a temperature computation means that computes the temperature of the third electrode on the basis of the resistance of the third electrode, obtained between the connection terminals; a correction means that, on the basis of the temperature computed by the temperature computation means, corrects the measured quantity of the target substance measured by the quantity measurement means; an attachment detection means that detects when the biosensor is attached; and a control means that has the temperature computation means compute the temperature of the third electrode if the attachment detection means has detected the attachment of the biosensor.

Description

バイオセンサを有する測定装置Measuring device having a biosensor
　本発明は、酵素が固定された第１電極と、第１電極に対応する第２電極とを有するバイオセンサが装置本体に着脱可能に設けられた測定装置に関する。 The present invention relates to a measuring apparatus in which a biosensor having a first electrode on which an enzyme is immobilized and a second electrode corresponding to the first electrode is detachably provided on the apparatus body.
　近年、糖尿病の患者が各国において増加している。糖尿病の治療としては、例えば、インスリン療法がある。インスリンは血糖値をコントロールする薬物として知られており、糖尿病の治療薬として糖尿病患者に投与されている。インスリンを投与する必要性は、糖尿病患者の血糖値に基づいて判断される。このため、糖尿病患者にとって、血糖値の把握が重要である。血糖値とは、血液中のグルコース濃度である。糖尿病患者自らが自分の血糖値を簡易に測定できることを目的として、簡易な血糖測定装置が開発されている。 In recent years, the number of diabetic patients is increasing in each country. As a treatment for diabetes, for example, there is insulin therapy. Insulin is known as a drug that controls blood glucose levels and is administered to diabetic patients as a therapeutic agent for diabetes. The need to administer insulin is determined based on the blood glucose level of the diabetic patient. For this reason, it is important for a diabetic patient to grasp a blood glucose level. The blood glucose level is the glucose concentration in the blood. A simple blood glucose measuring device has been developed for the purpose of allowing a diabetic patient to easily measure his blood glucose level.
　前述された血糖測定装置として、バイオセンサが用いられるものが知られている（特許文献１～４）。バイオセンサは、血糖と反応する酵素が固定された電極を有する。血糖値の測定に用いられる酵素として、グルコースオキシターゼ（以下、「ＧＯＤ」と略されることがある。）やグルコースデヒドロゲナーゼ（以下、「ＧＤＨ」と略されることがある。）が知られている。バイオセンサにおいて、酵素が固定された電極が作用極と称され、試料中に電子を供給する電極が対極と称される。 As the blood glucose measurement device described above, one using a biosensor is known (Patent Documents 1 to 4). The biosensor has an electrode on which an enzyme that reacts with blood sugar is fixed. Glucose oxidase (hereinafter sometimes abbreviated as “GOD”) and glucose dehydrogenase (hereinafter sometimes abbreviated as “GDH”) are known as enzymes used for blood glucose level measurement. . In a biosensor, an electrode on which an enzyme is immobilized is called a working electrode, and an electrode that supplies electrons into a sample is called a counter electrode.
　試料である血液がバイオセンサに導入され、その血液中のグルコースに作用極のＧＯＤが反応すると、グルコースがグルコン酸及び過酸化水素に分解され、その過酸化水素が水及び電子に分解される。このようにして発生した電子が作用極に伝達される。一方、対極からは血液中に電子が供給される。このようにして、ＧＯＤとグルコースとの反応によって、作用極と対極との間に電流が流れる。そして、流れた電流値に基づいて、血液中のグルコース濃度、つまり血糖値が算出される。また、作用極には、電子を伝達する物質が固定されることがある。この物質は、電子メディエータと称される。電子メディエータとして、例えば、フェリシアン化カリウム、ヘキサアンミンルテニウムやキノン誘導体類等の有機化合物、又は有機－金属錯体などが挙げられる。 When blood, which is a sample, is introduced into the biosensor and the working electrode GOD reacts with glucose in the blood, glucose is decomposed into gluconic acid and hydrogen peroxide, and the hydrogen peroxide is decomposed into water and electrons. The electrons generated in this way are transmitted to the working electrode. On the other hand, electrons are supplied from the counter electrode into the blood. In this way, a current flows between the working electrode and the counter electrode due to the reaction between GOD and glucose. Then, based on the flowing current value, the glucose concentration in the blood, that is, the blood glucose level is calculated. In addition, a substance that transmits electrons may be fixed to the working electrode. This material is referred to as an electron mediator. Examples of the electron mediator include organic compounds such as potassium ferricyanide, hexaammineruthenium and quinone derivatives, or organic-metal complexes.
　前述されたバイオセンサによるグルコースの測定において、温度が測定値に影響を及ぼすことが知られている。温度の影響の原因として、バイオセンサに流れる電流を電圧に変換するための抵抗の温度特性や、酵素の反応速度の温度依存性、メディエータの拡散速度の温度依存性などが指摘されている。 In the measurement of glucose by the biosensor described above, it is known that the temperature affects the measured value. As the cause of the temperature, the temperature characteristics of the resistance for converting the current flowing through the biosensor into voltage, the temperature dependence of the reaction rate of the enzyme, the temperature dependence of the diffusion rate of the mediator, etc. have been pointed out.
　グルコース測定値への温度の影響を回避することを目的として、バイオセンサが装着される測定装置に温度センサを設け、その温度センサの測定値に基づいてグルコース測定値を補正する構成が公知である（特許文献５～７）。また、バイオセンサにおいて血液が導入される箇所を測定装置の一部に接触させて、その接触する一部に温度センサを用いた構成が公知である（特許文献８）。また、バイオセンサに熱伝導層を設けて、その熱伝導層を通じて、バイオセンサに導入された血液の温度を測定する構成が公知である（特許文献９，１０）。また、バイオセンサに、グルコース以外の物質に対して酸化還元反応を生ずる電極対を別途に設けて、その酸化還元反応により得られた電流値に基づいて、グルコース測定値を補正する構成が公知である（特許文献１１）。 For the purpose of avoiding the influence of temperature on the glucose measurement value, a configuration is known in which a temperature sensor is provided in a measurement device to which a biosensor is attached and the glucose measurement value is corrected based on the measurement value of the temperature sensor. (Patent Documents 5 to 7). Further, a configuration is known in which a part where blood is introduced in a biosensor is brought into contact with a part of a measuring apparatus, and a temperature sensor is used for the part of the contact (Patent Document 8). Moreover, the structure which provides a heat conductive layer in a biosensor and measures the temperature of the blood introduced into the biosensor through the heat conductive layer is known (patent documents 9 and 10). Also, a configuration is known in which a biosensor is separately provided with an electrode pair that causes a redox reaction for substances other than glucose, and the measured glucose value is corrected based on the current value obtained by the redox reaction. Yes (Patent Document 11).
特開２００９－９７８７７号公報JP 2009-97877 A 特開２００５－４３２８０号公報JP 2005-43280 A 特開２００５－３７３３５号公報JP-A-2005-37335 特開２００２－１０７３２５号公報JP 2002-107325 A 特許第３４９４５６４号公報Japanese Patent No. 3494564 特許第４１２４５１３号公報Japanese Patent No. 4124513 特開２００７－１０３１７号公報JP 2007-10317 A 国際公開２００３－０６２８１２号パンフレットInternational Publication No. 2003-062812 Pamphlet 特開２００１－２３５４４４号公報JP 2001-235444 A 特開２００３－１５６４６９号公報JP 2003-156469 A 特開２００９－２５０８０６号公報JP 2009-250806 A
　しかしながら、特許文献５～７に開示されるように、測定装置に温度センサを設けたとしても、測定される温度は測定装置内あるいは測定装置周辺のものなので、バイオセンサに導入される血液の温度が正確に測定されるわけではない。そのため、例えば、血液が比較的体温に近い状態で導入された場合や、バイオセンサが測定装置に装着されるまでに手の温もりなどで暖められた場合では、測定装置の温度センサにより測定された温度と、バイオセンサに導入された血液の温度とが大きく解離し、適切な温度補正が実現されずに不正確な測定結果となるおそれがある。 However, as disclosed in Patent Documents 5 to 7, even if a temperature sensor is provided in the measurement device, the temperature to be measured is in or around the measurement device, so the temperature of blood introduced into the biosensor Is not accurately measured. Therefore, for example, when blood was introduced in a state that is relatively close to body temperature, or when the biosensor was warmed by the warmth of the hand before being attached to the measuring device, the temperature was measured by the temperature sensor of the measuring device. The temperature and the temperature of the blood introduced into the biosensor are greatly dissociated, and there is a possibility that an inaccurate measurement result may be obtained without realizing an appropriate temperature correction.
　また、特許文献８に開示されるように、測定装置の温度センサを、バイオセンサにおける血液導入箇所に合致させるには、バイオセンサの血液導入箇所が測定装置の一部と重なるように配置される必要がある。そうすると、指などから直接にバイオセンサへ血液を導入する作業がしづらくなったり、測定装置に血液が付着したりするおそれがある。 Further, as disclosed in Patent Document 8, in order to match the temperature sensor of the measurement device with the blood introduction location in the biosensor, the blood introduction location of the biosensor is arranged so as to overlap a part of the measurement device. There is a need. If it does so, there exists a possibility that the operation | work which introduces blood into a biosensor directly from a finger | toe etc. may become difficult, or blood may adhere to a measuring apparatus.
　また、特許文献９，１０に開示されるように、バイオセンサに設けられた熱伝導層を通じて血液の温度を測定する構成では、熱伝導層が比較的短ければ、血液から温度センサまで熱伝導層を通じて迅速に温度が伝わるが、熱伝導層が長ければ、血液の温度が温度センサまで伝わるに要する時間を待って、温度補正がなされた測定結果が表示されるので、全体として測定時間が長くなるおそれがある。また、熱伝導層の途中の環境温度が測定結果に影響するおそれもある。 Further, as disclosed in Patent Documents 9 and 10, in the configuration in which the temperature of blood is measured through the heat conductive layer provided in the biosensor, if the heat conductive layer is relatively short, the heat conductive layer from the blood to the temperature sensor is used. The temperature is transmitted quickly through, but if the heat conduction layer is long, the time required for the blood temperature to reach the temperature sensor is waited, and the measurement result with temperature correction is displayed, so the measurement time becomes longer as a whole There is a fear. In addition, the environmental temperature in the middle of the heat conductive layer may affect the measurement result.
　また、特許文献１１に開示されるように、バイオセンサにおいて、被検出物質と反応する電極対の他に、別途に電極対を設ける構成では、バイオセンサが大型化し、かつコストアップも避けられない。また、２つの酸化還元反応があらゆる温度範囲において再現性よく相関するとは限らないので、別途の電極対における酸化還元反応の種類を最適とするために多くの労力を要する。 Further, as disclosed in Patent Document 11, in the biosensor, in addition to the electrode pair that reacts with the substance to be detected, the configuration in which the electrode pair is separately provided increases the size of the biosensor and inevitably increases the cost. . In addition, since the two oxidation-reduction reactions do not necessarily correlate with good reproducibility in all temperature ranges, much effort is required to optimize the type of oxidation-reduction reaction in a separate electrode pair.
　本発明は、前述された事情に鑑みてなされたものであり、その目的は、バイオセンサの温度を正確且つ迅速に測定することが可能な手段を提供することにある。 The present invention has been made in view of the above-described circumstances, and an object thereof is to provide means capable of accurately and quickly measuring the temperature of a biosensor.
　本発明は、装置本体に着脱可能なバイオセンサを有する測定装置に関する。上記バイオセンサは、試料中の被検出物質と反応する酵素が固定された第１電極と、上記第１電極と電気的に対応する第２電極と、温度を検出するための第３電極と、を具備する。上記装置本体は、上記酵素が被検出物質と反応することにより上記第１電極と上記第２電極との間に流れた電流に基づいて、上記試料中の当該被検出物質を定量する定量手段と、上記第３電極と電気的に接触する一対の接続端子と、上記接続端子間において得られた上記第３電極の抵抗値に基づいて、上記第３電極の温度を演算する温度演算手段と、上記温度演算手段により演算された温度に基づいて、上記定量手段が定量した被検出物質の定量値を補正する補正手段と、上記温度補正手段により補正された被検出物質の定量値を表示する表示手段と、上記バイオセンサが装着されたことを検知する装着検知手段と、上記装着検知手段が上記バイオセンサの装着を検知したことを条件として、上記温度演算手段に上記第３電極の温度を演算させる制御手段と、を具備する。 The present invention relates to a measuring apparatus having a biosensor that can be attached to and detached from the apparatus main body. The biosensor includes a first electrode on which an enzyme that reacts with a substance to be detected in a sample is fixed, a second electrode electrically corresponding to the first electrode, a third electrode for detecting temperature, It comprises. The apparatus main body includes a quantification means for quantifying the substance to be detected in the sample based on a current flowing between the first electrode and the second electrode as a result of the enzyme reacting with the substance to be detected. A pair of connection terminals that are in electrical contact with the third electrode, and a temperature calculation means that calculates the temperature of the third electrode based on a resistance value of the third electrode obtained between the connection terminals; Based on the temperature calculated by the temperature calculation means, a correction means for correcting the quantitative value of the detected substance quantified by the quantitative means, and a display for displaying the quantitative value of the detected substance corrected by the temperature correction means Means for detecting that the biosensor is mounted, and the temperature calculation means calculates the temperature of the third electrode on condition that the mounting detection means detects the mounting of the biosensor. The Comprising a control unit that, the.
　バイオセンサは、生体試料中の被検出物質を電気化学的に検出するためのものである。生体試料としては、血液や唾液、尿などの主として液体が挙げられる。例えば、生体試料が血液であれば、被検出物質として、血糖やコルチゾール、コレステロール、中性脂肪、ヘモグロビン、ビリルビン並びに銅、亜鉛及び鉄等の微量金属などが挙げられる。生体試料がバイオセンサの電極と接触されることにより、生体試料と酵素とが混合されて、被検出物質が酵素反応を起こす。その酵素反応の過程において生成される電荷が電極に流れることによって、被検出物質が電気的に検出可能となる。 The biosensor is for electrochemically detecting a substance to be detected in a biological sample. Examples of biological samples include mainly liquids such as blood, saliva, and urine. For example, if the biological sample is blood, examples of the substance to be detected include blood glucose, cortisol, cholesterol, neutral fat, hemoglobin, bilirubin, and trace metals such as copper, zinc and iron. When the biological sample is brought into contact with the electrode of the biosensor, the biological sample and the enzyme are mixed, and the substance to be detected causes an enzyme reaction. A substance to be detected can be detected electrically by the charge generated in the course of the enzyme reaction flowing to the electrode.
　第１電極に固定される酵素は、前述された被検出物質の電気的な検出のために被検出物質又は反応生成物と反応するものであれば特に限定されないが、例えば、被検出物質が血液中のグルコースであれば、グルコースオキシダーゼ又はグルコースデヒドロゲナーゼが挙げられる。 The enzyme immobilized on the first electrode is not particularly limited as long as it reacts with the detected substance or the reaction product for electrical detection of the aforementioned detected substance. For example, the detected substance is blood. If it is medium glucose, glucose oxidase or glucose dehydrogenase is mentioned.
　第１電極には、更にメディエータが固定されていてもよい。メディエータとは、前述された酵素反応の過程において生成される電子を伝達する物質をいう。ＧＯＤやＧＤＨに用いられるメディエータとしては、フェリシアン化カリウム、ヘキサアンミンルテニウムやキノン誘導体類等の有機化合物、又は有機－金属錯体などが挙げられる。 A mediator may be further fixed to the first electrode. The mediator refers to a substance that transmits electrons generated in the above-described enzymatic reaction process. Examples of mediators used for GOD and GDH include organic compounds such as potassium ferricyanide, hexaammineruthenium and quinone derivatives, or organic-metal complexes.
　第３電極は、温度によって抵抗値が変動する材料からなる。その材料の基準温度における抵抗値と温度係数とが既知であれば、第３電極において測定された抵抗値から第３電極の温度を演算することができる。温度を正確に演算するためには、温度係数がある程度大きな値を示すものが好ましい。このような材料として、例えば、亜鉛やアルミニウム、アンチモン、金、銀、銅、ニッケルなどが挙げられる。 The third electrode is made of a material whose resistance value varies with temperature. If the resistance value and temperature coefficient of the material at the reference temperature are known, the temperature of the third electrode can be calculated from the resistance value measured at the third electrode. In order to accurately calculate the temperature, it is preferable that the temperature coefficient shows a certain large value. Examples of such materials include zinc, aluminum, antimony, gold, silver, copper, and nickel.
　バイオセンサは、装置本体に対して装着可能である。装着検知手段は、バイオセンサが装着されたことを検知する。バイオセンサが装着されると、装置本体の一対の接続端子が第３電極に電気的に接触する。そして、制御手段は、温度演算手段を動作させる。温度演算手段は、接続端子間の抵抗値に基づいて第３電極の温度を演算する。補正手段は、この第３電極の温度に基づいて、定量手段が定量した被検出物質の定量値を補正する。 Biosensor can be attached to the device body. The attachment detection means detects that the biosensor is attached. When the biosensor is attached, the pair of connection terminals of the apparatus main body are in electrical contact with the third electrode. And a control means operates a temperature calculating means. The temperature calculation means calculates the temperature of the third electrode based on the resistance value between the connection terminals. The correcting means corrects the quantitative value of the substance to be detected determined by the quantitative means based on the temperature of the third electrode.
　本発明に係るバイオセンサにおいて、第２電極は、第３電極を兼ねるものであってもよい。これにより、バイオセンサの構成が簡略化されて、バイオセンサ及び装置本体の小型化及びコストダウンが実現される。 In the biosensor according to the present invention, the second electrode may also serve as the third electrode. Thereby, the configuration of the biosensor is simplified, and the size and cost of the biosensor and the apparatus main body are reduced.
　本発明によれば、バイオセンサに第３電極が設けられ、第３電極の抵抗値に基づいて温度が演算されるので、バイオセンサの温度を正確且つ迅速に測定して、装置本体において当該温度に基づいて定量値を補正することができる。 According to the present invention, since the biosensor is provided with the third electrode and the temperature is calculated based on the resistance value of the third electrode, the temperature of the biosensor is measured accurately and quickly, and the temperature is measured in the apparatus main body. Based on this, the quantitative value can be corrected.
図１は、本発明の実施形態に係る血糖測定装置１０の外観を示す斜視図である。FIG. 1 is a perspective view showing an appearance of a blood glucose measurement device 10 according to an embodiment of the present invention. 図２は、バイオセンサ１１の分解斜視図である。FIG. 2 is an exploded perspective view of the biosensor 11. 図３は、血糖測定装置１０の内部構成を示すブロック図である。FIG. 3 is a block diagram showing an internal configuration of the blood glucose measurement device 10.
１０・・・血糖測定装置（測定装置）
１１・・・バイオセンサ
１２・・・装置本体
２４・・・対極（第２電極）
２６・・・作用極（第１電極）
３３，３７，４６，４７・・・接続端子
４０・・・空間
４２・・・温度検知極（第３電極）
５１・・・液晶ディスプレイ（表示手段）
６２，６３・・・接続端子（装着検知手段）
７０・・・制御部（制御手段）
７１・・・血糖定量部（定量手段）
７３・・・温度演算部（温度演算手段）
７４・・・補正部（補正手段） 10 ... blood glucose measuring device (measuring device)
11 ... Biosensor 12 ... Device body 24 ... Counter electrode (second electrode)
26 ... Working electrode (first electrode)
33, 37, 46, 47 ... connection terminal 40 ... space 42 ... temperature detection electrode (third electrode)
51 ... Liquid crystal display (display means)
62, 63 ... Connection terminal (mounting detection means)
70: Control unit (control means)
71 ... Blood sugar quantification part (quantitative means)
73 ... Temperature calculation part (temperature calculation means)
74... Correction unit (correction means)
　以下に、適宜図面が参照されて、本発明の好ましい実施形態が説明される。なお、以下に説明される各実施形態は本発明の一例にすぎず、本発明の要旨を変更しない範囲で、本発明の実施形態が適宜変更できることは言うまでもない。 Hereinafter, preferred embodiments of the present invention will be described with reference to the drawings as appropriate. Each embodiment described below is only an example of the present invention, and it is needless to say that the embodiment of the present invention can be changed as appropriate without departing from the gist of the present invention.
［血糖測定装置１０］
　図１に示されるように、血糖測定装置１０は、バイオセンサ１１と装置本体１２とを有する。バイオセンサ１１が装置本体１２の接続部１３に差し込まれることによって、バイオセンサ１１と装置本体１２とが電気的に接続される。バイオセンサ１１は、１回の血糖測定毎に取り替えられるものである。このバイオセンサ１１が、本発明におけるバイオセンサに相当する。血糖測定装置１０が、本発明に係る測定装置に相当する。 [Blood glucose measuring device 10]
As shown in FIG. 1, the blood glucose measurement device 10 includes a biosensor 11 and a device body 12. The biosensor 11 and the apparatus main body 12 are electrically connected by inserting the biosensor 11 into the connection portion 13 of the apparatus main body 12. The biosensor 11 is replaced for each blood glucose measurement. This biosensor 11 corresponds to the biosensor in the present invention. The blood glucose measurement device 10 corresponds to the measurement device according to the present invention.
［装置本体１２］
　図１に示されるように、装置本体１２は、筐体５０に電子部品が収容された電子装置である。筐体５０の表側には、液晶ディスプレイ５１及び操作キー５２，５３，５４が配置されている。操作キー５２，５３，５４は、ユーザの操作に基づいて対応するコマンドを発生させるためのものである。液晶ディスプレイ５１は、装置本体１２の状態や測定結果、エラー表示などを行う。液晶ディスプレイ５１が、本発明における表示手段に相当する。装置本体１２の内部構造については後述される。 [Apparatus body 12]
As shown in FIG. 1, the apparatus main body 12 is an electronic apparatus in which an electronic component is accommodated in a housing 50. A liquid crystal display 51 and operation keys 52, 53, and 54 are disposed on the front side of the housing 50. The operation keys 52, 53, and 54 are for generating corresponding commands based on user operations. The liquid crystal display 51 displays the state of the apparatus main body 12, measurement results, error display, and the like. The liquid crystal display 51 corresponds to display means in the present invention. The internal structure of the apparatus main body 12 will be described later.
［バイオセンサ１１］
　図１に示されるように、バイオセンサ１１は、細長なシート形状である。バイオセンサ１１の長手方向１０１の一端が、装置本体１２の接続部１３に差し込まれることによって、バイオセンサ１１が装置本体１２に装着される。装着されたバイオセンサ１１は、装置本体１２から長手方向１０１へ突出される。また、バイオセンサ１１が長手方向１０１に引き抜かれることによって、バイオセンサ１１が装置本体１０から取り外される。バイオセンサ１１において、接続部１３に差し込まれる側が本発明における第２端に相当し、その反対側が本発明における第１端に相当する。 [Biosensor 11]
As shown in FIG. 1, the biosensor 11 has an elongated sheet shape. The biosensor 11 is attached to the apparatus main body 12 by inserting one end of the biosensor 11 in the longitudinal direction 101 into the connection portion 13 of the apparatus main body 12. The attached biosensor 11 protrudes from the apparatus main body 12 in the longitudinal direction 101. Further, when the biosensor 11 is pulled out in the longitudinal direction 101, the biosensor 11 is removed from the apparatus main body 10. In the biosensor 11, the side inserted into the connecting portion 13 corresponds to the second end in the present invention, and the opposite side corresponds to the first end in the present invention.
　バイオセンサ１１の表裏は相対的な関係なので、いずれが表であっても裏であってもよい。本実施形態においては、図１に現れる側が表と称され、図１に現れない側が裏と称される。つまり、バイオセンサ１１は、第１面２１及び第２面２２が表裏面をなすシート形状である。 Since the front and back of the biosensor 11 are relative, any of them may be front or back. In this embodiment, the side that appears in FIG. 1 is referred to as the front, and the side that does not appear in FIG. 1 is referred to as the back. That is, the biosensor 11 has a sheet shape in which the first surface 21 and the second surface 22 are front and back surfaces.
　図２に示されるように、バイオセンサ１１は、主として、第１基板２３、対極２４、温度検知極４２、スペーサ２５、作用極２６、試料検知極２７及び第２基板２８を有する。図２における上側、つまり表側から順に、第１基板２３、対極２４及び温度検知極４２、スペーサ２５、作用極２６及び試料検知極２７、第２基板２８の順に積層されて、長手方向１０１に細長なシート形状のバイオセンサ１１が構成されている。 2, the biosensor 11 mainly includes a first substrate 23, a counter electrode 24, a temperature detection electrode 42, a spacer 25, a working electrode 26, a sample detection electrode 27, and a second substrate 28. 2, the first substrate 23, the counter electrode 24 and the temperature detection electrode 42, the spacer 25, the working electrode 26 and the sample detection electrode 27, and the second substrate 28 are stacked in this order, and are elongated in the longitudinal direction 101. A sheet-shaped biosensor 11 is configured.
［第１基板２３］
　図２に示されるように、第１基板２３は、平面視がバイオセンサ１１と概ね同じ形状のシートである。第１基板２３は、電気絶縁性の材料からなる。この電気絶縁性の材料として、例えばポリエチレンテレフタレート（ＰＥＴ）、ポリメタクリル酸メチル（ＰＭＭＡ）等のポリエステルや、フッ素樹脂及びポリカーボネイト、ガラスなどが挙げられる。 [First substrate 23]
As shown in FIG. 2, the first substrate 23 is a sheet having substantially the same shape as the biosensor 11 in plan view. The first substrate 23 is made of an electrically insulating material. Examples of the electrically insulating material include polyesters such as polyethylene terephthalate (PET) and polymethyl methacrylate (PMMA), fluororesin, polycarbonate, and glass.
　第１基板２３の一方の面は、第１面２１を構成する。後述されるように、第１面２１と反対側の面３２には対極２４及び温度検知極４２が設けられている。第１基板２３において、装置本体１２の接続部１３に差し込まれる長手方向１０１の一端側は、長手方向１０１と直交する方向１０２に沿った幅が狭い幅狭部２９とされている。 One surface of the first substrate 23 constitutes the first surface 21. As will be described later, a counter electrode 24 and a temperature detection electrode 42 are provided on the surface 32 opposite to the first surface 21. In the first substrate 23, one end side in the longitudinal direction 101 inserted into the connection portion 13 of the apparatus main body 12 is a narrow portion 29 having a narrow width along the direction 102 orthogonal to the longitudinal direction 101.
　第１基板２３の第１面２１には、方向１０２の両端に一対の着色部３０，３１が形成されている。着色部３０，３１は、第１面２１と色分けされたものである。着色部３０，３１は、後述される試料導入口４１の位置の視認を容易にするためのものである。したがって、着色部３０，３１は、試料導入口４１の直上に配置されている。 On the first surface 21 of the first substrate 23, a pair of colored portions 30 and 31 are formed at both ends in the direction 102. The colored portions 30 and 31 are color-coded with the first surface 21. The coloring portions 30 and 31 are for facilitating visual recognition of the position of a sample introduction port 41 to be described later. Therefore, the coloring portions 30 and 31 are arranged immediately above the sample introduction port 41.
［対極２４］
　図２に示されるように、対極２４は、第１基板２３における第１面２１と反対側の面３２に設けられている。対極２４は、第１基板２３の面３２において方向１０２の片側半分程度を占めている。対極２４としては、例えば、銀／塩化銀、金、パラジウム、白金などが挙げられる。対極２４は、第１基板２３に対して、スクリーン印刷法、インクジェット法、スパッタリング、真空蒸着、ゾルゲル法、クラスタビーム蒸着又はＰＬＤなどの手法によって面３２に積層されている。対極２４において、第１基板２３の幅狭部２９に対応する部分は、装置本体１２の接続部１３に挿入される接続端子３３である。対極２４が、本発明における第２電極に相当する。 [Counter electrode 24]
As shown in FIG. 2, the counter electrode 24 is provided on the surface 32 of the first substrate 23 opposite to the first surface 21. The counter electrode 24 occupies about one half of the direction 102 on the surface 32 of the first substrate 23. Examples of the counter electrode 24 include silver / silver chloride, gold, palladium, and platinum. The counter electrode 24 is laminated on the surface 32 with respect to the first substrate 23 by a method such as a screen printing method, an ink jet method, sputtering, vacuum deposition, sol-gel method, cluster beam deposition, or PLD. In the counter electrode 24, a portion corresponding to the narrow portion 29 of the first substrate 23 is a connection terminal 33 inserted into the connection portion 13 of the apparatus main body 12. The counter electrode 24 corresponds to the second electrode in the present invention.
［温度検知極４２］
　図２に示されるように、温度検知極４２は、第１基板２３における第１面２１と反対側の面３２に設けられている。温度検知極４２は、第１基板２３の面３２において対極２４と重複しないように配置されている。温度検知極４２は、その材料に固有の基準温度における抵抗値と温度係数とを有する。基準温度における抵抗値とは、例えば２０℃における抵抗値として既知である。また、温度係数は、温度が１℃上がる毎に変化する抵抗値として既知である。温度検知極４２として、例えば、亜鉛やアルミニウム、アンチモン、金、銀、銅、ニッケルなどが挙げられる。温度検知極４２は、第１基板２３に対して、スクリーン印刷法、インクジェット法、スパッタリング、真空蒸着、ゾルゲル法、クラスタビーム蒸着又はＰＬＤなどの手法によって面３２に積層されている。温度検知極４２が、本発明における第３電極に相当する。 [Temperature detection electrode 42]
As shown in FIG. 2, the temperature detection electrode 42 is provided on the surface 32 of the first substrate 23 opposite to the first surface 21. The temperature detection electrode 42 is disposed so as not to overlap the counter electrode 24 on the surface 32 of the first substrate 23. The temperature detection electrode 42 has a resistance value and a temperature coefficient at a reference temperature unique to the material. The resistance value at the reference temperature is known as a resistance value at 20 ° C., for example. The temperature coefficient is known as a resistance value that changes every time the temperature increases by 1 ° C. Examples of the temperature detection electrode 42 include zinc, aluminum, antimony, gold, silver, copper, and nickel. The temperature detection electrode 42 is laminated on the surface 32 with respect to the first substrate 23 by a method such as a screen printing method, an inkjet method, sputtering, vacuum deposition, sol-gel method, cluster beam deposition, or PLD. The temperature detection electrode 42 corresponds to the third electrode in the present invention.
　温度検知極４２は、幅狭部２９から長手方向１０１に沿って電気的に独立して延出された２本が、空間４０に対応する位置において一部４５が電気的に接続されたＵ字形状をなしている。空間４０には、温度検知極４２において、その一部４５を含む部分が配置されている。温度検知極４２の幅狭部２９に対応する部分は、電気的に独立した２本の端部であり、これら端部が、装置本体１２の接続部１３に挿入される接続端子４６，４７である。 The temperature detection electrode 42 is a U-shape in which two portions that are electrically independently extended from the narrow portion 29 along the longitudinal direction 101 are electrically connected at a portion 45 at a position corresponding to the space 40. It has a shape. In the space 40, a portion including a part 45 of the temperature detection electrode 42 is disposed. The portions corresponding to the narrow portion 29 of the temperature detection electrode 42 are two electrically independent end portions, and these end portions are connection terminals 46 and 47 inserted into the connection portion 13 of the apparatus main body 12. is there.
［第２基板２８］
　図２に示されるように、第２基板２８は、平面視がバイオセンサ１１と概ね同じ形状のシートである。第２基板２８は、電気絶縁性の材料からなる。この電気絶縁性の材料として、例えばポリエチレンテレフタレート（ＰＥＴ）、ポリメタクリル酸メチル（ＰＭＭＡ）等のポリエステルや、フッ素樹脂及びポリカーボネイト、ガラスなどが挙げられる。 [Second substrate 28]
As shown in FIG. 2, the second substrate 28 is a sheet having substantially the same shape as the biosensor 11 in plan view. The second substrate 28 is made of an electrically insulating material. Examples of the electrically insulating material include polyesters such as polyethylene terephthalate (PET) and polymethyl methacrylate (PMMA), fluororesin, polycarbonate, and glass.
　第２基板２８の一方の面は、第２面２２を構成する。後述されるように、第２面２２と反対側の面３４には作用極２６及び試料検知極２７が設けられている。第２基板２８において、装置本体１２の接続部１３に差し込まれる長手方向１０１の一端側は、方向１０２に沿った幅が狭い幅狭部３５とされている。 One surface of the second substrate 28 constitutes the second surface 22. As will be described later, a working electrode 26 and a sample detection electrode 27 are provided on a surface 34 opposite to the second surface 22. In the second substrate 28, one end side in the longitudinal direction 101 inserted into the connection portion 13 of the apparatus main body 12 is a narrow portion 35 having a narrow width along the direction 102.
　各図には現れていないが、第２基板２８の第２面２２には、着色部３０，３１と同様の着色部が形成されている。 Although not shown in the drawings, the second surface 22 of the second substrate 28 is formed with colored portions similar to the colored portions 30 and 31.
［作用極２６］
　図２に示されるように、作用極２６は、第２基板２８における第２面２２と反対側の面３４に設けられている。作用極２６は、第２基板２８の面３４の周縁以外の大半を占めているが、後述される空間４０に対応する位置において、方向１０２の幅が狭くなるように凹欠部３６が形成されている。作用極２６の素材としては、例えば、カーボンが挙げられる。作用極２６にカーボンが用いられることによって、銀／塩化銀、金、パラジウム、白金などが採用される第１電極２３の抵抗値が、カーボン製の作用極２６の抵抗値より低くなるので、空間４０の血液に電子が供給されやすくなる。作用極２６が、本発明における第１電極に相当する。 [Working electrode 26]
As shown in FIG. 2, the working electrode 26 is provided on a surface 34 of the second substrate 28 opposite to the second surface 22. The working electrode 26 occupies most of the second substrate 28 other than the periphery of the surface 34, but a recessed portion 36 is formed so that the width in the direction 102 becomes narrow at a position corresponding to a space 40 described later. ing. Examples of the material of the working electrode 26 include carbon. Since carbon is used for the working electrode 26, the resistance value of the first electrode 23 employing silver / silver chloride, gold, palladium, platinum or the like is lower than the resistance value of the working electrode 26 made of carbon. Electrons are easily supplied to 40 blood. The working electrode 26 corresponds to the first electrode in the present invention.
　作用極２６において、第２基板２８の幅狭部３５に対応する部分は、装置本体１２の接続部１３に挿入される接続端子３７である。接続端子３７には、スペーサ２５や対極２４、温度検知極４２、第１基板２３のいずれもが対向されておらず、バイオセンサ１１の外部に対して露出されている。作用極２６は、第２基板２８の面３４側に形成されているので、接続端子３７はバイオセンサ１１の第１面２１側にのみ露出されている。 In the working electrode 26, a portion corresponding to the narrow portion 35 of the second substrate 28 is a connection terminal 37 inserted into the connection portion 13 of the apparatus main body 12. None of the spacer 25, the counter electrode 24, the temperature detection electrode 42, or the first substrate 23 is opposed to the connection terminal 37 and is exposed to the outside of the biosensor 11. Since the working electrode 26 is formed on the surface 34 side of the second substrate 28, the connection terminal 37 is exposed only on the first surface 21 side of the biosensor 11.
　各図には現れていないが、作用極２６において、空間４０に対応する領域３８には、ＧＯＤ及びメディエータが固定されている。メディエータとしては、例えば、ルテニウムやオスミニウム、モリブデン、タングステン、鉄、コバルト等の遷移金属を含む化合物が挙げられる。ＧＯＤ及びメディエータは、ＧＯＤ及びメディエータが含まれる液が作用極２６に塗布されて乾燥させることにより固定されている。 Although not shown in each figure, in the working electrode 26, a GOD and a mediator are fixed to a region 38 corresponding to the space 40. As a mediator, the compound containing transition metals, such as ruthenium, osmium, molybdenum, tungsten, iron, cobalt, is mentioned, for example. The GOD and the mediator are fixed by applying a liquid containing the GOD and the mediator to the working electrode 26 and drying it.
［試料検知極２７］
　図２に示されるように、試料検知極２７は、第２基板２８における第２面２２と反対側の面３４に設けられている。試料検知極２７は、第２基板２８の面３４において、長手方向１０１に細長く延出されて、その一端が作用極２６の凹欠部３６に入り込むように屈曲されている。試料検知極２７の素材としては、例えば、銀／塩化銀、金、パラジウム、白金などが挙げられる。試料検知極２７は、空間４０へ血液が導入されたか否かを検出するための電極である。 [Sample detection electrode 27]
As shown in FIG. 2, the sample detection electrode 27 is provided on the surface 34 of the second substrate 28 opposite to the second surface 22. The sample detection electrode 27 is elongated in the longitudinal direction 101 on the surface 34 of the second substrate 28 and is bent so that one end thereof enters the recess 36 of the working electrode 26. Examples of the material of the sample detection electrode 27 include silver / silver chloride, gold, palladium, and platinum. The sample detection electrode 27 is an electrode for detecting whether blood is introduced into the space 40.
　試料検知極２７において、第２基板２８の幅狭部３５に対応する部分は、装置本体１２の接続部１３に挿入される接続端子３９である。接続端子３９には、スペーサ２５や対極２４、温度検知極４２、第１基板２３のいずれもが対向されておらず、バイオセンサ１１の外部に対して露出されている。試料検知極２７は、第２基板２８の面３４側に形成されているので、接続端子３９はバイオセンサ１１の第１面２１側にのみ露出されている。 In the sample detection electrode 27, the part corresponding to the narrow part 35 of the second substrate 28 is a connection terminal 39 inserted into the connection part 13 of the apparatus main body 12. None of the spacer 25, the counter electrode 24, the temperature detection electrode 42, or the first substrate 23 is opposed to the connection terminal 39, and is exposed to the outside of the biosensor 11. Since the sample detection electrode 27 is formed on the surface 34 side of the second substrate 28, the connection terminal 39 is exposed only on the first surface 21 side of the biosensor 11.
［スペーサ２５］
　図２に示されるように、スペーサ２５は、平面視がバイオセンサ１１と概ね同じ形状のシートである。スペーサ２５としては、電気絶縁性を有する両面テープが好適に用いられる。スペーサ２５が第１基板２３と第２基板２８との間に介在されることによって、対極２４及び温度検知極４２と作用極２６及び試料検知極２７とが電気的に絶縁される。スペーサ２５は、着色部３０，３１に対応する位置に、方向１０２へ延びる空間４０を有する。つまり、スペーサ２５は、長手方向１０１に対して空間４０によって分断された２枚のシートから構成されている。空間４０によって、対極２４及び温度検知極４２と作用極２６及び試料検知極２７との間に、スペーサ２５の厚み分の試料空間が形成される。つまり、空間４０が試料空間となる。空間４０には、対極２４の一部、温度検知極４２の一部４５、作用極２６の一部及び試料検知極２７の一部がそれぞれ露出されている。 [Spacer 25]
As shown in FIG. 2, the spacer 25 is a sheet having substantially the same shape as the biosensor 11 in plan view. As the spacer 25, a double-sided tape having electrical insulation is preferably used. By interposing the spacer 25 between the first substrate 23 and the second substrate 28, the counter electrode 24, the temperature detection electrode 42, the working electrode 26, and the sample detection electrode 27 are electrically insulated. The spacer 25 has a space 40 extending in the direction 102 at a position corresponding to the coloring portions 30 and 31. That is, the spacer 25 is composed of two sheets separated by the space 40 with respect to the longitudinal direction 101. The space 40 forms a sample space corresponding to the thickness of the spacer 25 between the counter electrode 24 and the temperature detection electrode 42 and the working electrode 26 and the sample detection electrode 27. That is, the space 40 becomes the sample space. In the space 40, a part of the counter electrode 24, a part 45 of the temperature detection electrode 42, a part of the working electrode 26, and a part of the sample detection electrode 27 are exposed.
　対極２４及び温度検知極４２と、作用極２６及び試料検知極２７とは、空間４０においてバイオセンサ１１の厚み方向に隔てられて対向される。図１に示されるように、空間４０は、バイオセンサ１１の端に開口されており、この開口が試料導入口４１となる。なお、図１には現れていないが、試料導入口４１と対向する位置においても空間４０が開口されている。試料導入口４１が血液に曝されると、毛細管作用によって血液が空間４０に流れ込む。 The counter electrode 24 and the temperature detection electrode 42, the working electrode 26 and the sample detection electrode 27 are opposed to each other in the space 40 while being separated in the thickness direction of the biosensor 11. As shown in FIG. 1, the space 40 is opened at the end of the biosensor 11, and this opening serves as the sample introduction port 41. Although not shown in FIG. 1, the space 40 is also opened at a position facing the sample introduction port 41. When the sample inlet 41 is exposed to blood, blood flows into the space 40 by capillary action.
［装置本体１２の内部構成］
　図３に示されるように、装置本体１２の接続部１３には、５つの接続端子６１～６５が設けられている。各接続端子６１～６５は、対極２４の接続端子３３、温度検知極４２の接続端子４６，４７、作用極２６の接続端子３７、試料検知極２７の接続端子３９に対応している。このうち、温度検知極４２の接続端子４６，４７には、２つの接続端子６２，６３がそれぞれ電気的に接続される。この接続端子６２，６３が、本発明における一対の接続端子に相当する。接続部１３にバイオセンサ１１が装着されることによって、それぞれが電気的に接続される。なお、図３においては、バイオセンサ１１の対極２４、温度検知極４２、作用極２６及び試料検知極２７が模式的に同一面に表されている。 [Internal configuration of apparatus main body 12]
As shown in FIG. 3, the connection portion 13 of the apparatus main body 12 is provided with five connection terminals 61 to 65. The connection terminals 61 to 65 correspond to the connection terminal 33 of the counter electrode 24, the connection terminals 46 and 47 of the temperature detection electrode 42, the connection terminal 37 of the working electrode 26, and the connection terminal 39 of the sample detection electrode 27. Among these, the two connection terminals 62 and 63 are electrically connected to the connection terminals 46 and 47 of the temperature detection electrode 42, respectively. The connection terminals 62 and 63 correspond to a pair of connection terminals in the present invention. By attaching the biosensor 11 to the connecting portion 13, each is electrically connected. In FIG. 3, the counter electrode 24, the temperature detection electrode 42, the working electrode 26, and the sample detection electrode 27 of the biosensor 11 are schematically shown on the same plane.
　装置本体１２には、制御部７０が設けられている。制御部７０は、各種演算を行うためのＣＰＵ、各種プログラムが格納されるＲＯＭ、各種演算のためのデータを一時保存するＲＡＭ、データを電送するバスなどによって構成される演算装置である。この制御部７０に対して、血糖定量部７１、試料検知部７２、温度演算部７３、補正部７４、液晶ディスプレイ５１及び操作キー５１，５２，５３が、電気信号を送受信可能に接続されている。制御部７０によって、血糖定量部７１、試料検知部７２、温度演算部７３、補正部７４、液晶ディスプレイ５１の各動作が制御される。制御部７０が、本発明における制御手段に相当する。 The apparatus main body 12 is provided with a control unit 70. The control unit 70 is an arithmetic unit configured by a CPU for performing various calculations, a ROM for storing various programs, a RAM for temporarily storing data for various calculations, a bus for transmitting data, and the like. A blood glucose determination unit 71, a sample detection unit 72, a temperature calculation unit 73, a correction unit 74, a liquid crystal display 51, and operation keys 51, 52, and 53 are connected to the control unit 70 so as to be able to transmit and receive electrical signals. . The control unit 70 controls each operation of the blood glucose determination unit 71, the sample detection unit 72, the temperature calculation unit 73, the correction unit 74, and the liquid crystal display 51. The control unit 70 corresponds to the control means in the present invention.
　血糖定量部７１は、バイオセンサ１１の対極２４と作用極２６との間に流れた電流値に基づいて血糖値を演算するものであり、対極２４と作用極２６との間に流れた電流を電圧に変換したり、電圧により表される電気信号を整形したり、数値表現されたデジタル信号に変換したりする回路を有する。また、対極２４と作用極２６との間に流れた電流値に基づいて血糖値を演算するプログラムを有する。このプログラムは、制御部７０に格納されていてもよい。演算された血糖値を示す電気信号は、制御部７０のＲＡＭに格納される。血糖定量部７１が、本発明における定量手段に相当する。 The blood glucose determination unit 71 calculates a blood glucose level based on the current value flowing between the counter electrode 24 and the working electrode 26 of the biosensor 11, and the current flowing between the counter electrode 24 and the working electrode 26 is calculated. It has a circuit that converts it into a voltage, shapes an electrical signal represented by the voltage, and converts it into a digital signal expressed numerically. Moreover, it has a program which calculates a blood glucose level based on the electric current value which flowed between the counter electrode 24 and the working electrode 26. This program may be stored in the control unit 70. An electrical signal indicating the calculated blood glucose level is stored in the RAM of the control unit 70. The blood sugar quantification unit 71 corresponds to the quantification means in the present invention.
　試料検知部７２は、対極２４と試料検知極２７との間に流れた電流値に基づいて、空間４０へ試料が導入されたか否かを判定するものであり、対極２４と試料検知極２７との間に流れた電流を電圧に変換したり、電圧により表される電気信号を整形したり、数値表現されたデジタル信号に変換したりする回路を有する。また、対極２４と試料検知極２７との間に流れた電流値に基づいて試料の有無を判定する閾値を有する。この閾値は、制御部７０に格納されていてもよい。制御部７０は、試料検知部７２が試料有りと判定したことを条件として、血糖定量部７１に血糖値の演算を要求し、温度演算部７３に温度の演算を要求する。 The sample detector 72 determines whether a sample has been introduced into the space 40 based on the current value flowing between the counter electrode 24 and the sample detection electrode 27. A circuit that converts a current flowing between the two into a voltage, shapes an electric signal represented by the voltage, and converts it into a digital signal expressed numerically. In addition, there is a threshold value for determining the presence or absence of the sample based on the current value flowing between the counter electrode 24 and the sample detection electrode 27. This threshold value may be stored in the control unit 70. The control unit 70 requests the blood glucose determination unit 71 to calculate the blood glucose level and the temperature calculation unit 73 to calculate the temperature on the condition that the sample detection unit 72 determines that there is a sample.
　温度演算部７３は、温度検知極４２の接続端子４６，４７と接続された接続端子６２，６３との間に生じた抵抗値に基づいて温度を演算するものである。温度演算部７３には、温度検知極４２の材料に固有の基準温度における抵抗値及び温度係数が格納されており、接続端子６２，６３の間に生じた抵抗値と基準温度における抵抗値との差を温度係数で除することによって温度検知極４２の温度が演算される。演算された温度を示す電気信号は、制御部７０のＲＡＭに格納される。温度検知極４２の材料に固有の基準温度における抵抗値及び温度係数は、制御部７０に格納されていてもよい。温度演算部７３が、本発明における温度演算手段に相当する。 The temperature calculation unit 73 calculates a temperature based on a resistance value generated between the connection terminals 46 and 47 of the temperature detection electrode 42 and the connection terminals 62 and 63 connected thereto. The temperature calculation unit 73 stores a resistance value and a temperature coefficient at a reference temperature unique to the material of the temperature detection electrode 42, and a resistance value generated between the connection terminals 62 and 63 and a resistance value at the reference temperature are stored. The temperature of the temperature detection electrode 42 is calculated by dividing the difference by the temperature coefficient. An electric signal indicating the calculated temperature is stored in the RAM of the control unit 70. The resistance value and the temperature coefficient at the reference temperature specific to the material of the temperature detection electrode 42 may be stored in the control unit 70. The temperature calculation unit 73 corresponds to the temperature calculation means in the present invention.
　補正部７４は、制御部７０のＲＡＭに格納されている血糖値及び温度を示す各電気信号に基づいて、血糖値の温度補正を行う。補正部７４は、温度と補正係数との関係を示すテーブルを有する。補正部７４は、制御部７０のＲＡＭに格納されている温度に対応する補正係数を選択し、ＲＡＭに格納されている血糖値に補正係数を乗じて補正後の血糖値を演算する。補正後の血糖値を示す電気信号は、制御部７０のＲＡＭに格納される。補正部７４が、本発明における補正手段に相当する。 The correction unit 74 performs temperature correction of the blood glucose level based on each electrical signal indicating the blood glucose level and temperature stored in the RAM of the control unit 70. The correction unit 74 has a table indicating the relationship between the temperature and the correction coefficient. The correction unit 74 selects a correction coefficient corresponding to the temperature stored in the RAM of the control unit 70, and calculates the corrected blood sugar level by multiplying the blood sugar level stored in the RAM by the correction coefficient. An electrical signal indicating the corrected blood glucose level is stored in the RAM of the control unit 70. The correction unit 74 corresponds to the correction unit in the present invention.
［血糖測定装置１０の動作］
　以下に、血糖測定装置１０の動作が説明される。 [Operation of Blood Glucose Measuring Device 10]
Below, operation | movement of the blood glucose measuring device 10 is demonstrated.
　被測定者は、バイオセンサ１１を装置本体１２の接続部１３に装着する。これにより、各接続端子６１～６５と、対極２４の接続端子３３、温度検知極４２の接続端子４６，４７、作用極２６の接続端子３７、試料検知極２７の接続端子３９とがそれぞれ電気的に接続される。 The person to be measured attaches the biosensor 11 to the connection portion 13 of the apparatus main body 12. Thus, the connection terminals 61 to 65, the connection terminal 33 of the counter electrode 24, the connection terminals 46 and 47 of the temperature detection electrode 42, the connection terminal 37 of the working electrode 26, and the connection terminal 39 of the sample detection electrode 27 are electrically connected. Connected to.
　バイオセンサ１１が装置本体１２に接続されると、装置本体１２の接続端子６２，６３間において温度検知極４２を介して電流が流れ得る。制御部７０は、装置本体１２の電源がオンされると、定期的に接続端子６２，６３間に微弱な電位を印可し、接続端子６２，６３間に流れた電流を検知することによってバイオセンサ１１が装着されたと判定する。このような制御部７０と接続端子６２，６３とによって、本発明における装着検知手段が実現されている。 When the biosensor 11 is connected to the apparatus main body 12, a current can flow between the connection terminals 62 and 63 of the apparatus main body 12 via the temperature detection electrode 42. When the power of the apparatus main body 12 is turned on, the control unit 70 periodically applies a weak potential between the connection terminals 62 and 63, and detects a current flowing between the connection terminals 62 and 63, thereby detecting the biosensor. 11 is attached. By such a control unit 70 and the connection terminals 62 and 63, the mounting detection means in the present invention is realized.
　制御部７０は、バイオセンサ１１が装着されたと判定したことを条件として、温度演算部７２から温度検知極４２に所定の電位及び電流を付与させて、温度検知極４２の抵抗値を測定させる。温度検知極４２の抵抗値は、接続端子４６から一部４５を経て接続端子４７へ流れる電流、又は接続端子４７から一部４５を経て接続端子４６へ流れる電流に対する抵抗値として測定される。温度演算部７２は、温度検知極４２の抵抗値と、基準温度における抵抗値及び温度係数とに基づいて、温度検知極４２の温度を演算する。演算された温度を示す電気信号は、制御部７０のＲＡＭに格納される。 The control unit 70 causes the temperature calculation unit 72 to apply a predetermined potential and current to the temperature detection electrode 42 and measure the resistance value of the temperature detection electrode 42 on the condition that the biosensor 11 has been mounted. The resistance value of the temperature detection electrode 42 is measured as a resistance value with respect to a current flowing from the connection terminal 46 through the part 45 to the connection terminal 47 or a current flowing from the connection terminal 47 through the part 45 to the connection terminal 46. The temperature calculation unit 72 calculates the temperature of the temperature detection electrode 42 based on the resistance value of the temperature detection electrode 42 and the resistance value and temperature coefficient at the reference temperature. An electric signal indicating the calculated temperature is stored in the RAM of the control unit 70.
　被測定者は、自らの血液を採取する。血液の採取は、例えばランセットを用いて、被測定者自らが行うことができる。この血液が、本発明における試料に相当する。採取された血液は試料としてバイオセンサ１１の試料導入口４１から空間４０へ導入される。試料導入口４１に血液が付着されると、毛細管現象によって空間４０へ血液が導かれる。空間４０に血液が満たされると、対極２４と試料検知極２７との間に電流が生じ、この電流に基づいて試料検知部７２が試料有りと判定する。 Measured person collects his own blood. The blood can be collected by the person himself / herself using, for example, a lancet. This blood corresponds to the sample in the present invention. The collected blood is introduced into the space 40 from the sample inlet 41 of the biosensor 11 as a sample. When blood adheres to the sample inlet 41, the blood is guided to the space 40 by capillary action. When the space 40 is filled with blood, a current is generated between the counter electrode 24 and the sample detection electrode 27, and the sample detection unit 72 determines that there is a sample based on this current.
　空間４０に導入された血液は、対極２４と作用極２６との間に保持されて電気化学的反応を起こす。この電気化学的反応により対極２４と作用極２６との間に血糖値に相関する電流が発生する。制御部７０は、試料検知部７２が試料有りと判定したことを条件として、血糖定量部７１に、対極２４と作用極２６との間に流れた電流に基づいて血糖値を演算させる。なお、空間４０に血液が導入されると、温度検知極４２の一部４５に血液が接触する。温度演算部７２は、バイオセンサ１１が装置本体１２に装着されると直ちに温度検知極４２の抵抗値を測定しており、この測定は試料検知部７２が試料有りと判断するまでに終了しているが、制御部７０は、試料検知部７２が試料有りと判定したことを条件として、接続端子６２，６３に電位及び電流を付与しない。 The blood introduced into the space 40 is held between the counter electrode 24 and the working electrode 26 and causes an electrochemical reaction. This electrochemical reaction generates a current that correlates with the blood glucose level between the counter electrode 24 and the working electrode 26. The control unit 70 causes the blood glucose determination unit 71 to calculate the blood glucose level based on the current flowing between the counter electrode 24 and the working electrode 26 on the condition that the sample detection unit 72 determines that there is a sample. Note that when blood is introduced into the space 40, the blood contacts the part 45 of the temperature detection electrode 42. The temperature calculation unit 72 measures the resistance value of the temperature detection electrode 42 as soon as the biosensor 11 is attached to the apparatus main body 12, and this measurement ends until the sample detection unit 72 determines that there is a sample. However, the control unit 70 does not apply the potential and current to the connection terminals 62 and 63 on condition that the sample detection unit 72 determines that there is a sample.
　制御部７０は、得られた血糖値に対して、既に測定された温度に基づいて、補正部７４に血糖値の温度補正を行わせる。そして、制御部７０は、得られた補正後の血糖値を液晶ディスプレイ５１に表示する。 The control unit 70 causes the correction unit 74 to perform temperature correction of the blood glucose level on the obtained blood glucose level based on the already measured temperature. Then, the controller 70 displays the obtained corrected blood glucose level on the liquid crystal display 51.
［本実施形態の作用効果］
　本実施形態によれば、バイオセンサ１１に温度検知極４２が設けられ、温度演算部７２が温度検知極４２の抵抗値に基づいて温度検知極４２の温度を演算するので、バイオセンサ１１の温度を正確且つ迅速に測定して、当該温度に基づく血糖値の補正を行うことができる。 [Operational effects of this embodiment]
According to this embodiment, the temperature detection electrode 42 is provided in the biosensor 11, and the temperature calculation unit 72 calculates the temperature of the temperature detection electrode 42 based on the resistance value of the temperature detection electrode 42. Can be measured accurately and quickly to correct the blood glucose level based on the temperature.
　また、バイオセンサ１１として、対極２４と作用極２６とが空間４０を介して対向配置されており、全体として細長なシート形状のものが用いられていても、温度検知極４２において熱伝導による損失の影響を受けることなく、バイオセンサ１１の温度が測定される。 Further, as the biosensor 11, the counter electrode 24 and the working electrode 26 are opposed to each other with the space 40 interposed therebetween, and even if an elongated sheet shape is used as a whole, the loss due to heat conduction in the temperature detection electrode 42. The temperature of the biosensor 11 is measured without being affected by the above.
　また、装置本体１２の接続部１３に接続される側と反対側に、空間４０及び試料導入口４１が配置されているので、装置本体１２から突出したバイオセンサ１１の先端側において血液を導入することができ、空間４０への血液の導入や容易となり、また、血液が装置本体１２に付着する可能性が低減される。 Further, since the space 40 and the sample introduction port 41 are arranged on the side opposite to the side connected to the connection portion 13 of the apparatus main body 12, blood is introduced at the distal end side of the biosensor 11 protruding from the apparatus main body 12. This facilitates introduction of blood into the space 40 and facilitates the attachment of blood to the apparatus main body 12.
［変形例］
　なお、本実施形態では、試薬に含まれる酵素がＧＯＤであるが、本発明における酵素がＧＯＤに限定されないことは言うまでもない。例えば、血糖測定に用いられるバイオセンサであれば、ＧＯＤに代えてＧＤＨが酵素として試薬に含まれてもよい。 [Modification]
In the present embodiment, the enzyme contained in the reagent is GOD, but it goes without saying that the enzyme in the present invention is not limited to GOD. For example, in the case of a biosensor used for blood glucose measurement, GDH may be included in the reagent as an enzyme instead of GOD.
　また、本実施形態で示されたバイオセンサ１１の構成は、本発明に係るバイオセンサのの構成の一態様に過ぎない。したがって、バイオセンサ１１のようにスペーサ２５を介して対極２４と作用極２６とが対向された立体型のものに代えて、同一の基板上に作用極と対極とが配置された平面型としてバイオセンサが実現されてもよい。 Further, the configuration of the biosensor 11 shown in the present embodiment is only one aspect of the configuration of the biosensor according to the present invention. Therefore, instead of the three-dimensional type in which the counter electrode 24 and the working electrode 26 are opposed to each other via the spacer 25 like the biosensor 11, the bio-type is a planar type in which the working electrode and the counter electrode are arranged on the same substrate. A sensor may be realized.
　また、本発明に係るバイオセンサは、血糖測定装置１０のように携帯型の血糖測定装置に限定されるものではない。したがって、血液中の他の成分の測定にバイオセンサが用いられる場合に、その測定に必要な酵素が含まれる試薬が電極に固定される態様においても利用可能である。また、試料も血液に限定されず、尿や唾液などの生体試料であってもよいし、被検出物質が含まれる水溶液であってもよい。 Further, the biosensor according to the present invention is not limited to the portable blood glucose measurement device like the blood glucose measurement device 10. Therefore, when a biosensor is used for measuring other components in blood, it can also be used in an embodiment in which a reagent containing an enzyme necessary for the measurement is fixed to the electrode. Further, the sample is not limited to blood, and may be a biological sample such as urine or saliva, or an aqueous solution containing a substance to be detected.
　また、本実施形態では、バイオセンサ１１において作用極２４、対極２６、試料検知極２７とは独立して温度検知極４２設けられているが、温度検知極４２が、対極２６又は試料検知極２７によって兼ねられていてもよい。その場合には、装置本体１２の接続部１３において、温度検知極４２を兼ねる対極２６の接続端子３７又は試料検知極２７の接続端子３９に、２つの接続端子が接続される。対極２６又は試料検知極２７には、酵素やメディエータが固定されていないので、バイオセンサ１１に血液が導入される前に、接続部１３の２つの接続端子を通じて電位や電流が付与されても、酵素やメディエータに電気的な影響が及ばない。これにより、バイオセンサ１１及び装置本体１２の小型化やコストダウンが実現される。 In this embodiment, the temperature detection electrode 42 is provided independently of the working electrode 24, the counter electrode 26, and the sample detection electrode 27 in the biosensor 11, but the temperature detection electrode 42 is provided as the counter electrode 26 or the sample detection electrode 27. May also be served. In that case, two connection terminals are connected to the connection terminal 37 of the counter electrode 26 that also serves as the temperature detection electrode 42 or the connection terminal 39 of the sample detection electrode 27 in the connection part 13 of the apparatus body 12. Since no enzyme or mediator is fixed to the counter electrode 26 or the sample detection electrode 27, even if a potential or current is applied through the two connection terminals of the connection unit 13 before blood is introduced into the biosensor 11, There is no electrical effect on the enzyme or mediator. Thereby, size reduction and cost reduction of the biosensor 11 and the apparatus main body 12 are implement | achieved.
　また、本実施形態では、接続端子６２，６３間の電流の変化に基づいて、制御部７０が、装置本体１２にバイオセンサ１１が装着されたことを検知する態様が示されているが、本発明における装着検知手段は、例えば、接続部１３にバイオセンサ１１により押下され得るメカニカルスイッチを設けることによって、バイオセンサ１１を機械的に検知する構成が採用されてもよいし、接続部１３にバイオセンサ１１により遮光されるフォトインタラプタを設けることによって、バイオセンサ１１を光学的に検知する構成が採用されてもよい。 In the present embodiment, a mode is shown in which the control unit 70 detects that the biosensor 11 is attached to the apparatus main body 12 based on a change in current between the connection terminals 62 and 63. For the mounting detection means in the invention, for example, a configuration may be adopted in which the biosensor 11 is mechanically detected by providing the connection portion 13 with a mechanical switch that can be pressed by the biosensor 11. A configuration in which the biosensor 11 is optically detected by providing a photo interrupter that is shielded by the sensor 11 may be employed.

Claims (2)

  1. 　装置本体に着脱可能なバイオセンサを有する測定装置であって、
    　上記バイオセンサは、
    　試料中の被検出物質と反応する酵素が固定された第１電極と、
    　上記第１電極と電気的に対応する第２電極と、
    　温度を検出するための第３電極と、を具備し、
    　上記装置本体は、
    　上記酵素が被検出物質と反応することにより上記第１電極と上記第２電極との間に流れた電流に基づいて、上記試料中の当該被検出物質を定量する定量手段と、
    　上記第３電極と電気的に接触する一対の接続端子と、
    　上記接続端子間において得られた上記第３電極の抵抗値に基づいて、上記第３電極の温度を演算する温度演算手段と、
    　上記温度演算手段により演算された温度に基づいて、上記定量手段が定量した被検出物質の定量値を補正する補正手段と、
    　上記温度補正手段により補正された被検出物質の定量値を表示する表示手段と、
    　上記バイオセンサが装着されたことを検知する装着検知手段と、
    　上記装着検知手段が上記バイオセンサの装着を検知したことを条件として、上記温度演算手段に上記第３電極の温度を演算させる制御手段と、を具備する測定装置。     A measuring device having a biosensor detachable from the device body,
    The biosensor is
    A first electrode on which an enzyme that reacts with a substance to be detected in a sample is fixed;
    A second electrode electrically corresponding to the first electrode;
    A third electrode for detecting the temperature,
    The device body is
    A quantification means for quantifying the substance to be detected in the sample based on a current flowing between the first electrode and the second electrode as a result of the enzyme reacting with the substance to be detected;
    A pair of connection terminals in electrical contact with the third electrode;
    Temperature calculating means for calculating the temperature of the third electrode based on the resistance value of the third electrode obtained between the connection terminals;
    Based on the temperature calculated by the temperature calculation means, correction means for correcting the quantitative value of the substance to be detected quantified by the quantitative means;
    Display means for displaying a quantitative value of the detected substance corrected by the temperature correction means;
    Wearing detection means for detecting that the biosensor is attached;
    And a control unit that causes the temperature calculation unit to calculate the temperature of the third electrode on condition that the mounting detection unit detects the mounting of the biosensor.
  2. 　上記第２電極は、上記第３電極を兼ねるものである請求項１に記載の測定装置。 2. The measuring apparatus according to claim 1, wherein the second electrode also serves as the third electrode.
PCT/JP2010/073829 2009-12-29 2010-12-29 Measuring device having a biosensor WO2011081211A1 (en)

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