JP2009276275A - Measurement device and measurement method using the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a measurement device capable of precisely measuring conductivity of a sample liquid and concentration of at least a component contained in the sample liquid in a simple construction, and a measurement method using the same. <P>SOLUTION: The measurement device includes a substrate having a space communicating a first opening functioning as a sample liquid introduction hole and a second opening functioning as an air vent; an electrode system located on a first surface of the insides of the substrate surrounding the space, containing at least tow electrodes, for measuring conductivity of the sample liquid introduced in the space and concentration of at least component contained in the sample fluid; and a reagent on the first surface, located on a position closer to the second opening than that of the electrode system, for measuring a component. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a measuring device capable of measuring the conductivity of a sample solution and the concentration of at least one component contained in the sample solution, and a measuring method using the measuring device.

  Conventionally, the conductivity of a sample solution and the concentration of components contained in the sample solution are measured using an electrode system including two or more electrodes (see, for example, Patent Documents 1 and 2). .

  For example, in Patent Document 1, the electrical conductivity meter provided with a cell provided with a pair of electrodes is used to measure the electrical conductivity of a sample solution introduced into the cell, and the measured electrical conductivity is converted to a salinity concentration. A measurement method for conversion is disclosed.

  In Patent Document 2, a sensor including a substrate, an electrode system including a measurement electrode and a counter electrode disposed on the substrate, and a reagent layer including an enzyme and an electron carrier disposed on the electrode system is used in blood. Measuring the concentration of contained glucose is disclosed.

  Conventionally, it has been proposed to measure a plurality of items for a single sample solution using at least one electrode system (see, for example, Patent Documents 2, 3, and 4).

  In the above-mentioned Patent Document 2, using a single electrode system, blood as a sample liquid is introduced into the sensor, that is, detecting the presence of the sample liquid, and using the same electrode system, It is disclosed that the concentration of glucose contained in is measured. Specifically, a step of introducing blood into the electrode system by capillary action, a step of detecting that blood has been introduced into the electrode system by detecting a change in resistance value between the measurement electrode and the counter electrode, Disclosed is a measurement method including a step of waiting for a reaction between an enzyme and blood to progress, a step of measuring an oxidation current flowing between a measurement electrode and a counter electrode, and a step of converting the measured current value into a glucose concentration. ing.

  Patent Document 3 discloses a sensor including a main electrode system and a sub electrode system each having a measurement electrode and a counter electrode. In the sensor described in Patent Literature 3, by combining an insulating substrate, a spacer, and a cover, a space portion, a sample supply hole communicating with one end portion of the space portion, and the other end portion of the space portion are provided. A communicating air hole is formed. The sub-electrode system is closer to the sample supply hole than the main electrode system in the space so that the sample solution introduced from the sample supply hole is introduced to the sub-electrode system before the main electrode system. A main electrode system and a sub-electrode system are arranged. Specifically, using a sensor in which a reagent layer containing an enzyme and an electron carrier is provided only on the main electrode, the step of introducing the sample liquid into the space from the sample supply hole, in the sample liquid in the sub-electrode system Discloses a measuring method including a step of measuring the concentration of ascorbic acid contained in the sample and a step of measuring the concentration of glucose contained in the sample solution in the main electrode system. In addition, in order to reduce the influence of hematocrit and to measure the glucose concentration with high accuracy, a space layer is formed from the sample supply hole using a sensor in which a reagent layer containing an enzyme and an electron carrier is provided only on the main electrode. The step of introducing the sample solution into the sub-electrode system, the step of detecting a change in impedance in the sub-electrode system when the sample solution is introduced into the sub-electrode system, the impedance in the main electrode system when the sample solution is introduced into the main electrode system A step of detecting a change in current, a step of measuring an oxidation current flowing between a measurement electrode and a counter electrode in the main electrode system, and a time when the measured current value and impedance change are detected in the sub-electrode system and the main electrode system And a measurement method including a step of obtaining a glucose concentration based on the difference between the two.

In Patent Document 4, in FIG. 11 and paragraphs (0086) to (0087), a first electrode system composed of a pair of electrodes provided on one outer surface among a plurality of outer surfaces surrounding a substrate. And a second electrode system composed of a pair of electrodes provided on another outer surface is disclosed. Specifically, an example is disclosed in which salt concentration is measured by detecting conductivity using a first electrode system, and urine sugar or creatinine is measured using a second electrode system.
JP-A-1-203952 JP-A-4-357542 JP-A-5-340915 International Publication No. 2007/049607 Pamphlet

  However, the above-described conventional measurement method using a plurality of items has the following problems.

  First, in the method described in Patent Document 2, when blood introduced by capillary action reaches the electrode system, the reagent layer disposed on the electrode system dissolves in the blood, thereby transferring electrons contained in the reagent layer. Components such as the body ionize in the blood. For this reason, the resistance value detected by the electrode system is lower than the resistance value of blood as the sample liquid.

  In the method described in Patent Document 3, two electrode systems, that is, a main electrode system and a sub electrode system are necessary, so that the device structure is complicated.

  In the method described in Patent Document 4, the first electrode system and the second electrode system are necessary, so that the device structure is complicated as in the method described in Patent Document 3.

  Therefore, in view of the above-described conventional problems, the present invention has a simple configuration, and a measuring device capable of accurately measuring the conductivity of a sample solution and the concentration of at least one component contained in the sample solution, and the same It aims at providing the measuring method using.

  In order to solve the above-described conventional problems, the measurement device of the present invention includes a base having a first opening that functions as a sample solution introduction hole and a second opening that functions as an air hole, and the space. An inner surface of the substrate surrounding the portion, disposed on the first surface, including at least two electrodes, the conductivity of the sample liquid introduced into the space and the at least one component included in the sample liquid An electrode system for measuring the concentration, and a reagent for measuring the component disposed on the first surface and closer to the second opening than the electrode system are provided.

Moreover, the measurement method of the present invention uses the measurement device,
(A) introducing the sample solution into the space through the first opening of the measurement device;
(B) measuring the conductivity of the sample solution using the electrode system after the sample solution reaches the electrode system;
(C) After the step B, waiting for the reagent dissolved in the sample solution to diffuse to the electrode system;
(D) After the step C, applying a voltage between at least two electrodes among the electrodes included in the electrode system;
(E) a step of measuring a current flowing between the two electrodes to which a voltage is applied in the step D; and (F) based on the current measured in the step E, the component contained in the sample liquid A step of determining the concentration.

  According to the present invention, the conductivity of the sample solution and the concentration of at least one component contained in the sample solution can be accurately measured with a simple configuration.

  The measuring device of the present invention is characterized in that an electrode system and a reagent for measuring a component contained in a sample solution are arranged at positions separated via a space.

  More specifically, in the measurement device of the present invention, a reagent for measuring a component contained in the sample solution is disposed on the surface on which the electrode system is disposed, and the electrode system is more than the reagent. It is arranged at a position close to the sample liquid introduction hole.

  The measuring device of the present invention includes a base having a space communicating with a first opening functioning as a sample solution introduction hole and a second opening functioning as an air hole, and a first of the inner surfaces of the base surrounding the space. And an electrode system for measuring the conductivity of the sample liquid introduced into the space and the concentration of at least one component contained in the sample liquid, and including at least two electrodes A reagent for measuring the component is provided on the first surface and located closer to the second opening than the electrode system.

  According to this configuration, the sample solution introduced into the space from the first opening that functions as the sample solution introduction hole first contacts the electrode system before contacting the reagent. Since the reagent is not dissolved in the sample liquid in contact with the electrode system when the sample liquid reaches the electrode system, the reagent does not affect the conductivity value of the sample liquid. Therefore, when the sample solution reaches the electrode system, first, if the conductivity of the sample solution is measured using the electrode system, the conductivity of the sample solution can be accurately measured. Next, the sample solution reaches the position where the reagent is placed, and after the reagent dissolved in the sample solution diffuses in the sample solution and reaches the electrode system, it is the same as the electrode system used for the measurement of conductivity. Using the electrode system, the concentration of the measurement target component contained in the sample solution is measured. In this way, it is possible to accurately measure the conductivity of the sample solution and the concentration of the measurement target component contained in the sample solution using a single electrode system.

  In the present invention, an insulating material such as glass, ceramic, rubber, ebonite, or plastic can be used as the base material.

  In the present invention, gold, platinum, palladium, copper, or the like can be used as a material for the electrode.

  The number of electrodes included in the electrode system may be at least two, and may be three or more. Here, it is preferable that the number of electrodes included in the electrode system is four.

  In the present invention, the sample liquid can be used without particular limitation as long as it is a liquid. The sample solution is preferably a biological sample such as blood or urine.

  In the present invention, examples of the reagent for measuring the components contained in the sample solution include redox substances, enzymes, and antibodies. Here, it is preferable that the reagent includes a redox substance, the redox substance is reduced by reacting with the component, and the reduced redox substance is oxidized in the electrode system.

  In the present invention, as the redox substance, ferricyanides such as potassium ferricyanide, phenazine compounds such as phenazine methosulfate, p-benzoquinone, methylene blue, ferrocene derivatives and the like can be used. Of these, the redox material is preferably potassium ferricyanide. Since potassium ferricyanide has a function of directly reacting with creatinine to oxidize creatinine, when potassium ferricyanide is used as the redox substance, the concentration of creatinine contained in the sample solution can be measured.

  When the sample solution is urine, the electrolyte concentration in urine can be obtained by measuring the conductivity in urine using the measuring device of the present invention. Further, by measuring the creatinine concentration in urine using the measuring device of the present invention, and correcting the obtained urinary electrolyte concentration using the measured creatinine concentration, estimating the daily salt intake Is possible. Quantitative measurement of daily salt intake is useful for preventing hypertension.

  The reagent used in the present invention may contain a plurality of types of redox substances.

  The measurement device of the present invention further includes, on the first surface, at least two leads connected to each of the at least two electrodes included in the electrode system, and the electrodes and the leads It is preferable that the connection is made at the end of the electrode on the first opening side.

  According to this configuration, since it is not necessary to provide a lead between the reagent and the electrode system on the first surface, the reagent dissolved in the sample solution can be smoothly diffused to the electrode system without being obstructed by the lead. can do. Therefore, the measurement accuracy of the concentration of the component contained in the sample solution can be further improved.

The measurement method of the present invention uses the above measurement device,
(A) introducing the sample solution into the space through the first opening of the measurement device;
(B) measuring the conductivity of the sample solution using the electrode system after the sample solution reaches the electrode system;
(C) After the step B, waiting for the reagent dissolved in the sample solution to diffuse to the electrode system;
(D) After the step C, applying a voltage between at least two electrodes among the electrodes included in the electrode system;
(E) a step of measuring a current flowing between the two electrodes to which a voltage is applied in the step D; and (F) based on the current measured in the step E, the component contained in the sample liquid A step of determining the concentration.

  According to this method, in Step B, since the reagent is not dissolved in the sample solution in contact with the electrode system, the conductivity of the sample solution can be measured with high accuracy. Next, in step D, since the reagent dissolved in the sample liquid diffuses in the sample liquid and reaches the electrode system, the same electrode system as that used for the measurement of conductivity is used. The concentration of the measurement target component contained in the liquid can be measured. Therefore, according to the measurement method of the present invention, it is possible to accurately measure the conductivity of the sample solution and the concentration of the measurement target component contained in the sample solution using a single electrode system.

  In step F, the concentration of the component contained in the sample solution may be obtained based on the current value measured in step E. Further, the concentration of the component contained in the sample solution may be obtained based on the amount of electricity that is the integral of the current value measured in step E.

Moreover, the measuring method of the present invention comprises:
(G) It is preferable to further include a step of detecting that the sample solution has reached the electrode system using the electrode system before the step B.

  In this way, the time at which the sample solution reaches the electrode system can be accurately known, and by what time should the measurement of the conductivity of the sample solution in step B be completed, the two electrodes in step E It is possible to accurately know when to measure the current flowing between them.

  The detection of the sample liquid in the process G can be performed, for example, by detecting a change in resistance between two electrodes included in the electrode system. When the sample solution reaches the electrode system, the resistance between the two electrodes contained in the electrode system decreases. Therefore, it is detected that the sample solution has reached the electrode system by detecting the change in resistance between the two electrodes. can do. The change in resistance between the two electrodes can be detected, for example, by measuring the change in the current flowing between the two electrodes in a state where a DC voltage is applied between the two electrodes.

  The distance δ at which the ion species generated by dissolving the reagent in the sample solution diffuses during the time t is expressed by the following (Equation 1). However, D represents the diffusion coefficient of the ion species, and π represents the circular ratio.

  Here, when the distance between the reagent-side end of the electrode system and the electrode-side end of the reagent is L, the reagent dissolves in the sample solution when the ionic species diffusion distance δ becomes equal to L. The ionic species generated by this will reach the electrode system. Therefore, when time t when δ = L is assumed to be T, T is expressed by the following equation (Equation 2).

Among a plurality of ionic species generated by dissolving the reagent in the sample solution, the ionic species having the largest diffusion coefficient first reaches the electrode system. Assuming that the time required for the ion species having the largest diffusion coefficient to reach the electrode system from the position where the reagent is provided is T ₁ , T ₁ is expressed by the following equation (Equation 3).

Here, D ₁ represents the diffusion coefficient of the ion species having the largest diffusion coefficient.

In the measurement method of the present invention, the electrode system is used in Step B from the time when the sample liquid reaches the electrode system in Step G until the time T ₁ represented by the above formula (Equation 3) elapses. It is preferable that the conductivity of the sample solution is measured.

  In this way, the conductivity of the sample solution is measured using the electrode system before the ion species generated by dissolution of the reagent in the sample solution reaches the electrode system. It can measure with high accuracy.

Here, when the reagent contains a redox substance, this redox substance is reduced by reacting with the component to be measured contained in the sample solution, and the reduced redox substance is oxidized in the electrode system After the elapse of time T ₂ represented by the following formula (Equation 4) after it is detected that the sample liquid has reached the electrode system in Step G, the current flowing between the two electrodes is measured in Step E. preferable.

However, in the above formula (Expression 4), D ₂ represents the diffusion coefficient of the redox species.

  In this way, since the current flowing between the two electrodes after the oxidation-reduction substance reaches the electrode system is measured, the concentration of the component to be measured contained in the sample liquid can be accurately measured. .

  Hereinafter, embodiments of the present invention will be described with reference to the drawings. In the following embodiment, an example in which the sample solution is urine and the urinary conductivity and the concentration of creatinine contained in the urine are measured using the measurement device according to the present invention will be described.

(Embodiment 1)
The configuration of the measuring device 100 according to Embodiment 1 of the present invention will be described with reference to FIG. FIG. 1 is an exploded perspective view showing a configuration of a measuring device 100 according to the present embodiment.

  The measurement device 100 includes a first substrate 102, a second substrate 104 having air holes 106, and a spacer 108 disposed between the first substrate 102 and the second substrate 104 and having a slit 110. Yes. By combining the first substrate 102, the second substrate 104, and the spacer 108, the space formed at the position of the slit 110 functions as a sample solution holding unit. One end of the sample solution holding part is open, and the opening functions as the sample solution introduction hole 112. Further, the slit 110 communicates with the air hole 106. Here, the first substrate 102, the second substrate 104, and the spacer 108 correspond to the base in the present invention.

  On the first substrate 102, a first electrode 122, a second electrode 124, a third electrode 126, and a fourth electrode 128 are disposed at a position exposed to the sample solution holding unit. The first electrode 122, the second electrode 124, the third electrode 126, and the fourth electrode 128 constitute an electrode system 120. A reagent 130 for measuring the target component contained in the sample solution is disposed on the surface of the first substrate 102 on which the electrode system 120 is provided and at a position closer to the air hole 106 than the electrode system 120. ing. At least a part of the reagent 130 is exposed to the sample solution holding unit.

  A method for manufacturing the measuring device 100 will be described.

  As a material of the first substrate 102, the second substrate 104, and the spacer 108, for example, polyethylene terephthalate (hereinafter abbreviated as PET) which is an insulating material is used. For example, after a palladium layer (hereinafter abbreviated as a Pd layer) is formed on the first substrate 102 made of PET by sputtering, a part of the Pd layer is etched using laser trimming to thereby form a first layer. An electrode system 120 including an electrode 122, a second electrode 124, a third electrode 126, and a fourth electrode 128 is formed. The dimensions of each electrode are, for example, a length of 3.1 mm, a width of 0.25 mm, and a thickness of several nm.

  A mixture containing, for example, potassium ferricyanide as a redox substance and a phosphate buffer solution at a position closer to the air hole 106 than the electrode system 120 on the surface of the first substrate 102 where the electrode system 120 is provided. An aqueous solution is added dropwise and dried to form reagent 130. The mixed aqueous solution is dropped into a rectangular region having a width of 7 mm and a length of 1 mm, for example, in a dropping amount of 1.4 μL. Here, the concentration of potassium ferricyanide in the mixed aqueous solution may be about 0.1M, and the concentration of the phosphate buffer solution may be about 0.4M. Further, as the phosphate buffer solution, for example, a solution adjusted to pH 6.0 with dipotassium hydrogen phosphate and potassium dihydrogen phosphate can be used. Potassium ferricyanide can be used to measure the concentration of creatinine contained in the sample solution. Here, the end of the electrode system 120 on the reagent 130 side, that is, the end farthest from the sample liquid introduction hole 112 (hereinafter, referred to as the most downstream part of the electrode system 120) and the end of the reagent 130 on the electrode system 120 side. That is, the reagent 130 is arranged at a position where the distance L from the end closest to the sample liquid introduction hole 112 (hereinafter referred to as the most upstream part of the reagent 130) is 180 μm.

  Finally, the first substrate 102, the spacer 108, and the second substrate 104 are bonded to each other with the spacer 108 interposed therebetween, whereby the measurement device 100 is completed. The dimensions of the space formed at the position of the slit 110 are set to, for example, a width of about 1 mm, a length of about 5 mm, and a thickness of about 0.7 mm.

  Of the Pd layer provided on the first substrate 102, portions exposed without being covered by the second substrate 104 are the first terminal 132, the second terminal 134, the third terminal 136, And functions as the fourth terminal 138. In addition, among the Pd layer provided on the first substrate 102, the portions exposed in the slit 110 of the spacer 108 are the first electrode 122, the second electrode 124, the third electrode 126, and It functions as the fourth electrode 128. The first terminal 132, the second terminal 134, the third terminal 136, and the fourth terminal 138 are the first electrode 122, the second electrode 124, the third electrode 126, and the fourth electrode, respectively. 128 is connected to the end portion of each electrode on the sample solution introduction hole 112 side.

  Next, the configuration of the measuring apparatus 200 used in the embodiment of the present invention will be described with reference to FIG. FIG. 2 is a perspective view showing the configuration of the measuring apparatus 200 used in the present embodiment.

  The measurement apparatus 200 includes a housing 202, a display 204, and a measurement start button 206, and the housing 202 has a measurement device insertion 208 for inserting the measurement device 100.

  The configuration inside the housing 202 of the measuring apparatus 200 will be described with reference to FIG. FIG. 3 is a functional block diagram showing a configuration inside the housing 202 of the measuring apparatus 200.

  A constant current AC power supply 302, a voltage detector 304, a control unit 306, a timer unit 308, a storage unit 310, a DC power supply 312 and a current detector 314 are provided inside the housing 202 of the measuring apparatus 200.

  The constant current AC power supply 302 is fixed between the first electrode 122 and the fourth electrode 128 of the measurement device 100 inserted into the measurement device insertion hole 208 via the first terminal 132 and the fourth terminal 138. It has a function of applying an alternating current. The frequency of the alternating current to be applied is 1 kHz, and the current value of the alternating current can be set to an arbitrary value within the range of 0.01 mA to 0.2 mA.

  The voltage detector 304 has a function of detecting a voltage between the second electrode 124 and the third electrode 126 via the second terminal 134 and the third terminal 136.

  The DC power supply 312 has a function of applying a DC voltage of 0.5 V between the second electrode 124 and the third electrode 126 via the second terminal 134 and the third terminal 136.

  The current detector 314 has a function of detecting a current value flowing between the second electrode 124 and the third electrode 126 via the second terminal 134 and the third terminal 136.

  Next, a measurement method according to the present embodiment using the measurement device 100 and the measurement apparatus 200 will be described with reference to FIG. FIG. 4 is a flowchart showing the steps of the measurement method according to the present embodiment.

  First, after the measurement device 100 is inserted into the measurement device insertion hole 208 so that the sample liquid introduction hole 112 side of the measurement device 100 is exposed, the measurement apparatus 200 is activated by pressing down the measurement start button 206 ( S101). At this time, a DC potential of +0.5 V is applied from the DC power source 312 to the third electrode 126 using the second electrode 124 as a counter electrode (S103).

  Next, when the sample solution is brought into contact with the sample solution introduction hole 112 of the measurement device 100, the sample solution is introduced into the sample solution holding portion from the sample solution introduction hole 112 by capillary action.

  When the sample solution reaches the electrode system 120, the second electrode 124 and the third electrode 126 are brought into conduction through the sample solution, so that the resistance between the second electrode 124 and the third electrode 126 decreases. This resistance change causes a current to flow between the second electrode 124 and the third electrode 126. When the control unit 306 detects that the current value detected by the current detector 314 exceeds a preset threshold value (S105), the control unit 306 detects that the sample liquid has reached the electrode system 120. (S107) Then, the timer 308 is controlled to start measuring time (S109).

  When the control unit 306 detects the arrival of the sample solution to the electrode system 120, the control unit 306 cancels the application of the DC voltage between the second electrode 124 and the third electrode 126 (S111), and the AC four electrodes. Start measuring the conductivity in the sample solution by the method. The AC four-electrode method will be described below. First, the control unit 306 controls the constant-current AC power supply 302 to provide +0.1 mA, 1 kHz between the first electrode 122 and the fourth electrode 128 via the first terminal 132 and the fourth terminal 138. A constant alternating current is applied (S113). After 5 seconds (S115), the voltage detector 304 detects the voltage value (effective value of the AC voltage) between the second electrode 124 and the third electrode 126 (S117). The control unit 306 calculates the conductivity of the sample solution based on the current value applied by the constant current AC power supply 302 and the voltage value detected by the voltage detector 304. When measurement based on the four-electrode method is performed, the conductivity of the sample solution can be measured without being affected by the lead resistance. In the present embodiment, since the AC voltage is measured 5 seconds after the application of the AC current, the AC current can be measured in a sufficiently stable state, so that the measurement accuracy can be further improved.

  When the sample solution reaches the position of the reagent 130, the reagent 130 is dissolved in the sample solution, and potassium ferricyanide contained in the reagent 130 is ionized to generate ferricyanide ions and potassium ions. Ferricyanide ions function as an oxidizing agent to oxidize creatinine contained in the sample solution, thereby generating ferrocyanide ions that are reduced forms of ferricyanide ions in the sample solution. Potassium ions, ferricyanide ions, and ferrocyanide ions begin to diffuse toward the electrode system 120.

In measurement device 100 according to the present embodiment, since the ion species having the largest diffusion coefficient among the plurality of ion species generated by dissolving the reagent in the sample solution is potassium ion, potassium ion is the electrode system first. 120 is reached. Since the diffusion coefficient D ₁ of potassium ions is 1.9 × 10 ⁻⁹ m ² s ⁻¹ , the time required for potassium ions to reach the electrode system 120 from the position where the reagent 130 is provided is T ₁ . It is calculated as 5.4 seconds by the above equation (Equation 3).

In this embodiment, 5 seconds after the sample solution to the electrode system 120 is detected that has been reached, i.e. the conductivity measurement of the sample liquid by the time T ₁ of the above formula (Expression 3) has elapsed Therefore, the conductivity of the sample solution is measured using the electrode system 120 before the ionic species generated by the dissolution of the reagent 130 in the sample solution reaches the electrode system 120. The rate can be measured with high accuracy.

  When the calculation of the conductivity of the sample solution is completed, the control unit 306 controls the constant current AC power supply 302 to stop the application of the AC current (S119).

Since the diffusion coefficient of ferricyanide ion and ferrocyanide ion is 0.6 × 10 ⁻⁹ m ² s ⁻¹ , the electrode system 120 is disposed from the position where the reagent 130 is provided to the ferricyanide ion and ferrocyanide ion. T ₂ is calculated as 17.1 seconds according to the above equation (Equation 4).

  After 17 seconds from the start of measurement by the time measuring unit 308 (S121), that is, 12 seconds after the application of alternating current is stopped, the control unit 306 controls the direct current power supply 312 so that the second terminal 134 and the third terminal 136 are connected. Then, a DC potential of +0.5 V is applied to the third electrode 126 using the second electrode 124 as a counter electrode (S123). By application of the DC potential, ferrocyanide ions accumulated in the sample solution are oxidized in the electrode system 120.

  The current detector 314 detects the value of the current flowing between the second electrode 124 and the third electrode 126 after 18 seconds from the start of measurement by the time measuring unit 308 (S125), that is, 1 second after the application of the DC voltage ( S127). Here, since the current value is detected 1 second after the application of the DC voltage, the influence of the double layer charging current accompanying the voltage application can be reduced.

  The concentration of ferrocyanide ions in the sample solution is proportional to the concentration of creatinine contained in the sample solution. Therefore, when a DC voltage is applied, the value of the oxidation current that flows based on the oxidation of ferrocyanide ions is proportional to the creatinine concentration. The control unit 306 reads the correlation data indicating the correlation between the current value and the creatinine concentration stored in the storage unit 310, refers to the correlation data (S129), and sets the current value detected by the current detector 314. Based on this, the current value is converted into the concentration of creatinine contained in the sample solution (S131).

In this embodiment, 18 seconds after the sample solution to the electrode system 120 is detected that has been reached, i.e. ferricyanide and ferrocyanide ions over time T ₂ of the formula (Formula 4) Since the current value flowing between the second electrode 124 and the third electrode 126 is detected after reaching the electrode system 120 from the position where the reagent 130 is provided, the concentration of creatinine contained in the sample solution can be accurately determined. Can be measured.

  Finally, the control unit 306 displays the creatinine concentration obtained on the display 204 (S133).

  According to the present embodiment, it is possible to accurately measure the conductivity of the sample solution and the concentration of the measurement target component contained in the sample solution using a single electrode system.

  In the first embodiment, the measurement apparatus 300 includes the constant current AC power supply 302, and the constant current AC power supply 302 measures the first electrode 122-fourth of the measurement device 100 when measuring the conductivity of the sample solution. Although an example in which a constant alternating current is applied between the electrodes 128 via the first terminal 132 and the fourth terminal 138 has been described, the present invention is not limited to this example. Instead of this configuration, the measurement apparatus includes a constant current direct current power source, and the constant current direct current power source is connected between the first electrode and the fourth electrode of the measurement device when measuring the conductivity of the sample solution. A constant direct current may be applied via the terminal and the fourth terminal.

  In addition, the second electrode 124 and the third electrode 126 are used to detect that the sample liquid has reached the electrode system 120. However, the present invention is not limited to this. Of the four electrodes included in the electrode system 120, Any two electrodes may be used.

(Embodiment 2)
Next, the configuration of the measuring device 400 according to Embodiment 2 of the present invention will be described with reference to FIG. FIG. 5 is an exploded perspective view showing the configuration of the measuring device 400 according to the present embodiment.

  In the measurement device 400 according to the present embodiment, unlike the measurement device 100 according to the first embodiment, the electrode system 420 is composed of two electrodes, a first electrode 422 and a second electrode 424. Further, when the first substrate 102, the spacer 108, and the second substrate 104 are bonded together, the exposed portion of the Pd layer formed on the first substrate 102 substrate is the first terminal. 432 and the second terminal 434 function. The first terminal 432 and the second terminal 434 are connected to the first electrode 422 and the second electrode 424, respectively. Since other configurations are the same as those of the measurement device 100 according to the first embodiment, the same reference numerals as those in the first embodiment are given and description thereof is omitted.

  Next, the internal configuration of the housing 202 of the measuring apparatus 500 used in this embodiment will be described with reference to FIG. FIG. 6 is a functional block diagram showing a configuration inside the housing 202 of the measuring apparatus 500.

  Inside the housing 202 of the measuring apparatus 500 used in the present embodiment, as in the measuring apparatus 200 used in the first embodiment, a control unit 306, a time measuring unit 308, a storage unit 310, a DC power supply 312, and a current detector. 314 is provided. Measuring apparatus 500 used in the present embodiment is different from measuring apparatus 200 used in Embodiment 1 in that it does not include a constant current AC power supply and a voltage detector.

  The DC power supply 312 has a function of applying a DC voltage between the first electrode 422 and the second electrode 424 through the first terminal 432 and the second terminal 434.

  The current detector 314 has a function of detecting a current value flowing between the first electrode 422 and the second electrode 424 through the first terminal 432 and the second terminal 434.

  Next, a measurement method according to the present embodiment using the measurement device 400 and the measurement apparatus 500 will be described.

  First, after the measurement device 400 is inserted into the measurement device insertion hole 208 so that the sample liquid introduction hole 112 side of the measurement device 400 is exposed, the measurement apparatus 500 is activated by depressing the measurement start button 206. At this time, a DC potential of +0.5 V is applied to the second electrode 424 by the DC power source 312 with the first electrode 422 as a counter electrode.

  Next, when the sample solution is brought into contact with the sample solution introduction hole 112 of the measuring device 400, the sample solution is introduced into the sample solution holding portion from the sample solution introduction hole 112 by capillary action.

  When the sample solution reaches the electrode system 420, the first electrode 422 and the second electrode 424 are brought into conduction through the sample solution, so that the resistance between the first electrode 422 and the second electrode 424 is reduced. This resistance change causes a current to flow between the first electrode 422 and the second electrode 424. When the control unit 306 detects that the current value detected by the current detector 314 exceeds a preset threshold value, the control unit 306 detects that the sample liquid has reached the electrode system 420 and measures the time. The unit 308 is controlled to start measuring time.

  When the control unit 306 detects the arrival of the sample solution to the electrode system 420, the control unit 306 maintains the application of the DC voltage between the first electrode 422 and the second electrode 424, and starts 5 times from the start of the measurement time measurement. After a second, the current detector 314 detects the value of the current flowing between the first electrode 422 and the second electrode 424. The control unit 306 calculates the conductivity of the sample solution based on the voltage value applied by the DC power supply 312 and the current value detected by the current detector 314. In the present embodiment, since the current value is measured 5 seconds after the application of the DC voltage, the influence of the double layer charging current due to the voltage change can be suppressed, so that the measurement accuracy can be further improved. .

  When the sample solution reaches the position of the reagent 130, the reagent 130 is dissolved in the sample solution, and potassium ferricyanide contained in the reagent 130 is ionized to generate ferricyanide ions and potassium ions. Ferricyanide ions function as an oxidizing agent to oxidize creatinine contained in the sample solution, thereby generating ferrocyanide ions that are reduced forms of ferricyanide ions in the sample solution. Potassium ions, ferricyanide ions, and ferrocyanide ions begin to diffuse toward the electrode system 420.

In the measurement device 400 according to the present embodiment, as in the measurement apparatus 200 used in the first embodiment, the ion species having the largest diffusion coefficient among a plurality of ion species generated by dissolving the reagent in the sample solution is Since it is a potassium ion, the potassium ion first reaches the electrode system 120. Since the diffusion coefficient D ₁ of potassium ion is 1.9 × 10 ⁻⁹ m ² s ⁻¹ , the time required for the potassium ion to reach the electrode system 420 from the position where the reagent 130 is provided is T ₁ . It is calculated as 5.4 seconds by the above equation (Equation 3).

In this embodiment, 5 seconds after the sample solution to the electrode system 420 is detected that has been reached, i.e. the conductivity measurement of the sample liquid by the time T ₁ of the above formula (Expression 3) has elapsed Therefore, the conductivity of the sample solution is measured using the electrode system 420 before the ion species generated by the dissolution of the reagent 130 in the sample solution reaches the electrode system 420. The rate can be measured with high accuracy.

  When the calculation of the conductivity of the sample solution is completed, the control unit 306 controls the DC power supply 312 to stop the application of the DC voltage.

  In the subsequent steps, the DC power source 312 applies a DC voltage not between the second electrode 124 and the third electrode 126 but between the first electrode 422 and the second electrode 424, and a current detector. The third embodiment is the same as the first embodiment except that the current value flowing between the first electrode 422 and the second electrode 424 is detected by 314 instead of between the second electrode 124 and the third electrode 126. Therefore, explanation is omitted.

  According to the present embodiment, it is possible to accurately measure the conductivity of the sample solution and the concentration of the measurement target component contained in the sample solution using a single electrode system.

(Embodiment 3)
Next, the configuration of the measuring device 600 according to Embodiment 3 of the present invention will be described with reference to FIG. FIG. 7 is an exploded perspective view showing the configuration of the measuring device 600 according to the present embodiment.

  Unlike the measurement device 100 according to the first embodiment, the measurement device 600 according to the present embodiment further includes a second electrode system 620 for detecting the supply of the sample liquid. The second electrode system 620 includes a fifth electrode 622 and a sixth electrode 624. The first electrode system 120, the second electrode system 620, and the reagent 130 are arranged so that the reagent 130 is positioned between the first electrode system 120 and the second electrode system 620. Further, when the first substrate 102, the spacer 108, and the second substrate 104 are bonded together, the Pd layer formed on the first substrate 102 is exposed without being covered by the second substrate 104. These portions function as the first terminal 132, the second terminal 134, the third terminal 136, the fourth terminal 138, the fifth terminal 632, and the sixth terminal 634. The fifth terminal 632 and the sixth terminal 634 are connected to the fifth electrode 622 and the sixth electrode 624, respectively. Since other configurations are the same as those of the measurement device 100 according to the first embodiment, the same reference numerals as those in the first embodiment are given and description thereof is omitted.

  Next, the internal structure of the housing 202 of the measurement apparatus 700 used in this embodiment will be described with reference to FIG. FIG. 8 is a functional block diagram showing a configuration inside the housing 202 of the measuring apparatus 700. As shown in FIG.

  In the housing 202 of the measuring apparatus 700 used in this embodiment, a constant current AC power source 302, a voltage detector 304, a control unit 306, a time measuring unit 308, a storage unit 310, a DC power source 312, and a current detector 314 are provided. In addition, it differs from the measuring apparatus 200 used in Embodiment 1 in that it includes a second DC power supply 712 and a second current detector 714.

  The second DC power supply 712 has a function of applying a DC voltage between the fifth electrode 622 and the sixth electrode 624 through the fifth terminal 632 and the sixth terminal 634.

  The second current detector 714 has a function of detecting a current value flowing between the fifth electrode 622 and the sixth electrode 624 via the fifth terminal 632 and the sixth terminal 634.

  Since the functions of the constant current AC power supply 302, the voltage detector 304, the DC power supply 312 and the current detector 314 are the same as those of the measuring apparatus 200 used in the first embodiment, description thereof is omitted.

  Next, a measurement method according to the present embodiment using the measurement device 600 and the measurement apparatus 700 will be described.

  First, after the measurement device 600 is inserted into the measurement device insertion hole 208 so that the sample solution introduction hole 112 side of the measurement device 600 is exposed, the measurement apparatus 700 is activated by pressing down the measurement start button 206. At this time, the second DC power source 712 applies a DC potential of +0.5 V to the sixth electrode 624 with the fifth electrode 622 as a counter electrode.

  Next, when the sample solution is brought into contact with the sample solution introduction hole 112 of the measuring device 600, the sample solution is introduced into the sample solution holding part from the sample solution introduction hole 112 by capillary action.

  When the sample solution reaches the second electrode system 620, the fifth electrode 622 and the sixth electrode 624 are brought into conduction through the sample solution, so that the resistance between the fifth electrode 622 and the sixth electrode 624 is reduced. descend. This resistance change causes a current to flow between the fifth electrode 622 and the sixth electrode 624. When the control unit 306 detects that the current value detected by the second current detector 714 exceeds a preset threshold value, the control unit 306 indicates that the sample solution has reached the second electrode system 620. Is detected and the time measuring unit 308 is controlled to start measuring the measurement time.

  In the measurement device 600 according to the present embodiment, the second electrode system 620 for detecting the supply of the sample solution is provided at a position far from the sample solution introduction hole 112 as compared with the reagent 130. In this way, since the output of the second electrode system 620 is generated only when the sample solution is sufficiently supplied up to the position of the reagent 130, the measurement is erroneously started when the sample solution is not supplied sufficiently. Can be prevented.

  When the control unit 306 detects the arrival of the sample solution to the second electrode system 620, the control unit 306 cancels the application of the DC voltage between the fifth electrode 622 and the sixth electrode 624, and the AC four electrodes. Start measuring the conductivity in the sample solution by the method.

  Since the subsequent steps are the same as those in the first embodiment, description thereof is omitted.

  According to the present embodiment, it is possible to accurately measure the conductivity of the sample solution and the concentration of the measurement target component contained in the sample solution using a single electrode system.

  In the above embodiment, the example in which the conductivity in the sample solution is measured by the AC four-electrode method or the DC two-electrode method has been described, but the present invention is not limited to this. Instead of these methods, for example, using an electrode system having four electrodes, a constant direct current is applied between two of the four electrodes, and a voltage value generated between the remaining two electrodes is detected. Alternatively, a method of detecting a voltage value generated between two electrodes by applying a constant alternating current between the two electrodes using an electrode system having two electrodes may be used.

  The present invention relates to measuring the conductivity of a sample solution and the concentration of a component contained in the sample solution, and particularly measuring the conductivity of a biological sample such as urine and the concentration of a component such as creatinine contained in the biological sample. Useful for.

1 is an exploded perspective view showing a configuration of a measuring device according to an embodiment of the present invention. The perspective view which shows the structure of the measuring apparatus used in the embodiment Functional block diagram showing the internal configuration of the measurement device Flowchart showing the steps of the measurement method according to the embodiment The disassembled perspective view which shows the structure of the measuring device which concerns on other embodiment of this invention. Functional block diagram showing the internal configuration of the measurement device The disassembled perspective view which shows the structure of the measuring device which concerns on other embodiment of this invention. Functional block diagram showing the internal configuration of the measurement device

Explanation of symbols

100, 400, 600 Measuring device 102 First substrate 104 Second substrate 106 Air hole 108 Spacer 110 Slit 112 Sample liquid introduction hole 120,420 Electrode system 122,422 First electrode 124,424 Second electrode 126 Second electrode 126 Three electrodes 128 Fourth electrode 130 Reagent 132,432 First terminal 134,434 Second terminal 136 Third terminal 138 Fourth terminal 200,500,700 Measuring device 202 Case 204 Display 206 Measurement start button 208 Measurement Device Insertion Hole 302 Constant Current AC Power Supply 304 Voltage Detector 306 Control Unit 308 Timekeeping Unit 310 Storage Unit 312 DC Power Supply 314 Current Detector 620 Second Electrode System 622 5th Electrode 624 6th Electrode 632 5th Terminal 634 Sixth terminal 712 Second DC power supply 714 Second current detector

Claims (8)

A substrate having a space communicating with a first opening that functions as a sample solution introduction hole and a second opening that functions as an air hole;
At least one electrode disposed on the first surface of the substrate surrounding the space and including at least two electrodes, the conductivity of the sample solution introduced into the space, and at least one included in the sample solution An electrode system for measuring the concentration of the component, and a reagent for measuring the component, which is disposed on the first surface and closer to the second opening than the electrode system Measuring device. The reagent includes a redox material;
The measurement device according to claim 1, wherein the redox substance is reduced by reacting with the component, and the reduced redox substance is oxidized in the electrode system. The measuring device according to claim 2, wherein the redox substance is potassium ferricyanide. On the first surface, further comprising at least two leads connected to each of the at least two electrodes included in the electrode system;
The measuring device according to claim 1, wherein the electrode and the lead are connected at an end portion of the electrode on the first opening side. Using the measuring device according to any one of claims 1 to 4,
(A) introducing the sample solution into the space through the first opening of the measurement device;
(B) measuring the conductivity of the sample solution using the electrode system after the sample solution reaches the electrode system;
(C) After the step B, waiting for the reagent dissolved in the sample solution to diffuse to the electrode system;
(D) After the step C, applying a voltage between at least two electrodes among the electrodes included in the electrode system;
(E) a step of measuring a current flowing between the two electrodes to which a voltage is applied in the step D; and (F) based on the current measured in the step E, the component contained in the sample liquid A measurement method including a step of obtaining a concentration. (G) The measurement method according to claim 5, further comprising a step of detecting that the sample liquid has reached the electrode system using the electrode system before the step B. From the time when it is detected that the sample solution has reached the electrode system in the step G until the time T ₁ represented by the following formula (Equation 1) elapses, the sample is used by using the electrode system in the step B. The measuring method according to claim 6, wherein the conductivity of the liquid is measured.

However, in the above formula (Equation 1),
L is the distance between the end of the electrode system on the reagent side and the end of the reagent on the electrode system side,
D ₁ is a diffusion coefficient of an ion species having the largest diffusion coefficient among a plurality of ion species generated by dissolving the reagent in the sample solution;
π represents the circumference ratio. The reagent includes a redox material;
The redox material is reduced by reacting with the component, and the reduced redox material is oxidized in the electrode system;
After the elapse of time T ₂ represented by the following formula (Equation 2) after it is detected that the sample solution has reached the electrode system in the step G, the current flowing between the two electrodes is measured in the step E. The measurement method according to claim 6.

However, in the above formula (Equation 2),
L is the distance between the end of the electrode system on the reagent side and the end of the reagent on the electrode system side,
D ₂ is the diffusion coefficient of the redox material,
π represents the circumference ratio.

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