JP2010008182A - Creatinine measuring method, creatinine measuring device, creatinine measuring apparatus, and urinary salinity measuring method, urinary salinity measuring device, and urinary salinity measuring apparatus using them - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a creatinine measuring method, a creatinine measuring device and a creatinine measuring apparatus capable of determining accurately creatinine included in a sample. <P>SOLUTION: This creatinine measuring method includes processes for: (A) generating a creatinine oxide by direct reaction of creatinine included in the sample with an osmium complex, caused by bringing the sample including creatinine into contact with a reagent for creatinine measurement including the osmium complex whose oxidation-reduction potential at pH7 and 25°C is more positive than 380 mV relative to a silver-silver chloride electrode; (B) measuring electrochemically the reaction in the process (A); and (C) determining the concentration or the amount of creatinine included in the sample based on a measured value in the process (B). <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a measurement method, a measurement device, and a measurement apparatus for quantifying creatinine and salt contained in a sample.

  Measurement of creatinine contained in a sample is important in the fields of clinical chemistry and analytical chemistry. Since creatinine is a product of the endogenous metabolism of muscle, it is known that the amount of creatinine in urine reflects the total muscle mass. Therefore, it is said that the amount of creatinine in urine excreted by humans in a day is generally constant for each individual and does not vary from day to day. Therefore, the amount of creatinine in urine is sometimes used as a measure of the density of excreted urine. Moreover, since the amount of creatinine in urine and blood increases or decreases due to uremia or a decrease in renal function, the presence or absence of uremia or a decrease in kidney function can be known by measuring the amount of creatinine in urine or blood.

  As a method for measuring creatinine, a method based on a Jaffe reaction using an alkaline picric acid solution is known. In this method, an orange-red product obtained by reacting picric acid with creatinine is measured spectroscopically (see, for example, Patent Document 1).

  As another creatinine measurement method, a method using an enzyme that specifically reacts with creatinine is known. As a method using an enzyme, for example, there is a method in which ammonia is obtained by decomposing creatinine using creatinine deiminase, and the concentration of creatinine is obtained by measuring the amount of ammonia from a pH change (for example, patents). Reference 2).

  As another method using an enzyme, there is a method of measuring creatinine by the following reactions (Chemical Formula 1) to (Chemical Formula 3).

  As enzymes that catalyze the reactions of (Chemical Formula 1) to (Chemical Formula 3), creatinine amide hydrolase (creatininase), creatine amidinohydrolase (creatinase), and sarcosine oxidase or sarcosine dehydrogenase are used, respectively. Here, as a method for quantifying creatinine, for example, a method in which a leuco dye or a Trinder reagent is used together with peroxidase and the hydrogen peroxide generated in (Chemical Formula 3) is colored and spectroscopically quantified is used. (For example, refer to Patent Document 3). As another creatinine quantification method, a method of electrochemically oxidizing the hydrogen peroxide generated in (Chemical Formula 3) with an electrode and quantifying creatinine from a flowing current is used (see, for example, Patent Documents 4 and 5). ).

  In addition to the reactions of (Chemical Formula 1) and (Chemical Formula 2), in addition to the reactions of (Chemical Formula 3), as another method using an enzyme, the reaction of sarcosine and an electron carrier is used. Has been proposed (see, for example, Patent Documents 6 and 7). Patent Document 6 discloses a reagent solution in which creatininase, creatinase, sarcosine oxidase and an electron carrier are dissolved in a pH 7 to 8.5 buffer in a sensor having at least a pair of working electrodes and counter electrodes on a substrate. A creatinine biosensor is disclosed which is immobilized by drying on an electrode or a substrate around the electrode. Specifically, it is disclosed that potassium ferricyanide is used as an electron carrier, and a phosphate buffer having a pH of 6.86 is used as a buffer. Further, it is disclosed that when the pH of the buffer solution is pH 7 or lower or pH 8.5 or higher, the enzyme activity decreases, which is not preferable. Patent Document 7 discloses that creatinine is measured by a colorimetric method or an electrochemical detection method using a mediator encapsulated by cyclodextrin together with sarcosine oxidase. Specifically, α-naphthoquinone (1,4-naphthoquinone) is mentioned as an example of a mediator incorporated by cyclodextrin. However, in Patent Document 7, when mediators such as α-naphthoquinone and 1-methoxy-5-methylphenazinium methyl sulfate (M-PMS) are not included in cyclodextrin, creatinine is measured using an enzyme. It is disclosed that it is inappropriate.

  In addition to the reactions of (Chemical Formula 1) and (Chemical Formula 2), in addition to the reactions of (Chemical Formula 3), as another method using an enzyme, a reaction between sarcosine and a tetrazolium indicator is used for spectroscopy. In particular, a method for measuring creatinine has been proposed (see, for example, Patent Document 8). Patent Document 8 discloses that a mixed reagent consisting of creatinine hydrolase, creatine amidinohydrolase, sarcosine dehydrogenase, tetrazolium indicator thiazolyl blue and potassium phosphate pH 7.5 is used as a composition for measuring creatinine. .

  In addition, as another method using an enzyme, creatinine amide hydrolase, creatine amidinohydrolase and sarcosine dehydrogenase are used to change creatinine into glycine and formaldehyde. Has been proposed (see, for example, Patent Document 9). In Patent Document 9, in addition to creatinine amide hydrolase, creatine amidinohydrolase, sarcosine dehydrogenase and a colorant, a pH 7.5 phosphate buffer and potassium ferricyanide as a reaction accelerator for promoting the formation of formaldehyde are used. It is disclosed.

  Further, as another method using an enzyme, a method of measuring creatinine using a polymer that catalyzes hydrolysis of creatinine, an electrode on which a sarcosine oxidase and a mediator are immobilized has been proposed (for example, Patent Document 10). reference). Patent Document 10 discloses that potassium ferricyanide, ferrocene, osmium derivatives, phenazine methosulfate (PMS), and the like can be used as mediators.

As another creatinine measurement method, a method using potassium 1,4-naphthoquinone-2-sulfonate has been proposed (see, for example, Patent Document 11 and Non-Patent Documents 1 to 3).
US Pat. No. 3,705,003 JP-T-2001-512692 JP-A-62-257400 Special table 2003-533679 gazette US Pat. No. 5,466,575 JP 2006-349412 A JP 2005-1118014 A Japanese Patent Laid-Open No. 55-023998 JP 54-151095 A JP 2003-326172 A JP-A-63-033661 Sullivan, 1 other, “Highly specific test of creatinine”, Journal of Biological Chemistry, 1958, Vol. 233, No. 2, p. 530-534 (Sullivan, “A Highly Specific Test for Creatine”, 1958, Vol. 233, No. 2, p. 530-534) Narayanan, 1 other, “Creatinine: Review”, Clinical Chemistry, 1980, Vol. 26, No. 8, p. 1119-1126 (Narayanan, “Creatinine: A Review”, Clinical Chemistry, 1980, Vol. 26, No. 8, p. 1119-1126) Cooper, et al., “Evaluation of four methods for measuring urinary creatinine”, Clinical Chemistry, 1961, Vol. 7, No. 6, p. 665-673 (Cooper, “An Evaluation of Four Methods of Measuring Primary Creatine”, 1961, Vol. 7, No. 6, P. 665-673)

  However, the conventional method has the following problems.

  In the method described in Patent Document 1, amino acids such as glycine, histidine, glutamine, and serine and sugars such as glucose react with picric acid, and therefore samples containing amino acids and sugars, for example, biological samples such as urine and blood It is difficult to accurately quantify creatinine in it.

  Further, in the method described in Patent Document 2, since changes in pH and potential are unstable, it is difficult to accurately quantify creatinine.

  In addition, in the methods described in Patent Documents 2 to 10, the presence of ionic species such as salinity and urea in the sample causes enzyme activity to be reduced due to denaturation of the enzyme. The reaction rate varies depending on the concentration of. Therefore, when creatinine is quantified in a sample containing ionic species and urea, for example, a biological sample such as urine and blood, an error occurs in the measurement result depending on the concentration of the ionic species and urea contained in the sample.

  In addition, regarding the method using potassium 1,4-naphthoquinone-2-sulfonate described in Patent Document 11 and Non-Patent Document 1, in Non-Patent Documents 2 and 3, the reproducibility of measurement results is very low. A problem has been reported.

  Therefore, in view of the above-described conventional problems, the present invention has a first object to provide a creatinine measurement method, a creatinine measurement device, and a creatinine measurement apparatus that can accurately quantify creatinine contained in a sample. To do.

  It is a second object of the present invention to provide a urinary salt content measuring method, a urinary salt content measuring device, and a urinary salt content measuring apparatus capable of accurately quantifying the salt content in urine. And

In order to solve the above-mentioned conventional problems, the creatinine measurement method of the present invention has (A) a sample containing creatinine, and the oxidation-reduction potential at pH 7 and 25 ° C. is more positive than 380 mV with respect to the silver-silver chloride electrode. A step in which an creatinine oxide is produced by directly reacting the creatinine contained in the sample with the osmium complex by contacting with a reagent for measuring creatinine containing a certain osmium complex;
(B) electrochemically measuring the reaction in the step A, and (C) determining the concentration or amount of the creatinine contained in the sample based on the measurement value in the step B.

Moreover, the urinary salt content measuring method of the present invention uses urine as a sample, and in addition to steps A and B of the creatinine measuring method,
(F) a step of measuring electrical characteristics of the urine before the urine and the reagent for measuring creatinine come into contact; and (G) a measured value in the process B and the electrical characteristics measured in the process F. And a step of obtaining a value reflecting the amount of salt excreted in the urine based on the above.

  Further, the creatinine measuring device of the present invention is a creatinine measuring device used in the creatinine measuring method, wherein the creatinine measuring device communicates with the sample storage chamber for storing a sample containing creatinine, and the sample storage chamber. A sample introduction port for introducing the sample into the sample storage chamber, at least two electrodes disposed in the sample storage chamber, and a redox potential at pH 7 and 25 ° C. disposed in the sample storage chamber is silver-silver chloride. And a reagent for measuring creatinine containing an osmium complex that is more positive than 380 mV with respect to the electrode.

  The urinary salt content measuring device of the present invention is a urinary salt content measuring device used in the urinary salt content measuring method, and includes a first sample storage chamber for storing urine as a sample, A first sample introduction port for communicating with the first sample storage chamber and for introducing the urine into the first sample storage chamber; and at least two electrodes disposed in the first sample storage chamber; A reagent for measuring creatinine, which is disposed in the first sample storage chamber and contains an osmium complex whose redox potential at pH 7 and 25 ° C. is more positive than 380 mV with respect to a silver-silver chloride electrode; A second sample storage chamber for storing the second sample storage chamber, a second sample introduction port for introducing the urine into the second sample storage chamber, and the second sample storage chamber. At least two electrodes arranged in the sample storage chamber Equipped with a.

  Further, the creatinine measuring apparatus of the present invention includes a measuring device mounting portion for mounting the creatinine measuring device, creatinine in the sample storage chamber of the creatinine measuring device mounted on the measuring device mounting portion, and the creatinine measuring reagent, A measurement unit that electrochemically measures this reaction, and a calculation unit that obtains the concentration or amount of the creatinine contained in the sample based on the measurement value in the measurement unit.

  Further, the urinary salt content measuring apparatus of the present invention is a measuring device mounting portion for mounting the urinary salt content measuring device, and the first urinary salt content measuring device mounted on the measuring device mounting portion. A first measurement unit for electrochemically measuring a reaction between creatinine and the reagent for measuring creatinine in a sample storage chamber, and the second sample storage of the urinary salt content measurement device attached to the measurement device attachment unit A second measuring unit that measures the electrical characteristics of the urine in the room, and the salinity in the urine based on the measured values in the first measuring unit and the electrical characteristics measured by the second measuring unit. A calculation unit for obtaining a value that reflects the amount of excretion of the animal.

  According to the creatinine measurement method of the present invention, creatinine contained in a sample can be accurately quantified.

  The inventor of the present invention relates to creatinine and an osmium complex whose oxidation-reduction potential at pH 7 and 25 ° C. is more positive than 380 mV with respect to a silver-silver chloride electrode (hereinafter abbreviated as “vs Ag / AgCl”). Was newly found to react directly. In this reaction, even in the absence of an enzyme that acts on creatinine, creatinine reacts with the osmium complex to produce a creatinine oxide and the reduced osmium complex.

  The present invention has been made on the basis of the above-mentioned new knowledge, and an osmium whose redox potential at pH 7 and 25 ° C. is more positive than 380 mV (vs Ag / AgCl) as an active ingredient of a reagent composition for measuring creatinine. It is characterized by using a complex.

The method for measuring creatinine of the present invention comprises: (A) a sample containing creatinine; a reagent for measuring creatinine containing an osmium complex whose oxidation-reduction potential at pH 7 and 25 ° C. is more positive than 380 mV with respect to a silver-silver chloride electrode; The creatinine contained in the sample and the osmium complex directly react with each other to produce an oxide of creatinine,
(B) a step of electrochemically measuring the reaction in the step A; and (C) a step of determining the concentration or amount of the creatinine contained in the sample based on the measurement value in the step B.

  According to this method, unlike the conventional measurement method, creatinine reacts directly with the osmium complex contained in the reagent for measuring creatinine in the absence of an enzyme or picric acid that acts on creatinine. The reaction proceeds without being affected by interfering components such as urea, amino acids and sugars. Therefore, even when a biological sample such as urine or blood is used, creatinine contained in the sample can be quantified with higher accuracy than conventional measurement methods.

Examples of the osmium complex used in the present invention include [Os (bpy) (5,5′-dmbpy) ₂ ] ^{2 + / 3 +} , [Os (4,4′-dmbpy) ₂ (5,5′-dmbpy)] ^{2 + / 3+} , [Os (5,5′-dmbpy) ₂ (dpa)] ^{2 + / 3 + and the} like. [Os (bpy) (5,5′-dmbpy) ₂ ] ^{2 + / 3 +} , [Os (4,4′-dmbpy) ₂ (5,5′-dmbpy)] ^{2 + / 3 +} , and [Os (5,5 '-Dmbpy) ₂ (dpa)] The redox potentials of ^{2 + / 3 +} at pH ⁷ and 25 ° C. are 600 mV, 500 mV and 380 mV (vs Ag / AgCl), respectively.

  The oxidation-reduction potential at pH 7 and 25 ° C. of the osmium complex used in the present invention is preferably more negative than 600 mV.

  In the step A, a buffer may be brought into contact with the sample.

  Examples of the buffer used in the present invention include phosphate buffers such as dipotassium hydrogen phosphate and potassium dihydrogen phosphate, citric acid buffers, phthalic acid buffers, acetic acid buffers, MES buffers, and the like. Is mentioned.

  In the creatinine measurement method of the present invention, in the step A, the pH of the sample is preferably adjusted to around 6 by bringing the phosphate buffer into contact with the sample.

  If it does in this way, since the reaction rate of the direct reaction of creatinine and an osmium complex becomes quick, measurement time can be shortened.

  In the creatinine measurement method of the present invention, the phosphate buffer is preferably composed of dipotassium hydrogen phosphate and potassium dihydrogen phosphate. If it does in this way, the pH of the sample after a phosphate buffer solution melt | dissolves can be adjusted to 6 vicinity because these phosphates melt | dissolve in a sample.

In the step B, at least two electrodes are brought into contact with the sample,
Step B is
(D) applying a voltage between the two electrodes, and (E) detecting a value of electric current or a charge amount flowing between the two electrodes,
In step C,
The concentration or amount of the creatinine contained in the sample may be obtained based on the current value or the charge amount detected in the step E.

  In this way, the concentration or amount of creatinine contained in the sample can be easily determined electrochemically.

The urinary salt content measuring method of the present invention uses urine as a sample, and in addition to steps A and B of the creatinine measuring method,
(F) a step of measuring electrical characteristics of the urine before the urine and the reagent for measuring creatinine come into contact; and (G) a measured value in the process B and the electrical characteristics measured in the process F. And a step of obtaining a value reflecting the amount of salt excreted in the urine based on the above.

  The electrical characteristics of urine before the urine and the creatinine measurement reagent come into contact with each other and the creatinine measurement reagent dissolves in the urine reflect the concentration of the electrolyte contained in the urine. The concentration of the electrolyte contained in urine has a correlation with the concentration of salt contained in urine. Ingredients such as salt are affected by water intake, sweating, etc., and concentrated or diluted to be excreted in urine. For this reason, the concentration of urine components such as salt contained in the urine collected at any time, which is urine collected at any time during the day and at night, varies under the influence of urine concentration / dilution.

  On the other hand, as described above, since creatinine is produced depending on muscle mass, it is known that the amount of creatinine excreted in urine per unit time is constant. Therefore, even when urine is used at any time, for example, the ratio of the measured urinary component concentration to the creatinine concentration (urine component / creatinine ratio) is determined to correct the influence of urine concentration / dilution. be able to.

  According to the urinary salt content measuring method of the present invention, by using the measured value in Step B that accurately reflects the creatinine concentration and the electrical characteristics measured in Step F that reflect the salinity concentration. Since the influence of urine concentration / dilution is accurately corrected, a value that appropriately reflects the amount of salt excreted in urine can be obtained.

  Here, as electrical characteristics of urine, resistance, conductivity, impedance, voltage (or current) signal output with respect to the input current (or voltage) signal, and phase of the input AC signal are output. For example, a phase difference from the phase of the AC signal.

  Values reflecting the amount of urinary salt excretion determined in step I include the amount of salt per unit creatinine, the amount of urinary salt excreted per unit time (for example, 1 day), and the unit time (for example, 1 day). The amount of salt intake per hit is listed.

  The creatinine measuring device of the present invention is a creatinine measuring device used in the creatinine measuring method, which is in communication with a sample storage chamber for storing a sample containing creatinine, the sample storage chamber, and the sample storage chamber. A sample introduction port for introducing a sample, at least two electrodes disposed in the sample storage chamber, and a redox potential at pH 7 and 25 ° C. disposed in the sample storage chamber are applied to the silver-silver chloride electrode. And a reagent for measuring creatinine containing an osmium complex that is more positive than 380 mV.

  According to this device, unlike conventional measurement devices, creatinine and the osmium complex contained in the reagent for measuring creatinine react directly in the sample storage chamber even in the absence of an enzyme or picric acid that acts on creatinine. The reaction proceeds without being affected by interfering components such as ionic species such as salt, urea, amino acids, and sugars. Therefore, even when a biological sample such as urine or blood is used, creatinine contained in the sample can be quantified with higher accuracy than conventional measurement devices.

  The creatinine measuring device of the present invention may further include a phosphate buffer disposed in the sample storage chamber.

  The urinary salt content measuring device of the present invention is a urinary salt content measuring device used in the urinary salt content measuring method, wherein the first sample storage chamber for storing urine as a sample, A first sample inlet for introducing the urine into the first sample storage chamber; at least two electrodes disposed in the first sample storage chamber; A reagent for measuring creatinine containing an osmium complex, which is disposed in the first sample storage chamber and has an oxidation-reduction potential at pH 7 and 25 ° C. of more than 380 mV with respect to the silver-silver chloride electrode, and the urine are stored. A second sample storage chamber for communicating with the second sample storage chamber, a second sample introduction port for introducing the urine into the second sample storage chamber, and the second sample storage With at least two electrodes arranged indoors That. According to this device, it is possible to accurately measure the amount of reaction between creatinine contained in urine and the reagent for measuring creatinine, which accurately reflects creatinine concentration, and electrical characteristics of urine, which reflects salt concentration. it can. By using the reaction amount and the electrical characteristics, the influence of urine concentration / dilution is corrected with high accuracy, so that a value that appropriately reflects the amount of salt excreted in urine can be obtained.

  The creatinine measuring apparatus of the present invention comprises a measuring device mounting portion for mounting the creatinine measuring device, and a reaction between creatinine and the creatinine measuring reagent in the sample storage chamber of the creatinine measuring device mounted on the measuring device mounting portion. And a calculation unit for obtaining the concentration or amount of the creatinine contained in the sample based on the measurement value in the measurement unit.

  According to this measuring apparatus, the concentration or amount of creatinine contained in the sample can be electrochemically measured using the creatinine measuring device mounted on the measuring device mounting portion. Unlike the conventional measurement apparatus, the creatinine measurement apparatus of the present invention directly contains creatinine and the osmium complex contained in the creatinine measurement reagent even in the absence of an enzyme or picric acid that acts on creatinine in the sample storage chamber. Since it reacts, the reaction proceeds without being affected by interfering components such as ionic species such as salt, urea, amino acids, and sugars. Therefore, even when a biological sample such as urine or blood is used, creatinine contained in the sample can be quantified with higher accuracy than conventional measurement devices.

  The creatinine measuring apparatus of the present invention is such that the creatinine measuring device further includes at least two electrodes arranged in the sample storage chamber, and the measuring unit applies a voltage between the two electrodes. And a detection unit that detects a value of electric current or a charge amount flowing between the two electrodes, and the calculation unit is included in the sample based on the current value or the charge amount detected by the detection unit. The concentration or amount of the creatinine contained may be determined.

  According to this configuration, the concentration or amount of creatinine contained in the sample can be easily determined electrochemically using the creatinine measurement device attached to the measurement device attachment portion.

  The urinary salt content measuring apparatus of the present invention includes a measurement device mounting portion for mounting the urinary salt content measuring device, and the first sample accommodation of the urinary salt content measuring device mounted on the measurement device mounting portion. A first measurement unit for electrochemically measuring a reaction between creatinine in the room and the creatinine measurement reagent; and the urinary salt content measurement device attached to the measurement device attachment unit in the second sample storage chamber. Based on the second measurement unit that measures the electrical characteristics of the urine, and the measured values in the first measurement unit and the electrical characteristics measured by the second measurement unit, the excretion of salt in the urine A calculation unit for obtaining a value reflecting the quantity is provided. According to this measuring device, the concentration of urine can be corrected with respect to the electrical characteristics of the measured urine using the urine creatinine concentration quantified with high accuracy. Can be determined.

  According to the urinary salt content measurement method of the present invention, the amount of reaction between creatinine contained in the urine and the reagent for measuring creatinine, which accurately reflects the creatinine concentration, and the urine electricity that reflects the salt concentration. By using the characteristics, the influence of concentration / dilution of urine is corrected with high accuracy, so that a value that appropriately reflects the amount of salt excreted in urine can be obtained.

  Examples of the sample include body fluids such as blood, serum, plasma, urine, interstitial fluid, lymph fluid, and saliva in addition to an aqueous solution. In particular, urine is a very effective sample for non-invasive daily health management at home. Since the concentrations of ionic species and urea in these body fluids are relatively high, the effects of the present invention can be obtained very high.

  The material of at least two electrodes in the present invention is preferably one containing at least one of gold, platinum, palladium, an alloy or mixture thereof, and carbon. These materials are chemically and electrochemically stable, and a stable measurement can be realized. As the third electrode, a stable electrode, for example, a reference electrode such as an Ag / AgCl or saturated calomel electrode may be used in combination with the above two electrodes. It is preferable to regulate the potential of one of the two electrodes with respect to the third electrode because the potential for measurement becomes stable. Further, for example, an Ag / AgCl or saturated calomel electrode may be used as the other of the two electrodes.

  In the measurement device of the present invention, it is preferable that the creatinine measurement reagent is provided in a dry state and is disposed so as to dissolve in the sample when the sample is introduced into the sample storage chamber.

  For example, after impregnating a porous carrier composed of glass fiber, filter paper, or the like with a solution containing a creatinine measurement reagent, the creatinine measurement reagent is supported on the carrier by drying, and the carrier contacts the sample. What is necessary is just to provide in a part. Alternatively, the reagent for measuring creatinine may be arranged by directly applying a solution containing the reagent for measuring creatinine on the wall surface of the part in contact with the sample in the measuring device and then drying.

  The measurement device is preferably attached to a measurement device attachment portion of the measurement apparatus in a detachable state. In particular, when a biological fluid such as urine or blood is used, the measuring device is preferably disposable from a hygienic viewpoint.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings.

(Embodiment 1)
A creatinine measuring device 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 creatinine measuring device according to the present embodiment.

  The creatinine measuring device 100 according to the present embodiment is used in a creatinine measuring method for electrochemically quantifying the concentration of creatinine contained in a sample. The creatinine measuring device 100 according to the present embodiment has a structure in which an insulating first substrate 102 and a second substrate 104 having air holes 108 are combined with a spacer 106 having a slit 110 interposed therebetween. Yes.

  The first substrate 102 is electrically connected to the first electrode 112, the second electrode 114, the first lead 122 electrically connected to the first electrode 112, and the second electrode 114. A second lead 124 is disposed. A reagent layer 130 containing a reagent for measuring creatinine is disposed on the first electrode 112 and the second electrode 114. The dimensions of the first substrate 102 may be set as appropriate. For example, the width is about 7 mm, the length is about 30 mm, and the thickness is about 0.7 mm.

Next, a method for manufacturing the creatinine measuring device 100 will be described. In the present embodiment, as an active ingredient of a reagent for measuring creatinine, [Os (bpy) (5,5′-dmbpy) which is an osmium complex having a redox potential of 600 mV (vs Ag / AgCl) at pH 7 and 25 ° C. ₂ ] ^{2 + / 3 +} is used.

  First, palladium is sputtered on a first substrate 102 made of polyethylene terephthalate with a resin electrode pattern mask placed thereon, whereby a first electrode 112, a second electrode 114, a first lead 122, And a second lead 124 is formed. The first electrode 112 and the second electrode 114 are electrically connected to terminals of a creatinine measuring device described later by a first lead 122 and a second lead 124, respectively.

Next, on the first electrode 112 and the second electrode 114 provided over the first substrate 102, [Os (bpy) (5,5′-dmbpy) ₂ ] (PF ₆ ) ₂ Cl, phosphorus After a certain amount of an aqueous solution in which potassium dihydrogen phosphate and dipotassium hydrogen phosphate are dissolved using a microsyringe or the like, the first substrate 102 is allowed to stand in an environment of room temperature to 30 ° C. and dried. Thus, the reagent layer 130 is formed. The concentration and amount of the aqueous solution containing the reagent to be applied may be selected according to the required characteristics and size of the device. For example, [Os (bpy) (5,5′-dmbpy) in the aqueous solution containing the reagent ₂ ] (PF ₆ ) ₂ Cl has a concentration of about 8 mg / dL and a dripping amount of about 0.7 mL. In addition, the area of the region in which the reagent layer 130 is formed may be appropriately selected in view of the solubility of the reagent with respect to the sample, but the area is, for example, about 3 mm ² .

  Next, the first substrate 102 on which the electrode and reagent layer 130 is formed, the polyethylene terephthalate spacer 106 having the slit 110, and the second substrate 104 having the air holes 108 are combined. An adhesive is applied to each joint portion of the first substrate 102, the spacer 106, and the second substrate 104, and these are bonded to each other, and then pressed to stand and adhere. Instead of this method, after combining without applying an adhesive, the joining portion may be welded by heat or ultrasonic waves using a commercially available welding machine.

  When the first substrate 102, the spacer 106, and the second substrate 104 are combined, the space formed by the slits 110 and the second substrate 104 provided in the first substrate 102, the spacer 106 is stored in the sample. Functions as a chamber. In addition, the opening of the slit 110 functions as the sample inlet 132.

  Next, a creatinine measuring apparatus according to the present embodiment and a creatinine measuring method using the same will be described with reference to FIGS. FIG. 2 is a perspective view showing the appearance of the creatinine measuring apparatus 200 according to the present embodiment, and FIG. 3 is a block diagram showing the configuration of the creatinine measuring apparatus 200.

  First, the configuration of the creatinine measuring apparatus 200 will be described with reference to FIG.

  The casing 202 of the creatinine measuring apparatus 200 has a measurement device mounting portion 208 for mounting the creatinine measuring device 100 on the creatinine measuring apparatus 200, a display 204 on which the measurement results are displayed, and the measurement of creatinine by the creatinine measuring apparatus 200. A measurement start button 206 for starting is provided. In addition, the measurement device attachment portion 208 includes a first terminal electrically connected to the first lead 122 and the second lead 124 of the creatinine measurement device 100 attached to the measurement device attachment portion 208, respectively. A second terminal is provided.

  Next, the configuration inside the housing 202 of the creatinine measuring apparatus 200 will be described with reference to FIG.

  The creatinine measuring apparatus 200 includes a voltage application unit 302, an electric signal detection unit 304, a control unit 306, a timing unit 308, and a storage unit 310 inside the housing 202.

  The voltage application unit 302 is connected to the first lead 122 and the second lead 124 of the creatinine measurement device 100 attached to the measurement device attachment unit 208 via a first terminal and a second terminal, respectively. Thus, the voltage or potential is applied to the first electrode 112 and the second electrode 114 of the creatinine measuring device 100.

  The electric signal detection unit 304 has a function of detecting and measuring the electric signals from the first electrode 112 and the second electrode 114 via the first terminal and the second terminal. The electric signal detection unit 304 corresponds to the detection unit in the present invention.

  The storage unit 310 stores correlation data corresponding to a calibration curve representing the correlation between the concentration of creatinine and the electrical signal detected by the electrical signal detection unit 304. As the storage unit 310, for example, a memory such as a RAM or a ROM can be used.

  The control unit 306 has a function of converting the electrical signal detected and determined by the electrical signal detection measurement unit 304 into a creatinine concentration with reference to the correlation data. The control unit 306 corresponds to the calculation unit in the present invention. As the control unit 306, for example, a microcomputer such as a CPU (Central Processing Unit) can be used.

  Next, the creatinine measuring method according to the present embodiment using the creatinine measuring device 100 and the creatinine measuring apparatus 200 will be described.

  First, the user inserts the lead side of the creatinine measuring device 100 into the measuring device mounting portion 208 of the creatinine measuring apparatus 200. As a result, the first lead 122 and the second lead 124 of the creatinine measuring device 100 come into contact with the first terminal and the second terminal provided inside the measuring device mounting portion 208, respectively. Conducted to.

  When the creatinine measurement device 100 is inserted into the measurement device attachment unit 208, a measurement device insertion detection switch including a micro switch provided in the measurement device attachment unit 208 is activated and outputs a signal to the control unit 306. When the control unit 306 detects the insertion of the creatinine measurement device 100 based on the output signal from the measurement device insertion detection switch, the control unit 306 controls the voltage application unit 302, via the first terminal and the second terminal, A voltage (for example, 0.2 V) is applied between the first electrode 112 and the second electrode 114.

  Next, the user brings the sample into contact with the sample inlet 132 of the creatinine measuring device 100. By this contact, the sample is sucked into the sample storage chamber of the creatinine measuring device 100 through the sample introduction port 132 by capillary action, and the sample storage chamber is filled with the sample. When the sample comes into contact with the first electrode 112 and the second electrode 114, current flows between the first electrode 112 and the second electrode 114 through the sample. The electrical signal detection unit 304 detects it.

  When the control unit 306 detects that the sample has been introduced into the sample storage chamber based on the output signal from the electrical signal detection unit 304, the control unit 306 controls the voltage application unit 302 to apply the voltage applied by the voltage application unit 302. Switch to a different voltage (eg 0V or open circuit). In addition, along with the detection of sample introduction, the control unit 306 starts timing by the timer unit 308 that is a timer.

When the reagent layer 130 exposed in the sample storage chamber comes into contact with the sample, [Os (bpy) (5,5′-dmbpy) ₂ ] (PF ₆ ) _{2 in the} reagent for measuring creatinine contained in the reagent layer 130. Cl dissolves in the sample. [Os (bpy) (5,5′-dmbpy) ₂ ] (PF ₆ ) ₂ Cl produced by dissolution in the sample [Os (bpy) (5,5′-dmbpy) ₂ ] ³⁺ in the sample The creatinine oxide and [Os (bpy) (5,5′-dmbpy) ₂ ] ²⁺ are produced by a direct reaction with creatinine contained in the.

When the control unit 306 determines that a predetermined time (for example, 60 seconds) has elapsed based on a signal from the time measuring unit 308, the control unit 306 controls the voltage application unit 302 to control the first electrode 112 and the second electrode. A different voltage is applied between the first electrode 112 and the second electrode 114 (for example, a voltage at which the first electrode 112 becomes +0.5 V compared to the second electrode 114). In this way, an electrical signal such as a current flowing between the first electrode 112 and the second electrode 114 is measured by the electrical signal detection unit 304 after a certain time (for example, 5 seconds) has elapsed since the voltage was applied. At this time, [Os (bpy) (5,5′-dmbpy) ₂ ] ²⁺ is oxidized at the first electrode 112. The electrical signal measured by the electrical signal detection unit 304 depends on the concentration of creatinine contained in the sample.

  The control unit 306 reads the correlation data representing the correlation between the electrical signal stored in the storage unit 310 and the creatinine concentration, and refers to it to convert the electrical signal detected by the electrical signal detection unit 304 into the creatinine concentration in the sample. Convert to.

  The obtained creatinine concentration is displayed on the display 204. By displaying the creatinine concentration on the display 204, the user knows that the creatinine concentration measurement has been completed. The obtained creatinine concentration is preferably stored in the storage unit 310 together with the time measured by the time measuring unit 308.

  According to the creatinine measuring device 100 according to the present embodiment, unlike the conventional measuring device, the creatinine and the creatinine measuring reagent described above in the reagent for measuring creatinine even in a state where there is no enzyme or picric acid acting on creatinine in the sample storage chamber. Since the osmium complex directly reacts with the osmium complex, the reaction proceeds without being affected by interference components such as ionic species such as salt, urea, amino acids, and sugars. Therefore, even when a biological sample such as urine or blood is used, creatinine contained in the sample can be quantified with higher accuracy than conventional measurement devices.

In the present embodiment, an example in which [Os (bpy) (5,5′-dmbpy) ₂ ] ^{2 + / 3 +} is used as an active ingredient contained in the creatinine measurement reagent has been described, but instead [Os ( 4,4′-dmbpy) ₂ (5,5′-dmbpy)] ^{2 + / 3 +} or [Os (5,5′-dmbpy) ₂ (dpa)] ^{2 + / 3 +} may be used. [Os (4,4′-dmbpy) ₂ (5,5′-dmbpy)] ^{2 + / 3 +} or [Os (5,5′-dmbpy) ₂ (dpa)] ²⁺ as an active ingredient contained in the reagent for measuring creatinine ^{Even when / 3 +} is used, creatinine contained in a sample can be quantified more accurately than conventional measurement devices without being affected by interference components such as ionic species such as salt, urea, amino acids, and sugars. .

  Moreover, in this Embodiment, it is not limited to this which showed the example in which a creatinine measuring device is provided with one reagent layer. The creatinine measuring device may include two reagent layers, for example, a first reagent layer containing a creatinine measuring reagent and a second reagent layer containing a phosphate buffer.

  In the present embodiment, an example in which the control unit detects that a sample has been introduced into the sample storage chamber and the voltage applied by the voltage application unit is switched to a different voltage has been described, but the present invention is not limited thereto. As long as a current dependent on the concentration of creatinine is obtained, the voltage value required for measurement (here, as described above, for example, the voltage at which the first electrode becomes +0.5 V compared to the second electrode) is used as the creatinine. If the voltage is applied from the time of detecting the insertion of the measuring device, the voltage value may be continuously applied after the sample is detected.

Further, although an example in which the potential applied to the first electrode for obtaining an electric signal is set to 500 mV with respect to the second electrode is described in this embodiment mode, the present invention is not limited to this. The voltage between the first electrode and the second electrode may be a voltage at which [Os (bpy) (5,5′-dmbpy) ₂ ] ²⁺ generated by the oxidation-reduction reaction with creatinine is oxidized. .

In the present embodiment, an example in which the time (reaction time) until detection of an electrical signal after detection of a sample is set to 60 seconds is shown, but the value is not necessarily required. As long as a difference in current value with respect to a difference in creatinine concentration can be detected significantly, a reaction time smaller than the above can be used. On the other hand, when the reaction time is made longer, the possibility that the reaction between creatinine and [Os (bpy) (5,5′-dmbpy) ₂ ] ³⁺ reaches a complete state or a steady state increases. It becomes easy to quantify the abundance of creatinine without being affected by the above.

  Moreover, although the example which detects an electrical signal 5 seconds after applying an electric potential to an electrode was shown, it is not limited to this time. This time should just be the time which can detect the difference of an electrical signal with respect to the difference in creatinine concentration significantly.

  In this embodiment, an example of the electrode system and the lead / terminal is shown, but the shape, number, arrangement, etc. thereof are not limited to these.

  Further, in order to more smoothly introduce the sample into the sample storage chamber of the creatinine measuring device, a solution obtained by dissolving lecithin in toluene or other organic solvent is applied to the inner wall of the second substrate and dried. A lecithin layer may be formed. By adopting such a structure, the amount of the sample can be made constant with higher reproducibility, so that creatinine contained in the sample can be quantified with higher accuracy.

  The creatinine measuring apparatus may further include a recording unit for recording the creatinine concentration obtained as a measurement result on a storage medium such as an SD card. By storing in a removable storage medium, the measurement result can be easily taken out from the creatinine measurement device, so that it becomes easy to request an analysis related company to analyze the measurement result.

  Moreover, the creatinine measuring device may further include a transmission unit for transmitting the creatinine concentration obtained as a measurement result to the outside of the creatinine measuring device. As a result, measurement results can be sent to analysis-related departments or analysis-related contractors in hospitals and analyzed at analysis-related departments or analysis-related contractors, so the time from measurement to analysis can be reduced. .

  The creatinine measuring apparatus may further include a receiving unit for receiving the result of analysis in an analysis related department or an analysis related business. As a result, the analysis result can be quickly fed back to the user.

(Embodiment 2)
Next, a urinary salt content measuring device according to Embodiment 2 of the present invention will be described with reference to FIGS. FIG. 4 is an exploded perspective view showing a configuration of the urinary salt content measuring device according to the present embodiment as viewed from the first surface side of the first substrate, and FIG. 5 is a urinary salt content according to the present embodiment. It is a disassembled perspective view which shows the structure which looked at the measuring device from the 2nd surface side of the 1st board | substrate.

  The urinary salt content measuring device 700 according to the present embodiment electrochemically measures creatinine contained in urine as a sample and measures the electrical characteristics of urine, and uses these measurement results for one day. It is used in a method for estimating the amount of salt contained in urine excreted in urine.

  In the urinary salt content measuring device 700 according to the present embodiment, the first substrate 102 having the insulating property and the second substrate 104 having the air holes 108 are connected to the first surface 702 of the first substrate 102 and the first substrate 702. The third substrate 704 having the first spacer 102 having the slit 110 and the insulating first substrate 102 and the air hole 708 is combined with the first spacer 106 so as to be in contact with the first spacer 106. 102 has a structure in which a second spacer 706 having a slit 710 is sandwiched so that the second surface 802 of 102 and the second spacer 706 are in contact with each other.

  Similar to the creatinine measurement device 100 according to Embodiment 1, the first electrode 112, the second electrode 114, and the first electrode 112 are electrically connected to the first surface 702 of the first substrate 102. A first lead 122 connected and a second lead 124 electrically connected to the second electrode 114 are disposed. A reagent layer 130 containing a reagent for measuring creatinine is disposed on the first electrode 112 and the second electrode 114.

  On the other hand, on the second surface 802 of the first substrate 102, the third electrode 712, the fourth electrode 714, the fifth electrode 716, the sixth electrode 718, and the third electrode 712 are electrically connected. The third lead 722 connected, the fourth lead 724 electrically connected to the fourth electrode 714, the fifth lead 726 electrically connected to the fifth electrode 716, and the sixth electrode A sixth lead 728 electrically connected to 718 is disposed. The dimensions of the first substrate 102 may be set as appropriate. For example, the width is about 7 mm, the length is about 30 mm, and the thickness is about 0.7 mm.

  Next, a method for manufacturing the urinary salt content measuring device 700 will be described.

  First, palladium is sputtered on the first surface 702 of the first substrate 102 made of polyethylene terephthalate with a resin electrode pattern mask placed thereon, whereby the first electrode 112 and the second electrode 114 are sputtered. First lead 122 and second lead 124 are formed. The first electrode 112 and the second electrode 114 are electrically connected to a terminal of a urinary salt content measuring device described later by a first lead 122 and a second lead 124, respectively.

  Next, palladium is sputtered on the second surface 802 of the first substrate 102 with an electrode pattern mask having a pattern different from the above electrode pattern mask, whereby the third electrode 712, The fourth electrode 714, the fifth electrode 716, the sixth electrode 718, the third lead 722, the fourth lead 724, the fifth lead 726, and the sixth lead 728 are formed. The third electrode 712, the fourth electrode 714, the fifth electrode 716, and the sixth electrode 718 are respectively a third lead 722, a fourth lead 724, a fifth lead 726, and a sixth lead. 728 is electrically connected to a terminal of a urinary salt content measuring device described later.

Next, on the first electrode 112 and the second electrode 114 provided on the first surface 702 of the first substrate 102, a reagent for measuring creatinine [Os (bpy) (5,5′− dmbpy) ₂ ] (PF ₆ ) ₂ Cl, potassium dihydrogen phosphate, and an aqueous solution in which dipotassium hydrogen phosphate are dissolved are dropped using a microsyringe or the like, and then the first substrate 102 is placed at room temperature to 30 ° C. The reagent layer 130 is formed by allowing it to stand in an environment of about 0 ° C. and drying. The concentration and amount of the aqueous solution containing the reagent to be applied may be selected according to the required characteristics and size of the device. For example, [Os (bpy) (5,5′-dmbpy) in the aqueous solution containing the reagent ₂ ] (PF ₆ ) ₂ Cl has a concentration of about 8 mg / dL and a dripping amount of about 0.7 mL. In addition, the area of the region in which the reagent layer 130 is formed may be appropriately selected in view of the solubility of the reagent with respect to the sample, but the area is, for example, about 3 mm ² .

  Next, the air holes 108 are formed so that the first surface 702 of the first substrate 102 is in contact with the first spacer 106 and the second surface 802 of the first substrate 102 is in contact with the second spacer 706. A second substrate 104 having a slit, a first spacer 106 made of polyethylene terephthalate having a slit 110, a first substrate 102, a second spacer 706 made of polyethylene terephthalate having a slit 710, and a third having an air hole 708. The substrate 704 is combined. An adhesive is applied to each joint portion of each member, and after pasting them together, they are pressed and allowed to stand and adhere. Instead of this method, after combining without applying an adhesive, the joining portion may be welded by heat or ultrasonic waves using a commercially available welding machine.

  When the first substrate 102, the first spacer 106, and the second substrate 104 are combined, the first substrate 102, the slit 110 provided in the first spacer 106, and the second substrate 104 are formed. The space functions as a first sample storage chamber for creatinine measurement. Further, the opening of the slit 110 functions as a first sample introduction port 132 for measuring creatinine.

  On the other hand, when the first substrate 102, the second spacer 706, and the third substrate 704 are combined, the first substrate 102, the slit 710 provided in the second spacer 706, and the third substrate 704 are formed. The space portion to be functioned as a second sample storage chamber for electrical characteristics of urine. Further, the opening of the slit 710 functions as a second sample introduction port 732 for electrical characteristics of urine.

  Next, a urinary salt content measuring apparatus and a urinary salt content measuring method using the same according to the present embodiment will be described with reference to FIGS. FIG. 6 is a perspective view showing the external appearance of the urinary salt content measuring apparatus 900 according to the present embodiment, and FIG. 7 is a block diagram showing the configuration of the urinary salt content measuring apparatus 900.

  First, the configuration of the urinary salt content measuring apparatus 900 will be described with reference to FIG.

  The housing 202 of the urinary salt content measuring apparatus 900 has a measurement device mounting unit 208 for attaching the urinary salt content measuring device 700 to the urinary salt content measuring apparatus 900, a display 204 on which measurement results and the like are displayed, and A measurement start button 206 for starting measurement of the electrical characteristics of creatinine and urine by the urinary salt content measuring apparatus 900 is provided. In addition, the measurement device attachment portion 208 includes a first lead 122, a second lead 124, a third lead 722, and a fourth lead of the urinary salt content measurement device 700 attached to the measurement device attachment portion 208. A first terminal, a second terminal, a third terminal, a fourth terminal, a fifth terminal, and a fifth terminal electrically connected to the lead 724, the fifth lead 726, and the sixth lead 728, respectively. Six terminals are provided.

  Next, the internal structure of the housing 202 of the urinary salt content measuring apparatus 900 will be described with reference to FIG.

  The urinary salt content measuring apparatus 900 includes a voltage application unit 302, an electric signal detection unit 304, a constant current AC power source 902, a voltage detector 904, a control unit 306, a timing unit 308, and a storage unit 310 inside the housing 202. I have.

  The voltage application unit 302 includes a first terminal and a second terminal that are electrically connected to the first lead 122 and the second lead 124 of the urinary salt content measurement device 700 attached to the measurement device attachment unit 208, respectively. It has a function of applying a voltage or a potential to the first electrode 112 and the second electrode 114 of the urinary salt content measuring device 700 via the terminal.

  The electric signal detection unit 304 has a function of detecting and measuring the electric signals from the first electrode 112 and the second electrode 114 via the first terminal and the second terminal. The electric signal detection unit 304 corresponds to the detection unit in the present invention.

  The constant current AC power source 902 includes a third terminal and a sixth terminal electrically connected to the third lead 722 and the sixth lead 728 of the urinary salt content measuring device 700 attached to the measuring device attachment unit 208, respectively. The terminal has a function of applying a constant alternating current between the third electrode 712 and the sixth electrode 718 of the urinary salt content measuring device 700 through the terminal. The alternating current to be applied has, for example, a frequency of about 1 kHz and a current value of about 0.1 mA.

  The voltage detector 904 has a function of detecting a voltage (effective value of an alternating voltage) between the fourth electrode 714 and the fifth electrode 716 through the fourth terminal and the fifth terminal.

  The storage unit 310 detects the first correlation data corresponding to the first calibration curve representing the correlation between the concentration of creatinine and the electrical signal detected by the electrical signal detection unit 304, and the salt concentration and voltage detector 904 detects the correlation. Second correlation data corresponding to a second calibration curve representing the correlation with the applied voltage, and a third calibration curve representing the correlation between the daily urinary salt excretion amount and the salt concentration corrected by the creatinine concentration The third correlation data corresponding to is stored. As the storage unit 310, for example, a memory such as a RAM or a ROM can be used.

  The control unit 306 refers to the first correlation data, functions to convert the electrical signal detected by the electrical signal detection measurement unit 304 into a creatinine concentration, and refers to the second correlation data by the voltage detector 904. The function of converting the detected voltage into a salinity concentration, the function of correcting the salinity concentration using the obtained creatinine concentration, and the third correlation data, the corrected salinity concentration per day in the urine salt Has a function to convert to excretion. The control unit 306 corresponds to the calculation unit in the present invention. As the control unit 306, for example, a microcomputer such as a CPU (Central Processing Unit) can be used.

  Next, the urinary salt content measuring method according to the present embodiment using the urinary salt content measuring device 700 and the urinary salt content measuring apparatus 900 will be described.

  First, the user inserts the lead side of the urinary salt content measurement device 700 into the measurement device mounting portion 208 of the urinary salt content measurement device 900. Accordingly, the first lead 122, the second lead 124, the third lead 722, the fourth lead 724, the fifth lead 726, and the sixth lead 728 of the urinary salt content measuring device 700 are measured. The first terminal, the second terminal, the third terminal, the fourth terminal, the fifth terminal, and the sixth terminal provided in the device mounting portion 208 are electrically connected to each other. Conduct.

  When the urinary salt content measurement device 700 is inserted into the measurement device attachment unit 208, a measurement device insertion detection switch including a micro switch provided in the measurement device attachment unit 208 is activated to output a signal to the control unit 306. To do. When the control unit 306 detects the insertion of the urinary salt content measurement device 700 based on the output signal from the measurement device insertion detection switch, the control unit 306 controls the voltage application unit 302 to switch the first terminal and the second terminal. Thus, a voltage (for example, 0.2 V) is applied between the first electrode 112 and the second electrode 114.

  Next, the user brings the sample into contact with the first sample inlet 132 and the second sample inlet 732 of the urinary salt content measuring device 700. By this contact, the sample is sucked into the two sample storage chambers of the urinary salt content measuring device 700 through the first sample introduction port 132 and the second sample introduction port 732 by capillary action, and thus the two sample storage chambers. Is filled with the sample. When the sample comes into contact with the first electrode 112 and the second electrode 114, current flows between the first electrode 112 and the second electrode 114 through the sample. The electrical signal detection unit 304 detects it.

  When the control unit 306 detects that the sample has been introduced into the sample storage chamber based on the output signal from the electrical signal detection unit 304, the control unit 306 controls the voltage application unit 302 to apply the voltage applied by the voltage application unit 302. Switch to a different voltage (eg 0V or open circuit). In addition, along with the detection of sample introduction, the control unit 306 starts timing by the timer unit 308 that is a timer.

  Along with the detection of the sample introduction, the control unit 306 controls the constant current AC power source 902 to be constant between the third electrode 712 and the sixth electrode 718 via the third terminal and the sixth terminal. AC current (for example, frequency 1 kHz, current value 0.1 mA) is applied. The voltage detector 904 measures the voltage (effective value of the alternating current) between the fourth electrode 714 and the fifth electrode 716 after a predetermined time has elapsed from the application of the alternating current (for example, after 5 seconds).

  The control unit 306 reads the second correlation data representing the correlation between the salinity concentration stored in the storage unit 310 and the voltage detected by the voltage detector 904, and the voltage detector 904 detects the correlation data by referring to it. The applied voltage is converted to the salinity concentration in the sample. The obtained salinity concentration is displayed on the display 204.

When the reagent layer 130 exposed in the first sample storage chamber for creatinine measurement comes into contact with the sample, [Os (bpy) (5,5′-dmbpy) in the creatinine measurement reagent contained in the reagent layer 130 ₂ ] (PF ₆ ) ₂ Cl dissolves in the sample. [Os (bpy) (5,5′-dmbpy) ₂ ] (PF ₆ ) ₂ Cl produced by dissolution in the sample [Os (bpy) (5,5′-dmbpy) ₂ ] ³⁺ in the sample The creatinine oxide and [Os (bpy) (5,5′-dmbpy) ₂ ] ²⁺ are produced by a direct reaction with creatinine contained in the.

  When the control unit 306 determines that a predetermined time (for example, 60 seconds) has elapsed based on a signal from the time measuring unit 308, the control unit 306 controls the voltage application unit 302 to control the first electrode 112 and the second electrode. A different voltage is applied between the first electrode 112 and the second electrode 114 (for example, a voltage at which the first electrode 112 becomes +0.5 V compared to the second electrode 114). In this way, an electrical signal such as a current flowing between the first electrode 112 and the second electrode 114 is measured by the electrical signal detection unit 304 after a certain time (for example, 5 seconds) has elapsed since the voltage was applied. At this time, the reduced form of the osmium complex is oxidized at the first electrode 112. The electrical signal measured by the electrical signal detection unit 304 depends on the concentration of creatinine contained in the sample.

  The control unit 306 reads the first correlation data representing the correlation between the electrical signal stored in the storage unit 310 and the creatinine concentration, and refers to the first correlation data to detect the electrical signal detected by the electrical signal detection unit 304 in the sample. Convert to creatinine concentration.

  Next, the control unit 306 corrects the salinity concentration using the obtained creatinine concentration. Subsequently, the control unit 306 stores third correlation data corresponding to a third calibration curve representing the correlation between the daily urinary salt excretion amount stored in the storage unit 310 and the salt concentration corrected by the creatinine concentration. Is read, and the corrected salt concentration is converted into the amount of urinary salt excretion per day.

  The obtained creatinine concentration and the daily urinary salt excretion amount are displayed on the display 204. By displaying the creatinine concentration and the daily urinary salt excretion amount on the display 204, the user knows that the measurement has been completed. The obtained creatinine concentration and daily urinary salt excretion amount are preferably stored in the storage unit 310 together with the time measured by the time measuring unit 308.

  According to the urinary salt content measuring device 700 according to the present embodiment, unlike the conventional measuring device, the creatinine and the reagent for measuring creatinine are present in the sample storage chamber even in the absence of an enzyme or picric acid that acts on creatinine. Since the osmium complex directly reacts with the osmium complex, the reaction proceeds without being affected by interference components such as ionic species such as salt, urea, amino acids, and sugars. Therefore, even when a biological sample such as urine or blood is used, creatinine contained in the sample can be quantified with higher accuracy than conventional measurement devices.

  Moreover, according to the urinary salt amount measuring apparatus 900 according to the present embodiment, the urinary salt excretion amount per day is calculated based on the salt concentration corrected by the creatinine concentration measured with high accuracy. Therefore, the amount of urinary salt excretion per day can be obtained with high accuracy.

In the present embodiment, an example in which [Os (bpy) (5,5′-dmbpy) ₂ ] ^{2 + / 3 +} is used as the active ingredient in the creatinine measurement reagent has been described. Instead, [Os (4 , 4′-dmbpy) ₂ (5,5′-dmbpy)] ^{2 + / 3 +} or [Os (5,5′-dmbpy) ₂ (dpa)] ^{2 + / 3 +} . [Os (4,4′-dmbpy) ₂ (5,5′-dmbpy)] ^{2 + / 3 +} or [Os (5,5′-dmbpy) ₂ (dpa)] ^{2 + /} as an active ingredient in the reagent for measuring creatinine ^{Even when 3+} is used, creatinine contained in a sample can be quantified more accurately than a conventional measurement device without being affected by interference components such as ionic species such as salt, urea, and amino acids.

  Moreover, in this Embodiment, it is not limited to this which showed the example in which the urinary salt content measuring device is provided with one reagent layer. The urinary salt content measuring device may include two reagent layers, for example, a first reagent layer containing a reagent for measuring creatinine and a second reagent layer containing a phosphate buffer.

  In the present embodiment, an example in which the control unit detects that a sample has been introduced into the sample storage chamber and the voltage applied by the voltage application unit is switched to a different voltage has been described, but the present invention is not limited thereto. As long as a current dependent on the concentration of creatinine is obtained, the voltage value required for measurement (here, as described above, for example, the voltage at which the first electrode becomes +0.5 V compared to the second electrode) is used as the creatinine. If the voltage is applied from the time of detecting the insertion of the measuring device, the voltage value may be continuously applied after the sample is detected.

Further, although an example in which the potential applied to the first electrode for obtaining an electric signal is set to 500 mV with respect to the second electrode is described in this embodiment mode, the present invention is not limited to this. The voltage between the first electrode and the second electrode may be a voltage at which [Os (bpy) (5,5′-dmbpy) ₂ ] ²⁺ generated by the oxidation-reduction reaction with creatinine is oxidized. .

In the present embodiment, an example in which the time (reaction time) until detection of an electrical signal after detection of a sample is set to 60 seconds is shown, but the value is not necessarily required. As long as a difference in current value with respect to a difference in creatinine concentration can be detected significantly, a reaction time smaller than the above can be used. On the other hand, when the reaction time is made longer, the possibility that the reaction between creatinine and [Os (bpy) (5,5′-dmbpy) ₂ ] ³⁺ reaches a complete state or a steady state increases. It becomes easy to quantify the abundance of creatinine without being affected by the above.

  Moreover, although the example which detects an electric signal 5 seconds after applying a voltage between a 1st electrode and a 2nd electrode was shown, it is not limited to this time. This time should just be the time which can detect the difference of an electrical signal with respect to the difference in creatinine concentration significantly.

  Further, in the present embodiment, the storage unit stores the first correlation data corresponding to the first calibration curve representing the correlation between the concentration of creatinine and the electrical signal detected by the electrical signal detection unit 304, the concentration of salinity, and the like. The second correlation data corresponding to the second calibration curve representing the correlation with the voltage detected by the voltage detector 904, and the correlation between the daily urinary salt excretion amount and the salt concentration corrected by the creatinine concentration Although the example in which the third correlation data corresponding to the third calibration curve to be expressed is stored is shown, the present invention is not limited to this. Instead, correlation data indicating the correlation between the electrical signal detected by the electrical signal detection unit, the voltage detected by the voltage detector, and the urinary salt excretion per unit time (for example, 1 day) is stored in the storage unit. It may be stored. In this case, the urinary salt excretion per unit time can be directly calculated using the electric signal detected by the electric signal detector and the voltage detected by the voltage detector without obtaining the creatinine concentration and the salt concentration. Can be sought.

  In this embodiment, an example of the electrode system and the lead / terminal is shown, but the shape, number, arrangement, etc. thereof are not limited to these.

  In order to more smoothly introduce the sample into the sample storage chamber of the urinary salt content measuring device, a solution obtained by dissolving lecithin in toluene or another organic solvent is used as the inner wall of the second substrate and the third substrate. You may form a lecithin layer by apply | coating to and drying. By adopting such a structure, the amount of the sample can be made constant with higher reproducibility, so that creatinine and salt contained in the sample can be quantified with higher accuracy.

  The urinary salt content measuring device may further include a recording unit for recording the creatinine concentration, the salinity concentration, and the daily urinary salt excretion obtained as a measurement result in a storage medium such as an SD card. Good. By storing in the removable storage medium, the measurement result can be easily taken out from the urinary salt content measuring device, so that it becomes easy to request the analysis related company to analyze the measurement result.

  The urinary salt content measuring device further includes a transmission unit for transmitting the creatinine concentration, the salinity concentration and the daily urinary salt excretion obtained as a measurement result to the outside of the urinary salt content measuring device. Also good. As a result, measurement results can be sent to analysis-related departments or analysis-related contractors in hospitals and analyzed at analysis-related departments or analysis-related contractors, so the time from measurement to analysis can be reduced. .

  In addition, the urinary salt content measuring device may further include a receiving unit for receiving the result of analysis in an analysis related department or an analysis related business. As a result, the analysis result can be quickly fed back to the user.

Example 1
In order to confirm the effect of the creatinine measuring method according to the present invention, the following experiment was conducted. In this example, [Os (bpy) (5,5′-dmbpy) ₂ ] which is an osmium complex having an oxidation-reduction potential of 600 mV (vs Ag / AgCl) at pH 7 and 25 ° C. as an active ingredient in the reagent for measuring creatinine. ^{2 + / 3 +} was used.

First, a 400 mM dipotassium hydrogen phosphate aqueous solution and a 400 mM potassium dihydrogen phosphate aqueous solution were prepared. The two aqueous solutions were alternately mixed while monitoring using a pH meter, thereby adjusting the pH of the resulting mixed aqueous solution to 6. [Os (bpy) (5,5′-dmbpy) ₂ ] (PF ₆ ) ₂ was dissolved in the thus obtained 400 mM phosphate buffer (pH = 6) to a concentration of 0.2 mM. did.

The obtained osmium complex aqueous solution was put in a glass cell container, a gold electrode (electrode area 2 mm ² ) was used as the first electrode, and a platinum wire having a length of 5 cm was wound as a second electrode, As an electrode, an Ag / AgCl (saturated KCl aqueous solution) reference electrode was used, and each was immersed in the aqueous solution in the cell container. All of these electrodes were commercially available from BAS Co., Ltd. The connection terminals of the first electrode, the second electrode, and the third electrode were sequentially connected to the connection terminal of the working electrode, the counter electrode, and the reference electrode of the ALS-660A electrochemical analyzer.

  Next, a small amount of a 500 mM creatinine aqueous solution was added to the aqueous solution in the cell container. The addition amount of the creatinine aqueous solution was adjusted for each measurement so that the creatinine concentration contained in the aqueous solution in the cell container became a predetermined value.

  Timing was started with the addition of creatinine. One minute after the addition of creatinine, a potential of 0.8 V was applied to the first electrode with respect to the third electrode, and the current value was measured 5 seconds after the potential application. This operation was repeated every minute until 10 minutes and 5 seconds after the addition of creatinine. The above experiment was performed at room temperature (about 25 ° C.).

  When the creatinine concentration contained in the aqueous solution in the cell container was 0, 3, 9, and 27 mM, the above measurements were performed.

FIG. 8 is a graph plotting the current value measured 10 minutes and 5 seconds after the addition of creatinine against the creatinine concentration. In FIG. 8, the horizontal axis represents the creatinine concentration (mM) contained in the aqueous solution in the cell container, and the vertical axis represents the measured current density (μA / cm ² ). As apparent from FIG. 8, the obtained current value increased linearly with the increase in the concentration of creatinine contained in the aqueous solution in the cell container, and the current value and the creatinine concentration showed a high correlation. Therefore, it can be seen that creatinine can be quantified based on the obtained current value by the creatinine measurement method according to the present invention.

  From the above results, the reaction in the creatinine measurement method according to the present invention can be explained as follows.

In the sample, [Os (bpy) (5,5′-dmbpy) ₂ ] ³⁺ is reduced by reacting with creatinine in the presence of a phosphate buffer, and [Os (bpy) (5,5′-dmbpy). ₂ ] Converted to ²⁺ . That is, creatinine is oxidized by donating electrons to [Os (bpy) (5,5′-dmbpy) ₂ ] ³⁺ by this reaction. Since a potential that accepts electrons from [Os (bpy) (5,5′-dmbpy) ₂ ] ²⁺ is applied to the first electrode, the generated [Os (bpy) (5,5 ′ -Dmbpy) ₂ ] ²⁺ is electrochemically oxidized at the first electrode. Along with this, a current flows through the first electrode. The concentration of [Os (bpy) (5,5′-dmbpy) ₂ ] ²⁺ generated in a certain time depends on the concentration of creatinine. Further, because it depends on the concentration of [Os (bpy) (5,5'- dmbpy) 2] oxidation current ²⁺ present in the sample [Os (bpy) (5,5'- dmbpy) 2] ^2+, The current value obtained depends on the concentration of creatinine.

(Example 2)
In this example, [Os (4,4′-dmbpy) ₂ (5,5) is an osmium complex having an oxidation-reduction potential of 500 mV (vs Ag / AgCl) at pH 7 and 25 ° C. as an active ingredient in the reagent for measuring creatinine. '-Dmbpy)] ^{2 + / 3 +} was used.

First, a 400 mM phosphate buffer solution (pH = 6) was prepared by the same procedure as in Example 1. [Os (4,4′-dmbpy) ₂ (5,5′-dmbpy)] (PF ₆ ) ₂ is added to the obtained 400 mM phosphate buffer solution (pH = 6) to a concentration of 0.05 mM. Dissolved. Since the apparatus configuration used for the measurement is the same as that of the first embodiment, description thereof is omitted.

  The obtained osmium complex aqueous solution was put into a glass cell container, and a creatinine aqueous solution having a concentration of 500 mM was added to the aqueous solution in the cell container to adjust the creatinine concentration in the osmium complex aqueous solution to 80 mM.

  The cyclic voltammogram was measured using an electrochemical analyzer before and after adding the creatinine aqueous solution to the osmium complex aqueous solution. The potential applied to the first electrode was swept at a rate of 1 mV / second in the range of 0.35 V to 0.65 V with respect to the third electrode.

  FIG. 9 shows the measurement result (cyclic voltammogram). In FIG. 9, the line A shows the cyclic voltammogram of the osmium complex aqueous solution measured before the addition of the creatinine aqueous solution, and the line B shows the cyclic voltammogram of the osmium complex aqueous solution measured after the addition of the creatinine aqueous solution.

In the absence of creatinine, redox reaction on the first electrode of [Os (4,4′-dmbpy) ₂ (5,5′-dmbpy)] ^{2 + / 3 +} with a redox potential around 0.5V. It was observed. The addition of creatinine significantly increased the current at a potential more positive than 0.55V. The above results indicate that creatinine is oxidized and produced by [Os (4,4′-dmbpy) ₂ (5,5′-dmbpy)] ³⁺ [Os (4,4′-dmbpy) ₂ (5,5 ′ -Dmbpy)] ²⁺ suggests oxidation at the first electrode. That is, it was found that the electrochemical catalytic oxidation reaction of creatinine proceeds through [Os (4,4′-dmbpy) ₂ (5,5′-dmbpy)] ^{2 + / 3 +} .

(Example 3)
In this example, [Os (5,5′-dmbpy) ₂ (dpa)] is an osmium complex having an oxidation-reduction potential of 380 mV (vs Ag / AgCl) at pH 7 and 25 ° C. as an active ingredient in the reagent for measuring creatinine. ^{2 + / 3 +} was used.

First, a 400 mM phosphate buffer solution (pH = 6) was prepared by the same procedure as in Example 1. [Os (5,5′-dmbpy) ₂ (dpa)] (PF ₆ ) ₂ was dissolved in the obtained 400 mM phosphate buffer solution (pH = 6) to a concentration of 0.05 mM. Since the apparatus configuration used for the measurement is the same as that of the first embodiment, description thereof is omitted.

  The obtained osmium complex aqueous solution was put into a glass cell container, and a creatinine aqueous solution having a concentration of 500 mM was added to the aqueous solution in the cell container to adjust the creatinine concentration in the osmium complex aqueous solution to 80 mM.

  The cyclic voltammogram was measured using an electrochemical analyzer before and after adding the creatinine aqueous solution to the osmium complex aqueous solution. The potential applied to the first electrode was swept at a rate of 1 mV / second in the range of 0.3 V to 0.6 V with respect to the third electrode.

  FIG. 10 shows the measurement result (cyclic voltammogram). In FIG. 10, the line A shows the cyclic voltammogram of the osmium complex aqueous solution measured before the addition of the creatinine aqueous solution, and the line B shows the cyclic voltammogram of the osmium complex aqueous solution measured after the addition of the creatinine aqueous solution.

In the absence of creatinine, a redox reaction on the first electrode of [Os (5,5′-dmbpy) ₂ (dpa)] ^{2 + / 3 +} was seen. By adding creatinine, the current at a potential more positive than 0.45 V was significantly increased. The above results indicate that creatinine is oxidized by [Os (5,5′-dmbpy) ₂ (dpa)] ³⁺ and the generated [Os (5,5′-dmbpy) ₂ (dpa)] ²⁺ is the first electrode. This suggests that it has been oxidized. That is, it was found that the electrochemical catalytic oxidation reaction of creatinine proceeds through [Os (5,5′-dmbpy) ₂ (dpa)] ^{2 + / 3 +} .

(Comparative Example 1)
Next, as Comparative Example 1, [Os (4m-Im) ₂ (5,5′-dmbpy) ₂ ] ^{2 + / 3 +} which is an osmium complex having a redox potential of 200 mV (vs Ag / AgCl) at pH 7 and 25 ° C. The same experiment as in Examples 2 and 3 was performed.

First, a 400 mM phosphate buffer solution (pH = 6) was prepared by the same procedure as in Example 1. [Os (4m-Im) ₂ (5,5′-dmbpy) ₂ ] (PF ₆ ) ₂ was dissolved in the obtained 400 mM phosphate buffer solution (pH = 6) to a concentration of 0.1 mM. It was. Since the apparatus configuration used for the measurement is the same as that of the first embodiment, description thereof is omitted.

  The obtained osmium complex aqueous solution was put into a glass cell container, and a creatinine aqueous solution having a concentration of 500 mM was added to the aqueous solution in the cell container to adjust the creatinine concentration in the osmium complex aqueous solution to 80 mM.

  The cyclic voltammogram was measured using an electrochemical analyzer before and after adding the creatinine aqueous solution to the osmium complex aqueous solution. The potential applied to the first electrode was swept at a rate of 1 mV / second in the range of 0.08 V to 0.38 V with respect to the third electrode.

  FIG. 11 shows the measurement result (cyclic voltammogram). In FIG. 11, the line A shows the cyclic voltammogram of the osmium complex aqueous solution measured before the addition of the creatinine aqueous solution, and the line B shows the cyclic voltammogram of the osmium complex aqueous solution measured after the addition of the creatinine aqueous solution.

In the absence of creatinine, a redox reaction on the first electrode of [Os (4m-Im) ₂ (5,5′-dmbpy) ₂ ] ^{2 + / 3 +} with a redox potential around 0.22 V was observed. It was. However, unlike Examples 2 and 3, no increase in current was observed due to the addition of creatinine. The above results show that [Os (4m-Im) ₂ (5,5′-dmbpy) ₂ ] ^{2 + / 3 +,} which is an osmium complex having a redox potential at pH 7 and 25 ° C. of 200 mV (vs Ag / AgCl), is creatinine. It indicates that there is no reaction.

(Comparative Example 2)
Next, as Comparative Example 2, using [Os (4m-Im) ₂ (4,4′-dmbpy) ₂ ], which is an osmium complex having a redox potential at pH 7 and 25 ° C. of 123 mV (vs Ag / AgCl), The same experiment as in Examples 2 and 3 was performed.

First, a 400 mM phosphate buffer solution (pH = 6) was prepared by the same procedure as in Example 1. [Os (4m-Im) ₂ (4,4′-dmbpy) ₂ ] (PF ₆ ) ₂ was dissolved in the obtained 400 mM phosphate buffer solution (pH = 6) to a concentration of 0.1 mM. It was. Since the apparatus configuration used for the measurement is the same as that of the first embodiment, description thereof is omitted.

  The obtained osmium complex aqueous solution was put into a glass cell container, and a creatinine aqueous solution having a concentration of 500 mM was added to the aqueous solution in the cell container to adjust the creatinine concentration in the osmium complex aqueous solution to 80 mM.

  The cyclic voltammogram was measured using an electrochemical analyzer before and after adding the creatinine aqueous solution to the osmium complex aqueous solution. The potential applied to the first electrode was swept at a rate of 1 mV / sec in the range of 0 V to 0.3 V with respect to the third electrode.

  FIG. 12 shows the measurement result (cyclic voltammogram). In FIG. 12, the line A shows the cyclic voltammogram of the osmium complex aqueous solution measured before the addition of the creatinine aqueous solution, and the line B shows the cyclic voltammogram of the osmium complex aqueous solution measured after the addition of the creatinine aqueous solution.

In the absence of creatinine, a redox reaction on the first electrode of [Os (4m-Im) ₂ (4,4′-dmbpy) ₂ ] ^{2 + / 3 +} with a redox potential around 0.15 V was observed. It was. However, unlike Examples 2 and 3, no increase in current was observed due to the addition of creatinine. The above results indicate that [Os (4m-Im) ₂ (4,4′-dmbpy) ₂ ] ^{2 + / 3 +,} which is an osmium complex having an oxidation-reduction potential of 123 mV (vs Ag / AgCl) at pH 7 and 25 ° C., is creatinine. It indicates that there is no reaction.

  From the results of Examples 2 and 3 and Comparative Examples 1 and 2, it was found that an osmium complex whose oxidation-reduction potential at pH 7 and 25 ° C. was more positive than 380 mV (vs Ag / AgCl) reacted well with creatinine.

  The present invention is useful for quantifying creatinine contained in a sample, particularly a biological sample such as urine.

The disassembled perspective view which shows the structure of the creatinine measuring device in one embodiment of this invention The perspective view which shows the external appearance of the creatinine measuring apparatus in the embodiment Block diagram showing the configuration of the creatinine measuring apparatus The disassembled perspective view which shows the structure which looked at the urinary salt content measuring device in other embodiment of this invention from the 1st surface side of the 1st board | substrate. The exploded perspective view which shows the structure which looked at the salt content measuring device in the urine from the 2nd surface side of the 1st board | substrate. The perspective view which shows the external appearance of the urinary salt content measuring apparatus in the embodiment Block diagram showing the configuration of the urinary salt content measuring device The graph which shows the relationship between the creatinine density | concentration in the sample in one Example of this invention, and the measured electric current value The graph which shows the relationship between the electric potential applied to the 1st electrode and the measured electric current value in the other Example of this invention. The graph which shows the relationship between the electric potential applied to the 1st electrode and the measured electric current value in the further another Example of this invention. The graph which shows the relationship between the electric potential applied to the 1st electrode in one comparative example of this invention, and the measured electric current value The graph which shows the relationship between the electric potential applied to the 1st electrode in the other comparative example of this invention, and the measured electric current value.

Explanation of symbols

100 Creatinine Measurement Device 102 First Substrate 104 Second Substrate 106 Spacer (First Spacer)
108,708 Air hole 110,710 Slit 112 First electrode 114 Second electrode 122 First lead 124 Second lead 130 Reagent layer 132 Sample inlet (first sample inlet)
200 creatinine measuring apparatus 202 casing 204 display 206 measurement start button 208 measuring device mounting unit 302 voltage applying unit 304 electrical signal detecting unit 306 control unit 308 timing unit 310 storage unit 700 urinary salt content measuring device 702 first surface 704 first 3rd substrate 706 2nd spacer 712 3rd electrode 714 4th electrode 716 5th electrode 718 6th electrode 722 3rd lead 724 4th lead 726 5th lead 728 6th lead 732 6th lead 2 Sample introduction port 802 Second surface 900 Urine salt content measuring device 902 Constant current AC power supply 904 Voltage detector

Claims (8)

(A) By contacting a sample containing creatinine with a reagent for measuring creatinine containing an osmium complex whose oxidation-reduction potential at pH 7 and 25 ° C. is more positive than 380 mV with respect to the silver-silver chloride electrode, A step of directly reacting the creatinine contained therein and the osmium complex to produce an oxide of creatinine;
(B) a step of electrochemically measuring the reaction in the step A; and (C) a creatinine measurement method including a step of determining the concentration or amount of the creatinine contained in the sample based on the measurement value in the step B. . In the step B, at least two electrodes are brought into contact with the sample,
Step B is
(D) applying a voltage between the two electrodes, and (E) detecting a value of electric current or a charge amount flowing between the two electrodes,
In step C,
The creatinine measurement method according to claim 1, wherein the concentration or amount of the creatinine contained in the sample is obtained based on the current value or the charge amount detected in the step E. Using urine as a sample,
In addition to steps A and B of the method for measuring creatinine according to claim 1,
(F) a step of measuring electrical characteristics of the urine before the urine and the reagent for measuring creatinine come into contact; and (G) a measured value in the process B and the electrical characteristics measured in the process F. A method for measuring urinary salt content, further comprising a step of obtaining a value reflecting the amount of salt excreted in urine based on the above. A creatinine measuring device used in the creatinine measuring method according to claim 1,
A sample storage chamber for storing a sample containing creatinine;
A sample inlet for communicating with the sample storage chamber and for introducing the sample into the sample storage chamber;
At least two electrodes disposed in the sample storage chamber;
A creatinine measuring device comprising a creatinine measuring reagent including an osmium complex, the redox potential at pH 7 and 25 ° C being more positive than 380 mV with respect to the silver-silver chloride electrode, disposed in the sample storage chamber. A urinary salt content measuring device used in the urinary salt content measuring method according to claim 3,
A first sample storage chamber for storing urine as a sample;
A first sample inlet for communicating with the first sample storage chamber and for introducing the urine into the first sample storage chamber;
At least two electrodes disposed in the first sample storage chamber;
A reagent for measuring creatinine, which is disposed in the first sample storage chamber and contains an osmium complex whose redox potential at pH 7 and 25 ° C. is more positive than 380 mV with respect to the silver-silver chloride electrode;
A second sample storage chamber for storing the urine;
A second sample inlet for communicating with the second sample storage chamber and for introducing the urine into the second sample storage chamber;
A urinary salt content measuring device comprising: at least two electrodes arranged in the second sample storage chamber. A measuring device mounting portion for mounting the creatinine measuring device according to claim 4,
A measurement unit that electrochemically measures a reaction between the creatinine measurement device attached to the measurement device attachment unit and the creatinine measurement reagent in the sample storage chamber, and the sample based on the measurement value in the measurement unit A creatinine measuring apparatus comprising a calculation unit for obtaining the concentration or amount of the creatinine contained therein. The creatinine measuring device further comprises at least two electrodes disposed in the sample storage chamber;
The measurement unit is
A voltage application unit that applies a voltage between the two electrodes, and a detection unit that detects a value of electric current or a charge amount flowing between the two electrodes,
The computing unit is
The creatinine measuring apparatus according to claim 6, wherein a concentration or amount of the creatinine contained in the sample is obtained based on the current value or the charge amount detected by the detection unit. A measuring device mounting portion for mounting the urinary salt content measuring device according to claim 5,
A first measurement unit that electrochemically measures a reaction between creatinine and the creatinine measurement reagent in the first sample storage chamber of the urinary salt content measurement device attached to the measurement device attachment unit;
A second measurement unit for measuring electrical characteristics of the urine in the second sample storage chamber of the urinary salt content measurement device attached to the measurement device attachment unit; and a measurement value in the first measurement unit; A urinary salt content measuring device including a calculation unit that obtains a value reflecting the amount of salt excreted in the urine based on the electrical characteristics measured by the second measuring unit.

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