Analysis device

Abstract

To provide a technique capable of ensuring long service life and measurement stability in a reference electrode using a porous member.SOLUTION: An analysis device comprises: a sensor having a detection portion that detects a specific substance in a test sample; a reference electrode that generates a constant electromotive force; and a connection block that connects the sensor and the reference electrode. The sensor has a flow path through which the test sample flows, and the detection portion is disposed so as to contact the test sample in the flow path. The reference electrode has a porous body, and an electrolyte solution is sealed inside the reference electrode. The connection block has a flow path having a first connection port, a second connection port, and a third connection port. The first connection port is connected to an outlet of the flow path of the sensor, the second connection port is connected to a flow path for discharging the test sample, and the opening surface of the third connection port faces downward. The porous body of the reference electrode is connected to the third connection port. The electrolyte solution inside the reference electrode and the test sample inside the flow path of the connection block are in contact with each other via the porous body.SELECTED DRAWING: Figure 3A

Description

[Technical Field]

[0001] The present disclosure relates to an analytical device. [Background technology]

[0002] Electrochemical measurement is a method for electrochemically measuring the properties of chemical substances. Among these, a flow-type electrochemical measurement device has a structure in which electrodes are arranged so as to be in contact with a sample in a flow channel.

[0003] For example, potentiometric methods using flow-type ion-selective electrodes can quickly and easily quantify the concentration of specific ions in a sample solution, and are therefore used in a wide range of fields, including water quality analysis and medicine. In particular, in the medical field, where metabolic reactions in living organisms are closely related to ion concentrations, quantifying specific ions contained in biological samples such as serum or urine is used to diagnose conditions such as hypertension, kidney disease, and neurological disorders. Because clinical testing requires the continuous analysis of a large number of samples, high-throughput automatic electrolyte analyzers equipped with ion-selective electrodes are routinely used.

[0004] The potentiometric method using an ion-selective electrode consists of an ion-selective electrode equipped with an ion-sensitive membrane and a reference electrode (comparison electrode) that serves as a potential standard. The concentration of electrolytes in the test sample can be calculated by measuring the electromotive force generated at the interface between the ion-selective electrode and the test sample, and the electromotive force generated at the interface between the test sample and the reference electrode. This reference electrode serves as a potential standard, and its potential must not change over time or due to external factors. The reference electrode generally consists of an ion-sensitive electrode and a reference solution. To accurately measure electrolytes in test samples with different concentrations, it is desirable for the reference solution to have similar transport numbers for cations and anions in the liquid.

[0005] For example, Non-Patent Document 1 discloses a configuration in which a reference liquid flows out of a stick-type reference electrode through Vycor glass in the direction of gravity. Patent Documents 1 and 2 disclose a configuration in which an internal electrolyte sealed in a reference electrode housing gradually seeps out. Patent Document 1 uses porous ceramic as a component constituting the liquid junction. Patent Document 2 uses hydrophilic porous polyethylene as a component constituting the liquid junction. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Japanese Patent Publication No. 62-231154 [Patent Document 2] Japanese Patent Application Laid-Open No. 2000-035414 [Non-patent literature]

[0007] [Non-Patent Document 1] Anal. Chem. 1986, 58 (12), 2585-2589. DOI:10.1021 / ac00125a053 Summary of the Invention [Problem to be solved by the invention]

[0008] In the case of the reference electrode described in Non-Patent Document 1, when the reference solution is sealed in a housing immersed in the sample, the electrolyte must be frequently replenished if it is discharged at a certain flow rate. In contrast, Patent Documents 1 and 2 use a porous material in the area of ​​contact with the sample, which somewhat suppresses the amount of electrolyte diffusion within the reference electrode. However, because the cylindrical porous material forms the flow path and has a large surface area of ​​contact with the sample, the amount of electrolyte discharge is large, resulting in the electrolyte discharged from the reference electrode being quickly depleted. In addition, the discharged electrolyte can penetrate the joints of adjacent ion-selective electrodes, affecting subsequent measurements and causing measurement errors. On the other hand, excessive suppression of electrolyte discharge can prevent the formation of an interface between the sample and the reference solution with a sharp concentration change, potentially resulting in an unstable liquid junction potential. Until now, it has been difficult to simultaneously suppress the amount of electrolyte discharge and stabilize the liquid junction potential.

[0009] Therefore, the present disclosure provides a technique that can ensure a long life and measurement stability in a reference electrode that uses a porous material. [Means for solving the problem]

[0010] In order to solve the above problem, the analytical device of the present disclosure comprises a sensor having a detection unit that detects a specific substance in a test sample, a reference electrode that generates a certain electromotive force, and a connection block that connects the sensor and the reference electrode, wherein the sensor has a flow path through which the test sample flows, and the detection unit is arranged so as to contact the test sample in the flow path, the reference electrode has a porous body and an electrolyte solution is sealed inside, the connection block has a flow path having at least a first connection port, a second connection port, and a third connection port, the first connection port is connected to the outlet of the flow path of the sensor, the second connection port is connected to a flow path for discharging the test sample, the opening surface of the third connection port faces downward, and the porous body of the reference electrode is connected to the third connection port, and the electrolyte solution inside the reference electrode and the test sample inside the flow path of the connection block come into contact with each other via the porous body.

[0011] Further features related to the present disclosure will become apparent from the description of this specification and the accompanying drawings. Also, aspects of the present disclosure are achieved and realized by the elements and combinations of various elements and the aspects of the following detailed description and the appended claims. The description of this specification is merely exemplary and does not limit the scope or application of the claims of the present disclosure in any way. [Effects of the Invention]

[0012] According to the technology of the present disclosure, it is possible to ensure a long life and measurement stability in a reference electrode using a porous material. Problems, configurations, and effects other than those described above will become clear from the description of the following embodiments. [Brief explanation of the drawings]

[0013] [Figure 1] FIG. 1 is a schematic diagram illustrating the main components of an electrolyte analyzer according to a first embodiment. [Figure 2] FIG. 2 is a cross-sectional view showing the structure of a reference electrode. [Figure 3A] FIG. 1 is a side cross-sectional view of a connection block connecting an ion-selective electrode and a reference electrode. [Figure 3B] FIG. 1 is a front cross-sectional view of a connection block that connects an ion-selective electrode and a reference electrode. [Figure 4] These are experimental results showing the difference in potassium chloride outflow depending on the direction of connection of the reference electrode. [Figure 5] FIG. 10 is a front cross-sectional view showing a state in which a connection block and a reference electrode according to a second embodiment are connected. [Figure 6A] FIG. 10 is a side cross-sectional view showing a state in which a connection block and a reference electrode according to a third embodiment are connected. [Figure 6B] FIG. 6B is an enlarged view of the dotted frame in FIG. 6A, showing the vicinity of the surface of the porous body. [Figure 7] FIG. 10 is a side cross-sectional view showing a structure in which a reference electrode is connected laterally to a connection block. [Figure 8]FIG. 10 is a front cross-sectional view showing a structure in which a reference electrode is connected to a connection block from the lateral direction. [Figure 9] FIG. 10 is a schematic diagram of the main components of an immunoassay analyzer according to a fourth embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0014] Hereinafter, embodiments of the present disclosure will be described with reference to the accompanying drawings. The accompanying drawings illustrate specific embodiments in accordance with the principles of the present disclosure, but the drawings are for understanding the present disclosure and are not to be used to interpret the present disclosure in a limiting manner.

[0015] [First embodiment] <Configuration example of a flow-type electrolyte analyzer> 1 is a schematic diagram illustrating the main components of an electrolyte analyzer 1 according to a first embodiment. The electrolyte analyzer 1 includes a connection block 101, a reference electrode 102, ion-selective electrodes 103, 104, and 105, electromagnetic valves 111, 112, 113, 114, 115, 116, and 117, syringe pumps 121, 122, and 123, a vacuum pump 124, a vacuum bottle 131, a diluent bottle 132, an internal standard bottle 133, a cup 141, a vacuum waste flow path 151, a test sample flow path 152, a diluent injection flow path 153, an internal standard injection flow path 154, a vacuum nozzle 155, and a sample aspiration nozzle 156.

[0016] The connection block 101 is made of, for example, resin. The connection block 101 connects the ion selective electrodes 103 to 105 and the reference electrode 102. The structure of the reference electrode 102 will be described in detail later, but the reference electrode 102 has a porous body 301 (see FIG. 2). The ion selective electrode 103 has a sodium ion-sensitive membrane. The ion selective electrode 104 has a potassium ion-sensitive membrane. The ion selective electrode 105 has a chloride ion-sensitive membrane. The diluent bottle 132 contains a diluent. The internal standard bottle 133 contains an internal standard solution. The internal standard solution is an aqueous solution with a constant concentration containing electrolytes such as sodium ions, potassium ions, and chloride ions. The ion selective electrodes 103 to 105 and the reference electrode 102 are arranged along the test sample flow path 152. The test sample is an analyte such as blood, body fluid, or urine.

[0017] The electrolyte analyzer 1 is connected to a control device 2. The control device 2 is configured, for example, by one or more arbitrary computer devices. The control device 2 includes an input unit 161, a device control unit 162, an output unit 163, a concentration calculation unit 164, and a potential measurement unit 165, which are functions realized by a processor executing a program or the like loaded in a memory.

[0018] The input unit 161 may be configured with an input device such as a mouse, keyboard, touch panel, or microphone. The input unit 161 accepts input of various information such as instructions from the user. The output unit 163 may be configured with an output device such as a display, touch panel, or speaker. The output unit 163 outputs the results of processing by the device control unit 162 and the concentration calculation unit 164, as well as an input screen for the user to input various information. The potential measurement unit 165 is connected to each of the ion selective electrodes 103 to 105 and the reference electrode 102, and measures the potential between the ion selective electrodes 103 to 105 and the reference electrode 102. The concentration calculation unit 164 calculates the electrolyte (ion) concentration of the test sample based on the measurement results of the potential measurement unit 165.

[0019] The following describes the flow of measuring electrolytes in a test sample using the electrolyte analyzer 1. Note that although the operation of each component of the electrolyte analyzer 1 is actually controlled by the device control unit 162, for the sake of simplicity, each component may be described as the subject of the operation. The measurement operation of the electrolyte analyzer 1 is executed when an instruction signal to start the operation is sent from the input unit 161 to the device control unit 162.

[0020] First, a test sample is placed into cup 141. Electromagnetic valve 116 is opened, and diluent is loaded into syringe pump 121 from diluent bottle 132. Electromagnetic valve 116 is closed, electromagnetic valve 112 is opened, and syringe pump 121 is operated to inject diluent into cup 141 via diluent injection flow path 153. Then, electromagnetic valve 112 is closed. Sample suction nozzle 156 is lowered to near the bottom of cup 141, electromagnetic valve 115 is opened, and the diluted test sample in cup 141 is aspirated by operating syringe pump 123. The diluted test sample is then circulated through test sample flow path 152 so as to come into contact with the sensitive membranes (detection units) of each ion selective electrode 103-105 (sensor). Then, sample suction nozzle 156 is raised, and a certain amount of air is sucked in. Then, electromagnetic valve 115 is closed. The potassium chloride concentration changes sharply between the diluted test sample filled near the reference electrode 102 and the porous body 301 of the reference electrode 102. The potassium chloride diffusion rate is sufficiently fast, and a potential immediately develops between the ion-selective electrodes 103, 104, and 105 and the reference electrode 102. The developed potentials are acquired by the potential measurement unit 165 and stored in the concentration calculation unit 164 as the diluted test sample potential. After a sufficient time has passed since the diluted test sample was filled, the high-concentration potassium chloride remains near the porous body 301 of the reference electrode 102, reducing potassium chloride leaching from the porous body 301. The diluted test sample remaining in the cup 141 is removed by suction using the vacuum pump 124 by lowering the vacuum nozzle 155 to the bottom of the cup 141 and opening the electromagnetic valve 111. The diluted test sample is then collected in the vacuum bottle 131. The electromagnetic valve 111 is then closed, and the vacuum nozzle 155 is raised. Next, the electromagnetic valve 117 is opened, and the internal standard solution is filled into the syringe pump 122 from the internal standard solution bottle 133. The electromagnetic valve 117 is closed, the electromagnetic valve 113 is opened, and the syringe pump 122 is operated to inject the internal standard solution into the cup 141 via the internal standard solution injection flow path 154. Thereafter, the electromagnetic valve 113 is closed. The sample suction nozzle 156 is lowered to the vicinity of the bottom of the cup 141, the electromagnetic valve 115 is opened, and the internal standard solution in the cup 141 is sucked in by operating the syringe pump 123 and circulated through the flow path so as to come into contact with the sensitive membrane of each ion selective electrode.The sample suction nozzle 156 is then raised to draw in a certain amount of air. The electromagnetic valve 115 is then closed. The potassium chloride concentration changes rapidly between the internal standard solution filled near the reference electrode 102 and the porous body 301 of the reference electrode 102. The potassium chloride diffusion rate is sufficiently fast, and a potential is instantly generated between the ion-selective electrodes 103, 104, and 105 and the reference electrode 102. The generated potentials are acquired by the potential measurement unit 165 and stored in the concentration calculation unit 164 as the internal standard solution potential. After a sufficient amount of time has passed since the internal standard solution was filled, the high-concentration potassium chloride remains near the porous body 301 of the reference electrode 102, reducing potassium chloride leaching from the porous body 301. The vacuum nozzle 155 is lowered to the bottom of the cup. The electromagnetic valve 111 is opened, and the remaining internal standard solution in the cup 141 is aspirated and removed by the vacuum pump 124 and collected in the vacuum bottle 131. Thereafter, the electromagnetic valve 111 is closed, and the vacuum nozzle 155 is raised. The concentration calculation unit 164 calculates the electrolyte concentration in the test sample using the stored diluted test sample potential and internal standard solution potential, and outputs the calculated value to the output unit 163.

[0021] <Example of reference electrode configuration> 2 is a cross-sectional view showing the structure of the reference electrode 102. The reference electrode 102 is composed of a porous body 301, a silver-silver chloride electrode 303, and a resin housing 305. The housing 305 contains a saturated potassium chloride-silver chloride aqueous solution 302, potassium chloride powder 304, and silver chloride powder 306. The silver-silver chloride electrode 303 is attached to the bottom of the housing 305, and its tip is in contact with the saturated potassium chloride-silver chloride aqueous solution 302. The opening of the housing 305 is sealed by the porous body 301.

[0022] Porous body 301 can be made of, for example, porous ceramic such as alumina, porous resin, or porous glass. In other words, the effects of the present disclosure can be achieved as long as porous body 301 is made of a material that is porous, does not dissolve in liquids such as water, and is not deteriorated by liquids it comes into contact with. The pore diameter of porous body 301 is several micrometers.

[0023] The potassium chloride aqueous solution in the reference electrode 102 is maintained at a saturated concentration until the potassium chloride powder 304 enclosed inside is depleted, allowing a stable reference electrode potential to be obtained. Although salt diffuses from the porous body, water flows in from the flow path, so the liquid in the reference electrode 102 does not deplete. In addition, although a potassium chloride aqueous solution is used in this embodiment, this is not limiting and any combination of anions and cations with similar transport numbers can be used. By changing the type of internal electrode according to the corresponding combination of ions, a stable reference electrode potential can be obtained.

[0024] In the reference electrode 102, the porous body 301 is rod-shaped, and only the tip surface comes into contact with the test sample. This has the advantage of reducing the liquid contact area by having the top surface of the cylinder come into contact with the test sample, as opposed to Patent Document 1, in which the inner diameter of the circumferential portion comes into contact with the test sample. Furthermore, when the reference electrode 102 is placed with the porous body 301 facing up, the internal liquid is sealed to prevent leakage from the housing 305. This allows the internal liquid to flow out only through the porous body 301. Furthermore, when the reference electrode 102 is placed with the porous body 301 facing up, the design ensures that at least the lower end of the porous body 301 comes into contact with the saturated potassium chloride / silver chloride aqueous solution 302. This allows the saturated potassium chloride / silver chloride aqueous solution 302 to keep the porous body 301 wet by capillary action, and also allows the electrolyte in the saturated potassium chloride / silver chloride aqueous solution 302 to move upward within the porous body.

[0025] <Connection block configuration example> 3A is a side cross-sectional view of a connection block 101 that connects the ion selective electrodes 103 to 105 and the reference electrode 102. FIG. 3B is a front cross-sectional view of the connection block 101. The connection block 101 has a channel 400 therein. The channel 400 has three channel ports: an inlet 410, an outlet 411, and a connection port 412. The inlet 410 is connected to a test sample channel 152 that passes through the ion selective electrodes 103 to 105. The test sample that flows in from the inlet 410 fills the connection port 412 and is then discharged from the outlet 411.

[0026] The connection port 412 extends vertically downward against gravity. With this configuration, the reference electrode 102 is connected to the connection port 412 from directly below the connection block 101, with the porous body 301 facing upward. Connecting the reference electrode 102 facing upward reduces the amount of potassium chloride leaching from the porous body 301 compared to when the reference electrode 102 is connected facing downward. This allows for a longer lifespan when the amount of potassium chloride powder 304 in the housing 305 is the lifespan of the reference electrode 102. This is because when the saturated potassium chloride and silver chloride aqueous solution 302 is leached from the bottom of the flow path 400 using capillary action, the saturated potassium chloride and silver chloride aqueous solution 302 has a higher specific gravity than the test sample and internal standard solution. Therefore, it remains in the flow path 400 near the porous body 301, reducing convection within the flow path 400. As a result, the potassium chloride concentration on the surface of the porous body 301 increases, and the concentration gradient between the test sample region and the porous surface decreases, slowing the leaching rate. Furthermore, when the liquid in the flow path 400 is replaced with the next test sample, the electrolyte concentration on the surface of the porous body 301 decreases, causing a steeper gradient in the electrolyte concentration inside and outside the reference electrode 102, and the diffusion flux of electrolyte seeping from the porous body 301 into the flow path 400 returns to normal. This reduces the amount of seepage of the saturated potassium chloride / silver chloride aqueous solution 302 while the liquid is stationary. Furthermore, since upward flow due to gravity does not occur, potassium chloride seepage into the test sample proceeds only by capillary action and diffusion. Furthermore, if small air bubbles are mixed into the test sample flow path 152, buoyancy causes the bubbles to move upward against gravity, making it difficult for the air bubbles to adhere to the surface of the porous body 301 in a structure with the surface facing upward. In this case, the saturated potassium chloride / silver chloride aqueous solution 302, which has wetted the porous body 301 by capillary action, comes into contact with the test sample that comes into contact with the surface of the porous body 301. After contacting the electrolyte solution, potassium chloride diffuses into the test sample due to the diffusion phenomenon.

[0027] In conventional free-flow electrochemical measurement devices, the reference solution must be brought into contact with the test sample by gravity, which makes it impossible to realize the configuration of this embodiment. Furthermore, when a cylindrical porous body is used as a flow path, small air bubbles may easily adhere to the surface of the porous body, causing the measured potential to become unstable.

[0028] <Difference in electrolyte outflow due to change in reference electrode connection direction> The amount of electrolyte outflow when the porous body 301 was connected to the flow channel 400 facing upward and the amount of electrolyte outflow when the porous body 301 was connected to the flow channel 400 facing downward were measured using the following method.

[0029] A potassium chloride solution of known concentration was injected into cup 141, sample suction nozzle 156 was lowered, electromagnetic valve 115 was opened, and syringe pump 123 was operated for suction, causing the potassium chloride solution to flow through the flow path. Then, electromagnetic valve 115 was closed, electromagnetic valve 114 was opened, syringe pump 123 was operated for discharge, and electromagnetic valve 114 was closed. Sample suction nozzle 156 was raised, electromagnetic valve 111 was opened, and vacuum nozzle 155 was lowered to aspirate the remaining test sample. Then, vacuum nozzle 155 was raised and electromagnetic valve 111 was closed. After waiting a certain number of seconds, another potassium chloride solution of known concentration was injected into cup 141, sample suction nozzle 156 was lowered, electromagnetic valve 115 was opened, and syringe pump 123 was operated for suction. Then, electromagnetic valve 115 was closed, electromagnetic valve 114 was opened, and syringe pump 123 was operated for discharge, resulting in the waste liquid being collected and its conductivity being measured to calculate the potassium chloride concentration. The above operation was carried out 15 times for each of the cases where the porous body 301 was connected facing upward and the case where it was connected facing downward, and the average amount of potassium chloride that flowed out was calculated.

[0030] Figure 4 shows the experimental results showing the difference in potassium chloride outflow depending on the orientation of the reference electrode. As shown in Figure 4, when the reference electrode 102 was connected facing downward, the amount of potassium chloride outflow was 1.52 μg / time. In contrast, when the reference electrode 102 was connected facing upward, the amount of potassium chloride outflow was 0.98 μg / time. As a result, the amount of potassium chloride outflow when the reference electrode 102 was connected facing upward was 30% less than when the reference electrode 102 was connected facing downward. When the reference electrode 102 was facing upward, the potassium chloride aqueous solution, which has a higher specific gravity than the test sample and internal standard solution, remained near the tip of the porous medium 301 at the reference electrode 102. Therefore, the amount of potassium chloride leaching from the interface between the test sample and the surface of the porous medium 301, where the concentration gradient was small, was small. On the other hand, when the reference electrode 102 was facing downward, the potassium chloride aqueous solution, which has a higher specific gravity than the test sample and internal standard solution, continued to leach downward without remaining at the tip of the reference electrode 102. Therefore, the amount of potassium chloride leaching decreases when the reference electrode 102 is facing upward. For this reason, by facing the reference electrode 102 upward, it is possible to achieve a lifespan that is approximately 1.5 times longer.

[0031] <Suppression of invasion to ion-selective electrodes> In the electrolyte analyzer 1, the measurement flow path formed by the ion-selective electrodes 103, 104, and 105 and the reference electrode 102 is not an ideal cylindrical shape. This structure creates gaps in the flow path, between the electrodes, and between the electrode and the analyzer, resulting in stagnation of the liquid flow. In conventional configurations, when the liquid in the flow path remains stationary for a while, potassium chloride contained inside the reference electrode diffuses into the test sample and internal standard solution contained in the flow path. This causes convection and diffusion due to the concentration difference in the liquid within the flow path, leading to potassium chloride entering the stagnant area, resulting in a high electrolyte concentration in the liquid in the stagnant area. When the test sample or internal standard solution is flowed through the measurement flow path for the next measurement, the high-concentration liquid in the stagnant area is not immediately replaced. Therefore, the high-concentration liquid in the stagnant area contaminates the test sample or internal standard solution, affecting the measured potential of each ion-selective electrode 103, 104, and 105. To avoid this, a large amount of liquid must be flowed until the high-concentration liquid in the stagnant area is replaced. In contrast, in this embodiment, the reference electrode 102 is connected facing upward, which reduces the amount of potassium chloride that leaks out, and therefore reduces the amount of potassium chloride that gets mixed into the gap between the electrodes. This effect suppresses fluctuations in the measured potential, enabling accurate measurements. Furthermore, depending on the type of sensor, the performance of the sensor may deteriorate if exposed to potassium chloride for a long period of time. This embodiment can reduce these adverse effects.

[0032] <Summary of the First Embodiment> As described above, the electrolyte analyzer 1 (analyzer) according to the first embodiment includes ion-selective electrodes 103-105 (sensors) each having a sensitive membrane (detection unit) for detecting a specific substance in a test sample, a reference electrode 102 that generates a constant electromotive force, and a connection block 101 that connects the ion-selective electrodes 103-105 to the reference electrode 102. The ion-selective electrodes 103-105 each have a test sample flow path 152 through which the test sample flows, and the sensitive membrane is disposed so as to come into contact with the test sample in the test sample flow path 152. The reference electrode 102 has a porous body 301, and a saturated potassium chloride / silver chloride aqueous solution 302 (electrolyte solution) is sealed inside. The connection block 101 has a flow path 400 having an inlet 410 (first connection port), an outlet 411 (second connection port), and a connection port 412 (third connection port). The inlet 410 is connected to the outlet of the test sample flow path 152 of the ion selective electrodes 103-105. The outlet 411 is connected to a flow path for discharging the test sample. The opening of the connection port 412 faces downward, and the porous body 301 of the reference electrode 102 is connected to the connection port 412. The saturated potassium chloride / silver chloride aqueous solution 302 inside the reference electrode 102 comes into contact with the test sample inside the flow path 400 of the connection block 101 via the porous body 301.

[0033] The technology of this embodiment makes it possible to suppress the amount of reference liquid seeping out of the porous reference electrode 102, thereby extending the life of the reference electrode 102 and reducing the invasive phenomenon to the ion-selective electrodes 103-105. The structure of this embodiment, which uses capillary action to make the electrolyte seep out of the porous body 301 from the bottom of the flow path 400 against gravity, can reduce convection in the flow path 400 that occurs due to a change in the specific gravity of the liquid in the flow path 400 caused by the seeped electrolyte. This reduces the amount of electrolyte that leaks out when the liquid is stationary. This structure of this embodiment has not been considered for conventional stick-type electrodes.

[0034] Furthermore, when the liquid in the flow path 400 is replaced with the next test sample, the electrolyte concentration on the surface of the porous body 301 decreases, causing a steeper electrolyte concentration gradient inside and outside the reference electrode 102, and the diffusion flux of electrolyte seeping from the porous body 301 into the flow path 400 returns to normal. This ensures measurement stability while reducing substantial electrolyte outflow, enabling stable potential measurement between the porous body 301 and the test sample in contact with the liquid. Furthermore, by using the present disclosure, the amount of electrolyte seeping from the porous body while the liquid is stationary is reduced, reducing the risk of the ion-selective electrodes 103-105 (sensor unit) being invaded by high-concentration electrolytes. This allows the sensor unit and the reference electrode 102 to be closer, allowing for a more compact device design.

[0035] [Second embodiment] In the first embodiment described above, a structure has been described in which the reference electrode 102 is connected directly below the connection block 101. As will be described in the second embodiment, the connection direction of the reference electrode 102 may be inclined with respect to the vertical direction.

[0036] 5 is a front cross-sectional view showing the state in which a connection block 500 and a reference electrode 102 according to the second embodiment are connected. The structure of the reference electrode 102 is the same as that of the first embodiment. As shown in FIG. 5, in the connection block 500, the connection port 412 of the flow path 400 faces diagonally downward. This allows the reference electrode 102 to be connected to the connection block 500 from diagonally downward. A feature of this embodiment is that the liquid surface 502 of the saturated potassium chloride / silver chloride aqueous solution 302 in the reference electrode 102 is positioned below the bottom surface 501 of the flow path 400.

[0037] Potassium chloride leaching from the porous body 301 accumulates near the porous body 301. As the potassium chloride concentration near the surface of the porous body 301 increases, the potassium chloride leaching rate decreases. In other words, the concentration gradient becomes smaller, resulting in a smaller diffusion flux. In the case of a downward connection, the potassium chloride leaching from the porous body 301 increases the specific gravity of the solution, and the solution with a higher specific gravity continuously flows downward due to gravity. As a result, a less concentrated solution flows into the vicinity of the porous surface, and the concentration gradient inside and outside the reference electrode 102 remains unchanged. Therefore, potassium chloride continues to leach into the test sample while maintaining its diffusion flux. This phenomenon is also observed in the cylindrical reference electrode of Patent Document 1 and in cases where the electrode is connected horizontally. In addition, since gravity does not cause a flow upward, potassium chloride leaching into the test sample proceeds only by capillary action and diffusion. Furthermore, if small air bubbles are mixed into the test sample flow path 152, the bubbles will move upward against gravity, and therefore, in a structure in which the surface of the porous body 301 faces upward, the air bubbles are less likely to adhere to the surface of the porous body 301. Therefore, the second embodiment can also improve the stability of the measurement. Furthermore, the configuration in which the reference electrode 102 is connected from an obliquely downward direction makes it easy for the operator to attach and detach the reference electrode 102.

[0038] [Third embodiment] In the first and second embodiments, a configuration has been described in which the flow channel 400 in the connection block is horizontal and the connection port 412 connecting the flow channel 400 and the reference electrode 102 faces downward. In the third embodiment, a connection block structure for suppressing the occurrence of a portion in the flow channel that is not filled with the test sample will be described.

[0039] 6A is a side cross-sectional view showing a state in which a connection block 600 and a reference electrode 102 according to the third embodiment are connected. The connection block 600 has a channel 401 with a V-shaped cross section. The bottom of this V-shaped channel 401 is open. When the reference electrode 102 is connected to the connection block 600 from below (directly below) with the porous body 301 facing upward, the bottom of the channel 401 and the porous body 301 of the reference electrode 102 are connected. In this way, the connection block 600 has the channel 401 in which the inlet 410 and outlet 411 for the test sample are each directly connected to the surface of the porous body 301 of the reference electrode 102.

[0040] Figure 6B is an enlarged view of the dotted frame in Figure 6A, showing the vicinity of the surface of porous body 301. It is characterized in that angles θ1 and θ2 formed by wall surface 701 of inlet 410 and wall surface 702 of outlet 411 with respect to surface 703 of porous body 301 are each 90 degrees or more and less than 180 degrees.

[0041] By connecting the reference electrode 102 from bottom to top to the V-shaped flow channel 401 as in this embodiment, it is possible to reliably fill the entire area of ​​the flow channel 401 with the test sample. In other words, no areas (air bubbles) are generated where the test sample is not filled. This is because there are no areas in the flow channel 401 where liquid convection does not occur, or areas that are shaded by the flux, so to speak.

[0042] [Comparative Example] Here, a structure in which there may be a portion in the flow path of the connection block where the test sample is not filled (a portion not filled with the test sample) will be described.

[0043] FIG. 7 is a side cross-sectional view showing a comparative example in which a reference electrode 102 is connected laterally to a connection block 101. The flow path 400 is parallel to the vertical direction, and the flow path 400 is shown filled with a test sample 801. In this structure, when the reference electrode 102 is connected or during the subsequent measurement operation, air bubbles are present, which may result in a test sample-free area 802, i.e., an air bubble, occurring at the connection port 412 with the reference electrode 102. When the test sample-free area 802 occurs, the electrical connection between the reference electrode 102 and electrodes 103, 104, and 105 is lost, making it impossible to obtain the potential formed with the test sample. In this structure, the presence of a region in the flow path that is shadowed by the flux can lead to the occurrence of such a test sample-free area 802.

[0044] FIG. 8 is a front cross-sectional view showing a comparative example in which the reference electrode 102 is connected laterally to the connection block 101. As shown in FIG. 8, the liquid level 502 of the saturated potassium chloride / silver chloride aqueous solution 302 in the reference electrode 102 is positioned above the bottom surface 501 of the flow channel 400. This structure does not extend the service life for the following reasons: When the flow channel 400 is filled with a test sample, the high-concentration potassium chloride with a high specific gravity that seeps through the porous body 301 drops down along the flow channel 400 in the direction of gravity. This creates a liquid convection, which increases the concentration gradient between the surface of the porous body 301 and the test sample, thereby increasing the diffusion flux. Assuming the flow channel 400 is sufficiently long, the high-concentration potassium chloride continues to drop down along the flow channel 400, and the potassium chloride continues to seep into the test sample while maintaining its diffusion flux. Therefore, the service life cannot be extended.

[0045] [Fourth embodiment] <Configuration example of a flow-type immunoassay analyzer> 9 is a schematic diagram of the main components of an immunoassay device 3 according to the fourth embodiment. The immunoassay device 3 is a device that generates an optically detectable signal by applying a potential to a test sample. The immunoassay device 3 includes a measurement cell 200, a power supply (not shown) for applying a potential to the measurement cell 200, and a detector (not shown) for detecting radiation from the sample liquid in the measurement cell 200.

[0046] The measurement cell 200 includes a connection block 101, a reference electrode 102, an upper member 201, a bottom member 208, a working electrode 202, a counter electrode 203, and a magnet 206. The upper member 201 and the bottom member 208 are both approximately L-shaped, defining an approximately L-shaped flow path 204 between them. A sample solution is introduced through an inlet 207 of the flow path 204. An opening 209 of the flow path 204 is connected to an inlet 410 of a flow path 400 in the connection block 101. The working electrode 202 is disposed on the upper surface of the bottom member 208 of the measurement cell 200. The counter electrode 203 is disposed on the bottom surface of the upper member 201 of the measurement cell 200, facing the working electrode 202. The working electrode 202 is connected to a first electrode of a power supply, and the counter electrode 203 is connected to a second electrode of the power supply. The upper member 201 of the measurement cell 200 functions as an optical window. The test sample contains an ECL labeling substance, and when an electric potential is applied, it emits electromagnetic radiation as a result of chemical and electrochemical reactions. A detector detects the radiation emerging from the optical window. The magnet 206 can be moved toward or away from the measurement cell 200 by a driving device (not shown). The test sample flows in through the inlet 207, fills the flow path 204, and comes into contact with the reference electrode 102 via the connection port 412. The test sample is discharged from the outlet 411 of the connection block 101.

[0047] In the immunoassay analyzer 3 configured as above, the reference electrode 102 is connected to the connection block 101 so as to face upward, thereby ensuring measurement stability.

[0048] [Variations] The present disclosure is not limited to the above-described embodiments and includes various modifications. For example, the above-described embodiments have been described in detail to clearly explain the present disclosure, and it is not necessary to include all of the described configurations. Furthermore, a part of one embodiment can be replaced with a configuration of another embodiment. Furthermore, a configuration of another embodiment can be added to a configuration of one embodiment. Furthermore, a part of the configuration of each embodiment can be added to, deleted from, or substituted for a part of the configuration of another embodiment. [Explanation of symbols]

[0049] 1: Electrolyte analyzer 2: Control device 3: Immunology analyzer 101, 500, 600: Connection block 102:Reference electrode 103, 104, 105: Ion-selective electrodes (sensors) 111, 112, 113, 114, 115, 116, 117: Solenoid valves 121, 122, 123: Syringe pump 124: Vacuum pump 131: Vacuum bottle 132: Dilution bottle 133: Internal standard solution bottle 141: Cup 151: Vacuum waste flow path 152: Test sample flow path 153: Diluent injection route 154: Internal standard solution injection channel 161: Input section 162: Device control unit 163: Output section 164: Concentration calculation section 165: Potential measurement unit 200: Measuring cell (sensor) 301: Porous material 302: Saturated potassium chloride and silver chloride aqueous solution 303: Silver-silver chloride electrode 304: Potassium chloride powder 305: Cabinet 400: Flow path 410: Inlet 411: Discharge outlet 412:Join the mouth

Claims

1. a sensor having a detection unit for detecting a specific substance in a test sample; A reference electrode that generates a constant electromotive force; a connection block connecting the sensor and the reference electrode; the sensor has a flow path through which a test sample flows, and the detection unit is disposed so as to come into contact with the test sample in the flow path; the reference electrode has a porous body and an electrolyte solution sealed therein; the connection block has a flow path having at least a first connection port, a second connection port, and a third connection port, the first connection port is connected to an outlet of the flow path of the sensor, the second connection port is connected to a flow path for discharging the test sample, the opening surface of the third connection port faces downward, and the porous body of the reference electrode is connected to the third connection port, so that the electrolyte solution inside the reference electrode and the test sample inside the flow path of the connection block come into contact with each other via the porous body; An analytical device characterized in that the reference electrode and the connection block are connected so that the liquid level of the electrolyte solution sealed in the reference electrode is located below the lower end of the flow path in the connection block.

2. 2. The analytical device according to claim 1, wherein an angle formed by a wall surface of the flow channel of the connection block with respect to a surface of the porous body is equal to or greater than 90 degrees and less than 180 degrees.

3. 2. The analytical device according to claim 1, wherein a portion of the porous body of the reference electrode is in contact with the electrolyte solution enclosed in the reference electrode.

4. 2. The analytical device of claim 1, wherein the electrolyte solution in the reference electrode comprises saturated aqueous potassium chloride and solid potassium chloride.

5. 5. The analytical device of claim 4, wherein the electrolyte solution in the reference electrode further comprises solid silver chloride.

6. 2. The analytical device according to claim 1, wherein the porous body is a porous ceramic.

7. 2. The analytical device according to claim 1, wherein the sensor is an electrolyte analytical sensor.

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