Analytical apparatus and analytical method

Abstract

The present invention provides an analytical apparatus and analytical method that suppress contamination by electrolytes seeping from the reference electrode during non-operational periods, thereby enabling longer intervals for continuous use without the need for initial operation. [Solution] The analyzer 10 comprises a flow path 130, a flow-type sensor 110, a reference electrode 120, a liquid delivery mechanism 141, and a device control unit 240. After an analysis mode and before a standby mode in which the device waits until the next analysis mode, the device control unit 420 controls the liquid delivery mechanism 141 to fill the wetted portion of the reference electrode 120 in the flow path 130 with liquid, and performs a gas suction sequence in which the liquid filling the wetted portion is divided by gas in at least one of the flow path between the flow-type sensor 110 and the reference electrode 120, and the flow path on the opposite side of the flow-type sensor from the reference electrode 120.

Description

Technical Field

[0001] The present invention relates to an analyzer and an analysis method for analyzing a specimen that is a liquid.

Background Art

[0002] Electrochemical measurement refers to a method of electrochemically measuring the properties of chemical substances. Among analyzers for performing electrochemical measurement, a flow-type electrochemical measurement device has a structure in which a working electrode and a reference electrode are arranged so as to be electrically in contact with a liquid in a flow path. Among these electrodes, since the reference electrode serves as a reference for potential, it is required that the potential does not change with time or external factors. The reference electrode is generally composed of an ion-sensitive electrode and a reference liquid, and various configurations have been proposed so far. For example, Non-Patent Document 1 discloses a stick-type reference electrode in which the reference liquid flows out in the direction of gravity through a bicor glass. Further, Patent Document 1 discloses a reference electrode in which a liquid junction member has a cylindrical shape and is made of porous ceramic, and a configuration in which an electrolyte enclosed in the housing of the reference electrode is gradually exuded from the liquid junction member.

Prior Art Documents

Non-Patent Documents

[0003]

Non-Patent Document 1

Patent Documents

[0004]

Patent Document 1

[0005] In flow-type electrochemical analyzers, the reference electrode, while in contact with a liquid such as a sample or internal standard solution, continuously leaks electrolytes from within the reference electrode's housing over time. Furthermore, electrolyte leakage from the reference electrode occurs regardless of whether the device is operating (analysis mode) or not (standby mode). However, during operation, the sample and internal standard solution flow continuously in a constant direction through the flow path, so no particular problems arise. On the other hand, during non-operation, the electrolyte leakage from the reference electrode can remain in the liquid within the flow path, potentially contaminating the flow path and working electrode, and shortening the interval during which continuous use is possible without initial operation.

[0006] Therefore, the object of the present invention is to provide an analytical apparatus and analytical method that can suppress contamination by electrolyte seeping from the reference electrode when not in operation, and that can extend the interval during which continuous use is possible without the need for initial operation. [Means for solving the problem]

[0007] To solve the aforementioned problems, the analytical apparatus according to the present invention comprises a flow path through which a liquid to be analyzed flows, a flow-type sensor for analyzing the liquid flowing through the flow path, a reference electrode for measuring the potential of the liquid flowing through the flow path, a liquid delivery mechanism for delivering the liquid in the flow path, and at least an apparatus control unit for controlling the liquid delivery mechanism. After an analysis mode in which the concentration of a specific substance in the liquid is calculated based on data acquired from the flow-type sensor and the reference electrode, and before a standby mode in which the apparatus control unit waits until the next analysis mode, the apparatus control unit controls the liquid delivery mechanism to fill the wetted portion of the reference electrode in the flow path with liquid, and to perform a gas suction sequence in which the liquid filling the wetted portion with gas in at least one of the flow path between the flow-type sensor and the reference electrode, and the flow path on the opposite side of the flow-type sensor from the reference electrode. [Effects of the Invention]

[0008] According to the present invention, it is possible to provide an analytical apparatus and analytical method that can suppress the amount of electrolyte seeping from the reference electrode and the extent of contamination when the apparatus is not in operation, reduce the number of flow path cleaning operations when transitioning to a non-operational state, and increase the service life of the reference electrode. [Brief explanation of the drawing]

[0009] [Figure 1] This is an overall configuration diagram of the analytical apparatus according to the first embodiment. [Figure 2] This is a schematic cross-sectional view showing the internal structure of the reference electrode according to the first embodiment. [Figure 3] This is an enlarged diagram of the flow channel, ion-selective electrode, and reference electrode according to the first embodiment. [Figure 4] This is an enlarged diagram showing the flow channel, ion-selective electrode, and a modified reference electrode according to the first embodiment. [Figure 5] This is a flowchart of the analysis method according to the first embodiment. [Figure 6A] This is a diagram showing the configuration of the analyzer when the gas is separating the liquid in the gas suction sequence of the first embodiment. [Figure 6B] Configuration diagram of the analyzer when the gas does not separate the liquid in the gas suction sequence of the first embodiment. [Figure 7] Configuration diagram of the flow-type sensor and reference electrode of the analyzer according to the second embodiment. [Figure 8] Graph showing the transition of the potential difference between the potassium ion-selective electrode and the reference electrode after 24 hours of standby mode. [Figure 9] Block diagram of the computer constituting the control unit.

Embodiments for Carrying Out the Invention

[0010] Hereinafter, the analyzer and the analysis method according to the present invention will be described with reference to the first and second embodiments. In describing the second embodiment, descriptions of configurations common to the already described embodiments will be omitted, and descriptions will focus on the different configurations.

[0011] [Analyzer According to the First Embodiment] FIG. 1 is an overall configuration diagram of the analyzer 10 according to the first embodiment. The analyzer 10 is roughly composed of a measurement unit 100 and a control unit 200. The analyzer 10 is a device that alternately performs analysis of a sample and analysis of an internal standard solution to obtain the potential difference between electrodes, and measures the concentration of a specific substance in the sample using the potential difference and a calibration curve. It is also called a so-called "flow-type electrochemical measurement device". The measurement unit 100 of the analyzer 10 mainly includes an ion-selective electrode 110, a reference electrode 120, a flow path 130, a syringe pump 141 for liquid feeding, a syringe pump 142 for diluent, a syringe pump 143 for internal standard solution, electromagnetic valves 151 to 157, a diluent bottle 161, an internal standard solution bottle 162, a supply tank 163, a drainage tank 164, and a vacuum pump 171. Hereinafter, each configuration of the measurement unit 100 of the analyzer 10 according to the first embodiment will be described.

[0012] (Ion-Selective Electrode) The ion-selective electrode 110 is a member for analyzing the concentration of a specific substance in the liquid flowing through the flow path 130, and corresponds to a "flow-type sensor". The ion-selective electrode 110 is composed of a chloride ion-selective electrode 111 provided with a chloride ion-sensitive membrane, a potassium ion-selective electrode 112 provided with a potassium ion-sensitive membrane, and a sodium ion-selective electrode 113 provided with a sodium ion-sensitive membrane. The chloride ion-selective electrode 111, the potassium ion-selective electrode 112, and the sodium ion-selective electrode 113 are arranged along the flow path 130 such that their respective ion-sensitive membranes are in contact with the liquid flowing through the flow path 130. Note that the ion-selective electrode 110 is not limited to the configuration including the three types of electrodes 111, 112, and 113 described above, and may be other electrodes, and the number of electrodes may be one or more.

[0013] (Reference electrode) The reference electrode 120 is an electrode that serves as a reference for the potential. The reference electrode 120 is arranged so as to be in contact with the liquid flowing through the flow path 130 on the downstream side of the ion-selective electrode 110 and on the upstream side of the liquid-feeding syringe pump 141 described later. FIG. 2 is a schematic cross-sectional view showing the internal structure of the reference electrode 120. The reference electrode 120 includes a resin housing 121 having an opening, a liquid junction member 122 provided so as to seal the opening of the housing 121, and a silver-silver chloride electrode 123 provided at a position facing the opening of the housing 121. Further, the inside of the housing 121 of the reference electrode 120 is filled with an internal liquid 124 which is a saturated potassium chloride silver chloride aqueous solution, potassium chloride powder 125, and silver chloride powder 126.

[0014] The liquid junction member 122 is rod-shaped, with one end exposed to the outside of the housing 121 and in contact with the liquid flowing through the channel 130, and the other end in contact with the internal liquid 124 filling the inside of the housing 121. With this configuration, the internal liquid 124 filling the housing 121 seeps out to the outside only through the liquid junction member 122. Furthermore, compared to the liquid junction member shown in Patent Document 1, which is cylindrical and has an inner surface in contact with the liquid, the liquid junction member 122 has a smaller contact area with the liquid, which can extend the service life of the reference electrode 102. The liquid junction member 122 only needs to be configured to allow the internal liquid 124 filled in the housing 121 to seep into the flow channel 130. Examples include porous ceramics, porous resins, gels, and ultrafine flow channels.

[0015] When the reference electrode 120 is positioned so that the liquid junction member 122 is on the upper side (as shown in Figure 3), the lower end of the liquid junction member 122 is immersed in the internal liquid 124. With this configuration, the liquid junction member 122 becomes wet in the internal liquid 124 due to capillary action, and the internal liquid 124 seeps into the flow path 130.

[0016] Since the internal liquid 124 filled in the housing 121 is maintained at a saturation concentration until the potassium chloride powder 125 and silver chloride powder 126 are depleted, the reference electrode 120 can obtain a stable potential. Furthermore, the internal solution 124 is not limited to saturated potassium chloride and silver chloride aqueous solution; any aqueous solution containing combinations of anions and cations with similar transport rates is acceptable, and the type of electrode inside the housing 121 can be changed according to these combinations.

[0017] (Flow channel) The flow path 130 is a pipe through which liquids such as the sample to be analyzed and internal standard solutions flow. A sample suction nozzle 181 capable of drawing liquid from the supply tank 163 is connected to the upstream end of the flow path 130. The downstream side of the flow path 130 is configured to allow liquid to be drained into the drain tank 164 via an electromagnetic valve 151, a liquid delivery syringe pump 141, and an electromagnetic valve 152. Figure 3 is an enlarged view of the flow path 130, the ion-selective electrode 110, and the reference electrode 120. In the flow path 130, a chloride ion selective electrode 111, a potassium ion selective electrode 112, a sodium ion selective electrode 113, and a reference electrode 120 are connected in a continuous manner from the upstream side to the downstream side. In addition, the flow path 130 has a branching passage 131 formed at the location where the reference electrode 120 is installed, such that the tip of the liquid junction member 122 comes into contact with the liquid. As will be described in detail later in the analysis method, in the gas suction sequence, gas is introduced in at least one of the two channels of the channel 130: channel 132 between the ion-selective electrode 110 and the reference electrode 120, and channel 133 downstream of the reference electrode 120.

[0018] The points where gas is introduced into channels 132 and 133 (points where the flow is divided by gas) are equipped with a gas retention mechanism that can maintain the state of liquid division by the gas. In other words, the gas retention mechanism is a mechanism that makes it easy for three phases—gas, liquid (internal standard liquid), and solid (inner wall surface of the channel)—to coexist simultaneously. Examples of gas retention mechanisms include those in which the inner walls of the channels 132 and 133 are hydrophobic, and in particular, mechanisms in which the contact angle between the inner walls of the channels 132 and 133 and water is 90° or more are preferred. Specifically, such gas retention mechanisms include those in which the channels 132 and 133 are made of Teflon, and those in which the inner walls of the channels 132 and 133 are treated with a water-repellent coating. Furthermore, gas retention mechanisms may include, for example, a mechanism in which the flow paths 132 and 133 at the gas introduction point are positioned higher vertically than the surrounding flow paths at that point, or a mechanism in which the inner diameter is reduced to increase the aspect ratio of the gas when the gas is introduced (long side of the gas cross-section / short side of the gas cross-section in the direction of liquid delivery). By providing such a gas retention mechanism, the introduced gas can appropriately separate the liquid in the flow paths 132 and 133.

[0019] Figure 4 is an enlarged view of the flow channel 130, the ion-selective electrode 110, and a modified example, the reference electrode 120a (in which the liquid junction member 122a has a cylindrical shape that covers the flow channel 130). In the case of Figure 4, as in the case of Figure 3, the flow path 130 has a chloride ion selective electrode 111, a potassium ion selective electrode 112, a sodium ion selective electrode 113, and a reference electrode 120 formed in a continuous manner from the upstream side to the downstream side, and the flow paths 132a and 133a where the gas is introduced are equipped with a gas retention mechanism.

[0020] (Syringe pump for liquid transfer) The liquid delivery syringe pump 141 is a mechanism for delivering liquid in the flow path 130 and falls under the category of "liquid delivery mechanism". The syringe pump 141 for liquid transfer can be any conventionally known syringe pump, and is not particularly limited as long as it has a mechanism that can transfer liquid from the supply tank 163 to the drain tank 164 via the flow path 130.

[0021] (Other components of the measuring unit) In addition to the above-mentioned configuration, the measuring unit 100 also includes a supply tank 163 for storing the liquid to be supplied, a diluent bottle 161 for containing the diluent, a syringe pump 142 for sending the diluent from the diluent bottle 161 to the supply tank 163, an internal standard solution bottle 162 for containing the internal standard solution, an internal standard solution syringe pump 143 for sending the internal standard solution from the internal standard solution bottle 162 to the supply tank 163, electromagnetic valves 151 to 157 for controlling the flow rate of fluid in each channel, and a vacuum pump 171 for sending any residual liquid remaining in the supply tank 163 to the drain tank 164.

[0022] (Control Unit) The control unit 200 of the analyzer 10 according to the first embodiment mainly comprises a potential measurement unit 210, a concentration calculation unit 220, a judgment unit 230, an apparatus control unit 240, an output unit 250, and an input unit 260. The potential measurement unit 210 acquires the potential difference between the ion-selective electrode 110 (chloride ion-selective electrode 111, potassium ion-selective electrode 112, sodium ion-selective electrode 113) and the reference electrode 120, as well as the potential difference in the conductive part. The concentration calculation unit 220 calculates the concentration of a specific substance in the liquid based on the data acquired by the potential measurement unit 210. The decision unit 230 executes the decision sequence described below based on the data acquired by the potential measurement unit 210. The device control unit 240 performs control over the measurement unit 100, including the liquid delivery syringe pump 141. The output unit 250 is a display or similar device for outputting calculation results from the concentration calculation unit 220. The input unit 260 is an interface for inputting various data and commands to the device control unit 240.

[0023] The processing of the control unit 200 is realized by program execution by the CPU (Central Processing Unit) or by dedicated circuits, etc. It may also include a memory unit (not shown), which can consist of common storage devices such as RAM (Random Access Memory), ROM (Read Only Memory), HDD (Hard Disk Drive), and flash memory. The hardware configuration of the control unit 200 will be described later with reference to Figure 9. Note that the control lines and information lines of the control unit 200 in Figure 1 are only shown if they are deemed necessary for explanation, and the connection method is not particularly limited; all parts may be interconnected. Also, the configuration of each part of the control unit 200 is not particularly limited; for example, the judgment unit 230 may be omitted by having the concentration calculation unit 220 or the device control unit 240 perform the functions of the judgment unit 230.

[0024] (Liquid used in analytical instruments) The liquid used in the analyzer 10 according to the first embodiment is not particularly limited as long as it is a liquid whose concentration of a specific substance you wish to analyze. Examples include specimens (also called test samples) such as blood, urine, and cerebrospinal fluid, which are diluted with a diluent as appropriate before being used for analysis. Another example of a liquid used in the analyzer 10 is an internal standard solution necessary for quantifying a specific substance. The specific substances contained in the sample are not limited to those mentioned above, but include, for example, chloride ions (Cl - ), potassium ions (K + ), sodium ions (Na + Examples include the following. Furthermore, the diluent used to dilute the sample is not particularly limited as long as it is a liquid with a lower concentration of the specific substance than the sample, but examples include pure water and buffer solutions. In addition, the internal standard solution is not particularly limited as long as it is a liquid with a concentration of the specific substance close to that of the diluted sample, and any liquid with a known concentration of the specific substance will suffice.

[0025] [Analysis method according to the first embodiment] Next, the analysis method according to the first embodiment will be described. The analysis method according to the first embodiment is an analysis method using the analysis apparatus 10 according to the first embodiment described above, and as shown in Figure 5, has an analysis mode S1 and a standby mode S4, and performs a gas suction sequence S2 and a decision sequence S3 between the analysis mode S1 and the standby mode S4. Various processes in each mode and each sequence are performed by the control unit 200 (specifically, the device control unit 240) controlling the measurement unit 100 of the analysis apparatus 10. In the present invention, the standby mode refers to a state other than when the device is performing an analysis cycle, and includes all non-operational states, from relatively short waiting periods in a sample waiting state to long periods of inactivity such as on weekends. The following describes each mode and sequence.

[0026] (Analysis mode) Analysis mode S1 is a mode in which the concentration of a specific substance in a liquid is calculated using data acquired from the ion-selective electrode 110 and the reference electrode 120 (diluted sample data and internal standard solution data), and can also be described as the operation of the analyzer 10. The details are as follows:

[0027] (Analysis mode: Acquisition of diluted sample data) Referring to Figure 1, in analysis mode S1, first, the sample is placed in the supply tank 163. The electromagnetic valve 153 is opened, and the diluent contained in the diluent bottle 161 is filled into the diluent syringe pump 142. The electromagnetic valve 153 is closed and the electromagnetic valve 154 is opened to operate the diluent syringe pump 142, injecting the diluent into the supply tank 163, after which the electromagnetic valve 154 is closed. Next, the sample suction nozzle 181 is lowered to near the bottom of the supply tank 163, the electromagnetic valve 151 is opened, and the liquid delivery syringe pump 141 is activated, so that the sample diluted in the supply tank 163 (referred to as diluted sample, as appropriate) is drawn into the pump 141. At this time, the diluted sample in the flow path 130 is delivered from the upstream side to the downstream side while in contact with each sensitive membrane of the ion-selective electrode 110 and the liquid junction member 122 of the reference electrode 120. When the diluted sample is in simultaneous contact with each sensitive membrane of the ion-selective electrode 110 and the reference electrode 120, the suction by the liquid delivery syringe pump 141 is stopped. In this state, the potential difference between each ion-selective electrode 110 and the reference electrode 120 is acquired by the potential measurement unit 210 and stored in the concentration calculation unit 220 as "diluted sample data". Subsequently, the electromagnetic valve 151 is closed and the electromagnetic valve 152 is opened to activate the syringe pump 141 for liquid delivery, thereby sending the diluted sample after measurement to the drain tank 164. Also, the vacuum nozzle 182 is lowered to near the bottom of the supply tank 163, the electromagnetic valve 157 is opened, and the vacuum pump 171 is activated to send the diluted sample remaining in the supply tank 163 to the drain tank 164. Then, the electromagnetic valve 157 is closed and the vacuum nozzle 182 is raised.

[0028] (Analysis mode: Acquisition of internal standard solution data) Next, the electromagnetic valve 155 is opened, and the internal standard solution contained in the internal standard solution bottle 162 is filled into the internal standard solution syringe pump 143. The electromagnetic valve 155 is closed and the electromagnetic valve 156 is opened to operate the internal standard solution syringe pump 143, injecting the internal standard solution into the supply tank 163, after which the electromagnetic valve 156 is closed. Next, the sample suction nozzle 181 is lowered to near the bottom of the supply tank 163, the electromagnetic valve 151 is opened, and the liquid delivery syringe pump 141 is activated, causing the internal standard solution injected into the supply tank 163 to be drawn into the pump 141. At this time, the internal standard solution in the flow path 130 is delivered from the upstream side to the downstream side, while contacting each sensitive membrane of the ion-selective electrode 110 and the liquid junction member 122 of the reference electrode 120. The suction by the liquid delivery syringe pump 141 stops when a single mass of internal standard solution is simultaneously in contact with each sensitive membrane of the ion-selective electrode 110 and the reference electrode 120. In this state, the potential difference between each ion-selective electrode 110 and the reference electrode 120 is acquired by the potential measurement unit 210 and stored in the concentration calculation unit 220 as "internal standard solution data". The subsequent steps are the same as those for obtaining the diluted sample data described above.

[0029] (Analysis mode: Calculation of concentration) Based on the "diluted sample data" and "internal standard solution data" obtained by the method described above, the concentration calculation unit 220 calculates the concentration of the specific substance in the sample and outputs it to the output unit 250. Furthermore, the method for calculating the concentration of specific substances can be carried out using conventionally known methods, such as using Henderson's equation or Nernst's equation.

[0030] (Gas suction sequence) The gas suction sequence S2 is a process performed after the analysis mode S1 and before the standby mode S4, and involves dividing the liquid filling the flow path 130 with gas at predetermined locations. Referring to Figure 1, in the gas suction sequence S2, first, the solenoid valve 155 is opened to fill the internal standard solution syringe pump 143 with the internal standard solution contained in the internal standard solution bottle 162. Then, the solenoid valve 155 is closed and the solenoid valve 156 is opened to operate the internal standard solution syringe pump 143, injecting the internal standard solution into the supply tank 163, after which the solenoid valve 156 is closed. Next, the sample suction nozzle 181 is lowered to a position where it is immersed in the internal standard solution of the supply tank 163, the electromagnetic valve 151 is opened, and the liquid delivery syringe pump 141 is activated, causing the internal standard solution injected into the supply tank 163 to be drawn towards the pump 141. As a result, the flow path 130, where the ion-selective electrode 110 and the reference electrode 120 are located, is filled with the internal standard solution. Next, the sample suction nozzle 181 is raised away from the internal standard solution in the supply tank 163, and the liquid delivery syringe pump 141 is activated to perform a "gas suction process" in which gas (air in the supply tank 163) is drawn towards the pump 141. As a result, a layer of gas is formed at the upstream end of the internal standard solution filling the flow path 130. Next, the sample suction nozzle 181 is lowered to a position where it is immersed in the internal standard solution of the supply tank 163, and the liquid delivery syringe pump 141 is operated to perform an "internal standard solution suction process" in which the internal standard solution injected into the supply tank 163 is drawn towards the pump 141. As a result, a layer of internal standard solution is formed at the upstream end of the gas formed in the flow path 130 during the gas suction process described above. Furthermore, the gas suction process and the internal standard solution suction process described above are repeated. Finally, the vacuum nozzle 182 is lowered to near the bottom of the supply tank 163, and the vacuum pump 171 is operated while the solenoid valve 157 is opened, thereby sending the internal standard liquid remaining in the supply tank 163 to the drain tank 164. Then, the solenoid valve 157 is closed, the vacuum nozzle 182 is raised, and the gas suction sequence S2 is completed. By performing these processes, the wetted portion of the reference electrode 120 in the flow path 130 becomes filled with the internal standard solution, and at the same time, the internal standard solution is divided by the gas in the flow paths 132 and 133 (flow paths 132a and 133a in the case of Figure 4) where the gas is introduced as shown in Figure 3.

[0031] The gas to be introduced should be introduced at least 5 mm in length through two channels 1 mm in diameter, 132 and 133 (channels 132a and 133a in Figure 4), but it is not particularly limited. Furthermore, while the introduced gas is assumed to be the air in the supply tank 163, it is not particularly limited to any gas with low solubility in liquids, such as nitrogen or helium. The following will describe in detail the ways in which a gas divides a liquid.

[0032] (Gas suction sequence: a manner in which gas divides a liquid) Figure 6A is a diagram of the analytical apparatus configuration when the gas is separating the liquid during the gas suction sequence S2. In the gas suction sequence S2, if the gas is properly introduced as shown in Figure 6A, first, the wetted portion of the reference electrode 120 in the flow path 130 is filled with liquid L (internal standard solution). Also, in the flow path 134 between the ion-selective electrode 110 and the reference electrode 120, liquid L is divided by gas A1. Furthermore, in the flow path 135 between the reference electrode 120 and the liquid delivery syringe pump 141, liquid L is divided by gas A2. In this way, gas A1 divides liquid L in the channel 134, preventing the diffusion of electrolyte seeping from the reference electrode 120 upstream and preventing contamination of the ion-selective electrode 110 by the seeped electrolyte. Furthermore, gas A2 divides liquid L in the channel 135, preventing the diffusion of electrolyte seeping from the reference electrode 120 downstream and preventing contamination of downstream components such as the liquid delivery syringe pump 141 by the seeped electrolyte. In addition, by dividing liquid L with gases A1 and A2, the amount of electrolyte seeping from the reference electrode 120 is limited. Furthermore, because the area from which the electrolyte seeps out of the reference electrode 120 is confined to a minute space separated by gases A1 and A2, the concentration of the electrolyte in this minute space becomes uniform more quickly. According to Fick's law, the diffusion rate of the electrolyte decreases, thus extending the service life of the reference electrode 120. In other words, by introducing gases A1 and A2 into the flow paths 134 and 135, contamination based on electrolyte seeping from the reference electrode 120 can be prevented in the standby mode S4 (non-operational state) described later, and the interval during which the analyzer 10 can be used continuously without initial operation can be extended.

[0033] Furthermore, in order for gases A1 and A2 to properly divide liquid L, it is preferable that the opposing liquid surfaces of liquid L flanking gases A1 and A2 be as parallel as possible. In other words, it is preferable that the opposing liquid surfaces of liquid L be as perpendicular as possible to the inner wall surface of the flow path 130. To achieve this state, it is preferable that the aforementioned gas holding mechanism be provided in the flow paths 134 and 135 where gases A1 and A2 are held.

[0034] Figure 6B is a diagram of the analyzer configuration when the gas does not divide the liquid during the gas suction sequence S2. If the gas is not properly introduced in the gas suction sequence S2 as shown in Figure 6B, gases A3 and A4 will not be able to divide the liquid L in the flow path 130. As a result, in the standby mode S4 described later, the electrolyte seeping from the reference electrode 120 will diffuse upstream and downstream, contaminating surrounding components such as the ion-selective electrode 110.

[0035] (Decision sequence) The determination sequence S3 is a process of determining whether the liquid filled in the liquid contact portion of the reference electrode 120 in the flow path 130 is separated by gas after the gas suction sequence S2. That is, the determination sequence S3 is a process of determining whether it is in the "separated" state as shown in FIG. 6A or the "non-separated" state as shown in FIG. 6B. As the determination method in the determination sequence S3, specifically, the following "determination method 1" and "determination method 2" can be mentioned.

[0036] (Determination sequence: Determination method 1) As shown in FIG. 6A, when the gas A1 separates the liquid L in the flow path 134 between the ion selection electrode 110 and the reference electrode 120, since the two members are not electrically conductive, the resistance value between the two members increases, and the potential difference also increases. Similarly, when the gas A2 separates the liquid L in the flow path 135 between the reference electrode 120 and the liquid feeding syringe pump 141, since the two members are not electrically conductive, the resistance value between the two members increases, and the potential difference also increases. On the other hand, as shown in FIG. 6B, when the liquid L is not separated by the gas A3 in the flow path 134 between the ion selection electrode 110 and the reference electrode 120, since the two members are electrically conductive, the resistance value between the two members decreases, and the potential difference also decreases. Similarly, when the liquid L is not separated by the gas A4 in the flow path 135 between the reference electrode 120 and the liquid feeding syringe pump 141, since the two members are electrically conductive, the resistance value between the two members decreases, and the potential difference also decreases. Therefore, in determination method 1, a conductive portion is provided at a position sandwiching the portions separated by gas (flow paths 134, 135) from both sides, the potential measurement unit 210 acquires data (potential difference) from the conductive portion, and the determination unit 230 can make a determination such as "separated" when the potential difference ≧ X and "non-separated" when the potential difference < X based on the data. Or, when the data obtained from the conductive portion is the resistance value, it may be determined such as "separated" when the resistance value ≧ Y and "non-separated" when the resistance value < Y. The conductive part may consist of an ion-selective electrode 110, a reference electrode 120, and a syringe pump 141 for liquid delivery, but a conductive component may also be provided in the flow path 130 to serve as the conductive part. Furthermore, while the potential measurement unit 210 may acquire data from the conductive part, a separate dedicated resistance meter or potential measuring instrument may also acquire the data.

[0037] (Decision sequence: Decision method 2) As shown in Figure 6A, when the liquid L (internal standard solution) is interrupted by gas A1 in the flow path 134, the potential difference between the ion-selective electrode 110 and the reference electrode 120 obtained by the potential measurement unit 210 will be significantly different from the value of the internal standard solution data acquired in analysis mode S1. On the other hand, as shown in Figure 6B, if the liquid L is not divided by gas A3 in the flow path 134, the potential difference between the ion-selective electrode 110 and the reference electrode 120 obtained by the potential measurement unit 210 will be approximately the same as the value of the internal standard solution data acquired in analysis mode S1. Therefore, in judgment method 2, if the difference between the "internal standard solution data acquired in judgment sequence S3" and the "internal standard solution data acquired in analysis mode S1 (internal standard solution data when the flow path 130 is completely filled with internal standard solution)" is outside the ±1% range, it can be determined that the system is "separated," and if it is within the ±1% range, it can be determined that the system is "not separated."

[0038] (Recovery sequence) The recovery sequence S10 is a series of processes consisting of the gas intake sequence S2 and the decision sequence S3. In the recovery sequence S10, the aforementioned decision sequence S3 is executed simultaneously with the completion of the aforementioned gas intake sequence S2. If the decision sequence S3 determines that "disconnection" has occurred, the system transitions to standby mode S4. If it determines that "disconnection" has occurred, the system transitions back to the gas intake sequence S2. If the judgment sequence S3 repeatedly determines that the system is "not separated," it may lead to a situation where the system cannot transition to standby mode S4. To avoid such a situation, if the judgment sequence S3 determines that the system is "not separated" N times (where N is an integer greater than or equal to 2), the system may not proceed to the gas suction sequence S2, and instead perform the cleaning process in the subsequent cleaning mode 5 more times than usual. By performing the cleaning process more times, electrolytes accumulated in the gaps of the ion-selective electrode 110 (electrolytes seeped out from the reference electrode 120) can be removed.

[0039] (Standby mode) Standby mode S4 is a mode in which analysis is not performed continuously, and can be described as a time when the analyzer 10 is not in operation. Specifically, Standby Mode S4 includes short waiting periods for analysis of 1 to 30 minutes, as well as longer waiting periods of 30 minutes or more, such as at night or on holidays.

[0040] (Washing mode) Washing mode S5 is a mode in which a washing process is performed on the analyzer 10 after standby mode S4 and before the next analysis mode S1. Referring to Figure 1, in cleaning mode S5, first, the solenoid valve 155 is opened, and the internal standard solution contained in the internal standard solution bottle 162 is filled into the internal standard solution syringe pump 143. The solenoid valve 155 is closed and the solenoid valve 156 is opened to operate the internal standard solution syringe pump 143, injecting the internal standard solution into the supply tank 163, after which the solenoid valve 156 is closed. Next, the sample suction nozzle 181 is lowered to near the bottom of the supply tank 163, the electromagnetic valve 151 is opened, and the liquid delivery syringe pump 141 is activated, causing the internal standard solution injected into the supply tank 163 to be drawn towards the pump 141. At this time, the internal standard solution in the flow path 130 is delivered from the upstream side to the downstream side, while contacting each sensitive membrane of the ion-selective electrode 110 and the liquid junction member 122 of the reference electrode 120. Subsequently, the electromagnetic valve 151 is closed and the electromagnetic valve 152 is opened to activate the liquid delivery syringe pump 141, and the internal standard solution is delivered to the drain tank 164. In cleaning mode S5, this series of cleaning processes (the process of sending the internal standard solution from the upstream side to the downstream side of the flow path 130) is usually repeated 20 times before the process ends.

[0041] The analytical method according to the first embodiment is as described above. However, for conditions and processing details not explicitly stated, conditions and processing details adopted in general measurement methods using ion-selective electrodes may be applied, and it goes without saying that these conditions and processing details can be appropriately changed as long as the desired effect is achieved.

[0042] [Analytical apparatus according to the second embodiment] Next, an analytical apparatus according to the second embodiment will be described. Figure 7 is a diagram showing the configuration of the flow sensor and reference electrode of the analyzer according to the second embodiment. The analyzer 20 according to the second embodiment is also called an immunoassay analyzer and is an apparatus based on electrochemiluminescence. The analyzer 20 applies an electric potential to the liquid to be analyzed, thereby generating an optically detectable signal and analyzing the concentration of a specific substance in the liquid. In the measuring cell 300 used in the analysis device 20, a working electrode 320, a counter electrode 310, an optical window 330, etc. are installed on the upstream side of the flow path 130, and a reference electrode 120b is installed on the downstream side. The combination of the working electrode 320, the counter electrode 310, and the optical window 330 constitutes a "flow-type sensor."

[0043] The analyzer 20 applies an electric potential to the liquid flowing through the channel 130 based on the working electrode 320 and the counter electrode 310. This application of electric potential generates an optical signal from the liquid, and the signal emitted through the optical window 330 is detected by a detector (a detector using a photomultiplier tube, semiconductor, etc.). The measurement cell 300 is equipped with a magnet 340, which, during measurement, attracts the target component, which has formed a composite with magnetic particles and luminescent labels contained in the liquid, to the surface of the working electrode 320 using the magnet 340, and electrochemiluminescence is performed by applying a voltage. However, this is not an essential component. Also, the liquid junction member 122b of the reference electrode 120b in Figure 7 has a cylindrical shape that surrounds the flow path 130, but of course, it may have a rod-shaped configuration as shown in Figure 2. Furthermore, the configuration of the measurement cell 300 of the analyzer 20 can be any configuration based on a conventionally known electrochemiluminescence measurement method, and is not limited to the configuration in Figure 7.

[0044] The analysis apparatus 20 according to the second embodiment differs from the analysis apparatus 10 according to the first embodiment only in the "flow-type sensor," therefore, explanations of other components and analysis methods will be omitted. When performing the gas aspiration sequence S2 using the analyzer 20 according to the second embodiment, depending on the inner diameter of the flow path 130 and the size of the device, for example, the procedure may involve aspirating 15 μL of internal standard solution, aspirating 5 μL of gas, aspirating 15 μL of internal standard solution, aspirating 5 μL of gas, and aspirating 15 μL of internal standard solution. Through this series of processes, the wetted portion of the reference electrode 120b within the flow path 130 is filled with the internal standard solution. In addition, the internal standard solution is interrupted by gas in the flow path 130 between the reference electrode 120b and the working electrode 320 or counter electrode 310, and in the flow path 130 downstream of the reference electrode 120b.

[0045] Although the present invention has been described using the first and second embodiments, it is not limited to these forms and includes various modifications. Furthermore, the first and second embodiments are described in detail to make the present invention easier to understand and are not necessarily limited to those having all the configurations described. In addition, it is possible to add, delete, or replace some of the configurations of the first and second embodiments with other configurations. For example, variations are as follows:

[0046] (modified version) In the analysis method according to the first embodiment, in "Decision Method 1" of the decision sequence S3, conductive parts are provided at positions that sandwich the gas-divided points (flow paths 134 and 135) shown in Figure 6A from both sides, and the "divided" / "not divided" status at the two points is determined. However, it is also possible to configure the system to determine only one of the points.

[0047] [Verification of effectiveness] Figure 8 is a graph showing the change in potential difference between the potassium ion selective electrode and the reference electrode after 24 hours in standby mode. Note that the graph in Figure 8 is a general representation and shows how the aforementioned potential difference changes as the number of liquid flow cycles increases after standby mode. Data D1 in Figure 8 is the result obtained using an analytical instrument to which the present invention is not applied. A large potential difference is generated during liquid flow after a 24-hour standby mode, resulting in a large concentration error when converted to concentration. Therefore, at least several dozen liquid flow operations are required to suppress the concentration error and obtain a constant potential difference. On the other hand, data D2 in Figure 8 shows the results obtained using an analytical apparatus to which the present invention is applied. Immediately after liquid flow following a 24-hour standby mode, no large potential difference occurs, and a constant potential difference is observed from the beginning. Therefore, it was found that accurate analysis is possible without concentration errors from immediately after the standby mode using an analytical apparatus to which the present invention is applied. We surmise that this result is because the ion-selective electrode was not contaminated by electrolyte seeping from the reference electrode during standby mode. In addition to the effect of extending the interval for continuous use without requiring initial operation of the analyzer, the present invention has been confirmed to exhibit other excellent effects. Based on the above, it has been confirmed that the analytical apparatus and analytical method according to the present invention are extremely effective in practical applications such as clinical testing.

[0048] Figure 9 is a block diagram of the computer 980 that constitutes the control unit 200. The control unit 200 described above includes one or more computers 980 as shown in Figure 9. In Figure 9, the computer 980 includes a CPU 981, a storage unit 982, a communication port 983, an input / output port 984, and a media port 985. Here, the storage unit 982 includes a RAM 982a, a ROM 982b, and an SSD (Solid State Drive) 982c. The communication port 983 is connected to the communication circuit 986. The input / output port 984 is connected to the input / output device 987. The media port 985 reads and writes data to the recording medium 988. The ROM 982b stores the IPL (Initial Program Loader) and other programs executed by the CPU. The SSD 982c stores application programs and various data. The CPU 981 implements various functions by executing application programs and other data read from the SSD 982c into the RAM 982a. In Figure 1 shown above, the control unit 200, including the potential measurement unit 210 and the concentration calculation unit 220, is shown as a block representing functions primarily implemented by application programs, etc. [Explanation of Symbols]

[0049] 10 Analytical apparatus according to the first embodiment 20 Analytical apparatus according to the second embodiment 100 Measuring part 110 Ion-selective electrode (flow-type sensor) 111 Chloride ion selective electrode 112 Potassium ion selective electrode 113 Sodium ion selective electrode 120 Reference electrode 130 flow channels 141 Syringe pump for liquid delivery (liquid delivery mechanism) 142 Syringe pump for diluents 143 Syringe pump for internal standard solutions 151-157 Electromagnetic valves 161 Bottle for diluent 162 Bottles for internal standard solutions 163 Supply tank 164 Drainage tank 171 Vacuum pump 200 Control Unit 210 Potential measurement unit 220 Concentration calculation section 230 Judgment Department 240 Device Control Unit 250 Output section 260 Input section

Claims

1. The channel through which the liquid to be analyzed flows, A flow-type sensor analyzes the liquid flowing through the aforementioned channel, A reference electrode for measuring the potential of the liquid flowing through the aforementioned channel, A liquid delivery mechanism for delivering liquid in the aforementioned flow path, It comprises at least a device control unit for controlling the liquid delivery mechanism, An analytical apparatus characterized in that, after an analysis mode in which the concentration of a specific substance in a liquid is calculated based on data acquired from the flow-type sensor and the reference electrode, and before a standby mode in which the apparatus waits until the next analysis mode, the apparatus control unit controls the liquid delivery mechanism to fill the wetted portion of the flow path of the reference electrode with liquid, and performs a gas suction sequence in which the liquid filling the wetted portion with gas in at least one of the flow path between the flow-type sensor and the reference electrode, and the flow path on the opposite side of the flow-type sensor from the reference electrode.

2. The analytical apparatus according to claim 1, characterized in that the point of division by the gas is the flow path between the flow-type sensor and the reference electrode.

3. The analytical apparatus according to claim 2, characterized in that the location where the gas is interrupted is a flow path on the opposite side of the flow-type sensor when viewed from the reference electrode.

4. The analytical apparatus according to any one of claims 1 to 3, characterized in that it is equipped with a gas holding mechanism capable of maintaining the state of liquid separation by gas at the point where the gas is used for separation.

5. The analytical apparatus according to claim 4, characterized in that the gas retention mechanism is a mechanism in which the inner wall surface of the flow path exhibits hydrophobicity.

6. The analytical apparatus according to claim 5, characterized in that the gas holding mechanism is a mechanism in which the contact angle between the inner wall surface of the flow path and water is 90° or more.

7. The analytical apparatus according to claim 4, characterized in that the gas holding mechanism is a mechanism in which the flow path at the point of division by the gas is positioned at a higher vertical position than the flow path surrounding that point.

8. The analytical apparatus according to any one of claims 1 to 3, further comprising a determination unit for determining whether or not the liquid filling the wetted portion is divided by the gas.

9. The conductive parts are provided at positions that sandwich the portion to be divided by the aforementioned gas from both sides. The analytical apparatus according to claim 8, characterized in that the determination unit determines whether or not the device is disconnected based on data from the conductive part.

10. The analytical apparatus according to claim 9, characterized in that one of the conductive parts is the flow-type sensor.

11. The analytical apparatus according to claim 8, characterized in that the determination unit determines to perform the gas suction sequence again when it determines that the liquid filling the wetted portion is not divided by the gas.

12. The analytical apparatus according to claim 11, characterized in that when the determination unit determines N times (where N is an integer of 2 or more) that the liquid filling the wetted portion is not divided by the gas, it determines to perform the cleaning process in the cleaning mode after the standby mode and before the next analysis mode more times than usual without performing the gas suction sequence further.

13. An analytical method using an analytical apparatus comprising: a channel through which the liquid to be analyzed flows; a flow-type sensor for analyzing the liquid flowing through the channel; a reference electrode for measuring the potential of the liquid flowing through the channel; and a liquid delivery mechanism for delivering the liquid in the channel, The system includes an analysis mode that calculates the concentration of a specific substance in a liquid based on data acquired from the flow sensor and the reference electrode, and a standby mode that waits until the next analysis mode. An analysis method characterized in that, after the analysis mode and before the standby mode, the liquid delivery mechanism is controlled to fill the wetted portion of the reference electrode in the flow path with liquid, and a gas suction sequence is performed in which the liquid filling the wetted portion is interrupted with gas in at least one of the flow path between the flow-type sensor and the reference electrode, and the flow path on the opposite side of the flow-type sensor from the reference electrode.

14. The analytical method according to claim 13, characterized in that, after the gas suction sequence, a determination sequence is performed to determine whether or not the liquid filling the wetted area is divided by the gas.

15. The analysis method according to claim 14, characterized in that, in the judgment sequence, if it is determined that the liquid filling the wetted area is not divided by the gas, the gas suction sequence is performed again.

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