JP2008046140A - Detector using cartridge - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a cartridge type detector that is convenient for carrying, capable of detecting an object to be inspected, even if the concentration of the object is very low. <P>SOLUTION: The detector comprises a detecting cartridge having a passage that flows a liquid to be inspected that contains a substance to be detected and a process unit that produces information, concerning the substance to be inspected contained in the liquid to be inspected that is circulated through the cartridge. The detecting cartridge has a storage section of the substance to be inspected, a liquid passage that passes through the storage section, a plurality of ports that are led to the liquid passage; and a liquid feed pump, in which at least a part of a detecting mechanism is provided downstream of the storage section. The process unit has a piping switching valve mechanism that switches and connects one, which is selected, from among a plurality of ports that are provided in the detecting cartridge and a valve mechanism switches a passage connection so that the liquid to be inspected that has been supplied to the detecting cartridge passes through the storage section to the outside of the cartridge and a passage connection in which a reagent is supplied to the storage section by a liquid feed pump and the reagent that has passed through the storage section is discharged from another port outside of the cartridge. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a detection apparatus used for detecting a target substance contained in a liquid specimen. In particular, the present invention relates to a detection device including a cartridge and a processing unit combined with the cartridge. More specifically, the present invention is for generating information relating to the presence / absence, concentration, composition and other properties of a substance to be detected in a liquid object containing the substance to be detected, and a flow path through the liquid object. And a processing unit that can connect to the cartridge and generates information about a substance to be detected contained in a liquid specimen passed through the cartridge.

  Japanese Patent Laid-Open No. 10-311829 discloses a card-type portable disposable analysis system. This analysis system includes a card-type disposable inspection tool having a sensor that detects at least one test value in a body fluid of a person or an animal and generates an output signal corresponding thereto, and receives a signal from the test tool to perform an arithmetic process. And a portable analysis unit including a calculation processing unit and a display unit.

  The card-type disposable inspection tool is composed of two substrates that are liquid-tightly superimposed on each other with a thin partition plate in between. One of the substrates is provided on its inner surface with a passage through which a body fluid of a person or animal to be inspected is passed and a body fluid storage section so as to communicate with one end of the passage. A body fluid injection hole that penetrates the substrate in the thickness direction is provided at the other end of the passage. The sensor is provided on the inner surface of the other substrate. Furthermore, a recess for receiving a sensor container for sensor calibration and a second body fluid storage unit communicating with the body fluid storage unit provided on the one substrate through the opening of the partition plate are provided on the inner surface of the other substrate. It is done.

  The portable analysis unit has an insertion port for inserting a test tool, and when the test tool is inserted, the reagent container located in the reagent container receiving recess is broken and flows to the sensor, and prior to actual analysis, the portable test unit is inserted. The sensor is calibrated. Thereafter, human or animal bodily fluid is injected from the bodily fluid inlet and flows to the sensor through a passage formed on the inner surface of the substrate to perform measurement. The electrical signal generated by the measurement is sent to the analysis unit, processed by the arithmetic processing unit, and the analysis result is displayed on the display unit.

  This analysis system is convenient, can be inspected in the field, and can directly inject the body fluid to be inspected with an injector such as a syringe, so that the body fluid to be inspected can be avoided from touching the atmosphere. is there. However, the test object is a high-concentration liquid such as a human or animal body fluid, and cannot be used for concentration measurement or chromatographic analysis of a very small amount of a detected substance such as a harmful heavy metal contained in soil.

  U.S. Pat. No. 6,110,354 discloses an analyzer with a microband electrode array used for the analysis of drinking water and waste water, and biological fluids such as blood and urine. The principle of analysis is to detect the Faraday component of the current generated when the electrolyte liquid to be analyzed contacts the electrode. The structure shown as an example of this analyzer is provided with a flat sensor made of a flat substrate. By using a micro band electrode array, the generation of non-Faraday components can be suppressed and the detection sensitivity can be increased. Therefore, it is considered possible to detect harmful metals contained in minute amounts in aqueous solutions. However, when a very small amount of a substance to be detected such as harmful heavy metals contained in soil is used, it is difficult to measure the concentration using this apparatus because of insufficient detection sensitivity.

  The main object of the present invention is to provide a detection device including a cartridge that can be used easily and a processing unit that is used in combination with the cartridge with few restrictions on a detection target and a use place.

  Another object of the present invention is to provide a concentration detection device, a liquid chromatographic analysis, an immunoassay (immunoassay), and a detection device that can be used in a method for detecting a liquid analyte containing a substance to be detected. Is to provide.

  In particular, another object of the present invention is to provide a simple detection device that is convenient to carry using a cartridge.

  Another object of the present invention is to provide a portable cartridge-type detection device having a structure capable of accommodating a flow channel pipe for liquid flow necessary for detection in an extremely compact manner.

  Another object of the present invention is to provide a concentration detection apparatus that can perform concentration detection without hindrance even if the concentration of a substance to be detected contained in a subject is extremely small.

  Still another object of the present invention is to provide a cartridge-type portable simple detection apparatus that can easily perform analysis such as chromatographic analysis of a liquid specimen even at a sampling site.

  Another object of the present invention is to provide a portable and easy-to-use analyzer that can easily perform concentration detection, liquid chromatographic analysis, analysis by immunoassay, and other detections at any place without any restriction on the inspection place. Is to provide.

  It is a further object of the present invention to provide a detection cartridge and / or processing unit for use in the cartridge-type detection device and / or analysis device described above.

  In order to solve the above problems, in the broadest aspect, the present invention can be connected to a detection cartridge having a flow path for passing a test liquid containing a substance to be detected, and the cartridge. Provided is a cartridge type detection device comprising a processing unit for generating information on a substance to be detected contained in a test liquid. The detection cartridge includes a storage part that temporarily stores a substance to be detected, at least a part of the detection mechanism, a liquid channel that passes through one or both of the storage part and at least a part of the detection mechanism, and the liquid flow And a plurality of ports leading to the road. As used in connection with the present invention, the term “detection” means generating information related to the presence, concentration, composition or other properties of the substance to be detected, such as quantitative and / or qualitative analysis. Includes analysis.

  The processing unit includes a reagent tank and a liquid feed pump. In this aspect of the present invention, the combination of the detection cartridge and the processing unit allows the test liquid supplied in the cartridge to pass through the reservoir and be discharged out of the detection cartridge, and the reagent. The liquid flow path that is supplied from one port of the detection cartridge to the storage unit by the stratified liquid pump and continuously passes through the storage unit and at least a part of the detection mechanism can be switched.

  In one embodiment of the present invention, the test liquid can be supplied to the detection cartridge independently of the processing unit. The test liquid supplied to the detection cartridge reaches the storage part, where the target substance contained in the test liquid is temporarily stored in the storage part. The reservoir can be formed of a porous material such as porous ceramic, or a material having a large surface area such as fibers or fine particles, and a functional group that performs a chemical reaction or an adsorption action on the detected substance on the surface. A modified configuration may be used. With this configuration, the substance to be detected is attached and held on the material forming the storage portion. The remaining test liquid that has passed through the reservoir is sent out of the cartridge from the above-described port of the detection cartridge. Alternatively, a waste liquid reservoir can be formed in the detection cartridge, and the test liquid from the reservoir can be guided to the waste liquid reservoir.

  Next, the reagent is fed from the liquid feed pump of the processing unit to the detection cartridge and passed through the storage section. This reagent has an action of eluting the substance to be detected held in the reservoir by chemical reaction or adsorption. By passing the reagent through the storage part, the substance to be detected held in the storage part is eluted from the storage part, and flows in the cartridge together with the reagent in the form of being contained in the reagent. The reagent containing the substance to be detected temporarily goes out of the cartridge and enters the cartridge again, or passes through the internal flow path of the cartridge without going out of the cartridge, and is provided on the downstream side. It flows toward the mechanism.

  The reagent tank disposed in the processing unit can be connected to a liquid feed pump. In this case, a tank switching valve mechanism can be provided for disposing a plurality of reagent tanks in the processing unit and connecting a desired one of the plurality of reagent tanks to the liquid feed pump. . A waste liquid tank can be disposed in the processing unit so that the liquid produced from the detection cartridge can be guided to the waste liquid tank.

  Furthermore, in another aspect of the present invention, the liquid flow in which the test liquid supplied into the cartridge passes through the reservoir and is discharged out of the detection cartridge without the detection cartridge being installed in the processing unit. The reagent is supplied from one port of the detection cartridge to the storage section by the liquid feed pump in a state where the detection path and the detection cartridge are installed in the processing unit, and the storage section and at least a part of the detection mechanism And a liquid flow path that continuously passes through each of them. In this case, a valve mechanism for switching the liquid flow paths can be provided, and the valve mechanism can be disposed in the processing unit.

  The detection apparatus according to the present invention can be applied to detection of various substances. In one aspect, the detection device is a concentration detection device that provides information related to the concentration of a detection target substance contained in a test solution. In this case, the detection cartridge generates an electrical signal relating to the concentration of the substance to be detected. As an example, the test solution is formed by dissolving a sample such as soil or mud containing a trace amount of a substance to be detected in water or other liquid.

  A detection cartridge according to an aspect when the present invention is applied to a concentration detection apparatus includes a test liquid introduction unit that introduces a test solution in which a test sample is dissolved, and a liquid flow path from the test solution introduction unit. Prepare. The reservoir is disposed in the liquid channel. In this aspect, the storage unit is configured as a concentration unit that concentrates and holds the detection target substance in the test solution. This concentrating part can be configured in the form of a filter having the ability to adsorb the substance to be detected. The detection mechanism provided in the detection cartridge has a detection electrode configuration. The substance to be detected adsorbed on the filter is sent to the detection electrode configuration that constitutes a detection mechanism by eluting into the eluent supplied as a reagent. When the eluent eluted from the substance to be detected reaches the detection electrode configuration, a detection electric signal is generated at the electrode.

  In the detection apparatus of the present invention in this aspect, the processing unit includes a reading unit that reads an electric signal from the cartridge and generates information related to the concentration of the substance to be detected. The detection cartridge in this aspect can be configured to have a waste liquid reservoir, and in this case, a liquid flow path is provided from the test liquid introduction part to the waste liquid reservoir.

  The reading unit includes processing means for receiving and processing an electrical signal from the cartridge and generating information related to the concentration of the substance to be detected in the subject. The processing unit can optionally be provided with a display unit for displaying the detection result.

  The cartridge type concentration detection apparatus according to this aspect of the present invention can be used for detection of heavy metals contained in soil, mud and the like. In this case, the detection cartridge generates an electric signal related to the concentration of heavy metal in the test liquid containing heavy metal in the electrode configuration, and the electric signal from the cartridge is read by the reading unit to detect the substance to be detected. Is configured to generate information regarding the concentration of.

  In the cartridge type concentration detection apparatus for detecting the concentration of heavy metal, as described above, the cartridge includes a test liquid introduction part that introduces a test liquid, and a liquid channel that communicates with the test liquid introduction part. A reservoir that functions as a concentration unit for concentration of the test solution disposed in the liquid flow path from the test solution introduction unit, and a detection electrode configuration are provided. Here, the storage unit, that is, the concentration unit includes an adsorption carrier that is disposed in the flow path and acts to adsorb heavy metal, and an eluent that elutes the heavy metal adsorbed on the adsorption carrier is contained in the concentration unit. Combined with an eluent supply unit that flows through the adsorbent carrier toward the detection electrode configuration, the heavy metal adsorbed on the adsorbent carrier is dissolved in a predetermined amount of eluent from the eluent supply unit and contacts the detection electrode configuration As a result, an electric signal related to the concentration of the substance to be detected is generated at the detection electrode.

  In the cartridge type concentration detection apparatus according to another aspect of the present invention, the storage section of the cartridge, that is, the concentration section receives the test liquid from the test liquid introducing section and adsorbs the target substance contained in the test liquid. And an eluent supply section for supplying an eluent for eluting the detection substance adsorbed on the adsorption carrier through the adsorption carrier toward the detection electrode configuration. Are combined, and the substance to be detected adsorbed on the adsorption carrier is dissolved in a predetermined amount of eluent from the eluent supply unit and brought into contact with the detection electrode configuration, whereby an electrical signal related to the concentration of the substance to be detected is generated. It is generated in the detection electrode configuration.

  In the cartridge type concentration detection apparatus according to still another aspect of the present invention, the detection cartridge includes a test liquid introduction unit that introduces a test solution in which the test sample is dissolved, and a test sample that is introduced into the test liquid introduction unit. A concentration unit for concentrating the test solution, a detection electrode configuration, and a flow path connecting the test solution introduction unit, the concentration unit, and the detection electrode configuration are provided. The concentrating unit includes an adsorption carrier that receives the test liquid from the test liquid introducing unit and acts to adsorb the target substance contained in the test liquid. Further, the concentration unit is combined with an eluent supply unit that allows an eluent that elutes the substance to be detected adsorbed on the adsorption carrier to flow through the adsorption carrier toward the detection electrode. A valve mechanism is provided, and the valve mechanism opens a test liquid introduction flow path from the test liquid introduction section to the concentration section, and closes the eluate supply flow path from the eluent supply section to the concentration section. Between the working position and the eluent supply position that closes the test liquid introduction flow path from the test liquid introduction section to the concentration section and opens the eluate supply flow path from the eluent supply section to the concentration section Switching can be done. Further, in order to send the eluent from the eluent supply part to the concentration part at the eluent supply position, a liquid feed pump means is provided.

  In this aspect, the substance to be detected adsorbed on the adsorption carrier is dissolved in a predetermined amount of the eluent from the eluent supply unit and brought into contact with the detection electrode configuration, so that the electric power related to the concentration of the substance to be detected is obtained. A signal is generated in the detection electrode configuration. In this configuration, the eluent supply unit, the valve mechanism, and the liquid feed pump means can be provided in the casing of the processing unit.

  The cartridge is formed with a discharge channel for discharging the test liquid after passing through the adsorption carrier to the outside of the cartridge and a waste liquid reservoir for storing the eluent after passing through the electrode configuration. In the introduction stage, the discharge flow path is opened and the flow path between the electrode configuration and the waste liquid reservoir is closed, and in the eluent supply stage, the discharge flow path is closed and the flow between the electrode configuration and the waste liquid reservoir is closed. The road can be opened. The adsorption carrier may be in any form of a membrane, fine particles, or a porous body.

  The adsorption carrier can be a cationic substance adsorption carrier. In this case, the adsorption carrier can be formed by treating the material constituting the carrier with a sulfonic acid group. Further, the adsorption carrier can be an anionic substance adsorption carrier. In this case, the adsorption carrier can be formed by treating the material constituting the carrier with a quaternary amine group. Further, the adsorption carrier can be formed by treating the material constituting the carrier with a heavy metal accepting substance. The heavy metal accepting substance can be any one of a chelate substance, an inclusion body, and a heavy metal adsorbing substance. The chelating substance can be either iminodiacetic acid or an ethylenediamine group. The clathrate can be either porphyrin or calixarene. The heavy metal adsorbing substance can be either an apoenzyme or a heavy metal adsorbing antibody.

  The cartridge can be formed in a card shape, and the processing unit in this case preferably forms an insertion portion for inserting the card-shaped cartridge into the casing.

  The electrode configuration preferably includes at least one microelectrode element whose size is not greater than 10 μm. In this case, it is preferable to form the microelectrode element by disposing an insulating sheet on the upper surface of the electrode element and forming a hole having a dimension not larger than 10 μm in the insulating sheet.

  The electrode configuration shall include a plurality of working electrode elements, at least one counter electrode element, and at least one reference electrode element, the plurality of working electrode elements having different areas and different concentration range measurements. Can work for.

  Further, the electrode configuration may include at least one working electrode element, at least one counter electrode element, and at least one reference electrode element.

  In addition, the concentrating part constituting the storage part has a structure in which a cation adsorbing carrier that adsorbs a cationic substance and an anion adsorbing carrier that adsorbs an anionic substance are arranged in parallel. An electrode set is included, and each electrode set can correspond to a cation adsorption carrier and an anion adsorption carrier, respectively.

  In the cartridge type concentration detection apparatus according to still another aspect of the present invention, the detection cartridge includes a test liquid introduction part that introduces a test liquid that is a concentration detection target, and a liquid channel that is connected to the test liquid introduction part. And a concentration detection electrode configuration disposed in the liquid flow path, and the test liquid is related to the concentration of the specific substance contained in the test liquid by contacting the test liquid with the concentration detection electrode configuration in the liquid flow path. The electrical signal to be generated is generated by the concentration detection electrode configuration. The electrode configuration includes a plurality of working electrode elements, at least one counter electrode element, and at least one reference electrode element, the plurality of working electrode elements having different areas and measuring different concentration ranges. To work.

  In the cartridge-type concentration detection device according to still another aspect of the present invention, the detection cartridge has a flat card shape, and the casing is provided with an insertion portion for inserting the card-shaped cartridge. This cartridge includes a test liquid introduction part for introducing a test liquid to be a concentration detection target, a liquid channel connected to the test liquid introduction part, and a concentration detection electrode configuration arranged in the liquid channel. In preparation for the above, an electric signal related to the concentration of a specific substance contained in the test liquid is generated by the concentration detection electrode configuration by flowing the test solution on the concentration detection electrode configuration in the liquid flow path. ing.

  This cartridge has a resin-made first sheet material in which a concave portion constituting at least a part of the liquid channel is formed on one surface, and a concave portion for accommodating a through-hole and a detection electrode configuration constituting a test liquid introducing portion. A resin-made second sheet material and a resin-made third sheet in which a through-hole constituting the test liquid introducing portion is formed, and the first, second, and third sheets are respectively They are laminated in order with an insulating material sheet in between. An electrode element having a detection electrode configuration is disposed in the electrode housing recess of the second sheet, and the second sheet and the third sheet are laminated so that the electrode element faces the third sheet. The insulating sheet between the second sheet and the third sheet is formed with a hole that exposes the required area of the electrode in a portion corresponding to the electrode element, and the side of the third sheet facing the second sheet is covered with A liquid flow path for guiding the test solution to the electrode element is formed.

  In this case, the first sheet of the cartridge can be formed with a recess constituting a waste liquid reservoir for storing the waste liquid from the electrode elements on the side facing the second sheet.

  According to the above aspect of the present invention, since the concentration channel for concentrating and storing the substance to be detected is provided in the fluid flow path of the detection cartridge, the concentration of the substance to be detected is very low. However, concentration detection can be performed without any problem. If the soil is contaminated with harmful heavy metals, etc., even if the concentration is very low, it is subject to regulation. Conventionally, it was thought that such a low concentration substance could not be detected in the field, but if the cartridge type concentration detector according to this aspect of the present invention is used, the soil to be examined is collected. This makes it easy to detect contaminants at the locations where they are used. In this case, the test sample solution may be formed by dissolving the sample soil. The concentration unit for concentrating the substance to be detected preferably includes an adsorption carrier that adsorbs the substance to be detected, but may be based on another concentration principle. For example, there are a concentration method by evaporating a liquid component by heating, a method using a reverse osmosis membrane, and the like.

  The concentration detection apparatus according to the above aspect of the present invention may be any substance as long as electrical information relating to the concentration of the substance to be detected is generated on the electrode when the liquid containing the substance to be detected contacts the detection electrode. It can also be applied to the concentration detection of various substances. As an electrode configuration to be used, typically, an electrode composed of a working electrode, a counter electrode and a reference electrode is usually used. The working electrode is an electrode that adsorbs a substance to be detected and releases the substance to be detected into the eluent when it comes into contact with the eluent. The desired conditions for the working electrode are that the potential range that can be applied is wide, that is, that the potential window is wide, and that it is resistant to corrosion and oxidation. The potential window refers to a potential region where hydrogen ions are not generated electrochemically or an oxide film is not generated. This region varies depending on the material of the electrode and the pH value of the solution to be measured.

  Preferred materials for use as the working electrode are platinum, gold, mercury, silver, bismuth, carbon and the like. In forming the working electrode, these materials may be selected as appropriate. However, a material that easily adsorbs a target substance to be measured is preferable. When the substances to be detected are cadmium, lead and mercury, it is appropriate to use an electrode having a carbon surface as the working electrode and an electrode having a gold surface as the working electrode for measuring arsenic and mercury. is there. For detection of hexavalent chromium, an electrode having a carbon surface may be used. This is because an electrode having a carbon surface has a property of adsorbing an aggregate of hexavalent chromium and diphenylcarbazide well.

  The electrode having a carbon surface is preferably a carbon electrode made of a graphite carbon sintered body having a graphite / glassy carbon ratio of 70/30. In general, graphite easily adsorbs lead, cadmium, mercury, and the like, but it is difficult to align the crystal orientation, so that there is a problem that the adsorption of the substance varies and the liquid that is in contact swells. However, by mixing glass-like carbon into graphite and sintering it, the sintered body can be densified and the penetration of the liquid can be suppressed. Further, the variation in adsorption can be made extremely small by randomizing the orientation direction of graphite by vitreous carbon. The above-mentioned sintered body having a graphite / glassy carbon ratio of about 70/30 is advantageous for constructing a working electrode having high sensitivity and good reproducibility.

  There are no particular restrictions on the material of the electrode having a gold surface. In this invention, the working electrode which operate | moves favorably can be obtained by using the structure which coat | covered gold | metal | money via the chromium layer on the glass substrate. In this case, chromium and gold can be formed by sputtering. The thickness of the film is not particularly limited, but the chromium layer may be about 40 nm and the gold layer may be about 400 nm.

  The counter electrode is for flowing a current between the working electrode. Any conductive material can be used as the counter electrode.

  The reference electrode is an electrode that can be used as a reference of potential by showing a known stable potential. Typical reference electrodes in this case include a hydrogen electrode, a saturated calomel electrode (mercury / mercury chloride electrode), a silver silver halide electrode, and the like. As a silver / silver halide electrode, there is a silver / silver chloride electrode in which the silver surface forms silver chloride by an equilibrium reaction with a solution containing chlorine. In this electrode, even when a voltage is applied, the equilibrium state between silver and silver chloride is always maintained, so that the potential developed is always constant and can be used as a reference electrode. Although a silver / silver bromide electrode and a silver / silver iodide electrode can also be used, a silver / silver chloride electrode is preferable from the viewpoint of versatility of materials and processing cost.

  The size of the electrode is not particularly limited. For example, a small plate having a rectangular planar shape of 3 × 8.4 mm and a thickness of 0.5 mm is formed on a thin plate electrode having a diameter of about 1 to 2.5 mm. A sheet such as an opened double-sided pressure-sensitive adhesive tape can be attached to expose the electrode surface of a predetermined area. Although it is preferable from the viewpoint of easiness of molding and attachment that the electrode is formed by sticking a thin plate-shaped pre-formed electrode material to the cartridge substrate, the electrode can also be directly formed on the cartridge substrate.

  Detection is most commonly by electrochemical measurements. In an electrochemical reaction in an aqueous solution, since the reaction on the electrode is faster than the mass transfer in the solution, there is a response delay due to the mass transfer rate called solution resistance, and the peak becomes unclear. When a microelectrode with an electrode size of the order of μm is used, the problematic mass transfer changes from surface diffusion to point diffusion, and the response delay per unit area is alleviated. Therefore, a peak having a smaller scale can be discriminated, and the sensitivity is improved. In order to be able to expect this effect, it is preferable that the short dimension of the electrode is 10 μm or less. Moreover, a high total current can be obtained by arranging a large number of such electrodes in an array. In order to create a microelectrode having such a size, a semiconductor microfabrication technique can be used. For example, a minute circular electrode can be obtained by forming an insulating layer on the electrode material and providing a hole smaller than 10 μm in the insulating layer. Further, the same effect can be exhibited even when the comb electrode has a shape in which working electrodes and counter electrodes smaller than 10 μm are alternately arranged.

  When detecting heavy metals by electrochemical measurement, it is desirable to reduce the charging current for raising the working electrode to a predetermined potential as much as possible. For this purpose, it is necessary to make electrons move more easily in a solution containing heavy metals, and an appropriate electrolyte can be added for that purpose. Any substance that forms a salt in the solution may be used, but potassium chloride, sulfuric acid, nitric acid, potassium nitrate, sodium hydroxide, and the like are preferable from the viewpoint of price. In addition, since the potential window of the working electrode has the property of shifting to the negative side or the positive side depending on the pH, hydrogen generation and action from the working electrode in the potential range to be measured can be achieved by adjusting the pH with an electrolyte. Problems such as the formation of the finest oxygen film can be prevented.

  The eluent described below is typically a solution containing an electrolyte. By feeding the eluent containing the electrolyte at a constant flow rate, elution to detection can be performed continuously. With this configuration, piping and operation can be simplified, and it is not necessary to manage the mixing ratio and mixing speed of the solution. When preparing the eluent and the electrolyte solution separately, it is necessary to manage the absolute amount of each solution. However, when the space for providing the flow path and electrodes is extremely small as in the concentration detection device of the present invention. However, it is difficult to control the absolute amount of the solution, and it is extremely important to perform elution and electrochemical measurement with only one type of solution.

  Further, as described above, in the reference electrode, in order to produce silver chloride on the printed silver, a solution containing chlorine is brought into contact with the printed silver as a reference electrode activation liquid, and a very weak current is applied. Flow to the reference electrode. Therefore, if chlorine is contained in the eluent, it is not necessary to separately use an activation liquid used to activate the reference electrode, and a simple structure can be obtained. However, in the case of selenium measurement, chlorine acts as an obstruction when performing electrochemical measurement, and therefore it is not possible to contain chlorine in the eluent. For this reason, it is necessary to use the reference electrode activation liquid described below.

  The reference electrode activation liquid is made to contact with the printed silver, and by causing a very weak current to flow through the reference electrode, silver chloride is generated on the printed silver to act as a reference electrode. Is. The reference electrode activation liquid generally contains an appropriate amount of chlorine. The preferred chlorine content is 0.05M to 3M. If the content is too small, the formation of silver chloride becomes unstable, and if it is too large, it will be difficult to handle because it will precipitate solids. The activation liquid can be prepared by dissolving a predetermined amount of potassium chloride, sodium chloride, or the like in water.

  Since the reference electrode needs to have an electrical interaction between the working electrode and the counter electrode, the reference electrode activation liquid needs to be in contact with the eluent. However, one of the purposes of using the electrical reference electrode activation liquid separately from the eluent is to avoid chlorine becoming an obstruction during electrochemical measurements. That is, since it is necessary to prevent the reference electrode activation liquid from flowing into the working electrode part, a reference electrode chamber is provided separately, and a structure is formed in which the reference electrode chamber and the eluent are connected by a liquid path. Keep it. The liquid channel is preferably a fine channel so that molecular diffusion does not easily occur. A structure in which the reference electrode chamber and the eluent are separated by a porous membrane may be used, but in this case, it takes a certain amount of time for the reference electrode activation liquid to penetrate into the porous membrane. For the purpose of detecting a substance to be detected in a short time as in the invention, the fine channel is more preferable. A reference electrode is installed in the reference electrode chamber, and the reference electrode activation liquid is preliminarily included in the reference electrode quality, or the reference electrode activation liquid is supplied as necessary. It is desirable. When the reference electrode activation liquid is mounted in advance on the detection cartridge, it is useful to enclose the reference electrode activation liquid in an aluminum pack or the like in order to prevent the solid substance from precipitating due to the evaporation of the liquid. is there.

  Some adsorbent carriers require a liquid that activates the adsorbent carrier to pass through before passing the sample liquid. For example, quaternary amines that adsorb arsenic, selenium, and hexavalent chromium exhibit adsorption performance when they come into contact with OH- ions. This is because the target anions replace OH- ions. The reaction is used. In this case, an adsorption carrier activation liquid is used. As the adsorption carrier activating liquid, sodium hydroxide, potassium hydroxide or the like is used.

  The adsorption carrier is provided in the channel on the upstream side of the electrode configuration. As already described, the adsorption carrier may be in any form of a film, fine particles, and a porous body, or a combination thereof. The present invention can also be applied to chromatographic analysis, immunoassay, and other detections, and the adsorption carrier may be selected in accordance with its purpose. Below, each form is demonstrated concretely.

[Membrane structure]
The filter is formed mainly by fibers. An appropriate hole may be formed in the polymer film or the metal film. Examples of membrane structures include those that have an adsorption function for the substance to be measured depending on the form of the surface, those that have the same adsorption function by modifying the surface with functional groups, and particles having a specific function carried on the fiber Things.
Fine particles: Some of these structures have the function of adsorbing the substance to be measured depending on the form of the fine particle surface, and the same adsorption function by modifying the fine particle surface with a functional group. Chromatography can be performed if the fine particles are packed in a column shape extending about 10 mm or more in the longitudinal direction of the flow path. The filling shape may be either a rectangular parallelepiped shape or a cylindrical shape.

[Porous body]
A carrier having a large number of communication holes. Examples include monolithic porous inorganic materials such as porous ceramics and porous glass, or polyacrylamide gel, styrene divinylbenzene copolymer and the like made porous. Some have a function of adsorbing the substance to be measured depending on the form of the surface of the communication hole, and others have the same adsorption function by modifying the surface of the communication hole with a functional group. In the case where the carrier having the communication hole has an integral structure, this is hereinafter referred to as a monolith. If the length is smaller than the length that can be chromatographed, this is called a monolith disk, and the length that can be chromatographed is called a monolith column, and both terms can be used according to the purpose. Monolithic columns can pass at relatively low pressure compared to resin-filled columns, so low-pressure liquid feed pumps can be used, and equipment with the same analytical performance is smaller and consumes less power. Electricity becomes possible. The monolith disk can also be supplied at a low pressure for the same reason, so that the device can be easily downsized. Since both the monolith column and the monolith disk have an integrated structure, they are easy to handle when installed in a cartridge type microreactor.

  Examples of the material constituting the adsorption carrier include styrene-divinylbenzene copolymer, polymethacrylate resin, polyhydroxymethacrylate resin, polyvinyl alcohol, polyethylene, polypropylene, ethylene-propylene copolymer, and other polyolefins, ethylene- Halogenation represented by tetrafluoroethylene copolymer, olefin-halogenated olefin copolymer represented by ethylene-chlorotrifluoroethylene copolymer, polytetrafluoroethylene, polyvinylidene fluoride, polychlorotrifluoroethylene, etc. Examples include polyolefin and polysulfone, silica, alumina and the like. In the case of fibrous adsorbent carriers, cellulosic materials, plant fibers such as cotton and hemp, various natural fibers typified by animal fibers such as silk and wool, polyester fibers, polyamide fibers, etc. Fibrous materials such as various synthetic fibers are used.

  Even when the above structure is not adopted, if the wall surface of the flow path has an adsorption function for the substance to be measured, a concentration function can be similarly produced.

  In order to give the surface of the adsorption carrier an adsorption function for the substance to be measured, the surface has a complementary structure to the substance to be measured, or an ionic bond, a coordination bond, a chelate bond, a hydrophobic interaction, What is necessary is just to make it fix the functional molecule which causes the interaction by an intramolecular polarity.

  Examples of the functional molecule having an interaction include a sulfo group, a quaternary ammonium group, an octadecyl group, an octyl group, a butyl group, an amino group, a trimethyl group, a cyanopropyl group, an aminopropyl group, a nitrophenylethyl group, and a pyrenylethyl group. Group, diethylaminoethyl group, sulfopropyl group, carboxyl group, carboxymethyl group, sulfoxyethyl group, orthophosphoric acid group, diethyl (2-hydroxypropyl) aminoethyl group, phenyl group, iminodiacetic acid group, ethylenediamine, sulfur atom Chelate-forming groups such as various functional groups such as mercapto groups, dithiocarbamic acid groups, thiourea groups, avidin, biotin, gelatin, heparin, lysine, nicotinamide adenine dinucleotide, protein A, protein G, phenylalanine, and castor Merekuchin, dextran sulfate, adenosine 5 'phosphate, glutathione, ethylenediamine diacetic acid, Procion red, aminophenyl boronic acid, bovine serum albumin, polynucleotides (e.g. DNA), protein atomic groups such as (e.g., antibody) and the like. These substances may be used alone or in combination of two or more.

  The eluent is for detaching the substance to be detected adsorbed on the adsorption carrier from the adsorption carrier. Since the effective eluent varies depending on the form of adsorption, the eluent is selected based on the chemical characteristics of adsorption. For example, a solution containing ions that are easily adsorbed on the surface of the adsorption carrier, and when the solution passes through the adsorption carrier, the component to be measured in the form of ions already adsorbed on the adsorption carrier is contained in the eluent. By exchanging with ions, the component to be measured can be released from the adsorption carrier. In the present invention, an eluent having the following composition can be used depending on the substance to be detected.

  For the measurement of cadmium, lead and mercury, Empor (TM) disk cartridge available from 3M under the trademark Cation-SR is used as the adsorption carrier, and 0.4M potassium chloride, 10mM citric acid, 3.5m as the eluent. A liquid (pH = about 4) containing mM ethylenediamine is used. This adsorption carrier is a film having a thickness of 0.5 to 0.75 mm obtained by fixing fine particles having a particle diameter of 50 to 100 μm to fibrous Teflon (registered trademark). It is composed of 10% fine particles and 90% fibrous Teflon (registered trademark). Sulfonic acid groups are formed on the surface of the fine particles.

  For the measurement of arsenic, selenium and hexavalent chromium, Empore (TM) disk cartridge available from 3M under the Anion-SR trademark is used as the adsorption carrier, and 1M sulfuric acid (pH = About 2) is used. This adsorption carrier is also a film having a thickness of 0.5 to 0.75 mm obtained by fixing fine particles having a particle size of 50 to 100 μm to fibrous Teflon (registered trademark). A quaternary amine group is formed on the surface of the fine particles.

  Some adsorbent carriers need to be passed through a liquid that activates the adsorbent carrier before allowing the sample liquid to pass through. For example, quaternary amines that adsorb arsenic, selenium, and hexavalent chromium exhibit adsorption performance when they come into contact with OH- ions. This is because the target anions replace OH- ions. The reaction is used. In this case, an adsorption carrier activation liquid is used. As the adsorption carrier activating liquid, sodium hydroxide, potassium hydroxide or the like is used.

  The size of the adsorption carrier can be freely determined as long as the adsorption capacity of the adsorption carrier is not saturated when adsorbing the target component. The size of the adsorption carrier is determined by assuming in advance how much a substance that can be adsorbed on the adsorption carrier is contained in the solution containing the substance to be measured. When the adsorption capacity of the adsorption carrier is small, it is easy to increase the concentration factor, but it is easy to achieve saturated adsorption, and therefore it is necessary to make the adsorption carrier large enough to obtain a desired adsorption capacity. In addition, when a chromatographic action is expected in the adsorption part, it is necessary to form a column shape having a length of at least 10 mm in the flow path direction.

  The porosity of the adsorption carrier, the size of the communication hole, and the like are determined in such a range that the contact with the solution can be reliably performed and clogging does not become a problem. In the case of a membrane structure, the coarseness of the mesh is preferably about 0.3 μm or more. When fine particles are used, the particle diameter is preferably about 2 to 50 μm, and the communication hole in the case of a monolith column is preferably about 1 to 50 μm.

  In this aspect of the invention, favorable results can be obtained by using the 3M Empor ™ disk cartridge described above. Since this disc cartridge is very thin, the amount of the eluent used when removing the adsorbed heavy metal is specifically small, such as 9 to 15 μl. Therefore, the concentration of the heavy metal in the eluent can be reduced. As a result, highly sensitive analysis can be realized. Regardless of the form of the adsorbent carrier, it is important that the volume is extremely small in the case of analysis of trace components.

  Further, by using such a thin film structure, the liquid feeding pressure necessary for passing the liquid is hardly applied. In order to reduce the size of the apparatus, it is essential to reduce the size of the pump, and it is effective to reduce the liquid feeding pressure. From this viewpoint, it is preferable to take the form of a thin film structure.

In order to transfer and store various liquids in the detection cartridge, a microchannel is formed. The flow path for transferring the liquid has a width on the order of several hundred μm to several mm and is formed by a groove having a depth of several hundred μm, and the cross-sectional area of the flow path is about 100 μm ^{2 to 1} mm ^2. preferable. If the flow path is too large, turbulent flow is likely to occur in the flow path, and transport of the target substance is not uniform. If the flow path is too small, there may be a problem that the flow path is clogged by fine particles or the like existing in the flow path or bubbles are difficult to escape. In order to reliably transfer the liquid, the inside of the flow path may be hydrophilized. The hydrophilization treatment also has an effect of making it difficult for bubbles to stay.

  In order to connect the cartridge to the reading unit of the processing unit, it is preferable to mechanically couple the cartridge to the casing of the reading unit. In order to obtain an arrangement that ensures that the positions corresponding to the electrodes and openings in the cartridge and the terminals of the reading unit, the valve mechanism, and the inlets of various solutions are correctly connected, the casing of the processing unit includes It is preferable to provide a holder portion for holding the cartridge in a predetermined position. The cartridge and the casing are provided with a recess and a protrusion so as to be fitted in conformity with each other, and these engage with each other to securely hold the cartridge in the casing of the processing unit.

  Electrochemical detection is performed via a pin-shaped terminal fixed to the holder part. These terminals and the processing unit are connected in advance. This terminal is preferably provided at a position where the electrode is located when the cartridge is installed in the processing unit, and is provided with a spring inside thereof so that it can be expanded and contracted to ensure connection. In a state where the cartridge is installed in the holder portion, the terminal fixed to the holder in advance so as to be positioned above the electrode reliably contacts the electrode by the force of the spring. A voltage is applied to these electrodes according to a preset measurement profile, a current flowing through the electrodes is detected, and a signal is sent to a recording or display unit.

  The liquid feeding function unit can be constituted by a liquid feeding pump, a valve mechanism that opens and closes an opening during liquid feeding, and an electronic substrate for controlling these pump and valve mechanism. The valve mechanism is connected to a container in which the corresponding eluent, electrolyte solution, pretreatment liquid for the adsorption carrier, washing water and the like are stored.

  The liquid feed pump is preferably one that can stably feed a small amount of liquid, has no pulsation, and has a constant flow rate. It is preferable that a flow rate of about 5 to 100 μl / min can be stably realized, and the pressure at which the pump can send liquid is preferably 0.01 to 10 MPa. Moreover, it is preferable that the main body is small and light and consumes little power. An example of a pump that meets these conditions is a syringe pump. A suitable syringe pump is a Uniflow pencil pump.

  In the concentration detection apparatus which is one embodiment of the present invention, it is preferable to perform measurement while flowing a test solution containing a target substance at a constant flow rate during the measurement. For this purpose, it is preferable to employ a flow rate detecting means. By flowing the solution, the number of heavy metal ions passing through the vicinity of the electrode surface per unit time increases, and as a result, the amount of the detected substance to be precipitated increases, so that the measurement can be performed with high sensitivity. . In addition, since the solution can be constantly updated at a constant flow rate, there is no need to consider the effect of the remaining amount of the adsorption carrier activation liquid or cleaning liquid, or to manage the total volume of the solution. It becomes possible to perform highly accurate analysis only by managing only. Furthermore, by changing the flow rate according to the analysis target and concentration, measurement can be performed under appropriate conditions, and a common chip can be used for various analysis targets.

  Moreover, in the above-described aspect of the present invention, by controlling the linear velocity of the flow of the test solution, it is possible to simultaneously analyze the high concentration / low concentration and increase the measurement accuracy. Such an effect can be expected by the control as a result of adopting the flow rate detecting means.

  In the embodiment of the present invention that controls the flow rate described above, the amount of the substance to be measured adsorbed on the electrode surface is changed by changing the electrode area or the width and depth of the flow path in which the electrode is stored for each electrode. It is possible to perform analysis in a low concentration range and a high concentration range at the same time. For example, if an electrode area with a diameter of 1 mm and a diameter of 2.5 mm is used in combination, a sensitivity of about 19 times can be properly used. In this case, it is preferable to arrange an electrode for low concentration detection on the upstream side of the flow path and an electrode for high concentration detection on the downstream side.

  The present invention can also be configured as an analyzer for liquid chromatography analysis. That is, in another aspect of the present invention, the cartridge type detection device may use a detection cartridge for liquid chromatography analysis. In this case, the detection cartridge may be provided with a column for adjusting a test liquid and an absorbance measurement cell, and the processing unit directs light from the light source and the absorbance measurement cell of the cartridge. An incident optical system and a spectroscope that receives light that has passed through the absorbance measurement cell and generates information about the substance to be detected can be provided. Also in this aspect, as in the case of the concentration detection apparatus, it is preferable to perform the measurement while flowing the test solution containing the target substance at a constant flow rate during the measurement.

  The target of liquid chromatography analysis is protein, nucleic acid oligomer, DNA, RNA, peptide, agricultural chemical, organic acid synthetic molecule oligomer, polymer, additive, monosaccharide, disaccharide, small sugar, polysaccharide, saturated fatty acid, unsaturated Examples include fatty acids, glycerides, phospholipids, steroids, anions and cations. The measurement principle is well known, and a method based on the known principle can be adopted in the present invention. What is necessary is just to comprise the storage part in the case of a liquid chromatography analysis similarly to the case of a density | concentration detection apparatus.

  Further, according to the present invention, the processing unit can include a cartridge mounting portion to which the detection cartridge can be detachably mounted and a reagent tank mounting portion to which the reagent tank can be detachably mounted. Further, the cartridge can be provided with a waste liquid port, and a waste liquid tank that receives the waste liquid from the cartridge can be provided in the processing unit. In this case, the pipe switching valve mechanism is configured to selectively connect the waste liquid port of the cartridge to the waste liquid tank.

  The pipe switching valve mechanism and the tank switching valve mechanism can be disposed on the pipe switching valve plate and the tank switching valve plate, respectively. At least one of the pipe switching valve plate and the tank switching valve plate can have a structure in which a plurality of plate elements formed by plastic material injection molding or plate material cutting are stacked and fixed. In this case, at least one plate element is preliminarily formed with a required pattern of holes and flow channels required for liquid flow. The other plate element may or may not have holes and grooves. By laminating and fixing a plurality of plate elements, a plate having a required flow path is formed inside, and a valve attached to the valve plate is appropriately connected to these flow paths through the holes. .

  By configuring the valve plate in this way, it is possible to store the piping for the necessary flow path in a compact manner. In addition, this configuration is useful for preventing mistakes in piping, finding clogged channels and leaks, and reducing the number of parts, which is advantageous from the viewpoint of manufacturing and maintenance. In addition, there is an advantage that the replacement is easy. Furthermore, when the plate element is made of a transparent plastic material, there is an advantage that visibility inside the plate is improved. In an actual design, the valve plate can be as small as a few cubic centimeters, with the advantage that most of the required piping can be accommodated in this small space.

  Examples of the method for laminating and fixing the plate elements include a method using an adhesive or a pressure-sensitive adhesive, bonding using high temperature or ultrasonic waves, diffusion bonding, and the like. Diffusion bonding is a technology that is mainly applied to metals, where the materials to be bonded are exposed to a high-temperature and high-pressure atmosphere, causing the material atoms to diffuse, and causing the united fusion to occur on the bonding surface. Can also be applied. Examples of plastic materials to which diffusion bonding can be applied include acrylic resin, PEEK (polyether-ether-ketone resin), and PTFE (polytetrafluoroethylene).

  In the present invention, electronic processing means including a power source and information processing means can be built in the housing of the processing unit. The plurality of reagent tanks may be a cleaning liquid tank, an activation liquid tank, and an eluent tank. When the eluent is passed through the liquid flow path in the cartridge, it elutes the substance to be detected temporarily stored in the storage section of the cartridge and sends it to the flow path in the cartridge for the desired analysis. To do.

  As described above, the storage unit can be configured as an adsorption carrier having a property of adsorbing a substance to be detected, for example. Further, at least one of the reagent tanks can be an eluent tank. Here, the eluent is for detaching the substance to be detected, which is stored in a reservoir, which can be configured as an adsorption carrier having the property of adsorbing the substance to be detected, from the adsorption carrier. Since the effective eluent varies depending on the form of adsorption, the eluent is selected based on the chemical characteristics of adsorption. For example, a solution containing ions that are easily adsorbed on the surface of the adsorption carrier, and when the solution passes through the adsorption carrier, the component to be measured in the form of ions already adsorbed on the adsorption carrier is contained in the eluent. By exchanging with ions, the component to be measured can be released from the adsorption carrier. In the present invention, eluents having various compositions can be used depending on the substance to be detected.

  The present invention can also be implemented as an apparatus for detection by immunoassay (immunoassay). Measurement targets in this case are allergens such as egg yolk, egg white, milk, peanut, shrimp, crab, fish, shellfish, soybean, mango, and other foods known as allergens, dust mites, feathers, pollen , Fungi, bacteria, cockroaches, dog or cat hair. In addition, endocrine disruptors, pesticides, immunoglobulins such as IgE or IgG, histamine, genes (RNA), stress markers, various proteins, human or animal blood, blood components, urine, saliva, body fluids Or an antibody, the component which shows a specific disease, etc. can be mentioned.

  The immunoassay is classified into a labeling method and a non-labeling method, a competitive method and a non-competitive method (sandwich method), a homogeneous method and a heterogeneous method, etc., depending on the type of label used, the reacted antigen, and the method for separating the antibody. . A specific analysis example is constructed by a combination of these. Various combinations are possible, but combinations suitable for application to the present invention will be described later.

  Detection methods include immunoturbidimetry, latex agglutination turbidimetry, non-labeling methods such as immunosensors consisting of antigen electrodes and antibody electrodes, enzyme immunoassays, fluorescent immunoassays, luminescent immunoassays, spin immunoassays, metalloimmunoassays, particle immunoassays. In addition, there are labeling methods such as Bayreu-Munoassay, and any of them can be used in the present invention.

  In this embodiment, the reservoir of the detection cartridge can be configured as a filter, and a test substance such as an antigen and / or an antibody is immobilized on the surface of the filter. This immobilization can be performed directly on the filter surface, and may be performed via an appropriate ligand. For example, this immobilization can be performed by immersing a plastic material or carbon fiber in an antigen and / or antibody solution. Depending on the antigen and / or antibody to be used, it is better to interpose a metal during immobilization, for example, when using a gold-mercapto bond. In such a case, the metal coating can be easily formed by, for example, plating the carbon fiber, or performing a sputtering process or a plasma process.

  As the antibody and / or antigen, those according to the measurement target are used. Further, combinations of avidin for biotin, protein A for immunoglobulin G, hormone receptor for hormone, DNA receptor for DNA, RNA receptor for RNA, drug receptor for drugs, and the like are also conceivable.

  The immunoassay is roughly divided into a first stage in which an antigen-antibody reaction is performed and a second stage in which a label that has reacted with the antigen or antibody is detected. In the storage unit, the detection target component is separated from the non-detection component using the antigen-antibody reaction in the first step, and the qualitative characteristics of the separated component are detected in the detection mechanism including an electrode configuration or a cell provided downstream from the storage unit. And / or perform quantitative analysis. The detection mechanism in the second stage can be based on electrochemical analysis or optical analysis. In the case of electrochemical analysis, an electrode configuration similar to that of the above-described concentration detection device can be employed. In the case of optical analysis, an optical cell similar to that in the case of liquid chromatography analysis can be employed.

  As a labeling substance in the immunoassay, an enzyme label, a scientific luminescent label, a metal ion, or the like can be used. When an enzyme label is used, a substrate is allowed to flow through the reservoir in a state where the label is immobilized in the reservoir, and a reaction product to be generated is detected by a downstream detection mechanism. For example, hydrogen peroxide produced by oxidoreductase is detected by electrochemical analysis. Such combinations of label and substrate include: glucose for glucose oxidase, xanthine for xanthine oxidase, amino acid for amino acid oxidase, ascorbic acid for ascorbate oxidase, acyl CoA for acyl CoA oxidase, cholesterol for cholesterol oxidase, galactose for galactose oxidase Oxalic acid for oxalate oxidase, sarcosine for sarcosine oxidase, and the like.

  Optical analysis can also be performed using enzyme labels such as peroxidase, β-galactosidase, alkaline phosphatase and the like. As the optical analysis, a colorimetric method or a fluorescence method can be used.

  Furthermore, the detection apparatus of the present invention can be applied to analysis using other principles, for example, analysis using a specific binding reaction. In this case, by constructing the reservoir with a substance that performs a specific binding reaction, it can be applied to, for example, IMAC (immobilized metal ion affinity chromatography), complementary DNA hybridization, and analysis of various other proteins. Is possible.

  In any of the above-described embodiments, the cartridge type detection device according to the present invention can mount a portion that requires replacement for each measurement, complicated cleaning, renewal processing, and the like on the detection cartridge. For example, an electrode for electrochemical analysis, a chromatographic column in liquid chromatography, and an antigen or antibody stationary phase in immunoassay correspond to this, and are mounted on a detection cartridge.

  The optical cell can be easily incorporated into the detection cartridge, and from the viewpoint of reducing the labor of the operator, it is preferable to mount the optical cell on the detection cartridge. However, the optical cell can be washed with simple water. It may be mounted on the unit side.

Hereinafter, the present invention will be described based on embodiments shown in the drawings.
(Measurement of various heavy metals using detection cartridge)
FIG. 1 is an exploded view showing an example of a detection cartridge according to an embodiment of the present invention suitable for use in heavy metal concentration analysis. In the illustrated embodiment, the detection cartridge 1 is configured by combining four resin base substrates 11, 12, 13, and 14 in this order from the bottom. As a typical example, the size of each substrate is 35 mm × 50 mm in a planar shape, the thickness of one substrate is 1 mm, and is about 4 mm in a superposed state.

  Between the substrates 12 and 13, an adsorption carrier 22a that adsorbs an anionic substance, working electrodes 31 and 32 for detecting the anionic substance, a counter electrode 33 and a reference electrode 34 corresponding to the working electrodes 31 and 32, An adsorption carrier 22b that adsorbs the cationic substance, working electrodes 35 and 36 for detecting the cationic substance, a reference electrode 37, and a counter electrode 38 are arranged. A recess is formed in the substrate 12 in order to accommodate these electrodes in a predetermined position. In FIG. 1, the recesses 31 a and 32 a of the substrate 12 are working electrode chambers for storing the working electrodes 31 and 32, the recess 33 a is a counter electrode chamber for storing the counter electrode 33, and the recess 34 a is a reference electrode chamber for storing the reference electrode 34. . Similarly, the recesses 35a and 36a constitute a working electrode chamber, the recess 37a constitutes a reference electrode chamber, and the recess 38a constitutes a counter electrode chamber. The adsorption carriers 22a and 22b constitute a storage unit that temporarily stores a substance to be detected.

  As a working electrode for measuring arsenic and selenium, a gold electrode (for example, size 3.5 mm × 8.4 mm × 0.5 mm) in which a gold layer is formed on a glass substrate via a chromium layer is used, and cadmium, A plate-like carbon electrode (for example, size 3.5 mm × 8.4 mm × 0.5 mm) is used as a working electrode for measuring lead, mercury, and hexavalent chromium. In this embodiment, the working electrode 31 is a gold electrode for measuring arsenic and selenium, and the working electrodes 32, 35, and 36 are plate-like carbon electrodes for measuring cadmium, lead, mercury, and hexavalent chromium, respectively. it can. As the counter electrodes 33 and 38, plate-like carbon electrodes (for example, size 3.5 mm × 8.4 mm × 0.5 mm) similar to the working electrode 32 are used, and the reference electrodes 34 and 37 are formed on an alumina substrate. An electrode (for example, size 3.5 mm × 8.4 mm × 0.5 mm) coated with silver paste (Nihon Atchison 6022) may be used. Of course, other electrode configurations may be employed.

  The electrode sizes are all uniform, and the electrodes 31, 32, 33, 34, 35, 36, 37, and 38 are formed in the recesses 31a of the substrate 12 so that the electrode surface and the surface of the substrate 12 are the same surface. 32a, 33a, 34a, 35a, 36a, 37a, 38a. Between the board | substrate 11 and the board | substrate 12, between the board | substrate 12 and the board | substrate 13, and between the board | substrate 13 and the board | substrate 14, it fixes liquid-tightly with an adhesive tape. FIG. 1 shows an example of the adhesive tape 24 disposed between the substrates 12 and 13. The pressure-sensitive adhesive tape disposed between other substrates has a similar shape, and each pressure-sensitive adhesive tape has an opening or a hole formed at a required position.

  The surfaces of the working electrodes 31, 32, 35, 36 and other electrodes are masked by the adhesive tape 24. As shown in FIG. 1, each electrode is exposed by opening holes of a predetermined area at eight positions corresponding to the electrodes of the mask 24. In FIG. 1, holes 241 and 242 correspond to the working electrodes 31 and 32 for detecting an anionic substance, respectively, and similar holes are also provided at positions corresponding to an electrode array for detecting a cationic substance. Is formed. In the illustrated embodiment, the hole 241 corresponding to the working electrode 31 and the hole corresponding to the working electrode 35 are circular holes having a diameter of 1 mm, the holes corresponding to the working electrodes 32 and 36 and the holes corresponding to the remaining electrodes are 2 mm in diameter. It is a circular hole. These holes are for the electrodes 31 to 38 to come into contact with the liquid. Furthermore, holes 243 and 244 having the same size as the adsorption carriers 22a and 22 are formed in the adhesive tape 24 at positions corresponding to the adsorption carriers 22a and 22b. Although not individually described, the adhesive tape 24 and other adhesive tapes are each formed with holes or openings necessary at positions corresponding to the recesses formed on the substrate.

  As shown in FIG. 1, the substrate 11 is formed with a recess for forming a waste liquid reservoir 110, a pair of channel grooves 111 and a pair of channel grooves 112 forming a part of the liquid channel. The substrate 12 is formed with a pair of through-holes 201 for introducing the test solution, and each of the through-holes 201 has a pair of flow paths of the substrate 11 when the substrate 12 is overlaid on the substrate 11. The groove 111 is disposed at a position communicating with one end of each of the grooves 111. The other end of each flow path groove 111 communicates with a flow path groove of the substrate 14 described later through holes formed in the substrate 12 and the substrate 13. One end portion of each flow channel groove 112 is communicated with the accommodating recesses of the adsorption carriers 22a and 22b. The substrate 12 further has an opening 202 that overlaps the waste liquid reservoir 110 of the substrate 11.

  The substrate 13 has a pair of through holes 301 that overlap the pair of through holes 201 of the substrate 12 and a pair of recesses 302 that receive the upper portions of the adsorption carriers 22a and 22b when the substrate 13 is stacked on the substrate 12. Further, the substrate 13 has a flow channel 303 that overlaps the row of the electrodes 31, 32, 33, and 34 and a flow channel 304 that overlaps the row of the electrodes 35, 36, 37, and 38. In addition, the substrate 13 is formed with an electrolyte solution chamber 305 for accommodating an electrolyte solution pack containing an electrolyte solution as a reference electrode activation solution and a hole 306 communicating with the hole 202 of the substrate 12. The substrate 12 is provided with a needle-like body 203 extending into the electrolyte solution chamber 305 of the substrate 13. The substrate 14 is formed with a pair of through holes 401 that overlap the pair of through holes 301 of the substrate 13 and a through hole 402 that communicates with the electrolyte solution chamber 305 of the substrate 13. On the outer surface of the substrate 14, a flexible thin plate portion 402a is formed integrally with the substrate 14 so as to close the through hole 402 (see FIGS. 2A and 2C). The electrolyte solution that functions as the reference electrode activation solution is supplied in a state of being previously placed in an aluminum pack, and this electrolyte solution pack is stored in the electrolyte solution chamber 305. The electrolyte solution chamber 305 communicates with the reference electrode chamber.

  The substrate 14 is formed with a pair of flow channel grooves 403, and one end of each flow channel groove 403 is formed in the flow channel groove 111 of the substrate 11 through the holes of the substrates 12 and 13 as described above. It communicates with the other end. As can be seen from FIG. 1, the rows of electrodes 31, 32, 33, 34 and the rows of electrodes 35, 36, 37, 38 are exposed at the side edges of the substrate 12. The through-holes 201, 301, 401 constitute the test liquid introduction part 1a as a whole.

  FIG. 2A shows a state in which the detection cartridge is assembled by superimposing the substrates 11, 12, 13, and 14 of FIG. 2B is a cross-sectional view taken along the line AA in FIG. 2A, and shows a cross section passing through the adsorption carrier. FIG. 2C is a cross-sectional view taken along the line BB in FIG. , 38 and a cross section through the electrolyte solution chamber 305 for the reference electrode.

  FIG. 3 schematically shows the liquid flow path in the detection cartridge with the upstream side on the left and the downstream side on the right. The symbols in FIG. 3 correspond to the symbols shown in FIG. Here, an arsenic and selenium measurement flow path including the anion adsorption carrier 22a will be described as an example. The adsorption carrier 22a is a circular film having a diameter of 5 mm and a thickness of 600 μm, and the periphery of the adsorption carrier 22a is held by the edges of the adsorption carrier accommodation recesses 21a of the substrates 12 and 13. The edge of the adsorbing carrier accommodating recess 21a is formed so as not to leak liquid from the peripheral direction of the adsorbing carrier 22a. In addition, the recess is formed in a tapered shape so as not to cause a steep step in the flow path wall along the flow in the flow path direction. It becomes difficult to occur. As shown in FIG. 3, on the outer surface of the substrate 11, an external port 113 that communicates with the channel groove 111, an external port 114 that communicates with a position adjacent to the adsorption carrier accommodating recess 21 a of the channel groove 112, and the channel groove An external port 115 leading to a position adjacent to the downstream end of 112 is formed. Further, on the outer surface of the substrate 11, an external port 116 communicating with the flow channel groove 304 of the substrate 13 through the through hole of the substrate 12 is formed. The ports 113, 114, 115, and 116 are controlled by a valve mechanism 51 that switches each port as desired. FIG. 3 shows a part of a five-way valve for this purpose. The valve mechanism 51 will be described later with reference to FIG.

  When detecting a substance to be detected using the detection cartridge according to this embodiment, the external ports 113, 114, 116, 117 are closed and the external port 115 is opened. And first, the test solution containing the substance to be detected, and if necessary, the anion adsorption carrier activating liquid, using the syringe holder, through holes 401 and 301 constituting the test liquid introducing portion 1a of the detection cartridge. , 201. The liquid feeding form of the test liquid is shown in FIG. The test liquid injected by the syringe from the through holes 401, 301, 201 of the test liquid introducing portion 1a passes through the liquid flow path of the groove 111, passes through the holes of the substrates 12, 13 and moves upward in the vertical direction. The liquid flows through the groove 403 and reaches the adsorption carrier 22a. Here, the substance to be detected contained in the test liquid is adsorbed by the adsorption carrier 22a. The test liquid that has passed through the adsorption carrier 22a is discharged from the external port 115 opened by the valve mechanism. FIG.3 (b) is a figure which shows an example of the syringe holder used in order to operate a syringe. The holder has clamps 15 and 16, and has a structure in which the detection cartridge 1 is strongly sandwiched between the clamps 15 and 16. The clamp 16 has a structure in which the through hole 401 of the test liquid introduction part 1a which is not used is liquid-tightly closed. Further, the clamp 16 has an opening into which the syringe 17 is fitted.

  An electrolyte solution for activating the reference electrode 34 is injected into the electrolyte solution chamber 305 from the external port 117. Next, the valve mechanism 51 is switched, the external port 115 is closed, and the external port 113 is opened with respect to an eluent supply unit described later.

  FIG. 3C shows the flow path of the eluent. The eluent sent from the eluent supply unit reaches the adsorption carrier 22a from the port 113 through the liquid channel in the groove 403, passes through the adsorption carrier 22a, and flows into the liquid channel in the groove 112. During this time, the substance to be detected adsorbed on the adsorption carrier 22a is eluted into the eluent. The eluent containing the substance to be detected flows on the anion detection electrodes 31, 32, 33, 34 from the liquid flow path of the groove 112 along the liquid flow path of the groove 303 of the substrate 13. As the eluent containing the substance to be detected flows on the electrode continuously, an electrical signal related to the concentration information of the substance to be detected is generated at the electrode.

  FIG. 4 shows the configuration of the processing unit 2. The processing unit 2 includes an arithmetic processing device 21 housed in the casing 20 and an eluent supply unit 22. The eluent supply unit 22 includes an eluent cassette 50 containing eluent tanks 54, 55, and 56, a valve mechanism 51 for switching external ports 113, 114, 115, and 116 of the substrate 11, and a pump 52. . The eluent cassette 50 is structured to be fitted into the casing 20, and the valve mechanism 51 and the pump 52 are arranged outside the casing 20 for convenience of illustration in FIG. The valve mechanism 51 includes a five-way valve 53a and a four-way valve 53b, and the five-way valve 53a is connected to the solution tanks 54, 55, and 56 via the pump 52 and the four-way valve 53b. The five-way valve 53a is connected to the external ports 115, 116, 117 on the outflow side shown in FIG. FIG. 3 shows a flow path for detecting an anionic substance. For detecting a cationic substance, three similar external ports are formed on the substrate 11, and the five-way valve 53a is These ports are also switched. The port 113 on the eluent inflow side can be shared by the anionic substance detection channel and the cationic substance detection channel.

  The four-way valve 53 b is for switching the connection between the eluent tanks 54, 55, 56 and the pump 52. The eluent tanks 54, 55, and 56 store an eluent for an anionic substance adsorbing carrier, an eluent for a cationic substance adsorbing carrier (also used as an electrolyte solution), and washing water, respectively, and a four-way valve 53b. As a result, the solution fed to the pump 52 is switched.

  The eluent cassette 50 for storing the eluent tank has a structure that can be attached to and detached from the casing 20 of the processing unit 2. When the solution stored in each tank is insufficient, the solution tank is removed and the solution is replenished. Can do. As shown in the figure for the eluent tank 56, the eluent tank and the lid 57 are detachable, and the structure is such that the leakage of the solution can be completely sealed by the rubber ring. Further, the upper part of the lid 57 has a structure that can be coupled to the lid 58 of the cassette 50 with a single touch by a connector structure.

  Furthermore, the arithmetic processing unit 21 disposed in the casing 20 of the processing unit 2 includes an electronic board 66 on which a microprocessor and various drivers are mounted. On the upper surface 67 of the processing unit 2, a display unit, operation buttons, and the like are provided. A user interface is provided. A detection cartridge insertion case 62 is further provided on the outer surface of the processing unit. The insertion case 62 is configured as a hinge-type lid that can be opened and closed, and can be opened and closed with respect to the cartridge holder 61 into which the cartridge is fitted. The cartridge holder 61 has a structure that can be opened and closed.

  4A is a schematic diagram showing the cartridge holder 61 in an opened state, and FIG. 4B is a schematic diagram showing the cartridge holder 61 in a closed state. The cartridge holder 61 has a structure shown in FIG. The cartridge holder 61 includes a lower structure including an upper plate 613, a lower plate 612 to which the five-way valve 53a and various liquid feeding tubes are connected, and a pressing plate 614 movably coupled to the lower structure by a flange portion 611. It consists of. In FIG. 4C, the pressing plate 614 is shown facing down, and electrode pins 615 are provided on the back surface of the pressing plate 614, and the microprocessor of the processing unit is electrically connected with the wiring 616 on the surface of the pressing plate 614. Signals are exchanged. The electrode pins 615 are arrays corresponding to the rows of electrodes 31, 32, 33, and 34 and the rows of electrodes 35, 36, 37, and 38 of the detection cartridge 1.

  Further, an elastic seal member 411 for engaging with the through-hole 401 of the test liquid introducing portion 1a of the detection cartridge 1 to prevent the back flow of the liquid and the electrolyte solution chamber 305 are inserted on the back surface of the pressing plate 614. A protrusion 141 for allowing the reference electrode activation liquid to flow toward the reference electrode and an elastic protrusion 412 for pressing the detection cartridge 1 against the upper plate 613 to prevent leakage of various liquids are provided. The detection cartridge 1 is inserted into the cartridge holder 61 as shown in FIG.

  In the example shown in FIG. 3, the depth of the groove 304 facing the electrode is 200 μm and the width is 3 mm. In the section between the electrode 33 and the electrode 34, the groove 304 becomes shallow and a liquid junction 133 is formed. The liquid junction 133 has a depth of 100 μm and a width of about 100 μm. The other channels have a depth of 500 μm and a width of 500 μm. The through-hole 401 of the test liquid introduction part 1a has such a size that the tip of the syringe used for injection when the test liquid is injected just fits, and is closed when set in the processing unit. Is not configured. The volume of the flow path excluding the through hole 401 and the waste liquid reservoir 110 and the through hole 202 of the test liquid introducing portion in the detection cartridge 1 is about 1 ml. The volume per channel system excluding the waste liquid tank 123 is 45 μl.

  The cartridge insertion case 62 shown in FIG. 5 is opened, and the detection cartridge 1 can be attached or removed from the side surface of the processing unit as indicated by an imaginary line. The eluent tank cassette 50 in which the solution tanks 54, 55, and 56 are accommodated can be attached to and detached from the casing 20 of the processing unit 2 so that the solution can be easily replenished and replaced. The processing unit 2 includes a connection unit 64 that connects a power cord, a battery 63 that can operate without a power cord, and a communication device 65 that can wirelessly communicate with the outside.

  The processing unit 2 can be connected to the PDA device 500 as shown in FIG. 6A or connected to the computer 501 as shown in FIG. 6B to easily record and transfer data. To be able to do so. In addition, the processing unit 2 can be battery-driven so as to be suitable for mobile use, and can be configured to be compatible with both driving by an AC power source suitable for stationary measurement. FIG. 7 is a block diagram showing the configuration of the arithmetic processing unit in the processing unit. As shown in the figure, the processing unit 2 includes not only a control unit constituted by a microcontroller but also A / D converters and constituent components shown in various blocks. These components are all well known and will not be described in further detail.

  FIG. 8 shows a flow of operation when the detection target substance is detected by the casing cartridge 1 and the processing unit 2 shown in FIGS. Hereinafter, based on FIG. 8, it demonstrates according to the operation procedure, giving an example.

  In the first operation procedure, the detection cartridge 1 is not inserted into the processing unit 2 and is held by the clamps 15 and 16 of the syringe holder. The syringe holder is configured so as to be able to close the through hole 401 of the test liquid introducing portion 1a when the detection cartridge 1 is held. Instead of the syringe holder having the configuration shown in FIG. 3B, a closing plug 41 or a valve shown in FIG. 2A may be used. The reason why the through hole 401 is blocked is to make it easier for the eluent injected from the port 113 to flow out of the port 115 through the adsorption carrier 22a.

  First, in order to activate the adsorption ability of the anionic substance adsorption carrier 22a, an activation liquid for the anionic substance adsorption carrier 22a is injected from the through hole 401 of the test liquid introduction part 1a. The amount of the activation liquid may be wetted with the anionic substance adsorption carrier, and 50 μl is sufficient. Next, 10 ml of the test solution is injected from the through hole 401 of the test solution introduction part, passes through the anionic substance adsorption carrier 22a, and is discharged from the external port 115. At this time, arsenic and selenium to be measured are captured by the anionic substance adsorption carrier 22a by adsorption and are not included in the discharged solution. Subsequently, in order to fill the reference electrode chamber with a potassium chloride solution for forming silver chloride for the reference electrode 34, the pack containing the solution was placed in the electrolyte solution chamber 305 of the substrate 13 and provided on the substrate 14. The pressing portion, that is, the flexible thin plate portion 402a (FIGS. 1 and 2) is pressed. The substrate 12 is provided with a needle-like body 203 at a position corresponding to the container, and the pack containing the solution is broken by the needle-like body 203, and the potassium chloride leaked from this places the reference electrode 34. It flows into the reference electrode chamber. Potassium chloride forms a silver / silver chloride electrode on the surface of the reference electrode.

  In the second operation procedure, the detection cartridge 1 is inserted into the processing unit 2. When the detection cartridge 1 is inserted into the processing unit 2, the valve mechanism 51 is operated to inject potassium chloride from the port 117 into the anion reference electrode material. Thereafter, the eluent injection port 113 is opened and the eluent is injected. At the same time, the through hole 401 of the test liquid introducing portion 1a is closed, and the connection terminals 615 for the respective electrodes are connected to the working electrodes 31, 32, the counter electrode 33, and the reference electrode 34.

  Next, when the measurement start button on the processing unit 2 is pressed to start the measurement, an arsenic / selenium measurement eluent (= 1 M sulfuric acid; pH = about 2) is injected from the port 113 of the test liquid introduction part. The eluent flows through the adsorption carrier 22 a and further flows along the electrodes 31, 32, 33 and 34. Since the through-hole 401 is closed, the eluent does not flow backward in the direction of the test liquid introduction part. The flow path facing the electrodes 31, 32, 33 is connected to the flow path facing the reference electrode 34 via the liquid junction 133, but since the liquid junction 133 is very narrow, the potassium chloride solution in the reference electrode chamber is There is no reverse flow to the row of electrodes 31, 32, 33. The most downstream of this flow path is connected to the waste liquid reservoir of the processing unit via the port 116.

  In FIG. 3, for simplification, the liquid flow path facing the electrodes 31, 32, 33, the liquid junction 133, and the liquid flow path facing the reference electrode 34 are shown to communicate with the port 116. However, the actual arrangement is as shown in FIG. 1, and there is a channel facing the reference electrode 34 via the liquid junction 133 between the channel from the liquid channel facing the electrodes 31, 32, 33 to the port 116. It is connected. For this reason, the liquid channel facing the electrodes 31, 32 and 33 and the channel facing the reference electrode 34 are fluidly connected, but the potassium chloride solution on the reference electrode 34 side exchanges the eluent. There is nothing.

  The electrical connection is checked with the eluent filled in the liquid channel facing the electrode. Whether an eluent reaches the flow path and electrical connection is ensured by applying a current or voltage between the working electrodes 31 and 32 and the counter electrode 33 and checking the voltage or current applied to the working electrode, Check that the connection between the electrode and the terminal is secure. The amount of solution necessary to fill the eluent in the channel facing the electrode is about 40 μl.

Next, an arsenic / selenium measurement eluent is introduced from the eluent injection port 113 at a constant flow rate, and a potential (−0.4 V) for depositing arsenic and selenium is applied to the working electrodes 31 and 32. When the eluent passes through the adsorbent carrier 22a, arsenic and selenium trapped on the adsorbent carrier are separated and move into the eluent, and reach the vicinity of the electrode as the eluent flows. In the vicinity of the electrode, a reduction reaction of arsenic and selenium occurs and deposits on the working electrodes 31 and 32. The inflow of the eluent and the application of the deposition potential are performed until the trapped arsenic and selenium are completely desorbed. If 300 μl is deposited at a flow rate of 50 μl / min, elution of arsenic and selenium is almost completed, so the deposition time is set to about 6 minutes. As an operation, the inflow is continued until 5 minutes and 50 seconds, and the last 10 seconds is a time for stopping the liquid in the flow path, and the insertion of the potential is started after 6 minutes. The insertion conditions are as follows.
ASV measurement condition insertion method: LSV (method in which a constant frequency is not applied during potential sweep)
Deposition potential: -0.4V
Deposition time: 6 minutes Sweep speed: 0.2 V / s
Sweep start potential: -0.4V
Sweep end potential: 1.2V

  When a potential-current curve when the above operation is performed is recorded, a graph as shown in FIG. 9 is obtained. The area of the peak observed here is the current that flows when the heavy metal deposited on the working electrode during the deposition time re-dissolves due to an increase in potential, and corresponds to the amount of dissolved material. FIG. 9 shows a potential-current curve in the case where the above measurement is performed while changing the concentrations of arsenic and selenium.

This completes the arsenic and selenium measurement operations. Continue to measure cadmium, lead and mercury. The procedure is almost the same as that for arsenic and selenium, except for the following points. That is, in the measurement of cations, even if potassium chloride ions are contained as the eluent, the measurement is not hindered, so that the solution for the reference electrode can be used as the eluent. Since the eluent and the solution for the reference electrode chamber are common, it is not necessary to provide a channel facing the reference electrode independently from the channels facing the other electrodes, and the four electrodes 35, 36, What is necessary is just to arrange | position 37,38 continuously. In FIG. 1, four electrodes are arranged so as to face one flow path as electrodes on the cation side. The composition of the eluent in this case is as follows.
Eluent for cation measurement:
0.4M potassium chloride + 10mM citric acid + 3.5mM ethylenediamine (pH = approx. 4)

  The cationic substance adsorption carrier 22b does not require an activation liquid. For this reason, in the operation procedure corresponding to the first operation procedure, it is only necessary to inject the test liquid.

  These controls are executed according to the program in the processing device in the processing unit 2 as shown in the software flowchart of FIG.

FIG. 10 shows a potential-current curve when the measurement was performed in the same manner as the anion measurement except that the above points were changed. A sharp peak is obtained for all three types of cadmium, lead, and mercury, and it can be seen that the peak area changes according to the concentration of each metal. Quantitative analysis can be performed based on the calibration curve thus obtained. The conditions for the sweep are as follows.
ASV measurement condition insertion method: SWV (method of applying a constant frequency during potential sweep)
Deposition potential: -0.9V
Deposition time: 6 minutes Sweep speed: 0.255 V / s
Sweep start potential: -0.9V
Sweep end potential: 0.6V
Frequency: 100Hz
Step potential: 2.55mV
Amplitude: 25.5mV

When arsenic and selenium measurement and cadmium / lead / mercury measurement are performed continuously, the detection cartridge is set in the syringe holder and adsorbed from the through-hole 401 of the arsenic / selenium sample introduction section 1a. The activation liquid of the carrier 22a is injected. Next, 10 ml each of the test liquid is injected into the through hole 401 of the test liquid introducing part for arsenic / selenium and the through hole 401 of the test liquid introducing part 1a for cadmium / lead / mercury. After that, when the detection cartridge 1 is inserted into the processing unit 2 and the start button is pressed, first the supply of the eluent for arsenic / selenium measurement, the check of the electrical connection, the second supply of the eluent, and the electrochemical measurement Is done. Subsequently, an eluent for cadmium / lead / mercury measurement, an electrical connection check, a second eluent supply and an electrochemical measurement are performed. After completion of the cadmium / lead / mercury measurement, cleaning water for cleaning the valve mechanism 51, the pump 52, and the piping connecting them is sent from the cleaning water tank 503. The entire system is shown in FIG. The washing water is fed from the washing water tank 503 while switching the pipes in order, so that the washing water in the amount that just pushes the liquid in the valve mechanism 51, the pump 52, and the pipes. The combined capacity of the valve mechanism 51, the pump 52, and the pipe is about 600 μl, and about 600 μl of the eluent accumulated in the detection cartridge is pushed away by the feeding of the washing water and collected in the waste liquid reservoir 110.
Hexavalent chromium is measured in the same manner as arsenic and selenium, except that electrochemical measurement is performed by the cathodic stripping voltammetry method. Since the electrochemical measurement method for hexavalent chromium is different from the electrochemical measurement method for arsenic / selenium, the measurement of hexavalent chromium and arsenic / selenium is not performed at the same time, and each is performed using a separate cartridge for detection. However, following the measurement of hexavalent chromium, cadmium / lead / mercury measurement can be continuously performed with the same detection cartridge.

  FIG. 11 is a schematic cross-sectional view showing a second embodiment of the concentration section in the cartridge of the present invention. In this embodiment, the test liquid is concentrated by heat evaporation. A heating element such as a Peltier element 501 is disposed facing the liquid flow path 500 formed in the cartridge, and a current is supplied to the heating element 501 by a conducting wire 502. A vapor-permeable material film 503 is disposed on the side wall of the liquid channel 500 facing the heat generating element 501, and vapor generated by heating escapes from the film 503 to the outside of the channel 500. Concentrated.

  FIG. 12 shows another configuration of the test liquid concentration unit. This embodiment is an example using a porous membrane. In the test liquid channel 600, a valve 601 is arranged at the test liquid inlet, and a valve 602 is arranged at the test liquid outlet. A porous membrane 603 is disposed in the test solution flow channel 600 so as to separate the flow channel 600 into a concentration chamber 600a and a drainage chamber 600b.

  In this configuration, the test solution in the concentration chamber 600a can be concentrated by introducing the test solution from the inlet valve 601 with the outlet valve 602 closed and applying an appropriate pressure to the concentration chamber 600a. it can. After concentration, the outlet valve 602 can be opened to allow the test solution to flow through the electrode configuration. This configuration has an advantage that the concentration time can be shortened by arbitrarily increasing the area of the porous membrane 603.

  13a, 13b, and 13c are perspective views showing a portable analysis unit that can be used for the detection cartridge 1 described above. As shown in FIG. 13a, the analysis unit includes an analyzer body or housing 700 having a rectangular shape as a whole, and the analyzer body 700 includes a main body upper portion 701 and a main body lower portion 702 that are vertically stacked. . The main body 700 is provided with a handle 703 so as to be convenient for carrying. The main body upper portion 701 has a shape with an open upper surface, and a lid 704 is fixed to the upper surface.

  FIG. 13 b shows the inside of the upper body 701 with the lid 704 removed. In the main body upper portion 701, a waste liquid tank chamber 701b is formed by a partition wall 701a along one side portion in the longitudinal direction, and a waste liquid tank 705 is disposed in the waste liquid tank chamber 701b. The waste liquid tank 705 is detachably fixed to the upper main body 701.

  The opposite side of the waste liquid tank chamber 701b across the partition wall 701a is a chamber 701c for storing various functional components. A plurality of reagent tanks 706 are arranged in parallel from one longitudinal end of the chamber 701c to the vicinity of the central portion. Has been. In this embodiment, five reagent tanks are arranged. In FIG. 14, only the reagent tanks 706 at both ends are shown in order to show the arrangement below the reagent tank 706. In addition, the reagent tank 706 adjacent to the longitudinal end of the chamber 701c is notched upward so that the inside can be seen.

  A switching valve mechanism 707 including a plurality of switching valves is disposed below the reagent tank 706. A tank switching pipe plate 708 is disposed below the switching valve mechanism 707. In the chamber 701c, a cartridge holder 709 is further disposed as a cartridge mounting portion, and a liquid feed pump 710 is disposed beside the cartridge holder 709. A discharge destination switching valve mechanism 711 and a discharge destination switching pipe plate, which will be described later, are disposed below the cartridge holder 709.

  FIG. 13 c shows the inside of the main body lower part 702. In the lower part 702 of the main body, a battery box 712 is disposed along one side in the longitudinal direction, and an electronic board 713 incorporating a necessary control circuit and a processing unit such as a microprocessor is disposed beside the battery box 712.

  Returning to FIG. 13 a, the lid 704 attached to the upper surface of the main body upper portion 701 is provided with an opening / closing lid 714 for taking in and out the reagent tank corresponding to the attachment position of the reagent tank 706, and at the attachment position of the cartridge holder 709. Correspondingly, an open / close lid 714a for the cartridge is provided.

  FIGS. 14a, 14b (i) (ii) (iii) and 14c show detection cartridges for use in electrochemical analysis, and FIG. 1, FIG. 2 (a) (b) (c) and FIG. FIG. 4 is a diagram corresponding to FIG. 3, and corresponding portions are denoted by the same reference numerals. In this example, ports 116, 117 are formed on the lower surface of the cartridge in addition to the ports 113, 114, 115, the port 116 is connected to the waste liquid tank 705, and the port 117 is used for supplying the solution of the reference electrode 34. It is configured to be connected to a reagent tank. Further, the flow path between the ports 114 and 115 is formed inside the cartridge, not outside the cartridge.

  FIG. 46 shows another example of a detection cartridge for use in electrochemical analysis. In the detection cartridge for electrochemical analysis, a first sheet made of resin and a second sheet are laminated, and a recess for accommodating an electrode is formed in the first sheet, and an electrode is disposed in the recess, The second sheet is formed with a liquid flow path for allowing a reagent to flow at a position corresponding to the electrode, and a hole having a certain area is formed between the first sheet and the second sheet at a position corresponding to the electrode. A provided insulating sheet is disposed, a storage portion is formed at a position away from the electrode, and a third sheet is disposed on one or both of the opposite surfaces of the first sheet and the second sheet. The third sheet is provided with a groove constituting a flow path connected to the storage portion. In the cartridge shown in FIGS. 1 and 14, the first sheet (substrate 12) and the second sheet (substrate 13) are laminated, and the third sheet (substrates 11 and 14) is provided on both the lamination surface and the opposite surface. However, in this example, the third sheet is laminated only on one side (upper surface in FIG. 46). Further, there is one measurement system, which is configured to be compatible with both anion measurement and cation measurement. The test solution is introduced from a dedicated holder (not shown) outside the cartridge.

  FIG. 15a is a view corresponding to FIG. 3a showing the flow of fluid in the cartridge for chromatographic analysis, and FIG. 15b is a view corresponding to FIG. 3c. The channel 303 constitutes a column for chromatographic analysis. In the cartridge, at least a portion of the column 303 is formed of a transparent plastic material, and analysis is performed by transmitting detection light through this portion as described later.

  Referring to FIGS. 16 and 17, a plurality of reagent tank fitting portions 715 are provided in parallel on the upper surface of the tank switching pipe plate 708. FIG. 16 shows a state where the reagent tank 706 is attached to one fitting portion 715. FIG. 17 is a cross-sectional view showing this attachment state. The fitting portion 715 has a circular annular protrusion 715a formed on the upper surface of the plate 708, and a reagent tank opening pin 715b protruding upward at the circular center of the protrusion 715a, and around the pin 715b. Are formed with slits 715c that open on the upper surface of the plate 708 at four points along the virtual arc. An annular seal groove 715d is formed adjacent to the inner periphery of the protrusion 715a, and an O-ring 715e is disposed in the seal groove 715d.

  On the other hand, a downward projecting portion 706a is formed below one end of the reagent tank 706, and an annular groove 706b corresponding to the annular projection 715a of the plate 708 is formed on the downward surface of the projecting portion 706a. In addition, a reagent discharge hole 706c is formed in the reagent tank 706 at a position corresponding to the slit 715c of the plate 708. The discharge hole 706c is provided with a valve 706e urged in the closing direction by a spring 706d. A vent hole 706f is formed on the upper surface of the reagent tank 706, and the vent hole 706f is sealed with a material that is gas permeable but does not allow liquid to pass therethrough.

  The reagent tank 706 configured as described above is attached to a predetermined position by fitting the annular groove 706b to the annular protrusion 715a of the plate 708. At this time, the pin 715b of the plate 708 pushes up the valve 706e of the reagent tank 706, opens the reagent discharge hole 706c, and connects the inside of the tank 706 to the slit 715c. The slit 715 c communicates with a flow path formed in the plate 708. Liquid leakage between the reagent tank 706 and the plate 708 is prevented by the O-ring 715e.

  Referring to FIG. 18, details of the reagent flow path 708 a and the pump suction flow path 708 b formed in the tank switching pipe plate 708 are shown in relation to the switching valve 707. Each of the reagent channels 708a has one end connected to a slit 715c formed in the plate 708 at the fitting portion 715, and the other end opened to the upper surface of the plate 708 below the switching valve 707 and connected to the switching valve 707. Has been. FIG. 19 shows an example of a connection relationship between the flow path 708a and the flow path 707a of the switching valve 707.

  FIG. 18 further shows a liquid feed pump 710. The liquid feed pump 710 is shown in FIG. 14 so as to be arranged in the longitudinal direction of the main body upper portion 701. However, in FIG. 18, for convenience of illustration, the liquid feed pump 710 is shown in an orientation rotated by 90 ° from the orientation shown in FIG. It is. A pump suction channel 708b is formed in the tank switching pipe plate 708. The flow path 708 b is connected to the switching valve 707 at one end port P <b> 1 and connected at the other end to the suction port of the liquid feed pump 710. This connection is made by a tube as shown in FIG.

  The liquid feed pump 710 is preferably small and capable of stably delivering a liquid in the order of microliters without pulsation, and the one used for the portable analysis unit needs to have low power consumption. The flow rate may be 5 to 100 microliters / minute, and the discharge pressure may be 0.01 to 10 MPa. Pumps having this characteristic include syringe pumps such as “Pencil pump” manufactured by Uniflow and “Confluent PDP” manufactured by Cybex.

  Referring to FIG. 18 again, the discharge destination switching pipe plate 716 is shown. The plate 716 is disposed above the discharge destination switching valve 711 on the lower side of the cartridge holder 709 in FIG. 13B. As shown in FIG. 18, a pump discharge flow path 716 a is formed in the discharge destination switching pipe plate 716. As shown in FIG. 20, one end of the flow path 716a is connected to the discharge port of the pump 710 by a tube, and the other end is connected to the discharge destination switching valve 711.

  Next, FIG. 21 showing details of the cartridge holder 709 will be referred to. The cartridge holder 709 has the same basic structure as the cartridge holder shown in FIG. 4A, and has an upper plate 709a and a lower plate 709b that are connected to each other by a funnel. A recess 709c for fitting the detection cartridge is formed in the lower plate 709b. Similar to the upper plate of the cartridge holder shown in FIG. 4A, the upper plate 709a is provided with electrode pins and wirings that contact the electrodes of the cartridge, but these are omitted in FIG. An elastic material (not shown) is disposed on the back side of the upper plate 709a of the cartridge holder 709. This elastic material absorbs the variation in the thickness of the detection cartridge at the position where the upper plate 709a is closed, and prevents liquid leakage.

  On the bottom surface of the concave portion 709c formed on the lower plate of the cartridge holder 709, fluid ports are formed at positions corresponding to various fluid ports formed on the lower surface of the cartridge fitted in this position. FIG. 22 shows, as an example, ports formed on the lower surface of the detection cartridge 1 described above with reference to FIGS. 13 to 15, and these ports include G ′ and F ″, respectively. , F ′ ″, H ′, I ′, K ′, L ′. Ports H ′ and L ′ correspond to the port 113 in FIG. 3, and ports G ′ and K ′ correspond to the port 114 in FIG. 3. The ports F ″ and F ″ ″ become the waste liquid port 116. The port I ′ is a port 117 that communicates with the reference electrode of the detection cartridge 1.

  Returning to FIG. 18, the flow paths and ports formed in the discharge destination switching pipe plate 716 are shown. In FIG. 18, ports corresponding to the respective ports in FIG. 22 are opened on the upper surface of the plate 716, and these ports are assigned the same reference numerals as those in FIG. The port J 'is not used in this example, and therefore there is no corresponding port in the cartridge 1 of FIG.

  Ports G, F, H, I, J, K, L, and P2 are opened on the lower surface of the discharge destination switching pipe plate 716, and these ports are opened by a switching valve 711 partially shown in FIG. , Optionally connected to pump 710. As shown in FIG. 18, a port P2 communicating with the pump discharge flow path 716a is opened on the lower surface of the plate 716, and this port P2 is connected to the pump 710 as shown in FIG. FIG. 23 shows the switching connection relationship by the switching valve mechanisms 707 and 711 between the liquid feed pump 710 and the tank switching piping plate 708 and the discharge destination piping plate 716. In FIG. 23, a reagent tank 706 with washing water is used.

  FIG. 24 is an exploded perspective view showing the structure of the discharge destination switching pipe plate 716. The plate 716 has a structure in which an upper plate member 720 and a lower plate member 721 formed by molding a plastic material are stacked. The flow path 716a and other flow paths are configured by grooves formed on the upper surface of the lower plate member 721 by molding. At the same time, a port opening in the lower surface is also formed during molding. In the upper plate member 720, a port that opens to the upper surface is formed at a required position so as to penetrate in the thickness direction. By bonding the upper plate member 720 and the lower plate member 721 together, the discharge destination switching piping plate 716 is formed. Referring to FIG. 18, the tank switching pipe plate 708 also has a structure in which an upper plate member 722 and a lower plate member 723 formed by molding a plastic material are laminated, and a flow path is formed as a groove on the upper surface of the lower plate member 723. The upper plate member 722 is formed with a port and a slit 715c that are open on the upper surface when the plate member is molded.

  25 and 26 show the connection of the waste liquid tank 705. As shown in the figure, a waste liquid inlet 705 a is formed at one end of the waste liquid tank 705. For example, a seal member 705b made of Teflon (registered trademark) is disposed at the waste liquid inlet 705a. On the other hand, a waste liquid discharge member 731 having a hollow needle 730 is fixed to a protrusion formed on the bottom plate of the waste liquid tank chamber 701b, and a flow path leading to the hollow needle 730 of this member 731 is discharged via a tube. It is connected to a port opened on the lower surface of the tip switching piping plate 716. The waste liquid tank 705 is attached at a predetermined position by passing the hollow needle 730 of the member 731 through the seal member 705b.

  In the above embodiment, the tank switching pipe plate 708 and the discharge destination switching pipe plate 716 are formed by separate members, but they can also be formed as an integral molded product.

  Although not shown in FIG. 13 a, the analysis unit is provided with a switch and a display unit necessary for operation on the lid 704 of the main body 700, and these are connected to the electronic substrate 713 as appropriate.

  FIG. 27 shows an example of a system applied to chromatographic analysis. In this case, wash water, eluent, and activation liquid are stored in the reagent tank 706 of the analysis unit, respectively. Each reagent tank 706 is switched and connected to a liquid feed pump 710 via switching valves 707-1, 707-2, and 707-3. The detection cartridge 1-1 includes a storage unit 21-1 having a sample storage filter and a chromatographic column 21-2. The reservoir 21-1 is connected to a liquid inlet port 21-3 and a liquid outlet port 21-4 that are opened on the lower surface of the cartridge 1-1 by a flow path. The column 21-2 has a liquid inlet port 21-5 and a liquid outlet port 21-6.

  On the analysis unit side, switching valves 711-1, 711-2, 711-3, 711-4, and 711-5 are provided for switching and connecting the discharge port of the liquid feeding pump 710 to each port. In FIG. 27, Roman letters A, B, C, D, and E assigned to the valves correspond to the reference numerals assigned to the valves in FIGS. 18 and 23, respectively.

The operation in this chromatographic analysis is as follows.
(1) Before setting the analysis unit, the sample is passed through the cartridge and passed through the filter of the concentration unit (the target substance is trapped in the filter).
(2) Install the cartridge in the analysis unit.
(3) The activation liquid is sent to the storage filter (in order to prevent bubbles from entering the column in this measurement, the bubbles in the filter are expelled in advance).
(4) The eluent is sent to the column.
(5) Perform this measurement. The eluent is passed through the storage filter → the flow path in the analysis unit → the column → the optical detection unit analysis unit in the analysis unit → the waste liquid tank.
(6) The target substance is identified and quantified from the signal detected by the optical detection unit.
(7) Wash the flow path.

  FIGS. 28A, 28B and 29A, 29B show the temporal flow of operation in the form of a table when the analysis unit is used with a cartridge for concentration measurement. Here, the system 1 represents one of the two electrode arrays shown in FIG. 1, for example, the array of the electrodes 35, 36, 37, and 38, and the system 2 represents the other electrode array, for example, the electrode 31. , 32, 33, 34. Also in this figure, the Roman character code | symbol attached | subjected to the valve | bulb corresponds to the code | symbol in FIG. In addition, the auto zero of a pump means that a liquid feeding pump is automatically set to a zero position.

  FIG. 30 shows a temporal flow when the analysis unit is used with a cartridge for chromatographic analysis. In this figure, the Romaji code corresponds to the code given to the valve in FIG. “(F)” means that liquid passes through the cartridge.

  FIG. 31 is an external view showing an analyzer according to an embodiment of the present invention used for liquid chromatographic analysis. This analyzer has an analysis unit 800 comprising a substantially rectangular body or housing 801. A cartridge insertion opening 803 that is opened and closed by an opening / closing lid 802 is formed on the upper surface of the housing 801, and a cartridge 804 for liquid chromatograph analysis is inserted through the opening 803. A housing 801 of the analysis unit 800 shown in FIG. 31 also includes a main body upper part 801a and a main body lower part 801b, similar to the analysis unit housing 700 described with reference to FIGS. 13a, 13b, and 13c. The main body lower part 801b has the same configuration as that of the main body lower part 702 of the housing 700 shown in FIG. 13c, and includes a battery box and an electronic board similar to those shown in FIG. FIG. 31 shows an electrical connection plug 805 connected to this battery box via an AC adapter and a connection plug 806 to a personal computer.

  FIG. 32 is a schematic sectional view of a cartridge 810 for liquid chromatographic analysis. The cartridge 810 has a laminated structure in which four molded plastic plates 811, 812, 813, and 814 are overlapped, and at least the upper and lower plastic plates 811 and 814 are made of a transparent plastic material.

  The lower plastic plate 814 has four ports 814a, 814b, 814c, 814d. The port 814a is a reagent injection port, and the port 814b functions as a test solution injection port. The port 814c is a test liquid circulation port, and the port 814d is a waste liquid port. At the interface between the plastic plates 812 and 813, a filter recess 816 for accommodating a filter 815 serving as a temporary storage for the test substance is formed, and two flow paths 817 passing from the port 814b to the filter recess 816 are provided. These plastic plates 812 and 813 are formed to penetrate in the thickness direction. In addition, a liquid circulation channel 818 is formed through the two plastic plates 812 and 813 in the thickness direction from the port 814a, and these channels 817 and 818 are connected to the upper plastic plate 811 inside the cartridge 810. They are connected to each other by a flow path 819 formed of grooves formed on the inner surface.

  The port 814c is connected to a liquid flow path 820 that penetrates the plastic plate 813 in the thickness direction. The liquid flow path 820 is a liquid formed by a groove formed in the plastic plate 812 at the interface between the plastic plates 812 and 813. It is connected to one end of the chromatographic analysis column 821. The other end of the column 821 is connected to one end of the liquid channel 823 through a liquid channel 822 that penetrates the plastic plate 813 in the thickness direction. The liquid channel 823 includes a groove formed in the plastic plate 813 at the interface between the plastic plates 813 and 814.

  The liquid channel 823 communicates with one end of an absorbance measurement cell 824 formed of a liquid channel formed through the plastic plates 812 and 813 in the thickness direction. The other end of the absorbance measurement cell 824 has a liquid flow path 825 formed of a groove formed in the plastic plate 812 at the interface between the plastic plates 811 and 812 and a liquid flow formed through the plastic plates 812 and 813 in the thickness direction. It is connected to a waste liquid port 814d through a path 826.

  FIG. 33 shows the arrangement of the ports, grooves and recesses on the upper and lower surfaces of each plastic plate 811, 812, 813, 814 of the cartridge 810. FIG. 33 (a) shows the lower surface, and FIG. ) Indicates the upper surface. Note that FIG. 33B shows the relationship upside down with respect to (a), and the lower edge in (a) corresponds to the upper edge in (b).

  Referring to FIG. 33A, the uppermost plastic plate 811 has a groove that forms a liquid channel 819 at the interface with the plastic plate 812. The outer surface remains smooth as can be seen from FIG. 33 (b). As described above, the plastic plate 811 is formed of a transparent plastic material.

  In the second plastic plate 812, the concave portions for the filter 816 and the flow paths 818 and 826 are arranged as shown in FIG. The column 821 is formed as a spiral flow path, and an absorbance measurement cell 824 is formed at the center of the spiral. A groove constituting a flow path 825 for connecting the absorbance measurement cell 824 to the flow path 826 is formed at the interface with the plastic plate 811. The arrangement of the ports and the liquid flow paths formed in the plastic plates 813 and 814 is shown by assigning the same reference numerals as those in FIG. 32 to the respective ports and flow paths, and detailed description thereof is omitted. The plastic plate 814 is also formed of a transparent plastic material. The other plastic plates 812 and 813 are not necessarily transparent, but may be transparent.

  34 (a) and 34 (b) are cross-sectional views taken along lines aa and bb in FIG. 33 (a), respectively, and show the plastic plates separately.

  FIG. 35 is a plan view showing the inside of the main body upper portion 801a of the housing 801. As shown in FIG. Inside the main body upper part 801a, a liquid feed pump 830, a light source 831, and a waste liquid tank 832 are arranged in parallel from one end side to the central part in the length direction of the main body upper part 801a. The liquid feed pump 830 has the same configuration as the liquid feed pump 710 shown in FIG. 14 in relation to the above-described embodiment. The waste liquid tank 832 has the same configuration as the waste liquid tank 705 in the above-described embodiment.

  In the present embodiment, the above-described light source 831 is provided for liquid chromatographic analysis. The light source 831 may be anything as long as it can emit light having a wavelength of 200 to 1100 nm and can fit in the space of the main body upper portion 801a. The wavelength is changed depending on the substance to be detected. A suitable light source for use as the light source 831 is a FiberLight light source (deuterium lamp-tungsten lamp combined type) manufactured by Sentronic GmbH. A collimating lens 833 for collimating the emitted light is disposed at the light exit of the light source 831, and a slit plate 834 having a slit for narrowing the emitted light to a predetermined diameter on the exit side of the collimating lens 833. A cartridge holding plate 835 is provided on the outside of the fixed plate.

  Further, similarly to the switching valve 707 used in the previous embodiment, a discharge destination switching valve plate 837 having five switching valves 836 indicated by A, B, C, D, and E is provided on the main body upper portion 801a. The main body upper portion 801a is disposed in a fixed relationship. The discharge destination switching valve plate 837 is arranged vertically. The cartridge 810 is inserted vertically between the cartridge holding plate 835 and the discharge destination switching valve plate 837.

  In order to facilitate the insertion of the cartridge 810, the cartridge holding plate 835 is shown together with the slit plate 834, the collimating lens 833, and the light source 831 in a direction away from the discharge destination switching valve plate 837, that is, upward in FIG. Can be retracted from position. More specifically, the light source 831, the collimating lens 833, the slit plate 834, and the cartridge holding plate 835 are mounted on the base plate 838 so as to be movable together, and the base plate 838 is attached by a rail (not shown). It is movably supported in the direction indicated by the arrow in FIG. A coil spring 839 disposed at the end of the base plate 838 biases the base plate 838 toward the discharge destination switching plate 837. Therefore, the base plate 838 that supports the light source 831, the collimating lens 833, the slit plate 834, and the cartridge holding plate 835 is moved against the biasing force of the coil spring 839, and the cartridge holding plate 835 and the discharge destination switching valve plate 837 are moved. The cartridge 810 can be inserted with the interval between them increased.

  As shown in FIG. 35, a guide member 840 for guiding and positioning the cartridge 810 is fixed to the discharge destination switching valve plate 837 at a position where the cartridge 810 is inserted. FIG. 36 is a perspective view showing the configuration of the discharge destination switching valve plate 837 and the guide member 840 in an easily understandable manner in relation to the cartridge 810. The guide member 840 has a U-shaped guide cutout 840a, and the cartridge 810 is positioned by fitting the cartridge 810 into the cutout 840a. The discharge destination switching valve plate 837 has a protruding portion 837a protruding in the direction of the cartridge 810. When the cartridge 810 is positioned at a predetermined position, the protruding portion 837a is fitted into the port 814b of the cartridge 810.

  Referring to FIG. 35 again, the discharge destination switching valve plate 837 has a second slit plate 841 on the side opposite to the light source 831 at a position aligned with the slits of the collimator lens 833 and the slit plate 834 in the optical axis direction. And a focusing lens 842 are arranged and fixed to the plate 837. Although not shown, the discharge destination switching valve plate 837 has an opening through which the light passing through the measurement cell 824 of the cartridge 810 passes through the second slit plate 841 through the slit of the slit plate 834 and the cartridge holding plate 835. Has been. Further, a spectroscope 843 serving as an analysis unit is disposed in the main body upper portion 801a so as to receive light from the focusing lens 843. As the spectrometer 843, a SAS series OEM module (1024 element CMOS mounting type) manufactured by Ocean Optics can be used. This spectrometer has an analysis capability in the wavelength range of 200 to 700.

  As shown in FIG. 35, three reagent tank attachment portions 844 with symbols F, G, and H are provided on the bottom plate portion of the main body upper portion 801a. The reagent tank mounting portion 844 has the same structure as the fitting portion 715 shown in FIG. A tank switching valve plate 845 configured as shown in FIG. 37 is disposed above the bottom plate of the main body upper portion 801a. The tank switching valve plate 845 is provided with three switching valves 846 indicated by reference signs F, G, and H on the lower surface, and the valve F, on the other hand, is a reagent tank attaching portion indicated by reference sign F via a pipe 847. On the other hand, it is connected to a liquid feed pump 830 via a pipe 848. The valves G and H of the switching valve 846 are connected to a reagent tank mounting portion 844 indicated by reference numerals G and H via pipes 849 and 850, respectively.

  Referring back to FIG. 32, an activation liquid tank 851, an eluent tank 852, and a washing water tank 853 are shown as reagent tanks connected to the switching valves 846 indicated by symbols F, G, and H, respectively. ing. These tanks can have the same configuration as the reagent tank 706 in the above-described embodiment, and are attached to the reagent tank attachment portion 844.

  FIG. 32 further shows the connection relationship of five switching valves 836 arranged on the discharge destination switching valve plate 837. The liquid feed pump 830 is connected to the valve B of the switching valve 836, and the valve B is further connected to the port 814 a of the cartridge 810. The valve B is also connected to the other two valves A and D. The valve A is connected to the port 814b of the cartridge 810 on the one hand and to the port 814c via the valve E on the other hand. Valve D is directly connected to port 814c. The valve C connects between the port 814a and the waste liquid tank 832. These connections are made by flow paths formed as grooves in the switching plates 837 and 845 and appropriate piping, as in the previously described embodiment. When the cartridge 810 is positioned at a predetermined position, each port of the cartridge 810 and the flow path of the switching plate 837 are connected so that each port of the cartridge 810 and the flow path of the discharge destination switching valve plate 837 are connected. It is positioned. The protrusion 837a shown in FIG. 36 connects the valve A of the switching valve 836 and the port 814b of the cartridge 810, and has a liquid flow path for that purpose.

  Next, the operation of this embodiment will be described. First, a cartridge 810 is prepared, and a test solution is quantitatively injected into the cartridge 810 from the port 814b. The injection amount is appropriately determined according to the concentration of the substance to be measured. As a result, the substance to be detected is stored in the filter 815 of the cartridge 810. Liquid other than the substance to be detected is discharged from the port 814a. Now turn on the instrument and launch the measurement program. The measurement program executes the operation flow shown in FIG. FIG. 39 shows a time-series flow of operation. 38 and 39, the cartridge 810 into which the test liquid has been injected is inserted into the analysis unit 800. Next, the valves B and C of the discharge destination switching valve 836 are opened, and the pump 830 is operated. This is an operation for performing idle discharge of the flow path in the discharge destination switching valve plate 837. Next, the valve F of the tank switching valve 846 is opened, and a predetermined amount of activation liquid is sucked into the liquid feed pump 830. The activation liquid facilitates elution of the substance to be detected stored in the filter 815 from the filter 815. Thereafter, the valve F is closed, the valves A and C are opened, the liquid feed pump 830 is operated, and the activation liquid is sent to the filter 815 of the cartridge 810. The activation liquid passes from the pump 830 through the valve A, enters the filter 815 through the port 814b, and flows to the waste liquid tank 832 through the flow paths 817, 819, 818, the port 814a and the valve C.

  Next, the valve G is opened, a predetermined amount of eluent is sucked into the liquid feed pump 830, and the valve G is closed. Here, the valve D is opened to operate the pump 830, and the eluent is sent to the column 821 through the port 814c. This is a preprocessing for the column 821. Thereafter, the valve D is closed, the valve G is opened, a predetermined amount of eluent is sucked into the liquid feeding pump 830, and then the valves B and E are opened to operate the liquid feeding pump 830. The eluent enters the filter 815 from the flow path 818, 819, 817 from the valve B through the port 814a, elutes the detection target substance stored in the filter 815, passes through the port 814b and the valve E, passes through the port 814c, Follow the path of the flow path 820 and reach the column 821. Further, the eluent is discharged from the column 821 through the flow paths 822 and 823, through the absorbance measurement cell 824, through the flow paths 825 and 826 and the port 814d, and into the waste liquid tank 832. In this process, the light source 831 is turned ON (FIG. 38), and the absorbance of the liquid passing through the cell 824 is measured by the spectroscope 843.

  The filter 815 and the column 821 contain a functional group that chemically interacts with the substance to be detected. In the filter 815, the functional group traps the substance to be detected. The eluent acts to elute the trapped substance to be detected and carry it to the column 821. In the column, the particles of the functional groups contained therein are fine and the flow path of the column is long. The substance to be detected contained in the eluent passes through the column while chemically interacting with the functional group molecules in the column. The strength of this interaction varies depending on the type of molecule of the substance to be detected. As a result, the rate of adsorption and desorption that the substance to be detected receives from the column while the eluent passes through the column 821 varies depending on the type of the substance. Therefore, the timing detected as a change in absorbance by the spectroscope 843 differs depending on the substance to be detected. As a result, the substance contained in the eluent can be detected.

  The detection result can be displayed on a display window that can be appropriately provided on the surface of the analysis unit or on a display unit of a computer connected to the analysis unit.

  Thereafter, the analysis unit is cleaned. This cleaning is performed, for example, by the following procedure. That is, by first opening the valve H of the switching valve 846 and then operating the pump 830, a predetermined amount of cleaning liquid is sucked into the pump 830, then the valve H is closed and the valves A and C are opened to operate the pump 830. Then, the filter 815 is washed. Next, the valves A and C are closed, the valve D is opened, the pump 830 is operated, and the washing liquid is passed through the column 821. Further, the valve D is closed, the valves B and E are opened, the pump 830 is operated, and the cleaning liquid is passed through both the filter 815 and the column 821.

  Next, an embodiment in which the present invention is applied to an immunoassay will be described. FIG. 41 shows the analysis principle of an immunoassay. FIG. 41a shows an example of the competitive method, and FIG. 41b shows another example of the competitive method. FIG. 41c is an example of a non-competitive method.

  In the example of FIG. 41a, stage I is a process performed outside the detection cartridge, and the sample antigen is added to the reagent containing the labeled antibody with the label attached to the antibody, and the pre-stage reaction is performed. By this preliminary reaction, a part of the labeled antibody contained in the reagent reacts with the sample antigen, and the sample antigen binds to a part of the labeled antibody. The remainder of the labeled antibody remains unreacted. In this state, the reagent is injected into the storage unit, and the process of stage II is performed. A solid-phased antigen is attached to the reservoir in advance, and unreacted antibodies in the reagent are captured by the solid-phased antigen in Step II. The reagent is discharged from the reservoir while leaving the labeled antibody captured by the immobilized antigen in the reservoir. Here, in stage III, a substrate for reaction with the labeled antibody is sent to the reservoir, and the reaction proceeds between the substrate and the labeled antibody. The reaction product is sent to the next detection mechanism in the detection cartridge and detected. Thus, when applying an immunoassay to this invention, a storage part will achieve a part of effect | action of a detection mechanism.

  In the example of FIG. 41b, the pretreatment in the stage I is the same as in the example of FIG. 41a, but unlike the case of FIG. 41a, the solid-phased antibody is previously attached to the reservoir. The reagent that has undergone the pre-stage reaction in stage I is injected into the reservoir of the detection cartridge in stage II, where only the labeled antibody that has reacted with the sample antigen in stage I is captured by the antibody in the reservoir. Capture at this time is also called a sandwich method because the antibody attached to the reservoir and the labeled antibody carried by the reagent sandwich the antigen. Next, in Step III, a substrate for reaction is sent to the reservoir, the reaction proceeds, and the reactive organism is detected by the detection mechanism.

  In the example of FIG. 41c, the immobilized antibody is attached to the reservoir in advance, and in stage I, the sample antigen is sent to the reservoir, and is bound to and captured by a part of the immobilized antibody. Next, in Step II, a reagent containing a labeled antibody is sent to the reservoir, and the labeled antibody is captured in the same manner as in Step II of FIG. 41b. In Step III, a substrate for reaction is sent to the reservoir. The reaction proceeds with the labeled antibody that has been liquefied and captured in the reservoir. The subsequent steps are the same as those in FIGS. 41a and 41b described above.

  The present invention can be applied to any of the above-described methods, or any known immunoassay method other than those described above. There are many literatures on immunoassays. To name a few, there are, for example, Japanese Unexamined Patent Publication Nos. 2000-155122 and 2003-987171. In FIG. 41, an example of an enzyme label is shown, but other labels can be used in the same manner.

  When the present invention is applied to an immunoassay, the reaction product can be detected by electrochemical analysis or optical analysis. As already described, when detecting hydrogen peroxide produced by an oxidoreductase, an electrochemical analysis technique is used. Further, optical analysis is used depending on the detection target. FIG. 42 is a bottom view showing an example of a detection cartridge 1001 when detection by electrochemical analysis is performed in an immunoassay. A flow path 1004 from the liquid inlet 1003 communicates with the storage unit 1002, and a liquid outlet of the storage unit 1002 is connected to the electrode chamber 1006 through the flow path 1005. In the electrode chamber 1006, although not shown, a working electrode, a counter electrode, and a reference electrode are arranged in the same manner as shown in FIG. The basic configuration of the detection cartridge 1001 is the same as that shown in FIG. Therefore, external ports 1007, 1008, 1009, and 1010 for communicating with the piping of the processing unit are formed on the bottom surface of the detection cartridge 1001. A processing unit similar to that in the concentration detection apparatus can be used. FIG. 43 shows a cross section of a detection cartridge applied to optical analysis in an immunoassay. This figure corresponds to FIG. 32 in the example of chromatography. Accordingly, corresponding parts are denoted by the same reference numerals. The example of FIG. 44 differs from the example of FIG. 32 only in that there is no flow path 824 in FIG. 32 and the port 814c directly communicates with the flow path 823. A wash buffer, an elution buffer, and a CBB solution are placed in each of the reagent tanks 851, 852, and 853 arranged in the processing unit.

  FIG. 47 shows a detection cartridge composed of three plastic substrates, and is an exploded view corresponding to FIG. The cartridge 1000 includes substrates 1011, 1012, and 1013 made of a plastic material, and these substrates are bonded to each other with an adhesive sheet 1014 interposed therebetween. The substrates 1011 and 1012 are respectively formed with a recess 1015a and an opening 1015b that form a reservoir. In addition, a reference electrode R and three working electrodes S are arranged on the substrate 1011, and small holes 104 a are formed in the adhesive sheet 1014 at positions corresponding to them. In this example, the detection cartridge 1000 is provided with a waste liquid reservoir, and the substrate 1011 and 1013 are provided with a recess 1016 for that purpose, and the intermediate substrate 1012 is provided with an opening 1017 connecting the two recesses 1016. Yes. The groove 1018 formed in the substrate 1012 is a reference electrode chamber corresponding to the reference electrode R, and the groove 1019 is a working electrode chamber corresponding to the working electrode S. Grooves 1020, 1021, and 1022 are formed in the substrate 1012 and the substrate 1013 for flow paths connecting the reservoir, the electrode chamber, and the waste liquid reservoir. Other points are the same as those of the above-described embodiment.

  Examples of the present invention are shown below.

(Method for manufacturing substance concentration detection cartridge)
Step 1: Injection molding 1) Production of molded product Substrates 11 to 14 were molded using an injection molding machine (manufactured by MEIKI). The molding conditions are a cylinder temperature of 280 ° C., a fixed part temperature of 290 ° C., and a mold temperature of 60 ° C. The runner was separated from the molded product to obtain a predetermined molded product.
2) Attaching parts to the molded product The molded product of the substrate 12 was provided with a carbon electrode and a silver paste electrode serving as a working electrode and a counter electrode. These were fixed by applying an adhesive in advance on the part to be installed and placing an electrode on the adhesive. The substrate 13 was provided with a container 23 containing potassium chloride for wetting the reference electrode during arsenic / selenium measurement and forming a silver-silver chloride reference electrode. This container is directly above the needle-like body 122 formed on the substrate 12 and directly below the pressing portion 141 formed on the substrate 14.
Step 2: Adhesive tape sticking 1) Preparation of adhesive tape A double-sided adhesive tape was set in a punching machine, a hole-opening process was performed according to the shape of each molded product, and a punched adhesive tape was produced.
2) Bonding of molded product A molded product having an adhesive tape attached to the upper surface and a molded product laminated thereon were set in a positioning device with a vacuum chamber. This apparatus has an alignment mechanism based on image recognition and a vacuum mechanism for the alignment portion. With this apparatus, both can be bonded together at an accurate position without bubbles.

Using the analysis unit and cartridge for liquid chromatographic analysis having the configuration shown in FIGS. 31 to 37, a separation test of an organic acid mixed solution composed of oxalic acid and succinic acid was performed.
The analyzer used was as follows.
Light source Sentronic GmbH FiberLight (200 to 1100 nm)
Spectroscope SAS series OEM module manufactured by Ocean Optics
(1024 element CMOS mounted type) (200-700 nm)
Cartridge Structure shown in Fig. 32-37 Column packing material Wako Pure Chemical Industries, Ltd. Wakosil-II 5C18-100 (particle size 5μm)
Furuta Filler Wakosil-II 25C18 (25-30μm 70% up)
Set flow rate and temperature 10 μl / min, room temperature Measurement wavelength 210 nm
The following sample was prepared by mixing 0.1 g of succinic acid (special grade manufactured by Wako Pure Chemical Industries) and 0.1 g of oxalic acid (special grade manufactured by Wako Pure Chemical Industries) with 100 ml of purified water (manufactured by Wako Pure Chemical Industries, Ltd.).
Oxalic acid 10 μg / 10 μl (MW = 126: dihydrate)
Succinic acid Same as above (MW = 60)
The analysis was performed according to the procedure described on the left based on FIGS. The amount of liquid fed from the liquid feed pump was as described in the “Pump” column of FIG. Analysis was performed by monitoring time and absorbance within the analysis unit. The pump was stopped when the discharge of the eluent from the pump was completed. The obtained result is shown in FIG. In this example, the oxalic acid peak was detected at 3 minutes and the succinic acid peak was detected at 12 minutes.

The present invention was applied to measurement of BNP (brain natriuretic polypeptide), which is a hormone useful for estimation of heart disease. The method employed in this example corresponds to an enzyme labeling method, a heterogeneous method, and a competitive method as immunoassay classification.
Anti-BNP antigen was used as the reservoir, and a means for electrochemically detecting the action of the enzyme label was adopted as the detection mechanism. In this example, the method of Matsuura et al. Described in Analytical Chemistry, vol. 77, No. 13, 2005, pp. 4235-4240 is applied to the cartridge and the processing unit of the present invention. The related substances are as follows.
AChE: Acetylcholinesterase
ACh: Acetylcholine
sulfo-SMCC: Sulfosuccinimidyl-4-N-maleimidomethylcyclohexane-1-carboxylate
PBS: Phosphate buffer (phosphate buffer)
EDC: 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide [Preparation]
(1) Carbon fiber filter (Toyobo, product number P-1611H, thickness 0.32mm) is immersed in a 100mg / l gold solution (1M-sulfuric acid) and stirred at -0.4V for 20 minutes while stirring. Then, gold was deposited, and then cleaned at +0.75 V for 2 minutes to produce a carbon fiber filter having a surface plated with gold. This gold-plated filter was placed in a 0.1 mM cysteamine hydrochloride solution for 2 hours to bind cysteamine on the Au surface. Remove this gold-plated filter, transfer to 10 mM PBS, add EDC to 0.1 g / l, human BNP-32 to 20 mg / l, incubate for 1 hour, wash with PBS, and apply BNP on the surface. A gold-plated filter on which (antigen) was immobilized was obtained.
(2) This BNP-immobilized gold-plated filter was cut into a diameter of 6.5 mm and a thickness of 0.4 mm, and installed as a cartridge storage part shown in FIG. The working electrode and counter electrode were PFCE, and the reference electrode was an Ag-coated electrode. The electrode dimensions and the positions of the external ports in the detection cartridge are the same as those in the system 1 of Example 2, but the dimensions of the reservoir and the electrode chamber were changed. The same processing unit as in Example 2 was used. Tank 1 (reagent 4) in FIG. 23 was charged with 1 mM acetylthiocholine chloride (PBS solution). The processing unit used in this example was able to cope with both heavy metal analysis and immunoassay if the cartridge was replaced.
(3) Adjust 0.1M-PBS (pH = 8) to BNP antibody (rabbit vs. BNP-32 IgG) to 0.4g / l and sulfo-SMCC to 0.4g / l. After incubation for a period of time, filtration was performed to remove excess sulfo-SMCC. Similarly, cholinesterase 1 g / l and s-acetylmercaptosuccinic anhydride 0.3 g / l were added to 0.1 M PBS and incubated for 10 minutes, followed by filtration. These were mixed at an antibody: ACh = 1: 0.7 (molar ratio) and cultured for 1 hour to obtain an AChE-labeled anti-BNP antibody.
(4) AChE-labeled anti-BNP antibody (0.4mg / l in PBS solution) 2ml is mixed with the test solution (human blood) containing BNP at a 1: 1 ratio and stirred for 30 minutes. The product was injected from the inlet of the cartridge using a commercially available syringe, passed through a BNP-fixed gold-plated filter, and allowed to flow out from the intermediate port 115 (step (1)). Next, 4 ml of PBS solution was injected from the same inlet to wash the BNP-immobilized gold-plated filter and set in the analyzer. By this operation, the BNP-to-BNP antibody (AChE-labeled) reaction product in the test solution flows out from the intermediate port, and the unreacted component of the AChE-labeled anti-BNP antibody is the BNP on the gold-plated filter in the reservoir. Installed in the analyzer.
(5) 1.0 ml of 1 mM acetylthiocholine chloride (PBS solution) as a substrate was fed from the port 1007 at 200 μl / min, so that the reservoir and the electrode chamber were continuously passed (step (2 )). When the substrate reaches the reservoir, thiocholine corresponding to the amount of AChE label is generated by the action of the AChE label and sent to the electrode chamber. LSV measurement was performed under the following conditions, and the electrode activity of thiocholine was measured from the obtained voltage-current curve. Since the amount of thiocholine corresponds to the unreacted anti-BNP antibody and has a certain relationship with the amount of BNP in the test solution, measure the BNP concentration in the test solution to obtain a calibration curve Was made.
LSV condition: -0.7V x 2 minutes → 1.4V (insertion speed 50mV / sec)
FIG. 44 shows an operation flow in the processing unit.

The present invention was applied to separation and quantitative analysis of specific proteins by immobilized metal affinity chromatography (IMAC).
(1) Production of Cartridge Aside from the cross section of the flow path shown in FIG. 43, a detection cartridge having the same external shape and external port as shown in FIGS. 32, 33 and 34 was produced by injection molding. The difference is that the chromatographic column 821 is eliminated and the cell shape is 5 mm in diameter. Acrylic resin was used as the substrate material. Further, as the reservoir 816, IMAC resin (VIVA science, Vivapure Metal Chelate resin) was used. As the processing unit, the same processing unit as in Example 4 was used.
(2) Sample preparation A crude protein extract was prepared as follows.
First, 500 ml of E. coli holding a vector capable of expressing poly (histidine) -tag-LacZ protein was cultured. Bacteria were collected by centrifugation at 4 ° C. and 3000 × g for 15 minutes. Next, the bacteria recovered by the Vortex mixer were suspended in 40 ml of extraction buffer. Then, an extraction / washing buffer was added to a concentration of 0.50 mg / ml, and the mixture was allowed to stand at room temperature for 30 minutes. Next, Escherichia coli was crushed with an ultrasonic crusher for 10 seconds, and then the crushed liquid was cooled on ice. Next, the crushed liquid was centrifuged at 4 ° C. and 10,000 × g for 20 minutes to precipitate the insoluble fraction, and the supernatant was collected separately. The collected crude extract was passed through a disposable filter having a pore size of 0.45 μm to obtain a sample solution.
(3) Preparation and pretreatment of cartridge From the inlet of the cartridge, 2 ml of a 0.1 M sodium chloride aqueous solution was first passed, then 2 ml of a 0.5 M nickel sulfate aqueous solution, and finally 4 ml of a 0.1 M sodium chloride aqueous solution. Next, 2 ml of a membrane equilibration buffer (solution prepared to be 50 mM NaH2PO4, 300 mM NaCl, 10 mM imidazole, pH 8.0) was passed through. At this time, the solution passed through the reservoir 816 from the inlet 814b and was allowed to flow out of the intermediate port 814a.
(4) Injection of sample into cartridge 5 ml of the sample solution prepared in step (2) was injected from a cartridge inlet using a commercially available syringe. The solution passed through the reservoir 816 from the inlet 814b and flowed out from the intermediate port 814a.
(5) Analysis operation The cartridge was set in the analyzer, and a washing buffer (50 mM NaH2PO4, 300 mM NaCl, 20 mM imidazole solution, pH 8.0) was injected from the port 814b at 2 ml and 1 ml / min, and was discharged from the intermediate port 814a. Next, the valve 836 was switched so that the ports 814b and 814c communicated, and 0.2 ml of an elution buffer (50 mM NaH 2 PO 4, 300 mM NaCl, 250 mM imidazole solution, pH 8.0) was injected from the port 814 a at a rate of 50 μl / min. At this time, the elution buffer passed through the reservoir 816 and flowed into the cell 814. Next, the valve 836 was switched again, and 0.2 ml of protein assay CBB solution (manufactured by Nacalai Tesque) was added from the port 814c at a rate of 500 μl / min. By this operation, the liquid in the cell 824 was almost replaced with the elution buffer and the protein assay CBB solution. Next, the absorbance at 595 nm was observed with a spectroscope built in the analyzer and a light source (common with HPLC), and the amount of recovered protein was quantified from the peak intensity of the absorbance.
(6) Result The flow of the above operation is shown in FIG. By this method, the target protein could be recovered at a high speed of about 15 minutes from the preparation of the cartridge to the end of the analysis.
The present invention is not limited to the measurement method described above, and can be applied to various methods. Some examples of measurement methods to which the present invention can be applied are shown in FIG. 46 together with an outline of the detection principle and operation.

(The invention's effect)
As can be seen from the above description, in the present invention, the detection cartridge is connectable to the detection cartridge having a flow path for passing the test liquid containing the detection target substance, and the cartridge is passed through the cartridge. Provided is a cartridge type detection device comprising a processing unit for generating information on a substance to be detected contained in a test liquid. The detection cartridge includes a storage unit that temporarily stores a substance to be detected, a liquid channel that passes through the storage unit, and a plurality of ports that communicate with the liquid channel. In the detection cartridge, at least a part of the detection mechanism is provided on the downstream side of the storage portion. The processing unit includes a liquid feeding pump and a pipe switching valve mechanism that switches and connects the liquid feeding pump to a selected one of a plurality of ports provided in the detection cartridge. The valve mechanism has a flow path connection that allows the test liquid supplied into the detection cartridge to pass through the reservoir and out of the cartridge from one port of the detection cartridge, and the reagent is detected by the liquid feed pump. It operates so as to switch between a flow path connection that allows the reagent supplied from one port of the cartridge to the reservoir and passed through the reservoir to be sent out of the cartridge from the other port.

  Further, in a specific aspect of the present invention, a storage unit that temporarily stores a substance to be detected, a liquid channel that passes through the storage unit, and a plurality of ports that communicate with the liquid channel are provided. A processing unit that performs analysis and / or processing using the detection cartridge has a plurality of reagent tanks, a liquid feeding pump, and a tank that connects a selected one of the plurality of reagent tanks to the liquid feeding pump. A tank switching valve plate having a switching valve mechanism and a pipe switching valve plate having a pipe switching valve mechanism for connecting a liquid feed pump to a desired one of the ports formed in the cartridge. Then, the substance to be detected is analyzed while switching the valve mechanism of the tank switching valve plate and the valve mechanism of the piping switching valve plate to a desired position and operating the liquid feed pump.

Since the cartridge type analyzer of the present invention is configured as described above, the functional part necessary for the analysis can be accommodated in the housing of the processing unit in an extremely compact manner, and can be easily configured as a portable type. It is. Therefore, the analysis apparatus of the present invention can be used for quick analysis at the site where the substance to be detected is collected, and is an extremely useful apparatus.
Although the present invention has been illustrated and described in detail with respect to specific embodiments, the present invention is not limited to the details of these specific embodiments. The scope of the present invention is defined by the description of the appended claims.

It is a perspective view which decomposes | disassembles and shows the cartridge for detection of one Embodiment of this invention. (A) is a perspective view which shows the assembly state of the cartridge for a detection. (B) shows the AA cross section of (a), (c) shows the BB cross section of (a). It is sectional drawing which shows schematically the liquid flow path of the cartridge for a detection. It is a perspective view which shows the flow of the test liquid in a cartridge for detection. It is a perspective view which shows the attachment state of a syringe holder. It is a perspective view which shows the flow of the eluent in a detection cartridge. It is a perspective view which decomposes | disassembles and shows the structure of a processing unit. It is a perspective view which shows the state which inserts a cartridge in a cartridge holder. It is a perspective view shown in the state where a cartridge holder was closed. It is a perspective view which decomposes | disassembles and shows the internal structure of a cartridge holder. It is an external appearance perspective view of a processing unit. It is a figure which shows the connection state with the external apparatus of a processing unit. It is a block diagram of the electric system inside a processing unit. It is a flowchart which shows a part of operation procedure in a measurement. It is a flowchart which shows the operation procedure following Fig.8 (a). It is a flowchart which shows the operation procedure following FIG.8 (b). It is a systematic diagram showing the whole system of an embodiment of the present invention. It is a graph which shows the electric potential-voltage curve obtained by the arsenic and selenium measurement. It is a graph which shows the electric potential-voltage curve obtained by the cadmium, lead, and mercury measurement. It is a schematic sectional drawing which shows the concentration part by other embodiment. It is a schematic sectional drawing which shows the concentration part by other embodiment. It is a perspective view which shows an example of the analysis unit by this invention used with the cartridge for a detection. FIG. 14 is a perspective view showing the analysis unit of FIG. It is a perspective view which shows the main body lower part of an analysis unit. It is a disassembled perspective view which shows an example of the cartridge for detection of this invention used for an electrochemical analysis. 14A shows the cartridge of FIG. 14A in an assembled state, where (i) is a perspective view, (ii) is a cross-sectional view taken along line AA in (i), and (iii) is a cross-sectional view taken along line BB in (i). is there. It is a longitudinal cross-sectional view of the cartridge of FIG. FIG. 15 is a perspective view corresponding to FIG. 3 (a), showing a flow of liquid in the cartridge of FIG. 14 (a). FIG. 15 is a perspective view corresponding to FIG. 3 (c), showing a liquid flow in the cartridge of FIG. 14 (a). It is a perspective view which shows the arrangement | positioning relationship of the tank switching piping plate in the analysis unit shown in FIG. 13, a reagent tank, and a switching valve mechanism. It is sectional drawing for showing the connection part of a reagent tank. It is a perspective view which shows arrangement | positioning of the various components in the main body upper part of an analysis unit. It is sectional drawing which shows the connection of a tank switching piping plate and a switching valve. It is the schematic which shows the connection relation of a liquid feeding pump, a tank switching piping plate, and a discharge destination switching piping plate. It is a perspective view of the cartridge holder used for an analysis unit. It is a top view which shows the port of the lower surface of a cartridge for detection. It is a systematic diagram which shows the connection relation of the switching valve in an analysis unit. It is a disassembled perspective view which shows the structure of a discharge destination switching piping plate. It is a decomposition | disassembly partial figure which shows the connection of a waste liquid tank. It is the schematic which shows the connection of a waste liquid tank. It is a systematic diagram showing an example of a system applied to chromatographic analysis. 4 is a flowchart showing a first half of an operation flow when detection is performed in the system 1 using a detection cartridge used for concentration analysis. 4 is a flowchart showing the latter half of the operation flow when detection is performed in system 1 using a detection cartridge used for concentration analysis. 6 is a flowchart showing a first half of an operation flow when detection is performed in the system 2 using a detection cartridge for concentration analysis. 6 is a flowchart showing the latter half of the operation flow when detection is performed in system 2 using a detection cartridge for concentration analysis. It is a flowchart which shows the first half part of the operation | movement flow in the case of performing detection using the cartridge for detection for chromatographic analysis. It is a flowchart which shows the latter half part of the working flow at the time of performing detection using the cartridge for detection for chromatographic analysis. It is a perspective view which shows the external appearance of the liquid chromatograph analyzer by other embodiment of this invention. FIG. 32 is a view showing a cross section of a detection cartridge used in the analyzer according to the embodiment of FIG. 31 including a connection relationship with a valve mechanism. It is an exploded view which shows the structure of the cartridge for detection shown in FIG. 32, (a) shows the lower surface of each plastic board which is a component of a cartridge, (b) shows the upper surface. It is sectional drawing of a cartridge for detection, (a) shows the section taken along line aa of Drawing 33 (a), and (b) shows the section taken along line bb, respectively. FIG. 32 is a plan view showing the configuration of the upper part of the main body in the housing of the analysis unit of FIG. 31. It is a perspective view which shows the relationship between a discharge destination switching valve plate, a guide member, and a detection cartridge. It is a top view which shows a tank piping switching valve plate. It is a flowchart which shows the action | operation in the apparatus for liquid chromatograph analysis shown to FIGS. It is a flowchart which shows the time flow of analysis operation | movement. 6 is a graph showing a detection result in Example 2. It is a process flow figure showing roughly some examples in the case of applying the present invention to an immunoassay, (a) is an example of a competitive method, (b) is an example of a competitive method called a sandwich method, (C) shows one example of the non-competitive method. FIG. 10 is a bottom view of the detection cartridge used in Example 5. FIG. 10 is a cross-sectional view of a detection cartridge used in Example 6. 10 is a table showing a processing flow in Example 5. 10 is a table showing a processing flow in Example 6. FIG. 2 is an exploded view similar to FIG. 1 showing an example of a detection cartridge constituted by three plastic substrates.

Claims (1)

A detection cartridge that generates an electric signal related to the concentration of the substance to be detected in a subject containing the substance to be detected can be connected to the cartridge, and the electric signal from the cartridge is read to read the electric signal of the substance to be detected A cartridge type concentration detection device comprising a processing unit for generating information on concentration,
The cartridge includes a test liquid introduction unit that introduces a test solution in which the sample is dissolved, and a liquid channel from the test solution introduction unit, and the liquid channel is used to concentrate a detection substance. And a detection electrode configuration, and an electrical signal related to the concentration of the detected substance is detected by the detection electrode configuration while the concentrated detected substance is passed through the liquid flow path. Is generated in the electrode configuration for
The processing unit includes processing means for receiving and processing the electrical signal from the cartridge and generating information relating to the concentration of the substance to be detected in the subject.
A cartridge type concentration detection apparatus.

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