JP2005265575A - Biochemical reaction cartridge and treatment device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a biochemical reaction cartridge and a treatment device, for removing a trouble of reagent replenishment and an error in the kind of the reagent, preventing the reagent in a chamber from flowing into a flow path or another chamber even by a change in environment or by vibration during storage or transportation, and surely supplying the reagent to a reaction portion in inspection. <P>SOLUTION: A penetrable partition board is provided between the reaction portion, including the chamber and the flow path, and a solution storage portion separated therefrom for storing therein a solution at a position corresponding to the chamber. The partition board is penetrated in order to move the solution from the storage portion to the chamber of the reaction portion. Further, this device comprises a pressurizing means for pressurizing the interior of the chamber to make it easy for the solution to move to the chamber of the reaction portion or a depressurizing means for depressurizing the interior of the chamber where the solution moves. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a biochemical reaction cartridge that is used by being incorporated in an apparatus for analyzing cells, microorganisms, chromosomes, nucleic acids, and the like in a specimen using biochemical reactions such as antigen-antibody reaction and nucleic acid hybridization reaction. .

  Many analyzers for specimens such as blood use an immunological method utilizing an antigen-antibody reaction or a method utilizing nucleic acid hybridization. An example of such an analysis method is that a protein such as an antibody or an antigen that specifically binds to a substance to be detected or a single-stranded nucleic acid is used as a probe and immobilized on a solid surface such as a fine particle, a bead, or a glass plate. Then, an antigen-antibody reaction or nucleic acid hybridization is performed with the substance to be detected.

  And using a labeling substance having a specific interaction carrying a labeling substance with high detection sensitivity such as an enzyme, a fluorescent substance, a luminescent substance, such as a labeled antibody, a labeled antigen or a labeled nucleic acid, An antigen-antibody compound or double-stranded nucleic acid is detected to detect the presence or absence of a test substance or to quantify the test substance.

  As a development of these technologies, US Pat. No. 5,445,934 discloses a so-called DNA array in which a large number of DNA (deoxyribonucleic acid) probes having different base sequences are arranged in an array on a substrate. Has been. Anal. Biochem. 270 (1), 103-111, 1999 discloses a method for producing a protein array having a structure like a DNA array by arranging many types of proteins on a membrane filter. And it has become possible to perform inspection of a very large number of items at once by using a DNA array, a protein array or the like.

  In various specimen analysis methods, disposable biochemical reaction cartridges that perform necessary reactions internally have been proposed for the purpose of reducing contamination by specimens, improving reaction efficiency, miniaturizing equipment, and simplifying operations. JP-T-11-509094 discloses that a plurality of chambers are arranged in a biochemical reaction cartridge including a DNA array, a solution is moved by differential pressure, and DNA in a specimen is extracted or amplified inside the cartridge, or A biochemical reaction cartridge that enables reactions such as hybridization is disclosed.

As a reagent supply method using a biochemical reaction cartridge, Japanese Patent Application Laid-Open No. 2000-266759 discloses that a reagent is supplied from an external reagent bottle to a disposable analysis cassette. Discloses that a reagent is built in the chamber in advance.
US Pat. No. 5,445,934 Japanese National Patent Publication No. 11-509094 Japanese National Patent Publication No. 11-509094 JP 2000-266759 A Japanese National Patent Publication No. 11-509094

  However, when reagents are supplied from the outside, a plurality of reagents must be prepared separately from the biochemical reaction cartridge, and if there are more inspection items, the number of necessary reagents increases and replenishment only becomes troublesome. In addition, there is a possibility that the type of reagent is wrong. In the case of a reagent built in the chamber of the biochemical reaction cartridge, the reagent in the chamber flows into the flow path or other chambers due to environmental changes during storage or transportation, vibration during transportation, etc. May cause different reactions.

  The object of the present invention is to solve the above-mentioned problems, to eliminate the troublesome replenishment of reagents and the wrong type of reagent, and to allow the reagents in the chamber to flow through and other places even in environmental changes and vibrations during storage and transportation. It is another object of the present invention to provide a biochemical reaction cartridge that can reliably supply a reagent to a reaction section without flowing into the chamber.

  In order to achieve the above object, a biochemical reaction cartridge and a processing apparatus according to the present invention store a solution at a position corresponding to the reaction chamber, including a reaction portion including a chamber and a flow path, and separated from or separate from the reaction portion. A solution storage part, and in order to move the solution from the solution storage part to the chamber of the reaction part, a partition member penetrable between the solution storage part and the reaction part is provided, and the partition member When the solution passes through the reaction part chamber, it has at least one of a pressurizing means for pressurizing the chamber of the solution storage part or a decompression means for decompressing the reaction part chamber where the solution moves. It is characterized by that.

  As described above, the biochemical reaction cartridge according to the present invention includes a reaction part including a chamber and a flow path, and a solution storage part that stores a solution such as a reagent and a cleaning agent separately from the reaction part or separately from the reaction part. A partition member that can be penetrated by a member that is isolated to move the solution from the solution storage part to the reaction part, or that can be penetrated by contacting the solution storage part and the reaction part to pass through the wall, When the partition member is penetrated and the solution moves to the reaction portion chamber, a predetermined amount of solution is obtained by pressurizing the chamber of the solution storage portion or depressurizing the chamber of the reaction portion where the solution moves. Can be reliably prepared in the biochemical reaction cartridge, reducing the troublesome replenishment of reagents and mistakes in the type of reagent, as well as changes in environment and vibration during storage and transportation. Without reagent inner flow into the flow path or other chambers, there is an advantage that can not correctly cause a reaction intended.

  The present invention will be described in detail based on the illustrated embodiment.

  FIG. 1 is a perspective view of a biochemical reaction cartridge in the present embodiment. The cartridge has a two-layer structure of a reaction portion 1 where a reaction is performed and a solution storage portion 2 which is disposed on the cartridge and stores a solution such as a reagent / cleaning agent. The main body of the reaction part 1 and the solution storage part 2 is composed of a synthetic resin such as polymethyl methacrylate (PMMA), acrylonitrile-butadiene-styrene (ABS) copolymer, polystyrene, polycarbonate, polyester, polyvinyl chloride and the like. Yes. When performing optical measurements on the reactants, the reaction portion 1 requires a transparent or translucent plastic.

  A sample inlet 3 for injecting a sample such as blood using a syringe is provided above the reaction portion 1, and the sample inlet 3 is sealed with a rubber cap. Moreover, in order to move the solution in the reaction part 1, a plurality of nozzle inlets 4 for inserting a nozzle and performing pressurization or decompression are provided on both side surfaces of the reaction part 1. Is sealed with a rubber cap, and the opposite surface has the same configuration.

  In addition, three aluminum foil sheets 5 are attached to the upper portion of the solution storage portion 2 to block the upper portion of a solution storage chamber described later. The reaction portion 1 and the solution storage portion 2 are welded by ultrasonic waves. Note that the reaction portion 1 and the solution storage portion 2 may be configured separately and overlapped when used.

  FIG. 2 shows a plan cross-sectional view of the solution storage part 2 of FIG. 1, wherein independent chambers 6a to 6m containing the solution are provided, and the chambers 6a and 6b each include a first hemolytic agent containing EDTA that breaks the cell wall, A second hemolytic agent containing a protein denaturant such as a surfactant is accumulated. Silica-coated magnetic particles adsorbing DNA are accumulated in the chamber 6c, and the first and second extraction detergents used for purifying the DNA at the time of DNA extraction are stored in the chambers 6l and 6m. Is accumulated.

  The chamber 6d has an eluate composed of a low-concentration salt buffer that elutes DNA from magnetic particles, and the chamber 6g has a primer, polymerase, dNTP solution, buffer, and a mixed solution such as Cy-3dUTP containing a fluorescent agent. Is filled. The chambers 6h and 6j have a cleaning agent containing a detergent for washing the fluorescently labeled sample DNA and fluorescent label, and the chamber 6i has a chamber containing a DNA microarray to be described later dried. Because of the accumulation of alcohol. Each chamber 6a to 6m is provided with a pointed valve rod 7a to 7m for penetrating a sheet to be described later.

  FIG. 3 is a cross-sectional view showing the state of the biochemical reaction cartridge during storage. A valve stem 7 having a notch 8 is inserted into the chamber 6 of the solution storage portion 2 containing the solution, and two O-rings. 9 is held. The lower part of the solution chamber 6 is closed with an aluminum foil sheet 10, and a sealing material 12 is interposed between the chamber 6 and the chamber 11 of the reaction portion 1 to prevent air from entering and exiting. Changes in the volume and pressure of the solution and air due to the environment can be absorbed by the deformation of the aluminum foil sheet 10, and the solution in the chamber 6 does not enter the reaction portion 1 at any time.

  In FIG. 4, a tester injects a liquid sample such as blood from the sample inlet 3 and sets the sample in a processing apparatus to be described later, and then uses the short pressing rod 13 a of the tool needle 13 to use the valve rod 7 at the first stage. Is pushed, the aluminum foil sheet 10 is broken, and the solution starts to move from the chamber 6 to the chamber 11. In this state, the notches 8 provided in the valve stem 7 are connected to the upper and lower sides of the two O-rings 9, so that the air can pass between the chamber 6 and the outside so that the solution can move smoothly. At this time, the electric syringe pump 28 of the processing apparatus of FIG. 7 to be described later is operated, and the solution moves more reliably to the chamber 11 by sucking the air in the chamber 11 of the reaction portion 1 and reducing the pressure.

  As described above, since the penetrating aluminum foil sheet 10 is provided as the partition member, the tool needle 13 is not touched by simply pressing the pressing bar 13a of the tool needle 13 into the reaction portion 1 side. The solution can be poured into the chamber 11 from the chamber 6, and the electric syringe pump 28 of the processing apparatus is further operated to suck the air in the chamber 11 of the reaction portion 1, so that the solution is more reliably supplied to the chamber 11. Can be moved to. In the present embodiment, the corresponding chamber of the reaction portion 1 is directly below the position of the chamber of the solution storage portion 2, but the corresponding chamber may not be directly below by forming a flow path.

  Next, the inspector pulls out the tool needle 13 once and turns it upside down as shown in FIG. 5 to push down the valve rod 7 further by pushing in the second stage with the long side pressing rod 13b. Then, the air is sealed by the upper O-ring 9, and the solution can move within the reaction portion 1 described later. The inspector performs this process for all the chambers 6a to 6m. As described above, the solution can be poured by pushing the first stage using the tool needle 13 and sealed by pushing the second stage. Therefore, the solution can be poured into the chamber 11 and sealed by a simple operation of pushing. Two tasks can be performed simultaneously.

  FIG. 6 is a plan sectional view of the reaction portion 1. Ten nozzle inlets 4a to 4j are provided on one side surface, and ten nozzle inlets 4k to 4t are provided on the opposite side surface. The nozzle inlets 4a to 4t communicate with chambers 11a to 11t, which are places where solutions are stored or where reactions occur, via air flow paths 14a to 14t through which air flows. However, since the nozzle inlets 4n, 4p, 4q, and 4s are not used in the process of the present embodiment, they are not communicated with the chamber and are reserved.

  That is, the nozzle inlets 4a to 4j communicate with the chambers 11a to 11j via the flow paths 14a to 14j, and the nozzle inlets 4k, 4l, 4m, 4o, 4r, and 4t on the opposite side are respectively connected to the flow paths 14k and 14l. , 14m, 14o, 14r, and 14t communicate with the chambers 11k, 11l, 11m, 11o, 11r, and 11t.

  The specimen inlet 3 communicates with the chamber 16, the chambers 11a, 11b, 11c, and 11k communicate with the chamber 16, the chambers 11g and 11o communicate with the chamber 17, and the chambers 11h, 11i, 11j, 11r, and 11t communicate with the chamber 18. ing. Further, the chamber 16 communicates with the chamber 17 via the flow path 19, and the chamber 17 communicates with the chamber 18 via the flow path 20. Chambers 11d, 11e, 11f, 11l, and 11m communicate with the flow path 19 through flow paths 15d, 15e, 15f, 15l, and 15m, respectively.

  A square hole is formed in the bottom surface of the chamber 18, and a DNA microarray 21 made of a glass substrate is attached to the square hole with the probe surface facing upward. In the DNA microarray 21, different types of DNA probes are arranged in a high density of several hundreds to several hundreds of thousands on a solid phase surface such as a glass plate of about 1 inch square. By performing a hybridization reaction with the sample DNA using this DNA microarray 21, a large number of genes can be examined at once. Further, these DNA probes are regularly arranged in a matrix, and there is an advantage that the addresses (how many rows and what columns) of each DNA probe can be easily taken out as information. In addition to infectious disease viruses / bacteria and disease-related genes, genes to be tested include individual gene polymorphisms.

  In the chambers 11a and 11b of the reaction portion 1, the first hemolytic agent and the second hemolytic agent flowing from the chambers 6a and 6b of the solution storage portion 2 are accumulated, respectively. The magnetic particles flowing from the chamber 6c are accumulated in the chamber 11c, and the first and second extracted cleaning agents flowing from the chamber 6l and the chamber 6m are accumulated in the chamber 11l and the chamber 11m, respectively. The chamber 11d is filled with the eluate flowing from the chamber 6d, and the chamber 11g is filled with a liquid mixture required for PCR (Polymerase Chain Reaction) flowing from the chamber 6g. The chambers 11h and 11j store the cleaning agent that flows from the chambers 6h and 6j, respectively, and the chamber 11i stores the alcohol that flows from the chamber 6i.

  The chamber 11e is a chamber for collecting dust other than blood DNA, the chamber 11f is a chamber for collecting waste liquids of the first and second extraction detergents in the chambers 11l and 11m, and the chamber 11r is for the first and second detergents. Chambers 11k, 11o, and 11t are blank chambers provided to prevent the solution from flowing into the nozzle inlet.

  FIG. 7 shows a processing apparatus for controlling the movement of the solution and various reactions in the biochemical reaction cartridge. The table 22 is a place where a biochemical reaction cartridge is set. On the table 22, an electromagnet 23 that is operated when extracting DNA or the like from the sample in the cartridge, and amplifying the DNA from the sample by a method such as PCR. When performing hybridization between the Peltier element 24 for temperature control, the amplified sample DNA and the DNA probe on the DNA microarray in the cartridge, and when washing the sample DNA that has not been hybridized A Peltier element 25 for temperature control is disposed, and these are connected to a control unit 26 for controlling the entire processing apparatus.

  The table 22 of FIG. 7 includes an electric syringe pumps 27 and 28 and a pump block 31 provided with a plurality of pump nozzles 29 and 30 on each side at the inlet / outlet for discharging or sucking air by these pumps 27 and 28. , 32 are arranged. In addition, the control unit 26 is connected to an input unit 33 that is input by an inspector.

  A plurality of well-known electric switching valves (not shown) are arranged between the electric syringe pumps 27 and 28 and the pump nozzles 29 and 30, and are connected to the control unit 26 together with the pumps 27 and 28. The control unit 26 can control to selectively open one pump nozzle 29, 30 out of 10 on each side with respect to the pumps 27, 28, or to close all pump nozzles 29, 30. Has been.

  For example, as described in FIG. 4, after setting the biochemical reaction cartridge in the processing apparatus, the aluminum foil sheet 10a that spatially separates the chamber 6a of the solution storage portion 2 and the chamber 11a of the reaction portion 1 is used. When the valve rod 7 is pushed into the first stage using the short pressing rod 13a of the tool needle 13, the aluminum foil sheet 10a is broken, and the solution starts to move from the chamber 6a to the chamber 11a. -J, 30k-t is opened by 30k, all other pump nozzles are closed, the electric syringe pump 28 is operated, and the air in the chamber 11a of the reaction portion 1 is sucked and depressurized, thereby ensuring more certainty. The solution can be moved to the chamber 11a. Similarly, the solution is surely moved sequentially from the chamber 6 of the other storage part 2 to the chamber 11 of the reaction part 1.

  When the solution is moved from the solution storage part 2 to the reaction part 1 and a processing start signal is input, DNA and the like are extracted and amplified in the reaction part 1. Hybridization is performed with a DNA probe on a certain DNA microarray, and the fluorescence-labeled sample DNA that has not been hybridized and the fluorescence label are washed.

  In the present embodiment, when blood is used as a specimen and the examiner passes the rubber cap at the specimen inlet 2 through the syringe and injects blood, the blood flows into the chamber 16. Thereafter, the examiner places the biochemical reaction cartridge on the table 22, operates a lever (not shown), and moves the pump blocks 31 and 32 in the direction of the arrow in FIG. Then, pump nozzles 29 and 30 are inserted into the nozzle inlet 4 of the reaction portion 1.

  As explained in FIG. 6, since the nozzle inlet 4 is concentrated on the two surfaces on both sides of the biochemical reaction cartridge, the pump block incorporating the electric syringe pumps 27 and 28, the electric switching valve, and the pump nozzles 29 and 30 The shape and arrangement of 31 and 32 are simplified. Furthermore, the pump nozzles 29 and 30 can be inserted by a simple operation of sandwiching the cartridges at the same time with the pump blocks 31 and 32 while securing the necessary chambers and flow paths. It will be easy. And if all the nozzle inlets 4a-4t are arrange | positioned at the same height, ie, linear form, all the height of the flow paths 14a-14t connected to the nozzle inlets 4a-4t will become the same, and preparation of the flow paths 14a-14t will be carried out. It becomes easy.

  In the processing apparatus of FIG. 7, if the pump blocks 31 and 32 are made n times longer for n biochemical reaction cartridges, n cartridges can be arranged in series by arranging the n cartridges in series. On the other hand, necessary steps can be performed simultaneously, and a biochemical reaction can be performed on a large number of cartridges with a very simple configuration.

  The inspector performs the process of pouring and sealing the solution described with reference to FIGS. 4 and 5, and the process starts when a command for starting the process is input at the input unit 33. Of course, a robot arm may be provided on the apparatus side, and the tool needle 13 may be attached to the robot arm, and the steps described with reference to FIGS. 4 and 5 may be performed automatically. In this case, as described above, the electric syringe pump 28 can be operated to smoothly flow the solution. Further, as in the present embodiment, instead of performing the pouring process immediately before using the biochemical reaction cartridge, the robot arm provided on the apparatus side is operated immediately before the solution is required to move each solution. It can also be poured.

  FIG. 8 is a flowchart for explaining the processing procedure in the processing apparatus of the present embodiment. First, in step S1, the control unit 26 opens only the nozzle inlets 4a and 4k, discharges air from the electric syringe pump 27, sucks air from the pump 28, and blood enters the first hemolytic agent in the chamber 11a. Pour into chamber 16. At this time, depending on the viscosity of the hemolytic agent and the resistance of the flow path, if the suction of the air from the pump 28 is controlled to start 10 to 200 milliseconds after the start of the discharge of the air from the pump 27, at the head of the flowing solution The solution flows smoothly without splashing out.

  As described above, by controlling the pressurization and decompression by shifting the air supply and suction timings, the solution can flow smoothly. However, the suction of air from the electric syringe pump 28 If fine control is performed, such as increasing linearly from the start of discharge, it becomes possible to flow more smoothly. Further, by using both pressurization and decompression, the pressure generated in the reaction portion 1 can be reduced. As a result, when there are branch channels or chambers in which the solution is not desired to flow during the solution movement, , There is also an effect to prevent flowing into there. The same applies to the movement of the following solutions.

  Control of the air supply can be easily realized by using the electric syringe pumps 27 and 28. Only the nozzle inlets 4a and 4o are opened, and the discharge and suction of air are alternately repeated by the syringe pumps 27 and 28. The operation of flowing the solution into the flow path 19 and returning it to the flow path 19 is repeated to perform stirring. Alternatively, the air may be continuously discharged from the pump 28 and stirred while generating bubbles.

  FIG. 9 is a cross-sectional view of the reaction portion 1 passing through the chamber 11a, the chamber 16, and the chamber 11k of FIG. 6, and the pump nozzle 29 is inserted into the nozzle inlet 4a and pressurized, and the pump nozzle 30 is inserted into the nozzle inlet 4k. The pressure is reduced and the first hemolytic agent in the chamber 11a flows into the chamber 16 containing blood. The chamber 11a actually communicates with the solution storage portion 2, but for convenience, a ceiling is provided and is not communicated.

  In FIG. 8, only the nozzle inlets 4b and 4k are opened in the next step S2, and the second hemolytic agent in the chamber 11b is poured into the chamber 16 in the same manner. In step S3, only the nozzle inlets 4c and 4k are opened, and the same. The magnetic particles in the chamber 11 c are poured into the chamber 16. In steps S2 and S3, stirring is performed in the same manner as in step S1. In step S3, the DNA produced by the dissolution of the cells in steps S1 and S2 adheres to the magnetic particles.

  Then, when the electromagnet 23 is turned on in step S4, only the nozzle inlets 4e and 4k are opened, the air is discharged from the electric syringe pump 28, the air is sucked from the pump 27, and the solution in the chamber 16 is moved to the chamber 11e. During this movement, magnetic particles and DNA are captured on the electromagnet 23 of the flow path 19. The suction and discharge of the electric syringe pumps 27 and 28 are alternately repeated, and the solution is reciprocated twice between the chambers 16 and 11e to increase the DNA capture efficiency. Increasing the number of times further increases the capture efficiency, but increases the processing time.

  In this way, DNA is captured in a flowing state on a small channel having a width of about 1 to 2 mm and a height of about 0.2 to 1 mm using magnetic particles, so that it can be captured extremely efficiently. Can do. The same applies when the capture target substance is RNA or protein.

  Next, in step S5, the electromagnet 23 is turned off, only the nozzle inlets 4f and 4l are opened, the air is discharged from the electric syringe pump 28, the air is sucked from the pump 27, and the first extraction cleaning liquid in the chamber 11l is supplied to the chamber. Move to 11f. At this time, the magnetic particles and DNA captured in step S4 move together with the extraction cleaning liquid, and cleaning is performed. After reciprocating twice in the same manner as in step S4, the electromagnet 23 is turned on, and reciprocating twice in the same manner to collect the magnetic particles and DNA on the electromagnet 23 in the flow path 19, and return the solution to the chamber 11l. deep.

  In step S6, the second extraction cleaning liquid in the chamber 11m is further cleaned by performing the same process as in step S5 using the nozzle inlets 4f and 4m. In step S7, with the electromagnet 23 turned on, only the nozzle inlets 4d and 4o are opened, air is discharged from the electric syringe pump 27, air is sucked from the pump 28, and the eluate in the chamber 11d is moved to the chamber 17 To do.

  At this time, the magnetic particles and DNA are separated by the action of the eluate, and only the DNA moves to the chamber 17 together with the eluate, and the magnetic particles remain in the flow path 19, thus performing DNA extraction and purification. Is called. By preparing the chambers 11l and 11m containing the extraction washing liquid and the chamber 11f containing the washing waste liquid, it becomes possible to extract and purify the DNA in the biochemical reaction cartridge 1.

  Next, in step S8, only the nozzle inlets 4g and 4o are opened, the air is discharged from the electric syringe pump 27, the air is sucked from the pump 28, and the PCR drug in the chamber 11g is poured into the chamber 17. Further, only the nozzle inlets 4g and 4t are opened, and the electric syringe pumps 27 and 28 alternately discharge and suck air, and the solution in the chamber 16 is allowed to flow through the flow path 20, and then the operation of returning to it is repeated for stirring. Do. Then, after controlling the Peltier element 24 and holding the solution in the chamber 17 at a temperature of 96 ° C. for 10 minutes, the process of 96 ° C. · 10 seconds, 55 ° C. · 10 seconds, 72 ° C. · 1 minute is repeated 30 times. The amplified DNA is amplified by PCR.

  In step S9, only the nozzle inlets 4g and 4t are opened, air is discharged from the electric syringe pump 27, air is sucked from the pump 28, and the solution in the chamber 17 is moved to the chamber 18. Further, the Peltier element 25 is controlled to perform hybridization by keeping the solution in the chamber 18 at 45 ° C. for 2 hours. At this time, the pumps 27 and 28 alternately discharge and suck air, and move the solution in the chamber 18 to the flow path 15t, and then repeat the operation of returning to the subsequent, and the hybridization proceeds.

  Next, in step S10, while maintaining the same 45 ° C., this time, only the nozzle inlets 4h and 4r are opened, air is discharged from the electric syringe pump 27, air is sucked from the pump 28, and the solution in the chamber 18 is discharged. The first cleaning liquid in the chamber 11h is poured into the chamber 11r through the chamber 18 while moving to the chamber 11r. By alternately repeating suction and discharge of the pumps 27 and 28, the solution is reciprocated twice between the chambers 11h, 18 and 11r, and finally returned to the chamber 11h. In this way, the fluorescently labeled sample DNA and the fluorescent label that have not been hybridized are washed.

  FIG. 10 is a cross-sectional view passing through the chamber 11h, the chamber 18, and the chamber 11r of FIG. 6, the pump nozzle 29 is inserted into the nozzle inlet 4h and pressurized, the pump nozzle 30 is inserted into the nozzle inlet 4r, and the pressure is reduced. A state in which the first cleaning liquid in the chamber 11h flows into the chamber 11r through the chamber 18 is shown. The chamber 11h actually communicates with the solution storage portion 2, but for convenience, a ceiling is provided and is not communicated.

  In FIG. 8, while maintaining the same 45 ° C. in step S11, the second cleaning liquid in the chamber 11j is further cleaned by performing the same process as in step S10 using the nozzle inlets 4j and 4r, and finally the chamber 11j. Return to. Thus, since the chambers 11h and 11j containing the cleaning liquid and the chamber 11r containing the cleaned waste liquid are prepared, the DNA microarray 21 can be cleaned in the biochemical reaction cartridge.

  In step S12, only the nozzle inlets 4i and 4r are opened, air is discharged from the electric syringe pump 27, air is sucked from the pump 28, and the alcohol in the chamber 11i is moved through the chamber 18 to the chamber 11r. Thereafter, only the nozzle inlets 4i and 4t are opened, air is discharged from the pump 27, air is sucked from the pump 28, and the inside of the chamber 18 is dried.

  Thereafter, when the inspector operates a lever (not shown), the pump blocks 31 and 32 are moved away from the biochemical reaction cartridge by a mechanism (not shown), and the pump nozzles 29 and 30 are detached from the nozzle inlet 4 of the cartridge. Then, the examiner inserts this cartridge into a DNA microarray reader such as a well-known scanner (not shown) to perform measurement and analysis.

  In this embodiment, as described above, after setting the biochemical reaction cartridge in the processing apparatus, the aluminum foil sheet 10a that spatially separates the chamber 6a of the solution storage portion 2 and the chamber 11a of the reaction portion 1 is used. When the valve rod 7 is pushed into the first stage using the short pressing rod 13a of the tool needle 13, the aluminum foil sheet 10a is broken, and the solution starts to move from the chamber 6a to the chamber 11a. -J, 30k-t is opened by 30k, all other pump nozzles are closed, the electric syringe pump 28 is operated, and the air in the chamber 11a of the reaction portion 1 is sucked and depressurized, thereby ensuring more certainty. The solution can be moved to the chamber 11a. Similarly, the solution is surely moved sequentially from the chamber 6 of the other storage portion 2 to the chamber 11 of the reaction portion 1, but when the aluminum foil sheet 10a is broken and the solution starts moving from the chamber 6a to the chamber 11a. Even if the chamber 6a of the solution storage portion 2 is pressurized, the solution can be reliably moved to the chamber 11a.

  Furthermore, the chamber 6a of the solution storage part 2 may be pressurized and at the same time the pressure inside the chamber 11a of the reaction part 1 may be reduced. By doing so, the solution can be moved to the chamber 11a more reliably.

  As a method of pressurizing the chamber 6a of the solution storage portion 2, there is a pressurizing means as shown in FIGS.

  FIG. 11 is a cross-sectional view of the pressurizing means 39. The cylinder 40 includes a piston 41 having an air hole 42 and a valve 45, and a spring 43 that pushes the piston 41 upward.

  FIG. 12 shows that in the biochemical reaction cartridge, the valve rod 7 is pushed into the first stage using the short pressing rod 13 a of the tool needle 13 to break the aluminum foil sheet 10, and the solution moves from the chamber 6 to the chamber 11. It is the figure which removed the needle 13 for tools at the time of the beginning, and inserted the pressurization means 39 on the chamber 6 of a biochemical reaction cartridge. In this state, the notches 8 provided in the valve stem 7 are connected to the upper and lower sides of the two O-rings 9, so that the air can pass between the chamber 6 and the outside so that the solution can move smoothly. At this time, when the inspector pushes the piston 41 downward as shown in FIG. 13, the air in the air chamber 44 does not come out of the air hole 42 by the action of the valve 45, and the chamber 6 of the solution storage portion 2 is added. The solution remaining in the chamber 6 under pressure is pushed out into the chamber 11 of the reaction portion 1 and the solution can be moved reliably.

  Further, as in the case of the tool needle 13, the pressurizing means 39 may be attached to the robot arm, and the above steps may be performed automatically, and at the same time, by depressurizing the chamber 11 of the reaction portion 1 by the aforementioned method. The solution can be moved more smoothly.

  The method for pressurizing the chamber 6 of the storage portion 2 is not limited to this, and can be automatically performed using a pump provided in the processing apparatus.

  Some of the embodiments of the present invention are listed below.

(Embodiment 1)
A reaction portion including a chamber and a flow path; and a solution storage portion that stores the solution in a position corresponding to the chamber, separated or separated from the reaction portion, and the solution from the solution storage portion is a chamber of the reaction portion. A partition member that can penetrate between the solution storage portion and the reaction portion, and when the partition member is penetrated and the solution moves to the chamber of the reaction portion, A biochemical reaction cartridge and a processing apparatus, comprising at least one of a pressurizing means for pressurizing the inside of the chamber and a decompressing means for reducing the pressure in the chamber of the reaction part where the solution moves.

It is a perspective view of the biochemical reaction cartridge of an embodiment. It is a plane sectional view of a solution storage part. It is a partial cross section figure of a biochemical reaction cartridge at the time of preservation. It is sectional drawing of a part of biochemical reaction cartridge of the state which pushed in the valve stem 1 step | paragraph. It is a partial cross section figure of the biochemical reaction cartridge of the state which pushed in the valve stem 2 steps | paragraphs. It is a plane sectional view of a reaction part. It is a block block diagram of the processing apparatus which controls the movement of the solution in the biochemical reaction cartridge of this embodiment, and various reactions. It is a flowchart figure of a processing procedure. FIG. 7 is a cross-sectional view of a portion of the chamber of FIG. FIG. 7 is a cross-sectional view of a portion of the chamber of FIG. It is sectional drawing of a pressurizing means. It is sectional drawing of the pressurization means closely_contact | adhered on the storage part chamber of a biochemical reaction cartridge. It is sectional drawing of the pressurization means of the state which pushed in the piston.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Reaction part 2 Solution storage part 3 Sample inlet 4 Nozzle inlet 5, 10 Aluminum foil sheet 7 Valve rod 8 Notch 9 O-ring 11, 16-18 Chamber 13 Tool needle 15, 19, 20 Channel 21 DNA microarray 22 Table 26 Control unit 27, 28 Electric syringe pump 29, 30 Pump nozzle 31, 32 Pump block 39 Pressurizing means 40 Cylinder 41 Piston 42 Air hole 43 Spring 44 Air chamber 45 Valve

Claims (3)

  A reaction portion including a chamber and a flow path; and a solution storage portion that stores the solution in a position corresponding to the chamber, separated or separated from the reaction portion, and the solution is stored in the chamber of the reaction portion. A partition member that is piercable between the solution storage portion and the reaction portion, and when the partition member is penetrated and the solution moves to the chamber of the reaction portion, A biochemical reaction cartridge and a processing apparatus, comprising at least one of a pressurizing means for pressurizing the inside of the chamber and a decompressing means for reducing the pressure in the chamber of the reaction portion where the solution moves.   A reaction portion including a chamber and a flow path; and a solution storage portion that stores the solution in a position corresponding to the chamber, separated or separated from the reaction portion, and the solution is stored in the chamber of the reaction portion. A partition member that can penetrate between the solution storage part and the reaction part, and a penetrating means for penetrating the partition member, the partition member being penetrated by the penetrating means. When the solution is moved to the chamber of the reaction portion, it has at least one of a pressurizing means for pressurizing the inside of the chamber of the solution storage portion or a decompression means for decompressing the inside of the chamber of the reaction portion where the solution moves. A biochemical reaction cartridge and a processing apparatus.   The biochemical reaction cartridge and the processing apparatus include a plurality of chambers in the reaction portion, and a moving unit that moves the solution between the plurality of chambers. The biochemical reaction cartridge and the processing apparatus according to claim 1 or 2, wherein at least a part of the means is shared.

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