JP4458334B2 - Biochemical reaction cartridge - Google Patents

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 techniques, 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 in which many types of proteins are arranged 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.

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.
JP 2000-266759 A Special table flat 11-509094

  The object of the present invention is to reliably solve the above-mentioned problems, there is no risk of troublesome reagent replenishment, reagent type, and processing order, and there is no environmental change or vibration during storage, transportation, or processing. An object of the present invention is to provide a biochemical reaction cartridge in which a reagent in a chamber does not flow into a flow path or another chamber.

In order to solve the above-described problem, in the present invention, a reaction portion including a plurality of chambers and a plurality of flow paths, and a plurality of solutions that are separated from the reaction portion and store solutions at positions corresponding to the plurality of chambers. A solution storage part including a storage chamber, and a penetrable partition member for moving the solution from the solution storage part to the reaction part chamber and a valve rod for penetrating the partition member. A biochemical reaction processing method using a biochemical reaction cartridge, wherein the solution is moved through the partition member in a state where the reaction portion and the solution storage portion are overlapped at the time of use. there, the biochemical reaction cartridge, the in the first stage of depression of the valve stem by the needle tool for the partition member, said solution storage chamber is opened to the outside and The solution solution reservoir portion is moved into the chamber of the reaction section, which said solution storage chamber by pushing the second stage is sealed to the outside I,
The solution storage chamber is opened to the outside by penetrating at least one of the partition members, and the first stage of the valve rod is pushed, and the solution in the corresponding storage chamber is opened to the corresponding reaction portion. The first step of moving to the chamber, the solution storage chamber being sealed from the outside by pushing the second stage of the valve stem, and processing is performed using the solution moved to the chamber of the reaction part Storage other than the storage chamber that selectively penetrates at least one second partition member other than the partition member selectively used in the second step and the first step and moves the solution in the first step. A third step of moving the solution in the working chamber to the corresponding reaction portion chamber, the second step using the solution in the storage chamber moved in the third step Respect treated article to be treated, a biochemical reaction treatment method characterized in that it comprises a fourth step, performing the further processing.

  Other objects and solutions will be described in detail in the following examples.

As described above, the biochemical reaction cartridge according to the present invention has 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. In order to move from the solution storage part to the reaction part, the solution storage part and the reaction part are brought into contact with each other so that their walls can be penetrated. Each solution is prepared in a biochemical reaction cartridge immediately before each processing step. Therefore, the reagent in the chamber does not flow into the flow path or the other chamber even when the environment changes or vibrates during the processing step using another solution, and there is an advantage that the intended reaction can be caused correctly.

  In particular, since each solution in the solution storage unit is moved to the reaction part immediately before use, even if there is a vibration of the processing apparatus or a pressure control error during the processing of each step, it is transferred to the adjacent chamber or flow path. A reliable reaction can be performed without flowing in.

  In addition, the processing device automatically reads the barcode reader attached to the cartridge, determines the type of cartridge, and automatically sets the necessary processing steps. It is not necessary to set a complicated processing order, and processing can be performed easily and reliably.

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

Further, 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. Then, the reaction portion 1 and the solution storage portion 2 in the configuration of the separate, so that the superimposed upon use.

  A bar code label 40 for identifying the type of cartridge is attached to the side surface of the cartridge. When this cartridge is set in a processing apparatus, which will be described later, the bar code is read, the type of the cartridge is determined based on the result, and the processing apparatus is automatically set so as to perform an appropriate processing order.

  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, when a tester injects a liquid specimen such as blood from the specimen inlet 3 and sets it in a processing apparatus described later, a robot arm (not shown) of the processing apparatus uses a short pressing rod 13 a of the tool needle 13. The valve rod 7 is pushed into the first stage, 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.

  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 pushing the pressing rod 13a of the tool needle 13 into the reaction portion 1 side, and is extremely simple. The solution can be poured into the chamber 11 from the chamber 6. 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.

  In this embodiment, the reaction portion 1 chamber and the solution storage portion 2 have a one-to-one correspondence. However, a plurality of solution storage chambers are arranged in one reaction portion 1 chamber. Also good. Further, in the embodiment, the solution is moved from the solution storage chamber to the empty chamber of the reaction portion 1, but the chamber of the reaction portion 1 that already contains the sample or solution being processed from the solution storage chamber. It is good also as a structure which moves a solution directly to. Furthermore, in this embodiment, an aluminum foil sheet is used as the partition member. However, the partition member itself may be a member that does not penetrate and a general valve may be added thereto, and the solution may be poured by opening or closing the valve.

  Next, the processing apparatus pulls out the tool needle 13 once using the robot arm, and as shown in FIG. 5, it is inverted, and the valve rod 7 is further pushed down by pushing in the second stage with the long side pressing rod 13 b. Then, the air is sealed by the upper O-ring 9, and the solution can move within the reaction portion 1 described later. 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 transferred from the chambers 6a and 6b of the solution storage portion 2 are accumulated, respectively. In the chamber 11c, magnetic particles moved from the chamber 6c are accumulated, and in the chamber 11l and the chamber 11m, the first and second extracted cleaning agents moved from the chamber 6l and the chamber 6m, respectively, are accumulated. The chamber 11d is filled with an eluate flowing from the chamber 6d, and the chamber 11g is filled with a mixed solution necessary for PCR (Polymerase Chain Reaction) moved from the chamber 6g. The chambers 11h and 11j accumulate the cleaning agent moved from the chambers 6h and 6j, respectively, and the chamber 11i accumulates the alcohol moved 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. Further, as described above, the processing apparatus moves the tool needle 13 onto a predetermined chamber on the cartridge, reads a robot arm (not shown) for pushing down the valve rod, and a barcode reader attached to the cartridge. A barcode reader (not shown) is provided.

  On the upper and lower sides of the table 22 in FIG. 7, electric syringe pumps 27 and 28 and pump blocks in which a plurality of pump nozzles 29 and 30 are provided on each side at the inlet / outlet for discharging or sucking air by these pumps 27 and 28. 31 and 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.

  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 injects the blood through the rubber cap of the specimen inlet 3 using a syringe, 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.

  When the inspector sets the cartridge in the processing device and then inputs a processing start command through the input unit 33, first, the barcode attached to the cartridge is read by a barcode reader (not shown) of the processing device. The processing sequence required for each type of cartridge is stored in advance in the apparatus, and when the type of cartridge is determined by the read bar code, the processing contents and procedure required for that cartridge are automatically determined. It is determined and processing is started. When the barcode cannot be read, or when the read barcode is not a predetermined code, the operator can manually input the processing steps by the input unit 33.

  FIG. 8 is a flowchart for explaining an example of a processing procedure in the processing apparatus according to the present embodiment. First, in step S1, the solution storage chamber 6a containing the hemolytic agent 1 is subjected to solution pouring and sealing steps as described with reference to FIGS. 4 and 5, and the hemolytic agent 1 is moved to the reaction chamber 11a. In the next step S2, 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 puts the first hemolytic agent in the chamber 11a into the blood. Into the 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 the next step S3, the solution storage chamber 6b containing the hemolytic agent 2 is also subjected to a solution pouring and sealing process in the same manner as in step S1, and the hemolytic agent 2 is moved to the reaction portion chamber 11a. In FIG. 8, only the nozzle inlets 4b and 4k are opened in the next step S4, the second hemolytic agent in the chamber 11b is poured into the chamber 16 in the same manner, and the magnetic particles are moved from 6c to 11c in the step S5. Only the nozzle inlets 4 c and 4 k are opened, and the magnetic particles in the chamber 11 c are poured into the chamber 16 in the same manner. In steps S4 and S6, stirring is performed in the same manner as in step S2. In step S6, the DNA produced by the dissolution of the cells in steps S2 and S4 adheres to the magnetic particles.

  In step S7, the electromagnet 23 is turned on, only the nozzle inlets 4e and 4k are opened, air is discharged from the electric syringe pump 28, 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, the extraction cleaning liquid 1 is moved from 6 l to 11 l in step S8, the electromagnet 23 is turned off in step S9, only the nozzle inlets 4f and 4l are opened, air is discharged from the electric syringe pump 28, and air is discharged from the pump 27. To move the first extraction cleaning liquid from the chamber 11l to the chamber 11f. At this time, the magnetic particles and DNA captured in step S7 move together with the extraction cleaning liquid, and cleaning is performed. After reciprocating twice in the same manner as in step S7, 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 S10, the extraction cleaning liquid 2 is moved from 6 m to 11 m, and in step S11, the second extraction cleaning liquid in the chamber 11m is further cleaned by using the nozzle inlets 4f and 4m by performing the same process as in step S9. To do. In step S12, the eluate is moved from 6d to 11d. In step S13, with the electromagnet 23 turned on, only the nozzle inlets 4d and 4o are opened, air is discharged from the electric syringe pump 27, and air is sucked from the pump 28. Then, the eluate in the chamber 11 d is moved to the chamber 17.

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. Extraction cleaning liquid containing chamber 11l, by providing a chamber 11f which waste liquid after washing with 11m enters, it is possible to perform the extraction of DNA with biochemical reaction cartridge in di- purification.

  Next, in step S14, the PCR drug is moved from 6g to 11g, and in step S15, 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 chamber 11 g of PCR drug 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 S16, 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, after the cleaning liquid 1 is moved from 6h to 11h in Step 17, in Step S18, only the nozzle inlets 4h and 4r are opened while maintaining the same 45 ° C., and air is discharged from the electric syringe pump 27. Then, air is sucked from the pump 28 and the solution in the chamber 18 is moved to the chamber 11r, and the first cleaning liquid in the chamber 11h is poured into the chamber 11r through the chamber 18. 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, after the cleaning liquid 2 is moved from 6j to 11j in step S19, the same 45 ° C. is maintained in step S20, and the second cleaning liquid in the chamber 11j is used for the second cleaning liquid in the chamber 11j using the nozzle inlets 4j and 4r. The same process is performed for further cleaning, and finally the chamber is returned to the chamber 11j. 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.

  After the alcohol is moved from 6i to 11i in step S21, in step S22, only the nozzle inlets 4i and 4r are opened, the air is discharged from the electric syringe pump 27, the 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.

  Other embodiments of the present invention are listed below.

[Embodiment 2]
In the above embodiment, the barcode label is used to identify the cartridge. However, the present invention is not limited to this, and a two-dimensional barcode, IC chip, RFID, or the like can be used. Also, the same effect can be obtained by identifying the cartridge type by various methods such as external dimensions such as the height and length of the cartridge, the number of depressions and protrusions on the side, top and bottom surfaces of the cartridge, or combinations thereof. be able to.

[Embodiment 3]
In the above embodiment, the cartridge is identified and the processing step corresponding to its type is set. However, information indicating the contents and order of the processing steps is written on a two-dimensional barcode or the like, and processing is performed based on the information. A sequence can also be set. When it is desired to change the inspection conditions such as the reaction time for each cartridge, a desired reaction step can be surely performed by writing different processing steps on the two-dimensional bar code and attaching them to the cartridge.

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 the valve rod 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.

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 40 Bar code label for cartridge identification

Claims (4)

A reaction portion including a plurality of chambers and a plurality of flow paths; and a solution storage portion including a plurality of storage chambers separately storing the reaction portion and storing a solution at a position corresponding to each of the plurality of chambers. A penetrable partition member for moving the solution from the solution storage portion to the reaction portion chamber and a valve rod for penetrating the partition member are provided in the solution storage portion, and the reaction portion and the solution storage A biochemical reaction processing method using a biochemical reaction cartridge, wherein the solution is moved through the partition member in a state where the portion is overlapped in use, wherein the biochemical reaction cartridge includes the partition Pushing the first stage of the valve stem with the tool needle into the member opens the solution storage chamber to the outside, so that the solution in the solution storage portion reacts with the reaction. Go to the minute of the chamber, which said solution storage chamber by pushing the second stage is sealed to the outside,
The solution storage chamber is opened to the outside by penetrating at least one of the partition members, and the first stage of the valve rod is pushed, and the solution in the corresponding storage chamber is opened to the corresponding reaction portion. A first step to move into the chamber,
A second step of performing processing using the solution transferred to the reaction portion chamber , with the solution storage chamber sealed against the outside by pushing the second stage of the valve stem ;
A solution in a storage chamber other than the storage chamber that selectively passes through at least one second partition member other than the partition member selectively used in the first step and moves the solution in the first step. A third step of moving the
A fourth step of performing further processing on the workpiece processed in the second step using the solution in the storage chamber moved in the third step;
The biochemical reaction processing method characterized by having.   The biochemical reaction processing method according to claim 1, further comprising a step of superimposing the reaction portion and the solution storage portion at the time of use for performing the processing of the first to fourth steps. A reaction portion comprising a plurality of chambers and a plurality of flow paths;
A solution storage part including a plurality of storage chambers separately storing the reaction part and storing a solution at a position corresponding to each of the plurality of chambers, and transferring the solution from the solution storage part to the chamber of the reaction part A reaction member having a penetrable partition member for movement and a valve rod penetrating the partition member in the solution storage portion, and a code representing information relating to a processing sequence including a penetration order of the partition member; In the biochemical reaction cartridge in which the solution is transferred through the partition member in a state where the solution storage portion is overlapped with the solution storage portion at the time of use , the first stage of the valve stem by the tool needle with respect to the partition member By pushing, the solution storage chamber is opened to the outside, and the solution in the solution storage portion moves to the reaction portion chamber, and the second-stage press is performed. Biochemical reaction cartridge, wherein said solution storage chamber is sealed against the outside lump.   The biochemical reaction cartridge according to claim 3, wherein the code is an identification code indicating a type of the cartridge.

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