JP2008139096A - Biochemical treatment apparatus, and method and apparatus for testing biochemical reaction cartridge - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To easily and precisely determine presence or absence of abnormalities such as a defect causing a flow channel of the biochemical reaction cartridge to be clogged or a fluid to leak. <P>SOLUTION: Pump nozzles 17e, 18m are inserted into two nozzle inlets 3e, 3m of the biochemical reaction cartridge 1 and connected to electric syringe pumps 15, 16 through tubes 21, 22, respectively. Then, pressure changes at the time when a flow of air advancing from the nozzle inlet 3e to the nozzle inlet 3m is generated by operating the electric syringe pumps 15, 16, are measured by using pressure sensors 23, 24. Next, respective measurement values of the pressure sensors 23, 24 are compared with pressure change values being caused by the fluid flow in a normal channel and obtained previously, thereby determining the presence or absence of the abnormalities. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a biochemical reaction cartridge inspection method and inspection apparatus for detecting a sample of cells, microorganisms, chromosomes, nucleic acids, and the like in a specimen using a biochemical reaction such as an antigen-antibody reaction or a nucleic acid hybridization reaction. The present invention relates to a biochemical processing apparatus.

  Analyzing apparatuses for analyzing specimens such as blood include an immunological method using an antigen-antibody reaction and a method using nucleic acid hybridization. In an example of an immunological method, a protein such as an antibody or an antigen that specifically binds to a substance to be detected is used as a probe and immobilized on a solid phase surface such as a microparticle, a bead, or a glass plate, and a target in a specimen is detected. An antigen-antibody reaction with the detection substance is performed. In an example of a method using nucleic acid hybridization, a single-stranded nucleic acid is used as a probe and immobilized on a solid phase surface such as a fine particle, a bead, or a glass plate, and nucleic acid hybridization is performed with a target substance in a specimen. . These methods include labeled antibodies, labeled antigens, or labeled nucleic acids, which are labeled substances having a specific interaction carrying a labeling substance with high detection sensitivity, such as an enzyme, a fluorescent substance, or a luminescent substance. Etc. are used. Then, an antigen-antibody compound or a hybridized double-stranded nucleic acid is detected, and the presence or absence of a substance to be detected (target) is detected or quantified.

  As a development of these techniques, for example, Patent Document 1 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. .

  Non-Patent Document 1 discloses a method for preparing a protein array having the same structure as a DNA array by arranging many types of proteins on a membrane filter. As described above, by using a DNA array, a protein array, or the like, it has become possible to inspect a very large number of items at once.

  In addition, disposable biochemical reaction cartridges that allow biochemical reactions to be performed internally are proposed for the purpose of reducing sample contamination, improving reaction efficiency, miniaturizing equipment, and simplifying operations in various sample analyses. Has been. For example, Patent Document 2 discloses a configuration in which a plurality of chambers are disposed in a biochemical reaction cartridge including a DNA array. According to this biochemical reaction cartridge, a reaction such as extraction, amplification, or hybridization of DNA in a specimen can be performed internally by moving a solution to each chamber using a pressure difference.

  As a method for injecting a solution from the outside into such a biochemical reaction cartridge, there is a method using an external electric syringe pump or a vacuum pump. As a method for moving a solution inside a biochemical reaction cartridge, a method using gravity, capillary action or electrophoresis is known in addition to a pressure difference. Further, as micro pumps that can be disposed inside the biochemical reaction cartridge, Patent Document 2 includes a diaphragm pump, Patent Document 3 uses a heat generating element, and Patent Document 4 uses a piezoelectric element. Each is disclosed.

  On the other hand, Patent Document 5 discloses an apparatus that draws a liquid sample from a test tubular container and dispenses it into a test tubular or dish-like reaction container, although it is not a biochemical reaction cartridge. In this dispensing apparatus, the pressure in the pipe line connecting the sample probe and the pump is measured at a predetermined timing after the operation of sucking the liquid sample is completed and before the operation of discharging the liquid sample is started. . When the measured pressure is lower than a predetermined pressure value, it is determined that the sample probe is clogged.

Moreover, in patent document 6, in the dispensing apparatus similar to patent document 5, the 1st point located in the sample probe side in a tube, and the 2nd point located in the dispensing syringe side in a tube A dispensing device for measuring the pressure difference is disclosed. Based on this pressure difference, it is determined whether or not the inside of the sample probe is closed.
US Pat. No. 5,445,934 Japanese National Patent Publication No. 11-509094 Japanese Patent No. 2832117 JP 2000-274375 A Japanese Patent Laid-Open No. 11-083868 JP 2001-242182 A Angelika Lueking and five others, “Protein Microarrays for Gene Expression and Antibody Screening”, Analytical Biochemistry Vol.270 (1), Academic Press (Academic Press), May 15, 1999, p.103-111

  In the biochemical reaction cartridge, if there is an abnormality such as clogging of a flow path or fluid leakage, the movement of the liquid is not performed correctly and the reaction is greatly affected. However, the conventional biochemical reaction cartridge has a structure that can easily inspect the presence or absence of clogging of the flow path and the presence of defects such as cracks, holes, and peeling that cause fluid leakage in the entire biochemical reaction cartridge. is not. Patent Documents 5 and 6 disclose a method for detecting clogging in a dispensing apparatus having a probe that moves between a test tubular container and a container. However, an inspection apparatus for easily detecting clogging of a fine flow path in a small biochemical reaction cartridge or fluid leakage has not been realized.

  The present invention has been made in view of the above-described problems, and an inspection method and inspection for easily and accurately inspecting whether there is an abnormality such as a clogged flow path of a biochemical reaction cartridge or a malfunction that causes fluid leakage. An object is to provide an apparatus and a biochemical processing apparatus.

  The present invention relates to a method for inspecting a biochemical reaction cartridge having a plurality of flow paths and a plurality of fluid inlets / outlets communicating with the flow paths, wherein the flow paths are substantially sealed except for the fluid inlet / outlet. At least one of the fluid inlets / outlets is set for inflow, at least one of the other fluid inlets / outlets is set for outflow, and the fluid inlet / outlet set for inflow is connected to one pipeline and set for outflow Connecting the fluid inlet / outlet connected to another pipe and sealing the fluid inlet / outlet not set for inflow or outflow; and from the pipe connected to the fluid inlet / outlet set for inflow A step of causing the fluid to flow in a path communicating with another pipe connected to the fluid inlet / outlet set for outflow, and a fluid inlet / outlet set for inflow when the fluid flows in the path. Pressure or pressure change in the pipeline or the inflow of fluid from the pipeline, and / or pressure or pressure change in other pipelines connected to the fluid inlet / outlet set for outflow or to other pipelines The step of measuring the outflow amount of the fluid and the measured pressure or pressure change or inflow amount or outflow amount are obtained in advance, and the pressure or pressure change or inflow amount or outflow accompanying the flow of the fluid in the normal path is obtained in advance. Comparing with the amount, and determining whether or not there is an abnormality.

  The present invention provides a testing apparatus for a biochemical reaction cartridge having a plurality of flow paths and a plurality of fluid inlets / outlets communicating with the flow paths, wherein the flow paths are substantially sealed except for the fluid inlet / outlet. A valve mechanism for selectively opening or closing a plurality of fluid inlets and outlets; a plurality of pipes each connectable to at least one of the fluid inlets and outlets opened by the valve mechanism; and a plurality of pipes Opened by the valve mechanism from at least one pressure sensor or flow sensor connected to at least one of the channels and one conduit connected to at least one of the fluid inlets and outlets opened by the valve mechanism The pump can be actuated to produce a fluid flow leading to another conduit connected to the other fluid inlet and outlet, and the pressure sensor when the fluid flow is produced. Alternatively, a control unit that compares the pressure or pressure change or flow rate measured by the flow sensor with the pressure or pressure change or flow rate that is obtained in advance in accordance with the flow of fluid in a normal path, and determines whether there is an abnormality. It is another feature to have.

  According to the present invention, it is possible to easily detect defects that cause clogging or leakage in fine flow paths or chambers in the biochemical reaction cartridge.

  Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings.

[First Embodiment]
1 and 2 schematically show an inspection apparatus for a biochemical reaction cartridge 1 according to an embodiment of the present invention. FIG. 1 shows a state where the biochemical reaction cartridge 1 is not attached, and FIG. 2 shows a state where the biochemical reaction cartridge 1 is attached.

  The inspection apparatus of this embodiment has a table 14 on which a biochemical reaction cartridge 1 is placed on a base 13. On both sides of the table 14, electric syringe pumps 15 and 16 and nozzle blocks 19 and 20 respectively communicating with the electric syringe pumps 15 and 16 via tubes (pipe lines) 21 and 22 are arranged. The nozzle blocks 19 and 20 are inlets and outlets for discharging or sucking air by the electric syringe pumps 15 and 16 and have ten pump nozzles 17a to 17j and 18k to 18t, respectively. Further, a plurality of known electric switching valves (valve mechanisms) (not shown) are disposed in the nozzle blocks 19 and 20. Pressure sensors 23 and 24 are connected to the tubes 21 and 22, respectively. The electric syringe pumps 15 and 16, the electric switching valves in the nozzle blocks 19 and 20, and the pressure sensors 23 and 24 are connected to the control unit 25.

  The electric switching valve is controlled by the control unit 25 to control the connection of the pump nozzles 17a to 17j and 18k to 18t to the electric syringe pumps 15 and 16 independently. That is, a state in which only selected ones of the plurality of pump nozzles 17a to 17j and 18k to 18t are connected to the electric syringe pumps 15 and 16, and a state in which all are connected to the electric syringe pumps 15 and 16, Any state can be switched between the closed state and the closed state.

  The nozzle blocks 19 and 20 are movable in the direction of the arrow in FIG. 1 so as to be close to each other toward the table 14 by operating a lever (not shown). Thereby, the pump nozzles 17a to 17j and 18k to 18t of the nozzle blocks 19 and 20 are inserted (see FIG. 2) and escaped from the nozzle inlets 3a to 3t described later of the biochemical reaction cartridge 1 on the table 14. Is possible.

  Next, an example of the biochemical reaction cartridge 1 to be inspected by this inspection apparatus will be described in detail with reference to FIGS. The biochemical reaction cartridge 1 of the present embodiment is injected with a liquid sample such as blood, and internally performs steps such as DNA extraction and amplification, hybridization reaction, sample DNA with fluorescent label and washing of the fluorescent label. Is done. Details of each step will be described later.

  The main body (housing) of the biochemical reaction cartridge 1 is made of a synthetic resin such as polymethyl methacrylate (PMMA), acrylonitrile-butadiene-styrene (ABS) copolymer, polystyrene, polycarbonate, polyester, polyvinyl chloride or the like. ing. These are transparent or translucent, but may not be a transparent material if optical measurement of the reactant in the biochemical reaction cartridge 1 is not required.

  As shown in FIG. 3, a specimen inlet (fluid inlet / outlet) 2 a for injecting a specimen such as blood using a syringe or the like is provided at the top of the biochemical reaction cartridge 1 and sealed with a rubber cap 2. Yes. In addition, on one side surface of the biochemical reaction cartridge 1, a plurality of nozzle inlets (fluid inlets / outlets) 3a to 3j for inserting and pressurizing or depressurizing in order to move the solution inside are provided, Sealed with a rubber cap 3. In addition, nozzle inlets 3k to 3t are also provided on the other side surface.

  FIG. 4 shows a plan sectional view of the biochemical reaction cartridge 1. As described above, ten nozzle inlets 3a to 3j are provided on one side surface, and ten nozzle inlets 3k to 3t are provided on the opposite side surface. Most of the nozzle inlets 3a to 3t communicate with the chambers 5a to 5t, which are places where solutions are stored or where reactions occur, via air flow paths 4a to 4t through which air flows. That is, the nozzle inlets 3a to 3j communicate with the chambers 5a to 5j through the flow paths 4a to 4j. The opposite nozzle inlets 3k, 3l, 3m, 3o, 3r, 3t communicate with the chambers 5k, 5l, 5m, 5o, 5r, 5t via the flow paths 4k, 4l, 4m, 4o, 4r, 4t, respectively. ing. However, in this embodiment, the nozzle inlets 3n, 3p, 3q, 3s are not communicated with the chamber and are reserved, and are not used.

  The specimen inlet 2a communicates with the chamber 7, and the chamber 7 communicates with the chambers 5a, 5b, 5c, 5k through the flow paths 6a, 6b, 6c, 6k, and communicates with the chamber 8 through the flow path 10. is doing. The chamber 8 communicates with the chambers 5 g and 5 o through the flow paths 6 g and 6 o and also communicates with the chamber 9 through the flow path 11. The chamber 9 communicates with the chambers 5h, 5i, 5j, 5r, and 5t via the flow paths 6h, 6i, 6j, 6r, and 6t. The flow path 10 communicates with the chambers 5d, 5e, 5f, 5l, and 5m via the flow paths 6d, 6e, 6f, 61, and 6m.

A square hole is formed in the bottom surface of the chamber 9, and a DNA microarray 12 is attached to the square hole with the probe surface facing upward. The DNA microarray 12 is obtained by arranging several tens to hundreds of thousands of different DNA probes at high density on a solid phase surface of a glass plate having a size of about 1 square inch (about 645 mm ² ). In the present embodiment, by using this DNA microarray 12 to perform a hybridization reaction with DNA in a specimen, a large number of genes can be examined at a time. These DNA probes are regularly arranged in a matrix, and addresses (positions indicated by how many rows and columns) of each DNA probe can be easily taken out as information. Examples of genes to be examined include infectious disease viruses, bacteria, disease-related genes, and individual gene polymorphisms.

  In the present embodiment, the biochemical reaction cartridge 1 shown in FIGS. 3 and 4 is attached to the inspection apparatus shown in FIG. 1 (see FIG. 2), and the flow path of the biochemical reaction cartridge 1 is clogged or fluid is leaked. Inspect for abnormalities such as malfunctions. A flowchart of this inspection method is shown in FIG. The example described here is an example in which an abnormality inspection of the flow path from the nozzle inlet 3e to the nozzle inlet 3m in the biochemical reaction cartridge 1 is performed.

  In the example shown below, the nozzle inlet 3e is set as an inflow fluid inlet / outlet, the nozzle inlet 3m is set as an outflow fluid inlet / outlet, and the tube 21 connected to the nozzle inlet 3e is one pipe line, the nozzle inlet 3m. This means that the tube 22 connected to the other pipe is another pipe line. However, these are merely referred to as such for convenience, and are not limited to such settings. For each inspection, the fluid inlet / outlet for inflow and the fluid inlet / outlet for outflow are arbitrarily selected from among a large number of nozzle inlets 3a to 3t. For example, the tube 22 becomes one conduit and the tube 21 becomes the other. It may be a pipeline. Therefore, when one inspection is completed, the settings of the fluid inlet / outlet for inlet, the fluid inlet / outlet for outlet, one pipeline, and other pipelines are reset. In addition, it is not meaningful to call such a case when the inspection is not performed.

  First, the worker places the biochemical reaction cartridge 1 on the table 14 of the inspection apparatus shown in FIG. And an operator moves the nozzle blocks 19 and 20 to the arrow direction of FIG. 1 by operating the lever which is not shown in figure. Then, as shown in FIG. 2, the pump nozzles 17a to 17j and 18k to 18t are inserted through the rubber cap 3 into the nozzle inlets 3a to 3t on both sides of the biochemical reaction cartridge 1 (step S1). .

  Then, the electric switching valve of the nozzle block 19 is operated so that only the nozzle 17 e communicates with the electric syringe pump 15. Further, the electric switching valve of the nozzle block 20 is operated so that only the nozzle 18m communicates with the electric syringe pump 16 (step S2).

  Next, the piston of the electric syringe pump 15 is moved in the direction of the arrow in FIG. 2 to generate pressure (step S3). At this time, the electric syringe pump 16 is fixed so that the piston does not move. If there is no clogging or leakage by operating the electric syringe pump 15 in this way, most of the fluid (for example, air) flows through the following path. That is, the pressure and fluid first travel through the tube 21, the nozzle 17e of the nozzle block 19, the nozzle inlet 3e, the flow path 4e, the chamber 5e, and the flow path 6e. The fluid flows through a portion of the flow channel 10 between the flow channel 6e and the flow channel 6m, and further through the flow channel 6m, the chamber 5m, the flow channel 4m, the nozzle inlet 3m, and the nozzle 18m of the nozzle block 20. To the tube 22. A fluid flow also occurs in a communicating channel other than the above-described channels as the pressure increases. Since the inside of the biochemical reaction cartridge 1 is in communication, the pressure in the biochemical reaction cartridge 1 should increase uniformly by the operation of the electric syringe pump 15 if there is no clogging or leakage. In order to confirm this, in the present embodiment, the pressure sensor 23 measures the pressure rise in the inflow side tube 21 and the pressure sensor 24 measures the pressure rise in the outflow side tube 22 ( Step S4). If the pressure increase measured by the pressure sensors 23 and 24 is within a predetermined range, it is considered that there is no abnormality in the path from the nozzle inlet 3e to the nozzle inlet 3m.

For example, in this embodiment, when there is no abnormality, the electric syringe pump 15 is operated for 5 seconds, so that the piston moves 10 mm, and the pressure in the entire path is increased by 2 kPa. For example, if the allowable error is ± 0.4 kPa, the allowable minimum value P _A is set to 1.6 kPa, and the maximum value P _B is set to 2.4 kPa. Then, it is checked whether or not the pressure increase values P ₂₃ and P ₂₄ measured by the pressure sensors 23 and ₂₄ are within the range of 1.6 to 2.4 kPa (step S5). When the pressure increase values P ₂₃ and P _{24 of} the pressure sensors ₂₃ and ₂₄ are both within the range of 1.6 to 2.4 kPa, it is determined as normal and “normal” is displayed on the display means (not shown). A display is performed (step S6). Then, the inspection of the flow path from the nozzle inlet 3e to the nozzle inlet 3m is completed.

When at least one of the pressure increase values P ₂₃ and P ₂₄ of the pressure sensors 23 and 24 is out of the range of 1.6 to 2.4 kPa, the pressure increase values P ₂₃ and P of the pressure sensors 23 and 24, respectively. Consider ₂₄ . That is, the pressure increase value P ₂₃ measured by the pressure sensor 23 is compared with the maximum value P _B, and the pressure increase value P ₂₄ measured by the pressure sensor 24 is compared with the minimum value P _A (step S7). When the pressure increase value P ₂₃ measured by the pressure sensor 23 is larger than the maximum value P _B and the pressure increase value P ₂₄ measured by the pressure sensor 24 is smaller than the minimum value P _A , Judge that clogging has occurred. Pressure increase value P ₂₃ of the pressure sensor 23 represents the inflow into the flow path of the fluid, the pressure increase value P ₂₄ of the pressure sensor 24 represents the outflow from the flow path of the fluid outflow than inflow This is because when the amount is small, it is considered that the flow is hindered by clogging of the flow path. And the display which shows "clogging" is performed on the display means which is not illustrated (step S8).

If it is not determined with both "normal", "Jam" in step S5, S7, a pressure increase value P _23, P ₂₄ of the pressure sensor 23, 24 is measured is compared with the minimum value P _A (step S9). When both the pressure increase values P ₂₃ and P ₂₄ measured by the pressure sensors ₂₃ and ₂₄ are smaller than the minimum value P _A , it is determined that a leak has occurred in the flow path. This is because the inflow amount and the outflow amount obtained by the measurement of the pressure sensors 23 and 24 are smaller than the original inflow amount of the fluid (the amount of the fluid sent by the electric syringe pump 15). Since there is no portion that blocks the flow of the fluid in the flow path from the nozzle inlet 3e to the nozzle inlet 3m, the pressure sensors 23, 24 no matter where the leakage occurs in the flow path from the nozzle inlet 3e to the nozzle inlet 3m. The pressure rise values P ₂₃ and P ₂₄ measured by are both reduced. Therefore, a display indicating “leak” is performed on a display means (not shown) (step S10). Incidentally, when the leakage detection in the step S9, apart from the minimum value P _A, to set the reference value P _C (e.g. 1.0 kPa) for detecting leakage, at step S9, the pressure sensors 23 and 24 is measured the pressure rise value P _23, P ₂₄ may be compared with a reference value P _C. As for detection of leakage, instead of obtaining the values of the pressure sensors 23 and 24 for a moment after the electric syringe pump 15 is operated, the fluctuations in the measured values during a certain period (for example, 1 second) are obtained. It is effective. That is, since the fluid (for example, air) leaks during that period and the pressure decreases, for example, if it is confirmed whether or not the pressure has decreased in one second, the determination of leakage can be made easier. .

  If neither “normal”, “clogged”, or “leak” is determined in steps S5, S7, S9, “other abnormality” is displayed on a display means (not shown) (step S11).

As described above, in this embodiment, if the pressure increase values P ₂₃ and P ₂₄ detected by the pressure sensors ₂₃ and ₂₄ are both within a predetermined range (for example, 1.6 to 2.4 kPa), biochemistry is performed. It can be determined that the reaction cartridge 1 is normal. On the other hand, if at least one of the pressure increase values P ₂₃ and P ₂₄ is out of the range, it can be determined that the biochemical reaction cartridge 1 is abnormal. Further, when the pressure increase value P ₂₃ measured by the pressure sensor ₂₃ is large and the pressure increase value P ₂₄ measured by the pressure sensor ₂₄ is small, it can be determined as “clogged”, and the pressure increase measured by the pressure sensors 23, 24. When the values P ₂₃ and P ₂₄ are both small, it can be determined that “leakage”.

  In the above-described example, for the sake of convenience, it has been described that steps S5, S7, and S9 for determining an abnormality are performed separately, but in reality, these steps S5, S7, and S9 are performed substantially simultaneously. Is preferred.

  If it is determined as abnormal in steps S5, S7, and S9, the biochemical reaction cartridge 1 is determined to be defective and discarded. However, if it is determined to be normal in step S5, the other channel of the biochemical reaction cartridge is inspected. That is, the settings of the fluid inlet / outlet, the fluid outlet / outlet, the one pipeline, and the other pipeline are reset and newly set. For example, the nozzle inlet 3g is set as an inflow fluid inlet / outlet, the nozzle inlet 3o is set as an outflow fluid inlet / outlet, and the tube 21 connected to the nozzle inlet 3g is set as one conduit and connected to the nozzle inlet 3o. The tube 22 can be another conduit. In this case, as shown in FIG. 6, the electric switching valves of the nozzle blocks 19 and 20 are operated so that only the nozzle 17g communicates with the electric syringe pump 15 and only the nozzle 18o communicates with the electric syringe pump 16. To do. Then, the above-described steps S3 to S11 are performed to inspect the flow path from the nozzle inlet 3g to the nozzle inlet 3o. Similarly, the same inspection may be performed on all the flow paths of the biochemical reaction cartridge 1. However, for example, the inspection may be performed only on the main flow path except for the flow path where only the cleaning liquid flows.

  The flow path inspection described above may be performed as a pre-shipment inspection at the time of manufacture of the biochemical reaction cartridge 1, or may be performed as an inspection immediately before performing a biochemical reaction using the biochemical reaction cartridge 1. Good.

  In the present embodiment, air is used as a fluid flowing through the flow path when performing inspection, and it is not necessary to prepare a special fluid for inspection. However, another gas or liquid may be used as long as the biochemical reaction cartridge 1 and the biochemical reaction performed in the biochemical reaction cartridge 1 are not adversely affected.

  Furthermore, the inspection apparatus of the present embodiment can also have a function as a biochemical processing apparatus that causes the biochemical reaction cartridge 1 to perform a biochemical reaction. Such a configuration will be described in detail below.

  An inspection apparatus that also functions as a biochemical processing apparatus is provided with an electromagnet and two Peltier elements around the table 14 (not shown). The electromagnet is for applying an electromagnetic force in the biochemical reaction cartridge 1, and the two Peltier elements are for controlling the temperature of the biochemical reaction cartridge 1. Specifically, one Peltier element is for temperature control during DNA amplification by PCR (polymerase chain reaction) described later. The other Peltier element is used for temperature control during hybridization between the amplified sample DNA and the DNA probe 32, which will be described later, and for temperature control during washing of the sample DNA that has not been hybridized.

  Various liquids for processing the specimen are injected into the respective chambers 5 a to 5 t of the biochemical reaction cartridge 1 from the upper part or the nozzle inlet 3. As an example, the chamber 5a contains a first lysing agent that lyses cells containing EDTA (ethylenediaminetetraacetic acid), which is an anticoagulant, and the chamber 5b contains a protein denaturant such as a surfactant. Each of the second solubilizers is accommodated. The chamber 5c accommodates silica-coated magnetic particles to which DNA is adsorbed. The chambers 5l and 5m accommodate first and second extraction detergents used for DNA purification during DNA extraction, respectively. The chamber 5d accommodates an eluate composed of a low-concentration salt buffer that elutes DNA from magnetic particles. The chamber 5g contains a mixture of a chemical necessary for PCR, that is, a primer, a polymerase, a dNTP solution, a buffer, a Cy3-dUTP (fluorescent label manufactured by Amersham Biosciences) containing a fluorescent agent, and the like. In the chambers 5h and 5j, a cleaning agent containing a surfactant for cleaning the sample DNA with the fluorescent substance (fluorescent label) that has not been hybridized and the fluorescent substance (fluorescent label) is accommodated. Alcohol for drying the inside of the chamber 9 including the DNA microarray 12 is accommodated in the chamber 5i.

  The chamber 5e is a chamber for collecting dust other than blood DNA. The chamber 5f is a chamber for storing waste liquids of the first and second extracted cleaning agents from the chambers 5l and 5m. The chamber 5r is a chamber for storing waste liquids of the first and second cleaning agents. The chambers 5k, 5o, and 5t are blank chambers provided to prevent the solution from flowing into the nozzle inlet.

  In the present embodiment, a liquid specimen such as blood is injected into the biochemical reaction cartridge 1 and set in the above-described inspection apparatus (see FIG. 1). Then, DNA and the like are extracted and amplified inside the biochemical reaction cartridge 1, and hybridization is performed between the amplified sample DNA and the DNA probe of the DNA microarray 12 inside the biochemical reaction cartridge 1. Let it be done. On the other hand, the sample DNA with the fluorescent substance (fluorescent label) that has not been hybridized and the fluorescent substance (fluorescent label) can be washed.

  A method of causing a biochemical reaction of a specimen in the biochemical reaction cartridge 1 in the present embodiment using the inspection apparatus and the biochemical reaction cartridge 1 will be specifically described.

  First, an operator passes a rubber cap 2 that closes the specimen inlet 2a of the biochemical reaction cartridge 1 through a needle (not shown) of a syringe containing blood, which is a specimen, and removes blood in the syringe from the specimen. Injection into the chamber 7 from the inlet 2a. Then, the operator places the biochemical reaction cartridge 1 on the table 14. Further, the operator operates a lever (not shown) to move the nozzle blocks 19 and 20 in the direction of the arrow in FIG. 1 as in step S1 described above. Then, the pump nozzles 17 a to 17 j and 18 k to 18 t are inserted through the rubber cap 3 into the nozzle inlets 3 a to 3 t on both sides of the biochemical reaction cartridge 1.

  When an operator inputs an instruction to start an experiment from an input unit (not shown), the process starts. FIG. 7 is a flowchart for explaining the procedure of biochemical reaction and subsequent treatment.

  First, in step S21, the control unit 25 controls the pump nozzles 17a to 17j and 18k to 18t to open only the nozzle inlets 3a and 3k, and ejects air from the electric syringe pump 15 and air from the electric syringe pump 16. Aspirate. Thereby, the first hemolytic agent in the chamber 5a is poured into the chamber 7 containing blood. In this way, the pump nozzle 17a is inserted into the nozzle inlet 3a to eject and pressurize the air, and the pump nozzle 18k is inserted into the nozzle inlet 3k to suck in the air and depressurize the first in the chamber 5a. Of lysate flows into the chamber 7 containing the blood.

  In the present embodiment, the solution in the cartridge 1 can flow smoothly by controlling the pressurization and depressurization of each chamber by shifting the timing of air supply and suction. Furthermore, it is possible to flow the solution more smoothly by performing fine control such as linearly increasing the suction of air by the electric syringe pump 16 from the start of the ejection of air from the electric syringe pump 15. For example, depending on the viscosity of the dissolving agent and the resistance of the flow path, in step S21, the suction of air from the electric syringe pump 19 is started and the ejection of air from the electric syringe pump 18 is started for 10 to 200 milliseconds. Control to start later. According to this, the solution does not jump out at the beginning of the flowing solution, and the solution flows smoothly. The same applies to the movement of the solution in the following steps.

  Further, while the air supply is easily controlled using the electric syringe pumps 15 and 16, only the nozzle inlets 3 a and 3 o are opened, and the electric syringe pumps 15 and 16 alternately repeat the ejection and suction of air. In this way, the solution in the chamber 7 is caused to flow through the flow path 10 and then returned to the agitation to repeat the stirring. Alternatively, stirring is performed while bubbles are generated by continuously ejecting air from the electric syringe pump 16. In this way, the first dissolving agent flow and stirring step (step S21) is performed.

  Next, in step S22, the second dissolving agent is flowed and stirred. That is, only the nozzle inlets 3b and 3k are opened, and the second dissolving agent in the chamber 5b is poured into the chamber 7 by the same principle as in step S21. And the same stirring as step S21 is performed.

  In step S23, a process of flowing and stirring magnetic particles is performed. That is, only the nozzle inlets 3c and 3k are opened, and the magnetic particles in the chamber 5c are poured into the chamber 7 on the same principle as in steps S21 and S22. And the same stirring as step S21 is performed. By this step S23, the DNA obtained by dissolving the cells in steps S21 and S22 adheres to the magnetic particles.

  In step S24, a magnetic particle and DNA capturing step is performed. That is, the electromagnet is turned on, only the nozzle inlets 3e and 3k are opened, air is ejected from the electric syringe pump 16, the air is sucked from the electric syringe pump 15, and the solution in the chamber 7 is moved to the chamber 5e. During this movement, the magnetic particles and DNA are captured at a position above the electromagnet in the flow path 10. In addition, the efficiency of DNA capture is improved by alternately repeating the suction and ejection of air by the electric syringe pumps 15 and 16 to reciprocate the solution between the chambers 7 and 5e twice. If the number of reciprocations is further increased, the capture efficiency can be further increased. However, extra processing time is required.

  In this way, in steps S21 to S24, DNA in a fluid state is captured very efficiently using magnetic particles on the small flow path 10 having a width of about 1 to 2 mm and a height of about 0.2 to 1 mm. To do. It should be noted that if the capture target substance is not DNA but RNA or protein, efficient capture can be performed similarly.

  In step S25, after washing with the first extraction washing liquid, a step of capturing the magnetic particles and DNA is performed. That is, the electromagnet is turned off and only the nozzle inlets 3f and 3l are opened. Then, air is ejected from the electric syringe pump 16 and air is sucked from the electric syringe pump 15 to move the first extraction cleaning liquid in the chamber 5l to the chamber 5f. At this time, the magnetic particles and DNA captured in step S24 are moved together with the extraction cleaning liquid for cleaning. Further, the electromagnet is turned on, and the magnetic particles, DNA, and extraction cleaning liquid are reciprocated twice between the chamber 5l and the chamber 5f by the same principle as in step S24. Thereby, the washed magnetic particles and DNA are collected at a position above the electromagnet of the flow path 10 and the first extraction washing liquid is returned to the chamber 5l.

  In step S26, a step of capturing the magnetic particles and DNA is performed after washing with the second extraction washing liquid. Here, only the nozzle inlets 3f and 3m are opened, and the same process as step S25 is performed. That is, the second extraction washing liquid in the chamber 5m, the magnetic particles and the DNA are moved, and the magnetic particles and the DNA are further washed and then recovered at a position above the electromagnet 14, and the second extraction washing liquid is used as the second extraction washing liquid. Return to chamber 5m.

  In step S27, with the electromagnet 14 turned on, only the nozzle inlets 3d and 3o are opened, air is ejected from the electric syringe pump 15, and air is sucked from the electric syringe pump 16. Thereby, the eluate in the chamber 5 d is moved to the chamber 8. Due to the action of the eluate, the magnetic particles and DNA are separated, and only the DNA moves to the chamber 8 together with the eluate, and the magnetic particles remain in the flow path 10.

  Next, in step S28, an amplification process of the eluted DNA is performed. That is, only the nozzle inlets 3 g and 3 o are opened, air is ejected from the electric syringe pump 15, and air is sucked from the electric syringe pump 16. Thereby, the PCR agent (for example, a mixed solution of primer, polymerase, dNTP solution, buffer, fluorescent label, etc.) in the chamber 5 g is poured into the chamber 8. Further, only the nozzle inlets 3g and 3t are opened, and the ejection and suction of air by the electric syringe pumps 15 and 16 are alternately repeated, and the operation of flowing the solution in the chamber 8 into the flow path 11 and returning to the subsequent is repeated. Do. After controlling the Peltier device and holding the solution in the chamber 8 at a temperature of 96 ° C. for 10 minutes, a cycle of 96 ° C. · 10 seconds, 55 ° C. · 10 seconds, 72 ° C. · 1 minute is repeated 30 times. PCR is performed to amplify the eluted DNA.

  In step S29, a hybridization step is performed. That is, only the nozzle inlets 3 g and 3 t are opened, air is ejected from the electric syringe pump 15, air is sucked from the electric syringe pump 16, and the solution in the chamber 8 is moved to the chamber 9. Further, the Peltier element is controlled to hold the solution in the chamber 9 at 45 ° C. for 2 hours to perform hybridization. At this time, the ejection and suction of air by the electric syringe pumps 15 and 16 are alternately repeated, the solution in the chamber 9 is moved to the flow path 6t, and the subsequent return operation is repeated to perform the hybridization while stirring. .

  In step S30, a cleaning process using the first cleaning liquid is performed. That is, while maintaining the temperature at 45 ° C. as in step S29, this time, only the nozzle inlets 3h and 3r are opened, air is ejected from the electric syringe pump 15, and air is sucked from the electric syringe pump 16. Accordingly, the solution in the chamber 9 is moved to the chamber 5r, and the first cleaning liquid in the chamber 5h is poured into the chamber 5r through the chamber 9. Thus, the first cleaning liquid in the chamber 5h is inserted by inserting the pump nozzle 17h into the nozzle inlet 3h and ejecting air to pressurize it, and inserting the pump nozzle 18r into the nozzle inlet 3r and sucking air to reduce the pressure. Flows into the chamber 5r through the chamber 9. By alternately repeating the suction and ejection of the electric syringe pumps 15 and 16, this solution is reciprocated twice between the chambers 5h, 9 and 5r, and finally returned to the chamber 5h. In this way, the fluorescently labeled sample DNA and the fluorescent label that have not been hybridized are washed.

  In step S31, a cleaning process using the second cleaning liquid is performed. That is, while maintaining the temperature at 45 ° C. as in steps S29 and S30, only the nozzle inlets 3j and 3r are opened, and the same process as in step S30 is performed. That is, the second washing liquid in the chamber 5j is poured into the chamber 5r through the chamber 9 to further wash the DNA, and finally the solution is returned to the chamber 5j.

  In step S32, alcohol flow and drying steps are performed. That is, only the nozzle inlets 3 i and 3 r are opened, air is ejected from the electric syringe pump 15, air is sucked from the electric syringe pump 16, and the alcohol in the chamber 5 i is moved to the chamber 5 r through the chamber 9. Thereafter, only the nozzle inlets 3i and 3t are opened, air is ejected from the electric syringe pump 15, and air is sucked from the electric syringe pump 16 to dry the inside of the chamber 9.

  Through the steps S21 to S32 described above, the biochemical reaction (for example, DNA hybridization) of the specimen can be performed in the biochemical reaction cartridge 1.

  In the present embodiment, the nozzle inlets 3a to 3t are concentrated on the two surfaces of the cartridge 1, that is, both side portions. Therefore, the shape and arrangement of the electric syringe pumps 15 and 16, the electric switching valve, the nozzle blocks 19 and 20 incorporating the pump nozzles 17a to 17j and 18k to 18t, and the like can be simplified. Furthermore, the pump nozzles 17a to 17j and 18k to 18t are connected to the nozzle inlets 3a to 3t only by a simple operation of simultaneously sandwiching the biochemical reaction cartridge 1 by the nozzle blocks 19 and 20 while securing the necessary chambers and flow paths. Can be inserted. Thereby, the configuration of the nozzle blocks 19 and 20 can be simplified. Further, by arranging the nozzle inlets 3a to 3t so as to be all linearly arranged at the same height, the heights of the flow paths 4a to 4t connected to the nozzle inlets 3a to 3t are all the same, and the flow path 4a. Production of ˜4t is facilitated.

  After the processing steps described above (steps S21 to S32), the operator operates a lever (not shown) to move the nozzle blocks 19 and 20 away from the biochemical reaction cartridge 1. Accordingly, the pump nozzles 17 a to 17 j and 18 k to 18 t are detached from the nozzle inlets 3 a to 3 t of the biochemical reaction cartridge 1. Then, the hybridized DNA captured by the DNA microarray 12 is detected by a fluorescence detection unit (not shown) (step S33).

  As described above, the biochemical reaction cartridge 1 according to the present embodiment includes the sample inlet, the chamber for the sample, the chamber for the reagent, the chamber for the mixture of the sample / reagent and the reaction solution, A passage and a plurality of nozzle inlets. The nozzle inlet communicates with the chamber, and air exists in the flow path between the nozzle inlet and the chamber. When nozzles 17a to 17j and 18k to 18t for pressurizing or depressurizing are inserted into the nozzle inlets 3a to 3t, and the air is pressurized or depressurized by the nozzles 17a to 17j and 18k to 18t, the specimen and the reagent are placed in each chamber. Move between. As a result, a series of biochemical reactions are performed inside the biochemical reaction cartridge 1. As described above, when DNA labeled with a fluorescent substance is used as a specimen, the result of a biochemical reaction can be obtained by detecting the intensity of fluorescence.

  In the present embodiment, the above-described inspection apparatus also functions as a biochemical reaction apparatus. Conversely, according to the present embodiment, the biochemical reaction apparatus to which the biochemical reaction cartridge 1 is attached can include a flow path abnormality inspection apparatus that did not exist conventionally. In particular, the electric syringe pumps 15 and 16, the tubes 21 and 22, the nozzle blocks 19 and 20, the pump nozzles 17a to 17j and 18k to 18t, the electric switching valve, and the control unit 25 are used to check for abnormalities in the flow path and biochemical reactions. And can be used in common. Therefore, the effects of simplification of the apparatus, space saving, and cost reduction are extremely large. In addition, since the abnormality inspection and the biochemical reaction can be continuously performed with the same apparatus, the operation is facilitated and the operation time can be shortened.

[Second Embodiment]
Next, an inspection apparatus according to a second embodiment of the present invention will be described. As shown in FIG. 8, in the inspection apparatus of the present embodiment, only one pressure sensor 23 is arranged in the tube 21 and the pressure sensor 24 is omitted, but all other configurations are the first embodiment. It is the same.

  The abnormality inspection method for the biochemical reaction cartridge 1 in this embodiment will be described with reference to the flowchart of FIG. Here, an example in which a flow path from the nozzle inlet 3d to the nozzle inlet 3l is inspected will be described. First, the pump nozzles 17a to 17j and 18k to 18t of the nozzle blocks 19 and 20 are inserted into the nozzle inlets 3a to 3t on both sides of the biochemical reaction cartridge 1 through the rubber cap 3 (step S41). Next, the electric switching valves of the nozzle blocks 19 and 20 are operated so that only the nozzle 17d and the nozzle 18l communicate with the electric syringe pumps 15 and 16, respectively (step S42).

  Next, the negative pressure is generated by moving the piston of the electric syringe pump 16 in the direction of the arrow in FIG. 8 (step S43). At this time, the electric syringe pump 15 is fixed so that the piston does not move. By operating the electric syringe pump 16 as described above, if there is no clogging or leakage, most of the fluid (for example, air) is sucked through the following path. This flow path is the tube 21, the nozzle 17d, the nozzle inlet 3d, the flow path 4d, the chamber 5d, the flow path 6d, the portion of the flow path 10 between the flow path 6d and the flow path 6l, the flow path 6l, the chamber 5l. , Flow path 4 l, nozzle inlet 3 l, nozzle 18 l, and tube 22. A fluid flow also occurs in a communicating channel other than this channel according to a pressure drop. Since the inside of the biochemical reaction cartridge 1 is in communication, if there is no clogging or leakage, the pressure in the biochemical reaction cartridge 1 should be uniformly reduced by the operation of the electric syringe pump 16. In order to confirm this, in this embodiment, the pressure drop in the inflow side tube 21 is measured by the pressure sensor 23 (step S44). If the pressure drop measured by the pressure sensor 23 is within a predetermined range, it is considered that there is no abnormality in the path from the nozzle inlet 3d to the nozzle inlet 3l.

For example, in this embodiment, when there is no abnormality, the electric syringe pump 15 is operated for 5 seconds so that the piston moves 10 mm, and the pressure in the entire path is reduced by 2 kPa. Here, for example, the tolerance to 0.4 kPa, the minimum value P _A allowable is set to 1.6 kPa. Then, the pressure drop values P ₂₃ measured by the pressure sensor 23, determine whether not less than the 1.6 kPa (step S45). If the pressure drop value P ₂₃ of the pressure sensor 23 is not less than 1.6kPa, it is determined that a normal, performs display indicating "normal" is displayed on the display means (not shown) (step S46). Then, the inspection of the flow path from the nozzle inlet 3d to the nozzle inlet 3l is completed.

Determining the pressure drop value P ₂₃ of the pressure sensor 23 when 1.6kPa less than, the abnormality such as failure such as cracks or holes causing leakage of clogging in the flow path or fluid, is occurring Then, the display means (not shown) displays “abnormal” (step S47). In addition, if the value of the pressure sensor 23 for only a moment after the electric syringe pump 16 is operated is not obtained, but the fluctuation of the measured value for a certain period (for example, 1 second) is obtained, a crack that causes leakage in particular. It is effective in detecting defects such as holes and holes. That is, since the fluid (for example, air) flows into the flow path during the period, the pressure increases. For example, if the pressure is increased or not increased in one second, it causes a leak. Defects can be detected more easily.

  In the present embodiment, in step S42, the electric syringe pump 16 is operated to decompress the flow path. According to this method, when any fluid is accommodated in the biochemical reaction cartridge 1, it is accommodated even if a defect such as a crack or a hole causing fluid leakage occurs in the biochemical reaction cartridge 1. There is an advantage that the fluid that is flowing does not leak outside during inspection.

  However, similarly to the first embodiment, even when pressurizing the inside of the flow path, the abnormality inspection can be performed by only one pressure sensor 23 as in the present embodiment.

  It is also possible to perform inspection by using two pressure sensors 23 and 24 as in the first embodiment and reducing the pressure in the flow path as in the second embodiment.

  In both the first and second embodiments described above, the biochemical reaction cartridge 1 has a chamber, but a biochemical reaction cartridge that does not have a chamber can also be used. Even in such a case, it is possible to inspect for abnormalities such as clogging of the flow path inside the biochemical reaction cartridge and malfunctions causing fluid leakage by the same method as described above.

  Furthermore, in any of the embodiments, the pressure or the change in pressure is measured using a pressure sensor, but the flow rate may be measured using a flow sensor.

  In the above-described embodiment, the pressure or pressure change (or inflow or outflow) actually measured in the flow path of the biochemical reaction cartridge to be inspected is obtained in advance as the pressure associated with the normal fluid flow. Or compared with pressure change (or inflow or outflow). The pressure or pressure change (or inflow or outflow) associated with the normal fluid flow to be compared may be a theoretical value obtained by calculation, but it is known that there is no abnormality in advance. It may be an experimental value obtained experimentally using a chemical reaction cartridge. Further, in the determination of abnormality, when these are compared, it may be determined that there is no abnormality only when both match, but as described above, an upper limit value and a lower limit value are allowed with a certain degree of error. May be determined to be within the range. The allowable error range may be arbitrarily set by the user each time.

1 is a schematic plan view of a biochemical reaction cartridge inspection apparatus according to a first embodiment of the present invention in a state where a biochemical reaction cartridge is not mounted. FIG. FIG. 2 is a schematic plan view of the biochemical reaction cartridge inspection device shown in FIG. 1 in a state where the biochemical reaction cartridge is mounted. It is a perspective view of the biochemical reaction cartridge used in the 1st Embodiment of the present invention. FIG. 4 is a plan sectional view of the biochemical reaction cartridge shown in FIG. 3. It is a flowchart of the test | inspection method of the biochemical reaction cartridge by the test | inspection apparatus shown in FIG. It is a schematic plan view which shows the state which test | inspects the other flow path of a biochemical reaction cartridge of the test | inspection apparatus of the biochemical reaction cartridge shown in FIG. It is a flowchart of the processing method at the time of making the test | inspection apparatus shown in FIG.1, 2 function as a biochemical reaction processing apparatus. It is a typical top view of the state with which the biochemical reaction cartridge was mounted | worn of the inspection apparatus of the biochemical reaction cartridge of the 2nd Embodiment of this invention. It is a flowchart of the test | inspection method of the biochemical reaction cartridge by the test | inspection apparatus shown in FIG.

Explanation of symbols

1 Biochemical reaction cartridge 2a Sample inlet (fluid inlet / outlet)
3a-3t Nozzle inlet (fluid inlet / outlet)
4a to 4t, 6a to 6t, 10, 11 Channels 5a to 5t, 7, 8, 9 Chambers 15, 16 Electric syringe pumps 21, 22 Tube (pipe)
23, 24 Pressure sensor

Claims (12)

A method for inspecting a biochemical reaction cartridge having a plurality of flow paths and a plurality of fluid inlets / outlets communicating with the flow paths, wherein the flow paths are substantially sealed except for the fluid inlet / outlet,
At least one of the plurality of fluid inlets / outlets is set for inflow, at least one of the other fluid inlets / outlets is set for outflow, and the fluid inlet / outlet set for inflow is connected to one pipe line. Connecting the fluid inlet / outlet set for outflow with another pipe and sealing the fluid inlet / outlet not set for inflow or outflow;
Flowing a fluid in a path communicating from the pipe connected to the fluid inlet / outlet set for inflow to the other pipe connected to the fluid inlet / outlet set for outflow;
When the fluid flows in the path, pressure or pressure change in the pipe connected to the fluid inlet / outlet set for inflow or inflow of the fluid from the pipe, and / or for outflow Measuring the pressure or pressure change in the other conduit connected to the fluid inlet / outlet set as or the flow rate of the fluid into the other conduit;
The measured pressure or pressure change or inflow or outflow is compared with the previously determined pressure or pressure change or inflow or outflow associated with the fluid flow in the normal path. A method for inspecting a biochemical reaction cartridge, comprising the step of determining the presence or absence. The step of causing the fluid to flow in the path is a step of pressurizing and flowing the fluid from the pipe line connected to the fluid inlet / outlet set for inflow,
The step of determining the presence / absence of the abnormality includes determining the measured pressure or pressure increase or inflow amount or outflow amount in advance, and obtaining the pressure or pressure increase or inflow amount accompanying the normal flow of the fluid in the path. Or a step to compare with the spill amount,
The biochemical reaction cartridge inspection method according to claim 1.   3. The biochemistry of claim 2, wherein the step of flowing a fluid in the path comprises pressurizing the fluid with a pump connected to the conduit connected to the fluid inlet / outlet set for inflow. Reaction cartridge inspection method. The step of causing a fluid to flow in the path is a step of sucking the fluid from the other pipe connected to the fluid inlet / outlet set for outflow,
The step of determining the presence / absence of the abnormality includes a step of determining the measured pressure or pressure drop or inflow amount or outflow amount in advance, and the pressure or pressure drop or inflow amount accompanying the flow of the fluid in the normal path obtained in advance. Or a step to compare with the spill amount,
The biochemical reaction cartridge inspection method according to claim 1.   The step of causing a fluid to flow in the path includes the step of generating a negative pressure by a pump connected to the other pipe connected to the fluid inlet / outlet set for outflow. Inspection method for biochemical reaction cartridge.   6. The pump according to claim 3 or 5, wherein the pump generates a positive pressure or a negative pressure for moving a fluid inside the biochemical reaction cartridge in order to cause a biochemical reaction in the biochemical reaction cartridge. The biochemical reaction cartridge inspection method described.   The biochemical reaction cartridge inspection method according to any one of claims 1 to 6, wherein the fluid to be flowed into the path is air. An inspection apparatus for a biochemical reaction cartridge having a plurality of flow paths and a plurality of fluid inlets / outlets communicating with the flow paths, wherein the flow paths are substantially sealed except for the fluid inlet / outlet. ,
A valve mechanism for selectively opening or sealing each of the plurality of fluid ports independently;
A plurality of conduits each connectable to at least one of the fluid inlets and outlets opened by the valve mechanism;
At least one pressure sensor or flow sensor connected to at least one of the plurality of conduits;
Fluid from one pipeline connected to at least one of the fluid inlets and outlets opened by the valve mechanism to another pipeline connected to another fluid inlet and outlet opened by the valve mechanism. The pump can be actuated to produce a flow, and the pressure or pressure change or flow measured by the pressure sensor or flow sensor when the fluid flow is produced is determined in advance. And a control unit that determines whether or not there is an abnormality in comparison with the pressure, pressure change, or flow rate associated with the flow of the fluid in the normal path. The two pressure sensors or flow sensors are respectively connected to the one pipe line and the other pipe line;
The control unit obtains in advance the pressure or pressure change or flow rate respectively measured by the two pressure sensors or flow rate sensors when the fluid flows by the operation of the pump, and the normal path in the normal path is obtained. The biochemical reaction cartridge inspection apparatus according to claim 8, wherein the presence or absence of abnormality is determined by comparison with pressure, pressure change, or flow rate associated with fluid flow, respectively. The pump pressurizes the fluid from the one pipe line,
The control unit obtains the pressure, the pressure increase, or the flow rate measured by the pressure sensor or the flow rate sensor when the fluid flows by the operation of the pump, and the flow of the fluid in the normal path, which is obtained in advance. The biochemical reaction cartridge inspection apparatus according to claim 8 or 9, wherein the presence or absence of an abnormality is determined by comparison with the pressure, pressure increase, or flow rate associated with. The pump sucks the fluid from the other pipe line,
The control unit obtains the pressure or pressure drop or flow rate measured by the pressure sensor or flow rate sensor when the fluid flows by the operation of the pump in advance, and the flow of the fluid in the normal path is obtained in advance. The biochemical reaction cartridge inspection apparatus according to claim 8 or 9, wherein the presence or absence of an abnormality is determined by comparison with the pressure, pressure drop, or flow rate associated with. A biochemical reaction is caused in a biochemical reaction cartridge having a plurality of flow paths and a plurality of fluid inlets / outlets communicating with the flow paths, wherein the flow paths are substantially sealed except for the fluid inlet / outlet. A biochemical treatment apparatus for causing
The biochemical reaction cartridge inspection device according to any one of claims 8 to 11,
In order to inspect the biochemical reaction cartridge, the pump can pressurize or depressurize the path from the one pipe line to the other pipe line, and cause the biochemical reaction to occur. A positive pressure or a negative pressure for moving a fluid inside the biochemical reaction cartridge can be generated.
Biochemical processing equipment.

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