JP2006329767A - Sample analyzer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a sample analyzer capable of controlling a flow condition of a fluid in a fluid passage by simple structure. <P>SOLUTION: This sample analyzer Z is constituted to make the first fluid passage 11 with the first solution flowing down therethrough and provided with a pair of the first valve elements 21a-21b synchronizedly opened and closed, and the second fluid passage 12 with the second solution flowing down therethrough and provided with a pair of the second valve elements 22a-22b synchronizedly opened and closed, commonized in one part of the first fluid passage 11 sandwiched with the pair of the first valve elements 21a-21b and one part of the second fluid passage 12 sandwiched with the pair of the second valve elements 22a-22b, and is provided with a microchip X for bioassay with a fluid control valve having an analytical means 14 for analyzing the second solution provided in the first fluid passage 11, and a valve control part Y capable of opening-and-closing-controlling the first valve elements 21a-21b and the second valve elements 22a-22b alternately. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a sample analyzer including a bioassay microchip provided with a fluid flow path through which a liquid sample flows and an analysis means for analyzing the liquid sample.

  Patent Document 1 discloses an optical sample analyzer for detecting a measurement substance, which is a specific molecule contained in a liquid sample, for example, an antigen. In the sample analyzer, a block unit (member 15 in Patent Document 1) for handling a liquid sample is provided. In this unit, an introduction hole for introducing the liquid sample, an exhaust hole for discharging the liquid sample, and a liquid sample flow down. And an analysis region for analyzing a measurement substance contained in the liquid sample.

  In the analysis area, a sensor unit (member 10 in Patent Document 1) separate from the block unit is detachably provided. The sensor unit is configured to include a substance that interacts with a specific measurement substance contained in the liquid sample (interactive substance). Therefore, the measurement substance contained in the liquid sample flowing down the fluid channel reacts with the interaction substance on the sensor unit and is optically analyzed.

  In this sample analyzer, the liquid sample is introduced from the inlet and then flows down the fluid flow path. At this time, the flow state of the liquid sample is controlled by a valve body (for example, member 88 in Patent Document 1) such as a pneumatically operated valve or a solenoid operated valve provided in the block unit. This valve body opening / closing control is performed by a control device (member 8 in Patent Document 1).

Japanese Patent No. 3294605 (see columns 23 and 27)

Although a pneumatically operated valve or a solenoid operated valve can be applied as the valve body in the sample analyzer described above, a driving mechanism for operating each valve structure is required.
For example, in order to operate a pneumatically operated valve, it is necessary to provide a compressed air supply line, an electromagnetically operated compressed air valve, a compressed air source, and the like, which inevitably makes the apparatus complicated and large.
Moreover, in the analyzer of patent document 1, although the valve body is provided with two or more, it is necessary to control the opening / closing operation | movement of each valve body separately by a control apparatus at this time. For this reason, in the control device, software or the like for issuing a command for individually controlling the opening / closing timing of each valve element is required, and the configuration becomes complicated.

  Therefore, an object of the present invention is to provide a sample analyzer that can control the flow state of a fluid in a fluid flow path with a simple structure.

The first characteristic configuration of the sample analyzer according to the present invention for achieving the above object is as follows:
A first fluid flow path including a pair of first valve bodies in which the first solution flows down and synchronizes opening and closing, and a second fluid including a pair of second valve bodies in which the second solution flows down and synchronizes opening and closing A part of the first fluid channel sandwiched between the pair of first valve bodies and a part of the second fluid channel sandwiched between the pair of second valve bodies are common. And a microchip for bioassay with a fluid control valve provided with analysis means for analyzing the second solution in the first fluid flow path, and the first valve body and the second valve body And a valve control unit capable of alternately opening and closing.

According to the first characteristic configuration, in the bioassay microchip provided with the fluid flow path through which the fluid flows and the analysis means for analyzing the fluid, the valve body for controlling the flow state of the fluid in the fluid flow path is provided. It is as a structure.
That is, in this configuration, the valve body is directly attached to the microchip. Therefore, it is not necessary to provide a support (for example, the block unit in Patent Document 1) different from the microchip in order to attach the valve body, and the flow state of the fluid in the fluid flow path can be controlled.

  The valve control is provided with a pair of first valve bodies whose opening and closing are synchronized as a valve structure, and a pair of second valve bodies whose opening and closing are synchronized, respectively, and valve control capable of alternately opening and closing the first valve body and the second valve body A part. That is, when the pair of first valve bodies is in the open state, the pair of second valve bodies can be controlled to be in the closed state. At this time, the first fluid channel is filled with the first solution. In this configuration, since a part of the first fluid channel and a part of the second fluid channel are configured in common, the common part is filled with the first solution.

  Subsequently, when the pair of second valve bodies are opened, the pair of first valve bodies can be controlled to be closed. At this time, the second fluid channel is filled with the second solution. In this configuration, since the part of the first fluid channel and the part of the second fluid channel are configured in common, the common part is filled with the second solution. At this time, if bubbles exist in the second solution, the second solution is caused to flow down to the second fluid channel until the bubbles can be discharged, so that a part of the first fluid channel and the second fluid channel Bubbles can be removed from a site that is partly in common.

  In this state, control is performed so that the pair of first valve bodies is opened again and the pair of second valve bodies is closed. At this time, when the first solution is caused to flow down in the first fluid channel, the second solution present in the common site is pushed away by the first solution, and flows down through the first fluid channel and is guided to the analysis means.

Thus, by alternately opening and closing the pair of first valve bodies and the pair of second valve bodies, a desired amount of the second solution can be filled in the common part, and then the first By extruding the two solutions with the first solution, a desired amount of the second solution can be introduced to the analytical means. That is, the common site is a section where the second solution can be measured.
And since the 2nd solution can be guide | induced to an analysis means in the state without a bubble, the analysis in an analysis means can be accurately performed in the state which is not influenced by a bubble.

As described above, according to this configuration, since the paired valve bodies can be controlled in a synchronized state, the paired valve bodies need not be individually controlled. Furthermore, since the first and second valve bodies can be alternately opened and closed, it is not necessary to individually control the opening and closing timings of the plurality of valve bodies, and the operation of the valve bodies can be controlled with a simple structure. Can do.
Therefore, with this configuration, the structure of the sample analyzer can be simplified.

  A second characteristic configuration of the sample analyzer according to the present invention is that the valve control unit is a cam mechanism capable of controlling the first valve body and the second valve body separately.

According to said 2nd characteristic structure, it becomes a structure which provides the cam body which can control opening / closing of a 1st valve body and a 2nd valve body alternately to the shaft body rotated around an axial center.
And, for example, when the first valve body is in the open state, if the cam bodies are respectively arranged with different circumferential positions on the surface of the shaft body so that the second valve body is in the closed state, The valve control unit that can simultaneously control the operations of the first valve body and the second valve body can be configured with a simple structure.

  The third characteristic configuration of the sample analyzer according to the present invention is that the first valve body and the second valve body are arranged in a straight line.

  According to the third characteristic configuration, since each valve body can be controlled by a straight member, the structure of the valve control unit that controls the operation of each valve body can be further simplified.

  According to a fourth characteristic configuration of the sample analyzer of the present invention, the microchip for bioassay with a fluid control valve includes a channel substrate on which the first fluid channel and the second fluid channel are formed, and the channel. A support substrate that supports the substrate; and a resilient member that forms a flow path together with the flow path substrate and is sandwiched between the flow path substrate and the support substrate. The first valve body and the second valve body are inserted, and the first valve body and the second valve body are arranged so as to be able to contact the elastic member.

  According to the fourth characteristic configuration, since the elastic member can be sandwiched between the flow path substrate and the support substrate, each flow path can be reliably sealed. Therefore, it is possible to reliably prevent the fluid flowing down through the microchip for bioassay with a fluid control valve from leaking from each flow channel between the time when the first solution and the second solution are introduced and discharged. .

  Furthermore, since the first valve body and the second valve body are brought into direct contact with the elastic member and the flow state of the first solution and the second solution can be controlled, reliable fluid control can be performed.

Embodiments of the present invention will be described below with reference to the drawings.
The present invention is a sample analyzer provided with a microchip for bioassay for detecting a measurement substance contained in a liquid sample. 1 to 3 show a sample analyzer Z of the present embodiment.

A microchip is a kind of so-called biochip, and in recent years, a microchip manufactured by applying a microfabrication technology (MEMS) such as a semiconductor is widely used in fields such as biochemistry and medicine.
The microchip is, for example, a sample injection hole, a sample discharge hole, a minute capillary fluid flow path in a substrate, or a chamber, an electrophoresis column, a membrane separation mechanism, etc. as an analysis region connected to the flow path. A structure is formed. Such a microchip is mainly used for measuring a measurement substance contained in a liquid sample, such as a DNA analysis device, a microelectrophoresis device, a microchromatography device, and a microsensor.

In the microchip X in the sample analyzer Z of the present embodiment, the first solution flows down, the first fluid channel 11 including the pair of first valve bodies 21 whose opening and closing are synchronized, and the second solution flows down, It is a microchip for bioassay with a fluid control valve provided with a second fluid flow path 12 provided with a pair of second valve bodies 22 whose opening and closing are synchronized.
A part of the first fluid flow path 11 sandwiched between the pair of first valve bodies 21 and a part of the second fluid flow path 12 sandwiched between the pair of second valve bodies 22 are common. It is configured. In this way, a portion where a part of the first fluid channel 11 and a part of the second fluid channel 12 are common is referred to as a common part 13.
Further, the first fluid channel 11 is provided with an analysis means 14 for analyzing the second solution.
In addition, the sample analyzer Z is provided with a valve control unit Y that can alternately open and close the first valve body 21 and the second valve body 22.

(Microchip)
The microchip X can be obtained at a low cost, and a glass plate having advantages such as excellent chemical resistance is used as a constituent material.
In addition to glass, quartz plates, silicon resins, acrylic resins, etc. are used as constituent materials for microchips. Among silicon resins, polydimethyl is particularly preferred from the viewpoint of ease of molding and optical characteristics. A PDMS substrate mainly composed of siloxane (hereinafter abbreviated as PDMS) can be suitably used.
The PDMS substrate itself has a good adhesion property to glass / acrylic resin and the like, and by bringing a flat glass / acrylic resin member into contact with the finely processed PDMS substrate, It is possible to form a chamber serving as an analysis region.

Fluid component In this embodiment, the fluid component flowing down the fluid flow path of the microchip X is exemplified as a buffer solution as the first solution and a liquid sample as the second solution.

“Liquid sample” refers to a liquid sample that contains or may contain a measurement substance to be analyzed. The liquid sample may be from any source. For example, it can be obtained from environmental samples, cells, cultures, tissues, body fluids, urine, serum and biopsy samples.
Examples of environmental samples include soil collected from factory sites, water collected from rivers, and the like. Then, the sample collected from the environment is adjusted so as to be a liquid sample having a viscosity that can flow down through the flow path formed in the microchip.

  The “measurement substance” contained in the liquid sample is captured by the binding of this measurement substance and a binding substance (described later) that can form a specific conjugate. The specific complex is the result of the binding pair assay. As described later, the immunochemical complex resulting from the antigen-antibody reaction, the complex resulting from the hybridization of complementary nucleic acids, etc. Is preferably exemplified.

  The measurement substance can be any substance such as chemical substances, polymers such as proteins, DNA fragments, microorganisms or viruses, fragments thereof, hormones, and the like. Examples of measurement substances applicable to the sample analyzer Z of the present invention include substances that can cause environmental pollution, such as toxic substances (PCB, dioxins) and oily substances (heavy oil) contained in soil, or rivers. Suitable examples include pathogenic Escherichia coli cells contained in water.

  The buffer solution may be any known solution as long as it can be a buffer solution for the applied liquid sample.

Detailed Configuration of Microchip As shown in FIG. 3, a first introduction hole 31 a for introducing a buffer solution (first solution) is provided at the upstream end of the first fluid channel 11. At the downstream end, first discharge holes 31b for discharging fluid components flowing down the first fluid flow path 11 are provided.
A pair of first valve bodies 21 a to 21 b whose opening and closing is synchronized with each of the upstream region and the downstream region of the first fluid flow path 11 are provided. The first valve body 21a is provided between the first introduction hole 31a and the second valve body 22a, and the first valve body 21b is provided between the second valve body 22b and the first discharge hole 31b. .

  The second fluid channel 12 is connected to the first fluid channel 11 between the first valve body 21 a and the first valve body 21 b of the first fluid channel 11. However, the present invention is not limited to such an embodiment, and the first fluid passage 11 is connected to the second fluid passage 12 between the second valve body 22a and the second valve body 22b of the second fluid passage 12. You may comprise.

  A second introduction hole 32 a for introducing a liquid sample (second solution) is provided at the upstream end of the second fluid flow path 12, and the second fluid flow path 12 flows down at the downstream end of the second fluid flow path 12. Second discharge holes 32b for discharging fluid components are provided respectively.

  A pair of second valve bodies 22a to 22b whose opening and closing is synchronized with each of the upstream region and the downstream region of the second fluid flow path 12 are provided. The second valve body 22a is between the second introduction hole 32a and the first fluid flow path 11 (common part 13), and the second valve body 22b is between the first fluid flow path 11 (common part 13) and the second fluid flow path 11 (common part 13). They are respectively provided between the discharge holes 32b.

  In the present embodiment, the common portion 13 is bent. Thereby, since the liquid sample containing the measurement substance flows down while bending, a desired amount of the liquid sample can be held in a space-saving manner.

The length or cross-sectional area of each fluid channel can be determined as appropriate. In particular, since the common part 13 is involved in the measurement of the liquid sample (second solution), these parameters are important. That is, the common unit 13 determines the channel length, the cross-sectional area of the channel, the number of bends, and the like in consideration of the degree of stirring of the liquid sample during the flow and the fluid volume filled in the common unit 13. .
Specifically, the liquid sample that can be measured by the common unit 13 is, for example, about 5 to 10 μL.

The first valve body 21 and the second valve body 22 can be arranged on a straight line. Thereby, the structure of the valve control part Y which controls operation | movement of each valve body 21-22 can be simplified more. Specifically, as described later, a simple valve control unit can be obtained by applying a cam mechanism including a linear shaft body.
However, arrangement | positioning of the 1st valve body 21 and the 2nd valve body 22 is not restricted to the aspect made into a straight line.

  The microchip X forms a flow path together with the flow path substrate 41 in which the first fluid flow path 11 and the second fluid flow path 12 are formed, a support substrate 42 that supports the flow path substrate 41, and the flow path substrate 41. The elastic member 43 is sandwiched between the flow path substrate 41 and the support substrate 42 (see FIGS. 1 and 2).

  By configuring the microchip X in this manner, the elastic member 43 can be sandwiched between the flow path substrate 41 and the support substrate 42, so that each flow path can be reliably sealed. Therefore, it is possible to reliably prevent the fluid flowing down in the microchip X from leaking from each flow channel during the period from the introduction of the buffer solution or the liquid sample to the discharge.

  Further, the first valve body 21 and the second valve body 22 are inserted through the through holes 44 to 45 penetrating the support substrate 42, respectively, and the first valve body 21 and the second valve body 22 are brought into contact with the elastic member 43. It is arranged so that it can touch.

  As a result, the first valve body 21 and the second valve body 22 are brought into direct contact with the elastic member 43 to control the flow state of the buffer liquid or the liquid sample, so that reliable fluid control can be performed.

  In the present embodiment, the support substrate 42 can be a glass substrate, the flow path substrate 41 can be an acrylic resin substrate or a PDMS substrate, and the elastic member 43 can be a PDMS. However, the present invention is not limited to these combinations. The elastic member 43 may be a known rubber resin or the like in addition to PDMS. The dimensions of the flow path substrate 41 and the support substrate 42 can be appropriately set. For example, the long dimension is about 3 to 5 cm and the short dimension is about 1 to 2 cm.

The analyzing means analyzing means 14 is provided downstream of the second valve body 22b in the first fluid flow path 11.
The analysis means 14 in the present embodiment exemplifies an analysis means using an immunological technique based on an antigen-antibody reaction as a binding pair assay, but is not limited to this, and a biochemical method based on hybridization of a known nucleic acid or the like. An analysis means using a technique can also be applied.
In the case of the analysis means 14 using an immunological technique, an immobilizing substance carrying a binding substance that binds to a measurement substance contained in a liquid sample to form a specific complex is arranged. Can do.

“Binding substance” means a substance capable of recognizing a measurement substance, that is, a substance having molecular recognition ability capable of selectively detecting a measurement substance having an affinity for a binding substance. Examples of molecular discriminating ability include, for example, hybridization (complementary binding) ability between antibody (monoclonal antibody and polyclonal antibody) / antibody fragment-antigen, DNA-DNA / DNA-RNA / RNA-RNA nucleic acid Or, a biological response ability between a regulator / receptor-hormone / cytokine / neurotransmitter / lectin or the like, or between enzyme-substrate / coenzyme and the like is preferably exemplified.
Therefore, the “binding substance” is a concept including any substance as long as it has a molecular recognition ability capable of selectively detecting a measurement substance having an affinity for the binding substance, and includes an antigen, an antibody, a DNA fragment, an oligo Nucleic acids such as nucleotides, polynucleotides, and peptide nucleic acids, proteins, peptides, sugars, cells, microorganisms and the like are preferably exemplified, but are not limited thereto. For example, the binding substances for PCB and dioxin as measurement substances are an anti-PCB antibody and an anti-dioxin antibody, respectively.

  The binding substance is solid-phased on the surface of the member forming the analysis means 14 or is housed in the analysis means 14 in a state where the binding substance is supported on the surface of the immobilized substance. Can be arranged.

  The “immobilized substance” can be applied as long as it is a water-insoluble substance that can carry a binding substance on its surface. For example, carriers made of polymers such as latex, polyethylene, polystyrene, polypropylene, inorganic silicate carriers (glass, silica gel, etc.), organic carriers (plastic, nitrocellulose, dextran, etc.), carbon materials such as activated carbon, metal particles, Examples thereof include a magnetic material such as magnetite.

  Furthermore, the shape of the immobilization substance can take various forms such as particles (beads), sheets, and tubes. Preferable examples are beads having a particle size of about 0.1 to 1000 μm, preferably about 1 to 100 μm, and particularly preferably about 1 to 50 μm.

  On the other hand, porous materials such as nylon, nitrocellulose, cellulose acetate, glass fiber and porous polymer can be used as the immobilizing material.

  The method for immobilizing the binding substance on the immobilization substance can be performed by a known method. For example, the method for physically adsorbing the antibody (binding substance) on the polystyrene carrier, the functional group provided on the surface of the immobilization substance There is a method of covalently bonding an amino group or the like of the “binding substance”. After the binding, the surface of the carrier and the unreacted functional group on the surface can be blocked with an appropriate protein / surfactant or the like to suppress nonspecific reactions.

  As the “immunochemical technique”, for example, the presence of a measurement substance in a liquid sample can be detected or quantitatively measured by applying an immunoassay technique based on a solid phase method. In the so-called “sandwich method” known as an immunoassay, for example, a target measurement substance such as an antigen is sandwiched between a labeled antibody and an antibody (binding substance) immobilized on the surface of the immobilized substance. In the analysis means 14, a specific complex can be formed and the measurement substance can be captured.

Thus, by labeling an antibody or the like that forms a specific complex, the presence of the measurement substance can be detected or quantitatively measured. Note that either the measurement substance or the binding substance may be labeled.
In this way, the measurement substance in the liquid sample can be detected with high sensitivity.

The specific complex formed by the antigen-antibody reaction is detected as follows.
For example, by labeling an antibody with a fluorescent (luminescent) substance and detecting its fluorescence (luminescent) intensity directly, or by binding an enzyme to the antibody and performing an enzymatic reaction using a chemiluminescent substrate, optical changes can be detected. To do.

  The fluorescent material applicable to the present embodiment is not particularly limited, and examples of applicable fluorescent materials include fluorescein, rhodamine, phycocyanin and the like. Moreover, the chemiluminescent substrate applicable to this embodiment is not specifically limited, As a chemiluminescent substrate which can be applied, luminol, isoluminol, an isoluminol derivative, etc. can be mentioned.

The reaction temperature, the composition of the solution in which the reaction is carried out, the pH and the like can be performed under the conditions used in normal immunoassay. For example, the temperature is preferably about 5 to 60 ° C. and the pH is preferably about 5 to 9.

As a result of the reaction when a fluorescently labeled antibody is used, a labeling substance is present in the specific complex produced depending on the amount of “measurement substance”. Quantifying the “measurement substance” by introducing a washing buffer or the like through the first introduction hole 31a to flow down the first fluid flow path 11 and removing unreacted substances and then measuring the amount of the labeling substance. Can do. The quantification of the labeling substance can take various methods along with the type of the labeling substance. For example, the fluorescence intensity of the fluorescent substance is measured by a fluorescence measuring device. By comparing the measured label intensity with the label intensity when a known amount of “measurement substance” is measured, the amount of the measurement substance in the liquid sample can be determined.

(Valve control part)
In the present embodiment, the valve control unit capable of alternately opening and closing the first valve body 21 and the second valve body 22 is, for example, a cam mechanism 50 capable of controlling the first valve body 21 and the second valve body 22 separately. The case where is applied is illustrated (see FIGS. 1 and 2).

  The cam mechanism 50 includes a shaft body 51 and cam bodies 52 to 53. The shaft body 51 is connected to driving means such as a motor that drives the shaft body 51. And it is set as the structure which provides the cam bodies 52-53 which can carry out the opening-and-closing control of the 1st valve body 21 and the 2nd valve body 22 in the shaft body 51 rotating around an axis center respectively. That is, the cam bodies 52 to 53 are disposed such that the distance from the rotation shaft of the shaft body 51 is not constant, and the positions in the axial direction on the surface of the shaft body 51 are different.

  For example, when the first valve body 21 is in the open state, the second valve body 22 is in the closed state, so that the cam bodies 52 to 53 are respectively set so that the circumferential positions on the surface of the shaft body 51 are different. Arrange.

  When the cam bodies 52 to 53 have a projecting structure, the cam bodies 52 to 53 are separated from the rotation axis of the shaft body 51 as compared to a portion without the cam body. And it comprises so that the cam bodies 52-53 may contact | abut with the 1st valve body 21 or the 2nd valve body 22 with rotation of the shaft body 51, respectively.

  For example, when the first valve body 21a-21b does not contact the cam bodies 52a-52b and the second valve bodies 22a-22b contact the cam bodies 53a-53b at a certain point in the rotation of the shaft body 51. (FIG. 1 (a), FIG. 2 (a)), the 1st valve bodies 21a-21b will be in an open state, and the 2nd valve bodies 22a-22b will be in a closed state. On the other hand, when the first valve bodies 21a to 21b are in contact with the cam bodies 52a to 52b and the second valve bodies 22a to 22b are not in contact with the cam bodies 53a to 53b (FIG. 1 (b), FIG. 2 (b)). ), The first valve bodies 21a to 21b are closed, and the second valve bodies 22a to 22b are opened.

  The shaft body 51 may be rotated in one direction, or may be configured such that the rotation direction is reversed by a step motor or the like. At this time, it can be configured to reverse within a certain rotation angle. In order to make the first valve body 21 and the second valve body 22 open and close in a desired state, the timing of rotation and stop of the shaft body 51 can be set as appropriate. For example, when any one of the first valve body 21 and the second valve body 22 is opened, the opened state is maintained when the operation of the shaft body 51 is stopped. Then, when the operation of the shaft body is resumed at a desired timing, the open state can be released.

  The cam body 52 may have a semicircular protrusion structure or a protrusion structure having a certain length along the circumferential direction of the shaft body 51. Furthermore, the cam body 52 is not limited to the protrusion structure, and may be any structure as long as the distance from the rotation axis of the shaft body 51 is not constant. For example, the cam body can have a concave structure.

  As described above, the valve control unit Y that can simultaneously control the operations of the first valve body 21 and the second valve body 22 can be configured with a simple structure.

  The microchip X including the flow path substrate 41, the support substrate 42, and the elastic member 43 may be securely fixed by a holding unit that holds the microchip X so as not to be displaced with respect to the valve control unit Y.

(Fluid control by valve control unit)
The sample analyzer Z of the present invention has a structure in which the valve body and the valve control unit for controlling the fluid flow state in the fluid flow path are provided in the above-described microchip X.

  That is, when the pair of first valve bodies 21 is in an open state, the valve control unit can control the valve bodies so that the pair of second valve bodies 22 are in a closed state. At this time, when the buffer solution is introduced from the first introduction hole 31a, the first fluid flow path 11 is filled with the buffer solution (FIG. 3A). In the microchip X of the present invention, since a part of the first fluid channel 11 and a part of the second fluid channel 12 are configured in common, the common part 13 which is a common part is a buffer. Filled with liquid.

Subsequently, when the pair of second valve bodies 22 is opened, the pair of first valve bodies 21 is controlled to be closed. At this time, when the liquid sample is introduced from the second introduction hole 32a, the second fluid channel 12 is filled with the liquid sample.
In the microchip X of the present invention, since a part of the first fluid channel 11 and a part of the second fluid channel 12 are configured in common, the common part 13 which is a common part is a liquid. The sample is filled (FIG. 3 (b)).

  At this time, since the first valve element 21 a is closed on the upstream side of the common part 13, the liquid sample does not flow to the upstream side of the common part 13. Similarly, since the first valve body 21 b is in the closed state on the downstream side of the common portion 13, the liquid sample does not flow to the downstream side of the common portion 13.

  Further, when bubbles are present in the liquid sample, the bubbles can be removed from the common portion 13 by allowing the liquid sample to flow down to the second fluid channel 12 until the bubbles can be discharged.

In this state, control is performed so that the pair of first valve bodies 21 is opened again and the pair of second valve bodies 22 is closed. At this time, when the buffer liquid is caused to flow down from the first introduction hole 31a to the first fluid flow path 11, the liquid sample existing in the common portion 13 is pushed away by the buffer liquid, and flows down through the first fluid flow path 11 to perform analysis. 14 (FIGS. 3C to 3D).
At this time, the liquid sample can flow down the analyzing means 14 to form a specific complex by a reaction between the measurement substance contained in the liquid sample and the binding substance arranged in the analyzing means 14.

  Thus, by alternately opening and closing the pair of first valve bodies 21 and the pair of second valve bodies 22, a desired amount of liquid sample can be filled in the common portion 13, and thereafter the liquid sample A desired amount of the liquid sample can be introduced to the analysis means 14 by extruding with the first solution. That is, the common part 13 is a section where the liquid sample can be measured.

  Since the liquid sample can be guided to the analysis unit 14 without bubbles, the optical analysis of the specific complex formed by the analysis unit 14 is accurately performed without being affected by the bubbles. Can do.

As described above, in the sample analyzer Z of the present invention, the paired valve bodies (for example, the first valve bodies 21a to 21b) can be controlled in a synchronized state, and therefore the paired valve bodies need not be individually controlled. Also good. Further, since the first valve body 21 and the second valve body 22 can be alternately opened and closed, the first valve body 21 and the second valve body 22 are simultaneously controlled. It is not necessary to individually control the opening / closing timing of the valve body, and the operation of the valve body can be controlled with a simple structure.
Therefore, the structure of the sample analyzer Z can be simplified.

  The present invention relates to a sample analysis apparatus including a bioassay microchip provided with a fluid flow path through which a liquid sample as a fluid flows and an analysis means for analyzing the liquid sample. Can be used for control.

Schematic diagram of the sample analyzer of the present invention Schematic showing the operation of the valve body by the valve controller Schematic top view of microchip

Explanation of symbols

X Microchip for bioassay with fluid control valve Y Valve control unit Z Sample analyzer 11 First fluid channel 12 Second fluid channel 13 Common unit 14 Analyzing means 21a-21b First valve body 22a-22b Second valve body 41 Flow path substrate 42 Support substrate 43 Elastic members 44 to 45 Through hole 50 Cam mechanism

Claims (4)

A first fluid flow path including a pair of first valve bodies in which the first solution flows down and is synchronized in opening and closing;
A second fluid flow path including a pair of second valve bodies in which the second solution flows down and is synchronized in opening and closing;
A part of the first fluid flow path sandwiched between the pair of first valve bodies and a part of the second fluid flow path sandwiched between the pair of second valve bodies are configured in common. ,further,
A microchip for bioassay with a fluid control valve provided with analysis means for analyzing the second solution in the first fluid flow path; and
A sample analyzer provided with a valve control unit capable of alternately opening and closing the first valve body and the second valve body.   The sample analyzer according to claim 1, wherein the valve control unit is a cam mechanism that can control the first valve body and the second valve body separately.   The sample analyzer according to claim 1 or 2, wherein the first valve body and the second valve body are arranged in a straight line. The bioassay microchip with a fluid control valve comprises:
A channel substrate in which the first fluid channel and the second fluid channel are formed;
A support substrate for supporting the flow path substrate;
Forming a flow path together with the flow path substrate, and comprising an elastic member sandwiched between the flow path substrate and the support substrate,
The first valve body and the second valve body are inserted through a through-hole penetrating the support substrate, and the first valve body and the second valve body are disposed so as to be in contact with the elastic member. The sample analyzer according to any one of claims 1 to 3.

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