Valve opening / closing system and analysis system

Abstract

A valve opening / closing system disclosed herein comprises: a pin that extends in a Z-axis direction and acts on a valve of a flow path device; a sliding plate that has a range of motion in an X-axis direction and has irregularities on the surface in the positive Z-axis direction; a first spring that connects a pin head and a pin lower portion (base portion); a pin guide that has a through-hole; and a second spring that connects the pin guide and the pin lower portion. The valve is opened and closed by moving the pin in the Z-axis direction by moving the sliding plate in the X-axis direction by means of a control unit. Here, it is important that the pin head not be in contact with the valve (made of a plastically deforming film) when the valve is opened. When this is expressed as a conditional expression, the relations Z0≦Z1<Z2 and Zn≦Z1 hold, where the Z coordinate of the Z-axis minus end of the pin is Zp, the Z coordinates of a concave portion and a convex portion of the sliding plate are Z0 and Z2, respectively, the minimum Zp at which the first spring elastically deforms is Z1, and the Zp at which the second spring elastically deforms is Zn (see FIG. 7).

Description

Valve opening and closing systems and analytical systems

[0001] The present disclosure relates to a valve opening and closing system and an analytical system.

[0002] When analyzing genes, for example, preprocessing involves dissolving the sample, purifying and amplifying the nucleic acid, and then detecting the amplified product. This process involves the risk of contamination and the need for complex sample preparation. For this reason, the conventional procedure has been to send samples to an environment with well-equipped experimental facilities, such as a research institute, where inspectors with specialized knowledge and skills prepare the samples, measure them, and then analyze the data. However, problems include the time required to transport samples and the large capital and labor costs required to maintain the experimental equipment. Furthermore, in laboratories that use batch processing, it is difficult to interrupt urgent samples.

[0003] In recent years, sample-to-answer analysis systems, which perform all processes from sample introduction to measurement and data acquisition in an automated manner, have begun to appear in a variety of fields. Sample-to-answer analysis systems sometimes use flow path devices that integrate chambers, flow paths, and stored reagents. Sample-to-answer analysis systems using flow path devices have the following advantages: (1) Measurements can be easily performed even by non-experts; (2) Data can be acquired in a short time; (3) Highly portable analysis systems can be designed; (4) Variability due to procedures is reduced; and (5) Reagents can be easily stored. Examples of sample-to-answer analysis systems include those described in Patent Documents 1 and 5, which dissolve, purify, PCR, and detect human-derived samples to perform fully automated DNA analysis.

[0004] The fields of use for sample-to-answer analytical systems, including potential applications, include forensic science, in vitro diagnostics, identification of plant and animal species, biodefense, medicine, biotechnology, life sciences, defense, public health, and agriculture. Sample-to-answer analytical systems are required to be small in size, lightweight, durable, and operate stably with minimal maintenance. Furthermore, multiple samples must be analyzed simultaneously or sequentially.

[0005] When genetic analysis is performed using a sample-to-answer analysis system, it is desirable to dispose of flow path devices that may come into direct contact with the sample after each analysis to prevent sample contamination between analyses. To reduce the cost of flow path devices, it is desirable to design them so that they can be manufactured on a simple production line or to use inexpensive materials.

[0006] In particular, when complex biomolecular analyses are performed using flow channel devices, valves are often used to pressurize / depressurize appropriate flow channels and send fluids to appropriate flow channels or chambers. For example, in Patent Documents 1, 2, 3, 4, 5, and Non-Patent Document 1, part or all of the valve opening / closing drive mechanism is provided outside the flow channel device, allowing it to be used repeatedly between analysis rounds.

[0007] US Patent No. 11649496 International Publication No. 2022 / 112450 JP 2020-116568 A Japanese Patent No. 7156365 A US Patent No. 9354199 A

[0008] Jiwen Xiang, Ziliang Cai, Yong Zhang, Wanjun Wang, “Mechanically programmed valving technology and the active flow switching application in centrifugal microfluidics” ScienceDirect 2017

[0009] Analysis systems are required to have low analysis costs, stable fluid transport, high sensitivity, and a compact size. Stable fluid transport requires stable valve operation. One of the key elements to valve operation stability is the control of the pressure force of the valve drive mechanism. In other words, the pressure force when the valve is opened and closed must be controlled within an appropriate range.

[0010] To reduce analysis costs, it is necessary for the valve drive mechanism, which is a non-consumable item, to be inexpensive, or for the flow path device, which is a consumable item, to be inexpensive to produce. To achieve high sensitivity, the shape and material of the flow path device must be optimized for the analysis, or close to optimal. Examples of shapes that affect sensitivity include the length of the flow path, the simplicity of the valve shape, and the liquid contact area. Optimization, for example, requires a high degree of freedom in valve placement. To keep the analytical system compact, the flow path device or valve drive mechanism must be small. Furthermore, to make the valve drive mechanism smaller or simpler, multiple valves can be operated by a single drive system.

[0011] In Patent Documents 1 and 2, a convex portion on the rotating cam or sliding plate pushes up the pressing module, moving the head away from the valve and opening the valve, and a concave portion on the rotating cam or sliding plate returns the pressing module to its original position, closing the valve.

[0012] However, in the methods of Patent Documents 1 and 2, the contact point between the sliding plate and the pressing module is not on the same line as the direction in which force is applied to the valve, which tends to increase the size of the pressing module. Also, when performing complex analyses, the number of valve opening and closing steps increases, which poses a problem of increasing the size of the sliding plate or rotating cam.

[0013] Furthermore, Patent Document 3, Patent Document 4, and Non-Patent Document 1 employ a drive system in which a sliding plate with concave and convex portions that moves linearly or rotationally pushes up a pin at the convex portion, crushing the valve, and then the pin moves in a direction away from the valve at the concave portion, opening the valve. In this system, the axis along which the pin moves at the point where the sliding plate and pin meet coincides with the axis that applies force to the valve.

[0014] However, in Patent Document 4, a compression spring is provided on the pin, and the action of the compression spring presses the pin against the sliding plate relative to the pin guide. The action of the compression spring causes the pin to move up and down, tracing the surface, following the left and right movement of the sliding plate. In Patent Document 4, the pin acts as a rigid body relative to the valve, so there is a problem in that the force with which the pin presses the valve cannot be controlled.

[0015] In Patent Document 3 and Non-Patent Document 1, a compression spring is provided inside the pin, and the compression spring presses the pin against a sliding plate relative to the flow path device. Due to the action of the compression spring, the pin moves up and down, tracing the surface, following the left and right movement of the sliding plate. However, in Patent Document 3 and Patent Document 1, the pressing force of the pin against the flow path device remains even when the valve is opened, which causes an issue of insufficient valve opening. In view of this situation, the present disclosure provides a valve opening and closing system that is inexpensive, opens and closes the valve stably, has a high degree of freedom in valve placement, and can be miniaturized.

[0016] In order to solve the above problems, the present disclosure provides, as an example, a valve opening and closing system for opening and closing a valve provided on a first plate constituting a flow path device placed parallel to an XY plane in an XYZ Cartesian coordinate system, the system comprising: a second plate having a through hole; a pin having an upper part in the positive Z-axis direction and a lower part in the negative Z-axis direction, with a central axis parallel to the Z-axis; a third plate having a movable range in the X-axis direction and having unevenness on its surface in the positive Z-axis direction; a first elastic body connecting the upper part and the lower part of the pin when elastically deformed; a second elastic body connecting the second plate and the upper part or the lower part of the pin when elastically deformed; and a control unit for driving the third plate, the first plate, the second plate, and the third plate being arranged in order along the negative Z-axis direction perpendicular to the Z-axis, the pin being placed between the first plate and the third plate while passing through the through hole of the second plate, The control unit moves the third plate in the X-axis direction, thereby enabling the negative Z-axis end of the pin to move in the Z-axis direction to follow the unevenness on the surface of the third plate, and generates a first force that the upper part of the pin applies to the first plate, and the Z coordinate of the negative Z-axis end of the pin is Zp, the Z coordinates of the concave and convex parts on the surface of the third plate are Z0 and Z2, respectively, the minimum Zp at which the first elastic body elastically deforms is Z1, and the minimum Zp at which the second elastic body elastically deforms is Zn, the relationships Z0≦Z1<Z2 and Zn≦Z1 hold.

[0017] Further features related to the present disclosure will become apparent from the description of this specification and the accompanying drawings. Also, aspects of the present disclosure are achieved and realized by the elements and combinations of various elements and the aspects of the following detailed description and the appended claims. The description of this specification is merely exemplary and does not limit the scope or application of the claims of the present disclosure in any way.

[0018] According to the technology disclosed herein, it is possible to provide an analytical system equipped with a flow path device and a valve drive system that can achieve low-cost and stable opening and closing operations, and further, an analytical system that allows for a high degree of freedom in valve placement and can be made compact.

[0019] 1 is a block diagram showing an example of the functional configuration of an analysis system 101 according to this embodiment. FIG. 1 is a diagram showing an example of a valve designed so that the shape of the flow path 204 in the valve section and the shape of the head 203 roughly match. FIG. 2 is a diagram showing an example of a valve in which the tip of the head 203 has a shape (e.g., a sphere or a cone) that can be approximated by a body of revolution with respect to an axis parallel to the Z axis. FIG. 3 is a diagram showing an example of a valve in which the tip of the head 203 has a flat surface parallel to the αβ plane. FIG. 4 is a diagram showing the closure rate of a valve relative to the depression force of a valve in which the depression force and the closure rate are proportional to each other. FIG. 5 is a diagram showing the closure rate of a valve relative to the depression force when polypropylene is used for the film 202. FIG. 6 is a diagram showing actual measured values ​​of the closure rate of a valve relative to the depression force when polypropylene is used for the film 202. FIG. 7 is a diagram showing an example of the configuration of a sliding plate drive system 301 (valve opening and closing system). FIG. 8 is a diagram showing the Z coordinates of the concave and convex portions 312 and 311 of the sliding plate 303 and the sliding plate contact portion 308. FIG. 9 is a diagram showing an example of the configuration of the sliding plate drive system 301. 1 is a diagram showing a configuration example of a sliding plate drive system 301. FIG. 1 is a diagram showing an example in which a follow-up mechanism 307 is configured with an elastic body (spring). FIG. 1 is a diagram showing an example in which a follow-up mechanism 307 is configured with a magnet. FIG. 2 is a diagram showing an example in which a follow-up mechanism 307 is configured with a magnet. FIG. 3 is a diagram showing a guide structure of a sliding plate ground contact part 308. FIG. 4 is a diagram showing an example in which a transmission mechanism is configured with an elastic body. FIG. 5 is a diagram showing an example in which a transmission mechanism is configured by installing magnets 317 that repel each other at the lower end of an upper pin and the upper end of a lower pin. FIG. 6 is a diagram showing a configuration example in which a transmission mechanism 307 is provided on the flow channel device 104 side. FIG. 7 is a diagram showing a configuration example of a sliding plate 303 having recesses 312 at multiple height levels. FIG. 8 is a diagram showing an operation in which a reagent reservoir 402 is crushed and opened using the sliding plate drive system 301, thereby releasing a reagent into a flow channel 204. FIG. 9 is a diagram showing an arrangement example 1 of a second spring and a first spring. FIG. 10 is a diagram showing an arrangement example 2 of a second spring and a first spring. FIG. 11 is a diagram showing an arrangement example 3 of a second spring and a first spring. FIG. 10 is a diagram showing a fourth arrangement example of the second spring and the first spring. FIG. 11 is a diagram showing a first structural example of the pin 304 and the sliding plate drive system 301. FIG. 12 is a diagram showing a second structural example of the pin 304 and the sliding plate drive system 301. FIG. 13 is a diagram showing a cross-sectional structural example of a spring plunger 501. FIG. 14 is a diagram showing a structural example of the flow channel device 104 being aligned by the sliding plate drive system 301.1 is a diagram showing example 1 of a method for maintaining the posture of the head inside the pin or between the pin and the pin guide. FIG. 2 is a diagram showing example 2 of a method for maintaining the posture of the head inside the pin or between the pin and the pin guide. FIG. 3 is a diagram showing example 3 of a method for maintaining the posture of the head inside the pin or between the pin and the pin guide. FIG. 4 is a diagram showing an example of a pin design illustrating the structure of a sliding plate 303 and a roller 603. FIG. 5 is a diagram showing an example of a configuration in which a second spring 307 is provided for each of multiple valves. FIG. 6 is a diagram showing an example of a configuration in which a single second spring 307 is provided collectively for multiple valves. FIG. 7 is a diagram showing an example of a sliding plate pattern when three valves are installed on the same X coordinate. FIG. 8 is a diagram showing example 1 of a sliding plate pattern when three valves are installed on the same Y coordinate. FIG. 9 is a diagram showing example 2 of a sliding plate pattern when three valves are installed on the same Y coordinate. FIG. 10 is a diagram showing an example of a sliding plate pattern when three valves are not arranged on the same XY coordinate and the uneven lane is not shared between the valves. FIG. 11 is a diagram showing an example of a sliding plate pattern when two valves are arranged on the same Y coordinate and the distance between the two valves is a certain distance apart relative to the width of the uneven lane in the X-axis direction. 17A and 17B , viewed from the Y-axis direction. This figure shows an example of a sliding plate pattern in which valves V1 and V2 are arranged on the same Y-axis, and valve V3 is arranged on a different Y-axis from V1 and V2. This figure shows an example in which the flow path devices 104 are arranged along the Y-axis direction so as not to overlap in the Z-axis direction, with the valve drive direction being Z and the direction of movement of the sliding plate 303 being X. This figure shows an example in which the flow path devices 104 are arranged along the X-axis direction so as not to overlap in the Z-axis direction, with the valve drive direction being Z and the direction of movement of the sliding plate 303 being X. This figure shows an arrangement diagram of the arrangements of FIGS. 17A and 17B as viewed from the Y-axis direction. This figure shows an arrangement diagram and a movable range of the sliding plate 303 when four flow path devices are arranged in the X-axis direction as shown in FIG. 17B , a sliding plate 303 like the sliding plate diagram in FIG. 16D(2) is shared among the four flow path devices, and the valve opening / closing pattern is moved as shown in FIG. 16D(1). This figure shows an example of an arrangement in which multiple rotating sliding plates 303 are used for multiple flow path devices 104. 10 is a diagram showing the characteristics of the force applied by the pin 304 to the sliding plate 303 or the flow channel device 104. FIG. 11 is a diagram showing a state in which the second spring reaches its natural length midway.1 is a diagram showing a state when the relationships Z1≦Z0 and Zn≦Z0 are satisfied. It is a diagram showing a pin incorporating an appropriate spring plunger 501 and the pressing force characteristics of the pin. It is a diagram showing the change in the first force F1 relative to the amount of change in the uneven portion of the sliding plate 303 when a pin 304 having a first spring in a spring plunger 501 is pressed against a flow path device 104 with a PP film stretched thereon. It is a diagram showing the force applied to the sliding plate contact portion 308 on the inclined surface of the sliding plate 303. It is a diagram showing an example of a configuration in which an enclosure 604 is provided on the pin guide 302 to restrict the lower limit of the Z coordinate of the pin lower portion 305. It is a diagram showing the pin characteristics of Non-Patent Document 1. It is a diagram showing the pin characteristics of Patent Document 4. It is a diagram showing a configuration in which two springs are incorporated into a pin, and the first spring acts to press the pin against the sliding plate relative to the flow path device, and the second spring acts to press the pin against the sliding plate relative to the pin guide. 23A and 23B. FIG. 24A is a diagram comparing the characteristics of the force (first force) applied to the flow path device 104 by pins 304 with different configurations. Continuing from FIG. 20, this is a diagram comparing the characteristics of the force (first force) applied to the flow path device 104 by pins 304 with different configurations. FIG. 24B is a diagram showing an example of the detailed configuration of the analysis system 101. FIG. 24C is a diagram showing an example of the operation procedure of the analysis system 101. FIG. 24D is a diagram showing an example of connections of a plurality of flow paths, valves, etc. in the flow path device 104 used in the analysis system 101. FIG. 24D is a diagram for explaining the liquid transfer operation, etc. in the flow path device 104 of the analysis system 101. FIG. 24C is a diagram showing the configuration of the flow paths, etc. of the flow path device 104 of FIG. 23A and the valve opening and closing steps corresponding to the operation example shown in FIG. 23B. FIG. 24D is a table showing sliding plate steps. FIG. 24E is a table showing sliding plate steps corresponding to the analysis process. FIG. 24F is a diagram showing the concave and convex lanes of each valve included in the sliding plate 1 shown in FIG. 24A. FIG. 24F is a flowchart for explaining the analysis sequence in the analysis system 101.

[0020] <Points to Note in This Specification> (i) This specification mainly describes the system configuration and procedures for genetic analysis using a detection unit such as CE (Capillary Electrophoresis), but the application is not limited to genetic analysis and may be biomolecular analysis. Furthermore, the application is not limited to biomolecular analysis and may be a reaction / analysis system using a flow channel device. The application may also be one in which the pins are current contacts and control the on / off of the current in an electronic circuit.

[0021] In the following, the term "flow path device" will be used to refer to a flow path device consisting mainly of a flow path substrate with grooves for the flow path and a film bonded to cover the flow path, but flow path devices with different configurations that provide similar functions may also be used.

[0022] In addition, in the accompanying drawings, illustrations of the flow channels and films of the flow channel device may be omitted for simplicity. The flow channels and valves are assumed to be properly aligned with the head unless otherwise specified.

[0023] (ii) In this specification, "pressing" refers to the general action of applying force. "Depressing" refers to the action of applying force to deform a film. Furthermore, "joined" refers mainly to the state in which different components are joined by adhesives, heat welding, screw fastening, or interlocking, but also includes cases in which a single component that is integrally molded from the beginning has multiple functions. Components that are "elastically deformed" include components that are slightly plastically deformed.

[0024] The required depression force, for example, refers to the minimum depression force that can close the valve with a probability of 99% or more. However, the definition of closing may differ depending on the design of the flow path device. Furthermore, the maximum opening depression force, for example, refers to the maximum depression force that can open the valve. The valve closure rate may be 20% or less within 5 seconds, 10 seconds, or 30 seconds after the load is removed. The definition of opening may differ depending on the flow path device.

[0025] (iii) In this specification, the effect of gravity is assumed to exist even if not specifically mentioned. Furthermore, although the equations relating to force balance and pressure do not include terms for the effect of gravity, those skilled in the art can easily deduce the equations when gravity is taken into account.

[0026] The action of frictional force is assumed to exist even without any special mention. Although the equations relating to force balance and pressure do not include a term for the action of frictional force, those skilled in the art can easily deduce the equations when frictional force is taken into account.

[0027] (iv) In this specification, the sliding plate refers to a linear cam unless otherwise specified. Generally known cam design methods are used. Cams with other drive modes, including circumferential drive cams, may be used instead.

[0028] (v) In the following, the orientations of the fluid control system and the analytical system are expressed using the Cartesian coordinate system XY4 and the Cartesian coordinate system αβZ. The orientations of the XYZ and Cartesian coordinate system αβZ do not indicate any particular direction relative to the direction of gravity, and unless otherwise specified, they may be in any orientation. Furthermore, the Cartesian coordinate system XYZ and the Cartesian coordinate system αβZ may be either a right-handed system or a left-handed system.

[0029] The Cartesian coordinate system XYZ and the Cartesian coordinate system αβZ share the Z axis, and the XY plane and the αβ plane are the same. The X-axis and Y-axis may or may not coincide with the α-axis and β-axis.

[0030] The origins of the Cartesian coordinate system XYZ and the Cartesian coordinate system αβZ can be set anywhere. There is no problem if a different origin is set for each valve or each coordinate system. However, coordinates on drawings with the same drawing number and subnumber are considered to share the same coordinate system within the same drawing number and subnumber.

[0031] In a valve drive system using a sliding plate, the sliding plate has unevenness in the positive Z-axis direction, and when the sliding plate is moved in the X-axis direction, the pin moves in the Z-axis direction along the unevenness of the sliding plate. In the following, the direction in which the pin approaches the valve is referred to as the positive Z direction.

[0032] <Analysis System> FIG. 1 is a block diagram showing an example of the functional configuration of an analysis system 101 according to this embodiment. The analysis system 101 includes a control and analysis unit (composed of a computer 102) including a memory for storing program instructions and a processor for executing the program instructions, a function for receiving and analyzing raw data, optical data, and electropherogram data from a detection unit 105, a solution transport control mechanism such as a pump and valves, a detection unit, a flow path device, and a heater. The control and analysis unit may be connected to a network, enabling data to be uploaded to, collated, and accessed from an external database. The pump may be a diaphragm pump or a syringe pump. Examples of valves include valves that directly or indirectly transmit motor power to deform a film, or valves that deform using air pressure. The valves may be controlled by a control unit. The valves may be opened and closed by thermal deformation, or magnetic force may be used.

[0033] Various parameters related to the analysis protocol may be stored in advance in a database 103 of a computer 102 provided in the analysis system 101. The computer 102 may be responsible for controlling the opening and closing of valves in the flow path device 104, the detection unit 105, and their connecting parts, as well as controlling the temperature, applied pressure, and flow rate, based on the parameters recorded in the database 103. The parameters recorded in the computer 102 may include temperature, time, pressure, flow rate, and functions for setting parameters based on stored parameters and actual measured values.

[0034] The analysis system 101 can receive a sample and perform all processes from lysis to purification, PCR, detection and analysis in a fully automated manner. Note that the processes from lysis to purification, PCR, detection and analysis may be partially automated.

[0035] The flow channel device 104 may be disposable. By making it disposable, contamination between samples can be prevented. In the analysis procedure, pre-processing until the sample is ready for detection may be performed in the disposable flow channel device 104, and the part where the sample is detected may be performed in a detection unit provided outside the flow channel device 104. In particular, in the case of pre-processing where PCR is performed, the impact of contamination before PCR is significant. For this reason, pre-processing up to the PCR step may be performed in the disposable flow channel device 104, or the device may be thoroughly washed after each use.

[0036] The detection unit 105 may be disposable. By making it disposable, contamination between samples can be prevented. The detection unit 105 may also be integral with the flow path device 104. This integral structure facilitates storage, maintenance, and transportation. This integral structure simplifies the connection between the flow path device 104 and the detection unit 105, reducing the frequency of breakdowns and errors.

[0037] While the flow channel device 104 is disposable, the detection unit 105 may be reusable multiple times. The detection unit 105 requires precision manufacturing and is expensive, so making it reusable can reduce costs.

[0038] 1 , the computer 102 includes a user interface 106. The computer 102 can receive parameters related to the user interface 106 from a user, such as the time and temperature of each step, pressure, flow rate, procedure, divided liquid volume, number of PCR cycles, sample information, flow path device information, and analysis protocol, and store these in a database 103. In addition, various parameters may be stored in the database 103 in advance. The computer 102 may be responsible for controlling the opening and closing of valves of the flow path device 104, temperature control, and applied pressure and flow rate control based on the parameters recorded in the database 103.

[0039] The flow channel device 104, which is consumed for each analysis, has an internal tag. The analysis system 101 can set an appropriate analysis protocol by reading the information on the tag. The analysis time per analysis using the flow channel device 104 is, for example, typically within two days, more typically within 12 hours, and more typically within two hours.

[0040] <Configuration example of flow path device> The flow path device 104 includes reagents, chambers, and flow paths therein, and can be configured as a disposable or multiple-use consumable part. The flow path device 104 may include a pump therein as a power source for transporting fluids. Also, some or all of the reagents required for the reaction may be present within the flow path device 104. Some of the chambers provided within the flow path device 104 may be provided with a temperature control function, a molecule capture function, a detection function, and a voltage application function.

[0041] The material used for the flow channel device 104 is not particularly limited as long as it is a material commonly used in the relevant technical field. Preferably, materials with low DNA adsorption, such as polypropylene, polyethylene, cyclic olefin polymer (COP), cyclic olefin copolymer (COC), polycarbonate, polyethylene terephthalate, and polyurethane, are used. It is also desirable to suppress the amount of adsorption by modifying the surface so that it becomes negatively charged. Other materials include, for example, metals such as gold, silver, copper, aluminum, tungsten, molybdenum, chromium, platinum, titanium, and nickel; alloys such as stainless steel, Hastelloy, Inconel, Monel, and duralumin; silicon; glass materials such as glass, quartz glass, fused silica, synthetic quartz, alumina, sapphire, ceramics, forsterite, and photosensitive glass; plastics such as polyester resin, polystyrene, polyethylene resin, ABS resin (Acrylonitrile Butadiene Styrene resin), dimethylpolysiloxane (PDMS), nylon, acrylic resin, fluororesin, polycarbonate resin, polyurethane resin, methylpentene resin, phenolic resin, melamine resin, epoxy resin, and vinyl chloride resin; agarose, dextran, cellulose, polyvinyl alcohol, nitrocellulose, chitin, chitosan, or any combination thereof.

[0042] In one embodiment, the flow channel device 104 has a flow channel therein and is entirely made of a deformable material. In another embodiment, the flow channel device 104 is made by bonding a lid to a flow channel substrate 201 having holes and grooves formed therein with a film 202. In another embodiment, the part of the flow channel device 104 that corresponds to the lid and the part that corresponds to the flow channel are made of the same material.

[0043] In one embodiment, the parts that make up the flow channel device 104 are made by injection molding, 3D printing, cutting, blow molding, extrusion, hot embossing, laser cutting, press molding, or the like.

[0044] The flow channel substrate 201 is preferably made of a material that can be injection molded. Injection molding has the advantage of reducing the manufacturing cost of the flow channel device 104 when mass-producing it. When making the flow channel device 104 from an inexpensive material, a material that can be plastically deformed, such as polypropylene, polyethylene, or PET, is suitable.

[0045] The typical size of the flow channel device 104 is such that each side is 50 cm or less. In particular, a flow channel device 104 capable of analyzing one sample has each side of 20 cm or less. To make the system compact, it is preferable that the long side of the flow channel device 104 is 15 cm or less, the width is 10 cm or less, and the thickness is 1 cm or less.

[0046] 2A to 2C are diagrams showing the state of the valve according to this embodiment when it is opened and closed. The valve in the flow path device 104 is closed by applying a pressing force to the film 202 with the head 203 to deform it, and is opened by releasing the pressing force.

[0047] (i) In this embodiment, the lid of the flow path device 104 is made of a sheet having a thickness of 1 cm or less. Hereinafter, a sheet having a thickness of 1 cm or less will be referred to as a film 202. When a film 202 having an elastic modulus of 10 MPa or more is used, the thickness of the film 202 is preferably 1 mm or less. When a film 202 having an elastic modulus of 100 MPa or more is used, the thickness of the film 202 is preferably 500 μm or less. When a film 202 having an elastic modulus of 400 MPa or more is used, the thickness of the film 202 is preferably 100 μm or less.

[0048] Like the materials listed for the flow path device 104, the film 202 of the flow path device 104 is not particularly limited as long as it is a material commonly used in the relevant technical field. The film 202 may be formed by bonding or fusing multiple layers. Furthermore, the surface bonded to the flow path substrate 201 may be made of a material suitable for bonding, and the opposite surface may be made of a material resistant to tearing and thermal deformation of the film 202. Furthermore, the film 202 is bonded to the flow path substrate 201 by techniques such as heat welding, adhesive, laser welding, chemical bonding, and ultrasonic welding.

[0049] (ii) A valve closes a portion of a flow channel to select a desired path for fluid flow among multiple branched flow channels, or to seal a chamber and increase its internal pressure. By incorporating a valve into the components that make up the flow channel device, the cost of the flow channel device 104 can be reduced. For example, as described in Patent Documents 1, 2, 3, 4, and Non-Patent Document 1, there is a crush valve that crushes and deforms a film with a hard material called a head and presses it against the flow channel substrate 201 to close the flow channel.

[0050] In Figures 2A to 2C, the valve is provided in the flow path device 104 and is composed of a flow path substrate 201 and a film 202. The head 203 applies a downward force to the film 202, deforming it to close the valve, and releases the downward force to open the valve. In Figures 2A to 2C, the direction in which the head 203 moves is the Z axis, the longitudinal direction of the flow path is the β axis, and the direction perpendicular to the β axis of the flow path and the Z axis is the α axis. In a flow path device with multiple valves, the α and β axes may differ between valves. However, because different head and pin shapes for each valve can lead to complexity, it is best to keep the α and β axes consistent as much as possible. Here, the α and β axes do not need to coincide with the X and Y axes of the sliding plate drive system, which will be described later.

[0051] The head 203 can be made of, for example, a hard material (such as SUS or aluminum). By making the head 203 out of a hard material such as SUS or aluminum, the durability of the head 203 can be increased.

[0052] When the flow path substrate 201 is made of a thermoplastic resin, it is preferable that the film 202 is also made of a thermoplastic resin. Using a film made of a thermoplastic resin can reduce the manufacturing cost of the flow path device. Furthermore, by making the flow path substrate 201 and the film 202 from the same material, various physical properties become similar, making design easier. Alternatively, thermal bonding or ultrasonic bonding may be selected.

[0053] Figures 2A(1), 2B(1), and 2C(1) are views of the valve from the α-z plane. Figures 2A(2), 2B(2), and 2C(2) are views of the valve from the β-z plane. Figure 2A shows an example of a valve designed so that the shapes of the flow path 204 and head 203 in the valve section roughly match. In such a valve, the film 202 is deformed by the pressing force of the head 203 and contacts the bottom surface 205 of the flow path, thereby closing the valve. When closing, it is sufficient to sufficiently block the flow of fluid; the film 202 does not necessarily have to be in contact with the bottom surface 205 of the flow path. The valve and head 203 may have shapes that cannot be approximated by a body of revolution about an axis parallel to the Z axis. If the valve has a shape that cannot be approximated by a body of revolution, it is necessary to restrict the movement of the head 203 to prevent it from rotating.

[0054] 2B shows an example of a valve in which the tip of the head 203 has a shape (e.g., a sphere or a cone) that can be approximated by a body of revolution about an axis parallel to the Z axis. A vertical through-hole 206 is formed in the flow channel substrate 201, and the head 203 descends to close the hole.

[0055] 2C is a diagram showing an example of a valve in which the tip of head 203 has a flat surface parallel to the αβ plane. The tip of the valve may have a shape (e.g., a cylindrical shape) that can be approximated by a solid of revolution with respect to an axis parallel to the Z axis. A convex portion 207 is provided on film 202. The valve is closed when convex portion 207 is crushed by the head. If flow channel 204 that comes into contact with convex portion 207 when closed is not flat, the tip of head 203 may have a shape that is not flat so that the valve can be closed appropriately.

[0056] In the following, the structure shown in Figure 2A will be used as an example to explain the shape of the valve, but structures such as those shown in Figure 2B or 2C may also be used, and any shape may be used as long as the head 203 applies a downward force to the surface of the flow path to reduce the cross-sectional area of ​​the flow path and restrict the flow of fluid.

[0057] <Valve Closure Characteristics> The valve closure ratio is an index of the flow rate when a pump continuously delivers a fluid at a constant power or pressure. The ratio is calculated by dividing the flow rate by 0% when the valve is open and 100% when the flow rate is zero. The actual fluid flowing through the valve may be different from the fluid flowing through the valve when the closure ratio is measured. For example, the closure ratio may be measured using air, while an aqueous solution is used in the actual analysis. Alternatively, a diaphragm pump may be used for measuring the closure ratio, while a syringe pump may be used for actual liquid delivery. However, when the valve is closed, the closure ratio is preferably 90%, 99%, or 99.9% or greater. A higher closure ratio reduces the risk of unintended liquid delivery, air leakage, or liquid leakage, thereby achieving more reliable liquid delivery. The valve may be intentionally closed with less force and operated at a closure ratio of 99% or less. For example, when using a low-power actuator to block the flow of an aqueous solution, a low closure ratio can be achieved by making the liquid-contacting surface of the flow path device hydrophobic. Furthermore, by keeping the deformation of the film low, it becomes possible to use the film as a valve that reliably returns to a closure rate of 0% or close to 0% when opened.

[0058] Hereinafter, the term "valve pressure resistance" refers to the minimum pressure at which a fluid can flow past the valve at a rate of 1 L / min or more, 1 mL / min or more, or 1 μL / min or more. The definition of valve pressure resistance may be set appropriately depending on the valve's application and the required closing time. Different types of liquids may have different pressure resistances. The higher the closing ratio, the higher the valve pressure resistance. When blocking an aqueous solution with a valve, the more hydrophobic the liquid-contacting surface of the flow path device is, the higher the pressure resistance. Furthermore, if there is a distance between the branching part of the flow path and the valve part, it is preferable that liquid does not penetrate between the branching part and the valve part. Therefore, it is desirable for the valve to have a high closing ratio that can block both aqueous solutions and air.

[0059] The valve may be opened and closed once or multiple times during a single analysis. Furthermore, the valve may be opened and closed hundreds or thousands of times over multiple analyses. Variations in the valve closure rate or failure to open or close can result in problems such as data inability, sample waste, erroneous results, time waste, and system failure. Therefore, high stability in the valve opening and closing operation must be maintained. Factors that determine the stability of valve opening and closing include the stability of valve depression force control and the stability of valve position control. To prevent valve misalignment, the valve opening and closing system may be equipped with a configuration that limits the movement of the head 203. To ensure that the relative positions of the head 203 and the valve unit are aligned, the head 203 may have a likelihood, or the flow path device 104 may have a likelihood. For example, in Patent Document 1, the head is equipped with a guide blade, and the guide blade penetrates the flow path device to guide the head to the correct position.

[0060] When the film 202 and the flow path substrate 201 are joined with an adhesive, an adhesive layer is placed between the film 202 and the flow path substrate 201, causing the film 202 to deform significantly in order to close the valve, which tends to require a high pressing force to close the valve.

[0061] <Regarding the Depression Force When the Valve is Opened> In this embodiment, as an example, a valve in which the valve depression force and the closure rate are proportional is used. FIG. 3A is a diagram showing the closure rate versus the valve depression force for a valve in which the depression force and closure rate are proportional. Hereinafter, this will be referred to as the depression force-closure rate curve (all figures are conceptual diagrams, not actual measurements). If the depression force required to completely close such a valve is Fc, then if the depression force Fo when the valve is opened is less than half, less than one-fifth, less than one-tenth, or less than one-twentieth of Fc, the closure rate can be set to 50%, less than 20%, less than 10%, or less than 5%. The maximum depression force that can fully open the valve is defined as the maximum opening depression force Fopen.

[0062] In this embodiment, there are also examples in which the second derivative of the closure ratio with respect to the valve depression force exhibits a negative value. Figure 3B shows the closure ratio with respect to the depression force of the flow path valve in this case. In other words, if the required depression force is Fc, and the depression force Fo when the valve is open is equal to or less than one-fifth of Fc, the closure ratio can be reduced to 20% or less. When the film 202 is made of a material that exhibits properties similar to elastic deformation, such as PDMS or polyurethane, the depression force-closure ratio curve when closing the valve and the depression force-closure ratio curve when opening the valve generally coincide, provided that the deformation of the film is not too large. Some hysteresis may occur, but this can be ignored.

[0063] When the film 202 is made of a plastically deforming material such as polypropylene, polyethylene, or PET, the deviation in the push-down force-closing ratio curve between the closed and open states is significant. Figure 3C shows the push-down force-closing ratio curve when polypropylene is used for the film 202. Even with the same thickness, polypropylene films tend to require a higher push-down force than elastically deforming films 202. Because polypropylene exhibits viscoelastic properties, the strain gradually increases with continued application of a constant push-down force, and the elastic modulus decreases with continued application of a constant strain. Therefore, when compared with the same push-down force, the closure ratio is higher when opened than when closed. Therefore, when using polypropylene film, the push-down force (required push-down force) required for closure is higher than with elastic films, and to sufficiently reduce the closure ratio when opened, more careful unloading is required than with elastic films. For example, to achieve a closure ratio of 20% or less when opened relative to the required push-down force Fc, the unloaded push-down force must be 20%, 10%, 1%, or 0% of Fc. When the pressing force is removed, the valve gradually opens due to the internal pressure of the fluid flowing through the flow path and the elastic force of the film 202. If the pressing force remains when the valve is opened, it takes a long time to achieve a sufficient opening rate.

[0064] To achieve such a pressing force, it is preferable to design the sliding plate and pin so that they do not come into contact with the film 202 when released. Furthermore, even if there is slight contact, it is necessary to design the pin so that its pressing force falls within the above range. It is difficult to achieve zero pressing force while keeping the pin and the flow path device 104 in contact when the valve is opened or closed. Therefore, it is preferable to control the Z coordinate of the head 203 so that a distance of 0.5 mm or more is left between the flow path device 104 and the head 203 when the valve is opened. Because the shape of the film 202 does not completely return to its original state when the valve is opened, the head 203 may be in an open state when it is slightly inserted into the groove of the flow path.

[0065] <Depression force when closing the valve> The required depression force can be reduced by designing the valve to be shallow and narrow. Valve hysteresis can also be minimized. However, as the flow path becomes narrower, the flow path resistance increases when the flow path is open, making it necessary to pump liquid and air at high pressure. Furthermore, a narrow flow path increases the frequency of contact between the solution and the flow path wall, raising concerns about reduced sensitivity due to surface adsorption. Therefore, flow path devices 104 capable of highly sensitive analysis tend to require a higher depression force.

[0066] When closing a valve using a film 202 made of a material exhibiting viscoelastic properties, the generated pressing force varies depending on the speed of the head 203 in the Z direction. A faster driving speed of the head 203 in the Z direction increases the maximum pressing force, whereas a slower driving speed in the Z direction decreases the maximum pressing force. Even after closing, the film 202 and the flow path substrate 201 continue to deform. However, if the Z coordinate of the head 203 is fixed at the time of closing, the head 203 cannot keep up with this deformation, resulting in a gradual decrease in the valve's closure rate and pressure resistance. Therefore, when controlling the closure rate using the Z coordinate of the head 203, it is necessary to deform the valve significantly in the Z direction to prevent a decrease in the closure rate and pressure resistance after closing. On the other hand, if an attempt is made to further press the valve after the film 202 has contacted the flow path bottom surface 205, a pressing force equivalent to the elastic modulus of the film 202 and the flow path substrate 201 is generated. The rate of change (rate of increase) of this pressing force with respect to the coordinate in the Z direction is large, for example, 50 N / mm or more, 100 N / mm or more, or 200 N / mm or more.

[0067] If too much force is applied to the valve, the flow path device 104 will be deformed. Furthermore, the drive system and the holding members of the flow path device 104 may be deformed, damaged, or malfunction. Furthermore, the film 202 may be deformed too much, making it difficult to open. Furthermore, the motor of the drive system may lose synchronization and be damaged.

[0068] The maximum force that may be applied to the flow path device 104 is preferably 20 N or less, 15 N or less, or 10 N or less per valve. Furthermore, the force that the flow path device 104 can withstand as a whole is preferably 200 N or less, 100 N or less, or 50 N or less. When multiple valves are operated together with one actuator, if too much force is applied to one valve, it will be impossible to apply sufficient force to the other valves. Hereinafter, the maximum pressing force that will not damage or malfunction the device will be referred to as the allowable pressing force Fmax.

[0069] To summarize the above, in the case of a valve closing characteristic such as that shown in Figure 3C, when opening the valve, the pressing force Fo must be less than the maximum pressing force at opening, Fopen, in order for the valve to be opened. Also, when closing the valve, the pressing force Fc must be greater than the required pressing force, Fclose. However, if the pressing force at closing exceeds the maximum allowable pressing force, Fmax, the device will be damaged. Therefore, the pressing force Fo at opening must satisfy the relationship Fo<Fopen, and the pressing force Fc at closing must satisfy the relationship Fclose<Fc<Fmax.

[0070] Figure 3D shows the measured values ​​of the push-down force-closing ratio curve for a valve shaped as shown in Figure 2A(1) when polypropylene is used for the film 202. Because the film has a high elastic modulus, a fairly strong force is required to close it. Furthermore, because the film undergoes plastic deformation, the valve will not open unless the push-down force is sufficiently released when opening. For this valve, the required push-down force Fclose is 15 N, and Fmax is 20 N. Furthermore, if the closure ratio when opening is set to 20%, the maximum open push-down force Fopen will be 1 N or less. Therefore, it is appropriate to control the push-down force when closing to 15 N to 20 N, and the push-down force when opening to 1 N or less.

[0071] <Sliding Plate Drive System: Valve Opening and Closing System> In the analysis system (fluid control system) 101 according to this embodiment, a sliding plate drive system 301 is used to open and close a valve. (i) FIG. 4A is a diagram showing an example of the configuration of the sliding plate drive system 301 (valve opening and closing system). In FIG. 4A, the head 309 corresponds to the head 203 in FIG. 2A etc. Referring to FIG. 4A, the sliding plate drive system 301 includes, in an XYZ Cartesian coordinate system, a first plate (flow path device) 104, a second plate (pin guide) 302 having a through-hole 310, and a third plate (sliding plate) 303 having a range of motion in the X-axis direction and having irregularities on its surface in the positive direction of the Z-axis. The first plate (flow path device) 104, the second plate (pin guide) 302, and the third plate (sliding plate) 303 are arranged in order along the negative Z-axis direction perpendicular to the Z-axis, and a pin 304 with its central axis parallel to the Z-axis is installed between the first plate 104 and the third plate 303 while passing through a through-hole 310 in the second plate 302. The negative Z-axis end of the pin (sliding plate grounding portion 308) is structured so that the pin 304 can move in the Z-axis direction by following the unevenness of the surface of the third plate 303, which moves in the X-axis direction. In the sliding plate drive system 301 shown in FIG. 4A, the direction in which the pin 304 approaches the valve is defined as the positive Z-axis direction.

[0072] The sliding plate drive system 301 includes one or more sliding plates 303, one or more pin guides 302, and pins 304 having heads 309. The sliding plate drive system 301 can open and close multiple valves with a single actuator. Compared to using an actuator for each valve, the valve spacing is not limited by the size of the actuator, making it easier to use a powerful motor. Furthermore, the motor has ample power, which stabilizes the valve opening and closing operation. Furthermore, the actuator can be shared, allowing for a more compact system. It is also possible to configure the sliding plate drive system 301 without the pins 304, with the heads 309 bonded to the sliding plate 303. However, if the heads 309 are directly attached (bonded) to the sliding plate 303, the force in the X direction of the sliding plate 303 is directly transmitted to the valves, which could result in deformation or tearing of the flow channel device 104. Furthermore, the mechanical energy generated by the friction between the head 309 and the film 202 increases, shortening the life of the head and the sliding plate.

[0073] The sliding plate (third plate) 303 may also be configured to be drivable in the Z-axis direction. In this case, the head 309 can be lowered by lowering the sliding plate 303 in the negative Z-axis direction when inserting a chip (fluidic device 104), allowing for smooth chip insertion. Furthermore, lowering the sliding plate in the negative Z-axis direction when driving a valve reduces friction between the sliding plate and the pressure pin, thereby extending the life of the sliding plate drive system 301. Since the pressure pin only needs to contact the protrusion of the sliding plate 303, the width of the sliding plate 303 in the X-axis direction can be reduced. On the other hand, a drive system is required to move the sliding plate 303 in the Z-axis direction, increasing the number of motors and complicating the system. Furthermore, this system is likely to be larger than a sliding plate drive system 301 that is driven only in the X-axis direction. In this setup, the third plate 303 does not exhibit any sliding behavior against the pressure pin. For this reason, although it cannot be called the sliding plate 303, the part hereinafter referred to as the sliding plate 303 may be replaced with this configuration.

[0074] As shown in FIG. 4A , in the sliding plate drive system 301, the head 309 is installed at the positive end of the pin in the Z-axis direction. The pin 304 converts the movement of the sliding plate 303 in the X-axis direction into movement in the Z-axis direction, thereby applying a pressing force to the valve. Because the head 309 is not directly installed on the sliding plate 303, the movement of the head 309 is limited to the Z-axis direction, which prevents the film 202 of the flow channel device 104 from being torn by friction generated between the head 309 and the flow channel device 104. Furthermore, because the head 309 is not on the sliding plate 303, it is possible to limit the area where the head 309 presses the flow channel device 104 to only the target valve, thereby increasing the degree of freedom in the valve arrangement and valve drive pattern of the flow channel device 104.

[0075] In a typical pin 304, the head 309, the central axis of the pin 304, and the sliding plate ground contact portion 308 are aligned on the same line parallel to the Z axis, or the centers of gravity of each are aligned on the same line parallel to the Z axis. Furthermore, in a typical sliding plate drive system 301, the centers of gravity of the pin 304 and the valve are aligned on the same line parallel to the Z axis.

[0076] The sliding plate 303, pin guide 302, and pin 304 can be made of stainless steel, iron, aluminum, PTFE, elastomer, or a combination of two or more of these materials. Since the sliding plate drive system 301 is used repeatedly, it is desirable that it be made of a highly durable material. The parts that come into movable contact between the sliding plate 303, pin guide 302, and pin 304 may be made of fluorine-based resin to reduce friction. They can also be lubricated with oil. A system that detects wear and prompts replacement may be included.

[0077] (ii) Fig. 4B is a diagram showing the Z coordinate of the sliding plate contact portion 308 from the recessed portion 312 to the protruding portion 311 of the sliding plate 303. As shown in Fig. 4B, the protruding portion 311 and the recessed portion 312 are provided in the positive Z-axis direction of the sliding plate 303, and when the sliding plate is moved in the X-axis direction, the pin moves in the Z-axis direction along the uneven surface 313 of the sliding plate 303.

[0078] (iii) Figure 4C is a diagram showing an example of the configuration of the sliding plate drive system 301. In the sliding plate drive system 301, the sliding plate 303 is driven in the X-axis direction by an actuator 316 and a ball guide / linear guide 315. The rotational power of the actuator is transmitted to the ball guide, causing the sliding plate 303 to move. The actuator 316 is controlled by the computer 102. When driving the sliding plate 303, a stepping motor, a ball screw, and a linear guide 315 work together to move the sliding plate 303 in the X-axis direction. Note that the drive system is not limited to a stepping motor, and various motors and actuators may be used. Figure 4D is a diagram showing another example of the configuration of the sliding plate drive system 301. In the sliding plate drive system 301, the sliding plate 303 is connected to an actuator 316. The actuator 316 is controlled by the computer 102, and the actuator 316 drives the sliding plate 303 in the X-axis direction along the linear guide 315. For example, a hollow motor may be provided in the actuator 316, and the actuator may be driven by the motor. For example, a rack and pinion configuration may be used in which teeth are provided in the linear guide 315, a gear is provided in the actuator 316, and the rotational motion of the motor in the actuator is transmitted to the gear, and the rotation of the gear causes the actuator to run on the teeth of the linear guide. For example, a shaft motor configuration may be used in which the linear guide 315 is provided with a magnet, and the actuator 316 is provided with a coil. By using a configuration such as that shown in FIG. 4D, the space required to install the actuator can be reduced.

[0079] The speed at which the actuator 316 moves does not have to be constant, and it may move slowly in areas where a strong force is applied and quickly in areas where it is not. The time required for one step movement is preferably 0.1 to 10 seconds.

[0080] Furthermore, the size of a typical sliding plate drive system 301 is such that the longest side is 1 m or less, and more preferably 50 cm or less. In the case of a portable analysis system 101, it is preferable that the longest side is 30 cm or less. Therefore, it is necessary to adopt a drive system that matches the size of the analysis system 101.

[0081] The sliding plate 303 may be moved back and forth in the X-axis direction to repeatedly open and close one valve using the same concave and convex portions. Alternatively, the valve may be opened and closed using different concave and convex portions at each step, or concave and convex portions may be used repeatedly in some areas.

[0082] <Example of pin configuration> When multiple valves are driven together by a sliding plate, tilting of the sliding plate 303, pin guide 302, flow path device 104, or pin 304 can prevent other valves from closing. Furthermore, if the pressing force is too strong, damage will occur to the flow path device 104, the sliding plate driving system 301, and the analysis system 101. Therefore, it is preferable to design the pressing force so that the maximum possible value is within 20%, 50%, 100%, or 200% of the required pressing force.

[0083] To achieve such a pressing force, it is necessary to incorporate a structure in the pin 304 that can control the pressing force during closing. Examples include incorporating a compression spring (first spring 306) in the pin 304, making part or all of the pin 304 out of an elastic material, or installing a repulsive magnet in the pin 304. Such a mechanism is called a transmission mechanism. The transmission mechanism transmits a change in the position of the lower part of the pressing pin to the flow channel device 104 as a change in the pressing force.

[0084] Furthermore, the pins 304 may not move smoothly due to friction with the pin guide (pin holder) 302, the sliding plate 303, and / or the flow channel device 104. For this reason, a follow-up mechanism is needed to provide a force for pressing the pins 304 against the sliding plate 303.

[0085] 4A , the pin 304 according to this embodiment includes a sliding plate contact portion 308, a pin lower portion 305, a follower mechanism (second spring) 307, a pin upper portion 309, and a transmission mechanism (first spring) 306. The pin upper portion 309 may include a head 203 at the positive end of the Z axis, or the head 203 may constitute the pin upper portion 309. In the following description, it is assumed that the head 203 is included in the pin upper portion 309.

[0086] The pin upper part 309, the pin lower part 305, and the transmission mechanism 306 may have a separable structure, may be made of a single member, or may be joined together. The pin upper part 309 and the pin lower part 305 may be made of different materials. The entire pin 304 may be made of an elastic material. The pin upper part 309 and the pin lower part 305 may be joined to each other. Alternatively, the pin upper part 309 may be joined to the upper end of the transmission mechanism 306 in the Z-axis direction, and the pin lower part 305 may be joined to or in contact with the lower end of the transmission mechanism 306. Furthermore, if there are any unjoined portions between the pin upper part 309, the pin lower part 305, and the transmission part 306, the pin upper part 309 may be able to rotate freely relative to the pin lower part 305, so a non-jointed configuration is easier to manufacture and less likely to break.

[0087] The pin upper portion 309 may be configured so that the length in the Z-axis direction is variable. In this case, for example, the overall length of the pin 304 is shortened when the pin 304 is pressed against the flow path device 104, and is lengthened when the pin 304 is in contact with the recess 312 of the sliding plate 303.

[0088] The sliding plate contact portion 308 is configured, for example, as a rounded rod with its curved surface in contact with the sliding plate 303. Alternatively, the sliding plate contact portion 308 may be configured as a sphere and follow the sliding plate 303 in a rolling manner. Alternatively, the sliding plate contact portion 308 may be configured as a tire-shaped member. The tire-shaped member may be made of rubber, PTFE, or metal. The tire-shaped member may also have a bearing structure. In this case, the portion that contacts the bearing and bearing shaft may be made of metal. The portion of the sliding plate contact portion 308 that contacts the sliding plate 303 while rolling is preferably made of plastic such as PTFE or coated with plastic. Note that the cross-sectional area of ​​the pin in the XY plane can be made smaller when a cylindrical tire with a plane parallel to the XZ plane is used for the sliding plate contact portion 308 than when the sliding plate contact portion 308 is made of a sphere.

[0089] Furthermore, if the upper pin portion 309 and the lower pin portion 305 are configured to be separable, it is preferable that a catch structure be provided inside the pin 304, or between the pin 304 and the pin guide (pin holder) 302, or between the pin 304 and the sliding plate 303, so that the pin does not come loose after being incorporated into the drive system.

[0090] The length of the pin 304 in the Z-axis direction is preferably 10 cm or less, more preferably 3 cm or less. If the pin 304 is long, the accuracy of valve closure will decrease due to bending or tilting of the pin 304. It is also preferable that the radius of the pin 304 or the maximum distance from the central axis is 8 mm or less, more preferably 4 mm or less. It is preferable that the length in the Y-axis direction is 5 mm or less. Note that if the diameter or distance from the central axis of the pin 304 is large, multiple pins 304 will interfere with each other when multiple valves are installed. This requires that the valves be spaced apart, reducing the degree of freedom in valve placement.

[0091] <Pin Guide> The pin guide 302 is provided to limit (restrict) the movement of the pin 304. The pin guide 302 has a through hole 310. The pin 304 is installed in a state where it passes through the through hole 310. The through hole 310 may be designed to partially contact the pin 304 in order to support the posture of the pin 304. A portion of the through hole 310 that the pin 304 may contact may be provided with a bearing or may be filled with a lubricant. The pin guide 302 may also have a magnet as part of its configuration.

[0092] 4C , the flow channel device 104 is placed so as to be sandwiched between a device holder 314 and a pin guide 302. The device holder 314 and the pin guide 302 may be joined together or may be integrally molded. The device holder 314 may be provided with or have ports for connecting to a heater, an optical detection device, or a pump.

[0093] It is preferable that the distance between the pin guide 302 and the flow channel device 104 is set as short as possible. The pin guide 302 and the flow channel device 104 may be in contact with each other. The pin guide 302 may also serve as a fixing member for fixing the position of the flow channel device 104 in whole or in part. By reducing the distance between the pin guide 302 and the flow channel device 104, the degree of freedom (freedom of movement) of the pin 304 can be reduced. The movement distance in the Z-axis direction required for the pin 304 to move from a state where it does not protrude from the pin guide 302 to when it comes into contact with the flow channel device 104 can be minimized. This makes it possible to reduce the size of the unevenness of the sliding plate 303. It is preferable that the XYZ coordinate system of the pin guide 302 is always fixed during analysis.

[0094] <Regarding the Tracking Mechanism> The tracking mechanism 307 presses the pin 304 against the sliding plate 303, and maintains contact of the sliding plate grounding portion 308 with the unevenness of the sliding plate 303. Hereinafter, the force exerted by the second spring 307 as the tracking mechanism to repel the pin 304 against the sliding plate 303 with respect to the pin guide 302 will be referred to as a tracking force.

[0095] If the follower mechanism 307 is not provided, while the head 309 is in contact with the flow path device 104, the head 309 follows the sliding plate 303 due to a repulsive force from the flow path device 104. If gravity acts in the Z positive direction or if there is a frictional force between the pin 304 and the pin guide 302, the pin 304 will no longer follow the sliding plate 303 if the repulsive force is less than the frictional force. If the force of gravity acting in the Z positive direction and the frictional force act additively and exceed the maximum valve opening depression force, the valve will not open completely.

[0096] 5A to 5D are diagrams showing examples of various tracking mechanisms. In these figures, the transmission mechanism 306 is omitted. Note that multiple tracking mechanisms may be combined.

[0097] (i) Second spring-based tracking mechanism Fig. 5A is a diagram showing an example in which the tracking mechanism 307 is configured with an elastic body (spring). Hereinafter, the tracking mechanism configured with an elastic body will be referred to as a second spring.

[0098] The repulsive or contractile force of the follower mechanism 307 applies a downward force in the Z-axis direction to the pin 304 relative to the pin guide 302, thereby maintaining contact of the sliding plate grounding portion 308 with the sliding plate 303. For example, a compression spring or a tension spring can be used as the second spring 307. It is desirable to set the spring constant of the compression or tension spring as small as possible. When a spring is used in the follower mechanism, the spring constant is preferably in the range of 0.01 N / mm to 5 N / mm. It is desirable that the elastic force of the spring be 0.1 N to 5 N when the valve is closed and 0.05 N to 4 N when the valve is open.

[0099] In the following explanation, the case where a second spring is used as a representative of various follow-up mechanisms will be mentioned, but the follow-up mechanism is not limited to a spring and may have a similar function.

[0100] 5B and 5C are diagrams showing an example in which the tracking mechanism 307 is configured with a magnet. The magnet may be a permanent magnet or an electromagnet.

[0101] 5B, a magnet 317 is provided on the side surface of the sliding plate of pin guide 302, and a magnet 318 is provided on pin lower portion 305. In addition, the same poles of the magnets face each other, and when the magnet of pin 304 approaches the magnet of pin guide 302, a stronger repulsive force is obtained, which can be used as a tracking force.

[0102] As shown in Figure 5C, the tracking mechanism 307 is provided between the pin 304 and the sliding plate 303. A magnet or magnetic material 319 is provided on the pin lower part 305, and a magnet or magnetic material 320 is provided on the sliding plate 303. At least one of the member 319 or the member 320 needs to be a magnet, and if both are magnets, the poles face in opposite directions. The action of the magnet and the magnet or magnetic material attracts the pin 304 to the sliding plate 303, thereby maintaining contact.

[0103] The tracking mechanism 307 can be replaced by gravity. This can be achieved when the angle between the Z axis and gravity is 90° or less, more preferably 45° or less, and even more preferably 10° or less. When the tracking mechanism 307 is replaced by gravity, there is no need to use magnets, springs, or the like, and therefore the pin 304 can be designed to be small and easy to use. When the tracking mechanism 307 is replaced by gravity, it is desirable that the gravity acting on the pin 304 in the negative Z axis direction be 0.1 N or more, more preferably 0.5 N or more, and even more preferably 1 N or more.

[0104] (iii) Guide Structure of the Sliding Plate Grounding Portion 308 Figure 5D is a diagram showing the guide structure of the sliding plate grounding portion 308. As shown in Figure 5D, the sliding plate 303 may be configured so that the upper limit of movement of the sliding plate grounding portion 308 and the pin lower portion 305 in the Z-axis direction is limited by the sliding plate 303. For example, the sliding plate 303 may be configured in a U-shape to limit the movement of the pin 304 both above and below the Z-axis. The guide 321 located at the top of the U-shape of the sliding plate 303 may be configured to press against the sliding plate grounding portion 308 (roller) or to press against a protrusion 322 of the pin lower portion 305.

[0105] <Regarding the Transmission Mechanism> The transmission mechanism 306 has the function of transmitting the displacement applied to the pin 304 from the sliding plate ground contact portion 308 to the valve as a force so as to create an appropriate load. The transmission mechanism 306 can employ a mechanism whose length in the Z-axis direction is variable and which applies a repulsive force in the Z-axis direction when the length becomes shorter.

[0106] It is desirable that transmission mechanism 306 is a mechanism that can apply a highly reproducible pressing force F=f(z)n to the valve in the range of displacement z1≦z≦z2 when the valve is closed, relative to displacement z in the Z-axis direction when the valve is closed. For example, upper pin 309 and lower pin 305 are each in contact with transmission mechanism 307.

[0107] 6A to 6C are diagrams showing examples of various transmission mechanism configurations. Note that the tracking mechanism is omitted in these figures. Furthermore, multiple transmission mechanisms shown in FIGS. 6A to 6C may be combined to form a single transmission mechanism.

[0108] (i) Figure 6A is a diagram showing an example in which the transmission mechanism is configured with an elastic body. The elastic body can be a compression spring, rubber, or air. In the following, the transmission mechanism 307 using an elastic body is referred to as a first spring 307.

[0109] (ii) Fig. 6B shows an example of a transmission mechanism in which magnets 317 that repel each other are installed at the bottom end of the upper pin and the top end of the lower pin. In Fig. 6B, a stronger repulsive force is obtained when the bottom end of the upper pin (head) 309 and the top end of the lower pin 305 approach each other.

[0110] The sliding plate grounding portion 308 may be configured to also function as the transmission mechanism 307. For example, the sliding plate grounding portion 308 can be configured from an elastic body such as rubber or elastic resin, thereby realizing the function of the transmission mechanism 307.

[0111] (iii) Figure 6C shows a configuration example in which the transmission mechanism 307 is provided on the flow channel device 104 side. In this case, as described in U.S. Patent No. 11,305,278, attaching an elastic sheet 323 to the film 202 makes it possible to control the pressing force and repulsive force. Furthermore, if the film 202 is made of an elastic material, it may be possible to stably open and close the valve without providing a separate transmission mechanism 307. However, it is difficult to accurately control the pressing force during closing simply by attaching an elastic sheet to the film surface or if the film itself is made of an elastic material. Furthermore, if the elastic sheet 323 tends to stick to the head 309, there is a risk of damage to the head 309 or the film 202 when removing the flow channel device 104. To prevent this, it is necessary to install a second spring with sufficient strength so that the head 309 is sufficiently separated from the flow channel device 104 in the recess, and to set a sufficiently small Z0 (depth of the recess).

[0112] In the following description of this embodiment, we will refer to the case where a first spring is used as a representative of various transmission mechanisms, but the transmission mechanism is not limited to a spring and may also be a transmission mechanism with a similar function.

[0113] <Regarding the Surface of the Sliding Plate> With the sliding plate drive system 301 stopping the sliding plate 303, a specific flow path is pressurized / depressurized to transport the fluid. Alternatively, the flow rate may be gradually changed by transporting the fluid while moving the sliding plate 303. Immediately after the sliding plate 303 stops, the closing rate of the valve may change, but after a sufficient time, for example, 10 seconds or more, has passed, the closing rate will not change significantly.

[0114] The recessed portion 312 and the protruding portion 311 of the sliding plate 303 refer to portions that are lower and higher than adjacent portions of the sliding plate 303 in the X-axis direction. The uneven portions include slopes along the way. The uneven surface 313 where the uneven portions of the sliding plate 303 and the sliding plate contact portion 308 contact is basically a continuous surface in the X-axis direction. If there is a gap or an extreme step along the uneven surface 313, the sliding plate contact portion 308 may get caught. For convenience, corners are drawn at the boundaries between the slopes and flat portions in the drawing, but in reality, the uneven surface 313 is made smooth along the X-axis direction.

[0115] The angle (slope angle) formed by the slope of the sliding plate 303 and the X-axis must be a maximum of 90° or less. More preferably, the slope angle is 75° or less. For smooth movement, the slope angle (maximum angle) is 45° or less (the lower limit of the maximum slope angle can be, for example, 10° or more). A small slope angle increases the width of the sliding plate 303. It is preferable that the slope angle change continuously so that the sliding plate surface is smooth. If all slope angles are 10° or less, the width of the sliding plate 303 in the X-axis direction would need to be at least five times the height of the unevenness of the sliding plate 303, which is disadvantageous. More preferably, the maximum slope angle is 20° or more. A large slope angle (maximum slope angle) generates strong friction between the sliding plate 303 and the sliding plate contact portion 308, shortening the life of the sliding plate drive system 301. Also, since a heavy load is placed on the motor, a powerful motor must be used.

[0116] Hereinafter, the term "sliding plate step" refers to the uneven portion of the sliding plate that can determine the open / closed state of one valve or a combination of the open / closed states of multiple valves. In other words, the sliding plate step refers to either the recessed portion 312 or the protruding portion 311 of the sliding plate 303 when there is one valve, or to a combination of recessed or protruding portions that act simultaneously on multiple valves when multiple valves move in conjunction. The height of the uneven portion can control the open / closed state of the valve and the pressing force.

[0117] In the following description, a portion of the sliding plate that includes a series of concave and convex portions used to drive one valve will be referred to as a concave and convex lane 325. All the concave and convex portions on the same concave and convex lane are on the same Y coordinate.

[0118] <Tooth Height of Sliding Plate 303> The tooth height of the sliding plate 303 refers to the difference between the portion of the adjacent concave portion with the smallest Z coordinate and the portion of the adjacent convex portion with the largest Z coordinate (the height difference between the concave portion 312 and the convex portion 311), or the height of the portion of the convex portion with the largest Z coordinate relative to the reference Z coordinate. Typical tooth heights of the sliding plate 303 are 0.1 mm or less, 0.5 mm or less, 1 mm or less, 2 mm or less, 3 mm or less, 5 mm or less, 7 mm or less, or 10 mm or less.

[0119] The lower the tooth height, the smaller the size of the sliding plate drive system 301 in the Z-axis direction can be, and since the width of the slope can be designed to be shorter, the size in the X-axis direction can also be reduced. Among the uneven portions existing on the same uneven lane, there may be convex portions 311 for strongly crushing the valves and convex portions 311 for weakly crushing the valves. Furthermore, the flow path device 104 may be provided with valves of different shapes and sizes, and a sliding plate 303 that can apply the necessary pressing force to each may be used.

[0120] By allocating appropriate heights to the teeth, it is possible to reduce the height of the teeth and reduce the overall size of the sliding plate 303. In addition, by appropriately setting the pressing force, it is possible to reduce the load resistance required of the sliding plate drive system 301.

[0121] The height of the teeth may be different between the step of inserting the flow channel device 104 and the step of opening the valve during processing. The Z coordinate of the recess defining the step of opening the valve during processing may be greater than the Z coordinate of the recess 312 when inserting the flow channel device 104. By keeping the pins 304 sufficiently away from the flow channel device 104 when inserting the flow channel device 104 into the analysis system 101, the flow channel device 104 can be inserted smoothly without getting caught on the pins 304. In addition, the pins 304 are less susceptible to impact during insertion. Furthermore, when a valve is closed and then opened once, the film 202 may be plastically deformed and become recessed from its original shape. Therefore, even if a recess of a height that allows the head 309 to touch the film 202 before plastic deformation of the film 202 is formed during processing, this does not affect the liquid transfer performance after plastic deformation of the film 202. Furthermore, in steps other than the step of inserting the flow path device 104, the recess may be set to a height that allows the head 309 to touch the film 202 even before the film 202 is plastically deformed. In order to achieve the same opening rate before and after the film 202 is plastically deformed, the recess may be set higher by an amount that corresponds to the amount of plastic deformation remaining in the film 202 when opening after closing. In this configuration, when the sliding plate 303 transitions from the insertion step to the first valve opening / closing step, the film 202 on the valve that is maintained in the open state is also slightly deformed.

[0122] 7 is a diagram showing an example of the configuration of the sliding plate 303 having recesses 312 at multiple height levels. In this example, the sliding plate 303 includes a protrusion 311, a recess 312, and a second recess 324. The second recess 324 is configured so that the pin 304 can be pressed down deeper than the recess 312. Furthermore, the second recess 324 determines the Z coordinate of the lower end of the pin in step I.

[0123] Step I may be a recess that is used when inserting the flow path device 104 and when removing it after analysis. In step II, the protrusion 311 pushes up the pin 304, closing the valve. In step III, the recess 312 comes into contact with the lower end of the pin, pushing down the pin 304. In the recess 312, the upper end of the head 309 may protrude from the pin guide 302. By using different heights of the recesses in this way, the height of the teeth of each sliding plate step can be minimized and the width of the slope between them can be reduced, contributing to a smaller width of the sliding plate.

[0124] A connection port for a heater or a pump may be located in the positive Z-axis direction of the space for installing the flow path device 104. In this case, it is preferable to insert the flow path device 104 in the Y-axis or X-axis direction. If the pins 304 protrude from the pin guide 302 when installing the flow path device 104, the flow path device 104 may collide with the pins 304, making insertion difficult or even damaging the pins 304. When installing the flow path device 104 toward the pin guide 302 from the positive Z-axis direction, it may be possible to install the flow path device 104 without providing a step to lower all of the pins 304 below the top surface of the pin guide 302. However, the pins 304 may get caught in an unintended portion of the flow path device 104, preventing proper installation. In particular, when an unfamiliar person uses the analysis system 101, it is necessary to make the flow path device 104 easy to insert.

[0125] <Reagent Unsealing Operation by Sliding Plate Drive System 301> The sliding plate drive system 301 may open and push out the reagent reservoir 402 provided in the flow path device 104. Fig. 8 is a diagram showing the operation of using the sliding plate drive system 301 to crush and open the reagent reservoir 402 and release the reagent into the flow path 204.

[0126] The reagent reservoir 402 is provided with reagent sealing members 401 on the top and bottom, and the reagent stored therein is released into the flow path 204 by increasing the Z coordinate of the reagent sealing member on the negative side of the Z axis. At this time, the reagent sealing member 401 may be moved using a pin 304. When the reagent is released, the reagent is released according to the amount of movement of the reagent sealing member. The reagent sealing member may also be made of a material that easily deforms. When such a configuration is adopted, the first spring 306 may not be provided, particularly on the pin 304 for releasing the reagent. When releasing the reagent, a larger Z displacement is required than when closing the valve. Since the first spring 306 is not present, if the pin 304 does not compress, the reagent can be released with the same concave-convex height as the concave-convex height used to open and close the valve.

[0127] Furthermore, reagent storage sections 402 arranged on the same Y coordinate (X axis) may be sequentially opened and released using one concave-convex lane. If the released reagent flows back into the reagent storage section 402 due to the elasticity of the reagent sealing member or the like after the reagent is released, it is preferable to configure the reagent release pin 304 to always remain in contact with the convex section 311 of the sliding plate 303 after release.

[0128] A concave-convex lane for reagent unsealing may be incorporated into the sliding plate 303 used for valve opening and closing. However, since it is preferable that reagent unsealing begin after the valve opening and closing operations are completed, an independent valve step may be prepared. If reagent unsealing and valve opening and closing are incorporated into the same sliding plate 303, the sliding plate 303 will be longer by the length of the incorporated reagent unsealing step. Therefore, the sliding plate 303 for reagent opening and closing may be installed independently from the sliding plate 303 for valve opening and closing. If multiple crushing reagents are installed, they may all be unsealed using a single sliding plate 303.

[0129] 9A to 9D are diagrams showing examples of the arrangement of the second spring and the first spring. The second spring may be a tension spring or a compression spring.

[0130] 9A , the second spring 307 is a compression spring and is in contact with the pin lower portion 305 and the pin guide 302. The second spring 307 is in contact with the surface (bottom surface) of the pin guide 302 that can be seen from the negative Z direction. In this configuration, the pin guide 302 can be designed to be in contact with the pin upper portion 309 and the flow channel device 104. The second spring 307 does not need to be joined to other members. The second spring 307 can limit the movement of the pin upper portion 309 (head) and the flow channel device 104.

[0131] 9B, the second spring 307 is formed of a tension spring and is in contact with the pin lower part 305 and the pin guide 302. The second spring 307 is in contact with the surface (top surface) of the pin guide 302 that can be seen from the Z positive direction. In this configuration example, it is somewhat difficult to design the pin guide 302 so that it is in contact with the flow channel device 104 while also being in contact with the pin upper part, and this requires assembly by combining multiple components. In addition, the upper and lower ends of the second spring (tension spring) 307 must be joined to the pin lower part 305 and the pin guide 302, respectively.

[0132] 9C, the second spring 307 is formed of a compression spring and is in contact with the pin upper portion 309 and the pin guide 302. In this configuration example, similar to the configuration example shown in FIG. 9A, it is relatively easy to design the pin guide 302 so that it is in contact with the flow channel device 104 while being in contact with the pin upper portion.

[0133] 9D, the second spring 307 is a tension spring and is in contact with the pin upper part 309 and the pin guide 302. In this configuration example, it is somewhat difficult to design the pin guide 302 so that it is in contact with the flow channel device 104 while also being in contact with the pin upper part, and it is necessary to assemble it by combining multiple components. In addition, the upper and lower ends of the second spring (tension spring) 307 must be joined to the pin lower part 305 and the pin guide 302, respectively.

[0134] The second spring 307 shown in Figures 9B and 9D is shown as two tension springs in the drawings for ease of viewing, but in reality, one tension spring may be installed around the outer periphery of the pin.

[0135] 10A and 10B show an example of the structure of the pin 304 and the sliding plate drive system 301. FIG. 10C is a diagram showing an example of the cross-sectional structure of the spring plunger 501. The spring plunger 501 includes a spring storage portion 510, a protrusion 511 that is pushed out by the spring, and a first spring (compression spring) 306. In the following, the spring storage portion 510 is illustrated as constituting a part of the pin upper portion 309, and the protrusion 511 is illustrated as constituting a part of the pin lower portion 305, but they may be upside down. The first spring 306 is installed inside the spring plunger 501.

[0136] The second spring 307 is a compression spring that applies a repulsive force to the protrusion 322 of the pin lower portion 305 and the pin guide 302. The second spring 307 is installed so that the upper portion of the second spring 307 fits into a second spring recess 502 provided in the pin guide 302 to prevent buckling deformation, and is installed so that the second spring 307 is in contact with the outer periphery of a second spring base 503 provided in the pin lower portion 305. The second spring recess 502 is desirably formed to have the same or larger diameter as the second spring 307. The second spring base 503 is desirably formed to have the same or larger diameter as the second spring 307. Furthermore, the second spring base 503 does not need to be circular when viewed from the XY plane, and may have a shape such as an ellipse or rectangle extending in the X-axis direction. It is preferable to design the second spring base 503 so that its long side is longer than the second spring 307 to prevent the second spring 307 from slipping out.

[0137] When the pin 304 is in contact with the protrusion 311 of the sliding plate 303, the base 503 of the second spring is configured to be located in the negative Z-axis direction relative to the pin guide 302. The pin guide 302 is provided with a base recess 504, and it is preferable that the recess is formed larger than the outer periphery of the base 503 of the second spring so that the protrusion 322 fits into the base recess 504 when the pin 304 is in contact with the protrusion 311 of the sliding plate 303.

[0138] The upper and lower portions of the pin do not have to be joined to the second spring 307 and the first spring 306, respectively. It is preferable that when the pin 304 is in contact with the convex portion 311 of the sliding plate 303, the pin guide 302 and the lower portion of the pin or the upper and lower portions of the pin come into contact with each other to apply a repulsive force. Also, the second spring 307 does not have to be joined to the protrusion 322. Therefore, when the valve is open (when the second spring 307 is not elastically deformed), the second spring 307 does not have to be in contact with the protrusion 322. On the other hand, when the valve is closed (when the second spring 307 is elastically deformed), the second spring 307 is configured to come into contact with (connect to) the protrusion.

[0139] To prevent the spring plunger 501 from extending beyond its initial length or from coming apart from its upper and lower parts, a lip (barb) 505 can be provided at the negative Z end of the spring storage part 510, and a catch 506 can be provided at the positive Z end of the protrusion 507. In this case, it is preferable to configure the lip 505 so that it catches on the protrusion 507, and the catch 506 so that it is housed on the spring storage part side.

[0140] Fig. 10B shows a structure equivalent to Fig. 9C. In the example structure of Fig. 10B, the second spring 307 can be installed so as to contact the second spring base 503 provided on the pin upper portion 309.

[0141] 9A and 9B, the second spring 307 according to this embodiment is in contact with the pin lower portion 305 and presses the pin lower portion 305 against the sliding plate 303. An advantage of this structure is that the forces exerted by the second spring 307 and the first spring 306 on the sliding plate 303 are independent of each other, making spring design easy. Another advantage is that the force of the second spring 307 does not affect the first spring 306, allowing the first spring 306 to be designed with a lighter load capacity.

[0142] 9A and 9B, it is necessary to prevent a negative force from being applied to the first spring 306 due to frictional force or the action of the second spring, causing the first spring 306 to stretch beyond its reference length or causing the upper and lower pin portions to separate. For this reason, it is preferable that the spring plunger 501 has a structure such as a rim portion (barb) 505 and a catch portion 506 as shown in FIG. 10C.

[0143] 10B or 9C and 9D, the follower mechanism (second spring 307) is in contact with the upper part of the pin and presses the variable-length upper part of the pin and the fixed-length lower part of the pin together against sliding plate 303. In this structure, a compressive force is always applied to first spring 306, so the upper and lower parts of pin 304 do not come apart even if spring plunger 501 does not have lip (barb) portion 505 and catch portion 506. In this configuration, the upper part of the pin can be reliably pulled down when released.

[0144] <Regarding the pin movement direction and the position control of the valve and pin> (i) Overview It is desirable that the head 309 applies a pressing force to the flow channel device 104 while maintaining the correct posture. If the movement direction of the head 309 deviates from the Z axis, the tip of the head will not be positioned correctly at the valve. In the case of a valve such as that shown in Figure 2A, because the head 309 is not a rotating body about an axis parallel to the Z axis, if the upper part of the pin rotates relative to the lower part, it becomes difficult to close the valve, or the valve may not be closed at all.

[0145] A positioning mechanism may be provided between the flow path device 104 and the device holder 314 (see Figure 4C) or the pin guide 302 so that the αβ coordinates of the flow path device 104 do not change relative to the XY coordinates during or between analysis rounds.

[0146] Furthermore, if the central axis of pin 304 is misaligned and is no longer parallel to the Z axis, the distance between head 309 and the valve will change, making it impossible to close the valve or causing insufficient or excessive pressing force. One way to prevent pin 304 from losing its orientation is to position the center of gravity and contact point of pin 304 and the center of gravity of second spring 307 on the same XY coordinate system.

[0147] For example, as in Patent Document 1, a guide blade is attached to the head, a hole is provided in the flow path device through which the guide blade can be inserted, and the head orientation is given a margin of error so that the guide blade and the hole are aligned, allowing the head to be correctly inserted into the valve section. However, if the head position moves outside the range that can be corrected by the guide blade, it cannot be restored. Furthermore, since the head is connected to an arm and the structure does not create a rotation margin, there is no structure for controlling the rotation margin.

[0148] (ii) Alignment by the Slider Drive System 301 In this embodiment, an alignment mechanism may be provided between the analysis system 101 and the flow channel device 104 to align the αβ coordinates of the flow channel device 104 with the XY coordinates. For example, the flow channel device (chip) 104 may be provided with a depression or hole for alignment, or with a protrusion for alignment. Alternatively, the flow channel device 104 may be aligned by the slider drive system 301.

[0149] 11 is a diagram showing an example of a configuration in which the fluid channel device 104 is aligned by the sliding plate drive system 301. As shown in Fig. 11, the fluid channel device 104 is provided with alignment holes 403. After the fluid channel device 104 is inserted into the analysis system 101, the alignment pins 304' are moved in the positive direction of the Z axis by the sliding plate 303, and the alignment pins 304' are fitted into holes or recesses (alignment holes 403) in the fluid channel device (chip) 104, thereby achieving alignment.

[0150] During alignment, the alignment pin 304' only needs to be stopped at an appropriate height in the alignment hole 403 of the flow channel device 104, and therefore the alignment pin 304' does not need to have the first spring 306. It is preferable to provide two to four alignment pins 304' and alignment holes 403 for one flow channel device 104. The head 309 of the alignment pin 304' and the alignment hole 403 have a tapered structure and can be designed so that the likelihood of the XY coordinates decreases as the Z coordinate increases.

[0151] (iii) Control of Rotation Likelihood In this embodiment, a non-bonded transmission mechanism is inserted between the upper pin (head 309) and the lower pin 305. In addition, in this embodiment, the pin 304 is not bonded to the sliding plate 303. Therefore, the upper pin (head) 309 and the lower pin 305 are configured so that they are each given a likelihood of rotation and movement with respect to the XYZ coordinate system. When using such a pin 304, a method is required to limit the likelihood of rotation direction and positional deviation.

[0152] The transmission mechanism 306 uses an elastic body such as hard rubber or a leaf spring, and the elastic body is joined to the upper pin 309 and lower pin 305. Furthermore, if rotational deformation (twist) on the XY plane does not occur in the elastic body, the rotational likelihood of the upper pin 309 can be limited by the lower pin 305.

[0153] In the following, when the sliding plate contact portion 308, the lower pin 305, and the upper pin 309 have a rotational likelihood on a plane parallel to the XY plane, the longitudinal direction of the flow channel when each is oriented in the most favorable direction for valve closure is set as the β axis, the direction perpendicular to the β axis and the Z axis is set as the α axis, and the plane parallel to the XY plane is set as the αβ plane. The αβ axis of the valve of the flow channel device 104 is assumed to be fixed with respect to the XY axes.

[0154] It is desirable that the αβ axis direction of the flow channel device 104 and the αβ axes of the sliding plate grounding portion 308, the pin lower portion 305, and the pin upper portion 309 always coincide with each other when the sliding plate is driven or stopped. In particular, it is desirable that the αβ axis directions of the pin upper portion 309 and the flow channel device 140 always coincide with each other.

[0155] If the sliding plate contact portion 308 is designed to roll as a sphere, the αβ axis of the sliding plate contact portion 308 can rotate freely with respect to the XY axes of the sliding plate 303. In addition, the αβ axis of the lower part of the sliding plate 303 can also rotate freely with respect to the αβ axis of the sliding plate contact portion 308. On the other hand, if the sliding plate contact portion 308 is cylindrical and the pin lower part 305 is connected to the sliding plate contact portion 308 via a shaft, the αβ axis of the pin lower part 305 can be fixed with respect to the αβ axis of the sliding plate contact portion 308.

[0156] Several methods for restricting the movement of the head are listed below. A combination of the following methods may be used, which is preferable because it allows for more reliable restriction of the head movement. Figures 12A to 12C are diagrams showing examples of methods for maintaining the orientation of the head 309 inside the pin or between the pin 304 and the pin guide 302.

[0157] As shown in FIG. 12A , the rotational likelihood of the αβ axis of the pin upper portion 309 can be limited by the inner wall of the through-hole 310. In the method shown in FIG. 12A , the pin upper portion 309 has a portion that is not circular when cut in the XY plane, and a similarly shaped portion exists in the through-hole 310. Alternatively, a key groove may be formed in the through-hole 310, and a protrusion 601 that fits into the key groove may be provided on the pin upper portion 309. By adopting such a structure, the αβ axis of the pin upper portion 309 can be fixed relative to the XYZ coordinate system or its likelihood can be reduced. The smaller the gap between the through-hole 310 and the pin upper portion 309, the more precisely the head posture can be controlled. However, a smaller gap increases the frictional force acting between the inner wall of the through-hole 310 and the pin upper portion 309. Furthermore, if the posture of the pin lower portion 305 is disrupted, a force is applied in directions other than the Z axis, increasing the frictional force. It is necessary to design a tracking mechanism so that the tracking force exceeds the friction force and the pin 304 can follow the sliding plate 303. Furthermore, when the αβ axis of the pin upper portion 309 is aligned with the αβ axis of the flow channel device using only the method shown in Fig. 12A, a large tracking force and strict design are often required, so other methods must also be used for control.

[0158] The αβ axis of the pin upper part 309 can be aligned with the αβ axis of the pin lower part 305, or the rotational likelihood can be limited. FIG. 12B is a diagram showing an example of limiting rotation by generating a friction force between the outer wall of the pin lower part 305 and the inner wall of the pin. In this example, the pin lower part 305 is partially inserted into the interior of the pin upper part 309. As shown in FIG. 12B, the outer wall of the pin lower part 305 has a portion that is not circular when cut in the XY plane, and the pin upper part 309 has an inner wall of a similar shape. Furthermore, as shown in FIG. 12C, the range of motion of the pin upper part 309 may be limited by the outer wall of the pin upper part 309 and the inner wall of the pin lower part 305.

[0159] If the αβ axes are aligned above and below the pin, and if the αβ axis at the bottom of the pin is aligned with the αβ axis of the sliding plate contact area, and if the αβ axis of the sliding plate contact area has sufficient rotational flexibility limited relative to the XY axes, then the αβ axis at the top of the pin and the αβ axis of the flow path device can be controlled.

[0160] By using a sliding plate 303 having a structure as shown in Figures 13(1) and 13(2), the range of motion of the sliding plate ground contact portion 308 can be limited by the sliding plate 303. Rail guides 602 as shown in Figure 13(2) are provided on the sliding plate 303. Figure 13(2) shows a configuration example in which rail guides 602 are provided so as to contact both sides of the roller parallel to the XY plane, thereby limiting movement of the sliding plate ground contact portion 308 so as not to shift in the Y direction, and a configuration example in which grooves 603 are dug in the roller, and the guides of the sliding plate 303 fit into the grooves 603, limiting movement so as not to shift the sliding plate ground contact portion 308 in the Y direction.

[0161] As shown in Figure 13, the sliding plate contact part 308 is composed of a gear (pinion). A rack is provided on the sliding plate 303. The pinion and rack mesh together to limit the movement of the sliding plate contact part 308 to the Z direction. This shape is also seen in the Abt system, a rack-type railway system. By using this system, the movement of the pin can be accurately controlled even if the angle of the slope is large.

[0162] (iv) Example of Pin Structure Figure 14 is a diagram showing an example of pin design. The pin 304 includes a roller 308 including a bearing, a protrusion 322 provided on the pin lower portion 305, and a leg 513, and the roller 308 and the leg 513 are connected by a shaft 512. The pin 304 also includes two spring plungers 501. The upper portions of the two spring plungers 501 are configured to contact the through holes 310 provided in the pin guide 302, respectively.

[0163] The head 309 is provided on the Z-axis plus end of the spring plunger 501. The two spring plungers 501 and the through-hole 310 limit the rotational flexibility and swing of the head 309. A heavy load is applied to the shaft 512, particularly at the contact point between the leg 513 and the roller 308. For this reason, it is preferable that the shaft 512 be made of a material with high strength. For example, the shaft 512 can be made of SUS. The roller surface is also fluorine-treated.

[0164] <Other structural examples> Two or more valves that do not require the valves to open and close at the same time can be driven with a single pin. Figures 15A and 15B show examples of the configuration of pin 304 when two valves are opened and closed simultaneously using two heads. Valves that use such pins 304 are preferably not too far apart.

[0165] As shown in Fig. 15A, second springs 307 may be attached to each valve, or as shown in Fig. 15B, one second spring 307 may be attached to each valve. It is desirable that a first spring 306 is provided for each head 309. Furthermore, it is desirable that the centers of gravity of second springs 307, pin 304, and two or more valves are located on an axis parallel to the same Z axis.

[0166] When this type of configuration is adopted, one pin 304 presses two valves. This increases the load on the pressing pin (pin 304). Also, since the frictional force acting on the inside of pin 304 and on the pin-pin guide increases, it is necessary to select a second spring 307 with an appropriate strength.

[0167] <Regarding the sliding plate pattern and valve arrangement> (i) Example of dense valve arrangement It is desirable that the valves of the flow channel device 104 be arranged with a high degree of freedom to enable the desired operation. Increasing the degree of freedom in valve arrangement allows the flow channel device 104 to be designed to be smaller. In addition, the distance between the valve and the chamber, and between valves, can be reduced, preventing liquid loss and the intrusion of solutions into unintended flow channels. Furthermore, designing the length of the flow channel to be short prevents surface adsorption and increases sensitivity. In order to increase the degree of freedom in valve arrangement, it is necessary to have few restrictions on valve arrangement. Valve arrangement is mainly determined by the following four factors:

[0168] (Element 1) The pins do not interfere with each other when they move in the Z-axis direction; (Element 2) The pins do not interfere with the sliding plate when they move in the Z-axis direction, or the pins do not interfere with the uneven lane arranged for another valve, causing the pins to move in the Z-axis direction at an unintended timing; (Element 3) The sliding plates or the driving systems of the sliding plates do not interfere with each other; (Element 4) The multiple valves provided in the flow path do not interfere with each other, or the distance between valves, valve-chamber, and valve-flow path is large enough to prevent the joints of the valve parts from becoming loose (specifically, this is determined by the width of the flow path and the shape of the valve).

[0169] The spacing determined by element 4 is 5 mm or less, 3 mm or less, and 1 mm or less. On the other hand, due to the constraints imposed by elements 1, 2, and 3, the valve spacing must be 5 mm or more. Therefore, the valve placement constraints are primarily determined by elements 1, 2, and 3. In other words, it is necessary to eliminate the constraints of elements 1, 2, and 3 as much as possible.

[0170] The sliding plate 303 and sliding plate drive system 301 may be installed independently for each valve. In this case, all valves can be operated independently, making it easier to control complex valves. Also, multiple analysis procedures can be prepared, allowing analysis to be performed using different valve opening and closing patterns for each analysis. Since it is only necessary to control the two operations of opening and closing the valve, the number of sliding plate steps for one sliding plate 303 can be as small as two. This makes it possible to reduce the driving range of the sliding plate 303 in the X-axis direction. However, since the constraint of element 3 is imposed on each valve, the degree of freedom in valve placement is reduced. Furthermore, since as many actuators as there are valves are required, the system becomes complex.

[0171] (ii) Driving Multiple Valves With regard to element 3, by driving multiple valves with one sliding plate 303, it is possible to reduce the number of valves that are subject to the constraints of element 3. Compared to the case where a sliding plate 303 and sliding plate drive system 301 are installed independently for each valve, the opening and closing of multiple valves is controlled with a smaller number of sliding plate drive systems 301, which reduces the cost of the analysis system 101. Furthermore, because the constraints of element 3 are reduced, it is possible to arrange the valves more closely together. Therefore, the size of the analysis system 101 can be reduced.

[0172] When driving multiple pins 304, the shape of the slope facing the convex portion 311 may be different for each valve pin 304 so that the maximum load on the sliding plate 303 is dispersed. Also, valves driven to open and close by the same sliding plate 303 cannot open and close independently. For this reason, it is necessary to prepare sliding plate steps for the required valve opening and closing patterns.

[0173] <Arrangement Pattern of Concave and Convex Shapes on the Sliding Plate 303> Hereinafter, all the concave and convex lanes on one sliding plate 303 will be collectively referred to as the sliding plate pattern. Figures 16A to 16F are diagrams showing a table indicating valve opening and closing operations (opening and closing steps), valve arrangements, and examples of sliding plate patterns. Valve coordinates indicate the center of gravity of the valve. In the figures, the sliding plate 303 and the flow path device 104 are drawn side by side, but their relative positions are not shown. Furthermore, while the following describes an arrangement that minimizes valve spacing, in actual flow path devices 104, valves are arranged in appropriate positions based on the balance with other flow path device elements such as chambers and external connection ports. Complex valve opening and closing pattern combinations can be realized by increasing the number of sliding plate steps, not limited to Figure 16B.

[0174] (i) Arrangement pattern A: FIG. 16A is a diagram showing an example of a slider pattern when three valves are installed on the same X coordinate. The flow path device 104 has valve V1 at position (x1, y1), valve V2 at position (x1, y2), and valve V3 at position (x1, y3). FIG. 16A(1) shows the valve opening and closing patterns. FIG. 16A(2) shows the valve arrangement and the slider pattern of the slider 303 that can execute the valve opening and closing pattern shown in FIG. 16A(1). The slider 303 is driven in the positive X direction, and slider Steps 1, 2, and 3 sequentially drive the pins in the Z-axis direction, enabling the valve opening and closing pattern shown in FIG. 16A(1).

[0175] In this example, one concave-convex lane is used for one valve, so a total of nine concave-convex portions are provided on the slider. In this pattern, the minimum value of the valve spacing (y2-y1) is determined by the larger value of element 1 or element 2.

[0176] (ii) Arrangement pattern B: Fig. 16B is a diagram showing an example of a slider pattern when three valves are installed on the same Y coordinate. Fig. 16B(1) shows the valve drive pattern. Fig. 16B(2) shows the valve arrangement and the slider pattern of the slider 303 that can execute the valve opening and closing pattern shown in Fig. 16B(1). The flow channel device 104 is provided with valve V1 at the position (x1, y1), valve V2 at the position (x2, y1), and valve V3 at the position (x3, y1).

[0177] In this example, one concave-convex lane is used for three valves. To realize the drive pattern shown in Figure 16B (1), the sliding plate 303 only needs to have one convex portion. As the sliding plate 303 drives in the positive X direction, the convex portion sequentially closes the valves V1, V2, and V3. The sliding plate 303 does not need to have a concave portion that specifies the open state of the valve, as in the sliding plate 303 shown in Figure 16B (2). By omitting the concave portion, the width of the sliding plate in the X direction can be minimized.

[0178] (iii) Figure 16C shows an example of a sliding plate pattern when three valves are installed on the same Y coordinate. Figure 16C (1) shows the valve drive pattern. Figure 16C (2) shows the sliding plate pattern and the valve arrangement.

[0179] In this example, a sliding plate 303 consisting of one concave-convex lane with a total of five concave-convex portions is used for three valves. In Step 1, convex portion 1 comes to valve 1, closing valves V1 and V2, while V3 is open because the concave portion is in contact with it. In Step 2 and Step 3, convex portion 2 comes to valve 1 and the concave portion comes to valve 1, respectively, performing the opening and closing operations shown in the table.

[0180] In this pattern, the minimum valve spacing (x2 - x1) is constrained by element 1 as well as element 5 (the width of the uneven portion in the X direction), and is determined by the larger of the constraints imposed by element 1 and element 5.

[0181] In the patterns of Figures 16B and 16C, the valves do not have to be placed at exactly the same Y coordinate; by increasing the width of the sliding plate 303 in the Y direction, valves with different Y coordinates can be opened and closed in the same concave-convex lane.

[0182] When valves share a slider lane as shown in Figures 16B and 16C, for example, operation can be performed as a normally open state, where only one valve is closed, as shown in Figure 16B. Operation can also be performed as a normally closed state, where one of multiple valves is open. By placing multiple valves on the same Y coordinate, the unevenness of the slider 303 can be shared between the valves, making it possible to reduce the size of the slider 303.

[0183] It is preferable that all valves are in an open state in the step of inserting the flow path device 104. In the case of normally closed operation, if there is a mechanism that moves the sliding plate 303 in the negative Z-axis direction, the pin 304 that has been in contact with the convex portion 311 can be retracted when the flow path device 104 is inserted. Also, a concave portion 312 that opens all valves may be provided in the sliding plate 303, but this increases the length of the concave-convex lane in the X-axis direction.

[0184] (iv) Arrangement Pattern C: Figure 16D shows an example of a slider pattern when three valves are not aligned on the same XY coordinate system and the concave-convex lanes are not shared between the valves. Figure 16D(1) shows the valve drive pattern. Figure 16D(2) shows the valve arrangement and the slider pattern of the slider 303 that can execute the valve opening and closing pattern shown in Figure 16D(1). The flow path device 104 has valve V1 at position (x1, y1), valve V2 at position (x2, y2), and valve V3 at position (x3, y3). In this example, one concave-convex lane is used for each valve. Because the concave-convex lanes are not shared between the valves, the constraints of element 1 and element 2 work as follows:

[0185] (iv-1) The minimum value of the spacing in the y-axis direction (y2 - y1) is constrained by element 2; (iv-2) The minimum spacing between two valves, √(x2 - x1)^2 + (y2 - y1)^2, is constrained by element 1 (when the thickest part of the pin takes the shape of a body of revolution around an axis parallel to the Z-axis). Depending on the configuration and drive procedure of the flow path device, this constraint may be smaller than that of patterns A and B, making it possible to design a smaller flow path device.

[0186] (v) Figure 16E is a diagram showing an example of a sliding plate pattern when two valves are lined up on the same Y coordinate and the distance between the two valves is a certain distance relative to the width of the uneven lane in the X-axis direction. Figure 16E(1) shows the valve drive pattern. Figure 16E(2) shows the valve arrangement and the sliding plate pattern of the sliding plate 303 that can execute the valve opening and closing pattern shown in Figure 16E(1). In this arrangement, the uneven lanes of the two valves exist on the same Y coordinate, but the uneven portions are not shared between the valves.

[0187] (vi) Arrangement pattern D: Figure 16F shows an example of a slider pattern in which valves V1 and V2 are aligned on the same Y coordinate, and valve V3 is aligned on a different Y coordinate from V1 and V2. In this example, valves V1 and V2 share a concave-convex lane, and valve V3 is assigned a separate concave-convex lane.

[0188] <Mechanism for densely arranging valves> When arranging valves as in arrangement pattern B (see FIG. 16B ), the X-axis direction may be aligned with the longitudinal direction of the flow path device 104. Because the arrangement interval of the valves in the X-axis direction is restricted in the X-axis direction, aligning the valves with the longitudinal direction allows more valves to be arranged in a smaller flow path device 104.

[0189] When the valves are installed as in arrangement pattern C (see FIG. 16D), it is desirable that the sliding plate 303 slides in the X-axis direction, with the longitudinal direction of the flow channel device 104 being the Y-axis and the lateral direction of the flow channel device 104 being the X-axis. This is because by arranging multiple valves so that they do not overlap in the longitudinal direction, more valves can be installed in a smaller flow channel device 104.

[0190] Reducing the pin's thickness in the XY plane alleviates the constraints of element 1 and element 2. The pin's thickness in the X and Y directions does not need to be equal. Furthermore, reducing the width of roller 308 in the Y direction can alleviate the constraint of element 2. When valves are aligned on the same X axis or when an arrangement such as that shown in Figure 16D is adopted, the width of pin 304 in the X direction does not affect the valve placement constraints as long as it does not interfere with sliding plate 303. Therefore, it is preferable to confine elements that make pin 304 thick in the X direction. For example, protrusion 322, which receives the reaction force of second spring 307, is the portion of pin 304 that protrudes relatively far from the central axis. However, by making it thick in the X direction and thin in the Y direction, the impact of the constraint of element 1 on the Y direction can be minimized. Similarly, when the valves are arranged on the same Y axis as in Figures 16B and 16C, the width of the pin 304 in the X axis direction may be large, but it is preferable that the width in the Y axis direction is small.

[0191] The pin 304 may have a shape that protrudes from the corresponding uneven lane into the adjacent lane when viewed from the XY plane, as long as the shape is not restricted by the element 2. For example, the leg 513 may be made longer than the height of the uneven portion of the sliding plate 303 so that the protrusion 322 does not hit the sliding plate 303.

[0192] The longest part of the pin 304 may be any of the head 309 (upper pin part), the lower pin part 305, the transmission mechanism 306, the tracking mechanism 307, and the roller 308. In addition, by changing the Z coordinate of the thickest part among multiple pins 304, interference between the pins 304 may be prevented, allowing the valves to be arranged closely together.

[0193] <Miniaturization of sliding plate 303> (i) Relationship between the number of steps and the width of sliding plate 303 The width of the unevenness of the sliding plate 303 may be different for each sliding plate step, but in the following, for simplicity of explanation, it will be assumed that they are all the same.

[0194] To drive the sliding plate 303, it is necessary to ensure a range of movement of the sliding plate 303. FIG. 16A (3) shows the movable range of the sliding plate 303 in the X-axis direction when the sliding plate diagram shown in FIG. 16A (2) is moved in the valve opening / closing pattern (FIG. 16A (1)). In FIG. 16A (3), the X-coordinate of the center of gravity of the sliding plate 303 is smallest at Step 1, and largest at Step 3. The sliding plate 303 itself has a width of three steps, and the X-coordinate moves an additional two steps from Step 1 to Step 3. Therefore, the total driving range of the sliding plate 303 is 5a, where a is the width per step. In the case of an arrangement such as the above arrangement pattern A, more generally, the minimum driving range width Wx of the sliding plate 303 in the X-axis direction relative to the number of steps S is expressed by the following equation (1): Wx=a×(2×S-1)... (1)

[0195] FIG. 16C (3) is a diagram showing the movable range of the sliding plate 303 when the sliding plate diagram shown in FIG. 16C (2) is moved according to the valve opening and closing pattern (FIG. 16C (1)). The sliding plate 303 itself has a width of 5a, and the X coordinate moves two steps from Step 1 to Step 3, so the total driving range of the sliding plate 303 is 7a, where a is the width per step. Similarly, when operating a normally closed valve, Wx is expressed by the following equation (2), where b is the maximum value of the valve spacing. Wx = a × (2 × S - 1) + b ... (2)

[0196] Fig. 16D(3) is a diagram showing the driving range of the sliding plate 303 when the sliding plate diagram of Fig. 16D(2) is moved according to the valve opening and closing pattern (Fig. 16D(1)). Note that the valve V2 is omitted in Fig. 16D(3).

[0197] The sliding plate 303 itself has a width of three steps, and the X coordinate moves two steps from Step 1 to Step 3, so the total driving range of the sliding plate 303 is 5a, where a is the width per step. In the case of an arrangement like pattern B, if b is the maximum valve spacing from V1 to V3, then Wx of the sliding plate 303 in the X direction is expressed by the above formula (2).

[0198] As described above, the width of the sliding plate 303 and the driving X range of the sliding plate 303 increase according to the maximum interval and number of steps in the X-axis direction of the valve. If the sliding plate 303 is made rectangular as shown in Fig. 16D (4), a space that does not overlap with the movable range of the sliding plate 303 is created, and the freed up space can be used effectively.

[0199] <Division of Slider 303> When a complex analysis procedure is required, if multiple valves are driven by a single slider 303, the number of slider steps will increase to accommodate the various opening and closing patterns of the slider 303. For example, if 10 different valve opening and closing patterns are included during analysis, 10 or more slider steps will be required. According to the above formulas (1) and (2), the length in the X-axis direction increases as the number of slider steps increases. Therefore, the size of the analysis system 101 increases.

[0200] Therefore, the number of sliding plate steps per sliding plate can be reduced by driving the valves of one flow path device 104 with multiple sliding plates that move independently. For example, by dividing an analysis system 101 that requires 13 steps into three sliding plates 303, the number of steps per sliding plate 303 can be reduced to five.

[0201] (i) When using multiple sliding plates 303, it is preferable to provide each sliding plate 303 with a linear actuator or ball guide that can be driven independently. As shown in FIG. 4D, multiple sliding plate-actuator systems may be used in which the sliding plates 303 and actuators 316 are integrated and can run on a common linear guide. In this case, multiple sliding plates 303 can be installed while sharing the driving range.

[0202] When N independently moving sliders 303 are used for a valve opening / closing pattern with M steps, it is theoretically possible to reduce the number of valve opening / closing steps per valve to a minimum of M1 = N√M steps (M = M1^N). Driving all valves with independent sliders 303 would result in layout constraints and a complex system. There is an appropriate number of slider 303 divisions. For a number of steps N, it is preferable that one slider 303 has N-1 or fewer uneven lanes. For a number of steps N, it is desirable that one slider 303 has (N / 2) + 1 or fewer uneven lanes. For a number of steps N, when m sets of sliders 303 are used, it is desirable that one slider has (N / m) + 1 or fewer steps.

[0203] When a plurality of sliding plates 303 are used, it is desirable that the driving areas of the sliding plates 303 are installed so as not to overlap each other. In particular, it is preferable that the XY plane is shared but the XZ plane is not shared.

[0204] If the width of the sliding plate steps in the X-axis direction does not vary significantly for each valve and each step, the width of the sliding plate drive system 301 in the X-axis direction is determined by the maximum number of sliding plate steps. Therefore, it is preferable to group the sliding plates so that the maximum number of sliding plate steps is minimized. (ii) How to group the sliding plates

[0205] Valves whose opening and closing timing is perfectly synchronized, or valves that may be synchronized, may be driven on the same slider lane using a double-headed pin as shown in Figures 15A and 15B. On the other hand, even if the valves whose opening and closing timing is perfectly synchronized, or valves that may be synchronized, there may be cases where the distance between the valves is somewhat far and the use of a double-headed pin is disadvantageous. In such cases, the valves may be incorporated into the same slider. If the opening and closing timing is perfectly synchronized, the number of slider steps does not increase.

[0206] Valves whose open and closed states are completely reversed, and valves that don't mind being reversed, can be installed on the same sliding plate. If they are completely reversed, the number of sliding plate steps will not increase.

[0207] Depending on the valve step, there may be a valve (or valves) that may be either closed or open. Valves whose open / closed states are specified in inconsistent or inconsistent steps are advantageously incorporated into the same slider 303. For example, if in step A the open / closed state of valve V1 is specified but not the open / closed state of valve V2, and in step B the open / closed state of valve V1 is not specified but the open / closed state of valve V2 is specified, step A and step B can be combined into a single slider step that specifies the open / closed states of valves V1 and V2.

[0208] The valves directly below the pump are never open at the same time. Therefore, they may be operated as a normally closed valve set, where only one of them is open. In this case, the number of steps of the sliding plate 303 is equal to the number of valves.

[0209] When grouping the sliding plates 303 or when there are layout constraints, it is necessary to rearrange the valve layout from one that minimizes the flow path length and miniaturizes the flow path device 104 to one that takes into account the layout constraints and grouping. In this case, it is advisable to shift the flow paths starting with those that do not affect sensitivity, while maintaining the best possible layout for parts that are likely to affect sensitivity. Examples of flow paths that are prone to sensitivity or liquid transfer problems include the part where DNA is eluted from the purification membrane and brought into PCR, and the valves that seal the chamber during PCR. Conversely, examples of flow paths that are not directly related to sensitivity or liquid transfer problems include the flow path that transfers liquid from the purification membrane to the waste chamber, and the flow path that extends from the tank that stores the lysis and purification reagent to the lysis chamber or the purification membrane.

[0210] Valves provided in the flow paths connected to the purification membrane chamber and the PCR unit are preferably installed as close as possible to the purification membrane chamber. Valves belonging to the same sliding plate 303 can be arranged closer together than valves belonging to different sliding plates 303, so it is appropriate to group the valves on the same sliding plate 303.

[0211] As shown in equation (2) above, the driving range of the sliding plate 303 reflects the maximum spacing b between the valves included in the chip in the X-axis direction. Therefore, it is preferable to install the valves within as narrow a range in the X-axis direction as possible. Furthermore, the load on the ball guides of the linear actuator increases with the number of valves that are simultaneously closed. Therefore, it is preferable to minimize the maximum number of valves that can be closed by one sliding plate 303. The power of the actuator 316 must be determined by taking into account the increase in frictional force caused by the load when the valves are closed and the maximum number of valves that can be simultaneously closed by the actuator 316. It is preferable to set the motor power (thrust) with a margin of 2 to 5 times the required power derived from the maximum number of valves that can be closed. For these reasons, the number of valves that transition to closed during one valve step transition for the valves assigned to one sliding plate 303 should be minimized. The required power can also be reduced by intentionally shifting the position and inclination of the slope of the sliding plate 303 between valves.

[0212] By making the number of valves that open and the number of valves that close as close as possible, it is possible to offset the power. However, if the Z coordinate where the most force is required when closing a valve is different from the Z coordinate where the most force is applied when opening a valve, or if there is no reproducibility, it is preferable to set the power of actuator 316 with a margin of error.

[0213] Since the width of the sliding plate 303 increases roughly in proportion to the number of sliding plate steps, it is preferable to group the sliding plates 303 so that the maximum number of sliding plate steps of the sliding plates 303 is minimized.

[0214] The slider steps do not have to be arranged in the order of the valve opening and closing steps. The slider 303 may move two steps at a time, or may move in both the positive and negative X directions. However, the greater the number of steps the slider 303 moves in a single analysis, the shorter the lifespan of the slider 303. Therefore, it is preferable to determine the layout of the slider 303 steps so that the amount of movement of the slider 303 is as small as possible. For example, if there is a most frequently used step among the slider steps, that step may be located near the center of the uneven lane. Furthermore, having fewer slider steps is advantageous because it allows the slider 303 to have a smaller width in the X direction. However, if the total amount of movement in the X direction becomes too large, it may be designed to be divided into two locations to reduce the amount of movement.

[0215] <Multi-Sample Analysis> By enabling a single analysis system 101 to analyze multiple samples (multi-sample analysis), the analysis throughput can be improved.

[0216] The analytical system 101 capable of simultaneously analyzing multiple samples generally tends to be large, so it is desirable that the various parts that make up the analytical system 101 be as small as possible without sacrificing performance.

[0217] The flow channel device 104 may be configured to be used one per sample, or may be a flow channel device 104 that can analyze four samples simultaneously using one flow channel device 104. Analyzing one sample using one flow channel device 104 has the advantage that the cost per sample of the flow channel device 104 does not change depending on the number of samples analyzed simultaneously. On the other hand, a chip that can analyze four samples simultaneously using one flow channel device 104 tends to increase the analysis cost because even when only one sample is to be analyzed, four chips are consumed and discarded after use.

[0218] Therefore, when processing a plurality of flow path devices 104 in one analysis system 101, it is desirable to arrange the flow path devices 104 on the same Z coordinate, sharing the XY plane. By adopting such an arrangement, a common heater can be used, and the installation of other flow path device interface components can be simplified, allowing the analysis system 101 to be made smaller.

[0219] Furthermore, by installing a sliding plate drive system 301 for each flow channel device 104, it becomes possible to control each flow channel device 104 independently. For example, in a usage scenario where samples arrive one after another, analysis can be started each time a sample arrives, shortening the analysis time. In other words, it is possible to use it in a random access manner.

[0220] Furthermore, it is necessary to ensure a driving range in the X-axis direction so that the sliding plate 303 can move freely from the position where the center of gravity of the sliding plate 303 is at the most negative position on the X-axis to the position where it is at the most positive position on the X-axis. Therefore, when a sliding plate driving system 301 is installed for each flow path device 104, it is necessary to provide a gap in the X-axis direction in order to drive the sliding plate 303. Furthermore, as the number of flow path devices to be processed simultaneously increases, the number of actuators 316 that drive the sliding plate 303 also increases, making the system more complex.

[0221] 17A to 17D, by sharing the sliding plate 303 between the flow channel devices 104, it becomes possible to share the part on which the sliding plate 303 moves, and it becomes possible to narrow the distance in the X-axis direction. Furthermore, since the number of actuators does not increase even if the number of flow channel devices increases, multiple samples can be processed with a simple system configuration.

[0222] As shown in FIG. 17A , the valve drive direction is Z, and the sliding plate 303 movement direction is X. The flow channel devices 104 may be arranged along the Y-axis direction without overlapping in the Z-axis direction. In this arrangement, the spacing between the flow channel devices 104 does not need to be determined taking into account the drive range of the sliding plate 303 in the X-axis direction. However, when multiple sliding plates 303 are used, they must be arranged in a way that prevents interference between them. For example, the first sliding plate 303 may drive the valves located above the X-axis, and the second sliding plate 303 may drive the valves located below the X-axis, so that their drive ranges do not overlap in the X-axis direction. Alternatively, as shown in FIG. 16B , a drive system may be used in which three sliding plates 303 having a convex portion that defines only the closed state of one valve are arranged per chip, and the drive range in the X-axis direction is shared to close any of the three valves. When multiple sliding plates are arranged in the arrangement shown in FIG. 17A , a drive unit in which the sliding plate and actuator are integrated, as shown in FIG. 4D , may be used. Specifically, multiple integrated drive units are installed on one linear guide 315, the drive area is shared between the sliding plates, and each drive unit is configured to be able to drive independently in the X-axis direction.

[0223] As shown in FIG. 17B, the valve drive direction is Z, and the moving direction of the sliding plate 303 is X, and the flow path devices 104 may be arranged along the X-axis direction so as not to overlap in the Z-axis direction.

[0224] 17C is a layout diagram of the layout of FIG. 17B viewed from the Y-axis direction. The sliding plates 303 may be attached between the flow channel devices 104, or may be separated as long as they are driven by the same ball guide motor. Attached sliding plates are preferable because they do not slip. The device holder pin guides may be independent or attached.

[0225] FIG. 17D shows the layout and movable range of the sliding plate 303 when four flow path devices are aligned in the X-axis direction (repeatedly arranged at equal intervals) as shown in FIG. 17B , a sliding plate 303 like the sliding plate diagram in FIG. 16D(2) is shared among the flow path devices 104, and the sliding plate 303 is moved according to the valve opening / closing pattern shown in FIG. 16D(1). Note that valve V2 is omitted in FIG. 17D . According to FIG. 17D , the unevenness of the sliding plate 303, the through holes 310 of the pin guide 302, and the arrangement pattern 1701 of the pins 304 are arranged at equal intervals repeatedly for the number of flow path devices 104. By repeating this arrangement pattern 1701, a total of 10 or more pins 304 can be driven (in the example of FIG. 17D , 12 pins 304 can be driven).

[0226] Each uneven lane has a width of three steps per chip, and the X coordinate moves two steps from Step 1 to Step 3, with the flow channel devices arranged at intervals of c. In this case, the minimum driving range Wx is expressed by the following equation (3): Wx = a x (2 x S - 1) + b + 3c ... (3) More generally, if the number of flow channel devices 104 is represented by m, it can be expressed by the following equation (4): Wx = a x (2 x S - 1) + b + c x (m - 1) ... (4)

[0227] The flow path device interval is determined by the larger of the width of the uneven lane required to drive one valve or the width of the flow path device 104. If the width of the flow path device 104 is less than the width of the uneven lane, then it is expressed as c = a × S, and the above formula (4) can be transformed into the following formula (5): Wx = a × (S × (m + 1) - 1) + b ... (5)

[0228] 17C, the concave-convex lane is provided for each flow path device 104, but the concave-convex lane may be shared between the flow path devices 104. By sharing the concave-convex lane between the sliding plates 303, the amount of driving of the sliding plates 303 can be reduced.

[0229] From the above considerations, it can be seen that the smaller the number of steps of the sliding plate 303 and the narrower the maximum spacing b in the X direction of the valves driven by one sliding plate, the smaller the required driving range of the sliding plate 303 can be, and the more compact the analysis system 101 can be.

[0230] In this embodiment, the driving direction of the sliding plate 303 may be not only linear motion (X-axis direction) but also rotational motion. Fig. 17E is a diagram showing an example of arrangement when multiple sliding plates 303 performing rotational motion are used for multiple flow channel devices 104. In this case, the sliding plates S1, S2, and S3 have coaxial central axes.

[0231] <Relationship between Sliding Plate Drive Amount and Pressing Force> (i) Combination of Second Spring 307 and First Spring 306 It is desirable that the spring constant of the first spring 306 be greater than the spring constant of the second spring 307. In particular, when using the configuration shown in FIG. 10B or FIGS. 9C and 9D, the pressing force when the valve is closed corresponds to the amount of force obtained by subtracting the elastic force of the second spring 307 from the elastic force of the first spring 306. Therefore, it is necessary that the repulsive force exceeds the elastic force of the second spring 307. In the following, the compression ratio is calculated as (natural length - spring length) / (natural length - compressed length). In the case of a tension spring, a similar calculation formula is applied as the tension ratio. Instead of the compressed length, the minimum length at which the spring constant is maintained may be used.

[0232] The compression rate of the second spring 307 can be set to, for example, 40% in the recessed portion 312 and 70% in the protruding portion 311. When the second spring 307 reaches its contact length during operation, the repulsive force becomes uncontrollable, and a large load is applied to the sliding plate drive system 301. Therefore, it is desirable to set the length of the second spring 307 at the protruding portion 311 to be longer than the contact length. To prevent the follow-up force from applying a certain amount of pressure to the recessed portion 312 while preventing the pressure from becoming too strong at the protruding portion 311, it is preferable to use a small spring constant for the second spring 307. It is desirable that an elastic force of 1 N or more is applied from the second spring 307 to the pin 304 at the recessed portion 312. It is desirable that an elastic force of 4 N or less is applied from the second spring 307 to the pin 304 at the protruding portion 311. For example, if the concave-convex portion is 3 mm, the spring constant for the second spring 307 must be 1 N / mm or less.

[0233] When the valve is closed, the distance between the sliding plate contact portion 308 and the flow channel device 104 or the valve bottom surface 305 or the film 202 varies due to wear and tear on the sliding plate 303, tilt of the sliding plate 303, individual differences in the flow channel device 104, individual differences in the pins, wear and tear on the pins 304, and misalignment of the pins 304. The design limit is ±0.1 mm. More realistically, the design limit is ±0.5 mm. The pressing force at the furthest distance must exceed the required pressing force. For example, the design should be such that 20% more force than the required pressing force is applied at the furthest distance. On the other hand, if the pressing force at the shortest distance is too large compared to the required pressing force, this can damage the flow channel device 104 or the sliding plate drive system 301 and cause the actuator 316 to lose synchronization. Using a powerful actuator 316 can result in an increase in the size of the analysis system 101. For these reasons, it is preferable to design the depression force at the closest distance to be within 200% of the required depression force. Taking these constraints into account, it is preferable that the first spring 306 have a small change in elastic force relative to the amount of compression, and a small spring constant. Given the above requirements, it is preferable that the rate of increase in the valve depression force (first force F1) in the range Z1≦Zp≦Z2 be 40 N / mm or less. In other words, when using the configuration shown in FIG. 9A or FIG. 9B, it is preferable that the spring constant of the first spring be 40 N / mm or less.

[0234] On the other hand, if the first spring 307 is at its natural length when released and has a small spring constant, the required pressing force F1 cannot be obtained unless the tooth height of the concave and convex portions is larger. The spring constant of the first spring 307 is preferably a value that allows the required pressing force F1 to be achieved with a compression of 3 mm or less. A sliding plate with a larger tooth height also has a larger width in the X-axis direction, which leads to an increase in the size of the sliding plate drive system 301. Furthermore, when using the spring plunger 501, the tooth height of the concave and convex portions can be reduced by setting a larger initial load. However, a small spring constant requires the use of a long spring or a spring with a large diameter to obtain sufficient pressing force, which is disadvantageous because it requires the spring plunger 501 to be enlarged in the Z-axis direction or its radius on the XY plane to be increased. Due to these constraints, the spring constant of the first spring 306 is preferably 0.8 × F1 / mm or less and 0.33 × F1 / mm or more relative to the required pressing force F1.

[0235] 2A requires a depression force of typically 3 N or more, 5 N or more, 10 N or more, or 15 N or less. Therefore, the spring constant of first spring 306 is preferably 12 N / mm or less and 1 N / mm or more.

[0236] If the springs are combined in such a way that the valve cannot be opened or closed correctly, those springs will not function as the first spring 306 and the second spring 307. In this specification, the spring 306 connecting the pin upper part (head) 309 and the pin lower part 305 may be referred to as the first spring, and the spring 307 in contact with the pin 304 and the pin guide 302 may be referred to as the second spring. The respective spring constants are k1 and k2.

[0237] (ii) Basic Example As shown in Figure 4B, the Z coordinate of the lower end of the pin sliding plate ground contact portion 308 is Zp, the Z coordinates of the recessed portion 312 and the protruding portion 311 on the surface of the third plate (sliding plate 303) are Z0 and Z2, respectively, the minimum Zp at which the first elastic body (first spring: spring 306) elastically deforms when the head 309 contacts the flow path device 104 is Z1, and the minimum Zp at which the second elastic body (second spring: spring 307) elastically deforms is Zn. In the example of Figure 4B, the relationships Z0 ≦ Z1 ≦ Z2 and Zn ≦ Z0 hold.

[0238] In the case of a plastically deformable film (e.g., a PP film), Zp when the head 309 contacts the flow path device 104 changes between the first valve depression and the second or subsequent valve depressions. However, hereinafter, unless otherwise specified, Zp will refer to the smallest Zp value. Zp is typically smallest when the valve is first depressed.

[0239] Alternatively, Zp can be considered to change each time the valve is pressed. It should be considered in a way that can represent the behavior closest to the actual valve behavior depending on the valve configuration. Z0, Z1, and Z2 may be set differently for each sliding plate step. When actually setting the initial lengths of the various springs, the spacing between the first plate, second plate, and third plate, and the height of the unevenness, the valve may be opened and closed multiple times to confirm whether the desired valve opening and closing operation can actually be performed. Even if the change in pressing force relative to the Zp coordinate differs from the behavior specified here depending on the time, this is acceptable as long as there are no problems with actual opening and closing.

[0240] In the following, the force (pressing force) in the positive Z-axis direction that the pin upper part 309 applies to the flow path device will be referred to as the first force F1, and the force in the negative Z-axis direction that the pin sliding plate grounding part 308 applies to the sliding plate will be referred to as the second force F2.

[0241] To close the valve at the convex portion, it is desirable that the first force F1 exceeds the necessary closing pushing force Fc. That is, in Figures 3A to 3C, it is desirable that the Zp coordinate at which F1 = Fc is in the range of Zp < Z2.

[0242] FIG. 18A shows the characteristics of the force exerted by the pin 304 on the sliding plate 303 or the fluid path device 104. FIG. 18A(1) shows the positional relationship between the pin and the sliding plate corresponding to the value of Zp. FIG. 18A(2) shows the change in the first force F1 (valve pressing force) and the second force F2 (sliding plate pressing force) with respect to the value of Zp. Here, the fluid path device 104 is described as behaving as a rigid body. The first spring (spring 306) is assumed to be at its natural length when not in contact with the film (valve). Note that the various pressing forces can be calculated by inserting a pressure sensor or load cell into the relevant portion, detecting strain with an optical sensor, etc., and multiplying the strain by the elastic coefficient. However, since the actual fluid path device 104 deforms, its behavior will differ from the changes shown here, but this can be easily inferred from this description.

[0243] The horizontal axis of the graph in Figure 18A (2) can also be replaced with the distance Zq in the Z-axis direction between the sliding plate contact part 308 and the film that comes into contact with the channel when closed. In this case, when Zp = Z2, Zq roughly matches the distance between the sliding plate contact part 308 and the channel bottom 205. Also, when Zp = Z1, Zq matches the distance between the sliding plate contact part 308 and the film. Similar replacements can be applied to other figures.

[0244] (State I) When the pin 304 is in contact with the recess 312 (Zp = Z0), the pin 304 is not in contact with the film, and therefore the first force F1 is not generated. The second force F2 coincides with the magnitude of the elastic force of the second spring (spring 307). In the range of Z0 ≦ Zp ≦ Z1, the second force F2 increases by the spring constant k2 of the second spring as Zp increases.

[0245] (State II) When the pin 304 contacts the flow channel device 104 (Zp = Z1), the pin 304 contacts the film, generating a first force F1. Since the first force F1 is added to the second force F2, in the range of Z1 ≦ Zp ≦ Z2, the second force F2 increases with an increase in Zp by an increase in the spring constants of the first spring and the second spring (k1 + k2). Furthermore, the first force F1 increases with an increase in Zp by an increase in the spring constant k1 of the first spring. In other words, the slope (first derivative) of the second force F2 applied by the pin lower portion 305 to the sliding plate 303 increases before and after Zp = Z1.

[0246] (State III) When pin 304 is in contact with protrusion 311 (Zp=Z2), the valve is closed and the first force F1 is determined by the elastic force of the first spring. The first force F1 is calculated as F1=(Z2-Z1)k1, where k1 is the spring constant of the first spring. In the case of a configuration in which the second spring (spring 307) is in contact with the top of the pin, as shown in Figures 9C and 9D, the forces change as follows: Z0≦Zp≦Z1: F1=0, F2=k2(Zp-Z0) Z1≦Zp≦Z2: F1=(k1-k2)(Zp-Z1), F2=k2(Zp-Z0)

[0247] Since the elastic force of the second spring (spring 307) is transmitted to the sliding plate 303 via the first spring (spring 306), the first spring (spring 306) is compressed even when the head 309 is not in contact with the flow path device 104. Furthermore, in the case where the first spring (spring 306) is configured not to have an initial load of the spring plunger 501 described later, it is essential that the spring constant k1 is greater than k2.

[0248] (iii) When the second spring reaches its natural length midway. In the example of FIG. 18B , the relationship Z0≦Zn≦Z1≦Z2 holds. In this case, the sliding plate contact portion 308 cannot contact the portion of the recess 312 where Zp is smallest. Although the sliding plate contact portion 308 cannot reach the deepest portion of the recess 312, the head 309 moves away from the flow path device 104, allowing the valve to be fully opened. As such, the second spring does not need to constantly apply elastic force to the sliding plate 303 and the pin guide 302; it is sufficient to be able to sufficiently separate the pin 304 from the flow path device 104. Note that if the recess 312 is deep, Zp may become too small and the sliding plate contact portion 308 may fall out, or the sliding plate contact portion 308 may get caught in an unintended location when moving to the protrusion 311.

[0249] When the second spring is a tension spring as shown in Figures 9B and 9D, even if there is a portion where the sliding plate contact portion 308 separates from the recess, the tension spring prevents the pin 304 from falling, so the pin will not drop too far in the negative Z direction.

[0250] 9A and 9C, if the second spring is a compression spring and is not joined at the top and bottom to the pin 304 and pin guide 302, the pin can move in the negative direction until Zp falls below Zn. To prevent this situation, it is desirable that the second spring be joined at the top and bottom in a configuration where Zn≧0. Alternatively, the configuration may be such that the lower limit of extension of the second spring is restricted by the pin guide.

[0251] Because the second spring of the compression spring is prone to buckling when it reaches its free length, a structure that constantly applies a load is preferable. Figure 19 shows an example configuration in which a pin guide 302 is provided with an enclosure 604 to restrict the lower limit of the Z coordinate of the pin lower portion 305. The enclosure 604 is narrower than the protrusion 322 of the pin lower portion 305, preventing the pin lower portion 305 from protruding below the enclosure 604. Furthermore, by appropriately designing the connection between the sliding plate grounding portion 308 and the pin lower portion 305 so that the enclosure 604 and the sliding plate 303 do not interfere with each other, the pin 304 can be restricted from moving more than necessary in the negative Z coordinate direction. This configuration can be particularly used in a configuration where Zn≧0, as shown in Figure 18B.

[0252] (iv) When Z1≦Z0, Zn≦Z0 (contact with the flow channel device at the recess) In Figure 18C, the relationship Z1≦Z0, Zn≦Z0 holds. (State I) When the pin 304 is in contact with the recess 312 (Zp=Z0), the pin 304 is in contact with the film (valve), and a first force F1 of (Z0-Z1)×k1 is generated. The second force F2 is equal to the sum of the elastic force of the second spring 307 and the first force F1. In the range of Z0≦Zp≦Z1, the second force F2 increases by the spring constants of the second spring and the first spring as Zp increases.

[0253] (State II) When the pin 304 is in contact with the protrusion 311 (Zp = Z2), the valve is closed, and the first force F1 is determined by the elastic force of the first spring. The first force F1 is calculated by F1 = (Z2 - Z0) x k1, where k1 is the spring constant of the first spring. If the flow path device 104 is configured such that the closure rate is sufficiently low when a load of (Z0 - Z1) x k1 is applied, then this structure will not pose any problems.

[0254] In this case, since the head 309 pops out after the fluid path device 104 is removed, there is a possibility that it may get caught when the fluid path device 104 is inserted next time.

[0255] (v) When Z0≦Z1≦Zn≦Z2 (second spring reaches its natural length first) In the range Z0≦Z1≦Zn≦Z2, the elastic force of the second spring becomes 0 before the head 309 separates from the film (valve), so the head 309 remains in contact with the film. In this case, if gravity acts on the pin 304, the first force F1 becomes 0. On the other hand, if gravity is insufficient, or if gravity is not applied and the first force acts in the positive Z direction, the first force F1 is determined by the frictional force acting between the pin 304 and the pin guide 302. The frictional force fluctuates depending on the aging of the system and the environment, so the first force F1 becomes unstable.

[0256] <Spring Plunger> In this embodiment, the first spring 306 is built into the spring plunger 501. When the spring plunger 501 is assembled, the compression spring is stored in a compressed state, and an initial load corresponding to the compression force is generated. Even if a force equal to or less than the initial load is applied to the spring plunger 501, the overall length of the spring plunger 501 hardly changes due to the repulsive force of the compression spring. When a force equal to or greater than the initial load is applied to the spring plunger 501, the spring is compressed, and the overall length of the spring plunger 501 becomes shorter according to the spring constant.

[0257] Therefore, by setting the initial load appropriately, a sufficient pressing force can be obtained with a small spring constant even if the sliding plate 303 has few irregularities. It is preferable to set the initial load to a value equal to or less than the target pressing force. For example, it is preferable to set the initial load to an elastic force that is 50% or more of the elastic force when Z = Z2. Furthermore, for example, if the target pressing force of the valve is 10 N, it is preferable to set the initial load to 8 N. If the initial load is set too high, the force applied to the valve will become uncontrollable, and too much force will be applied to the valve.

[0258] (i) Figure 18D shows a pin incorporating an appropriate spring plunger 501 and the pressing force characteristics of the pin. (State I) When the pin 304 is in contact with the recess 312 (Zp = Z0), the pin 304 is not in contact with the film (valve), and therefore the first force F1 is not generated. The second force F2 coincides with the magnitude of the elastic force of the second spring 307. In the range of Z0 ≤ Zp ≤ Z1, the second force F2 increases by the spring constant of the second spring 307 as Zp increases.

[0259] (State II) When the pin 304 contacts the flow channel device 104 (Zp = Z1), the pin 304 contacts the film (valve), generating a first force F1. As Zp increases, immediately after contacting the film (valve), the spring plunger 501 behaves as a rigid body until the first force F1 reaches the initial load of the spring plunger 501. Therefore, the first force F1 and the second force F2 increase sharply. After the first force F1 reaches the initial load of the spring plunger 501, the second force F2 increases with an increase in Zp by an amount corresponding to the spring constants of the first spring 306 and the second spring 307 within the range of Zp≦Z2. Furthermore, the first force F1 increases with an increase in Zp by an amount corresponding to the spring constant of the first spring 306.

[0260] (State III) When the pin 304 is in contact with the protrusion 311 (Zp=Z2), the valve is closed. At this time, the first force F1 is determined by the elastic force of the first spring 306. Specifically, the first force F1 is calculated as F1=(Z2-Z1)×k1+initial load, where k1 is the spring constant of the first spring 306.

[0261] (ii) Figure 18E is a diagram showing the change in the first force F1 relative to the amount of change in the unevenness of the sliding plate 303 when the pin 304 having the first spring in the spring plunger 501 is pressed against the flow channel device 104 with a PP film stretched thereon. Here, it is assumed that the pin 304 follows the entire range of the unevenness. It is also assumed that the initial load of the pin 304 brings the valve (film) into contact with the bottom surface of the valve.

[0262] (State I) When the head 309 comes into contact with the film (valve), the pin 304 behaves as a rigid body until the pressure reaches the initial load. On the other hand, since the film deforms, the pressure increases gradually with changes in the Z coordinate.

[0263] (State II) The pressing force reaches the initial load when the film contacts the bottom surface of the flow channel. The Z coordinate of the head 309 changes little thereafter. Meanwhile, the first spring 306 begins to compress, so the first force F1 increases with an increase in Zp, corresponding to an increase in the spring constant of the first spring 306.

[0264] (State III) When the valve is opened, the film undergoes plastic deformation, causing the head 309 to separate from the film at a larger Z coordinate than when the valve is closing. The rate of decrease in pressure is also greater than the rate of increase when the valve is closing. If the film exhibits viscoelastic properties, repeated valve closures generally result in a cycle of State I → State II → State III.

[0265] (iii) An example of the spring configuration of the pin 304 for crushing a valve made of PP film with a required depression force of 10 N will be described below. First spring 306: spring constant 1.5 N / mm, outer diameter 3 mm, natural length 25 mm, maximum load 14.7 mm, closed length 15.2 mm; Second spring 307: spring constant 0.1 N / mm, outer diameter 5 mm, natural length 30 mm, maximum load 2.2 N, minimum length 8 mm; Spring plunger 501: contains the first spring 306 and is installed internally so that the first spring 306 has an initial length of 19 mm. With the above configuration, the initial load of the spring plunger 501 is 9 N.

[0266] Furthermore, the second spring 307 is installed so that its spring length is 15 mm when Zp = Z0. When Zp = Z0, the distance between the head 309 and the flow channel device 104 is 0.5 mm. Furthermore, the flow channel depth of the valve section (the portion where the valve is grounded) can be set to, for example, 0.5 mm. Note that if the concave-convex height (tooth height) of the sliding plate 303 is 3 mm, the second spring 307 will compress 3 mm when Zp = Z2, generating a total force of 1.8 N. Meanwhile, in this case, the first spring 306 will compress 2 mm when Zp = Z2, generating a total pressing force of 12 N.

[0267] From the above, the second force F2 is 13.8 N. If the value of Z2 fluctuates by ±0.5 mm, the pressing force fluctuates between 11.25 and 12.75 N, and the second force F2 fluctuates between 13 and 14.6 N.

[0268] <Regarding the slope angle of the uneven portion of the sliding plate 303> When the driving range of the sliding plate 303 is limited to the X-axis and the sliding plate 303 moves in both the positive and negative directions of the X-axis, it is desirable that the slope shape of the sliding plate 303 be symmetrical. On the other hand, when the sliding plate 303 is arranged in a circular shape as shown in Figure 17E and is driven only in one direction, the slope shape may be asymmetrical. Furthermore, when the sliding plate 303 can also be driven in the Z-axis direction, the pressing force can be generated only at the location Zp = Z2. Therefore, the slope shape may be any shape.

[0269] 18F is a diagram showing the force acting on the sliding plate ground contact portion 308 on the inclined surface of the sliding plate 303. As shown in FIG. 18F, when the sliding plate 303 moves in the positive direction of the X axis to move to the convex portion 311, and the pin 304 moves in the positive Z direction along the inclined surface, the inclined surface angle in the X axis direction of the uneven surface 313 with which the sliding plate ground contact portion 308 comes into contact is defined as θ. Also, the magnitude of the force that the sliding plate 303 applies to the sliding plate ground contact portion 308 is defined as F. At this time, the direction of the force that the sliding plate 303 applies to the sliding plate ground contact portion 308 is perpendicular to the inclined surface, so the balance between the second force F2 and the force applied to the sliding plate ground contact portion 308 is expressed by the following equation (6): F=F2 / cosθ (6)

[0270] Furthermore, the force acting on the sliding plate 303 in the negative X-axis direction is expressed as F2 × tan θ. The greater the inclination of the slope of the sliding plate 303, the greater the thrust required of the actuator 316. Furthermore, as the value of θ increases, the value of F increases, and the frictional force generated between the sliding plate ground contact portion 308 and the sliding plate 303 increases. Therefore, a greater thrust is required to overcome the frictional force and displace the pin 304 in the positive Z direction.

[0271] The force applied in the negative Z direction becomes a load on the sliding plate 303, and friction occurs in the ball screw, so the larger F2 becomes, the more thrust is required to counter the frictional force generated in the ball screw.

[0272] 18A(2), the second force F2 is typically small in the range of Zn<Z1, and the rate of change is also small, so the slope angle θ may be set somewhat higher. Furthermore, in the range of Zn>Z1, the second force F2 is large and the rate of change is also large, so it is preferable to set the slope angle θ somewhat lower. In other words, it is preferable that the uneven surface 313 be designed so that the slope angle decreases as Zn increases.

[0273] <Effects of the Pin 304 and Slider Plate Drive System 301> (i) By using the pin 304 and slider plate drive system 301 according to this embodiment, the reliability (reliability of the valve opening and closing operation) of the analytical system 101 equipped with the slider plate valve drive system (valve opening and closing system) can be improved. In other words, the valve can be opened and closed more reliably. Inexpensive flow path devices 104 made of materials such as PP require a high valve depression force when closing, and also require control of the depression force when opening. When multiple valves are driven by a common actuator, an extremely small actuator is not required, making it possible to create an inexpensive drive system. Driving multiple valves with a single slider plate increases the flexibility of valve placement. Since the depression force when closing can be controlled, a relatively small actuator can be used. The use of a slider plate drive unit allows for a compact analytical system. With appropriate placement and pin design, a compact analytical system can be created. By dividing the slider plate, a compact analytical system can be created. Since a flow path with a deep cross-sectional shape can be used, surface adsorption is reduced. Furthermore, since the degree of freedom in arranging the valves increases, the flow path can be made shorter.

[0274] (ii) Patent Document 3, Patent Document 4, and Non-Patent Document 1 drive the valve using a sliding plate drive system. These known examples use flow path devices with films made of elastic materials or elastomers. Therefore, the valve's closing rate characteristics have no hysteresis. As an example, as shown in Figures 3A and 3B, the depression force-closing rate characteristics of the flow path device exhibit little hysteresis. Valves made of elastic materials or elastomers can achieve a sufficient closing rate with little force. Furthermore, they open to some extent even if some depression force remains when they are opened.

[0275] If the pressing force is sufficiently removed, a lower closure rate can be obtained when the device is opened, but the known literature does not mention the closure rate when the device is opened. In this embodiment, the closure rate of the flow path device when the device is opened must be 50% or less, more preferably 20% or less. Therefore, the pressing force must be sufficiently small when the device is opened.

[0276] In contrast, in this embodiment, the film (valve) of the flow channel device 104 is made of polypropylene (PP). Materials with viscoelastic properties, such as polypropylene, exhibit the depression force-closing ratio characteristic shown in Figure 3C. Valves according to this embodiment tend to require a larger depression force than valves made of elastic materials. Unless the unloading force during opening is 10% or less, or 1% or less, of the minimum depression force during closing, the closing ratio will not be 50% or less, or 20% or less. Controlling the depression force during closing is more difficult than when an elastic material is used for the film, and the change in depression force during misalignment is more abrupt than when an elastic material is used. The valve characteristics shown in Figure 3C are a problem identified in this embodiment. To apply the sliding plate drive system 301 to such a valve, the pin 304 used must have a double spring structure containing a first spring 306 and a second spring 307.

[0277] (iii) Figure 20A is a diagram showing the pin characteristics of Non-Patent Document 1. A ball plunger 509, which is a type of spring plunger, is used for the pin, and as Zp increases, the pressing force increases by the spring constant of the spring plunger (ball plunger 509).

[0278] In this configuration, the force required to follow the sliding plate drive system is obtained by the repulsive force of the pin against the film, so a pressing force is applied to the film even in the recesses. In particular, because a spring plunger is used for the pin, the initial load described above exists, and a pressing force greater than the initial load is applied to the film in the recesses.

[0279] In Non-Patent Document 1, an elastic material is used for the film, but if a plastically deformable film like that used in this embodiment is used, a sufficient repulsive force cannot be obtained to follow the sliding plate when released. Alternatively, if a sufficient repulsive force is attempted, the valve will remain closed. If the pin does not receive a repulsive force from the film in the recess, the pin will not be able to follow the sliding plate. If the frictional force with the pin guide is large, the pin may get caught midway.

[0280] In Figure 20A, if the spring constant of the spring installed inside ball plunger 509 is reduced, the depression force can be stabilized. For a spring with a small spring constant, a higher initial load must be set to obtain sufficient necessary depression force with a small amount of contraction, but with the configuration in Figure 20A, the pressing force at the recessed portion becomes large. On the other hand, if the height of the recessed portion is increased to increase the amount of spring contraction, the diameter of ball plunger 509 must be increased to obtain a sufficient stroke. Because the diameter of ball plunger 509 is increased, the minimum valve spacing also increases.

[0281] If a downward force greater than the initial load is constantly applied to the fluidic device, the top of the pins will pop out of the pin guide when the fluidic device is removed. This requires either inserting the fluidic device from the positive direction of the Z axis, or a mechanism to drive the sliding plate in the negative direction of the Z axis. If the fluidic device cannot be inserted parallel to the Z axis, it may get caught on the pins.

[0282] The distance from the contact point of the sliding plate to the top of the pin cannot be increased for the ball plunger 509. Therefore, if an attempt is made to design the sliding plate so that it does not interfere with the sliding plate, the length in the X-axis direction will be increased.

[0283] (iv) Figure 20B shows the pin characteristics of Patent Document 4. When the pin is in the recess, if the head is away from the flow path device, it is possible to open the flow path. In the range of Z1≦Zp, the slope of the first force F1 increases rapidly as Zp increases. It is difficult to control the pressing force when closing. Patent Document 4 uses an elastic film, but if the film is not made of an elastic material, it is more difficult to control the pressing force by adjusting the height of the sliding plate.

[0284] In this prior art example, the valve is used as a pump. Therefore, it is not a problem if the convex portion is not 100% closed, but a fairly strong pressure is required to properly close the valve, which inevitably increases the load on the actuator.

[0285] (v) In Patent Document 4, the elastic force of the spring acts on the flow path device so as to press the pin against the sliding plate, whereas in Non-Patent Document 1, the elastic force of the spring acts on the pin guide (pin holder) so as to press the pin against the sliding plate.

[0286] Here, we consider a case where the configurations of Patent Document 4 and Non-Patent Document 1 are combined. Figure 20C shows a configuration in which two springs are incorporated into a pin, with the first spring acting to press the pin against the sliding plate relative to the flow path device, and the second spring acting to press the pin against the sliding plate relative to the pin guide. Note that Figure 18C (2) shows the changes in the first force F1 and second force F2 of the pin as shown in Figure 20C relative to Zn. In this example, the pressing force remains at the time of release, preventing sufficient release.

[0287] In contrast, in this embodiment, as described above, the relationships Zn≦Z1 and Z0≦Z1<Z2 hold, so the pressing force when the valve is opened can be sufficiently small. In this embodiment, the magnitude of the first force F1 when released is 1 / 5 or less of that when closed. Therefore, a sufficiently low closing rate can be obtained when released. Furthermore, because Zn<Z1, the head 309 separates from the flow path device 104 at the recess 312, and the pressing force can be reduced to zero. Furthermore, because Zn≦Z0, the pin 304 can stably follow the uneven portion of the sliding plate 303.

[0288] In this embodiment, the sliding plate contact portion 308 can be configured with rollers, allowing the valves to be arranged more densely than when configured with balls. Also, the sliding plate contact portion 308 can be designed so as not to be connected to the first spring (first spring 306).

[0289] In this embodiment, the second spring (second spring 307) is configured to contact the pin lower portion 305. Therefore, it is possible to apply a force to the sliding plate 303 independently of the first spring (first spring 306). Therefore, it is possible to reduce the size of the first spring (first spring 306).

[0290] Furthermore, in this embodiment, multiple valves in one flow path device 104 can be driven by multiple sliding plates 303. For example, if there are eight or more valves, attempting to open and close all the valves with one sliding plate 303 would require the sliding plate 303 to be long. However, using two or more sliding plates 303 can prevent the analysis system 101 from becoming large. On the other hand, the arrangement of the sliding plates 303 and the pin guides 302 / pins 304 can be repeated the number of times the number of flow path devices 104 is arranged so that one sliding plate 303 can drive the valves of multiple flow path devices 104. By sharing the sliding plate 303 among multiple flow path devices 104, the movement allowance of the sliding plate 303 can be shared, preventing the analysis system 101 from becoming large. The number of actuators required can be reduced.

[0291] 20D and 20E compare the characteristics of the force (first force) applied to the flow path device 104 by pins 304 of different configurations. FIG. 20D(1) shows the change in the first force in the configuration of FIG. 20B(1). Because the pin 304 closes the valve as a rigid body, the pressing force varies significantly around Zp = Z2. Therefore, even a slight mechanical error can cause Fc to exceed Fmax, damaging the device, or Fc to fall below Fclose, preventing the valve from closing. To prevent this situation, a design that minimizes fluctuations in Z2 between devices or analysis runs is required. For example, in a system where the difference between Fclose and Fmax is only 5 N, if the pressing force fluctuates by 50 N / mm relative to the amount of fluctuation in Zp around Zp = Z2, the required mechanical error is ±0.05 mm.

[0292] Figure 20D(2) is a diagram showing changes in the first force in the configuration of Figure 20A(1). Because the pin is in contact with the film even when opened, the first force Fo when opened satisfies Fo>0. Because the pressing force does not fall below Fopen when opened, the valve cannot be opened. Furthermore, if the pin is made of a spring plunger or if friction exists between the pin and the pin guide, the value of Fo will fluctuate, making it difficult to achieve a reproducible open state.

[0293] Figure 20E(1) is a continuation of Figure 20D and shows the change in the first force in the configuration of this method, as in Figure 9. Because the pin 304 is equipped with a first spring, the spring constant of the first spring can adjust the fluctuation in the pressing force before and after Zp = Z2. Even in a system where the difference between Fclose and Fmax is only 5 N, by using a spring with a spring constant of 5 N / mm as the first spring, for example, it is possible to close the valve with an apparatus configuration in which the fluctuation in Zp is ±0.5 mm or less. Furthermore, when the valve is opened, the pressing force becomes zero due to the action of the second spring, ensuring reliable opening of the valve.

[0294] When using a spring without a preload, there is a trade-off between the tolerance for mechanical error and the height of the unevenness of the sliding plate. For example, consider the case where this sliding plate drive system is applied to a valve with a depression force-closing rate characteristic shown in Figure 3D, where Fclose is 15 N and Fmax is 20 N. When using a spring with a spring constant of 15 N / mm without a preload, if the compression amount fluctuates by 1.5 ± 0.5 mm, the depression force fluctuates between 15 N and 30 N, exceeding Fmax. On the other hand, when using a spring with a spring constant of 5 N / mm without a preload, if the compression amount fluctuates by 3.5 ± 0.5 mm, the depression force fluctuates between 15 N and 20 N, which is appropriate, but it requires a larger height of the unevenness of the sliding plate than when the spring constant is 15 N / mm, which is disadvantageous. On the other hand, using a spring plunger with a preload can resolve this trade-off. As shown in Figure 20E(2), when a spring plunger with an appropriate initial load is used, the unevenness height of the sliding plate can be designed to be small while maintaining the tolerance for mechanical error. For example, by using a spring with a spring constant of 5 N / mm and an initial load of 10 N, a force greater than Fclose can be applied if the contraction amount is 1.5 mm. Even if the spring constant fluctuates by ±0.5 mm, the pressing force will fluctuate within the range of 15 N to 20 N, which is appropriate.

[0295] <Configuration Example of Analysis System 101> (i) Regarding Chambers and Reagent Storage Units A typical chamber or reagent storage unit is a space capable of storing liquids or solids and capable of reacting, waiting, heating, or changing solutions. A chamber may have a larger diameter than a flow channel, but it may also be visually indistinguishable from a flow channel. A chamber may have an internal membrane or microstructure, or may be made of a different composition than the flow channel, have a different surface treatment, or have a different hydrophilicity. A heater or laser light source may also be attached to the outside of the flow channel device. Reagents may be stored in the chamber, and PCR, lysis, purification, etc. may be performed in the chamber. A typical chamber volume is preferably 0.01 μL to 50 mL.

[0296] Reagents may be stored within the flow path device 104, or they may be supplied from outside the flow path device 104 and within the analytical system 101. As an example, the flow path device 104 may be configured to store one or more types of reagents in one or more reagent reservoirs. The reagents include at least one of a lysing solution, a cleaning solution, a PCR reagent that may contain a polymerase, a primer, a surfactant, etc., formamide, pure water, DNA fragments, and oil. Unintended mixing of these reagents can lead to performance degradation or other unexpected results. Therefore, it is desirable to separate the reagents until just before use with a partition mechanism consisting of a valve, film, air, or a flow path narrow enough to prevent spontaneous mixing, or a combination thereof. Furthermore, isolating the reagents from the outside air enables long-term storage and portability of the flow path device. When the same reagent is released in multiple steps, it may be stored in multiple reagent reservoirs. Similarly, when reagents are stored outside the flow path device 104, they are desirably stored in a state isolated from the outside air and separated from other purification system components by a valve, film, air, etc. Known reagent storage technologies include, for example, blister reagent storage units and the reagent storage units described in Patent Document 1 and Patent Document 5. Similar configurations to these may be incorporated into this embodiment. Furthermore, in Patent Document 5, the reagent storage unit is sealed with a film that is easily broken when pressure is applied, and the seal is broken by applying pressure, releasing the reagent inside into the flow path. In the case of such a reagent storage unit, the reagent can be opened and released simply by opening and closing a valve, allowing the system to be miniaturized. A reagent storage unit of this type may be incorporated into the flow path device 104 of this embodiment.

[0297] (ii) Orientation of the Flow Channel Device 104 The reagent storage units and chambers may be installed so as not to overlap in the XY plane of the flow channel device 104. By arranging them so as not to overlap in the XY plane of the flow channel device 104, the layer structure of the flow channel device 104 can be prevented from becoming complex. However, elements (components) with small volumes can be arranged on the Z-positive and Z-negative sides of the XY plane of the flow channel device 104, even if they are arranged in layers. By storing the solution in the Y-negative direction, making it easier for air to accumulate in the Y-positive direction, and removing the solution from an outlet provided in the Y-negative direction, the inclusion of air bubbles can be minimized. In this case, it is preferable that the Y-negative direction be parallel to gravity (0° angle) or form an angle of 45° or less with respect to gravity, or an angle less than 90° with respect to gravity. Furthermore, in this case, the Z-negative direction is not parallel to gravity. That is, gravity does not act much on the pin 304 in the Z-axis direction, but gravity acts in the Y-axis direction, creating a frictional force between the pin 304 and the pin guide 302, making it difficult to follow without the second spring 307.

[0298] <Examples of Sample Types> The sample provided to the analysis system (purification system) 101 according to this embodiment is not particularly limited as long as it is a biologically derived sample. The biological source of the sample is also not particularly limited, and samples derived from any biological source, such as vertebrates (e.g., mammals, birds, reptiles, fish, amphibians, etc.), invertebrates (e.g., insects, nematodes, crustaceans, etc.), plants, protozoa, fungi, bacteria, and viruses, can be used. Samples can be collected using a carrier such as a swab, filter paper, or cloth. The carrier may be introduced into the analysis system 101.

[0299] Forensic samples can also be analyzed using the analysis system 101. Here, forensic samples include cheek swabs, bone, muscle tissue, human organs, touch samples containing trace amounts of DNA, bloodstains, skin fragments, hair, bodily fluids, and artifacts presumably containing these. Many forensic samples contain unknown amounts of DNA. The DNA concentration ranges from 0.001 ng to 1000 μg, more frequently from 0.01 ng to 10 μg. Furthermore, forensic samples may contain only DNA from a single individual, DNA from multiple individuals, or degraded DNA. To increase the success rate of DNA identification, it is necessary to minimize DNA loss due to surface adsorption within the DNA flow path device 104.

[0300] <Solution Transport Control> The analysis system 101 may include pumps and valves for transporting a solution. As a transport means, a syringe pump, a diaphragm pump, an electrochemical pump, passive transport using surface tension, centrifugal force, or a combination thereof can be used.

[0301] Valves are used to specify the solution transport path and also to switch the path to which air pressure is applied. Valves can be diaphragm valves that operate with air pressure, mechanical valves, or valves that use surface tension. The flow paths that can be transported can also be switched based on the difference in pressure required for transport.

[0302] <Detection Method> After amplification, detection is performed by CE. CE can use a method in which the amplified product is injected into a capillary filled with a polymer by voltage injection. Furthermore, in CE, when a high voltage is applied to both ends of the capillary, fluorescent DNA fragments are separated by size and detected by a laser / camera system. While this specification primarily refers to CE analysis, in other embodiments, instead of the CE section, MPS (Massively Parallel Sequencing), pyrosequencing, Sanger sequencing, nanopore sequencing, chromatography, electrical measurement, spectroscopy, NMR, RFLP (Restriction Fragment Length Polymorphisms), microarrays, etc. may also be used.

[0303] <Configuration Example of Analysis System 101> Fig. 21 is a diagram showing a detailed configuration example of the analysis system 101. Fig. 22 is a diagram showing an example of the operation procedure of the analysis system 101. For details of the analysis procedure and transport procedure, reference can be made to Patent Documents 1 and 5, and the description of the QIAamp DNA Investigator Kit manufactured by QIAGEN, etc.

[0304] The analysis system 101 includes a computer 102 for performing biomolecular analysis and a flow path device 104. The flow path device 104 includes a lysis chamber 701 for introducing and lysing a collected sample, a purification membrane chamber 703 containing a purification membrane 702, a PCR chamber 704 for performing DNA amplification and the like, a waste liquid chamber 705, and an external connection port 706 fluidically connected to the outside of the flow path device 104. The solution is transported via the external connection port 706, allowing reagents, amplification products, and the like to be exchanged with the outside of the flow path device 104. In the analysis system 101, when transporting a solution, the liquid transfer can be controlled using a pump 707 and a valve. The pump 707 may be provided entirely outside the flow path device 104, or a portion of the pump 707 may be provided within the flow path device 104.

[0305] The PCR reagent reservoir 708 holds reagents necessary for the PCR reaction (polymerase, primer, dNTP, buffer, etc.). The migration reagent reservoir 710 may hold migration reagents. Furthermore, other reagent reservoirs for storing reagents necessary for pretreatment are also included.

[0306] In the sample loading step S801 of FIG. 22 , before and after the sample is stored in the lysis chamber 701, the lysis solution is transported from the lysis solution reservoir 712 to the lysis chamber 701. Next, in the lysis step S802, lysis begins. After lysis is completed, the binding solution is released from the binding solution reservoir 711. In the purification step S803, the lysis product is transferred from the lysis chamber 701 to the purification membrane chamber 703, where the DNA is bound to the purification membrane 702. A washing solution is then released from the PCR reagent reservoir 708, and purification is performed. After purification, a step of drying the washing solution, etc. may be included. An elution solution is released from the PCR reagent reservoir 708, and the DNA eluted from the purification membrane chamber 703 is transported to the PCR chamber 704. Furthermore, PCR reagents are released from the PCR reagent reservoir 708 to the PCR chamber 704 and mixed with the eluted DNA. In the amplification step S804, the purified DNA in the PCR chamber 704 is mixed with PCR reagents and subjected to a PCR reaction. In the detection step S805, the amplified DNA is mixed with the migration reagent stored in the migration reagent storage unit 710, and measurement is carried out in the CE unit 105.

[0307] After mixing the electrophoresis reagent and the PCR reaction solution, a step of heating the mixture to 80 to 100°C and then rapidly cooling it to 0 to 10°C may be added before CE analysis. By adding this step, the DNA is more completely converted into single strands, enabling highly accurate CE analysis.

[0308] <Operation in Analysis System 101> (Example of Connection of Flow Channels, Valves, and the Like in Flow Channel Device 104) Fig. 23A is a diagram showing an example of connection of a plurality of flow channels, valves, and the like in the flow channel device 104 used in the analysis system 101. Fig. 23B is a diagram for explaining a liquid transfer operation, etc. in the flow channel device 104 of the analysis system 101.

[0309] Referring to FIG. 23A , the flow path device 104 includes external connection ports 951, 952, 953, and 954. The flow path device 104 exchanges solutions with the analysis system 101 via the external connection ports 951, 952, 953, and / or 954, and can be controlled by air pressure. Here, the external connection port 951 is connected to a pressure pump, the external connection port 952 is connected to a detection unit, and the external connection ports 953 and 954 are connected to the atmosphere. If the external connection ports 953 and 954 are not directly connected to the atmosphere, there is a risk of liquid splashing and contamination due to unexpected operation. Therefore, a vent filter may be provided before connecting to the atmosphere. The vent filters may be fitted into the external connection ports 953 and 954, respectively. The external connection ports 953 and 954 may be connected to a single vent filter.

[0310] The external connection port 951 (external pressure connection port) is connected to a flow path 901 equipped with a valve V4, flow paths 902, 903, 904, and 905 equipped with a valve V12, and a flow path 906 equipped with a valve V10. The flow path 901 is connected to a flow path 907 and a flow path 908 equipped with a valve V2. The flow path 907 is connected to a lysis chamber 701. The flow path 908 is connected to an external connection port 953. The flow path 903 is connected to a binding liquid reservoir 711. The flow path 904 is connected to a cleaning liquid reservoir 713. The flow path 905 is connected to a lysis liquid reservoir 712. The flow path 902 is connected to a mixing chamber 955.

[0311] The binding liquid reservoir 711 is connected to a flow path 919 equipped with a valve V5. The lysis liquid reservoir 712 is connected to the lysis chamber 701 via a flow path 920 equipped with a valve V3 and a flow path 910. The lysis chamber 701 is connected to a flow path 909 equipped with a valve V1. The flow path 909 is connected to a flow path 911 equipped with a valve V15. The flow path 911 is connected to the silica membrane chamber 702. The flow path 906 is connected to the flow path 909 between the valves V15 and V1. The silica membrane chamber 702 is connected to a flow path 921. The flow path 921 is connected to a flow path 912 equipped with a valve V7 and a flow path 913 equipped with a valve V6. The flow path 912 is connected to a flow path 915 equipped with a flow valve V9 and a flow path 916 equipped with a valve V8.

[0312] The cleaning liquid reservoir 713 is connected to a flow channel 915. The flow channel 916 is connected to a waste liquid chamber (waste liquid tank) 705. The waste liquid chamber 705 is connected to an external connection port 954. The flow channel 913 is connected to a PCR chamber 704.

[0313] The PCR chamber 704 is connected to a flow path 914 equipped with a valve V11. The mixing chamber 955 is connected to the flow path 902, the flow path 914, a flow path 917 equipped with a valve V13, and a flow path 918 equipped with a valve V14. The flow paths 918 and 917 are connected to an external connection port 952. The eluate reservoir 709 is connected to a flow path 911 between the valve V15 and the reagent chamber. The PCR reagent reservoir 708 and the migration reagent reservoir 710 are connected to a flow path 913 between the valve V6 and the PCR chamber 704. It is assumed that the slider drive system 301 is provided with pins 304 and through-holes 310 corresponding to each of the valves V1 to V15.

[0314] (Valve Actuation by Multiple Sliding Plates) (i) Figure 24A is a diagram showing the flow channel configuration of the flow channel device 104 of Figure 23A and the valve opening and closing steps corresponding to the operation example shown in Figure 23B. In Figure 24A, ◯ indicates a step in which the valve must be open, and × indicates a step in which the valve must be closed. When liquid is pumped / depressurized to transfer, the upstream valve refers to the valve closest to the pump that pressurizes / depressurizes. The downstream valve refers to the valve closest to the outlet that is open to the atmosphere or the valve farthest from the pump. For example, when the upstream valve is closed, the downstream valve does not affect the liquid transfer operation whether it is open or closed. Furthermore, when there is no pump pressurization / depressurization, the liquid transfer operation is not affected whether the valves other than those closest to the chamber where the liquid is stored are open or closed. In Figure 23A, blank valves indicate valves that may be open or closed.

[0315] When the valve opening and closing operation of FIG. 24A is performed by one sliding plate 303, the sliding plate 303 must be provided with valve patterns for at least 14 steps in total, including the steps of inserting and removing the flow channel device 104.

[0316] The 14 steps of the sliding plate 303 correspond to, for example, a width of 100 mm in the X-axis direction and a drive range of 150 mm. If the sliding plate drive system 301 is shared among four flow path devices 104, a drive range of 450 mm is required. Furthermore, the maximum load borne by the sliding plate drive system 301 is 7 valves x number of flow path devices, and the number of valves that can be closed simultaneously is 6 valves x number of flow path devices.

[0317] A driving range of 450 mm is required for the sliding plate 303, which increases the size of the analysis system 101. In addition, since six valves are simultaneously closed and seven valves are simultaneously closed, a large actuator is required.

[0318] To solve the above problem, the sliding plate 303 is divided into two, three, or four or more sections. Here, for example, the sliding plate 303 is divided into three sections (sliding plates 1 to 3) as shown in FIG. 24A . In this example of sliding plate division, valves V10, V12, V13, and V14 are assigned to sliding plate 1 (S1). Valves V1, V2, V4, V8, and V9 are assigned to sliding plate 2 (S2). Valves V3, V5, V6, V7, V11, and V15 are assigned to sliding plate 3 (S3). The three sliding plates 303 are shared between chips and arranged as shown in FIG. 17B . As shown in FIG. 24A , at least one sliding plate (sliding plates 2 and 3 in the example of FIG. 24A ) can drive five or more pins.

[0319] (ii) Figure 24B is a table showing the sliding plate steps. In Figure 24B, the parts marked with a circle correspond to recesses that can open the valve. The parts marked with an x ​​correspond to protrusions that can close the valve.

[0320] (iii) Figure 24C is a table showing the slider steps corresponding to the analytical process. By assigning different slider steps S1, S2, and S3 to each analytical step, complex valve opening and closing processes can be analyzed using a slider 303 with a small number of slider steps. If the slider 303 is divided into sliders S1, S2, and S3, the number of valve opening and closing steps is four for slider 1, four for slider 2, and five for slider 3. In this case, the width in the X-axis direction is 40 mm, and the driving range is 80 mm. Furthermore, when the driving unit is shared among four flow path devices, the driving range is 240 mm. The maximum number of valves that can be simultaneously closed is three for slider 3, and the maximum number of valves that can be simultaneously closed is four.

[0321] (iv) Figure 24D is a diagram showing the concave-convex lanes of each valve included in the sliding plate 1 shown in Figure 24A unfolded. In an actual sliding plate, the concave-convex lanes of each valve are stacked in the Y-axis direction. The stacking order in the Y-axis direction varies depending on the actual valve arrangement. Furthermore, the thickness of each concave-convex lane in the Y-axis direction may be the same or may be different depending on the arrangement spacing of the valves in the Y-axis direction. The thickness of each concave-convex lane in the Y-axis direction may be determined by the valve arrangement constraints (element 1) and (element 2). In Figure 23D, all valves are shown on the same X-coordinate, but in reality, the X-coordinates of the valves may be different, and the sliding plate may be rectangular as shown in Figure 16D (4).

[0322] (Details of Operation Sequence) Fig. 25 is a flowchart for explaining the analysis sequence in the analysis system 101. Since the uneven driving steps of the sliding plate 303 and pre-processing steps are mixed, here, the uneven driving steps of the sliding plate are expressed as Step 0-0 (S0-0), and the pre-processing steps are expressed as "Step XXX." In the following explanation, Roman numerals I, II, III, etc. indicate each state of the flow channel device 104, such as liquid delivery and valve opening / closing, as shown in Figs. 23A and 23B.

[0323] (I) Before inserting the flow channel device 104, in step S851, the user inserts a sample such as a swab into the flow channel device 104 and closes the sample insertion port. In step S852, the user inserts the flow channel device 104 into the analysis system 101. At this time, Step 1-1 (S1-1) of the sliding plate S1 contacts the pin 304, Step 2-1 (S2-1) of the sliding plate S2 contacts the pin 304, and Step 3-1 (S3-1) of the sliding plate S3 contacts the pin 304.

[0324] (II) When the user presses the start button of the analysis system 101, sliding plates S1, S2, and S3 move. On sliding plate S1, S1-2 contacts pin 304, on sliding plate S2, S2-2 contacts pin 304, and on sliding plate S3, S3-3 contacts pin 304. As sliding plate S3 moves, valves V10, V12, V1, V4, V9, V3, V5, and V6 are closed. Then, external connection port 951 is pressurized. Flow paths 903, 904, and 905 are pressurized, and the seal on solution reservoir 712 is opened.

[0325] (III) In step S853 (step S801), the sliding plate S3 moves, and S3-2 comes into contact with the pin 304. At this time, the valves V7 and V15 are closed. Furthermore, the valves V3, V6, and V11 are opened. Subsequently, the external connection port 951 is pressurized. Then, the valve dissolving liquid is released from the dissolving liquid reservoir 712 and transported to the dissolving chamber 701 via the flow path 920.

[0326] (IV) When lysis is complete, sliding plate S3 moves and S3-5 contacts pin 304. At this time, valves V3, V6, and V7 are closed. Valves V1, V4, and V7 are opened. In step S855, the binding liquid is transported to the lysis chamber via flow path 919. Then, in step S856, the lysate is mixed with the binding liquid.

[0327] (V) When mixing is complete, sliding plates S2 and S3 move, and S2-3 and S3-3 contact pin 304. In step S857, valves V1, V4, V8, V7, and V15 are opened. Valves V2, V9, V3, V5, and V6 are closed. Next, external connection port 951 is pressurized. The lysate is sent from lysis chamber 701 to purification membrane chamber 703, and DNA binds to purification membrane 702. Waste liquid is discharged from vent filter 954 via flow paths 912 and 916.

[0328] (VI) In step S858, sliding plate S2 moves, and S2-4 contacts pin 304. At this time, valves V2 and V9 are opened. Valves V4 and V8 are closed. Then, external connection port 951 is pressurized. Cleaning solution is released from cleaning solution reservoir 713 and sent to purification membrane chamber 703 via flow path 920.

[0329] (VII) In step S859, sliding plates S1 and S2 move, and S1-3 and S2-2 come into contact with pin 304. At this time, valves V10 and V8 are opened. Valves V13, V1, and V9 are closed. Next, external connection port 951 is pressurized. Air is sent in via flow path 906, and this air dries the cleaning liquid. The air that has dried the cleaning liquid is discharged from vent filter 954 via flow paths 912 and 916.

[0330] (VIII) In step S860, sliding plate S3 moves, and S3-2 contacts pin 304. At this time, valves V7 and V15 are closed. Valves V3, V6, and V11 are opened. Subsequently, eluate is released from eluate reservoir 709, and DNA is eluted from purification membrane chamber 703.

[0331] (IX) In step S861, the sliding plate S3 moves, and S3-4 comes into contact with the pin 304. At this time, the valve V15 is opened. Also, the valve V3 is closed. Then, the external connection port 951 is pressurized. Then, the eluate is transported to the PCR chamber 704.

[0332] (X) In step S862, sliding plate S3 moves and S3-5 comes into contact with pin 304. At this time, valve V6 is closed. Valve V5 is opened. Next, PCR reagent is released from PCR reagent reservoir 708 in PCR chamber 704 and mixed with the eluted DNA.

[0333] (XI) In step S863 (amplification step S804), the slider S3 moves and S3-3 comes into contact with the pin 304. At this time, valves V11 and V15 are closed. Valve V7 is opened. Subsequently, the PCR chamber 704 is heated, and the amplification reaction begins.

[0334] (XII) When the PCR reaction is completed, in step S864, the slider S3 moves and S3-5 contacts the pin 304. At this time, valves V5 and V11 are opened. Valve V7 is closed. Next, the migration reagent reservoir 710 is collapsed, releasing the reagent. The PCR product is transported to the mixing chamber 755 via the flow path 914.

[0335] (XIII) In step S865, the sliding plate S3 is moved so that S3-4 contacts the pin 304. At this time, the valve V6 is opened. The valve V5 is closed. Furthermore, the valves V12, V4, V9, V3, V5, and V7 are closed. Next, the external connection port 951 is pressurized, and air is sent into the mixing chamber 955. Then, the lysate and the migration reagent are mixed. The air is discharged to the outside of the flow path device 104 via the flow path 918.

[0336] (XIV) In step S866, the sliders S1 and S3 move, and S1-4 and S3-3 come into contact with the pins 304. At this time, the valves V12, V13, and V7 are opened. Furthermore, the valves V10, V6, V11, and V14 are closed. Next, the external connection port 951 is pressurized, and air is sent from the flow path 902. As a result, the electrophoresis sample is transported out of the flow path device 104 via the flow path 917. Then, measurement is performed in the CE unit 105. After the preprocessing is completed or when all the analyses are completed, the sliders S1, S2, and S3 move, and S1-1, S2-1, and S3-1 come into contact with the pins 304. At this time, all the valves are opened, and the flow path device 104 can be removed.

[0337] The above steps are merely examples, and different transport steps can be performed with the same valve arrangement. The drying path may also be different from that described above. Furthermore, the lysate and the washing solution may flow from the same direction. The sliding plate 303 can also be divided according to a similar rule.

[0338] Summary of the Embodiment (i) In the valve opening and closing system (see FIGS. 4A and 7 ) included in the analysis system 101 according to this embodiment, the pin head 309 does not contact the valve of the flow path device 104 when the valve is open. In other words, a certain clearance exists between the pin head 309 and the valve of the flow path device 104 when the valve is open. This enables accurate valve opening and closing. To describe the conditional expressions in more detail, let Zp be the Z coordinate of the negative Z-axis end of the pin 304, Z0 and Z2 be the Z coordinates of the recessed and protruding portions on the surface of the sliding plate (third plate) 303, respectively, Z1 be the minimum Zp at which the first spring 306 elastically deforms, and Zn be the minimum Zp at which the second spring 307 elastically deforms. The valve opening and closing system is configured so that the relationships Z0≦Z1<Z2 and Zn≦Z1 hold. In order to keep the pin head 309 completely out of contact with the flow channel device 104 when the pin 304 is in the recess 312 of the sliding plate 303, it is necessary to satisfy Z0<Z1.

[0339] 3B, the force (first force F1) that the valve opening and closing system applies to the valve of the flow path device 104 when Zp=Z2 (Fc) is five times stronger than when Zp=Z0 (Fo). This makes it possible to maintain the valve opening and closing ratio in an appropriate state.

[0340] (iii) As shown in Figure 4B, if the Z coordinate of the lower end of the pin sliding plate ground contact portion 308 is Zp, the Z coordinates of the recessed portion 312 and the protruding portion 311 on the surface of the sliding plate 303 are Z0 and Z2, respectively, the minimum Zp at which the first spring 306 elastically deforms when the head 309 contacts the flow path device 104 is Z1, and the minimum Zp at which the second spring 307 elastically deforms is Zn, then in the example of Figure 4B, the relationships Z0 ≦ Z1 ≦ Z2 and Zn ≦ Z0 hold. Also, in Figure 18C, the relationships Z1 ≦ Z0 and Zn ≦ Z0 hold. In other words, by setting Zn ≦ Z0, the pin 304 can stably follow the uneven portion of the sliding plate 303.

[0341] (iv) As shown in Fig. 18A , the valve opening and closing system according to this embodiment is configured so that the first derivative (the slope of the graph in Fig. 18A (2)) of the second force F2 applied by the pin lower part 305 to the sliding plate 303 with respect to Zp (the Z coordinate of the negative Z-axis end of the pin 304) increases before and after Z1. In other words, the valve depressing force (first force F1) by the pin 304 and the force (second force F2) by which the pin 304 presses the sliding plate 303 can be separated (the contact points between the sliding plate ground contact part (e.g., roller) 308 and the first spring 306 can be separated), so that the diameter of the pin 304 can be reduced, and the valve opening and closing system, and therefore the analysis system 101, can be made smaller.

[0342] (v) When elastically deformed, the second spring (second elastic body) 307 is connected to (contacts) the pin lower portion 305. In other words, the lower end of the second spring 307 does not need to be in contact with the pin lower portion 305 when in its natural length.

[0343] Furthermore, the first spring (first elastic body) 306 and the second spring (second elastic body) 307 can be made independent, allowing the spring constants to be selected independently. By setting the spring constant of the first spring 306 to be greater than the spring constant of the second spring 307, the stability of the valve opening and closing operation can be improved. (vi) In this embodiment, the rate of increase of the valve depression force (first force F1) in the range Z1≦Zp≦Z2 is set to 40 N / mm or less.

[0344] (vii) The flow channel device 104 used in the analysis system 101 of this embodiment has a substrate on which a flow channel is formed and a flow channel lid material made of a film. The film deforms when a valve depression force is applied, and functions as a valve that suppresses the passage of fluid through the flow channel. The film is made of a plastically deformable film. The valve opening and closing system of this embodiment is well suited to stably opening and closing a valve made of such a plastically deformable film, because the valve depression force is completely removed when the valve is opened (there is clearance between the pin head 309 and the flow channel device 104).

[0345] (viii) In this embodiment, as shown in Fig. 24A, five or more pins 304 can be driven by one sliding plate 303. Since a large number of pins are driven by one sliding plate 303 in this way, the valve opening and closing operation can be performed efficiently.

[0346] (ix) When Zp<Z1 (when the Z coordinate Zp of the sliding plate contact portion 308 is smaller than the smallest Z coordinate Z1 of the sliding plate contact portion 308 when the first spring 306 elastically deforms), the first spring 306 applies an elastic force to the pin head 309 and the pin lower portion 305 that is 50% or more of the elastic force when Z=Z2 (when the sliding plate contact portion 308 is on the convex portion 311 of the sliding plate 303).

[0347] (x) In the analysis system 101 of this embodiment, as shown in Figures 17A and 17B, two or more flow path devices 104 can be arranged in the X-axis direction for analysis. In this case, the arrangement pattern of the concave and convex portions of the sliding plate 303, the through holes 310 of the pin guide 302, and the pins 304 is repeated at equal intervals for the number of flow path devices 104 (see Figure 17D). In this case, the sliding plate 303 is configured to drive a total of 10 or more pins (12 pins (the second pin is not shown) are shown in Figure 17D).

[0348] 101 Analysis system 102 Computer 103 Database 104 Flow path device (first plate) 105 Detection unit (CE unit) 106 User interface 201 Flow path substrate 202 Film 203 Head 204 Flow path 205 Flow path bottom (valve bottom) 301 Slider plate drive system 302 Pin guide 303 Slider plate 304 Pin 305 Pin bottom 306 Transmission mechanism (first spring) 307 Tracking mechanism (second spring, first spring) 308 Slider plate ground contact part (roller) 309 Pin top (head) 310 Through hole 311 Convex part 312 Concave part 313 Uneven surface 314 Device holder 315 Linear guide (ball guide) 316 Actuator 317, 318 Magnet 319, 320 Magnet / magnetic material 321 Guide 322 Protrusion 323 Elastic sheet 324 Second recess 325 Concave / convex lane 401 Reagent sealing member 402 Reagent storage section 403 Alignment hole 501 Spring plunger 502 Second spring recess 503 Second spring base 504 Base recess 505 Edge 506 Engagement section 507 Protrusion 508 Spring storage section 509 Ball plunger 510 Spring storage section 511 Protrusion 512 Shaft 513 Leg 601 Protrusion 602 Rail guide 603 Groove 604 Enclosure 701 Lysis chamber 702 Purification membrane 703 Purification membrane chamber 704 PCR chamber 705 Waste liquid chamber 706 External connection port 707 Pump 708 PCR reagent reservoir 709 Elution liquid reservoir 710 Migration reagent reservoir 711 Binding liquid reservoir 712 Dissolution liquid reservoir 713 Washing liquid reservoir 714 Dispensing chamber 715 Migration reagent reservoir 901 to 921 Flow paths 951 to 954 External connection port 955 Mixing chamber 1701 Arrangement pattern

Claims

1. A valve opening / closing system for opening and closing a valve provided on a first plate constituting a flow path device placed parallel to the XY plane in an XYZ orthogonal coordinate system, comprising: a second plate having a through hole; a pin having an upper portion in the +Z-axis direction and a lower portion in the -Z-axis direction, and having a central axis parallel to the Z-axis; a third plate having a movable range in the X-axis direction and having irregularities on a surface in the +Z-axis direction; a first elastic body that connects the upper portion and the lower portion of the pin during elastic deformation; a second elastic body that connects the second plate and the upper portion or the lower portion of the pin during elastic deformation; and a control unit that drives the third plate. The first plate, the second plate, and the third plate are arranged in order along the -Z-axis direction perpendicular to the Z-axis. The pin is installed between the first plate and the third plate in a state of passing through the through hole of the second plate. The control unit moves the third plate in the X-axis direction, so that the -Z-axis end of the pin can move in the Z-axis direction following the irregularities on the surface of the third plate, and generates a first force applied by the upper portion of the pin to the first plate. Let the Z coordinate of the -Z-axis end of the pin be Zp, the Z coordinates of the concave portion and the convex portion on the surface of the third plate be Z0 and Z2 respectively, the minimum Zp when the first elastic body elastically deforms be Z1, and the minimum Zp when the second elastic body elastically deforms be Zn. Then, a valve opening / closing system in which the relationship Z0≤Z1<Z2 and Zn≤Z1 holds.

2. The valve opening / closing system according to claim 1, wherein the first force applied to the first plate when Zp = Z2 is at least 5 times stronger than the first force when Zp = Z0.

3. The valve opening / closing system according to claim 1, wherein Z0<Z1, and the pin is in a non-contact state with the first plate when the pin is in the concave portion of the third plate.

4. The valve opening / closing system according to claim 1, wherein Zn≤Z0.

5. The valve opening / closing system according to claim 4, wherein the first derivative of the second force applied by the lower portion of the pin to the third plate with respect to Zp increases around Z1.

6. The valve opening / closing system according to claim 1, wherein the second elastic body is connected to the lower portion of the pin during elastic deformation.

7. In claim 1, a valve opening and closing system, wherein the spring constant of the first elastic body is greater than the spring constant of the second elastic body.

8. In claim 1, a valve opening and closing system, wherein the increase rate of the first force in the range of Z1 ≤ Zp ≤ Z2 is 40 N / mm or less.

9. In claim 1, a valve opening and closing system, wherein the first plate has a substrate in which a flow path is formed and a flow path cover material made of a film, and the film is deformed by the first force and functions as a valve that suppresses the passage of fluid in the flow path.

10. In claim 9, a valve opening and closing system, wherein the control unit deforms the film that undergoes plastic deformation with the first force by moving the third plate to increase the first force.

11. In claim 1, a valve opening and closing system, wherein the third plate drives 5 or more pins.

12. In claim 1, a valve opening and closing system, wherein when Zp < Z1, the first elastic body applies an elastic force of 50% or more of the elastic force when Z = Z2 to the upper part and the lower part of the pin.

13. In claim 1, a valve opening and closing system, wherein the pin has a wheel that rolls on the third plate, which is a sliding plate, and is arranged at the lower end of the pin so as not to be connected to the first elastic body.

14. In claim 1, a valve opening and closing system, wherein two or more of the first plates are arranged in the X-axis direction, the unevenness of the third plate, the through holes of the second plate, and the arrangement pattern of the pins are repeatedly arranged at equal intervals according to the number of the first plates, and the third plate drives a total of 10 or more pins.

15. An analysis system comprising: a flow path device placed parallel to the XY plane in an XYZ orthogonal coordinate system; the valve opening and closing system according to claim 1; a pump for transporting a solution in the flow path device; and a detection unit for measuring a reaction solution obtained by reacting the solution and a reagent.