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WO2025120718A1 - Système d'ouverture/de fermeture de vanne et système d'analyse - Google Patents

Système d'ouverture/de fermeture de vanne et système d'analyse Download PDF

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Publication number
WO2025120718A1
WO2025120718A1 PCT/JP2023/043403 JP2023043403W WO2025120718A1 WO 2025120718 A1 WO2025120718 A1 WO 2025120718A1 JP 2023043403 W JP2023043403 W JP 2023043403W WO 2025120718 A1 WO2025120718 A1 WO 2025120718A1
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WO
WIPO (PCT)
Prior art keywords
pin
sliding plate
valve
flow path
spring
Prior art date
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Pending
Application number
PCT/JP2023/043403
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English (en)
Japanese (ja)
Inventor
沙也可 手塚
祐美子 合志
隆 穴沢
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hitachi High Tech Corp
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Hitachi High Tech Corp
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Publication date
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Priority to PCT/JP2023/043403 priority Critical patent/WO2025120718A1/fr
Publication of WO2025120718A1 publication Critical patent/WO2025120718A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N37/00—Details not covered by any other group of this subclass

Definitions

  • This disclosure relates to a valve opening and closing system and an analysis system.
  • pre-processing 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 complicated sample preparation. For this reason, it was common in the past to send samples to an environment with well-equipped experimental equipment, such as a research laboratory, where inspectors with specialized knowledge and skills prepare and measure the samples and then analyze the data.
  • problems include the time it takes to transport samples, and the large facility and labor costs required to maintain the experimental equipment. Also, in laboratories that use batch processing, it is difficult to interrupt urgent samples.
  • sample-to-answer analysis systems that perform the entire process from sample introduction to measurement and data acquisition in an automated manner have begun to appear in various fields.
  • Sample-to-answer analysis systems may use flow path devices that integrate chambers, flow paths, and stored reagents.
  • Sample-to-answer analysis systems that use 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 manual techniques is reduced, and (5) Reagents can be easily stored. Examples of sample-to-answer analysis systems include the analysis systems described in Patent Documents 1 and 5, which dissolve, purify, PCR, and detect human-derived samples to perform DNA identification in a fully automated manner.
  • Sample-to-answer analytical systems are used in a variety of fields, including potential applications, including forensic medicine, 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. In addition, multiple samples must be analyzed simultaneously or sequentially.
  • valves are often used to pressurize/depressurize the appropriate flow path and send fluid to the appropriate flow path or chamber.
  • Patent Document 1 Patent Document 2, Patent Document 3, Patent Document 4, Patent Document 5, and Non-Patent Document 1
  • part or all of the valve opening/closing drive mechanism is provided outside the flow path device, and can be used repeatedly between analysis rounds.
  • 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.
  • valve drive mechanism which is a non-consumable item
  • flow path device which is a consumable item
  • 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. To optimize, for example, there must be a high degree of freedom in the placement of the valves.
  • the flow path device or valve drive mechanism must be small. To make the valve drive mechanism small or simple, multiple valves may be operated by a single drive system.
  • 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.
  • Patent Document 3 Patent Document 4, and Non-Patent Document 1 employ a drive system in which a sliding plate with projections and recesses that move linearly or rotationally pushes up a pin at the projections, crushing the valve, and the pin moves away from the valve at the recesses, opening the valve.
  • a sliding plate with projections and recesses that move linearly or rotationally pushes up a pin at the projections, crushing the valve, and the pin moves away from the valve at the recesses, opening the valve.
  • the axis along which the pin moves at the point of contact between the sliding plate and the pin coincides with the axis that applies force to the valve.
  • 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.
  • the pin acts as a rigid body relative to the valve, so there is an issue in that the force with which the pin presses the valve cannot be controlled.
  • Patent Document 3 and Non-Patent Document 1 a compression spring is provided inside the pin, and the pin is pressed against the sliding plate against the flow path device by the compression spring. Due to the action of the compression spring, the pin moves up and down, tracing the surface of the sliding plate in response to the left and right movement of the sliding plate.
  • the pressing force of the pin against the flow path device remains even when the valve is opened, which causes a problem that the valve is not fully opened.
  • the present disclosure provides a valve opening and closing system that is inexpensive, opens and closes valves stably, allows a high degree of freedom in valve arrangement, and can be made compact.
  • a valve opening and closing system that opens and closes a valve provided on a first plate that constitutes a flow path device that is placed parallel to an XY plane in an XYZ Cartesian coordinate system
  • the valve opening and closing system comprising: a second plate having a through hole; A pin having an upper portion in a positive direction of the Z axis and a lower portion in a negative direction of the Z axis, the central axis of the pin being parallel to the Z axis; A third plate having a movable range in the X-axis direction and having irregularities on its surface in the positive direction of the Z-axis; a first elastic body that connects the upper portion and the lower portion of the pin when elastically deformed; a second elastic body that connects the second plate to the upper portion or the lower portion of the pin when elastically deformed; A control unit that drives the third plate, the first plate, the second plate, and the third plate are arranged in order along a
  • the technology disclosed herein makes it 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 that allows for a high degree of freedom in valve placement and can be made compact.
  • FIG. 2 is a block diagram showing an example of a functional configuration of an analysis system 101 according to the present embodiment.
  • FIG. 2 is a diagram showing an example of a valve designed so that the shape of a flow path 204 in the valve section and the shape of a 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 that can be approximated by a solid of revolution about an axis parallel to the Z axis (e.g., a sphere or a cone).
  • FIG. 2 is a diagram showing an example of a valve in which the tip of the head 203 has a flat surface parallel to the ⁇ plane.
  • FIG. 1 is a diagram showing the closure rate versus valve depression force for a valve in which the depression force and the closure rate are in a proportional relationship.
  • FIG. 13 is a graph showing the closure rate versus valve depression force.
  • FIG. 13 is a graph showing the closure rate versus the valve depression force when polypropylene is used for the film 202.
  • FIG. 13 is a diagram showing the actual measured values of the closure rate versus the valve depression force when polypropylene is used for the film 202.
  • FIG. 2 is a diagram showing a configuration example of a sliding plate drive system 301 (valve opening and closing system).
  • 13 is a diagram showing the Z coordinates of the recessed portion 312 and the protruding portion 311 of the sliding plate 303 and the sliding plate ground contact portion 308.
  • FIG. 3 is a diagram showing a configuration example of a sliding plate driving system 301.
  • FIG. 3 is a diagram showing a configuration example of a sliding plate driving system 301.
  • FIG. 13 is a diagram showing an example in which the follow-up mechanism 307 is configured using an elastic body (spring).
  • FIG. 13 is a diagram showing an example in which the tracking mechanism 307 is configured using a magnet.
  • FIG. 13 is a diagram showing an example in which the tracking mechanism 307 is configured using a magnet.
  • FIG. 13 is a diagram showing a guide structure of a sliding plate ground contact portion 308.
  • FIG. 13A and 13B are diagrams illustrating an example in which a transmission mechanism is configured using an elastic body.
  • FIG. 13A and 13B are diagrams illustrating an example in which a transmission mechanism is configured using an elastic body.
  • FIG. 13 is a diagram showing an example in which the transmission mechanism is configured by installing mutually repelling magnets 317 at the lower end of the upper pin and the upper end of the lower pin.
  • 13 is a diagram showing a configuration example in which a transmission mechanism 307 is provided on the flow channel device 104 side.
  • FIG. 13A and 13B are diagrams showing an example of the configuration of a sliding plate 303 having recesses 312 at multiple height levels.
  • 13 is a diagram showing an operation of squeezing and opening the reagent storage section 402 using the sliding plate driving system 301 to release the reagent into the flow channel 204.
  • FIG. FIG. 13 is a diagram showing an arrangement example 1 of a second spring and a first spring.
  • FIG. 11 is a diagram showing a second example of arrangement of the second spring and the first spring.
  • FIG. 11 is a diagram showing an arrangement example 3 of the second spring and the first spring.
  • FIG. 11 is a diagram showing an arrangement example 4 of the second spring and the first spring.
  • 3A and 3B are diagrams showing a first structural example of a pin 304 and a sliding plate driving system 301.
  • 13 is a diagram showing a second structural example of a pin 304 and a sliding plate driving system 301.
  • FIG. 5A and 5B are diagrams illustrating an example of a cross-sectional configuration of a spring plunger 501.
  • 13 is a diagram showing a configuration example in which the position of the flow channel device 104 is adjusted by a sliding plate driving system 301.
  • FIG. 11A and 11B are diagrams showing example 1 of a method for maintaining the head attitude inside the pin or between the pin and the pin guide.
  • FIG. 11 is a diagram showing a second example of a method for maintaining the head attitude inside the pin or between the pin and the pin guide.
  • FIG. 11 is a diagram showing example 3 of a method for maintaining the head attitude inside the pin or between the pin and the pin guide.
  • FIG. 6 is a diagram showing the structure of a sliding plate 303 and a roller 603.
  • FIG. 13 is a diagram showing an example of a pin design.
  • FIG. 13 is a diagram showing an example of a configuration in which a second spring 307 is provided for each of a plurality of valves.
  • FIG. 13 is a diagram showing an example of a configuration in which one second spring 307 is provided for multiple valves collectively.
  • FIG. 13 is a diagram showing an example of a sliding plate pattern when three valves are installed on the same X coordinate.
  • FIG. 13 is a diagram showing an example 1 of a sliding plate pattern when three valves are installed on the same Y coordinate.
  • FIG. 13 is a diagram showing a second example of a sliding plate pattern when three valves are installed on the same Y coordinate.
  • FIG. 13 is a diagram showing an example of a slider pattern when three valves are not aligned on the same XY coordinates and the uneven lanes are not shared between the valves.
  • FIG. 13 is a diagram showing an example of a slider pattern when three valves are not aligned on the same XY coordinates and the uneven lanes are not shared between the valves.
  • FIG. 13 is a diagram showing an example of a sliding plate pattern in which two valves are arranged on the same Y coordinate and the distance between the two valves is a certain amount relative to the width of the uneven lane in the X-axis direction.
  • FIG. 13 is a diagram showing an example of a sliding plate pattern when valves V1 and V2 are arranged on the same Y coordinate, and valve V3 is arranged on a Y coordinate different from V1 and V2.
  • 13 is a diagram showing an example in which the valve drive direction is Z, the sliding plate 303 moves in the X direction, and the flow path devices 104 are arranged along the Y axis direction so as not to overlap in the Z axis direction.
  • FIG. 13 is a diagram showing 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, where the valve drive direction is Z and the moving direction of the sliding plate 303 is X.
  • FIG. 17B is viewed from the Y-axis direction.
  • FIG. 17B shows four flow path devices arranged in the X-axis direction as in FIG. 17B, a sliding plate 303 as in the sliding plate diagram of FIG. 16D(2) is shared among the four flow path devices, and the valve opening/closing pattern is moved as in FIG. 16D(1), showing the layout and movable range of the sliding plate 303.
  • FIG. 13 is a diagram showing an example of arrangement in which a plurality of rotating sliding plates 303 are used for a plurality of flow channel devices 104.
  • FIG. 11 is a diagram showing the characteristics of the force applied by the pin 304 to the sliding plate 303 or the flow path device 104.
  • FIG. 13 is a diagram showing a state in which the second spring reaches its natural length midway.
  • FIG. 13 is a diagram showing a state when the relationships Z1 ⁇ Z0 and Zn ⁇ Z0 hold.
  • FIG. 5 shows a pin incorporating a suitable spring plunger 501 and the compression force profile of the pin.
  • FIG. 13 is a diagram showing a change in a first force F1 relative to the change in the unevenness of a sliding plate 303 when a pin 304 having a first spring in a spring plunger 501 is pressed against a flow path device 104 having a PP film attached thereto.
  • FIG. 13 is a diagram showing the force applied to a sliding plate contact portion 308 on the inclined surface of the sliding plate 303.
  • FIG. 13 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.
  • FIG. FIG. 1 is a diagram showing pin characteristics of Non-Patent Document 1.
  • FIG. 1 is a diagram showing pin characteristics of Patent Document 4.
  • FIG. 13 is a diagram showing a configuration in which two springs are incorporated into a pin, the first of which acts to press the pin against a sliding plate relative to a flow path device, and the second spring acts to press the pin against a sliding plate relative to a pin guide.
  • 13 is a diagram comparing characteristics of the force (first force) applied to the flow channel device 104 by pins 304 having different configurations.
  • FIG. FIG. 21 is a continuation of FIG. 20 and is a diagram comparing the characteristics of the force (first force) applied to the flow channel device 104 by pins 304 of different configurations.
  • FIG. 2 is a diagram illustrating an example of a detailed configuration of the analysis system 101.
  • FIG. 2 is a diagram showing an example of an operation procedure of the analysis system 101.
  • FIG. 1 is a diagram showing an example of connections of a plurality of flow paths, valves, etc. in a flow path device 104 used in an analysis system 101.
  • FIG. 1 is a diagram for explaining a liquid delivery operation and the like in a flow path device 104 of the analysis system 101.
  • FIG. 23B is a diagram showing the configuration of flow paths and the like of the flow path device 104 in FIG. 23A and the opening and closing steps of valves corresponding to the operation example shown in FIG. 23B.
  • 13 is a table showing sliding plate steps. 1 is a table showing the slider steps corresponding to the analysis process.
  • 24B is a diagram showing the concave and convex lanes of each valve included in the sliding plate 1 shown in FIG. 24A developed.
  • 4 is a flowchart for explaining an analysis sequence in the analysis system 101.
  • flow path device will be used to refer to a flow path device that is mainly composed of a flow path substrate with grooves for the flow path and a film bonded to cover the flow path, but flow path devices of different configurations that provide similar functions may also be used.
  • the flow path device may omit illustrations of the flow paths and films for simplicity. Unless otherwise specified, the flow paths and valves are assumed to be properly aligned with the head.
  • pressing refers to the general action of applying force.
  • pressing down refers to the action of applying force to deform a film.
  • joined refers mainly to a state in which different components are joined by adhesives, heat welding, screwing, or fitting, but also includes cases in which a single component that is molded as a single unit from the beginning has multiple functions.
  • Components that are "elastically deformed” include components that are slightly plastically deformed.
  • the required depression force refers to the minimum depression force that can close the valve with a probability of 99% or more.
  • the definition of closed may differ depending on the design of the flow path device.
  • 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 open may differ depending on the flow path device.
  • Equations relating to force balance and pressure do not include terms for the action of frictional force, but those skilled in the art can easily deduce the equations when frictional force is taken into account.
  • the sliding plate refers to a linear cam unless otherwise specified.
  • cam design methods are used.
  • the orientation of the fluid control system and the analysis system are expressed using the Cartesian coordinate system XY4 and the Cartesian coordinate system ⁇ Z.
  • the orientation of XYZ and the Cartesian coordinate system ⁇ Z does not indicate a specific direction with respect to the direction of gravity, and unless otherwise specified, it may be any orientation.
  • the Cartesian coordinate system XYZ and the Cartesian coordinate system ⁇ Z may be a right-handed system or a left-handed system.
  • the Cartesian coordinate system XYZ and the Cartesian coordinate system ⁇ Z share the Z axis, and the XY plane and the ⁇ plane are considered to be identical.
  • the X-axis and Y-axis may or may not coincide with the ⁇ -axis and ⁇ -axis.
  • the origins of the Cartesian coordinate system XYZ and the Cartesian coordinate system ⁇ Z may be set at any location. There is no problem if a different origin is set for each valve and each coordinate system. However, coordinates in drawings with the same drawing number and branch number are considered to share the same coordinate system within the same drawing number and branch number.
  • the sliding plate has projections and recesses 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 projections and recesses of the sliding plate.
  • the direction in which the pin approaches the valve is described as the positive Z direction.
  • 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 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 a valve, a detection unit, a flow path device, and a heater.
  • the control analysis unit may be connected to a network, and may be capable of uploading data to an external database, collating data, and accessing the data.
  • the pump may be a diaphragm pump or a syringe pump.
  • a valve that directly/indirectly transmits motor power to deform a film, or a valve that deforms using air pressure may be used.
  • the valve may be controlled by a control unit.
  • the valve may be opened and closed by deformation using heat, or magnetic force may be used.
  • 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. Based on the parameters recorded in the database 103, the computer 102 may be responsible for opening and closing valves of the flow path device 104, the detection unit 105 and their connecting parts, controlling the temperature, and controlling the applied pressure and flow rate.
  • 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.
  • the analysis system 101 can accept samples and perform all processes from dissolution to purification, PCR, detection, and analysis in a fully automated manner. Note that it may also be possible to fully automate some of the processes from dissolution to purification to PCR to detection and analysis.
  • the flow path 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 in a state where it can be detected may be performed in the disposable flow path device 104, and the part where the sample is detected may be performed in a detection unit provided outside the flow path device 104. In particular, in the case of pre-processing where PCR is performed, the impact of contamination before PCR is large. For this reason, pre-processing up to the PCR step may be performed inside the disposable flow path device 104, or it may be thoroughly washed after each use.
  • 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. By making it an integral structure, storage, maintenance, and transportation become easier. By making it an integral structure, the connection between the flow path device 104 and the detection unit 105 becomes simple, and the frequency of breakdowns and errors can be reduced.
  • the detection unit 105 may be made to be reusable multiple times.
  • the detection unit 105 requires precision manufacturing and has a high unit price, so making it reusable can help reduce costs.
  • the computer 102 is equipped with a user interface 106.
  • the computer 102 can accept parameters related to the user interface 106 from the user, such as the time and temperature of each step, pressure, flow rate, procedure, amount of divided liquid, number of PCR cycles, sample information, flow path device information, and analysis protocol, and store them in the database 103.
  • various parameters may be stored in the database 103 in advance.
  • the computer 102 may be responsible for opening and closing the valves of the flow path device 104, controlling the temperature, and controlling the applied pressure and flow rate, based on the parameters recorded in the database 103.
  • the flow path 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 path device 104 is, for example, typically within two days, more typically within 12 hours, and more typically within two hours.
  • the flow channel device 104 may be configured as a disposable or multiple-use consumable part that includes reagents, chambers, and flow channels.
  • the flow channel device 104 may include a pump therein as a power source for transporting fluid.
  • some or all of the reagents required for the reaction may be present within the flow channel device 104.
  • Some of the chambers provided within the flow channel device 104 may be provided with a temperature control function, a molecular capture function, a detection function, and a voltage application function.
  • 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. It is preferable to use materials that have a low amount of DNA adsorption, such as polypropylene, polyethylene, cyclic olefin polymer (COP), cyclic olefin copolymer (COC), polycarbonate, polyethylene terephthalate, and polyurethane. It is also preferable to suppress the amount of adsorption by modifying the surface so that it becomes negatively charged.
  • materials that have a low amount of DNA adsorption such as polypropylene, polyethylene, cyclic olefin polymer (COP), cyclic olefin copolymer (COC), polycarbonate, polyethylene terephthalate, and polyurethane. It is also preferable 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 polyvinyl chloride resin; agarose, dextran, cellulose, polyvinyl alcohol, nitrocellulose, chitin, chitosan, or any combination thereof.
  • metals such as gold, silver,
  • the flow path device 104 has an internal flow path and is made entirely from a deformable material. In another embodiment, the flow path device 104 is made by bonding a lid to a flow path substrate 201 with holes and grooves using a film 202. In another embodiment, the part of the flow path device 104 that corresponds to the lid and the part that corresponds to the flow path are made from the same material.
  • the parts that make up the flow path device 104 are made by injection molding, 3D printing, cutting, blow molding, extrusion molding, hot embossing, laser cutting, press molding, etc.
  • the flow path substrate 201 is preferably made of a material that can be injection molded. Injection molding has the advantage of reducing the manufacturing costs of the flow path device 104 when mass-producing it.
  • a material that undergoes plastic deformation such as polypropylene, polyethylene, or PET, is preferable.
  • the typical size of the flow path device 104 is that each side is 50 cm or less.
  • a flow path device 104 capable of analyzing one sample has each side of 20 cm or less.
  • the long side of the flow path device 104 is 15 cm or less, the width is 10 cm or less, and the thickness is 1 cm or less.
  • ⁇ Film and bulb> 2A to 2C are diagrams showing the state of a 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 removing the pressing force.
  • the lid of the flow path device 104 is composed of a sheet having a thickness of 1 cm or less.
  • a sheet having a thickness of 1 cm or less will be referred to as a film 202.
  • the thickness of the film 202 is preferably 1 mm or less.
  • the thickness of the film 202 is preferably 500 ⁇ m or less.
  • the thickness of the film 202 is preferably 100 ⁇ m or less.
  • the film 202 of the flow path device 104 is not particularly limited as long as it is a material that is commonly used in the relevant technical field.
  • the film 202 may be a material in which multiple layers are bonded or fused together.
  • 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 that is resistant to tearing and thermal deformation of the film 202.
  • the film 202 is bonded to the flow path substrate 201 by techniques such as heat welding, adhesives, laser welding, chemical bonding, and ultrasonic welding.
  • a valve has the role of closing off a part of a flow channel in order to select a path through which a fluid is to flow among a flow channel with multiple branches, or to seal a chamber and increase the internal pressure.
  • the cost of the flow channel device 104 can be reduced by fabricating a valve within the components that make up the flow channel device. For example, as described in Patent Document 1, Patent Document 2, Patent Document 3, Patent Document 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.
  • 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 pressing force to the film 202 to deform it, which closes the valve, and releases the pressing force to open the valve.
  • the direction in which the head 203 moves is the Z axis
  • the longitudinal direction of the flow path is the ⁇ axis
  • the direction perpendicular to the ⁇ axis of the flow path and the Z axis is the ⁇ axis.
  • the ⁇ axis and ⁇ axis may be different between valves.
  • the ⁇ axis and ⁇ axis do not have to coincide with the X axis and Y axis of the sliding plate drive system described later.
  • the head 203 can be made of, for example, a hard material (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.
  • a hard material such as SUS or aluminum
  • the flow path substrate 201 is made of a thermoplastic resin
  • a film made of a thermoplastic resin the manufacturing costs of the flow path device can be reduced.
  • the various physical properties become similar, making design easier. Thermal bonding or ultrasonic bonding may also be selected.
  • FIG. 2A shows an example of a valve designed so that the shape of the flow path 204 and head 203 of the valve part are roughly the same.
  • the film 202 is deformed by the pressing force of the head 203 and contacts the bottom surface 205 of the flow path, closing the valve.
  • closing it is sufficient to be able to sufficiently block the flow of fluid, and it is not necessary for the film 202 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 rotating body centered on an axis parallel to the Z axis. If the valve has a shape that cannot be approximated by a rotating body, it is necessary to restrict the movement of the head 203 so that it does not rotate.
  • FIG. 2B shows an example of a valve in which the tip of the head 203 has a shape that can be approximated by a body of revolution about an axis parallel to the Z axis (e.g., a sphere or a cone).
  • the flow channel substrate 201 has upper and lower through-holes 206, and the head 203 descends to close the holes.
  • FIG. 2C shows an example of a valve in which the tip of head 203 has a flat surface parallel to the ⁇ plane.
  • the tip of the valve may have a shape that can be approximated by a solid of revolution with respect to an axis parallel to the Z axis (e.g., cylindrical).
  • Film 202 has convex portion 207. The valve is closed when convex portion 207 is crushed by the head. If flow path 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.
  • valve shape will be described using the structure shown in Figure 2A as an example, but it may have a structure like that of Figure 2B or Figure 2C, and any shape may be used as long as the head 203 applies a pressing force to the surface of the flow path to reduce the cross-sectional area of the flow path and restrict the flow of fluid.
  • the valve closure rate is an index calculated by setting the flow rate of a fluid discharged by a pump that continues to deliver a fluid at a constant power or a pump that continues to deliver a fluid at a constant pressure as 0% when the valve is open and 100% when the flow rate is 0.
  • the fluid that actually flows may be different from the fluid that is measured for the closure rate.
  • the closure rate may be measured with air, and an aqueous solution may be flowed in the actual analysis.
  • a diaphragm pump may be used for measuring the closure rate, and a syringe pump may be used for actual liquid delivery.
  • the closure rate is preferably 90% or more, 99% or more, or 99.9% or more.
  • the valve may be intentionally closed with a small force and operated with a closure rate of 99% or less.
  • a low-power actuator is used to stop the flow of an aqueous solution
  • the liquid can be sufficiently stopped even with a low closure rate by making the liquid-contacting surface of the flow path device hydrophobic.
  • the pressure resistance of a valve refers to the minimum pressure at which a fluid passes through the valve and flows at 1 L/min or more, 1 ml/min or more, or 1 ⁇ l/min or more.
  • the definition of the pressure resistance of a valve may be set appropriately according to the application of the valve and the required closing time.
  • the pressure resistance may differ depending on the type of liquid.
  • the pressure resistance of a valve tends to increase as the closing rate increases. When an aqueous solution is blocked by a valve, the pressure resistance is higher if the liquid contact surface of the flow path device is made of hydrophobic material. Also, if there is a distance between the part where the flow path branches and the valve part, it is preferable that no liquid enters between the branching part and the valve part. Therefore, it is better for the valve to have a high closing rate that can block both aqueous solutions and air.
  • the valve may be opened and closed once or multiple times during one analysis process.
  • the valve is opened and closed hundreds or thousands of times throughout multiple analyses. If the valve closing rate varies or fails to open and close, problems such as data not being acquired, samples being wasted, erroneous results being obtained, time being wasted, and the system breaking down may occur. Therefore, the stability of the valve opening and closing operation must be maintained at a high level.
  • factors that determine the stability of the valve opening and closing include the stability of the control of the valve pressing force and the stability of the valve position control.
  • a configuration for limiting the movement of the head 203 may be installed in the valve opening and closing system.
  • the head is equipped with a guide blade, and the guide blade is inserted into the flow path device to guide the head to the correct position.
  • FIG. 3A is a diagram showing the closing rate with respect to the valve pressing force of a valve in which the pressing force and the closing rate are in a proportional relationship.
  • this will be referred to as the pressing force-closing rate curve (all are not actual measurements but image diagrams).
  • the closing rate can be set to 50% or less, 20% or less, 10% or less, or 5% or less.
  • the maximum pressing force that can fully open the valve is set to the maximum opening pressing force Fopen.
  • FIG. 3B is a diagram showing the closure rate with respect to the depression force of the flow path valve in this case.
  • the closure rate can be made 20% or less.
  • the film 202 is made of a material that exhibits properties close to elastic deformation, such as PDMS or polyurethane, then as long as the deformation of the film is not too large, the depression force-closing rate curve when the valve is closed and the depression force-closing rate curve when the valve is opened will generally match. Some hysteresis may occur, but this can be ignored.
  • FIG. 3C shows the pressing force-closing rate curve when polypropylene is used for the film 202.
  • polypropylene film has the same thickness, the required pressing force tends to be higher than the elastically deforming film 202. Since polypropylene exhibits viscoelastic properties, the strain gradually increases when a constant pressing force is continuously applied, and the elastic modulus decreases when a constant strain is continuously applied. Therefore, when comparing with the same pressing force, the closing rate is higher when opened than when closed.
  • the pressing force (required pressing force) required for closing is higher than that of an elastic film, and in order to sufficiently reduce the closing rate when opened, it is necessary to properly unload the film more than with an elastic film.
  • the pressing force when unloaded must be 20%, 10%, 1%, or 0% of Fc.
  • the sliding plate and pin it is preferable to design the sliding plate and pin so that they do not come into contact with the film 202 when released. It is also necessary to design the pin so that the pressing force is within the above range even if there is slight contact. It is difficult to make the pressing force zero when opening and closing the valve while keeping the pin in contact with the flow path device 104. For this reason, it is preferable to control the Z coordinate of the head 203 so that there is a distance of 0.5 mm or more between the flow path device 104 and the head 203 when opened. Because the shape of the film 202 does not completely return to its original shape when opened, the head 203 may be opened at a position where it is slightly inserted into the groove of the flow path.
  • the pressing force generated changes depending on the speed of the head 203 in the Z direction. If the driving speed of the head 203 in the Z direction is fast, the maximum pressing force generated becomes large, and if the driving speed in the Z direction is slow, the maximum pressing force generated becomes small. Even after closing, the deformation of the film 202 and the flow path substrate 201 continues, but if the Z coordinate of the head 203 is fixed at the time of closing, it cannot follow this deformation, so the closing rate and pressure resistance of the valve gradually decrease.
  • the flow path device 104 will deform. There is also a possibility that the drive system and the holding members of the flow path device 104 will deform, break, or malfunction. Furthermore, the deformation of the film 202 will become too great, making it difficult to open. Also, the motor of the drive system will lose synchronization and be damaged.
  • the maximum force that may be applied to the flow path device 104 is preferably 20N or less, 15N or less, or 10N or less per valve. Also, it is preferable that the force that the flow path device 104 can withstand as a whole is 200N or less, 100N or less, or 50N or less. When multiple valves are operated together by a single actuator, if too much force is applied to any one valve, it will not be possible to apply sufficient force to the other valves. In the following, the maximum pressing force that does not damage or malfunction the device is defined as the allowable pressing force Fmax.
  • the depression force Fo when opening the valve, the depression force Fo must be lower than the maximum depression force when opening, Fopen, in order for the valve to be opened.
  • the depression force Fc when closing the valve, the depression force Fc must be higher than the required depression force Fclose, in order for the valve to be closed.
  • the depression force when closing exceeds the maximum allowable depression force Fmax, the device will be damaged. From the above, the depression force Fo when opening must satisfy the relationship Fo ⁇ Fopen, and the depression force Fc when closing must satisfy the relationship Fclose ⁇ Fc ⁇ Fmax.
  • Figure 3D shows the actual measured values of the pressing force-closing rate curve for a valve shaped as in Figure 2A (1) and using polypropylene for the film 202. Because the film has a high elastic modulus, it needs to be closed with a fairly strong force. Also, because the film undergoes plastic deformation, the valve will not open unless the pressing force is fully released when opened. In the case of this valve, the required pressing force Fclose is 15N, and Fmax is 20N. Also, if the closure rate when opened is set to 20%, the maximum opening pressing force Fopen will be 1N or less. Therefore, it is appropriate to control the pressing force when closing to 15N-20N, and the pressing force when opening to 1N or less.
  • FIG. 4A is a diagram showing a configuration example of a sliding plate driving system 301 (valve opening and closing system).
  • a head 309 corresponds to the head 203 in FIG. 2A and the like.
  • the sliding plate driving system 301 includes 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 movable range in the X-axis direction and having unevenness on the surface in the positive direction of the Z-axis in the XYZ orthogonal coordinate system.
  • 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 direction of the Z-axis perpendicular to the Z-axis, and the pin 304 whose central axis is parallel to the Z-axis is installed between the first plate 104 and the third plate 303 in a state where it penetrates the through hole 310 of 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 moving in the X-axis direction.
  • the direction in which the pin 304 approaches the valve is defined as the positive Z-axis direction.
  • the sliding plate drive system 301 includes one or more sliding plates 303, one or more pin guides 302, and a pin 304 having a head 309.
  • a single actuator can open and close multiple valves.
  • the valve spacing is not limited by the size of the actuator, making it easier to use a powerful motor.
  • the motor has ample power, so the valve opening and closing operation is stable.
  • the actuator can be shared, making it possible to miniaturize the system. Note that a configuration in which the sliding plate drive system 301 does not have the pin 304 and the head 309 is joined onto the sliding plate 303 is also possible.
  • the force in the X direction of the sliding plate 303 is directly transmitted to the valve, which may cause the flow path device 104 to deform or tear.
  • the mechanical energy generated by the friction between the head 309 and the film 202 increases, shortening the lifespan of the head and the sliding plate.
  • the sliding plate (third plate) 303 can be driven in the Z-axis direction.
  • the head 309 can be lowered by lowering the sliding plate 303 in the negative Z-axis direction when inserting the chip (flow path device 104), and the chip can be inserted smoothly.
  • the sliding plate is lowered in the negative Z-axis direction when driving the valve, the friction generated between the sliding plate and the pressing pin is reduced, so the life of the sliding plate driving system 301 can be extended. Since the pressing pin only needs to touch the convex part of the sliding plate 303, the width of the sliding plate 303 in the X-axis direction can be reduced.
  • the third plate 303 does not exhibit a sliding behavior against the pressing pin. For this reason, it cannot be called a sliding plate 303, but the part described below as a sliding plate 303 may be replaced with this configuration.
  • 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 to apply 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, and it is possible to prevent the film 202 of the flow path device 104 from being torn by the frictional force generated between the head 309 and the flow path device 104.
  • the head 309 is not on the sliding plate 303, it is possible to limit the area where the head 309 presses the flow path device 104 to only the target valve, which increases the degree of freedom in the valve arrangement of the flow path device 104 and the valve drive pattern.
  • the head 309, the central axis of the pin 304, and the sliding plate grounding portion 308 are aligned on the same line parallel to the Z axis, or their respective centers of gravity 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.
  • the sliding plate 303, pin guide 302, and pin 304 can be made of SUS, 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 is made of a highly durable material.
  • the parts where movable contact is made between the sliding plate 303, pin guide 302, and pin 304 may be made of a fluororesin to reduce friction. They may also be lubricated with oil. A system that detects wear and prompts replacement may be included.
  • Figure 4B is a diagram showing the Z coordinate of the sliding plate contact portion 308 from the concave portion 312 to the convex portion 311 of the sliding plate 303.
  • the convex portion 311 and the concave 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.
  • FIG. 4C is a diagram showing a configuration example of the sliding plate driving system 301.
  • the sliding plate driving system 301 the sliding plate 303 is driven in the X-axis direction by the actuator 316 and the ball guide/linear guide 315.
  • the rotational power of the actuator is transmitted to the ball guide, and the sliding plate 303 moves.
  • the actuator 316 is controlled by the computer 102.
  • the driving system is not limited to a stepping motor, and various motors and actuators may be used.
  • FIG. 4D is a diagram showing another example of the configuration of the sliding plate drive system 301.
  • the sliding plate 303 is connected to the actuator 316.
  • the actuator 316 is controlled by the computer 102, and the actuator 316 drives in the X-axis direction along the linear guide 315.
  • the actuator 316 may be provided with a hollow motor, and the actuator may be driven by driving the motor.
  • a rack and pinion configuration may be adopted in which teeth are provided on the linear guide 315, a gear is provided on the actuator 316, the rotational motion of the motor in the actuator is transmitted to the gear, and the gear rotates to cause the actuator to run on the teeth of the linear guide.
  • the linear guide 315 may be provided with a magnet, and the actuator 316 may be configured as a shaft motor equipped with a coil.
  • the speed at which the actuator 316 moves does not have to be constant; it can move slowly in areas where strong force is applied and quickly in areas where it is not. It is preferable that the time required for one step movement be 0.1 to 10 seconds.
  • 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. For this reason, it is necessary to adopt a drive system that matches the size of the analysis system 101.
  • 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 parts.
  • the valve may be opened and closed using different concave and convex parts at each step, or the concave and convex parts may be used repeatedly in some parts.
  • a structure in the pin 304 that can control the pressing force when closed. Examples include placing a compression spring (first spring 306) inside the pin 304, making part or all of the pin 304 out of an elastic material, or placing a repulsive magnet inside the pin 304.
  • This type of mechanism is called a transmission mechanism.
  • the transmission mechanism transmits the change in position of the lower part of the pressing pin to the flow path device 104 as a change in pressing force.
  • the pin 304 may not move smoothly due to friction with the pin guide (pin holder) 302, the sliding plate 303, and/or the flow path device 104. For this reason, a tracking mechanism is required to provide a force to press the pin 304 against the sliding plate 303.
  • the pin 304 includes a sliding plate grounding 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, it is assumed that the head 203 is included in the pin upper portion 309.
  • 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 together.
  • 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 the lower end of the transmission mechanism 306 or may be in contact with it.
  • the pin upper part 309 may be able to rotate freely relative to the pin lower part 305, so a configuration without joining is easier to manufacture and less likely to break.
  • the pin upper portion 309 may also be configured so that its length in the Z-axis direction is variable. In this case, for example, the overall length of the pin is shortened when the pin 304 is pressed against the flow path device 104, and is lengthened when the pin is in contact with the recess 312 of the sliding plate 303.
  • the sliding plate contact part 308 is, for example, a rounded rod with a curved surface that contacts the sliding plate 303.
  • the sliding plate contact part 308 may also be configured as a sphere and follow the sliding plate 303 as if rolling.
  • the sliding plate contact part 308 may also 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 part that contacts the bearing and the bearing shaft may be made of metal.
  • the part of the sliding plate contact part 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 the sliding plate contact part 308 is a cylindrical tire whose plane is parallel to the XZ plane, rather than when it is made of a sphere.
  • a catch structure be provided inside the pin 304, 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.
  • the length of the pin 304 in the Z-axis direction is preferably within 10 cm, and more preferably within 3 cm. 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 within 8 mm, and more preferably within 4 mm. It is preferable that the length in the Y-axis direction is within 5 mm. 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 freedom of valve placement.
  • the pin guide 302 is provided to limit (restrict) the movement of the pin 304.
  • the pin guide 302 includes a through hole 310.
  • the pin 304 is installed in a state where it penetrates the through hole 310.
  • the through hole 310 may be designed to partially contact the pin 304 in order to support the attitude of the pin 304.
  • a portion of the through hole 310 that may be in contact with the pin 304 may be provided with a bearing or may be filled with a lubricant.
  • the pin guide 302 may also include a magnet as a part of its configuration.
  • the flow path device 104 is placed so as to be sandwiched between the device holder 314 and the pin guide 302.
  • the device holder 314 and the pin guide 302 may be joined together or may be molded as one piece.
  • the device holder 314 may be provided with connection ports for connecting to or passing through a heater, an optical detection device, or a pump.
  • the distance between the pin guide 302 and the flow path device 104 is set as short as possible.
  • the pin guide 302 and the flow path device 104 may be in contact with each other.
  • the pin guide 302 may also function as a fixing member for fixing the position of the flow path device 104 in whole or in part.
  • the degree of freedom (freedom of movement) of the pin 304 can be reduced.
  • the required movement distance in the Z-axis direction from when the pin 304 does not protrude from the pin guide 302 until it comes into contact with the flow path device 104 can be minimized. This makes it possible to reduce the size of the unevenness of the sliding plate 303.
  • the XYZ coordinate system of the pin guide 302 is always fixed during analysis.
  • the follow-up mechanism 307 presses the pin 304 against the sliding plate 303, and maintains contact of the sliding plate grounding portion 308 with respect to the unevenness of the sliding plate 303.
  • the force that acts on the second spring 307 as the follow-up mechanism to repel the pin 304 against the sliding plate 303 with respect to the pin guide 302 will be referred to as a follow-up force.
  • the repulsive force from the flow path device 104 causes the head 309 to follow the sliding plate 303. If gravity acts in the Z positive direction or 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 falls below 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.
  • FIGS. 5A to 5D are diagrams showing examples of various tracking mechanisms.
  • the transmission mechanism 306 is omitted. Note that multiple tracking mechanisms may be combined.
  • 5A is a diagram showing an example in which the tracking mechanism 307 is configured with an elastic body (spring).
  • the tracking mechanism configured with an elastic body will be referred to as a second spring.
  • the repulsive or contracting force of the follower mechanism 307 applies a force to the pin 304 in the Z-axis downward direction relative to the pin guide 302, thereby maintaining contact of the sliding plate grounding portion 308 with the sliding plate 303.
  • 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, it is preferable for the spring constant to be in the range of 0.01 N/mm to 5 N/mm. It is desirable for the elastic force of the spring to be 0.1 N to 5 N when the valve is closed, and 0.05 N to 4 N when the valve is open.
  • a second spring is used as a representative of various tracking mechanisms, but the mechanism is not limited to a spring and may be any other tracking mechanism with a similar function.
  • FIGS. 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.
  • magnet 317 is provided on the side of the sliding plate of pin guide 302, and magnet 318 is provided on pin lower portion 305.
  • 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 following force.
  • the follower mechanism 307 is provided between the pin 304 and the sliding plate 303.
  • a magnet or magnetic body 319 is provided on the lower part 305 of the pin, and a magnet or magnetic body 320 is provided on the sliding plate 303.
  • At least one of the members 319 and 320 needs to be a magnet, and if both are magnets, the opposite poles are facing each other. The action of the magnet and the magnet or magnetic body attracts the pin 304 to the sliding plate 303, thereby maintaining contact.
  • 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.
  • the pin 304 can be designed to be small and simple.
  • FIG. 5D is a diagram showing the guide structure of the sliding plate grounding portion 308.
  • the sliding plate 303 may be configured so that the upper limit of the 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.
  • 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 upper portion of the U-shape of the sliding plate 303 may be configured to press the sliding plate grounding portion 308 (roller) or to press the protrusion 322 of the pin lower portion 305.
  • the transmission mechanism 306 has a function of transmitting the displacement applied to the pin 304 from the sliding plate grounding portion 308 as a force to the valve so as to provide 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.
  • the upper pin 309 and the lower pin 305 are each in contact with the transmission mechanism 307.
  • FIGS. 6A to 6C are diagrams showing examples of the configuration of various transmission mechanisms. Note that in these diagrams, the follower mechanism is omitted. In addition, multiple transmission mechanisms shown in FIG. 6A to FIG. 6C may be combined to form one transmission mechanism.
  • FIG. 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.
  • the transmission mechanism 307 that uses an elastic body is referred to as a first spring 307.
  • Figure 6B is a diagram showing 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.
  • 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.
  • the sliding plate grounding part 308 may be configured to also function as the transmission mechanism 307.
  • the sliding plate grounding part 308 can be configured from an elastic body such as rubber or elastic resin to achieve the function of the transmission mechanism 307.
  • FIG. 6C is a diagram showing a configuration example in which the transmission mechanism 307 is provided on the flow path device 104 side.
  • the transmission mechanism 307 is provided on the flow path device 104 side.
  • US Patent 11305278 by attaching an elastic sheet 323 on the film 202, it is possible to control the pressing force and the repulsive force.
  • 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.
  • the first spring is used as a representative of various transmission mechanisms, but the transmission mechanism is not limited to a spring and may be any transmission mechanism with a similar function.
  • the recessed portion 312 and the protruding portion 311 of the sliding plate 303 refer to the portions that are lower and higher than the 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 come into contact is basically a continuous surface in the X-axis direction. If there is a gap or an extreme step along the way of the uneven surface 313, the sliding plate contact portion 308 may get caught. For the sake of convenience, corners are drawn at the boundaries between the slopes and the flat portions in the drawings, but in reality the uneven surface 313 is made smooth in the X-axis direction.
  • the angle (slope angle) between 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). If the slope angle is small, the width of the sliding plate 303 becomes large. It is preferable that the slope angle changes 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 must be five times or more the height of the unevenness of the sliding plate 303, which is disadvantageous. More preferably, the maximum slope angle is 20° or more.
  • the 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.
  • the sliding plate step means either the concave portion 312 or the convex portion 311 of the sliding plate 303 when there is one valve, and means a combination of concave portions or convex portions that act simultaneously on multiple valves when multiple valves move in conjunction.
  • the open/closed state of the valve and the pressing force can be controlled by the height of the uneven portion.
  • the part of the sliding plate that contains a series of uneven parts used to drive one valve will be referred to as the uneven lane 325. All the uneven parts on the same uneven lane are on the same Y coordinate.
  • the height of the teeth of the sliding plate 303 refers to the difference between the part of the adjacent concave portion with the smallest Z coordinate and the part 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 part 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.
  • the uneven parts that exist on the same uneven lane there may be convex parts 311 for strongly crushing the valves and convex parts 311 for weakly crushing the valves.
  • the flow path device 104 may be equipped with valves of different shapes and sizes, and a sliding plate 303 that can apply the necessary pressing force to each may be used.
  • the height of the teeth may be different between the step when inserting the flow path device 104 and the valve opening step during processing.
  • the Z coordinate of the recess that defines the valve opening step during processing may be greater than the Z coordinate of the recess 312 when the flow path device 104 is inserted.
  • a recess of such height that the head 309 touches the film 202 before the film 202 is plastically deformed may be set.
  • the recess may be set higher by an amount equivalent to the amount of plastic deformation remaining in the film 202 when it is opened after being closed.
  • FIG. 7 is a diagram showing an example of the configuration of a sliding plate 303 having recesses 312 at multiple height levels.
  • the sliding plate 303 has a convex portion 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.
  • the second recess 324 determines the Z coordinate of the lower end of the pin in step I.
  • Step I may be a recess that is used when inserting the flow path device 104 and when removing it after analysis.
  • the convex portion 311 pushes up the pin 304, closing the valve.
  • the concave portion 312 comes into contact with the lower end of the pin, pushing down the pin 304.
  • the upper end of the head 309 may protrude from the pin guide 302.
  • a connection port for a heater or a pump may be arranged in the Z-axis plus direction of the space for installing the flow path device 104.
  • the insertion direction of the flow path device 104 is the Y-axis direction or the X-axis direction.
  • the sliding plate driving system 301 may open and push out the reagent storage section 402 provided in the flow path device 104.
  • Fig. 8 is a diagram showing an operation of squeezing and opening the reagent storage section 402 and discharging the reagent into the flow path 204 using the sliding plate driving system 301.
  • the reagent storage section 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 direction.
  • the reagent sealing member 401 may be moved using the pin 304.
  • the reagent is released according to the amount of movement of the reagent sealing member.
  • the reagent sealing member may be made of a material that is easily deformed.
  • the first spring 306 may not be provided in particular for the pin 304 for releasing the reagent. When releasing the reagent, a larger Z displacement is required than when closing the valve. If the pin 304 does not shrink due to the absence of the first spring 306, the reagent can be released at the same unevenness height as the unevenness height used to open and close the valve.
  • the reagent storage sections 402 arranged on the same Y coordinate (X axis) may be opened and released sequentially. If the released reagent flows back into the reagent storage section 402 due to the elasticity of the reagent sealing member 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 opening.
  • a concave and convex lane for reagent opening may be incorporated into the sliding plate 303 used for opening and closing the valve.
  • an independent valve step may be prepared. If reagent opening 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 opening step. Therefore, the sliding plate 303 for reagent opening and closing may be installed independently of the sliding plate 303 for valve opening and closing. If multiple crushing reagents are installed, they may all be opened using a single sliding plate 303.
  • 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.
  • the second spring 307 is composed of a compression spring, and is in contact with the lower pin part 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.
  • the pin guide 302 can be designed to be in contact with the upper pin part 309 and the flow path 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 upper pin part 309 (head) and the flow path device 104.
  • the second spring 307 is made of a tension spring, and is in contact with the lower pin 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 plus direction.
  • the upper and lower ends of the second spring (tension spring) 307 need to be joined to the lower pin part 305 and the pin guide 302, respectively.
  • the second spring 307 is a compression spring, and is in contact with the pin upper portion 309 and the pin guide 302.
  • the pin guide 302 it is relatively easy to design the pin guide 302 to be in contact with the flow path device 104 while also being in contact with the pin upper portion.
  • the second spring 307 is made of a tension spring, and is in contact with the pin upper part 309 and the pin guide 302.
  • the pin guide 302 it is somewhat difficult to design the pin guide 302 so that it is in contact with the flow path device 104 while also being in contact with the pin upper part, and it is necessary to assemble a combination of multiple parts.
  • the upper and lower ends of the second spring (tension spring) 307 need to be joined to the pin lower part 305 and the pin guide 302, respectively.
  • the second spring 307 shown in Figures 9B and 9D is shown as two tension springs for ease of viewing, but in reality, a single tension spring may be installed around the outer circumference of the pin.
  • FIG. 10C is a diagram showing an example of the cross-sectional configuration of the spring plunger 501.
  • the spring plunger 501 includes a spring storage section 510, a protruding section 511 pushed out by the spring, and a first spring (compression spring) 306.
  • the spring storage section 510 is illustrated as constituting a part of the pin upper section 309
  • the protruding section 511 is illustrated as constituting a part of the pin lower section 305, but they may be upside down.
  • the first spring 306 is installed in the spring plunger 501.
  • 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 the second spring recess 502 provided in the pin guide 302 to prevent buckling deformation, and is installed so that it is in contact with the outer periphery of the second spring base 503 provided in the pin lower portion 305.
  • the second spring recess 502 is made to have the same diameter as or larger than the second spring 307.
  • the second spring base 503 is made to have the same diameter as or larger than the second spring 307.
  • 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, and it is desirable to design it so that the long side is longer than the second spring 307 so that the second spring 307 does not come out.
  • the base 503 of the second spring is configured to be positioned in the negative Z-axis direction from the pin guide 302.
  • the pin guide 302 is provided with a base recess 504, and is preferably configured so that the recess is larger than the outer periphery of the base 503 of the second spring so that the protrusion 322 fits within the base recess 504 when the pin 304 is in contact with the protrusion 311 of the sliding plate 303.
  • the upper and lower parts of the pin do not have to be joined to the second spring 307 and the first spring 306, respectively, and 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 part of the pin, or the upper and lower parts of the pin, respectively, are in contact with each other to provide a repulsive force.
  • 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 be in contact (connected) with the protrusion.
  • a rim (return) portion 505 can be provided at the negative Z end of the spring storage portion 510, and a catch portion 506 can be provided at the positive Z end of the protrusion 507.
  • FIG. 10B shows a structure equivalent to that of FIG. 9C.
  • the second spring 307 can be installed so as to contact the second spring base 503 provided on the pin upper portion 309.
  • the second spring 307 in this embodiment is in contact with the lower part of the pin 305 and presses the lower part of the pin 305 against the sliding plate 303.
  • the advantage of this structure is that the forces that the second spring 307 and the first spring 306 impart to the sliding plate 303 are independent of each other, making it easy to design the springs.
  • Another advantage is that the force of the second spring 307 does not affect the first spring 306, so the load-bearing design of the first spring 306 can be lighter.
  • the spring plunger 501 has a structure such as the edge portion (rebound) 505 and the catch portion 506 shown in Figure 10C.
  • the follower mechanism (second spring 307) contacts 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 the sliding plate 303.
  • a compressive force is always applied to the first spring 306, so the upper and lower parts of the pin 304 do not come apart even if the spring plunger 501 does not have a lip (return) portion 505 and a catch portion 506.
  • the upper part of the pin can be reliably pulled down when released.
  • a positioning mechanism may be provided between the flow path device 104 and the device holder 314 (see FIG. 4C) or the pin guide 302 so that the ⁇ coordinates of the flow path device 104 do not change relative to the XY coordinates during an analysis or between analysis rounds.
  • pin 304 shifts 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 position is to position the center of gravity and contact points of pin 304 and the center of gravity of second spring 307 on the same XY coordinate system.
  • a guide blade is attached to the head, a hole is provided in the flow path device so that the guide blade can be inserted, and the head is given a degree of flexibility so that the orientation of the head can be changed so that the guide blade and the hole match, allowing the head to be inserted correctly into the valve section.
  • the head position moves outside the range that can be corrected by the guide blade, it cannot be returned to its original position.
  • the head is connected to an arm and the structure is such that no rotational likelihood occurs, no structure is provided for controlling the rotational likelihood.
  • an alignment mechanism may be provided between the analysis system 101 and the flow channel device 104.
  • the flow channel device (chip) 104 may be provided with a depression or hole for alignment, or with a protrusion for alignment.
  • the alignment of the flow channel device 104 may be performed by the sliding plate driving system 301.
  • FIG. 11 is a diagram showing an example of a configuration in which the flow path device 104 is aligned by the sliding plate drive system 301.
  • the flow path device 104 is provided with alignment holes 403.
  • the alignment pins 304' move in the positive direction of the Z axis on the sliding plate 303, and alignment is performed by fitting the alignment pins 304' into holes or recesses (alignment holes 403) in the flow path device (chip) 104.
  • the alignment pin 304' When aligning, the alignment pin 304' only needs to be stopped at an appropriate height in the alignment hole 403 of the flow path device 104, so the alignment pin 304' does not need to have the first spring 306. It is preferable to provide two or more and four or less alignment pins 304' and alignment holes 403 for one flow path 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 becomes smaller as the Z coordinate increases.
  • Transmission mechanism 306 uses an elastic body such as hard rubber or a leaf spring, which is joined to upper pin portion 309 and lower pin portion 305. Furthermore, if no rotational deformation (twist) occurs in the elastic body on the XY plane, the rotational likelihood of upper pin portion 309 can be limited by lower pin portion 305.
  • an elastic body such as hard rubber or a leaf spring
  • the longitudinal direction of the flow path when each of them is oriented in the most favorable direction for valve closure is set as the ⁇ axis, the direction perpendicular to the ⁇ axis and Z axis as the ⁇ axis, and the plane parallel to the XY plane as the ⁇ plane.
  • the ⁇ axis of the valve of the flow path device 104 is assumed to be fixed relative to the XY axes.
  • the ⁇ axis direction of the flow path device 104 and the ⁇ axis of the sliding plate grounding portion 308, the pin lower portion 305, and the pin upper portion 309 always coincide when the sliding plate is driven or stopped.
  • the ⁇ axis of the sliding plate grounding part 308 can rotate freely with respect to the XY axis of the sliding plate 303.
  • the ⁇ axis of the lower part of the sliding plate 303 can also rotate freely with respect to the ⁇ axis of the sliding plate grounding part 308.
  • the sliding plate grounding part 308 is cylindrical and the pin lower part 305 is connected to the sliding plate grounding part 308 via an axis, the ⁇ axis of the pin lower part 305 can be fixed with respect to the ⁇ axis of the sliding plate grounding part 308.
  • Figures 12A to 12C are diagrams showing examples of methods for maintaining the position of the head 309 inside the pin or between the pin 304 and the pin guide 302.
  • the rotational likelihood of the ⁇ axis of the pin upper part 309 can be limited by the inner wall of the through hole 310.
  • a key groove may be carved in the through hole 310, and a protrusion 601 that fits into the key groove may be provided on the pin upper part 309.
  • FIG. 12B is a diagram showing an example of limiting the range by generating a frictional force between the outer wall of the lower pin 305 and the inner wall of the pin.
  • the lower pin 305 is partially inserted into the inside of the upper pin 309.
  • the outer wall of the lower pin 305 has a portion that is not circular when cut in the XY plane, and the upper pin 309 has an inner wall of a similar shape.
  • the range of motion of the upper pin 309 may be limited by the outer wall of the upper pin 309 and the inner wall of the lower pin 305.
  • the ⁇ axes are aligned above and below the pin, and the ⁇ axis at the bottom of the pin is aligned with the ⁇ axis of the sliding plate contact part, and the ⁇ axis of the sliding plate contact part has a sufficiently limited rotational tolerance relative to the XY axes, then the ⁇ axis at the top of the pin and the ⁇ axis of the flow path device can be controlled.
  • the sliding plate 303 is provided with rail guides 602 as shown in Fig. 13 (2).
  • Fig. 13 (2) shows an example of a configuration in which rail guides 602 are provided so as to contact both sides of the roller parallel to the XY plane, restricting the movement of the sliding plate grounding portion so that it does not shift in the Y direction, and an example of a configuration in which grooves 603 are carved into the roller, the guides of the sliding plate 303 fit into the grooves 603, restricting the movement of the sliding plate grounding portion 308 so that it does not shift in the Y direction.
  • 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 a rack-type railway system known as the Abt system. By using this system, the movement of the pin can be accurately controlled even if the angle of the slope is large.
  • FIG. 14 is a diagram showing an example of the design of the pin.
  • 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 an axis 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.
  • the head 309 is provided on the Z positive end side of the spring plunger 501.
  • the rotational flexibility and oscillation of the head 309 are limited by the two spring plungers 501 and the through hole 310.
  • the shaft 512 a heavy load is applied, particularly at the contact point between the leg 513 and the roller 308.
  • the shaft 512 is made of a material with high strength.
  • the shaft 512 can be made of SUS.
  • the roller surface is fluorine-treated.
  • FIGS 15A and 15B are diagrams showing examples of the configuration of pins 304 when two valves are opened and closed simultaneously using two heads. Valves using such pins 304 are preferably not too far apart from each other.
  • the second springs 307 may be attached to each valve, or as shown in FIG. 15B, one for each valve. It is preferable that the first springs 306 are provided for each head 309. Furthermore, it is preferable that the centers of gravity of the second springs 307, the pins 304, and the two or more valves are located on an axis parallel to the same Z axis.
  • the spacing determined by element 4 is 5 mm or less, 3 mm or less, and 1 mm or less.
  • the valve spacing will be 5 mm or more. Therefore, the valve placement constraints are mainly determined by elements 1, 2, and 3. In other words, it is necessary to remove the constraints of elements 1, 2, and 3 as much as possible.
  • the sliding plate 303 and sliding plate drive system 301 may be installed independently for each valve. In this case, all valves can operate independently, making it easier to control complex valves. Also, multiple analysis procedures can be prepared, and analysis can be performed with different valve opening and closing patterns for each analysis. Since it is necessary to control only the two operations of opening and closing the valve, the number of sliding plate steps for one sliding plate 303 can be a minimum of two. This makes it possible to reduce the driving range of the sliding plate 303 in the X-axis direction. However, since the constraints of element 3 are imposed on each valve, the degree of freedom in valve placement is reduced. Also, since an actuator is required for each valve, the system becomes complex.
  • 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 distributed. Also, valves that are driven to open and close by the same sliding plate 303 cannot open and close independently. For this reason, it is necessary to prepare the number of sliding plate steps for the required valve opening and closing patterns.
  • FIGS. 16A to 16F are diagrams showing a table showing valve opening and closing operations (opening and closing steps), valve arrangements, and examples of sliding plate patterns.
  • the coordinates of the valves indicate the center of gravity of the valves.
  • the sliding plate 303 and the flow path device 104 are drawn side by side, but the positional relationship between the two is not shown.
  • valves are spaced as close as possible, but in the actual flow path device 104, the valves are arranged in appropriate positions in consideration of other flow path device elements such as chambers and external connection ports.
  • Figure 16B by increasing the number of sliding plate steps, it is possible to implement a combination of complex valve opening and closing patterns.
  • FIG. 16A is a diagram showing an example of a sliding plate pattern when three valves are installed on the same X coordinate.
  • the flow path device 104 is provided with valve V1 at the position (x1, y1), valve V2 at the position (x1, y2), and valve V3 at the position (x1, y3).
  • FIG. 16A(1) shows the valve opening and closing patterns.
  • FIG. 16A(2) shows the valve arrangement and the sliding plate pattern of the sliding plate 303 that can execute the valve opening and closing pattern as shown in FIG. 16A(1).
  • the sliding plate 303 is driven in the X plus direction, and the sliding plate Steps 1, 2, and 3 sequentially drive the pins in the Z axis direction, enabling the valve opening and closing pattern as shown in FIG. 16A(1).
  • valve spacing (y2-y1) is determined by the larger value of element 1 and element 2.
  • Fig. 16B is a diagram showing an example of a sliding plate 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 sliding plate pattern of the sliding plate 303 that can execute the valve opening and closing pattern as shown in Fig. 16B(1).
  • the flow path device 104 has valve V1 at the position (x1, y1), valve V2 at the position (x2, y1), and valve V3 at the position (x3, y1).
  • one concave-convex lane is used for three valves.
  • the sliding plate 303 only needs to have one convex part.
  • the convex part closes the valves V1, V2, and V3 in sequence.
  • the sliding plate 303 does not need to have a concave part that specifies the open state of the valve, as in the sliding plate 303 in FIG. 16B (2). By omitting the concave part, the width of the sliding plate in the X direction can be minimized.
  • 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 arrangement of the valves.
  • a sliding plate 303 consisting of one uneven lane with a total of five uneven parts is used for three valves.
  • Step 1 the convex part 1 comes to valve 1
  • valves V1 and V2 are closed
  • V3 is opened because the concave part is in contact with it.
  • Step 2 and Step 3 the convex part 2 comes to valve 1 and the concave part comes to valve 1, respectively, performing the opening and closing operations as shown in the table.
  • the minimum valve spacing (x2 - x1) is constrained by element 1 as well as element 5 (the width of the uneven part in the X direction), and is determined by the larger of the constraints imposed by elements 1 and 5.
  • valves do not have to be positioned at exactly the same Y coordinate; by lengthening 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.
  • valves share a sliding plate lane as shown in Figures 16B and 16C, for example, operation as normally open, where only one valve is closed, as shown in Figure 16B, is possible. Normally closed operation, where one of multiple valves is open, is also possible.
  • Normally closed operation where one of multiple valves is open, is also possible.
  • all valves are in an open state during the step of inserting the flow path device 104.
  • the pin 304 that is in contact with the convex portion 311 can be retracted when the flow path device 104 is inserted.
  • the sliding plate 303 may be provided with a concave portion 312 that allows all valves to be in an open state, but this will increase the length of the concave-convex lane in the X-axis direction.
  • Fig. 16D is a diagram showing an example of a sliding plate pattern in the case where three valves are not arranged on the same XY coordinates and the concave and convex lanes are not shared between the valves.
  • Fig. 16D (1) shows a valve drive pattern.
  • Fig. 16D (2) shows the arrangement of the valves and a sliding plate pattern of the sliding plate 303 that can execute the valve opening and closing pattern shown in Fig. 16D (1).
  • the flow channel device 104 is provided with a valve V1 at a position (x1, y1), a valve V2 at a position (x2, y2), and a valve V3 at a position (x3, y3).
  • one concave-convex lane is used for one valve. Since there are no shared concave-convex lanes between valves, the constraints of element 1 and element 2 work as follows:
  • 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 sliding plate 303 that can execute the valve opening and closing pattern shown in Figure 16E (1). With this arrangement, the uneven lanes of the two valves exist on the same Y coordinate, but the uneven parts are not shared between the valves.
  • FIG. 16F shows an example of a sliding plate pattern when valves V1 and V2 are arranged on the same Y coordinate, and valve V3 is arranged on a different Y coordinate from V1 and V2.
  • valves V1 and V2 share a concave-convex lane, and valve V3 is assigned a separate concave-convex lane.
  • the X-axis direction may be aligned with the longitudinal direction of the flow path device 104. Since the arrangement interval of the valves in the X-axis direction is restricted in the X-axis direction, by aligning the valves with the longitudinal direction, it is possible to arrange more valves in a smaller flow path device 104.
  • the constraints of element 1 and element 2 are relaxed.
  • the width of the pin in the X-direction and the Y-direction do not have to be the same.
  • the width of the roller 308 in the Y-axis direction the constraint of element 2 can be relaxed.
  • the width of the pin 304 in the X-axis direction does not affect the valve arrangement constraints as long as it does not interfere with the sliding plate 303. For this reason, it is preferable to store elements that make the pin 304 thick in the X-axis direction.
  • the protrusion 322 that receives the reaction force of the second spring 307 is a part of the pin 304 that protrudes relatively more from the central axis, but by making it thick in the X-axis direction and thin in the Y-axis direction, the influence of the constraint of element 1 in the Y-axis direction can be minimized.
  • the width of the pin 304 in the X-axis direction may be large, and it is preferable for the width in the Y-axis direction to be small.
  • the pin 304 may have a shape that is not restricted by element 2, it may have a shape that extends from the corresponding uneven lane into the adjacent lane when viewed from the XY plane. For example, it is sufficient if the leg 513 is made longer than the height of the uneven part of the sliding plate 303 and the protrusion 322 does not hit the sliding plate 303.
  • 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.
  • the Z coordinate of the thickest part among multiple pins 304 it is possible to prevent interference between the pins 304 and to arrange the valves closer together.
  • FIG. 16A(3) is a diagram showing the movable range in the X-axis direction of the sliding plate 303 when the sliding plate diagram shown in FIG. 16A(2) is moved like the valve opening and closing pattern (FIG. 16A(1)).
  • the X-coordinate of the center of gravity of the sliding plate 303 is smallest at Step 1
  • the X-coordinate of the center of gravity of the sliding plate 303 is largest at Step 3.
  • the sliding plate 303 itself has a width of three steps, and the X-coordinate moves by two steps from Step 1 to Step 3. Therefore, the total driving range of the sliding plate 303 is 5a, assuming a width per step.
  • Figure 16C (3) is a diagram showing the movable range of the sliding plate 303 when the sliding plate diagram shown in Figure 16C (2) is moved according to the valve opening and closing pattern (Figure 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, with a being the width per step.
  • 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 in the valve opening and closing pattern (FIG. 16D(1)). Note that valve V2 is omitted in FIG. 16D(3).
  • 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.
  • Wx in the X direction of the sliding plate 303 is expressed by the above formula (2).
  • 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 is created that does not overlap with the movable range of the sliding plate 303, and the freed up space can be used effectively.
  • the number of sliding plate steps per sliding plate can be reduced. 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 steps.
  • each sliding plate 303 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 that are integrated with the sliding plate 303 and actuator 316 and can run on a common linear guide may be used. In this case, multiple sliding plates 303 can be installed with a shared drive area.
  • the sliding plates 303 When multiple sliding plates 303 are used, it is desirable to install the sliding plates 303 so that their drive areas do not overlap each other. In particular, it is preferable that the XY plane is shared, but the XZ plane is not shared.
  • Valves whose opening and closing timing is perfectly synchronized, or valves that may be synchronized may be driven on the same sliding plate lane using a double-headed pin as shown in Figures 15A and 15B.
  • a double-headed pin as shown in Figures 15A and 15B.
  • 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 using a double-headed pin is disadvantageous. In this case, they may be incorporated into the same sliding plate. If the opening and closing timing is perfectly synchronized, the number of sliding plate steps will not increase.
  • 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.
  • valves that may be either closed or open. It is advantageous to incorporate valves whose open/closed states are specified in steps that do not match, or do not match very well, into the same sliding plate 303. For example, if in step A the open/closed state of valve V1 is specified but not that of valve V2, and in step B the open/closed state of valve V1 is not specified but that of valve V2 is, then steps A and B can be combined into a single sliding plate step that specifies the open/closed states of valves V1 and V2.
  • valves directly below the pump are never open at the same time. For this reason, they may be operated as a normally closed valve set in which 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.
  • examples of flow paths that are not directly related to sensitivity or liquid transfer problems include the flow path that sends liquid from the purification membrane to the waste chamber, and the flow paths that extend from the tank that stores the lysis and purification reagent to the lysis chamber or purification membrane.
  • valves belonging to the same sliding plate 303 can be spaced closer together than valves belonging to different sliding plates 303, so it is appropriate to group the valves on the same sliding plate 303.
  • the driving range of the sliding plate 303 reflects the maximum interval b in the X-axis direction of the valves included in the chip. For this reason, it is preferable to install the valves in as narrow a range in the X-axis direction as possible.
  • the load on the ball guide of the linear actuator increases according to the number of valves that are closed simultaneously. Therefore, it is preferable to set the maximum number of valves that one sliding plate 303 can close as small as possible.
  • the power of the actuator 316 needs to be determined taking into account the increase in frictional force caused by the load when the valves are closed and the maximum number of valves that the actuator 316 can close simultaneously.
  • the power (thrust) of the motor it is preferable to set the power (thrust) of the motor with a margin of 2 to 5 times the required power derived from the maximum number of valves to be closed. For this reason, for the valves assigned to one sliding plate 303, the number of valves that transition to closed during one valve step transition needs to be as small as possible. The required power can also be reduced by intentionally shifting the position and inclination of the slope of the sliding plate 303 between the valves.
  • the width of the sliding plate 303 increases roughly in proportion to the number of sliding plate steps, it is preferable to group the multiple sliding plates 303 so that the maximum number of sliding plate steps is minimized.
  • the sliding plate steps do not have to be arranged in the order of the valve opening and closing steps, and the sliding plate 303 may move two steps at a time, or may move in both the positive and negative directions of the X direction.
  • the more steps the sliding plate 303 moves in one analysis the shorter the life of the sliding plate 303 will be. Therefore, it is preferable to determine the step arrangement of the sliding plate 303 so that the amount of movement of the sliding plate 303 is as small as possible. For example, if there is a step that is used most frequently among the sliding plate steps, that step may be placed near the center of the uneven lane.
  • Analysis systems 101 that can simultaneously analyze multiple samples generally tend to be large. Therefore, it is desirable for the various parts that make up the analysis system 101 to be as small as possible without sacrificing performance.
  • the flow path device 104 may be one for each sample, or one flow path device 104 may be capable of analyzing four samples at once.
  • one sample is analyzed with one flow path device 104
  • a chip capable of analyzing four samples at once with one flow path device 104 tends to increase the analysis cost because even when only one sample is to be analyzed, a chip for four samples is consumed and discarded after use.
  • each flow path device 104 can be controlled independently. For example, in a scenario where samples arrive one after another, analysis can be started every time a sample arrives, shortening the analysis time. In other words, random access can be used.
  • the flow path devices 104 may be 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 sliding plate 303 moving direction being X. In this arrangement, it is not necessary to set the interval between the flow path devices 104 taking into account the drive range in the X-axis direction of the sliding plate 303. However, when using multiple sliding plates 303, it is necessary to arrange them in a way that they do not interfere with each other. For example, the first sliding plate 303 may drive the valve arranged above the X-axis and the second sliding plate 303 may drive the valve arranged below the X-axis so that the drive ranges do not overlap in the X-axis direction.
  • 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 per chip as shown in FIG. 16B are arranged, and the drive range in the X-axis direction is shared to close any three valves.
  • a drive unit in which the sliding plate and actuator are integrated as shown in Figure 4D may be used.
  • 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.
  • valve drive direction is Z
  • sliding plate 303 moves in X
  • the flow path devices 104 may be arranged along the X-axis direction without overlapping in the Z-axis direction.
  • FIG. 17C is a layout diagram of the arrangement of FIG. 17B as viewed from the Y-axis direction.
  • the sliding plates 303 may be attached between the flow path devices 104, or may be separate as long as they are driven by the same ball guide motor. Attached arrangement is preferable because it prevents misalignment.
  • the device holder pin guide may be independent or attached.
  • FIG. 17D shows the layout and movable range of the sliding plate 303 when four flow path devices are arranged in the X-axis direction as in FIG. 17B (repeatedly arranged at equal intervals), the sliding plate 303 as in the sliding plate diagram in FIG. 16D(2) is shared between the flow path devices 104, and the valve is moved as shown in the opening and closing pattern in FIG. 16D(1). Note that the valve V2 is omitted in 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 such an 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).
  • Each concave-convex lane has a width of three steps per chip, and the X coordinate moves two steps from Step 1 to Step 3, and the flow channel devices are arranged at intervals of c.
  • the minimum driving range Wx is expressed by the following equation (3).
  • Wx a ⁇ (2 ⁇ S-1)+b+3c... (3)
  • Wx a ⁇ (2 ⁇ S-1)+b+c ⁇ (m-1)... (4)
  • Wx a ⁇ (S ⁇ (m+1)-1)+b... (5)
  • the uneven lane is provided for each flow path device 104, but the uneven lane may be shared between the flow path devices 104.
  • the amount of drive of the sliding plates 303 can be reduced.
  • the driving direction of the sliding plate 303 may be not only linear motion (X-axis direction) but also rotational motion.
  • Figure 17E is a diagram showing an example of arrangement when multiple sliding plates 303 performing rotational motion are used for multiple flow path devices 104. In this case, the central axes of the sliding plates S1, S2, and S3 are coaxial.
  • the second spring 307 can be set to a compression rate of 40% in the recess 312 and 70% in the protrusion 311, for example.
  • the second spring 307 reaches the contact length during driving, the repulsive force becomes uncontrollable and a strong 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 protrusion 311 to a length with a margin larger than the contact length.
  • the spring constant used for the second spring 307 is small.
  • an elastic force of 1 N or more is applied from the second spring 307 to the pin 304.
  • an elastic force of 4 N or less is applied from the second spring 307 to the pin 304.
  • the spring constant used for the second spring 307 needs to be 1 N/mm or less.
  • the distance between the sliding plate grounding portion 308 and the flow path device 104 or the valve bottom surface 305 or the film 202 when the valve is closed varies due to wear of the sliding plate 303, the inclination of the sliding plate 303, individual differences in the flow path device 104, individual differences in the pins, wear of the pins 304, and misalignment of the pins 304, and is limited to a range of ⁇ 0.1 mm. More realistically, it is limited to a range of ⁇ 0.5 mm.
  • the pressing force when the distance is at its farthest must exceed the required pressing force, and for example, it should be designed so that 20% more force than the required pressing force is applied when the distance is at its farthest.
  • the pressing force when the distance is at its shortest is too large compared to the required pressing force, it will lead to damage to the flow path device 104 or the sliding plate drive system 301, and loss of synchronization of the actuator 316.
  • the use of an actuator 316 with high power will lead to an increase in the size of the analysis system 101. From the above, it is preferable to design the pressing force at the closest distance to be within 200% of the required pressing force. Taking these constraints into account, it is preferable for the first spring 306 to have a small variation in elastic force relative to the amount of contraction, and it is preferable for the spring constant to be small.
  • the rate of increase in the valve pressing force (first force F1) in the range Z1 ⁇ Zp ⁇ Z2 is preferable for the rate of increase in the valve pressing force (first force F1) in the range Z1 ⁇ Zp ⁇ Z2 to be 40 N/mm or less.
  • the spring constant of the first spring is preferable for the rate of increase in the valve pressing force (first force F1) in the range Z1 ⁇ Zp ⁇ Z2 to be 40 N/mm or less.
  • the spring constant of the first spring 307 is a value that can reach the required pressing force F1 with a contraction amount of 3 mm or less.
  • a sliding plate with a larger height of the teeth of the concaves and convexes 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.
  • the height of the teeth of the concaves and convexes can be reduced by setting the initial load to a large value.
  • the spring constant of the first spring 306 is 0.8 ⁇ F1/mm or less and 0.33 ⁇ F1/mm or more for the required pressing force F1.
  • the required depression force for a valve such as that shown in FIG. 2A is typically 3 N or more, 5 N or more, 10 N or more, and 15 N or less. Therefore, it is preferable that the spring constant of the first spring 306 is 12 N/mm or less and 1 N/mm or more.
  • spring 306 connecting pin upper part (head) 309 and pin lower part 305 may be called the first spring
  • spring 307 in contact with pin 304 and pin guide 302 may be called the second spring.
  • the respective spring constants are k1 and k2.
  • Zp when the head 309 comes into contact with the flow path device 104 changes between the first time the valve is pressed and the second or subsequent times the valve is pressed.
  • Zp refers to the smallest Zp value. Zp is typically smallest when the valve is pressed for the first time.
  • Zp can be considered as changing each time the valve is pressed. This should be considered in a way that can represent the behavior that is closest to the actual valve behavior depending on the valve shape. Different Z0, Z1, and Z2 may be set for each sliding plate step. In fact, when setting the initial lengths of the various springs and the spacing and unevenness height of the first, second, and third plates, the valve may be opened and closed multiple times to check whether the desired valve opening and closing operation can actually be performed. It is acceptable if the change in pressing force relative to the Zp coordinate shows a different behavior from the behavior specified here depending on the time, as long as there are no problems with actual opening and closing.
  • first force F1 the force (pressing force) in the positive Z-axis direction that the pin upper part 309 exerts on the flow path device
  • second force F2 the force in the negative Z-axis direction that the pin sliding plate grounding part 308 exerts on the sliding plate
  • FIG. 18A is a diagram showing the characteristics of the force applied by the pin 304 to the sliding plate 303 or the flow 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.
  • the flow 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).
  • the horizontal axis of the graph in FIG. 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 flow path when closed.
  • the first spring (spring 306) 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. In addition, if the first spring (spring 306) is configured not to have an initial load of the spring plunger 501 described below, it is essential that the spring constant k1>k2.
  • the tension spring prevents the pin 304 from falling, so the pin does not drop too far in the negative Z direction.
  • the pin can move in the negative direction to a point where Zp falls below Zn.
  • the configuration may be such that the lower limit of extension of the second spring is restricted by the pin guide.
  • FIG 19 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 part 305.
  • the enclosure 604 is narrower than the protrusion 322 of the pin lower part 305, and is structured so that the pin lower part 305 does not protrude below the enclosure 604.
  • This type of configuration can be used particularly in a configuration where Zn ⁇ 0 as shown in Figure 18B.
  • the head 309 pops out, so there is a possibility that it may get caught when inserting the flow path device 104 next time.
  • the first spring 306 is built into the spring plunger 501.
  • the spring plunger 501 When the spring plunger 501 is assembled, if the compression spring is stored in a compressed state, 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. If a force equal to or more than the initial load is applied to the spring plunger 501, the spring is compressed and the overall length of the spring plunger 501 is shortened according to the spring constant.
  • the initial load is set to a value equal to or less than the target pressing force.
  • it is preferable to set the initial load to an elastic force that is 50% or more of the elastic force when Z Z2.
  • 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 cannot be controlled, and too strong a force is applied to the valve.
  • FIG. 18D shows a pin incorporating a suitable spring plunger 501 and the compression force profile of the pin.
  • 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 a pin 304 having a first spring in a spring plunger 501 is pressed against a flow path device 104 with a PP film attached.
  • 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.
  • First spring 306 spring constant 1.5 N/mm, outer diameter 3 mm, natural length 25 mm, maximum load 14.7 mm, solid 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 The first spring 306 is built in, and is installed inside so that the first spring 306 has an initial length of 19 mm. In the above configuration, the initial load of the spring plunger 501 is 9 N.
  • the second force F2 is 13.8 N. If the value of Z2 varies by ⁇ 0.5 mm, the pressing force varies between 11.25 and 12.75 N, and the second force F2 varies between 13 N and 14.6 N.
  • the inclined surface shape of the sliding plate 303 is symmetrical.
  • the sliding plate 303 is arranged in a circular shape as shown in Fig. 17E and is driven in only one direction, the inclined surface shape may be asymmetrical.
  • 18F is a diagram showing the force applied to the sliding plate grounding portion 308 on the inclined surface of the sliding plate 303.
  • the inclined surface angle in the X-axis direction of the uneven surface 313 with which the sliding plate grounding portion 308 comes into contact when the pin 304 moves in the Z-axis positive direction along the inclined surface is ⁇ .
  • the magnitude of the force that the sliding plate 303 applies to the sliding plate grounding portion 308 is F.
  • the force acting on the sliding plate 303 in the negative X-axis direction is expressed as F2 x tan ⁇ .
  • ⁇ increases, the value of F increases, and the frictional force generated between the sliding plate contact portion 308 and the sliding plate 303 increases. For this reason, a greater thrust is required to overcome the frictional force and displace the pin 304 in the positive Z direction.
  • the force applied in the negative Z direction becomes a load on the sliding plate 303, which generates friction in the ball screw, so the larger F2 becomes, the more thrust is required to counter the frictional force generated in the ball screw.
  • the second force F2 is typically small in the range Zn ⁇ Z1 as shown in FIG. 18A (2), and the rate of change is also small, so the slope angle ⁇ may be set somewhat higher.
  • the second force F2 is large and the rate of change is also large, so it is preferable that the slope angle ⁇ be set somewhat lower.
  • the uneven surface 313 is designed so that the slope angle becomes smaller as Zn increases.
  • the analysis system can be made compact. With appropriate layout and pin design, a compact analysis system can be created. By dividing the sliding plate, a compact analysis system can be created. Since a flow channel with a deep cross-sectional shape can be used, surface adsorption is reduced. In addition, the degree of freedom in valve placement is increased, allowing the flow channel to be made shorter.
  • Patent Document 3 Patent Document 4, and Non-Patent Document 1
  • the valve is driven by a sliding plate drive system.
  • a flow path device is used in which the film is made of an elastic material or elastomer. Therefore, the closing rate characteristic of the valve has no hysteresis.
  • the pressing force-closing rate characteristic of the flow path device exhibits behavior with little hysteresis. Valves made of elastic materials or elastomers can achieve a sufficient closing rate with little force. In addition, they open to a certain extent even if some pressing force remains when they are opened.
  • the closure rate of the flow path device when opened must be 50% or less, and more preferably 20% or less. Therefore, the pressing force must be sufficiently small when opened.
  • the film (valve) of the flow path device 104 is made of polypropylene (PP).
  • PP polypropylene
  • a material that exhibits viscoelastic properties such as polypropylene exhibits the pressing force-closing rate characteristic shown in FIG. 3C.
  • the valve according to this embodiment tends to require a larger pressing force than when the valve is made of an elastic material. If the unloading at the time of opening is not 10% or less, or 1% or less, of the minimum pressing force at the time of closing, the closing rate will not be 50% or less, or 20% or less. Control of the pressing force at the time of closing is more difficult than when an elastic material is used for the film, and the change in pressing force at the time of positional deviation is more abrupt than when an elastic material is used.
  • the characteristics of the valve as shown in FIG. 3C are a problem found in this embodiment.
  • the pin 304 used it is necessary for the pin 304 used to have a double spring structure that houses a first spring 306 and a second spring 307.
  • Figure 20A is a diagram showing the pin characteristics of Non-Patent Document 1.
  • a ball plunger 509 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).
  • the force that follows 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 recess.
  • a spring plunger is used for the pin, the initial load mentioned above exists, and a pressing force equal to or greater than the initial load is applied to the film in the recess.
  • Non-Patent Document 1 an elastic material is used for the film, but if a plastically deforming film such as that used in this embodiment is used, sufficient repulsive force cannot be obtained to follow the sliding plate when released. Alternatively, if an attempt is made to obtain sufficient repulsive force, the valve will remain closed. If the pin does not receive 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.
  • the pressing force can be stabilized by reducing the spring constant of the spring installed inside ball plunger 509.
  • the spring constant of the spring installed inside ball plunger 509 For a spring with a small spring constant, it is necessary to set the initial load higher to obtain sufficient required pressing force with a small amount of contraction, but in the configuration of Figure 20A, the pressing force at the recess becomes large.
  • the diameter of ball plunger 509 must be increased to obtain a sufficient stroke. As the diameter of ball plunger 509 increases, the minimum valve spacing increases.
  • the top of the pin will pop out of the pin guide when the flow path device is removed. This requires that the flow path device be inserted from the positive direction of the Z axis, or a mechanism be provided to drive the sliding plate in the negative direction of the Z axis. If the flow path device cannot be inserted in a direction parallel to the Z axis, it may get caught on the pin.
  • the ball plunger 509 cannot increase the distance from the contact point of the sliding plate to the top of the pin. For this reason, if you try to design the sliding plate so that it does not interfere with the sliding plate, the length in the X-axis direction will become longer.
  • FIG. 20B is a diagram showing the pin characteristics of Patent Document 4.
  • the pin When the pin is in the recess, if the head is away from the flow path device, it is possible to bring the flow path to an open state.
  • 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 an elastic film is used, but if the film is not made of an elastic material, it is more difficult to control the pressing force by the height of the sliding plate.
  • the valve is used as a pump. For this reason, it is not a problem if the convex part is not 100% closed, but to close the valve properly, a relatively strong pressing force is required, which inevitably puts a large load on the actuator.
  • 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.
  • 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 such an example, the pressing force remains at the time of release, preventing sufficient release.
  • the relationships Zn ⁇ Z1 and Z0 ⁇ Z1 ⁇ Z2 hold, so the pressing force when the valve is opened can be made sufficiently small.
  • 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.
  • the head 309 separates from the flow path device 104 at the recess 312, and the pressing force can be made zero.
  • Zn ⁇ Z0 the pin 304 can stably follow the uneven portions of the sliding plate 303.
  • the sliding plate contact portion 308 can be configured with rollers, so the valves can be arranged more closely together than if they were configured with balls.
  • the sliding plate contact portion 308 can be designed so that it is not connected to the first spring (first spring 306).
  • the second spring (second spring 307) is configured to contact the lower part of the pin 305. Therefore, it is possible to apply 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).
  • multiple valves of one flow path device 104 can be driven by multiple sliding plates 303.
  • the number of valves is eight or more, if one sliding plate 303 is used to perform the opening and closing operations of all the valves, the sliding plate 303 becomes long, but by using two or more sliding plates 303, it is possible to prevent the analysis system 101 from becoming large.
  • the arrangement of the sliding plate 303 and the pin guide 302/pin 304 can be repeated for the number of flow path devices 104 so that one sliding plate 303 can drive the valves of multiple flow path devices 104.
  • the movement allowance of the sliding plate 303 can be shared, and the analysis system 101 can be prevented from becoming large. The number of actuators required can be reduced.
  • FIG. 20D and 20E are diagrams comparing the characteristics of the force (first force) applied to the flow channel device 104 by pins 304 of different configurations.
  • Figure 20D (2) is a diagram showing the change in the first force in the configuration of Figure 20A (1). Since the pin is in contact with the film even when opened, the first force Fo when opened satisfies Fo>0. Since 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 frictional force exists between the pin and the pin guide, the value of Fo will fluctuate, making it difficult to reproduce the open state.
  • FIG. 20E(1) is a continuation of FIG. 20D, and shows the change in the first force in the configuration of this method, as in FIG. 9.
  • pin 304 is equipped with a first spring
  • the valve can be closed with a device configuration in which the fluctuation in Zp is ⁇ 0.5 mm or less.
  • the pressing force becomes 0 due to the action of the second spring, so the valve can be opened reliably.
  • Chamber/Reagent Storage is a space that can store liquids or solids and can react, wait, heat, or change solutions.
  • the chamber may have a larger diameter than the flow path, but may not be distinguishable from the flow path by appearance.
  • the chamber may have a membrane or fine structure inside, may be made of a different composition than the flow path, may have a different surface treatment, or may have a different hydrophilicity.
  • the flow path device may also have a heater or laser light source on the outside.
  • Reagents may be stored in the chamber, and PCR, dissolution, purification, etc. may be performed in the chamber.
  • a typical chamber volume is preferably 0.01 ⁇ L to 50 mL.
  • the reagents may be stored in the flow path device 104, or may be supplied from outside the flow path device 104 and from inside the analysis system 101.
  • the flow path device 104 can be configured to store one or more types of reagents in one or more reagent storage sections.
  • the reagents include at least one of a dissolving solution, a cleaning solution, a PCR reagent that may contain a polymerase, a primer, a surfactant, etc., formamide, pure water, DNA fragments, oil, etc. If these are mixed at an unintended timing, performance may be reduced or other unexpected results may occur.
  • a partition mechanism consisting of a valve, a film, air, or a flow path that is thin enough to prevent spontaneous mixing, or a combination of these, until just before use.
  • a partition mechanism consisting of a valve, a film, air, or a flow path that is thin enough to prevent spontaneous mixing, or a combination of these, until just before use.
  • isolating the reagent from the outside air long-term storage and portability of the flow path device are achieved.
  • the same reagent is released in multiple steps, it may be stored in multiple reagent storage sections.
  • a reagent is stored outside the flow path device 104, it is desirable that it is stored in a state isolated from the outside air, and is separated from other purification system components by a valve, a film, air, etc.
  • reagent storage technologies include, for example, a blister reagent storage unit and the reagent storage unit mounted in Patent Document 1 and Patent Document 5. Configurations similar to these may be incorporated into this embodiment.
  • 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 to release the reagent inside into the flow path.
  • the reagent can be opened and released simply by opening and closing the valve, allowing the system to be made smaller.
  • a reagent storage unit of this type may be incorporated into the flow path device 104 of this embodiment.
  • the reagent storage section and the chamber may be installed so as not to overlap with the XY plane of the flow path device 104.
  • the layer structure of the flow path device 104 can be prevented from becoming complicated.
  • elements (members) that are not large in volume can be arranged on the Z plus and Z minus faces of the XY plane of the flow path device 104 even if they are arranged in layers.
  • the solution is stored in the Y minus direction, making it easier for air to accumulate in the Y plus direction, and the solution is taken out from an outlet provided in the Y minus direction, thereby minimizing the inclusion of air bubbles.
  • the Y minus direction is parallel to gravity (angle 0°) or forms an angle of 45° or less with respect to gravity, or an angle of less than 90° with respect to gravity.
  • the Z minus 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 guide 302 and the pin 304. Therefore, without the second spring 307, it is difficult to follow the movement.
  • the sample provided to the analysis system (purification system) 101 is not particularly limited as long as it is a sample derived from a living organism.
  • the living organism from which the sample is derived is also not particularly limited, and samples derived from any living organism such as vertebrates (e.g., mammals, birds, reptiles, fish, amphibians, etc.), invertebrates (e.g., insects, nematodes, crustaceans, etc.), plants, protozoa, plants, fungi, bacteria, and viruses can be used.
  • Samples can be collected using a swab, filter paper, cloth, etc. as a carrier. The carrier may be introduced into the analysis system 101.
  • forensic samples can be analyzed by the analysis system 101.
  • forensic samples include cheek swabs, bones, muscle tissues, human organs, samples containing very small amounts of DNA called touch samples, bloodstains, skin fragments, hair, body fluids, and remains that are presumed to have these attached.
  • Many forensic samples contain an unknown amount of DNA.
  • the concentration of DNA ranges from 0.001 ng to 1000 ⁇ g, and more frequently, 0.01 ng to 10 ⁇ g.
  • Forensic samples may contain only DNA from a single person, may contain DNA from multiple people, and may contain degraded DNA. To increase the success rate of DNA identification, it is necessary to minimize DNA loss due to surface adsorption in the DNA flow path device 104.
  • the analysis system 101 may include a pump and a valve for transporting the solution.
  • 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.
  • Valves are used to specify the solution transport path, as well as to switch the path to which air pressure is applied.
  • a valve a diaphragm valve that operates with air pressure, a mechanical valve, or a valve that uses surface tension can be used.
  • the flow path that can be transported may be switched based on the difference in pressure required for transport.
  • CE Detection method After amplification, detection by CE is performed.
  • the amplification product can be injected into a capillary filled with a polymer by voltage injection.
  • CE when a high voltage is applied to both ends of the capillary, the fluorescent DNA fragments are separated by size and detected by a laser/camera system.
  • MPS massively parallel sequencing
  • pyrosequencing pyrosequencing
  • Sanger sequencing nanopore sequencing
  • chromatography electrical measurement
  • spectroscopy NMR
  • RFLP Restriction Fragment Length Polymorphisms
  • microarrays etc.
  • Fig. 21 is a diagram showing a detailed configuration example of the analysis system 101.
  • Fig. 22 is a diagram showing an example of an operation procedure of the analysis system 101. Note that for details of the analysis procedure and the transport procedure, reference can be made to Patent Document 1, Patent Document 5, the explanation of the QIAamp DNA Investigator Kit manufactured by QIAGEN, and the like.
  • 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 dissolution chamber 701 for introducing and dissolving a collected sample, a purification membrane chamber 703 in which a purification membrane 702 is stored, a PCR chamber 704 for performing DNA amplification, a waste liquid chamber 705, and an external connection port 706 that is fluidically connected to the outside of the flow path device 104.
  • the solution is transported through the external connection port 706, and reagents, amplified products, and the like can be exchanged with the outside of the flow path device 104.
  • 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 part of it may be provided inside the flow path device 104.
  • the PCR reagent storage unit 708 holds the reagents necessary for the PCR reaction (polymerase, primer, dNTP, buffer, etc.).
  • the migration reagent storage unit 710 may hold the migration reagent.
  • a reagent storage unit for storing reagents necessary for pre-processing is also included.
  • the dissolution liquid is transported from the dissolution liquid storage section 712 to the dissolution chamber 701.
  • dissolution step S802 dissolution begins.
  • the binding liquid is released from the binding liquid storage section 711.
  • the purification step S803 the dissolution product is sent from the dissolution chamber 701 to the purification membrane chamber 703, the DNA is bound to the purification membrane 702, a cleaning liquid is released from the PCR reagent storage section 708, and purification is performed. After purification, a step of drying the cleaning liquid etc. may be inserted.
  • the elution liquid is released from the PCR reagent storage section 708, and the DNA eluted from the purification membrane chamber 703 is transported to the PCR chamber 704.
  • PCR reagent is released from the PCR reagent storage section 708 to the PCR chamber 704 and mixed with the eluted DNA.
  • the purified DNA is mixed with a PCR reagent in the PCR chamber 704 and subjected to a PCR reaction.
  • the amplified DNA is mixed with the migration reagent stored in the migration reagent storage unit 710 and measurement is performed in the CE unit 105.
  • a step can be added in which the mixture is heated to 80-100°C and then rapidly cooled to 0-10°C before CE analysis. By adding this step, the DNA is more completely converted into single strands, enabling highly accurate CE analysis.
  • Fig. 23A is a diagram showing an example of connections of a plurality of flow paths, valves, and the like in a flow path device 104 used in the analysis system 101.
  • Fig. 23B is a diagram for explaining a liquid delivery operation, etc. in the flow path device 104 of the analysis system 101.
  • the flow path device 104 has external connection ports 951, 952, 953, and 954.
  • the flow path device 104 exchanges solutions with the analysis system 101 through the external connection ports 951, 952, 953, and/or 954, and can be controlled by air pressure.
  • the external connection port 951 is connected to a pressure pump
  • the external connection port 952 is connected to a detection unit
  • 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 due to unexpected operation, causing contamination. 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.
  • the external connection port 951 (external pressurization connection port) is connected to flow path 901 with valve V4, flow paths 902, 903, 904, and 905 with valve V12, and flow path 906 with valve V10.
  • Flow path 901 is connected to flow path 907 and flow path 908 with valve V2.
  • Flow path 907 is connected to the dissolution chamber 701.
  • Flow path 908 is connected to the external connection port 953.
  • Flow path 903 is connected to the binding liquid reservoir 711.
  • Flow path 904 is connected to the cleaning liquid reservoir 713.
  • Flow path 905 is connected to the dissolution liquid reservoir 712.
  • Flow path 902 is connected to the mixing chamber 955.
  • the binding liquid reservoir 711 is connected to a flow path 919 equipped with a valve V5.
  • the dissolution liquid reservoir 712 is connected to the dissolution chamber 701 via a flow path 920 equipped with a valve V3 and a flow path 910.
  • the dissolution 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 path valve V9 and a flow path 916 equipped with a valve V8.
  • the cleaning liquid storage section 713 is connected to a flow path 915.
  • the flow path 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 path 913 is connected to a PCR chamber 704.
  • 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, the flow path 917 equipped with a valve V13, and the flow path 918 equipped with a valve V14.
  • the flow paths 918 and 917 are connected to an external connection port 952.
  • the elution liquid reservoir 709 is connected to a flow path 911 between the valve V15 and the reagent chamber.
  • the PCR reagent reservoir 708 and the electrophoresis reagent reservoir 710 are connected to a flow path 913 between the valve V6 and the PCR chamber 704.
  • the sliding plate drive system 301 is provided with pins 304 and through holes 310 corresponding to each valve for the valves V1 to V15.
  • FIG. 24A is a diagram showing the flow path configuration of the flow path device 104 of FIG. 23A and the opening and closing steps of the valves corresponding to the operation example shown in FIG. 23B.
  • ⁇ indicates a step in which the valve must be open
  • ⁇ indicates a step in which the valve must be closed.
  • the upstream valve refers to a valve close to the pump that pressurizes/depressurizes.
  • the downstream valve refers to a valve close to the outlet that is open to the atmosphere, or a valve far from the pump.
  • the downstream valve does not affect the liquid sending operation whether it is open or closed.
  • the liquid sending operation is not affected whether the valve is open or closed except for the valve close to the chamber in which the liquid is stored.
  • the valves in the blank spaces indicate valves that may be open or closed.
  • valve opening and closing operation of FIG. 24A is performed using one sliding plate 303, the sliding plate 303 must provide valve patterns for a total of at least 14 steps, including the flow path device 104 insertion and flow path device 104 removal steps.
  • 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 between 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 are closed simultaneously is 6 valves x number of flow path devices.
  • the sliding plate 303 requires a driving range of 450 mm, which results in a large analysis system 101.
  • a large actuator is required.
  • the sliding plate 303 is divided into two, three, or four or more.
  • the sliding plate 303 is divided into three (sliding plates 1 to 3) as shown in FIG. 24A.
  • the valves V10, V12, V13, and V14 are assigned to sliding plate 1 (S1).
  • the valves V1, V2, V4, V8, and V9 are assigned to sliding plate 2 (S2).
  • the 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 are arranged as shown in FIG. 17B. According to FIG. 24A, it can be seen that at least one sliding plate (sliding plates 2 and 3 in the example of FIG. 24A) can drive five or more pins.
  • Figure 24B is a table showing the sliding plate steps.
  • the parts marked with a circle correspond to the recesses, which can open the valve.
  • the parts marked with an x correspond to the protrusions, which can close the valve.
  • FIG. 24C is a table showing the sliding plate steps corresponding to the analysis process.
  • S1, S2, and S3 are different sliding plate steps, so that a complicated valve opening and closing process can be analyzed with the sliding plate 303, which consists of a small number of sliding plate steps.
  • the sliding plate 303 is divided into sliding plates S1, S2, and S3, the number of valve opening and closing steps is four for sliding plate 1, four for sliding plate 2, and five for sliding plate 3.
  • the width in the X-axis direction is 40 mm
  • the driving range is 80 mm.
  • the driving range is 240 mm when the driving unit is shared between four flow path devices.
  • the maximum number of valves that can be closed simultaneously is three for sliding plate 3, and the number of valves that can be closed simultaneously is four.
  • FIG. 24D is a diagram showing the concave-convex lanes of each valve included in the sliding plate 1 shown in FIG. 24A expanded.
  • 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 arrangement of the valves.
  • the thickness of each concave-convex lane in the Y-axis direction may be the same, or may be different depending on the arrangement interval 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).
  • the valve arrangement constraints (element 1) and (element 2).
  • FIG. 23D all the valves are shown as being 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 FIG. 16D (4).
  • Step 0-0 S 0-0
  • Step 000 the uneven steps of the sliding plate
  • Step 000 the pre-processing steps
  • Roman numerals I, II, III, etc. indicate each state of the flow channel device 104 shown in Figs. 23A and 23B, such as liquid delivery and valve opening and closing.
  • step S851 Before inserting the flow path device 104, in step S851, the user inserts a sample such as a swab into the flow path device 104 and closes the sample insertion port. In step S852, the user inserts the flow path 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.
  • 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
  • Step 3-1 (S3-1) of the sliding plate S3 contacts the pin 304.
  • step S853 step S801
  • the sliding plate S3 moves and S3-2 comes into contact with the pin 304.
  • the valves V7 and V15 are closed.
  • the valves V3, V6, and V11 are opened.
  • the external connection port 951 is pressurized.
  • the valve dissolving liquid is released from the dissolving liquid storage section 712 and transported to the dissolving chamber 701 via the flow path 920.
  • step S855 the binding liquid is transported to the dissolution chamber via flow path 919. Then, in step S856, the dissolution product is mixed with the binding liquid.
  • step S857 valves V1, V4, V8, V7, and V15 are opened. Valves V2, V9, V3, V5, and V6 are closed. The external connection port 951 is then pressurized.
  • the lysis product is sent from the lysis chamber 701 to the purification membrane chamber 703, where the DNA binds to the purification membrane 702.
  • the waste liquid is discharged from the vent filter 954 via the flow paths 912 and 916.
  • step S858 the sliding plate S2 moves and S2-4 comes into contact with the pin 304.
  • valves V2 and V9 are opened.
  • Valves V4 and V8 are closed.
  • the external connection port 951 is pressurized.
  • the cleaning liquid is released from the cleaning liquid storage section 713 and sent to the purification membrane chamber 703 via the flow path 920.
  • step S859 sliding plates S1 and S2 move, and S1-3 and S2-2 come into contact with pin 304.
  • valves V10 and V8 are opened. Valves V13, V1, and V9 are closed.
  • external connection port 951 is pressurized. Air is pumped in via flow path 906, and this air dries the cleaning liquid. The air that has dried the cleaning liquid is exhausted from vent filter 954 via flow paths 912 and 916.
  • step S860 the sliding plate S3 moves and S3-2 comes into contact with the pin 304. At this time, valves V7 and V15 are closed. Valves V3, V6, and V11 are opened. Then, the eluate is released from the eluate reservoir 709, and DNA is eluted from the purification membrane chamber 703.
  • 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. Next, the external connection port 951 is pressurized. Then, the eluate is transported to the PCR chamber 704.
  • step S862 the sliding plate S3 moves and S3-5 comes into contact with the pin 304.
  • the valve V6 is closed.
  • the valve V5 is opened.
  • the PCR reagent is released from the PCR reagent reservoir 708 and the PCR chamber 704, and mixed with the eluted DNA.
  • step S863 (amplification step S804), the sliding plate 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. Next, the PCR chamber 704 is heated and the amplification reaction begins.
  • step S864 When the PCR reaction is completed, in step S864, the sliding plate S3 moves and S3-5 comes into contact with the pin 304. At this time, valves V5 and V11 are opened. Valve V7 is also closed. Next, the migration reagent reservoir 710 is crushed, and the reagent is released from there. The PCR product is transported to the mixing chamber 755 via the flow path 914.
  • step S865 the sliding plate S3 is moved so that S3-4 comes into contact with the pin 304.
  • the valve V6 is opened.
  • the valve V5 is closed.
  • the valves V12, V4, V9, V3, V5, and V7 are closed.
  • the external connection port 951 is pressurized, and air is sent into the mixing chamber 955.
  • the lysate and the migration reagent are mixed.
  • the air is discharged outside the flow path device 104 via the flow path 918.
  • step S866 the sliding plates S1 and S3 move, and S1-4 and S3-3 come into contact with the pin 304.
  • the valves V12, V13, and V7 are opened.
  • the valves V10, V6, V11, and V14 are closed.
  • the external connection port 951 is pressurized, and air is sent from the flow path 902.
  • the electrophoretic sample is transported outside the flow path device 104 via the flow path 917.
  • measurement is performed in the CE unit 105.
  • the sliding plates S1, S2, and S3 move, and S1-1, S2-1, and S3-1 come into contact with the pin 304.
  • all the valves are opened, and the flow path device 104 can be removed.
  • the drying path may also be different from that described above.
  • the dissolved product and the washing solution may flow from the same direction.
  • the sliding plate 303 can also be divided according to a similar rule.
  • the pin head 309 does not contact the valve of the flow path device 104 when the valve is open. In other words, when the valve is open, a certain clearance exists between the pin head 309 and the valve of the flow path device 104. In this way, the valve can be opened and closed accurately.
  • the Z coordinate of the Z-axis minus end of the pin 304 is Zp
  • the Z coordinates of the concave and convex parts on the surface of the sliding plate (third plate) 303 are Z0 and Z2, respectively
  • the minimum Zp at which the first spring 306 elastically deforms is Z1
  • the minimum Zp at which the second spring 307 elastically deforms is Zn
  • the valve opening and closing system is configured so that the relationships Z0 ⁇ Z1 ⁇ Z2 and Zn ⁇ Z1 hold.
  • the valve opening and closing system is configured such 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 around Z1.
  • valve pressing force by the pin 304 (first force F1) and the force by which the pin 304 presses the sliding plate 303 (second force F2) can be separated (the contact point between the sliding plate grounding 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.
  • the second spring (second elastic body) 307 is connected (contacts) with the pin lower portion 305 when elastically deformed. 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.
  • first spring (first elastic body) 306 and the second spring (second elastic body) 307 can be separated, and the spring constants can be selected independently.
  • the rate of increase of the valve depression force (first force F1) within the range of Z1 ⁇ Zp ⁇ Z2 is set to 40 N/mm or less.
  • the flow path device 104 used in the analysis system 101 of this embodiment has a substrate on which a flow path is formed, and a flow path lid material made of a film.
  • the film deforms when a valve pressing force is applied, and functions as a valve that suppresses the passage of fluid through the flow path.
  • the film is made of a plastically deforming film.
  • the valve opening and closing system according to this embodiment is fully suitable for stably opening and closing a valve made of such a plastically deforming film, because the valve pressing force is completely removed when the valve is opened (there is a clearance between the pin head 309 and the flow path device 104).
  • two or more flow path devices 104 can be arranged in the X-axis direction for analysis.
  • the arrangement pattern of the uneven portion of the sliding plate 303, the through holes 310 of the pin guide 302, and the pins 304 is arranged at equal intervals repeatedly for the number of flow path devices 104 (see Figure 17D).
  • 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).

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
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Abstract

L'invention divulgue un système d'ouverture/de fermeture de vanne qui comprend : une tige qui s'étend dans une direction d'axe Z et agit sur une vanne d'un dispositif de chemin d'écoulement ; une plaque coulissante qui possède une plage de mouvement dans une direction d'axe X et possède des irrégularités sur la surface dans la direction d'axe Z positive ; un premier ressort qui relie une tête de tige et une partie inférieure de tige (partie de base) ; un guide de tige qui possède un trou traversant ; et un second ressort qui relie le guide de tige et la partie inférieure de tige. La vanne est ouverte et fermée par le déplacement de la tige dans la direction d'axe Z par le déplacement de la plaque coulissante dans la direction d'axe X au moyen d'une unité de commande. Ici, il est important que la tête de tige ne soit pas en contact avec la vanne (constituée d'un film à déformation plastique) lorsque la vanne est ouverte. Lorsque cela-ci est exprimé sous la forme d'une expression conditionnelle, les relations Z0 ≦ Z1 < Z2 et Zn ≦ Z1 sont valides, la coordonnée Z de l'axe Z moins l'extrémité de la tige étant Zp, les coordonnées Z d'une partie concave et d'une partie convexe de la plaque coulissante étant Z0 et Z2, respectivement, le minimum Zp auquel le premier ressort se déforme élastiquement est Z1, et le Zp auquel le second ressort se déforme élastiquement est Zn (voir FIG. 7).
PCT/JP2023/043403 2023-12-05 2023-12-05 Système d'ouverture/de fermeture de vanne et système d'analyse Pending WO2025120718A1 (fr)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003500674A (ja) * 1999-05-28 2003-01-07 シーフィード 化学反応を制御するためのカートリッジ
JP2011030522A (ja) * 2009-08-04 2011-02-17 Aida Engineering Ltd マイクロ流体デバイス
JP6760845B2 (ja) * 2014-05-16 2020-09-23 クヴェッラ コーポレーション 自動式遠心分離を行うための装置、システム、および方法
WO2022112450A1 (fr) * 2020-11-25 2022-06-02 Oxford NanoImaging Limited Cartouche de réactif et dispositifs de mesure incorporant de telles cartouches
JP7187880B2 (ja) * 2018-08-09 2022-12-13 株式会社ニコン 制御装置
JP7261129B2 (ja) * 2019-09-03 2023-04-19 京セラ株式会社 ピペット、液体吸引装置及び液体の吸引方法

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003500674A (ja) * 1999-05-28 2003-01-07 シーフィード 化学反応を制御するためのカートリッジ
JP2011030522A (ja) * 2009-08-04 2011-02-17 Aida Engineering Ltd マイクロ流体デバイス
JP6760845B2 (ja) * 2014-05-16 2020-09-23 クヴェッラ コーポレーション 自動式遠心分離を行うための装置、システム、および方法
JP7187880B2 (ja) * 2018-08-09 2022-12-13 株式会社ニコン 制御装置
JP7261129B2 (ja) * 2019-09-03 2023-04-19 京セラ株式会社 ピペット、液体吸引装置及び液体の吸引方法
WO2022112450A1 (fr) * 2020-11-25 2022-06-02 Oxford NanoImaging Limited Cartouche de réactif et dispositifs de mesure incorporant de telles cartouches

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