WO2009125676A1 - Inspection system - Google Patents

Inspection system Download PDF

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Publication number
WO2009125676A1
WO2009125676A1 PCT/JP2009/056092 JP2009056092W WO2009125676A1 WO 2009125676 A1 WO2009125676 A1 WO 2009125676A1 JP 2009056092 W JP2009056092 W JP 2009056092W WO 2009125676 A1 WO2009125676 A1 WO 2009125676A1
Authority
WO
WIPO (PCT)
Prior art keywords
liquid
pump
unit
inspection system
detection unit
Prior art date
Application number
PCT/JP2009/056092
Other languages
French (fr)
Japanese (ja)
Inventor
晋治 原田
Original Assignee
コニカミノルタエムジー株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by コニカミノルタエムジー株式会社 filed Critical コニカミノルタエムジー株式会社
Priority to JP2010507209A priority Critical patent/JPWO2009125676A1/en
Publication of WO2009125676A1 publication Critical patent/WO2009125676A1/en

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502769—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
    • B01L3/502784—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0605—Metering of fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/143—Quality control, feedback systems
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/087—Multiple sequential chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • 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
    • G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
    • G01N2035/00099—Characterised by type of test elements
    • G01N2035/00158—Elements containing microarrays, i.e. "biochip"
    • 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
    • G01N2035/1027—General features of the devices
    • G01N2035/1034—Transferring microquantities of liquid
    • 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
    • G01N35/1095—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers

Definitions

  • the present invention relates to an inspection system.
  • the present applicant encloses a reagent or the like in the microchannel of the microchip, injects a driving liquid into the microchannel by a micropump, moves the liquid such as the specimen and the reagent, and flows the liquid to the reaction unit and then to the detection unit Therefore, a test system capable of measuring the reaction result with a specimen such as blood has been proposed (for example, see Patent Document 2).
  • This invention is made in view of the said subject, Comprising: It aims at providing the test
  • the object of the present invention can be achieved by the following configuration.
  • An inspection system that measures the result of injecting or aspirating a fluid into a microchip channel using a pump, moving a sample and a reagent stored in the channel to fill a detection unit, and reacting them.
  • a liquid reservoir for storing liquid flowing in the flow path; Liquid detecting means for detecting the liquid accumulated in the liquid reservoir, Pump drive control means for controlling the drive of the pump; Arrival determination means for determining the presence or absence of the liquid based on the detection output of the liquid detection means; Have The pump drive control means controls the drive of the pump based on the determination of the arrival determination means.
  • the liquid reservoir is 2.
  • the microchip is A mixing unit that mixes the sample and the reagent in a flow channel upstream of the detection unit;
  • the liquid reservoir is 3.
  • the liquid reservoir is 4.
  • the inspection system according to any one of 1 to 3, wherein the inspection system is provided in a flow channel on a downstream side close to a flow channel in which the specimen or the reagent is stored.
  • the liquid reservoir is 5.
  • the microchip is A divided flow path for dividing the reagent or the specimen;
  • the liquid reservoir is The inspection system according to any one of 1 to 5, wherein the inspection system is provided in a flow path downstream of the divided flow path.
  • the pump drive control means includes The inspection system according to any one of claims 1 to 6, wherein the driving of the pump is stopped based on the determination of the arrival determination means.
  • the pump drive control means includes 8. The inspection system according to any one of claims 1 to 7, wherein a flow rate of fluid injected or sucked from the pump into the flow path of the microchip is changed based on the determination of the arrival determination means.
  • the pump drive control means includes 9. The inspection system according to any one of claims 1 to 8, wherein the fluid is sucked or injected in a direction opposite to the direction in which the pump has been infused or sucked until then based on the determination of the arrival judging means. .
  • the fluid is a gas, and has a valve that opens the pressure of the gas applied to the flow path of the microchip to the atmosphere side
  • the pump drive control means includes 10.
  • the inspection system according to any one of 1 to 9, wherein the valve is opened to the atmosphere side based on the determination of the arrival determination means.
  • a liquid reservoir that accumulates the liquid flowing in the flow path and a liquid detection means that detects the liquid accumulated in the liquid reservoir, and the arrival determination means is based on the detection output of the liquid detection means. Based on the result of determining the presence or absence, the pump drive control means controls the drive of the pump. In this way, it is possible to provide an inspection system that can move or stop the top of the liquid in the flow path to a desired position.
  • FIG. It is an external view of the test
  • FIG. It is a perspective view which shows an example of an internal structure of the test
  • FIG. 1 is an external view of an inspection apparatus 80 according to an embodiment of the present invention.
  • the inspection device 80 is a device that automatically detects a reaction between a specimen previously injected into the microchip 1 and a reagent, and displays the result on the display unit 84.
  • the housing 82 of the inspection apparatus 80 has an insertion port 83, and the microchip 1 is inserted into the insertion port 83 and set inside the housing 82.
  • the insertion port 83 is sufficiently higher than the thickness of the microchip 1 so as not to contact the insertion port 83 when the microchip 1 is inserted.
  • Reference numeral 85 denotes a memory card slot
  • 86 denotes a print output port
  • 87 denotes an operation panel
  • 88 denotes an input / output terminal
  • 89 denotes a power switch.
  • the inspector turns on the power switch 89, inserts the microchip 1 in the direction of the arrow in FIG. 1, and operates the operation panel 87 to start the inspection.
  • the reaction in the microchip 1 is automatically inspected, and when the inspection is completed, the result is displayed on the display unit 84 constituted by a liquid crystal panel or the like.
  • the inspection result can be output from the print output port 86 or stored in a memory card inserted into the memory card slot 85 by operating the operation panel 87. Further, data can be stored in the personal computer or the like from the external input / output terminal 88 using, for example, a LAN cable.
  • the person in charge of inspection takes out the microchip 1 from the insertion slot 83 after the inspection is completed.
  • FIG. 2 is an external view of the microchip 1 according to the first embodiment of the present invention
  • FIG. 3 is an enlarged view of the periphery of the detection unit 111.
  • the microchip 1 includes a groove forming substrate 108 and a covering substrate 109 that covers the groove forming substrate 108.
  • An arrow in FIG. 2A indicates an insertion direction in which the microchip 1 is inserted into the inspection apparatus 80.
  • FIG. 2B is a plan view of the microchip 1, and illustrates the grooves of the groove forming substrate 108 that can be seen through the transparent coated substrate 109.
  • a flow path is formed by covering the grooves of the groove forming substrate 108 with the covering substrate 109.
  • the microchip 1 is provided with minute groove-like channels 250 (microchannels) and functional parts (channel elements) for performing inspections, sample processing, and the like in an appropriate manner according to the application. Has been.
  • the flow path is formed in the order of micrometers, for example, the width is several ⁇ m to several hundred ⁇ m, preferably 10 to 200 ⁇ m, and the depth is about 25 to 500 ⁇ m, preferably 25 to 250 ⁇ m.
  • microchip 1 used for the process of performing amplification and detection of a specific gene will be described as an example.
  • 110a and 110b are injection ports communicating with the flow path inside the microchip 1, and a driving liquid is injected from each injection port 110 to drive an internal specimen or reagent.
  • the configuration of the flow path starting from the injection port 110a is completely the same as the configuration of the flow path starting from the injection port 110b. Distinguish between calls.
  • Each component is distinguished by adding a and b.
  • the sample storage units 121a and 121b are sample storage units for storing samples.
  • the sample storage units 121a and 121b have deeper grooves than other flow paths in order to store a predetermined amount of sample.
  • a description will be given assuming that samples are stored in the sample storage units 121a and 121b in advance.
  • 120a and 120b are reagent storage units for storing the first reagent
  • 122a and 122b are reagent storage units for storing the second reagent
  • 123a and 123b are reagent storage units for storing the third reagent.
  • the sample stored in the sample storage units 121a and 121b is pushed out to the flow channel 250 and is injected into the downstream reagent storage units 120a and 120b, respectively.
  • the sample and the first reagent pushed out from the reagent storage units 120a and 120b are respectively injected into the downstream reagent storage units 122a and 122b through the flow channel 250.
  • the specimen and the first reagent push out the second reagent from the reagent storage parts 122a and 122b.
  • the specimen, the first reagent, and the second reagent are respectively injected into the downstream reagent storage units 123a and 123b through the flow path 250 to push out the third reagent.
  • a mixing unit 130a, a mixing unit 130b, a mixing unit 131a, and a mixing unit 131b are provided downstream of the reagent storage units 123a and 123b.
  • the flow channel 250aa, the sample flowing through the flow channel 250ba, the first reagent, The second reagent and the third reagent are mixed in each mixing unit.
  • Liquid reservoirs 140a and 140b are provided in the flow channel 250aa and the flow channel 250ba on the upstream side near the mixing unit 130a and the mixing unit 130b.
  • the liquid reservoirs 140a and 140b are provided to detect that the third reagent has been pushed out of the reagent storage parts 123a and 123b and the leading portion has reached the vicinity of the mixing part 130a and the mixing part 130b.
  • the liquid reservoirs 140 a and 140 b have shallower grooves than the mixing parts 130 a and 130 b and deeper grooves than the other flow paths 250.
  • the depth of the grooves of the mixing portion 131a and the mixing portion 131b is, for example, 1.5 mm
  • the depth of the grooves of the liquid reservoir portions 140a, 140b is, for example, 0.6 mm
  • the depth of the grooves of the other flow paths is, for example, 0.25 mm. is there.
  • the mixing unit 130a, the mixing unit 130b and the mixing unit 131a, and the specimen, the first reagent, the second reagent, and the third reagent mixed in the mixing unit 131b are injected into the detection units 111a and 111b.
  • the detection units 111a and 111b are heated or absorbed in the inspection apparatus 80 to cause the specimen and the reagent to react at a predetermined temperature for a predetermined time.
  • the detection units 111a and 111b are provided for optically detecting the reaction between the specimen and the reagent, and have a groove deeper than the other flow paths to accommodate a predetermined amount of the specimen and the reagent.
  • Liquid reservoirs 141a and 141b are provided downstream of the detection units 111a and 111b, so that it can be detected that the detection units 111a and 111b are filled with a liquid such as a reagent or a specimen.
  • the liquid reservoirs 141a and 141b are shallower than the detectors 111a and 111b, and deeper than the other channels.
  • FIG. 3A is a plan view
  • FIG. 3B is a cross-sectional view of the detection unit 111.
  • the groove depth d3 of the detectors 111a and 111b is, for example, 1.5 mm
  • the groove depth d2 of the liquid reservoirs 141a and 141b is, for example, 0.6 mm
  • the groove depth d1 of the other flow paths is, for example, 0.25 mm. It is. It is desirable that the liquid reservoirs 141a and 141b be provided as close as possible to the downstream of the detection units 111a and 111b so that it can be detected as soon as possible that the detection units 111a and 111b are filled.
  • Reference numeral 20 denotes a liquid detector using, for example, a photo reflector, which irradiates the liquid reservoirs 141a and 141b with light to detect reflected light and outputs an electrical signal.
  • the detection unit 22 measures the amount of fluorescence and displays the reaction result. measure.
  • the microchip 1 is desired to be excellent in processability, non-water absorption, chemical resistance, weather resistance, cost and the like.
  • the material of chip 1 is selected. Various known materials can be used as the material, and usually the substrate and the flow path element are formed by appropriately combining one or more materials in accordance with individual material characteristics.
  • a chip for a large number of measurement specimens, especially clinical specimens at risk of contamination and infection be of a disposable type. Therefore, a plastic resin that can be mass-produced, is lightweight, is strong against impact, and can be easily discarded by incineration, for example, polystyrene that is excellent in transparency, mechanical properties, and moldability and is easy to be finely processed is preferable.
  • a resin having excellent heat resistance for example, polycarbonate.
  • polypropylene when protein adsorption becomes a problem, it is preferable to use polypropylene.
  • Resin and glass have low thermal conductivity, and by using these materials in the locally heated region of the microchip, heat conduction in the surface direction is suppressed, and only the heated region is selectively heated. Can do.
  • the detection unit 111 optically detects a color reaction product or a fluorescent substance
  • at least this portion of the coated substrate 109 is made of a light-transmitting material (for example, alkali glass, quartz glass, transparent plastics). It is necessary to use and transmit light.
  • At least the portion covering the liquid reservoirs 140a and 140b and the liquid reservoirs 141a and 141b of the coated substrate 109 is It is necessary to configure with a transparent member such as glass or resin.
  • a transparent member such as glass or resin.
  • FIG. 4 is a perspective view for explaining an example of the internal configuration of the inspection apparatus 80 according to the first embodiment of the present invention.
  • FIG. 5 is an example of the internal configuration of the inspection apparatus 80 according to the first embodiment of the present invention.
  • FIG. 6 is an explanatory diagram for explaining the liquid filled in the detection unit 111. Each part will be described with reference to the coordinate axes of X, Y, and Z shown in FIGS.
  • the inspection device 80 includes a temperature adjustment unit 152, a detection unit 22, a micro pump unit 75, a packing 90, a driving liquid tank 91, a feed screw 301, a feed screw 351, a joint 302, a joint 352, a detection board drive motor 60, and a detection unit drive. It is composed of a motor 61 and the like. 4 and 5 show a state in which the microchip 1 is in close contact with the packing 90b.
  • the temperature adjustment unit 152 and the microchip 1 are driven by a driving member (not shown) and can move in the Z-axis direction.
  • the temperature adjustment unit 152 is raised from the state of FIG. 4 by the thickness of the microchip 1 by the driving member.
  • the microchip 1 can be inserted and removed in the Y-axis direction, and the person inspecting inserts the microchip 1 from the insertion port 83 until it comes into contact with a regulating member (not shown).
  • the chip detection unit 95 using a photo interrupter or the like detects the microchip 1 and is turned on.
  • the temperature adjustment unit 152 includes a Peltier element, a power supply device, a temperature control device, etc., performs heat generation or heat absorption to adjust the surface of the microchip 1 to a predetermined temperature, and reacts the liquid filled in the detection unit 111. It is a unit to promote.
  • the temperature adjustment unit 152 and the microchip 1 are lowered by the driving member, and the microchip 1 is brought into close contact with the temperature adjustment unit 152 and the packing 90b.
  • the range that can be heated by the temperature adjustment unit 152 is up to the liquid reservoir 141.
  • FIG. 5 illustrates the liquid detection unit 20 in a position where the liquid stored in the liquid storage unit 140 (any one of the liquid storage units 140a and 140b) can be optically detected.
  • liquid detection unit 20 For example, light is irradiated from the liquid detection unit 20 to the liquid storage unit 140, and the light reflected by the liquid storage unit 140 is received by the liquid detection unit 20, and the liquid storage unit 140 is filled with liquid due to a change in the amount of light and color.
  • the detection of the liquid storage unit 141 is performed in the same procedure.
  • the liquid detection unit 20 shown in FIG. 5 is a photo reflector provided with, for example, a light emitting unit and a light receiving unit, and the liquid detection unit 20 is mounted on a detection substrate 21. As will be described later, in the present embodiment, two liquid detection units 20 a and 20 b are mounted on the detection substrate 21.
  • the liquid detector 20 is a liquid detector of the present invention.
  • FIG. 6A shows a state where the detection unit 111 is not sufficiently filled with the liquid 57
  • FIG. 6B shows a state where the detection unit 111 is filled with the liquid 57.
  • the liquid reservoir 140 is also filled with the liquid 57. Therefore, it is possible to know that the detection unit 111 is filled with the liquid 57 by detecting the liquid 57 in the liquid reservoir 140 with the liquid detection unit 20.
  • the number of liquid detection units 20 is not limited to two, and may be any number as long as it is one or more.
  • liquid reservoirs 140a and 140b and the liquid reservoirs 141a and 141b are irradiated with light and reflected light is detected, but the liquid reservoirs 140a and 140b and the liquid reservoirs 141a and 141b are described. You may make it detect the light, an ultrasonic wave, or an electromagnetic wave which permeate
  • one end of the detection substrate 21 is supported by a guide member 354 having a screw portion screwed with the feed screw 351, and moves in the Y-axis direction when the feed screw 351 rotates.
  • the other end of the detection substrate 21 is supported by a member (not shown) through which the guide rod 353 passes, and the detection substrate 21 moves in parallel with the microchip channel 250.
  • the liquid detection units 20a and 20b can detect the liquid in the liquid detection units 20a and 20b at the central portions of the liquid storage units 140a and 140b and the liquid storage units 141a and 141b. It is arranged on the detection substrate 21 so that various ranges coincide with each other.
  • the liquid reservoirs 140a and 140b or the liquid reservoirs 141a and 141b are sequentially irradiated with light, the reflected light is received, and an electrical signal is output.
  • the feed screw 351 is driven by the detection board drive motor 60 via the joint 352.
  • the detection board drive motor 60 is a pulse motor, for example, and rotates by a predetermined amount by a pulse.
  • the first position sensor 40 is a sensor such as a photo reflector provided for detecting the initial position of the detection substrate 21 or a mechanical switch.
  • the detection unit 22 includes a light emitting unit and a light receiving unit, and is configured to optically separate the fluorescence emitted from the reagent that has reacted with the specimen by irradiating the detection unit 111 with light and to receive the light in the light receiving unit.
  • the detection unit 22 has a screw portion that is screwed with the feed screw 301, and moves in the X-axis direction when the feed screw 301 rotates.
  • the feed screw 301 is disposed in parallel with the straight line F, and when the detection unit 22 is moved by the feed screw 301, the optical axis of the lens 23 of the detection unit 22 coincides with the center of each of the detection units 111a and 111b.
  • the detection unit 22 sequentially irradiates the detection units 111a and 111b with excitation light from the lens 23, receives fluorescence emitted from the fluorescent material, and outputs an electrical signal.
  • the feed screw 301 is driven via the joint 302 by the detection unit drive motor 61.
  • the detection unit drive motor 61 is a pulse motor, for example, and rotates by a predetermined amount by a pulse.
  • the second position sensor 41 is a sensor such as a photo reflector or a mechanical switch provided to detect the initial position of the detection unit 22.
  • the detection unit 22 is provided with a guide hole (not shown in FIG. 4) for preventing rotation, and moves along a guide rod that penetrates the guide hole.
  • the guide bar is disposed in parallel with the feed screw 301.
  • the number of the detection units 111 may be any number as long as it is one or more.
  • FIG. 5 illustrates a case where the liquid detection unit 20 (any one of the liquid detection units 20a and 20b) is in a position for detecting the liquid in the liquid storage unit 140 (any one of the liquid storage units 140a and 140b). ing. Moreover, the case where the detection unit 22 exists in the position which can optically detect the reaction result of the reagent which occurs in the detection part 111 (any of detection part 111a, 111b) is illustrated.
  • the injection port 110 of the microchip 1 is provided at a position communicating with a corresponding opening provided in the packing 90b.
  • the suction port 145 of the micropump unit 75 is connected to a driving liquid tank 91 via a packing 90a, and sucks the driving liquid filled in the driving liquid tank 91 via the packing 90a.
  • the discharge port 146 communicates with the injection port 110 of the microchip 1 through the packing 90b.
  • the driving liquid sent out from the micropump unit 75 is injected from the injection port 110 of the microchip 1 into the channel 250 formed in the microchip 1. In this way, the driving liquid is injected from the micropump unit 75 into the injection port 110.
  • the micro pump unit 75 is provided with at least one micro pump. When the microchip 1 illustrated in FIG. 2 is driven, two micropumps corresponding to the two inlets 110a and 110b are necessary.
  • FIG. 7 is a circuit block diagram of the detection device 80 according to the first embodiment of the present invention.
  • the control unit 99 includes a CPU 98 (central processing unit), a RAM 97 (Random Access Memory), a ROM 96 (Read Only Memory), and the like, and reads a program stored in the ROM 96 which is a nonvolatile storage unit to the RAM 97. Each part of the detection device 80 is centrally controlled according to the program.
  • the control unit 99 is a control means of the present invention.
  • the arrival determination unit 412 compares the output signal obtained by detecting the light reflected by the liquid reservoir 140a or the liquid reservoir 141a with the light emitted from the liquid detection unit 20a, and determines the result. Similarly, the output signal obtained by detecting the light reflected from the liquid reservoir 140b or the liquid reservoir 141b by the light emitted from the liquid detector 20b is compared with a predetermined signal level to determine the result.
  • the detection unit drive control unit 413 instructs the detection unit drive detection unit drive motor 61 to move the detection unit 22.
  • the pump drive unit 500 drives the piezoelectric element 112 of each micropump. Based on the program, the pump drive control unit 411 controls the pump drive unit 500 to inject or suck a predetermined amount of drive fluid. The pump drive unit 500 receives a command from the pump drive control unit 411 and generates a drive voltage to drive the piezoelectric element 112.
  • the CPU 98 performs inspection in a predetermined sequence and stores the inspection result in the RAM 97.
  • the inspection result can be stored in the memory card 501 by the operation of the operation unit 87 or printed by the printer 503.
  • FIG. 8 is a flowchart for explaining a main routine in which the inspection apparatus 80 of the first embodiment performs an inspection
  • FIG. 9 shows that the inspection apparatus 80 of the first embodiment of the present invention reaches the liquid reservoir at the top of the liquid. It is a flowchart explaining the subroutine which detects this.
  • FIG. 10 is a flowchart for explaining a subroutine in which the inspection apparatus 80 of the embodiment performs reaction measurement.
  • the microchip 1 is set at a position where inspection can be performed as shown in FIG. 5, and the CPU is instructed to start inspection by operating the operation unit 87. Moreover, the detection board
  • S201 This is a step for performing calibration.
  • the arrival determination unit 412 causes the liquid detection unit 20a and the liquid detection unit 20b to emit light, and outputs the output signals detected by the liquid detection unit 20a and the liquid detection unit 20b respectively from the light reflected from the liquid storage unit 140a and the liquid storage unit 140b. Compare with a predetermined signal level. If it is not within the predetermined signal level range, the arrival determination unit 412 performs calibration so that the current flowing through the light emitting units of the liquid detection unit 20a and the liquid detection unit 20b is increased or decreased to be within the predetermined signal level range.
  • S202 This is a step of starting the pump.
  • the pump drive control unit 411 instructs the pump drive unit 500 to send liquid from the micropump unit 75 to the microchip 1.
  • step S204 If the error flag is 1 (step S204; Yes), the process proceeds to step S205.
  • step S210 If the error flag is 1 (step S210; Yes), the process proceeds to step S211.
  • the control unit 99 displays an error warning on the display unit 84 and stops the inspection device 80.
  • step S105 If output signal level ⁇ threshold (step S105; No), the process proceeds to step S107.
  • a second embodiment will be described with reference to FIGS.
  • a syringe is used to inject a gas into a microchip flow path, and a specimen and a reagent are fed.
  • the difference between the first embodiment and the liquid feeding method will be mainly described, and the description of the parts common to the first embodiment will be omitted.
  • the 2nd Embodiment demonstrates the example by which the liquid detection part is arrange
  • FIG. The liquid detector 26 is disposed at a position corresponding to the liquid reservoir 142, the liquid detector 27 is disposed at a position corresponding to the liquid reservoir 140, and the liquid detector 28 is disposed at a position corresponding to the liquid reservoir 141.
  • the liquid detection unit 26, the liquid detection unit 27, and the liquid detection unit 28 are also arranged in the a and b channels, respectively.
  • the arrival determination unit 412 causes the liquid detection unit 26, the liquid detection unit 27, and the liquid detection unit 28 to emit light, and reflects light reflected from the liquid storage unit 140, the liquid storage unit 141, and the liquid storage unit 142.
  • the output signals detected by the unit 27 and the liquid detection unit 28 are compared with predetermined signal levels. When it is not within the predetermined signal level range, the arrival determination unit 412 increases or decreases the current flowing through the light emitting units of the liquid detection unit 26, the liquid detection unit 27, and the liquid detection unit 28 so as to be within the predetermined signal level range. Perform calibration.
  • the arrival determination unit 412 sets a threshold value for determining the arrival of the liquid based on the output voltage at that time. Determine and store in RAM 97. Also, the error flag is initialized and the value is set to zero.
  • S401 A step of driving the pump in the discharge direction at a speed A.
  • the pump drive control unit 411 instructs the driver 11 to drive the syringe pump 10 in the discharge direction at the drive pulse rate A as shown in FIG. Then, as shown in FIG. 14 (e), the flow rate is 0 for a while even after starting to drive the syringe pump 10, but suddenly starts to flow at a large flow rate after a while.
  • S403 This is a step of comparing the received light level with the threshold value.
  • the arrival determination unit 412 compares the output signal level proportional to the light reception level of the liquid detection unit 26 with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level ⁇ the threshold. .
  • step S403 If the received light level ⁇ the threshold value (step S403; No), the process returns to step S402.
  • step S403 If the light reception level ⁇ the threshold value (step S403; Yes), the process proceeds to step S404.
  • S404 This is a step of stopping the pump.
  • the pump drive control unit 411 stops the syringe pump 10. When the leading portion of the liquid reaches the liquid reservoir 142, the liquid reservoir 142 is filled with the liquid and the light receiving level ⁇ threshold. When this state is detected at t ⁇ b> 1 in FIG. 14A, the pump drive control unit 411 stops the syringe pump 10.
  • S405 A step of waiting for a predetermined time.
  • the pump drive control unit 411 stops the syringe pump 10 and waits for a predetermined time. Thereby, the step-out of the pulse motor that drives the syringe pump 10 can be prevented.
  • the period from t1 to t2 in FIG. 14A is the standby time.
  • S406 This is a step of driving the pump at the speed B in the suction direction.
  • the pump drive control unit 411 instructs the driver 11 to drive the syringe pump 10 in the suction direction at the drive pulse rate B from t2 to t3 in FIG. As a result, the pressure in the flow path is lowered so that the flow rate does not increase rapidly, so that a flow rate within a predetermined range can be obtained as shown in FIG.
  • S408 This is a step of driving the pump at the speed C in the discharge direction.
  • S409 A step of measuring the reflected light of the liquid reservoir 140.
  • the liquid detector 27 measures the reflected light of the liquid reservoir 140.
  • S410 This is a step of comparing the light reception level with the threshold value.
  • the arrival determination unit 412 compares the output signal level proportional to the light reception level of the liquid detection unit 27 with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level ⁇ the threshold. .
  • S411 This is a step of driving the pump in the discharge direction at a speed D.
  • S412 This is a step of measuring the reflected light of the liquid reservoir 141.
  • the arrival determination unit 412 compares the output signal level proportional to the light reception level of the liquid detection unit 28 with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level ⁇ the threshold. .
  • step S413 If the received light level ⁇ the threshold value (step S413; No), the process proceeds to step S414.
  • S414 This is a step of determining time over.
  • the CPU 98 determines that an error has occurred and ends the process.
  • step S414 If the time is over (step S414; Yes), the process ends.
  • S415 This is a step of stopping the pump.
  • the pump drive control unit 411 stops the syringe pump 10. When the leading portion of the liquid reaches the liquid reservoir 141, the liquid reservoir 141 is filled with the liquid, and the light receiving level ⁇ threshold. When this state is detected at t ⁇ b> 6 in FIG. 14A, the pump drive control unit 411 stops the syringe pump 10.
  • the pump drive control unit 411 switches the switching valve inside the three-way valve 25 so that the pipe 16 communicates with the pipe 50 whose one end is open to the atmosphere side. As a result, the pressure of the gas applied to the flow path of the microchip 1 can be released to the atmosphere, and the liquid can be prevented from moving.
  • S417 This is a step of waiting for a minute time.
  • the pump drive control unit 411 waits for a minute time.
  • S418 This is a step of switching the three-way valve 25 so that the pipe 15 and the pipe 16 communicate with each other.
  • S419 This is a step for starting the amplification reaction process.
  • CPU 98 instructs temperature adjustment unit 152 to heat to a predetermined temperature.
  • S420 This is a step of measuring the reflected light of the liquid reservoir 141.
  • the liquid detector 28 measures the reflected light of the liquid reservoir 141.
  • the gas that drives the liquid may expand, and the leading portion of the liquid may be pushed downstream from the liquid reservoir 141.
  • the reflected light of the liquid reservoir 141 is measured in this step, and the head portion of the liquid is moved backward until it cannot be detected by the liquid reservoir 141 in the following steps.
  • S421 This is a step of comparing the received light level with a threshold value.
  • the arrival determination unit 412 compares the output signal level proportional to the light reception level of the liquid detection unit 28 with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level ⁇ the threshold. .
  • step S421 If received light level ⁇ threshold (step S421; No), the process proceeds to step S425.
  • step S421 If the light reception level ⁇ the threshold value (step S421; Yes), the process proceeds to step S422.
  • S422 This is a step of driving the pump in the suction direction at a speed E.
  • S423 This is a step of waiting for a predetermined time.
  • the pump drive control unit 411 waits for a predetermined time.
  • S424 This is a step of stopping the pump.
  • the pump drive control unit 411 stops the syringe pump 10.
  • S425 This is a step of determining whether or not the amplification reaction time has ended.
  • CPU 98 determines whether or not the predetermined amplification reaction time has ended.
  • step S425 If the amplification reaction time has not ended (step S425; No), the process returns to step S420.
  • the syringe pump 10 is driven in the suction direction for a predetermined time at timings indicated by t7, t8, and t9 in FIG. The leading position of the liquid is retracted until the liquid can no longer be detected.
  • step S425 If the amplification reaction time has ended (step S425; Yes), the process proceeds to step S213.
  • FIG. 15 is an external view of the microchip 1 according to the third embodiment of the present invention.
  • the microchip 1 used in the third embodiment has a sample injection port 156 for injecting a sample and a division quantification unit 151 for dividing and quantifying the sample, and performs a test by dividing and quantifying the sample injected from the sample injection port 156.
  • Other configurations are almost the same as those of the microchip 1 described in the first embodiment and the second embodiment, and the same components are denoted by the same reference numerals and description thereof is omitted.
  • FIG. 15 is a plan view of the microchip 1, and illustrates the grooves of the groove forming substrate 108 that can be seen through the transparent coated substrate 109.
  • 410e, 410f, 410g, and 410h are suction ports that communicate with the flow path inside the microchip 1, and inhale air from each suction port 410 to drive the specimens, reagents, and the like inside.
  • the configuration of the flow path starting from the injection port 410f and the configuration of the flow path starting from the suction port 410g are exactly the same, and are hereinafter referred to as f channel and g channel. .
  • Each component is distinguished by adding f and g.
  • a flow path starting from the suction port 410e is a dummy flow path 251e through which an extra specimen flows.
  • the flow path starting from the suction port 410h is also a dummy flow path 251h provided for sucking the specimen.
  • a liquid reservoir 144 is provided between the dummy channel 251h and the divided quantification unit 151.
  • 155f and 155g are divided flow paths for dividing and sending the sample from the divided quantification unit 151.
  • Liquid reservoirs 147f and 147g are provided downstream of the divided flow paths 155f and 155g.
  • 120f and 120g are reagent storage units for storing the first reagent
  • 122f and 122g are reagent storage units for storing the second reagent
  • 123f and 123g are reagent storage units for storing the third reagent.
  • a mixing unit 130f, a mixing unit 130g, a mixing unit 131f, and a mixing unit 131g are provided downstream of the reagent storage units 123f and 123g, and the sample, the first reagent, the second reagent, and the third reagent are mixed. Mixed in parts.
  • the mixing unit 130f, the mixing unit 130g and the mixing unit 131f, and the specimen, the first reagent, the second reagent, and the third reagent mixed in the mixing unit 131g are injected into the detection units 111f and 111g.
  • the detection units 111f and 111g are heated inside the inspection apparatus 80, and the specimen and the reagent are reacted at a predetermined temperature for a predetermined time.
  • Liquid reservoirs 141f and 141g are provided downstream of the detection units 111f and 111g so that it can be detected that the detection units 111f and 111g are filled with a liquid such as a reagent or a specimen.
  • FIG. 16 is a block diagram of a detection apparatus 80 according to the third embodiment of the present invention.
  • the difference from the first embodiment is mainly shown, and the drawing is simplified.
  • one flow path of the three-way valve 25 branches into four by the branch piping 17, and is connected with valve 58e, 58f, 58g, 58h. ing.
  • the valves 58e, 58f, 58g, and 58h are connected to the pipes 18e, 18f, 18g, and 18h, and communicate with the suction ports 410e, 410f, 410g, and 410h.
  • valves 58e, 58f, 58g, and 58h open and close the flow paths between the syringe pump 10 and the suction ports 410e, 410f, 410g, and 410h, respectively, according to a control signal from the control unit 99.
  • the three-way valve 25 has a switching valve that allows the pipe 15 and the branch pipe 17 to communicate with each other according to a control signal from the control unit 99, or allows the pipe 15 and one end to communicate with the pipe 50 that is open to the atmosphere side. .
  • the liquid detection units 28, 29, and 30 are arranged at positions corresponding to the respective liquid reservoirs of the inspection apparatus 80.
  • the liquid detector 30 is disposed at a position corresponding to the liquid reservoir 144
  • the liquid detector 29 is disposed at a position corresponding to the liquid reservoir 147
  • the liquid detector 28 is disposed at a position corresponding to the liquid reservoir 141.
  • the liquid detection unit 28 and the liquid detection unit 29 are also arranged in the f and g channels, respectively.
  • FIGS. 17, 18, and 19 are flowcharts illustrating a main routine in which the inspection apparatus 80 according to the third embodiment performs an inspection.
  • the inspection is performed using the microchip 1 described with reference to FIG.
  • FIG. 20 is a plan view of the microchip 1 illustrating the liquid feeding state for each step of liquid feeding control.
  • S201 This is a step for performing calibration.
  • the arrival determination unit 412 causes the liquid detection unit 28, the liquid detection unit 29, and the liquid detection unit 30 to emit light, and the light reflected from the liquid storage unit 144, the liquid storage unit 147, and the liquid storage unit 141.
  • the output signals detected by the unit 29 and the liquid detection unit 30 are compared with predetermined signal levels. When it is not within the predetermined signal level range, the arrival determination unit 412 increases or decreases the current flowing through the light emitting units of the liquid detection unit 28, the liquid detection unit 29, and the liquid detection unit 30 so as to be within the predetermined signal level range. Perform calibration.
  • the arrival determination unit 412 sets a threshold value for determining the arrival of the liquid based on the output voltage at that time. Determine and store in RAM 97. Also, the error flag is initialized and the value is set to zero.
  • S501 This is a step of opening the valve 58h by switching the three-way valve to the pump side.
  • the pump drive control unit 411 switches the three-way valve 25 so that the branch pipe 17 and the pipe 15 communicate with each other, and opens the valve 58h.
  • S502 This is a step of driving the pump in the suction direction.
  • the pump drive control unit 411 instructs the driver 11 to drive the syringe pump 10 in the suction direction.
  • S503 This is a step of measuring the reflected light of the liquid reservoir 144.
  • the liquid detection unit 30 measures the reflected light from the liquid reservoir 144.
  • S504 This is a step of comparing the light reception level with the threshold value.
  • the arrival determination unit 412 compares the output signal level proportional to the light reception level of the liquid detection unit 30 with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level ⁇ the threshold. .
  • step S504 If the received light level ⁇ the threshold (step S504; No), the process returns to step S503.
  • step S504 If the received light level ⁇ the threshold value (step S504; Yes), the process proceeds to step S505.
  • S505 This is a step of opening the three-way valve to the atmosphere and stopping the pump.
  • the pump drive controller 411 causes the three-way valve 25 to communicate with the branch pipe 17 and the pipe 50 and stops the syringe pump 10. As shown in FIG. 20A, when the leading portion of the specimen 35 reaches the liquid reservoir 144, the liquid reservoir 144 is filled with the specimen 35, and the light receiving level ⁇ threshold. When this state is detected, the pump drive control unit 411 stops the syringe pump 10.
  • S506 This is a step of closing the valve 58h.
  • the pump drive control unit 411 closes the valve 58h.
  • S507 This is a step of opening the valve 58e.
  • the pump drive control unit 411 opens the valve 58e.
  • S508 This is a step of driving the pump in the suction direction.
  • the pump drive control unit 411 instructs the driver 11 to drive the syringe pump 10 in the suction direction for a predetermined time.
  • S509 This is a step of closing the valve 58e.
  • the pump drive control unit 411 closes the valve 58e. As shown in FIG. 20B, when an extra sample 35 is caused to flow through the dummy channel 251e, a predetermined amount of the sample 35 remains in the divided quantification unit 151.
  • S510 This is a step of opening the valve 58f.
  • the pump drive control unit 411 opens the valve 58f.
  • S511 This is a step of measuring the reflected light of the liquid reservoir 147f.
  • the liquid detector 30 measures the reflected light of the liquid reservoir 147f.
  • S512 This is a step of comparing the received light level with a threshold value.
  • the arrival determination unit 412 compares the output signal level proportional to the light reception level of the liquid detection unit 29f with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level ⁇ the threshold. .
  • step S512 If the received light level ⁇ the threshold value (step S512; No), the process returns to step S512.
  • step S512 If received light level ⁇ threshold (step S512; Yes), the process proceeds to step S513.
  • S513 This is a step of opening the three-way valve to the atmosphere and stopping the pump.
  • the pump drive controller 411 causes the three-way valve 25 to communicate with the branch pipe 17 and the pipe 50 and stops the syringe pump 10.
  • the liquid reservoir 147f is filled with the specimen 35, and the light receiving level ⁇ threshold.
  • the pump drive control unit 411 stops the syringe pump 10. In this way, a predetermined amount of the specimen 35f is filled in the divided flow path 155f.
  • the pump drive control unit 411 closes the valve 58f.
  • S515 This is a step of opening the valve 58g.
  • the pump drive control unit 411 opens the valve 58g.
  • S516 This is a step of driving the pump in the suction direction.
  • the pump drive control unit 411 instructs the driver 11 to drive the syringe pump 10 in the suction direction for a predetermined time.
  • S517 This is a step of measuring the reflected light of the liquid reservoir 147g.
  • the liquid detector 30 measures the reflected light of the liquid reservoir 147g.
  • S518 This is a step of comparing the light reception level with the threshold value.
  • the arrival determination unit 412 compares the output signal level proportional to the light reception level of the liquid detection unit 29g with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level ⁇ the threshold. .
  • step S518 If the light reception level ⁇ the threshold value (step S518; No), the process returns to step S518.
  • step S518 If received light level ⁇ threshold (step S518; Yes), the process proceeds to step S519.
  • S519 This is a step of opening the three-way valve to the atmosphere and stopping the pump.
  • the pump drive controller 411 causes the three-way valve 25 to communicate with the branch pipe 17 and the pipe 50 and stops the syringe pump 10.
  • the pump drive control unit 411 stops the syringe pump 10. In this way, a predetermined amount of the specimen 35 is filled in the divided flow path 155g.
  • the sample 35 is divided into the sample 35f and the sample 35g in equal amounts and filled in the divided flow path 155f and the divided flow path 155g.
  • the pump drive control unit 411 closes the valve 58g.
  • the CPU 98 instructs the temperature adjustment unit 152 to heat to a predetermined temperature, and waits until the temperature reaches the predetermined temperature.
  • S522 This is a step of opening the valve 58f.
  • the pump drive control unit 411 opens the valve 58f.
  • S523 This is a step of driving the pump in the suction direction.
  • the pump drive control unit 411 instructs the driver 11 to drive the syringe pump 10 in the suction direction for a predetermined time.
  • S524 This is a step of measuring the reflected light of the liquid reservoir 141f.
  • the liquid detector 28 measures the reflected light of the liquid reservoir 141.
  • S525 This is a step of comparing the received light level with a threshold value.
  • the arrival determination unit 412 compares the output signal level proportional to the light reception level of the liquid detection unit 28 with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level ⁇ the threshold. .
  • step S525 If the received light level ⁇ the threshold value (step S525; No), the process returns to step S525.
  • step S525 If the received light level ⁇ the threshold value (step S525; Yes), the process proceeds to step S526.
  • S526 A step of opening the three-way valve to the atmosphere and stopping the pump.
  • the pump drive controller 411 causes the three-way valve 25 to communicate with the branch pipe 17 and the pipe 50 and stops the syringe pump 10.
  • the liquid 57f mixed when the specimen 35f and the first reagent, the second reagent, and the third reagent pass through the mixing sections 130f and 131f is detected by the detection section 111f. Is filled.
  • the pump drive control unit 411 closes the valve 58f.
  • the pump drive control unit 411 opens the valve 58g.
  • S529 This is a step of driving the pump in the suction direction.
  • the pump drive control unit 411 instructs the driver 11 to drive the syringe pump 10 in the suction direction for a predetermined time.
  • S530 This is a step of measuring the reflected light of the liquid reservoir 141g.
  • the liquid detector 28 measures the reflected light of the liquid reservoir 141g.
  • S531 A step of comparing the light reception level with the threshold value.
  • the arrival determination unit 412 compares the output signal level proportional to the light reception level of the liquid detection unit 28 with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level ⁇ the threshold. .
  • step S531 If the light reception level ⁇ the threshold value (step S531; No), the process returns to step S531.
  • step S531 If the received light level ⁇ the threshold value (step S531; Yes), the process proceeds to step S532.
  • S532 This is a step of opening the three-way valve to the atmosphere and stopping the pump.
  • the pump drive controller 411 causes the three-way valve 25 to communicate with the branch pipe 17 and the pipe 50 and stops the syringe pump 10.
  • the liquid 57g mixed when the specimen 35g and the first reagent, the second reagent, and the third reagent pass through the mixing sections 130g and 131g is detected by the detection section 111g. Is filled.
  • S533 This is a step of closing the valve 58g.
  • the pump drive control unit 411 closes the valve 58g.
  • S534 This is a step of determining whether or not the time for the amplification reaction has ended.
  • CPU 98 determines whether or not the predetermined amplification reaction time has ended.
  • step S534 If the amplification reaction time has not ended (step S534; No), the process returns to step S534.
  • step S534 If the amplification reaction time has ended (step S534; Yes), the process proceeds to step S213.
  • the CPU 98 calls a reaction measurement routine and measures the reaction result from the detection unit 111g and the detection unit 111h.

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Abstract

An inspection system includes: a liquid pool for pooling liquid flowing through a liquid channel; liquid detection means for detecting a liquid pooled in the liquid pool; pump drive means for driving a pump; pump drive control means for controlling the pump drive means; and achievement judgment means for judging whether liquid is present according the detection output from the liquid detection means. The pump drive control means controls pump drive according to the judgment made by the achievement judgment means.

Description

検査システムInspection system
　本発明は、検査システムに関する。 The present invention relates to an inspection system.
　近年、マイクロマシン技術および超微細加工技術を駆使することにより、従来の試料調製、化学分析、化学合成などを行うための装置、手段（例えばポンプ、バルブ、流路、センサなど）を微細化して１チップ上に集積化したシステムが開発されている（例えば、特許文献１参照）。これは、μ－ＴＡＳ（Ｍｉｃｒｏ　Ｔｏｔａｌ　Ａｎａｌｙｓｉｓ　Ｓｙｓｔｅｍ：マイクロ総合分析システム）、バイオリアクタ、ラボ・オン・チップ（Ｌａｂ－ｏｎ－ｃｈｉｐｓ）、バイオチップとも呼ばれ、医療検査・診断分野、環境測定分野、農産製造分野でその応用が期待されている。特に遺伝子検査に見られるように、煩雑な工程、熟練した手技、機器類の操作が必要とされる場合には、μ－ＴＡＳを用いることによりコスト、必要試料量、所要時間を削減できる。 In recent years, by making full use of micromachine technology and ultrafine processing technology, devices and means (for example, pumps, valves, flow paths, sensors, etc.) for performing conventional sample preparation, chemical analysis, chemical synthesis, etc. have been miniaturized. A system integrated on a chip has been developed (see, for example, Patent Document 1). This is also called μ-TAS (Micro Total Analysis System), bioreactor, lab-on-chip, biochip, medical inspection / diagnosis field, environmental measurement field, Its application is expected in the field of agricultural production. In particular, as seen in genetic testing, when complicated processes, skilled procedures, and equipment operations are required, the use of μ-TAS can reduce costs, required sample amount, and required time.
　本出願人は、マイクロチップの微細流路内に試薬などを封入し、マイクロポンプによって微細流路に駆動液を注入して検体と試薬などの液体を移動させ、反応部、次いで検出部へ流すことにより、血液など検体との反応結果を測定することができる検査システムを提案している（例えば、特許文献２参照）。 The present applicant encloses a reagent or the like in the microchannel of the microchip, injects a driving liquid into the microchannel by a micropump, moves the liquid such as the specimen and the reagent, and flows the liquid to the reaction unit and then to the detection unit Therefore, a test system capable of measuring the reaction result with a specimen such as blood has been proposed (for example, see Patent Document 2).
　このような検査システムでは、流路内の液体の先頭位置を正確に制御することが重要である。特に、流路や検出部などから成る検査チャネルを複数有するマイクロチップを用いて各検査チャネルで同時に反応させた結果を測定する検査システムでは、試薬や検体を各検査チャネルの検出部に同時に流入させて反応時間を等しくする必要がある。 In such an inspection system, it is important to accurately control the leading position of the liquid in the flow path. In particular, in a test system that measures the results of simultaneous reaction in each test channel using a microchip having a plurality of test channels consisting of flow paths and detection units, reagents and specimens are allowed to flow into the detection unit of each test channel simultaneously. It is necessary to equalize the reaction time.
　一方、流路を流れる液体の移動を制御する方法として、流路に液体の通過を検出する通過検出器を設け、通過検出器からの出力に基づいて液体の移動または停止を制御する方法が提案されている（例えば、特許文献３参照）。
特開２００４－２８５８９号公報 特開２００６－１４９３７９号公報 特開２００５－２８３１６３号公報 On the other hand, as a method for controlling the movement of the liquid flowing in the flow path, a method is proposed in which a flow detector for detecting the passage of the liquid is provided in the flow path and the movement or stop of the liquid is controlled based on the output from the passage detector (For example, see Patent Document 3).
JP 2004-28589 A JP 2006-149379 A JP 2005-283163 A
　しかしながら、特許文献３に開示されている方法では、液体が流路に設けられた通過検出器を通過したことを検出して液体の流れを制御するので、制御に遅れが生じ液体の先頭位置がばらついてしまう。そのため、複数の検査チャネルを有するマイクロチップに適用すると、液体の先頭位置が検査チャネル間でばらつくため反応結果に誤差が生じるという問題が生じる。 However, in the method disclosed in Patent Document 3, since the liquid flow is controlled by detecting that the liquid has passed through the passage detector provided in the flow path, the control is delayed and the leading position of the liquid is It will vary. Therefore, when applied to a microchip having a plurality of inspection channels, there is a problem that an error occurs in the reaction result because the liquid leading position varies between inspection channels.
　本発明は、上記課題に鑑みてなされたものであって、流路内の液体の先頭部分を所望の位置に移動または停止させることができる検査システムを提供することを目的とする。 This invention is made in view of the said subject, Comprising: It aims at providing the test | inspection system which can move or stop the head part of the liquid in a flow path to a desired position.
　本発明の目的は、下記構成により達成することができる。 The object of the present invention can be achieved by the following configuration.
　１．
ポンプを用いて流体をマイクロチップの流路に注入または吸引し、該流路に貯蔵された液体である検体と試薬とを移動させて検出部に充填し、反応させた結果を測定する検査システムにおいて、
前記流路を流れる液体を溜める液溜部と、
前記液溜部に溜まった前記液体を検知する液体検知手段と、
前記ポンプの駆動を制御するポンプ駆動制御手段と、
前記液体検知手段の検知出力に基づいて前記液体の有無を判定する到達判定手段と、
を有し、
前記ポンプ駆動制御手段は、前記到達判定手段の判定に基づいて前記ポンプの駆動を制御することを特徴とする検査システム。 1.
An inspection system that measures the result of injecting or aspirating a fluid into a microchip channel using a pump, moving a sample and a reagent stored in the channel to fill a detection unit, and reacting them. In
A liquid reservoir for storing liquid flowing in the flow path;
Liquid detecting means for detecting the liquid accumulated in the liquid reservoir,
Pump drive control means for controlling the drive of the pump;
Arrival determination means for determining the presence or absence of the liquid based on the detection output of the liquid detection means;
Have
The pump drive control means controls the drive of the pump based on the determination of the arrival determination means.
　２．
前記液溜部は、
前記検出部の下流側の流路に設けられていることを特徴とする１に記載の検査システム。 2.
The liquid reservoir is
2. The inspection system according to 1, wherein the inspection system is provided in a flow path on a downstream side of the detection unit.
　３．
前記マイクロチップは、
前記検出部の上流側の流路に前記検体と前記試薬とを混合する混合部を有し、
前記液溜部は、
前記混合部に近い上流側の流路に設けられていることを特徴とする１または２に記載の検査システム。 3.
The microchip is
A mixing unit that mixes the sample and the reagent in a flow channel upstream of the detection unit;
The liquid reservoir is
3. The inspection system according to 1 or 2, wherein the inspection system is provided in a flow path on the upstream side near the mixing unit.
　４．
前記液溜部は、
前記検体または前記試薬が貯蔵された流路に近い下流側の流路に設けられていることを特徴とする１から３の何れか１項に記載の検査システム。 4).
The liquid reservoir is
4. The inspection system according to any one of 1 to 3, wherein the inspection system is provided in a flow channel on a downstream side close to a flow channel in which the specimen or the reagent is stored.
　５．
前記マイクロチップの一部を外側から加熱して前記流路の内部にある前記液体を加熱する加熱手段を有し、
前記液溜部は、
前記流路の前記加熱手段により加熱可能な先頭の位置に設けられていることを特徴とする１から４の何れか１項に記載の検査システム。 5).
Heating means for heating a part of the microchip from the outside to heat the liquid in the flow path;
The liquid reservoir is
5. The inspection system according to claim 1, wherein the inspection system is provided at a leading position of the flow path that can be heated by the heating unit.
　６．
前記マイクロチップは、
前記試薬または前記検体を分割する分割流路を有し、
前記液溜部は、
前記分割流路の下流の流路に設けられていることを特徴とする１から５の何れか１項に記載の検査システム。 6).
The microchip is
A divided flow path for dividing the reagent or the specimen;
The liquid reservoir is
The inspection system according to any one of 1 to 5, wherein the inspection system is provided in a flow path downstream of the divided flow path.
　７．
前記ポンプ駆動制御手段は、
前記到達判定手段の判定に基づいて前記ポンプの駆動を停止することを特徴とする１から６の何れか１項に記載の検査システム。 7).
The pump drive control means includes
The inspection system according to any one of claims 1 to 6, wherein the driving of the pump is stopped based on the determination of the arrival determination means.
　８．
前記ポンプ駆動制御手段は、
前記到達判定手段の判定に基づいて前記ポンプから前記マイクロチップの流路に注入または吸引する流体の流量を変更することを特徴とする１乃至７の何れか１項に記載の検査システム。 8).
The pump drive control means includes
8. The inspection system according to any one of claims 1 to 7, wherein a flow rate of fluid injected or sucked from the pump into the flow path of the microchip is changed based on the determination of the arrival determination means.
　９．
前記ポンプ駆動制御手段は、
前記到達判定手段の判定に基づいてそれまで前記ポンプから注入または吸引している方向と逆方向に前記流体を吸引または注入することを特徴とする１から８の何れか１項に記載の検査システム。 9.
The pump drive control means includes
9. The inspection system according to any one of claims 1 to 8, wherein the fluid is sucked or injected in a direction opposite to the direction in which the pump has been infused or sucked until then based on the determination of the arrival judging means. .
　１０．
前記流体は気体であり、前記マイクロチップの前記流路に加わっている前記気体の圧力を大気側に開放する弁を有し、
前記ポンプ駆動制御手段は、
前記到達判定手段の判定に基づいて前記弁を大気側に開放することを特徴とする１から９の何れか１項に記載の検査システム。 10.
The fluid is a gas, and has a valve that opens the pressure of the gas applied to the flow path of the microchip to the atmosphere side,
The pump drive control means includes
10. The inspection system according to any one of 1 to 9, wherein the valve is opened to the atmosphere side based on the determination of the arrival determination means.
　本発明によれば、流路を流れる液体を溜める液溜部と液溜部に溜まった前記液体を検知する液体検知手段とを設け、液体検知手段の検知出力に基づいて到達判定手段が液体の有無を判定した結果に基づいて、ポンプ駆動制御手段はポンプの駆動を制御する。このようにして、流路内の液体の先頭を所望の位置に移動または停止させることができる検査システムを提供することができる。 According to the present invention, there is provided a liquid reservoir that accumulates the liquid flowing in the flow path and a liquid detection means that detects the liquid accumulated in the liquid reservoir, and the arrival determination means is based on the detection output of the liquid detection means. Based on the result of determining the presence or absence, the pump drive control means controls the drive of the pump. In this way, it is possible to provide an inspection system that can move or stop the top of the liquid in the flow path to a desired position.
本発明の実施形態における検査装置８０の外観図である。It is an external view of the test | inspection apparatus 80 in embodiment of this invention. 本発明の第１の実施形態に係わるマイクロチップ１の説明図である。It is explanatory drawing of the microchip 1 concerning the 1st Embodiment of this invention. 検出部１１１の周辺の拡大図である。It is an enlarged view of the periphery of the detection part 111. FIG. 本発明の第１の実施形態の検査装置８０の内部構成の一例を示す斜視図である。It is a perspective view which shows an example of an internal structure of the test | inspection apparatus 80 of the 1st Embodiment of this invention. 本発明の第１の実施形態の検査装置８０の内部構成の一例を示す断面図である。It is sectional drawing which shows an example of the internal structure of the test | inspection apparatus 80 of the 1st Embodiment of this invention. 検出部１１１に充填された液体を説明する説明図である。It is explanatory drawing explaining the liquid with which the detection part 111 was filled. 本発明の第１の実施形態における検査装置８０の回路ブロック図である。It is a circuit block diagram of the inspection apparatus 80 in the 1st Embodiment of this invention. 第１の実施形態の検査装置８０が検査を行うメインルーチンを説明するフローチャートである。It is a flowchart explaining the main routine which the test | inspection apparatus 80 of 1st Embodiment performs a test | inspection. 本発明の第１の実施形態の検査装置８０が液溜部に液体が到達したことを検知するサブルーチンを説明するフローチャートである。It is a flowchart explaining the subroutine which the test | inspection apparatus 80 of the 1st Embodiment of this invention detects that the liquid reached | attained the liquid storage part. 第１の実施形態の検査装置８０が反応測定を行うサブルーチンを説明するフローチャートである。It is a flowchart explaining the subroutine with which the test | inspection apparatus 80 of 1st Embodiment performs reaction measurement. 本発明の第２の実施形態におけるマイクロチップ１の外観図である。It is an external view of the microchip 1 in the 2nd Embodiment of this invention. 本発明の第２の実施形態における検出装置８０のブロック図である。It is a block diagram of the detection apparatus 80 in the 2nd Embodiment of this invention. 第２の実施形態の検査装置８０が検査を行うメインルーチンを説明するフローチャートである。It is a flowchart explaining the main routine which the test | inspection apparatus 80 of 2nd Embodiment performs a test | inspection. 第２の実施形態の送液制御を説明するためのタイムチャートである。It is a time chart for demonstrating the liquid feeding control of 2nd Embodiment. 本発明の第３の実施形態におけるマイクロチップ１の外観図である。It is an external view of the microchip 1 in the 3rd Embodiment of this invention. 本発明の第３の実施形態における検出装置８０のブロック図である。It is a block diagram of the detection apparatus 80 in the 3rd Embodiment of this invention. 第３の実施形態の検査装置８０が検査を行うメインルーチンを説明するフローチャート１である。It is the flowchart 1 explaining the main routine which the test | inspection apparatus 80 of 3rd Embodiment performs a test | inspection. 第３の実施形態の検査装置８０が検査を行うメインルーチンを説明するフローチャート２である。It is the flowchart 2 explaining the main routine which the test | inspection apparatus 80 of 3rd Embodiment performs a test | inspection. 第３の実施形態の検査装置８０が検査を行うメインルーチンを説明するフローチャート３である。It is the flowchart 3 explaining the main routine which the test | inspection apparatus 80 of 3rd Embodiment performs a test | inspection. 送液制御のステップ毎の送液状態を図示したマイクロチップ１の平面図である。It is a top view of the microchip 1 which illustrated the liquid feeding state for every step of liquid feeding control.
符号の説明Explanation of symbols
　１　マイクロチップ
　２０、２６、２７、２８、２９、３０　液体検知部
　２１　検知基板
　２２　検出ユニット
　６０　検知基板駆動モータ
　６１　検出ユニット駆動モータ
　７５　マイクロポンプユニット
　８０　検査装置
　８２　筐体
　８３　挿入口
　８４　表示部
　８７　操作ボタン
　９０　パッキン
　１１０　注入口
　１１１　検出部
　１２１　検体収容部
　１２０、１２２、１２３　試薬収容部
　１３０、１３１　混合部
　１４０、１４１、１４２、１４４、１４７　液溜部
　１５０　光検出部
　１５２　温度調整ユニット
　１５６　検体注入口
　２５０　流路
　４１０　吸引口
　４１１　ポンプ駆動制御部
　４１２　到達判定部 DESCRIPTION OF SYMBOLS 1 Microchip 20, 26, 27, 28, 29, 30 Liquid detection part 21 Detection board 22 Detection unit 60 Detection board drive motor 61 Detection unit drive motor 75 Micro pump unit 80 Inspection apparatus 82 Case 83 Insertion port 84 Display part 87 Operation button 90 Packing 110 Inlet 111 Detection unit 121 Sample storage unit 120, 122, 123 Reagent storage unit 130, 131 Mixing unit 140, 141, 142, 144, 147 Liquid storage unit 150 Light detection unit 152 Temperature adjustment unit 156 Sample injection Inlet 250 Flow path 410 Suction port 411 Pump drive control unit 412 Arrival determination unit
　以下、図面に基づき本発明の実施形態を説明する。 Hereinafter, embodiments of the present invention will be described with reference to the drawings.
　図１は、本発明の実施形態における検査装置８０の外観図である。 FIG. 1 is an external view of an inspection apparatus 80 according to an embodiment of the present invention.
　検査装置８０はマイクロチップ１に予め注入された検体と、試薬との反応を自動的に検出し、表示部８４に結果を表示する装置である。 The inspection device 80 is a device that automatically detects a reaction between a specimen previously injected into the microchip 1 and a reagent, and displays the result on the display unit 84.
　検査装置８０の筐体８２には挿入口８３があり、マイクロチップ１を挿入口８３に差し込んで筐体８２の内部にセットするようになっている。なお、挿入口８３はマイクロチップ１を挿入時に挿入口８３に接触しないように、マイクロチップ１の厚みより十分高さがある。８５はメモリカードスロット、８６はプリント出力口、８７は操作パネル、８８は入出力端子、８９は電源スイッチである。 The housing 82 of the inspection apparatus 80 has an insertion port 83, and the microchip 1 is inserted into the insertion port 83 and set inside the housing 82. The insertion port 83 is sufficiently higher than the thickness of the microchip 1 so as not to contact the insertion port 83 when the microchip 1 is inserted. Reference numeral 85 denotes a memory card slot, 86 denotes a print output port, 87 denotes an operation panel, 88 denotes an input / output terminal, and 89 denotes a power switch.
　検査担当者は電源スイッチ８９をオンにした後、図１の矢印方向にマイクロチップ１を挿入し、操作パネル８７を操作して検査を開始させる。検査装置８０の内部では、マイクロチップ１内の反応の検査が自動的に行われ、検査が終了すると液晶パネルなどで構成される表示部８４に結果が表示される。検査結果は操作パネル８７の操作により、プリント出力口８６よりプリントを出力したり、メモリカードスロット８５に挿入されたメモリカードに記憶することができる。また、外部入出力端子８８から例えばＬＡＮケーブルを使って、パソコンなどにデータを保存することができる。 The inspector turns on the power switch 89, inserts the microchip 1 in the direction of the arrow in FIG. 1, and operates the operation panel 87 to start the inspection. Inside the inspection device 80, the reaction in the microchip 1 is automatically inspected, and when the inspection is completed, the result is displayed on the display unit 84 constituted by a liquid crystal panel or the like. The inspection result can be output from the print output port 86 or stored in a memory card inserted into the memory card slot 85 by operating the operation panel 87. Further, data can be stored in the personal computer or the like from the external input / output terminal 88 using, for example, a LAN cable.
　検査担当者は、検査終了後、マイクロチップ１を挿入口８３から取り出す。 The person in charge of inspection takes out the microchip 1 from the insertion slot 83 after the inspection is completed.
　次に、本発明の第１の実施形態に係わるマイクロチップ１の一例について、図２を用いて説明する。 Next, an example of the microchip 1 according to the first embodiment of the present invention will be described with reference to FIG.
　図２は本発明の第１の実施形態におけるマイクロチップ１の外観図、図３は、検出部１１１の周辺の拡大図である。 FIG. 2 is an external view of the microchip 1 according to the first embodiment of the present invention, and FIG. 3 is an enlarged view of the periphery of the detection unit 111.
　図２（ａ）のマイクロチップ１の側面図に示すように、マイクロチップ１は溝形成基板１０８と、溝形成基板１０８を覆う被覆基板１０９から構成されている。図２（ａ）の矢印は、検査装置８０にマイクロチップ１を挿入する挿入方向である。 As shown in the side view of the microchip 1 in FIG. 2A, the microchip 1 includes a groove forming substrate 108 and a covering substrate 109 that covers the groove forming substrate 108. An arrow in FIG. 2A indicates an insertion direction in which the microchip 1 is inserted into the inspection apparatus 80.
　図２（ｂ）はマイクロチップ１の平面図であり、透明な被覆基板１０９を通して見える溝形成基板１０８の溝を図示している。溝形成基板１０８の溝を被覆基板１０９が覆うことにより流路を形成している。マイクロチップ１には、検査、試料の処理などを行うための、微小な溝状の流路２５０（微細流路）および機能部品（流路エレメント）が、用途に応じた適当な態様で配設されている。 FIG. 2B is a plan view of the microchip 1, and illustrates the grooves of the groove forming substrate 108 that can be seen through the transparent coated substrate 109. A flow path is formed by covering the grooves of the groove forming substrate 108 with the covering substrate 109. The microchip 1 is provided with minute groove-like channels 250 (microchannels) and functional parts (channel elements) for performing inspections, sample processing, and the like in an appropriate manner according to the application. Has been.
　流路はマイクロメーターオーダーで形成されており、例えば幅は数μｍ～数百μｍ、好ましくは１０～２００μｍで、深さは２５～５００μｍ程度、好ましくは２５～２５０μｍである。 The flow path is formed in the order of micrometers, for example, the width is several μm to several hundred μm, preferably 10 to 200 μm, and the depth is about 25 to 500 μm, preferably 25 to 250 μm.
　本実施形態では、特定の遺伝子の増幅およびその検出を行う処理に用いるマイクロチップ１を例に説明する。 In this embodiment, the microchip 1 used for the process of performing amplification and detection of a specific gene will be described as an example.
　図２（ｂ）の１１０ａ、１１０ｂはマイクロチップ１内部の流路に連通する注入口であり、各注入口１１０から駆動液を注入し内部の検体や試薬等を駆動する。本実施形態のマイクロチップ１では図２（ｂ）に示すように注入口１１０ａから始まる流路の構成と、注入口１１０ｂから始まる流路の構成は全く同じであり、以降ａチャンネル、ｂチャンネルと呼び区別する。また、各構成要素にはａ、ｂを付けて区別する。 In FIG. 2 (b), 110a and 110b are injection ports communicating with the flow path inside the microchip 1, and a driving liquid is injected from each injection port 110 to drive an internal specimen or reagent. In the microchip 1 of the present embodiment, as shown in FIG. 2B, the configuration of the flow path starting from the injection port 110a is completely the same as the configuration of the flow path starting from the injection port 110b. Distinguish between calls. Each component is distinguished by adding a and b.
　１２１ａ、１２１ｂは検体を収容する検体収容部である。検体収容部１２１ａ、１２１ｂは所定量の検体を収容するために他の流路より溝が深くなっている。本実施形態では予め、検体収容部１２１ａ、１２１ｂには検体が収容されているものとして説明する。 121a and 121b are sample storage units for storing samples. The sample storage units 121a and 121b have deeper grooves than other flow paths in order to store a predetermined amount of sample. In the present embodiment, a description will be given assuming that samples are stored in the sample storage units 121a and 121b in advance.
　１２０ａ、１２０ｂは第１の試薬を収容する試薬収容部、１２２ａ、１２２ｂは第２の試薬を収容する試薬収容部、１２３ａ、１２３ｂは第３の試薬を収容する試薬収容部である。 120a and 120b are reagent storage units for storing the first reagent, 122a and 122b are reagent storage units for storing the second reagent, and 123a and 123b are reagent storage units for storing the third reagent.
　注入口１１０ａ、１１０ｂから駆動液を注入すると、検体収容部１２１ａ、１２１ｂに収容された検体は流路２５０に押し出されて、それぞれ下流の試薬収容部１２０ａ、１２０ｂに注入される。検体と試薬収容部１２０ａ、１２０ｂから押し出された第１の試薬は、それぞれ流路２５０を通って下流の試薬収容部１２２ａ、１２２ｂに注入される。検体と第１の試薬は第２の試薬を試薬収容部１２２ａ、１２２ｂから押し出す。 When the driving liquid is injected from the injection ports 110a and 110b, the sample stored in the sample storage units 121a and 121b is pushed out to the flow channel 250 and is injected into the downstream reagent storage units 120a and 120b, respectively. The sample and the first reagent pushed out from the reagent storage units 120a and 120b are respectively injected into the downstream reagent storage units 122a and 122b through the flow channel 250. The specimen and the first reagent push out the second reagent from the reagent storage parts 122a and 122b.
　検体と第１の試薬と第２の試薬は、それぞれ流路２５０を通って下流の試薬収容部１２３ａ、１２３ｂに注入され第３の試薬を押し出す。 The specimen, the first reagent, and the second reagent are respectively injected into the downstream reagent storage units 123a and 123b through the flow path 250 to push out the third reagent.
　試薬収容部１２３ａ、１２３ｂの下流には混合部１３０ａ、混合部１３０ｂと混合部１３１ａ、混合部１３１ｂが設けられており、流路２５０ａａ、流路２５０ｂａを流れてきた検体、第１の試薬、第２の試薬、第３の試薬は各混合部で混合される。 A mixing unit 130a, a mixing unit 130b, a mixing unit 131a, and a mixing unit 131b are provided downstream of the reagent storage units 123a and 123b. The flow channel 250aa, the sample flowing through the flow channel 250ba, the first reagent, The second reagent and the third reagent are mixed in each mixing unit.
　混合部１３０ａ、混合部１３０ｂの近くの上流側にあたる流路２５０ａａ、流路２５０ｂａには液溜部１４０ａ、１４０ｂが設けられている。液溜部１４０ａ、１４０ｂは、第３の試薬が試薬収容部１２３ａ、１２３ｂから押し出されて、先頭部分が混合部１３０ａと混合部１３０ｂの近くまで到達したことを検知するために設けられている。 Liquid reservoirs 140a and 140b are provided in the flow channel 250aa and the flow channel 250ba on the upstream side near the mixing unit 130a and the mixing unit 130b. The liquid reservoirs 140a and 140b are provided to detect that the third reagent has been pushed out of the reagent storage parts 123a and 123b and the leading portion has reached the vicinity of the mixing part 130a and the mixing part 130b.
　液溜部１４０ａ、１４０ｂは、混合部１３０ａ、混合部１３０ｂより溝が浅く、他の流路２５０より溝が深くなっている。混合部１３１ａ、混合部１３１ｂの溝の深さは例えば１．５ｍｍ、液溜部１４０ａ、１４０ｂの溝の深さは例えば０．６ｍｍ、他の流路の溝の深さは例えば０．２５ｍｍである。 The liquid reservoirs 140 a and 140 b have shallower grooves than the mixing parts 130 a and 130 b and deeper grooves than the other flow paths 250. The depth of the grooves of the mixing portion 131a and the mixing portion 131b is, for example, 1.5 mm, the depth of the grooves of the liquid reservoir portions 140a, 140b is, for example, 0.6 mm, and the depth of the grooves of the other flow paths is, for example, 0.25 mm. is there.
　混合部１３０ａ、混合部１３０ｂと混合部１３１ａ、混合部１３１ｂで混合された検体、第１の試薬、第２の試薬、第３の試薬は検出部１１１ａ、１１１ｂに注入される。後に説明するように、検査装置８０の内部で検出部１１１ａ、１１１ｂを加熱または吸熱して所定の温度で検体と試薬とを所定の時間反応させる。 The mixing unit 130a, the mixing unit 130b and the mixing unit 131a, and the specimen, the first reagent, the second reagent, and the third reagent mixed in the mixing unit 131b are injected into the detection units 111a and 111b. As will be described later, the detection units 111a and 111b are heated or absorbed in the inspection apparatus 80 to cause the specimen and the reagent to react at a predetermined temperature for a predetermined time.
　検出部１１１ａ、１１１ｂは検体と試薬との反応を光学的に検出するために設けられ、所定量の検体と試薬を収容するために他の流路より溝が深くなっている。 The detection units 111a and 111b are provided for optically detecting the reaction between the specimen and the reagent, and have a groove deeper than the other flow paths to accommodate a predetermined amount of the specimen and the reagent.
　検出部１１１ａ、１１１ｂの下流には液溜部１４１ａ、１４１ｂが設けられており、検出部１１１ａ、１１１ｂが試薬や検体などの液体で充填されたことを検出できるようになっている。液溜部１４１ａ、１４１ｂは検出部１１１ａ、１１１ｂより溝が浅く、他の流路より溝が深くなっている。 Liquid reservoirs 141a and 141b are provided downstream of the detection units 111a and 111b, so that it can be detected that the detection units 111a and 111b are filled with a liquid such as a reagent or a specimen. The liquid reservoirs 141a and 141b are shallower than the detectors 111a and 111b, and deeper than the other channels.
　図３を用いて検出部１１１と液溜部１４１の形状例を説明する。図３（ａ）は平面図、図３（ｂ）は検出部１１１の断面図である。 An example of the shapes of the detection unit 111 and the liquid storage unit 141 will be described with reference to FIG. FIG. 3A is a plan view, and FIG. 3B is a cross-sectional view of the detection unit 111.
　検出部１１１ａ、１１１ｂの溝の深さｄ３は例えば１．５ｍｍ、液溜部１４１ａ、１４１ｂの溝の深さｄ２は例えば０．６ｍｍ、他の流路の溝の深さｄ１は例えば０．２５ｍｍである。検出部１１１ａ、１１１ｂが充填されたことをできるだけ早く検出できるように、液溜部１４１ａ、１４１ｂは検出部１１１ａ、１１１ｂの下流のできるだけ近い位置に設けることが望ましい。２０は例えばフォトリフレクタなどを用いた液体検知部であり、液溜部１４１ａ、１４１ｂに光を照射して反射光を検知し、電気信号を出力する。 The groove depth d3 of the detectors 111a and 111b is, for example, 1.5 mm, the groove depth d2 of the liquid reservoirs 141a and 141b is, for example, 0.6 mm, and the groove depth d1 of the other flow paths is, for example, 0.25 mm. It is. It is desirable that the liquid reservoirs 141a and 141b be provided as close as possible to the downstream of the detection units 111a and 111b so that it can be detected as soon as possible that the detection units 111a and 111b are filled. Reference numeral 20 denotes a liquid detector using, for example, a photo reflector, which irradiates the liquid reservoirs 141a and 141b with light to detect reflected light and outputs an electrical signal.
　検出部１１１ａ、１１１ｂは、図３には図示せぬ検出ユニット２２から光を照射すると、検体と反応した試薬が例えば蛍光を発光するので、検出ユニット２２で蛍光の光量を測定して反応結果を計測する。 When the detection units 111a and 111b emit light from the detection unit 22 (not shown in FIG. 3), the reagent that has reacted with the specimen emits, for example, fluorescence. Therefore, the detection unit 22 measures the amount of fluorescence and displays the reaction result. measure.
　次に、マイクロチップ１を構成する溝形成基板１０８と被覆基板１０９に用いる材料について説明する。 Next, materials used for the groove forming substrate 108 and the covering substrate 109 constituting the microchip 1 will be described.
　マイクロチップ１は、加工成形性、非吸水性、耐薬品性、耐候性、コストなどに優れていることが望まれており、マイクロチップ１の構造、用途、検出方法などを考慮して、マイクロチップ１の材料を選択する。その材料としては従来公知の様々なものが使用可能であり、個々の材料特性に応じて通常は１以上の材料を適宜組み合わせて、基板および流路エレメントが成形される。 The microchip 1 is desired to be excellent in processability, non-water absorption, chemical resistance, weather resistance, cost and the like. In consideration of the structure, application, detection method, etc. of the microchip 1, The material of chip 1 is selected. Various known materials can be used as the material, and usually the substrate and the flow path element are formed by appropriately combining one or more materials in accordance with individual material characteristics.
　特に、多数の測定検体、とりわけ汚染、感染のリスクのある臨床検体を対象とするチップは、ディスポーサブルタイプであることが望ましい。そのため、量産可能であり、軽量で衝撃に強く、焼却廃棄が容易なプラステック樹脂、例えば、透明性、機械的特性および成型性に優れて微細加工がしやすいポリスチレンが好ましい。また、例えば分析においてチップを１００℃近くまで加熱する必要がある場合には、耐熱性に優れる樹脂（例えばポリカーボネートなど）を用いることが好ましい。また、タンパク質の吸着が問題となる場合にはポリプロピレンを用いることが好ましい。樹脂やガラスなどは熱伝導率が小さく、マイクロチップの局所的に加熱される領域に、これらの材料を用いることにより、面方向への熱伝導が抑制され、加熱領域のみ選択的に加熱することができる。 Especially, it is desirable that a chip for a large number of measurement specimens, especially clinical specimens at risk of contamination and infection, be of a disposable type. Therefore, a plastic resin that can be mass-produced, is lightweight, is strong against impact, and can be easily discarded by incineration, for example, polystyrene that is excellent in transparency, mechanical properties, and moldability and is easy to be finely processed is preferable. For example, when it is necessary to heat the chip to near 100 ° C. in analysis, it is preferable to use a resin having excellent heat resistance (for example, polycarbonate). In addition, when protein adsorption becomes a problem, it is preferable to use polypropylene. Resin and glass have low thermal conductivity, and by using these materials in the locally heated region of the microchip, heat conduction in the surface direction is suppressed, and only the heated region is selectively heated. Can do.
　検出部１１１において、呈色反応の生成物や蛍光物質などの検出を光学的に行うので、少なくとも被覆基板１０９のこの部位は光透過性の材料（例えばアルカリガラス、石英ガラス、透明プラスチック類）を用い、光が透過するようにする必要がある。 Since the detection unit 111 optically detects a color reaction product or a fluorescent substance, at least this portion of the coated substrate 109 is made of a light-transmitting material (for example, alkali glass, quartz glass, transparent plastics). It is necessary to use and transmit light.
　液溜部１４０ａ、１４０ｂ、液溜部１４１ａ、１４１ｂに収容されている液体を光学的に検知する場合は、少なくとも被覆基板１０９の液溜部１４０ａ、１４０ｂ、液溜部１４１ａ、１４１ｂを覆う部分はガラスや樹脂などの透明な部材で構成する必要がある。なお、超音波、電波などを用いて液体を検知する場合は、必ずしも透明な部材を用いる必要はない。 When optically detecting the liquid stored in the liquid reservoirs 140a and 140b and the liquid reservoirs 141a and 141b, at least the portion covering the liquid reservoirs 140a and 140b and the liquid reservoirs 141a and 141b of the coated substrate 109 is It is necessary to configure with a transparent member such as glass or resin. In addition, when detecting a liquid using an ultrasonic wave, an electromagnetic wave, etc., it is not necessary to use a transparent member.
　図４は、本発明の第１の実施形態における検査装置８０の内部構成の一例を説明するための斜視図、図５は、本発明の第１の実施形態における検査装置８０の内部構成の一例を示す断面図、である。図６は検出部１１１に充填された液体を説明する説明図である。図４、図５に示すＸ、Ｙ、Ｚの座標軸を基準に各部の説明を行う。 FIG. 4 is a perspective view for explaining an example of the internal configuration of the inspection apparatus 80 according to the first embodiment of the present invention. FIG. 5 is an example of the internal configuration of the inspection apparatus 80 according to the first embodiment of the present invention. FIG. FIG. 6 is an explanatory diagram for explaining the liquid filled in the detection unit 111. Each part will be described with reference to the coordinate axes of X, Y, and Z shown in FIGS.
　検査装置８０は、温度調節ユニット１５２、検出ユニット２２、マイクロポンプユニット７５、パッキン９０、駆動液タンク９１、送りネジ３０１、送りネジ３５１、ジョイント３０２、ジョイント３５２、検知基板駆動モータ６０、検出ユニット駆動モータ６１などから構成される。図４、図５はマイクロチップ１をパッキン９０ｂに密着させている状態を示している。 The inspection device 80 includes a temperature adjustment unit 152, a detection unit 22, a micro pump unit 75, a packing 90, a driving liquid tank 91, a feed screw 301, a feed screw 351, a joint 302, a joint 352, a detection board drive motor 60, and a detection unit drive. It is composed of a motor 61 and the like. 4 and 5 show a state in which the microchip 1 is in close contact with the packing 90b.
　以下、図４、図５、図６を用いて検査装置８０の内部構成の例を説明する。 Hereinafter, an example of the internal configuration of the inspection apparatus 80 will be described with reference to FIGS. 4, 5, and 6.
　温度調節ユニット１５２とマイクロチップ１は、図示せぬ駆動部材により駆動され、Ｚ軸方向に移動可能である。初期状態において、駆動部材により温度調節ユニット１５２を、図４の状態からマイクロチップ１の厚み以上上昇させる。すると、マイクロチップ１はＹ軸方向に挿抜可能であり、検査担当者は挿入口８３から図示せぬ規制部材に当接するまでマイクロチップ１を挿入する。所定の位置までマイクロチップ１を挿入するとフォトインタラプタなどを用いたチップ検知部９５がマイクロチップ１を検知し、オンになる。 The temperature adjustment unit 152 and the microchip 1 are driven by a driving member (not shown) and can move in the Z-axis direction. In the initial state, the temperature adjustment unit 152 is raised from the state of FIG. 4 by the thickness of the microchip 1 by the driving member. Then, the microchip 1 can be inserted and removed in the Y-axis direction, and the person inspecting inserts the microchip 1 from the insertion port 83 until it comes into contact with a regulating member (not shown). When the microchip 1 is inserted to a predetermined position, the chip detection unit 95 using a photo interrupter or the like detects the microchip 1 and is turned on.
　温度調節ユニット１５２は、ペルチェ素子、電源装置、温度制御装置などを内蔵し、発熱または吸熱を行ってマイクロチップ１の面を所定の温度に調整し、検出部１１１に充填された液体の反応を促進させるユニットである。 The temperature adjustment unit 152 includes a Peltier element, a power supply device, a temperature control device, etc., performs heat generation or heat absorption to adjust the surface of the microchip 1 to a predetermined temperature, and reacts the liquid filled in the detection unit 111. It is a unit to promote.
　駆動部材により温度調節ユニット１５２とマイクロチップ１は下降し、マイクロチップ１を温度調節ユニット１５２とパッキン９０ｂに密着させる。 The temperature adjustment unit 152 and the microchip 1 are lowered by the driving member, and the microchip 1 is brought into close contact with the temperature adjustment unit 152 and the packing 90b.
　本実施形態では、温度調節ユニット１５２によって加熱可能な範囲は液溜部１４１までである。次に、マイクロチップ１の液溜部１４０ａ、１４０ｂ、液溜部１４１ａ、１４１ｂにそれぞれ収容されている液体を光学的に検知する方法の一例を説明する。 In the present embodiment, the range that can be heated by the temperature adjustment unit 152 is up to the liquid reservoir 141. Next, an example of a method for optically detecting the liquid stored in the liquid reservoirs 140a and 140b and the liquid reservoirs 141a and 141b of the microchip 1 will be described.
　図５の断面図では、液溜部１４０（液溜部１４０ａ、１４０ｂの何れか）に収容されている液体を光学的に検知できる位置にある液体検知部２０を図示している。 The cross-sectional view of FIG. 5 illustrates the liquid detection unit 20 in a position where the liquid stored in the liquid storage unit 140 (any one of the liquid storage units 140a and 140b) can be optically detected.
　たとえば、液体検知部２０から光を液溜部１４０に照射し、液溜部１４０で反射する光を液体検知部２０で受光し、光量や色の変化から液溜部１４０に液体が充填されていることを検知する。後に詳しく説明する手順で駆動部６０が液体検知部２０を液溜部１４１を光学的に検知できる位置に移動させた後、液溜部１４１の検知も同様の手順で行う。 For example, light is irradiated from the liquid detection unit 20 to the liquid storage unit 140, and the light reflected by the liquid storage unit 140 is received by the liquid detection unit 20, and the liquid storage unit 140 is filled with liquid due to a change in the amount of light and color. Detect that After the drive unit 60 moves the liquid detection unit 20 to a position where the liquid storage unit 141 can be optically detected by a procedure described in detail later, the detection of the liquid storage unit 141 is performed in the same procedure.
　図５に示す液体検知部２０は、例えば発光部と受光部を備えたフォトリフレクタであり、液体検知部２０は検知基板２１に搭載されている。後に説明するように本実施形態では検知基板２１に２つの液体検知部２０ａ、２０ｂが搭載されている。液体検知部２０は本発明の液体検知手段である。 The liquid detection unit 20 shown in FIG. 5 is a photo reflector provided with, for example, a light emitting unit and a light receiving unit, and the liquid detection unit 20 is mounted on a detection substrate 21. As will be described later, in the present embodiment, two liquid detection units 20 a and 20 b are mounted on the detection substrate 21. The liquid detector 20 is a liquid detector of the present invention.
　図６（ａ）は検出部１１１に液体５７が十分充填されていない状態、図６（ｂ）は検出部１１１に液体５７が充填された状態を示している。図６（ｂ）のように検出部１１１の下流側まで液体５７の先頭部分が到達すると、液溜部１４０にも液体５７が充填される。したがって、液体検知部２０で液溜部１４０の液体５７を検知することにより、検出部１１１が液体５７で充填されたことを知ることができる。 6A shows a state where the detection unit 111 is not sufficiently filled with the liquid 57, and FIG. 6B shows a state where the detection unit 111 is filled with the liquid 57. As shown in FIG. 6B, when the leading portion of the liquid 57 reaches the downstream side of the detection unit 111, the liquid reservoir 140 is also filled with the liquid 57. Therefore, it is possible to know that the detection unit 111 is filled with the liquid 57 by detecting the liquid 57 in the liquid reservoir 140 with the liquid detection unit 20.
　なお、液体検知部２０の数は２つに限定されるものではなく、１つ以上であればいくらでも良い。図２で説明したマイクロチップ１のように複数のチャネルで検査を行う場合は、チャネル毎に設けた液溜部１４１を同時に検査できるように複数の液体検知部２０を設けると良い。 It should be noted that the number of liquid detection units 20 is not limited to two, and may be any number as long as it is one or more. When the inspection is performed with a plurality of channels as in the microchip 1 described with reference to FIG. 2, it is preferable to provide a plurality of liquid detection units 20 so that the liquid reservoirs 141 provided for the respective channels can be inspected simultaneously.
　なお、本実施形態では液溜部１４０ａ、１４０ｂ、液溜部１４１ａ、１４１ｂに光を照射し、反射する光を検知する例を説明するが、液溜部１４０ａ、１４０ｂ、液溜部１４１ａ、１４１ｂを透過する光や超音波または電波を検知するようにしても良い。 In this embodiment, an example will be described in which the liquid reservoirs 140a and 140b and the liquid reservoirs 141a and 141b are irradiated with light and reflected light is detected, but the liquid reservoirs 140a and 140b and the liquid reservoirs 141a and 141b are described. You may make it detect the light, an ultrasonic wave, or an electromagnetic wave which permeate | transmits.
　図４に示すように、検知基板２１の一端は、送りネジ３５１と螺合するネジ部を有するガイド部材３５４に支持され、送りネジ３５１が回転することによりＹ軸方向に移動する。検知基板２１の他端は、ガイド棒３５３が貫通する図示せぬ部材に支持されており、検知基板２１はマイクロチップの流路２５０と平行に移動する。 As shown in FIG. 4, one end of the detection substrate 21 is supported by a guide member 354 having a screw portion screwed with the feed screw 351, and moves in the Y-axis direction when the feed screw 351 rotates. The other end of the detection substrate 21 is supported by a member (not shown) through which the guide rod 353 passes, and the detection substrate 21 moves in parallel with the microchip channel 250.
　液体検知部２０ａ、２０ｂは、検知基板２１が送りネジ３５１によって移動すると、液溜部１４０ａ、１４０ｂ、液溜部１４１ａ、１４１ｂのそれぞれの中心部に、液体検知部２０ａ、２０ｂの液体を検知可能な範囲が一致するように検知基板２１上に配置されている。 When the detection substrate 21 is moved by the feed screw 351, the liquid detection units 20a and 20b can detect the liquid in the liquid detection units 20a and 20b at the central portions of the liquid storage units 140a and 140b and the liquid storage units 141a and 141b. It is arranged on the detection substrate 21 so that various ranges coincide with each other.
　液体検知部２０ａ、２０ｂは、所定の位置に移動した後、液溜部１４０ａ、１４０ｂまたは液溜部１４１ａ、１４１ｂに順次光を照射し、反射光を受光して電気信号を出力する。 After the liquid detectors 20a and 20b have moved to predetermined positions, the liquid reservoirs 140a and 140b or the liquid reservoirs 141a and 141b are sequentially irradiated with light, the reflected light is received, and an electrical signal is output.
　送りネジ３５１は検知基板駆動モータ６０によりジョイント３５２を介して駆動される。検知基板駆動モータ６０は例えばパルスモータであり、パルスにより所定量回転する。第１位置センサ４０は、検知基板２１の初期位置を検知するために設けられたフォトリフレクタなどのセンサまたはメカニカルスイッチなどである。 The feed screw 351 is driven by the detection board drive motor 60 via the joint 352. The detection board drive motor 60 is a pulse motor, for example, and rotates by a predetermined amount by a pulse. The first position sensor 40 is a sensor such as a photo reflector provided for detecting the initial position of the detection substrate 21 or a mechanical switch.
　検出ユニット２２は発光部と受光部から成り、検出部１１１に光を照射して検体と反応した試薬が発光する蛍光を、光学的に分離して受光部に受光するように構成されている。検出ユニット２２は送りネジ３０１と螺合するネジ部を有し、送りネジ３０１が回転することによりＸ軸方向に移動する。送りネジ３０１は直線Ｆと平行に配設されており、検出ユニット２２が送りネジ３０１によって移動すると、検出部１１１ａ、１１１ｂのそれぞれの中心部に、検出ユニット２２のレンズ２３の光軸が一致するように配置されている。検出ユニット２２は、所定の位置に移動した後、検出部１１１ａ、１１１ｂにレンズ２３から順次励起光を照射し、蛍光物質が発光する蛍光を受光して電気信号を出力する。 The detection unit 22 includes a light emitting unit and a light receiving unit, and is configured to optically separate the fluorescence emitted from the reagent that has reacted with the specimen by irradiating the detection unit 111 with light and to receive the light in the light receiving unit. The detection unit 22 has a screw portion that is screwed with the feed screw 301, and moves in the X-axis direction when the feed screw 301 rotates. The feed screw 301 is disposed in parallel with the straight line F, and when the detection unit 22 is moved by the feed screw 301, the optical axis of the lens 23 of the detection unit 22 coincides with the center of each of the detection units 111a and 111b. Are arranged as follows. After moving to a predetermined position, the detection unit 22 sequentially irradiates the detection units 111a and 111b with excitation light from the lens 23, receives fluorescence emitted from the fluorescent material, and outputs an electrical signal.
　送りネジ３０１は検出ユニット駆動モータ６１によりジョイント３０２を介して駆動される。検出ユニット駆動モータ６１は例えばパルスモータであり、パルスにより所定量回転する。第２位置センサ４１は検出ユニット２２の初期位置を検知するために設けられたフォトリフレクタなどのセンサまたはメカニカルスイッチなどである。 The feed screw 301 is driven via the joint 302 by the detection unit drive motor 61. The detection unit drive motor 61 is a pulse motor, for example, and rotates by a predetermined amount by a pulse. The second position sensor 41 is a sensor such as a photo reflector or a mechanical switch provided to detect the initial position of the detection unit 22.
　なお、検出ユニット２２には回転防止用に図４には図示せぬガイド穴が設けられており、ガイド穴を貫通するガイド棒に沿って移動する。ガイド棒は送りネジ３０１と平行に配設されている。 The detection unit 22 is provided with a guide hole (not shown in FIG. 4) for preventing rotation, and moves along a guide rod that penetrates the guide hole. The guide bar is disposed in parallel with the feed screw 301.
　なお、本実施形態ではマイクロチップ１に検出部１１１ａ、１１１ｂが２つ設けられている場合について説明したが、検出部１１１の数は１つ以上であればいくつでも良い。 In the present embodiment, the case where two detection units 111a and 111b are provided in the microchip 1 has been described. However, the number of the detection units 111 may be any number as long as it is one or more.
　図５では、液体検知部２０（液体検知部２０ａ、２０ｂの何れか）が液溜部１４０（液溜部１４０ａ、１４０ｂのうち対応する何れか）の液体を検知する位置にある場合を図示している。また、検出ユニット２２は検出部１１１（検出部１１１ａ、１１１ｂの何れか）でおこる試薬の反応結果を光学的に検出できる位置にある場合を図示している。 FIG. 5 illustrates a case where the liquid detection unit 20 (any one of the liquid detection units 20a and 20b) is in a position for detecting the liquid in the liquid storage unit 140 (any one of the liquid storage units 140a and 140b). ing. Moreover, the case where the detection unit 22 exists in the position which can optically detect the reaction result of the reagent which occurs in the detection part 111 (any of detection part 111a, 111b) is illustrated.
　マイクロチップ１の注入口１１０は、マイクロチップ１をパッキン９０ｂを介してマイクロポンプ７５と密着させたときに、パッキン９０ｂに設けられた対応する開口とそれぞれ連通する位置に設けられている。 When the microchip 1 is brought into close contact with the micropump 75 via the packing 90b, the injection port 110 of the microchip 1 is provided at a position communicating with a corresponding opening provided in the packing 90b.
　マイクロポンプユニット７５の吸入口１４５は、パッキン９０ａを介して駆動液タンク９１が接続され、駆動液タンク９１に充填された駆動液をパッキン９０ａを介して吸い込むようになっている。一方、吐出口１４６はパッキン９０ｂを介してマイクロチップ１の注入口１１０と連通している。 The suction port 145 of the micropump unit 75 is connected to a driving liquid tank 91 via a packing 90a, and sucks the driving liquid filled in the driving liquid tank 91 via the packing 90a. On the other hand, the discharge port 146 communicates with the injection port 110 of the microchip 1 through the packing 90b.
　圧電素子１１２を駆動することにより、マイクロポンプユニット７５から送り出された駆動液は、マイクロチップ１の注入口１１０からマイクロチップ１内に形成された流路２５０に注入される。このようにして、マイクロポンプユニット７５から注入口１１０に駆動液を注入する。 By driving the piezoelectric element 112, the driving liquid sent out from the micropump unit 75 is injected from the injection port 110 of the microchip 1 into the channel 250 formed in the microchip 1. In this way, the driving liquid is injected from the micropump unit 75 into the injection port 110.
　マイクロポンプユニット７５には少なくとも一つのマイクロポンプが設けられている。図２に図示したマイクロチップ１を駆動する場合は、２つの注入口１１０ａ、１１０ｂに対応する２つのマイクロポンプが必要である。 The micro pump unit 75 is provided with at least one micro pump. When the microchip 1 illustrated in FIG. 2 is driven, two micropumps corresponding to the two inlets 110a and 110b are necessary.
　図７は、本発明の第１の実施形態における検出装置８０の回路ブロック図である。 FIG. 7 is a circuit block diagram of the detection device 80 according to the first embodiment of the present invention.
　制御部９９は、ＣＰＵ９８（中央処理装置）とＲＡＭ９７（Ｒａｎｄｏｍ　Ａｃｃｅｓｓ　Ｍｅｍｏｒｙ），ＲＯＭ９６（Ｒｅａｄ　Ｏｎｌｙ　Ｍｅｍｏｒｙ）等から構成され、不揮発性の記憶部であるＲＯＭ９６に記憶されているプログラムをＲＡＭ９７に読み出し、当該プログラムに従って検出装置８０の各部を集中制御する。制御部９９は本発明の制御手段である。 The control unit 99 includes a CPU 98 (central processing unit), a RAM 97 (Random Access Memory), a ROM 96 (Read Only Memory), and the like, and reads a program stored in the ROM 96 which is a nonvolatile storage unit to the RAM 97. Each part of the detection device 80 is centrally controlled according to the program. The control unit 99 is a control means of the present invention.
　以下、いままでに説明した機能と同一機能を有する機能ブロックには同番号を付し、説明を省略する。 Hereafter, functional blocks having the same functions as those described above will be given the same reference numerals and description thereof will be omitted.
　ＣＰＵ９８はポンプ駆動制御部４１１、到達判定部４１２、検出ユニット駆動制御部４１３、検知基板駆動制御部４１４を有する。到達判定部４１２は本発明の到達判定手段、ポンプ駆動制御部４１１は本発明のポンプ駆動制御手段である。 The CPU 98 includes a pump drive control unit 411, an arrival determination unit 412, a detection unit drive control unit 413, and a detection board drive control unit 414. The arrival determination unit 412 is an arrival determination unit of the present invention, and the pump drive control unit 411 is a pump drive control unit of the present invention.
　本実施形態では、液体検知部２０ａと液体検知部２０ｂの２つが検知基板２１に搭載されている例について説明する。到達判定部４１２は、液体検知部２０ａの発光する光が液溜部１４０ａまたは液溜部１４１ａから反射した光を検出した出力信号を、所定の信号レベルと比較し結果を判定する。同様に、液体検知部２０ｂの発光する光が液溜部１４０ｂまたは液溜部１４１ｂから反射した光を検出した出力信号を、所定の信号レベルと比較し結果を判定する。 In the present embodiment, an example in which two of the liquid detection unit 20a and the liquid detection unit 20b are mounted on the detection substrate 21 will be described. The arrival determination unit 412 compares the output signal obtained by detecting the light reflected by the liquid reservoir 140a or the liquid reservoir 141a with the light emitted from the liquid detection unit 20a, and determines the result. Similarly, the output signal obtained by detecting the light reflected from the liquid reservoir 140b or the liquid reservoir 141b by the light emitted from the liquid detector 20b is compared with a predetermined signal level to determine the result.
　検出ユニット駆動制御部４１３は、検出ユニット駆動検出ユニット駆動モータ６１に指令し検出ユニット２２を移動させる。 The detection unit drive control unit 413 instructs the detection unit drive detection unit drive motor 61 to move the detection unit 22.
　検知基板駆動制御部４１４は、検知基板駆動モータ６０に指令し液体検知部２０ａ、液体検知部２０ｂを搭載した検知基板２１を移動させる。 The detection substrate drive control unit 414 instructs the detection substrate drive motor 60 to move the detection substrate 21 on which the liquid detection unit 20a and the liquid detection unit 20b are mounted.
　ポンプ駆動部５００は、各マイクロポンプの圧電素子１１２を駆動する。ポンプ駆動制御部４１１はプログラムに基づいて、所定量の駆動液を注入または吸入するようにポンプ駆動部５００を制御する。ポンプ駆動部５００はポンプ駆動制御部４１１の指令を受けて、駆動電圧を発生して圧電素子１１２を駆動する。 The pump drive unit 500 drives the piezoelectric element 112 of each micropump. Based on the program, the pump drive control unit 411 controls the pump drive unit 500 to inject or suck a predetermined amount of drive fluid. The pump drive unit 500 receives a command from the pump drive control unit 411 and generates a drive voltage to drive the piezoelectric element 112.
　ＣＰＵ９８は所定のシーケンスで検査を行い、検査結果をＲＡＭ９７に記憶する。検査結果は、操作部８７の操作によりメモリカード５０１に記憶したり、プリンタ５０３によってプリントすることができる。 The CPU 98 performs inspection in a predetermined sequence and stores the inspection result in the RAM 97. The inspection result can be stored in the memory card 501 by the operation of the operation unit 87 or printed by the printer 503.
　次に、本発明の第１の実施形態の検査装置８０が検査を行う手順を図８～図１０を用いて説明する。 Next, the procedure in which the inspection apparatus 80 according to the first embodiment of the present invention performs an inspection will be described with reference to FIGS.
　図８は第１の実施形態の検査装置８０が検査を行うメインルーチンを説明するフローチャート、図９は本発明の第１の実施形態の検査装置８０が液溜部に液体の先頭部分が到達したことを検知するサブルーチンを説明するフローチャートである。図１０は実施形態の検査装置８０が反応測定を行うサブルーチンを説明するフローチャートである。 FIG. 8 is a flowchart for explaining a main routine in which the inspection apparatus 80 of the first embodiment performs an inspection, and FIG. 9 shows that the inspection apparatus 80 of the first embodiment of the present invention reaches the liquid reservoir at the top of the liquid. It is a flowchart explaining the subroutine which detects this. FIG. 10 is a flowchart for explaining a subroutine in which the inspection apparatus 80 of the embodiment performs reaction measurement.
　最初に図８のフローチャートの順に検査の概略の手順を説明する。 First, the outline procedure of the inspection will be described in the order of the flowchart of FIG.
　マイクロチップ１は、図５のように検査が可能な位置にセットされ、操作部８７の操作によってＣＰＵに検査の開始が指令されているものとする。また、検知基板２１と検出ユニット２２は図５に示す初期位置にあるものとする。 Suppose that the microchip 1 is set at a position where inspection can be performed as shown in FIG. 5, and the CPU is instructed to start inspection by operating the operation unit 87. Moreover, the detection board | substrate 21 and the detection unit 22 shall be in the initial position shown in FIG.
　Ｓ２０１：キャリブレーションを行うステップである。 S201: This is a step for performing calibration.
　到達判定部４１２は、液体検知部２０ａ、液体検知部２０ｂを発光させ、液溜部１４０ａ、液溜部１４０ｂから反射した光を液体検知部２０ａ、液体検知部２０ｂがそれぞれ検出した出力信号を、所定の信号レベルと比較する。所定の信号レベルの範囲で無い場合、到達判定部４１２は液体検知部２０ａ、液体検知部２０ｂの発光部に流す電流を増加または減少させて所定の信号レベルの範囲になるようキャリブレーションを行う。到達判定部４１２は、液体検知部２０ａ、液体検知部２０ｂの出力信号がそれぞれ所定の信号レベルの範囲になると、そのときの出力電圧を基に液体の到達を判定する閾値を決定しＲＡＭ９７に記憶する。また、エラーフラッグを初期化し値を０にする。 The arrival determination unit 412 causes the liquid detection unit 20a and the liquid detection unit 20b to emit light, and outputs the output signals detected by the liquid detection unit 20a and the liquid detection unit 20b respectively from the light reflected from the liquid storage unit 140a and the liquid storage unit 140b. Compare with a predetermined signal level. If it is not within the predetermined signal level range, the arrival determination unit 412 performs calibration so that the current flowing through the light emitting units of the liquid detection unit 20a and the liquid detection unit 20b is increased or decreased to be within the predetermined signal level range. When the output signals of the liquid detection unit 20a and the liquid detection unit 20b are in a predetermined signal level range, the arrival determination unit 412 determines a threshold value for determining the arrival of the liquid based on the output voltage at that time, and stores it in the RAM 97. To do. Also, the error flag is initialized and the value is set to zero.
　Ｓ２０２：ポンプを始動するステップである。 S202: This is a step of starting the pump.
　ポンプ駆動制御部４１１は、ポンプ駆動部５００に指令しマイクロポンプユニット７５からマイクロチップ１に送液を行う。 The pump drive control unit 411 instructs the pump drive unit 500 to send liquid from the micropump unit 75 to the microchip 1.
　Ｓ２０３：液到達を検知するステップである。 S203: This is a step of detecting the arrival of the liquid.
　到達判定部４１２は、後に詳しく説明する液到達検知ルーチンをコールし、液溜部１４０ａ、液溜部１４０ｂに液体の先頭部分が到達したことを検知してポンプの駆動を停止する。このステップでａチャンネル、ｂチャンネルの流路を流れる試薬等の先頭位置を液溜部１４０ａ、液溜部１４０ｂに揃えることができるので、後のステップ２０８でポンプを始動すると混合部１３０ａ、混合部１３０ｂに同時に試薬等を注入することができる。 The arrival determination unit 412 calls a liquid arrival detection routine which will be described in detail later, detects that the liquid leading portion has reached the liquid reservoir 140a and the liquid reservoir 140b, and stops driving the pump. In this step, since the leading position of the reagent or the like flowing through the flow channels of the a channel and the b channel can be aligned with the liquid reservoir 140a and the liquid reservoir 140b, the mixing unit 130a and the mixing unit are started when the pump is started in step 208 later. A reagent or the like can be simultaneously injected into 130b.
　Ｓ２０４：エラーフラッグを判定するステップである。 S204: This is a step of determining an error flag.
　到達判定部４１２は、エラーフラッグを判定する。液到達検知ルーチンが所定時間内に正常終了した場合はエラーフラッグが０であり、液溜部１４０ａ、液溜部１４０ｂに液体が到達した状態でマイクロポンプユニット７５は停止している。一方、所定時間内に正常終了しなかった場合は、エラーフラッグが１になっている。 The arrival determination unit 412 determines an error flag. When the liquid arrival detection routine is normally completed within a predetermined time, the error flag is 0, and the micropump unit 75 is stopped while the liquid has reached the liquid reservoir 140a and the liquid reservoir 140b. On the other hand, the error flag is set to 1 when the process does not end normally within a predetermined time.
　エラーフラッグが１の場合、（ステップＳ２０４；Ｙｅｓ）、ステップＳ２０５に進む。 If the error flag is 1 (step S204; Yes), the process proceeds to step S205.
　Ｓ２０５：警告を表示するステップである。 S205: This is a step of displaying a warning.
　制御部９９は、表示部８４にエラーの警告を表示し、検査装置８０を停止する。 The control unit 99 displays an error warning on the display unit 84 and stops the inspection device 80.
　エラーフラッグが０の場合、（ステップＳ２０４；Ｎｏ）、ステップＳ２０６に進む。 If the error flag is 0 (step S204; No), the process proceeds to step S206.
　Ｓ２０６：液体検知部２０を移動するステップである。 S206: This is a step of moving the liquid detection unit 20.
　検知基板駆動制御部４１４は、検知基板駆動検知基板駆動モータ６０に所定の数のパルスを送り図４の矢印Ｓ１方向に検知基板２１を移動させ、検知基板２１に実装されている液体検知部２０ａ、液体検知部２０ｂが液溜部１４１ａと液溜部１４１ｂの充填状態を検知可能な位置に停止させる。 The detection substrate drive control unit 414 sends a predetermined number of pulses to the detection substrate drive detection substrate drive motor 60 to move the detection substrate 21 in the direction of the arrow S1 in FIG. 4 and the liquid detection unit 20a mounted on the detection substrate 21. The liquid detector 20b stops at a position where the filling state of the liquid reservoir 141a and the liquid reservoir 141b can be detected.
　Ｓ２０７：キャリブレーションを行うステップである。 S207: This is a step for performing calibration.
　到達判定部４１２は、液体検知部２０ａ、液体検知部２０ｂを発光させ、液溜部１４１ａ、液溜部１４１ｂから反射した光を液体検知部２０ａ、液体検知部２０ｂがそれぞれ検出した出力信号を、所定の信号レベルと比較する。所定の信号レベルの範囲で無い場合、到達判定部４１２は液体検知部２０ａ、液体検知部２０ｂの発光部に流す電流を増加または減少させて所定の信号レベルの範囲になるようキャリブレーションを行う。到達判定部４１２は、液体検知部２０ａ、液体検知部２０ｂの出力信号がそれぞれ所定の信号レベルの範囲になると、そのときの出力電圧を基に液体の到達を判定する閾値を決定しＲＡＭ９７に記憶する。また、エラーフラッグを初期化し値を０にする。 The arrival determination unit 412 causes the liquid detection unit 20a and the liquid detection unit 20b to emit light, and the output signals detected by the liquid detection unit 20a and the liquid detection unit 20b respectively from the light reflected from the liquid storage unit 141a and the liquid storage unit 141b. Compare with a predetermined signal level. If it is not within the predetermined signal level range, the arrival determination unit 412 performs calibration so that the current flowing through the light emitting units of the liquid detection unit 20a and the liquid detection unit 20b is increased or decreased to be within the predetermined signal level range. When the output signals of the liquid detection unit 20a and the liquid detection unit 20b are in a predetermined signal level range, the arrival determination unit 412 determines a threshold value for determining the arrival of the liquid based on the output voltage at that time, and stores it in the RAM 97. To do. Also, the error flag is initialized and the value is set to zero.
　Ｓ２０８：ポンプを始動するステップである。 S208: This is the step of starting the pump.
　ポンプ駆動制御部４１１は、ポンプ駆動部５００に指令し、マイクロポンプユニット７５からマイクロチップ１に送液を行う。 The pump drive control unit 411 instructs the pump drive unit 500 to send liquid from the micropump unit 75 to the microchip 1.
　Ｓ２０９：液到達を検知するステップである。 S209: This is a step of detecting the arrival of the liquid.
　到達判定部４１２は液到達検知ルーチンをコールし、液溜部１４１ａ、液溜部１４１ｂに液体が到達したことを検知してポンプの駆動を停止する。このステップでａチャンネル、ｂチャンネルの流路を流れる検体と試薬の混合液の先頭部分を液溜部１４１ａ、液溜部１４１ｂに揃えるので、混合液が検出部１１１ａ、検出部１１１ｂに充填された状態にすることができる。 The arrival determination unit 412 calls the liquid arrival detection routine, detects that the liquid has reached the liquid reservoir 141a and the liquid reservoir 141b, and stops driving the pump. In this step, since the head portion of the mixed liquid of the specimen and the reagent flowing through the channel of the a channel and the b channel is aligned with the liquid reservoir 141a and the liquid reservoir 141b, the mixed liquid is filled in the detector 111a and the detector 111b. Can be in a state.
　Ｓ２１０：エラーフラッグを判定するステップである。 S210: A step of determining an error flag.
　到達判定部４１２は、エラーフラッグを判定する。液到達検知ルーチンが所定時間内に正常終了した場合はエラーフラッグが０であり、液溜部１４１ａ、液溜部１４１ｂに液体が到達した状態でマイクロポンプユニット７５は停止している。一方、所定時間内に正常終了しなかった場合は、エラーフラッグが１になっている。 The arrival determination unit 412 determines an error flag. When the liquid arrival detection routine ends normally within a predetermined time, the error flag is 0, and the micropump unit 75 is stopped in a state where the liquid has reached the liquid reservoir 141a and the liquid reservoir 141b. On the other hand, the error flag is set to 1 when the process does not end normally within a predetermined time.
　エラーフラッグが１の場合、（ステップＳ２１０；Ｙｅｓ）、ステップＳ２１１に進む。 If the error flag is 1 (step S210; Yes), the process proceeds to step S211.
　Ｓ２１１：警告を表示するステップである。 S211: This is a step of displaying a warning.
　制御部９９は、表示部８４にエラーの警告を表示し、検査装置８０を停止する。 The control unit 99 displays an error warning on the display unit 84 and stops the inspection device 80.
　エラーフラッグが０の場合、（ステップＳ２１０；Ｎｏ）、ステップＳ２１２に進む。 When the error flag is 0 (step S210; No), the process proceeds to step S212.
　Ｓ２１２：液体検知部２０を移動するステップである。 S212: This is a step of moving the liquid detection unit 20.
　検知基板駆動制御部４１４は、検知基板駆動検知基板駆動モータ６０に所定の数のパルスを送り図４の矢印Ｓ１と逆方向に検知基板２１を移動させ所定の位置に退避させる。 The detection board drive control unit 414 sends a predetermined number of pulses to the detection board drive detection board drive motor 60, moves the detection board 21 in the direction opposite to the arrow S1 in FIG. 4 and retracts it to a predetermined position.
　Ｓ２１３：反応結果を測定するステップである。 S213: This is a step of measuring the reaction result.
　所定の時間経過後、ＣＰＵ９８は反応測定ルーチンをコールし、検出部１１１ａ、検出部１１１ｂから反応結果を測定する。 After a predetermined time has elapsed, the CPU 98 calls a reaction measurement routine and measures the reaction result from the detection unit 111a and the detection unit 111b.
　メインルーチンの説明は以上である。 This completes the explanation of the main routine.
　次に、図９のフローチャートを用いて液到達検知ルーチンを説明する。 Next, the liquid arrival detection routine will be described using the flowchart of FIG.
　以下の説明では、液溜部１４０ａまたは液溜部１４１ａをａチャンネルの液溜部、液溜部１４０ｂまたは液溜部１４１ｂをｂチャンネルの液溜部、注入口１１０ａから駆動液を注入するポンプをａチャンネルのポンプ、注入口１１０ｂから駆動液を注入するポンプをｂチャンネルのポンプと呼ぶ。 In the following description, the liquid reservoir 140a or the liquid reservoir 141a is used as the a-channel liquid reservoir, the liquid reservoir 140b or the liquid reservoir 141b is used as the b-channel liquid reservoir, and the pump for injecting the driving liquid from the inlet 110a is used. An a-channel pump and a pump that injects the driving liquid from the inlet 110b are referred to as a b-channel pump.
　Ｓ１０１：ａチャンネルの液溜部からの反射光を測定するステップである。 S101: This is a step of measuring the reflected light from the liquid reservoir of the a channel.
　到達判定部４１２は、液体検知部２０ａを発光させ、ａチャンネルの液溜部から反射した光を受光した液体検知部２０ａの出力信号レベルを測定する。 The arrival determination unit 412 causes the liquid detection unit 20a to emit light and measures the output signal level of the liquid detection unit 20a that has received the light reflected from the liquid reservoir of the a channel.
　Ｓ１０２：受光レベルと閾値とを比較するステップである。 S102: This is a step of comparing the light reception level with the threshold value.
　到達判定部４１２は、液体検知部２０ａの受光レベルに比例する出力信号レベルと、ステップＳ２０１でキャリブレーションを行ったときに求めた閾値と比較し、出力信号レベル＜閾値か、否か、を判定する。 The arrival determination unit 412 compares the output signal level proportional to the light reception level of the liquid detection unit 20a with the threshold value obtained when the calibration is performed in step S201, and determines whether or not the output signal level <the threshold value. To do.
　受光レベル＜閾値の場合、（ステップＳ１０２；Ｙｅｓ）、ステップＳ１０３に進む。 If received light level <threshold (step S102; Yes), the process proceeds to step S103.
　Ｓ１０３：ａチャンネルのポンプを停止するステップである。 S103: This is a step of stopping the pump of the a channel.
　ポンプ駆動制御部４１１は、ａチャンネルのポンプを停止する。ａチャンネルの液溜部に液体の先頭部分が到達すると液溜部１４０ａには液体が充填され受光信号レベル＜閾値になる。この状態を検出するとポンプ駆動制御部４１１は、ａチャンネルのポンプを停止し、ｂチャンネルと流路を流れる液体の先頭の位置を揃える。 The pump drive control unit 411 stops the pump of the a channel. When the leading portion of the liquid reaches the liquid reservoir of the a channel, the liquid reservoir 140a is filled with the liquid, and the light receiving signal level <threshold. When this state is detected, the pump drive control unit 411 stops the pump of the a channel and aligns the positions of the liquid channel flowing through the channel with the b channel.
　受光信号レベル≧閾値の場合、（ステップＳ１０２；Ｎｏ）、ステップＳ１０４に進む。 If the received light signal level ≧ the threshold value (step S102; No), the process proceeds to step S104.
　Ｓ１０４：ｂチャンネルの液溜部からの反射光を測定するステップである。 S104: This is a step of measuring the reflected light from the liquid reservoir of the b channel.
　到達判定部４１２は、液体検知部２０ｂを発光させ、ｂチャンネルの液溜部から反射した光を受光した液体検知部２０ｂの出力信号レベルを測定する。 The arrival determination unit 412 causes the liquid detection unit 20b to emit light and measures the output signal level of the liquid detection unit 20b that has received the light reflected from the b channel liquid reservoir.
　Ｓ１０５：受光レベルと閾値とを比較するステップである。 S105: This is a step of comparing the light reception level with the threshold value.
　到達判定部４１２は、液体検知部２０ｂの受光レベルに比例する出力信号レベルと、ステップＳ２０１でキャリブレーションを行ったときに求めた閾値と比較し、受光レベル＜閾値か、否か、を判定する。 The arrival determination unit 412 compares the output signal level proportional to the light reception level of the liquid detection unit 20b with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level <the threshold. .
　受光信号レベル＜閾値の場合、（ステップＳ１０５；Ｙｅｓ）、ステップＳ１０６に進む。 If the received light signal level <the threshold value (step S105; Yes), the process proceeds to step S106.
　Ｓ１０６：ｂチャンネルのポンプを停止するステップである。 S106: This is a step of stopping the pump of the b channel.
　ポンプ駆動制御部４１１は、ｂチャンネルのポンプを停止する。ｂチャンネルの液溜部に液体の先頭部分が到達するとｂチャンネルの液溜部には液体が充填され出力信号レベル＜閾値になる。この状態を検出するとポンプ駆動制御部４１１は、ｂチャンネルのポンプを停止し、ａチャンネルと流路を流れる液体の先頭の位置を揃える。 The pump drive control unit 411 stops the b-channel pump. When the leading portion of the liquid reaches the liquid reservoir of the b channel, the liquid reservoir of the b channel is filled with the liquid, and the output signal level <threshold. When this state is detected, the pump drive control unit 411 stops the b-channel pump, and aligns the leading positions of the liquid flowing through the a-channel and the flow path.
　出力信号レベル≧閾値の場合、（ステップＳ１０５；Ｎｏ）、ステップＳ１０７に進む。 If output signal level ≧ threshold (step S105; No), the process proceeds to step S107.
　Ｓ１０７：ａ、ｂ両チャンネルのポンプが停止したか、否か、を判定するステップである。 S107: A step of determining whether or not the pumps of both the channels a and b are stopped.
　ポンプ駆動制御部４１１は、ａ、ｂ両チャンネルのポンプが停止したか、否か、を判定する。 The pump drive control unit 411 determines whether or not the pumps of both channels a and b are stopped.
　ａ、ｂ両チャンネルのポンプが停止した場合、（ステップＳ１０７；Ｙｅｓ）、処理を終了し元のルーチンに戻る。 When the pumps of both channels a and b are stopped (step S107; Yes), the process is terminated and the process returns to the original routine.
　ａまたはｂチャンネルのポンプが停止していない場合、（ステップＳ１０７；Ｎｏ）、ステップＳ１０８に進む。 If the a or b channel pump is not stopped (step S107; No), the process proceeds to step S108.
　Ｓ１０８：タイムアウトか、否か、を判定するステップである。 S108: This is a step of determining whether it is time-out or not.
　ＣＰＵ９８は、内部タイマーから経過時間を読み取り、タイムアウトの時間を経過したか、否か、を判定する。 The CPU 98 reads the elapsed time from the internal timer and determines whether or not the timeout time has elapsed.
　タイムアウトの場合、（ステップＳ１０８；Ｙｅｓ）、ステップＳ１０９に進む。 In the case of timeout (step S108; Yes), the process proceeds to step S109.
　Ｓ１０９：エラーフラッグを１にするステップである。 S109: This is a step of setting the error flag to 1.
　ＣＰＵ９８は、エラーフラッグを１にして元のルーチンに戻る。 CPU 98 sets the error flag to 1 and returns to the original routine.
　タイムアウトではない場合、（ステップＳ１０８；Ｎｏ）、ステップＳ１０１に戻る。 If it is not time-out (step S108; No), the process returns to step S101.
　タイムアウトでない場合は、処理を継続し液溜部に液体が到達するのを待つ。 If not timed out, continue processing and wait for liquid to reach the reservoir.
　液到達ルーチンの説明は以上である。 This completes the explanation of the liquid arrival routine.
　次に、反応測定ルーチンについて図１０のフローチャートの順に説明する。 Next, the reaction measurement routine will be described in the order of the flowchart of FIG.
　Ｓ３０１：検出ユニット２２を移動するステップである。 S301: This is a step of moving the detection unit 22.
　検出ユニット駆動制御部４１３は、検出ユニット駆動モータ６１に所定の数のパルスを送り図４の矢印Ｓ２方向に検出ユニット２２を移動させ、検出ユニット２２が検出部１１１ａの反応結果を検出する位置に停止させる。 The detection unit drive control unit 413 sends a predetermined number of pulses to the detection unit drive motor 61 to move the detection unit 22 in the direction of the arrow S2 in FIG. 4, and the detection unit 22 detects the reaction result of the detection unit 111a. Stop.
　Ｓ３０２：反応結果を測定するステップである。 S302: This is a step of measuring the reaction result.
　所定の時間経過後、ＣＰＵ９８は、検出ユニット２２の発光部を発光させ、検出ユニット２２からの出力信号レベルを測定し、結果をＲＡＭ９７に記憶する。 After a predetermined time has elapsed, the CPU 98 causes the light emitting unit of the detection unit 22 to emit light, measures the output signal level from the detection unit 22, and stores the result in the RAM 97.
　Ｓ３０３：検出ユニット２２を移動するステップである。 S303: This is a step of moving the detection unit 22.
　検出ユニット駆動制御部４１３は、検出ユニット駆動検出ユニット駆動モータ６１に所定の数のパルスを送り図４の矢印Ｓ２方向に検出ユニット２２をさらに移動させ、検出部１１１ｂの反応結果を検出する位置に停止させる。 The detection unit drive control unit 413 sends a predetermined number of pulses to the detection unit drive detection unit drive motor 61 to further move the detection unit 22 in the direction of the arrow S2 in FIG. 4, and to a position where the detection result of the detection unit 111b is detected. Stop.
　Ｓ３０４：反応結果を測定するステップである。 S304: This is a step of measuring the reaction result.
　ＣＰＵ９８は、検出ユニット２２の発光部を発光させ、検出ユニット２２からの出力信号レベルを測定し、結果をＲＡＭ９７に記憶する。 The CPU 98 causes the light emitting unit of the detection unit 22 to emit light, measures the output signal level from the detection unit 22, and stores the result in the RAM 97.
　以上検査を終了し、検出ユニット駆動制御部４１３は、検出ユニット２２を初期位置に戻す。 The inspection is finished as described above, and the detection unit drive control unit 413 returns the detection unit 22 to the initial position.
　反応測定ルーチンの手順の説明は以上である。 This completes the explanation of the procedure for the reaction measurement routine.
　次に、図１１、図１２を用いて第２の実施形態について説明する。第２の実施形態ではシリンジポンプを用いて気体をマイクロチップの流路に注入し、検体と試薬を送液する例を説明する。第１の実施形態と送液方法の異なる点を中心に説明し、第１の実施形態と共通する部分については説明を省略する。 Next, a second embodiment will be described with reference to FIGS. In the second embodiment, an example will be described in which a syringe is used to inject a gas into a microchip flow path, and a specimen and a reagent are fed. The difference between the first embodiment and the liquid feeding method will be mainly described, and the description of the parts common to the first embodiment will be omitted.
　図１１は本発明の第２の実施形態におけるマイクロチップ１の外観図である。第２の実施形態では注入口１１０ａ、１１０ｂから空気を注入し、検体や試薬を送液する。 FIG. 11 is an external view of the microchip 1 according to the second embodiment of the present invention. In the second embodiment, air is injected from the inlets 110a and 110b, and a specimen and a reagent are fed.
　マイクロチップ１の流路の第１の実施形態と異なる点は、液溜部１４２ａ、１４２ｂが試薬収容部１２３ａ、１２３ｂの近傍の下流側に設けられている点である。液溜部１４２ａ、１４２ｂを利用した送液制御について後に説明する。 The difference of the flow path of the microchip 1 from the first embodiment is that the liquid reservoirs 142a and 142b are provided on the downstream side in the vicinity of the reagent storage units 123a and 123b. Liquid feed control using the liquid reservoirs 142a and 142b will be described later.
　図１２は本発明の第２の実施形態における検出装置８０のブロック図である。図１２では第１の実施形態と異なる点を中心に図示し、図を簡略化している。 FIG. 12 is a block diagram of the detection apparatus 80 in the second embodiment of the present invention. In FIG. 12, the difference from the first embodiment is mainly illustrated, and the drawing is simplified.
　１０はシリンジポンプ、１１はシリンジポンプ１０を駆動するドライバである。三方弁２５は制御部９９からの制御信号により、配管１５と配管１６とを連通させるか、または配管１６と一端が大気側に開放されている配管５０に連通させるか、を切り替える切替弁を有している。シリンジポンプ１０は、配管１５と配管１６が連通した状態でパッキン６を介してマイクロチップ１に空気を注入する。注入口１１０ａ、１１０ｂにはそれぞれ配管１５、三方弁２５、シリンジポンプ１０、ドライバ１１などからなる空気注入機構が接続されておりそれぞれ独立して制御できるが、本実施形態では一つのチャンネルの制御について説明する。 10 is a syringe pump, and 11 is a driver for driving the syringe pump 10. The three-way valve 25 has a switching valve that switches between communication between the pipe 15 and the pipe 16 or communication between the pipe 16 and the pipe 50 whose one end is open to the atmosphere side by a control signal from the control unit 99. is doing. The syringe pump 10 injects air into the microchip 1 through the packing 6 with the pipe 15 and the pipe 16 communicating with each other. The inlets 110a and 110b are connected to an air injection mechanism including a pipe 15, a three-way valve 25, a syringe pump 10, a driver 11, and the like, and can be controlled independently. In this embodiment, one channel is controlled. explain.
　第２の実施形態では、液体検知部が検査装置８０の各液溜部に対応する位置に配置されている例を説明する。液体検知部２６は液溜部１４２に対応する位置に、液体検知部２７は液溜部１４０に対応する位置に、液体検知部２８は液溜部１４１に対応する位置にそれぞれ配置されている。液体検知部２６、液体検知部２７、液体検知部２８もａ、ｂチャンネルにそれぞれ配置されている。 2nd Embodiment demonstrates the example by which the liquid detection part is arrange | positioned in the position corresponding to each liquid reservoir part of the test | inspection apparatus 80. FIG. The liquid detector 26 is disposed at a position corresponding to the liquid reservoir 142, the liquid detector 27 is disposed at a position corresponding to the liquid reservoir 140, and the liquid detector 28 is disposed at a position corresponding to the liquid reservoir 141. The liquid detection unit 26, the liquid detection unit 27, and the liquid detection unit 28 are also arranged in the a and b channels, respectively.
　次に、本発明の第２の実施形態の検査装置８０が検査を行う手順を図１３を用いて説明する。 Next, the procedure in which the inspection apparatus 80 according to the second embodiment of the present invention performs an inspection will be described with reference to FIG.
　図１３は第２の実施形態の検査装置８０が検査を行うメインルーチンを説明するフローチャート、図１４は第２の実施形態の送液制御を説明するためのタイムチャートである。図１４（ａ）はドライバ１１の出力する駆動パルスレートＰのタイムチャートである。図１４（ｂ）は液体検知部２６の出力のタイムチャート、図１４（ｃ）は液体検知部２７の出力のタイムチャート、図１４（ｄ）は液体検知部２８の出力のタイムチャートである。図１４（ｅ）は流路を流れる液体の流量Ｑのタイムチャートである。 FIG. 13 is a flowchart for explaining a main routine in which the inspection apparatus 80 of the second embodiment performs an inspection, and FIG. 14 is a time chart for explaining the liquid feeding control of the second embodiment. FIG. 14A is a time chart of the drive pulse rate P output from the driver 11. 14B is a time chart of the output of the liquid detection unit 26, FIG. 14C is a time chart of the output of the liquid detection unit 27, and FIG. 14D is a time chart of the output of the liquid detection unit 28. FIG. 14E is a time chart of the flow rate Q of the liquid flowing through the flow path.
　図１４のタイムチャートを参照しながら図１３のフローチャートの順に検査の概略の手順を説明する。 Referring to the time chart of FIG. 14, the outline procedure of the inspection will be described in the order of the flowchart of FIG.
　マイクロチップ１は、図１２のように検査が可能な位置にセットされ、操作部８７の操作によってＣＰＵに検査の開始が指令されているものとする。 Suppose that the microchip 1 is set at a position where inspection can be performed as shown in FIG. 12, and the start of inspection is instructed to the CPU by operation of the operation unit 87.
　Ｓ２０１：キャリブレーションを行うステップである。 S201: This is a step for performing calibration.
　到達判定部４１２は、液体検知部２６、液体検知部２７、液体検知部２８を発光させ、液溜部１４０、液溜部１４１、液溜部１４２から反射した光を液体検知部２６、液体検知部２７、液体検知部２８がそれぞれ検出した出力信号を、所定の信号レベルと比較する。所定の信号レベルの範囲で無い場合、到達判定部４１２は液体検知部２６、液体検知部２７、液体検知部２８の発光部に流す電流を増加または減少させて所定の信号レベルの範囲になるようキャリブレーションを行う。到達判定部４１２は、液体検知部２６、液体検知部２７、液体検知部２８の出力信号がそれぞれ所定の信号レベルの範囲になると、そのときの出力電圧を基に液体の到達を判定する閾値を決定しＲＡＭ９７に記憶する。また、エラーフラッグを初期化し値を０にする。 The arrival determination unit 412 causes the liquid detection unit 26, the liquid detection unit 27, and the liquid detection unit 28 to emit light, and reflects light reflected from the liquid storage unit 140, the liquid storage unit 141, and the liquid storage unit 142. The output signals detected by the unit 27 and the liquid detection unit 28 are compared with predetermined signal levels. When it is not within the predetermined signal level range, the arrival determination unit 412 increases or decreases the current flowing through the light emitting units of the liquid detection unit 26, the liquid detection unit 27, and the liquid detection unit 28 so as to be within the predetermined signal level range. Perform calibration. When the output signals of the liquid detection unit 26, the liquid detection unit 27, and the liquid detection unit 28 are in a predetermined signal level range, the arrival determination unit 412 sets a threshold value for determining the arrival of the liquid based on the output voltage at that time. Determine and store in RAM 97. Also, the error flag is initialized and the value is set to zero.
　Ｓ４０１：ポンプを速度Ａで吐出方向に駆動するステップである。 S401: A step of driving the pump in the discharge direction at a speed A.
　ポンプ駆動制御部４１１はドライバ１１に指令し、図１４（ａ）に示すように駆動パルスレートＡで吐出方向にシリンジポンプ１０を駆動する。すると、図１４（ｅ）に示すようにシリンジポンプ１０の駆動を開始してもしばらく流量は０であるが、しばらくすると急に大きな流量で流れ始める。 The pump drive control unit 411 instructs the driver 11 to drive the syringe pump 10 in the discharge direction at the drive pulse rate A as shown in FIG. Then, as shown in FIG. 14 (e), the flow rate is 0 for a while even after starting to drive the syringe pump 10, but suddenly starts to flow at a large flow rate after a while.
　Ｓ４０２：液溜部１４２の反射光を測定するステップである。 S402: This is a step of measuring the reflected light of the liquid reservoir 142.
　液体検知部２６は液溜部１４２の反射光を測定する。 The liquid detector 26 measures the reflected light from the liquid reservoir 142.
　Ｓ４０３：受光レベルと閾値とを比較するステップである。 S403: This is a step of comparing the received light level with the threshold value.
　到達判定部４１２は、液体検知部２６の受光レベルに比例する出力信号レベルと、ステップＳ２０１でキャリブレーションを行ったときに求めた閾値と比較し、受光レベル＜閾値か、否か、を判定する。 The arrival determination unit 412 compares the output signal level proportional to the light reception level of the liquid detection unit 26 with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level <the threshold. .
　受光レベル≧閾値の場合、（ステップＳ４０３；Ｎｏ）、ステップＳ４０２に戻る。 If the received light level ≧ the threshold value (step S403; No), the process returns to step S402.
　受光レベル＜閾値の場合、（ステップＳ４０３；Ｙｅｓ）、ステップＳ４０４に進む。 If the light reception level <the threshold value (step S403; Yes), the process proceeds to step S404.
　Ｓ４０４：ポンプを停止するステップである。 S404: This is a step of stopping the pump.
　ポンプ駆動制御部４１１は、シリンジポンプ１０を停止する。液溜部１４２に液体の先頭部分が到達すると液溜部１４２には液体が充填され受光レベル＜閾値になる。図１４（ａ）のｔ１でこの状態を検出するとポンプ駆動制御部４１１は、シリンジポンプ１０を停止する。 The pump drive control unit 411 stops the syringe pump 10. When the leading portion of the liquid reaches the liquid reservoir 142, the liquid reservoir 142 is filled with the liquid and the light receiving level <threshold. When this state is detected at t <b> 1 in FIG. 14A, the pump drive control unit 411 stops the syringe pump 10.
　Ｓ４０５：所定時間待つステップである。 S405: A step of waiting for a predetermined time.
　ポンプ駆動制御部４１１は、シリンジポンプ１０を停止して所定時間待機する。このことにより、シリンジポンプ１０を駆動するパルスモータの脱調を防止することができる。図１４（ａ）のｔ１～ｔ２の期間が待機時間である。 The pump drive control unit 411 stops the syringe pump 10 and waits for a predetermined time. Thereby, the step-out of the pulse motor that drives the syringe pump 10 can be prevented. The period from t1 to t2 in FIG. 14A is the standby time.
　Ｓ４０６：ポンプを速度Ｂで吸引方向に駆動するステップである。 S406: This is a step of driving the pump at the speed B in the suction direction.
　ポンプ駆動制御部４１１はドライバ１１に指令し、図１４（ａ）のｔ２からｔ３まで駆動パルスレートＢで吸引方向にシリンジポンプ１０を駆動する。このことにより流路内の圧力を下げ流量が急激に増えないようにするので、図１４（ｅ）のように所定の範囲内の流量を得ることができる。 The pump drive control unit 411 instructs the driver 11 to drive the syringe pump 10 in the suction direction at the drive pulse rate B from t2 to t3 in FIG. As a result, the pressure in the flow path is lowered so that the flow rate does not increase rapidly, so that a flow rate within a predetermined range can be obtained as shown in FIG.
　Ｓ４０７：所定時間待つステップである。 S407: This is a step of waiting for a predetermined time.
　ポンプ駆動制御部４１１は、シリンジポンプ１０を駆動するパルスモータの脱調を防止するためシリンジポンプ１０を停止して所定時間待機する。図１４（ａ）のｔ３～ｔ４の期間が待機時間である。 The pump drive control unit 411 stops the syringe pump 10 and waits for a predetermined time in order to prevent the pulse motor that drives the syringe pump 10 from stepping out. The period from t3 to t4 in FIG. 14A is the standby time.
　Ｓ４０８：ポンプを速度Ｃで吐出方向に駆動するステップである。 S408: This is a step of driving the pump at the speed C in the discharge direction.
　ポンプ駆動制御部４１１はドライバ１１に指令し、ｔ４から駆動パルスレートＣで吐出方向にシリンジポンプ１０を駆動する。この期間は比較的低いパルスレートＣで駆動するので、図１４（ｅ）に示すように所定の安定した流量が得られる。 The pump drive control unit 411 instructs the driver 11 to drive the syringe pump 10 in the discharge direction at the drive pulse rate C from t4. Since this period is driven at a relatively low pulse rate C, a predetermined stable flow rate can be obtained as shown in FIG.
　Ｓ４０９：液溜部１４０の反射光を測定するステップである。 S409: A step of measuring the reflected light of the liquid reservoir 140.
　液体検知部２７は液溜部１４０の反射光を測定する。 The liquid detector 27 measures the reflected light of the liquid reservoir 140.
　Ｓ４１０：受光レベルと閾値とを比較するステップである。 S410: This is a step of comparing the light reception level with the threshold value.
　到達判定部４１２は、液体検知部２７の受光レベルに比例する出力信号レベルと、ステップＳ２０１でキャリブレーションを行ったときに求めた閾値と比較し、受光レベル＜閾値か、否か、を判定する。 The arrival determination unit 412 compares the output signal level proportional to the light reception level of the liquid detection unit 27 with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level <the threshold. .
　受光レベル≧閾値の場合、（ステップＳ４１０；Ｎｏ）、ステップＳ４０９に戻る。 If the received light level ≧ the threshold value (step S410; No), the process returns to step S409.
　受光レベル＜閾値の場合、（ステップＳ４１０；Ｙｅｓ）、ステップＳ４１１に進む。 If the received light level <the threshold value (step S410; Yes), the process proceeds to step S411.
　Ｓ４１１：ポンプを速度Ｄで吐出方向に駆動するステップである。 S411: This is a step of driving the pump in the discharge direction at a speed D.
　ポンプ駆動制御部４１１はドライバ１１に指令し、ｔ５から駆動パルスレートＤで吐出方向にシリンジポンプ１０を駆動する。液溜部１４０まで液体が到達した後は、さらに低い駆動パルスレートＤで駆動し、図１４（ｅ）に示すように少ない流量で液体を駆動するようにする。このことにより混合部１３０、混合部１３１で泡の発生を抑えることができる。 The pump drive control unit 411 instructs the driver 11 to drive the syringe pump 10 in the discharge direction at the drive pulse rate D from t5. After the liquid reaches the liquid reservoir 140, the liquid is driven at a lower driving pulse rate D, and the liquid is driven at a small flow rate as shown in FIG. As a result, the generation of bubbles can be suppressed in the mixing unit 130 and the mixing unit 131.
　Ｓ４１２：液溜部１４１の反射光を測定するステップである。 S412: This is a step of measuring the reflected light of the liquid reservoir 141.
　液体検知部２８は液溜部１４１の反射光を測定する。 The liquid detector 28 measures the reflected light of the liquid reservoir 141.
　Ｓ４１３：受光レベルと閾値とを比較するステップである。 S413: This is a step of comparing the received light level with the threshold value.
　到達判定部４１２は、液体検知部２８の受光レベルに比例する出力信号レベルと、ステップＳ２０１でキャリブレーションを行ったときに求めた閾値と比較し、受光レベル＜閾値か、否か、を判定する。 The arrival determination unit 412 compares the output signal level proportional to the light reception level of the liquid detection unit 28 with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level <the threshold. .
　受光レベル≧閾値の場合、（ステップＳ４１３；Ｎｏ）、ステップＳ４１４に進む。 If the received light level ≧ the threshold value (step S413; No), the process proceeds to step S414.
　Ｓ４１４：時間オーバーを判定するステップである。 S414: This is a step of determining time over.
　ＣＰＵ９８は、所定の時間までに液体が液溜部１４１に到達しない場合はエラーと判定し処理を終了する。 When the liquid does not reach the liquid reservoir 141 by a predetermined time, the CPU 98 determines that an error has occurred and ends the process.
　時間オーバーの場合、（ステップＳ４１４；Ｙｅｓ）、終了する。 If the time is over (step S414; Yes), the process ends.
　時間オーバーではない場合、（ステップＳ４１４；Ｎｏ）、ステップＳ４１２に戻る。 If the time is not over (step S414; No), the process returns to step S412.
　受光レベル＜閾値の場合、（ステップＳ４１３；Ｙｅｓ）、ステップＳ４１５に進む。 If received light level <threshold (step S413; Yes), the process proceeds to step S415.
　Ｓ４１５：ポンプを停止するステップである。 S415: This is a step of stopping the pump.
　ポンプ駆動制御部４１１は、シリンジポンプ１０を停止する。液溜部１４１に液体の先頭部分が到達すると液溜部１４１には液体が充填され受光レベル＜閾値になる。図１４（ａ）のｔ６でこの状態を検出するとポンプ駆動制御部４１１は、シリンジポンプ１０を停止する。 The pump drive control unit 411 stops the syringe pump 10. When the leading portion of the liquid reaches the liquid reservoir 141, the liquid reservoir 141 is filled with the liquid, and the light receiving level <threshold. When this state is detected at t <b> 6 in FIG. 14A, the pump drive control unit 411 stops the syringe pump 10.
　Ｓ４１６：三方弁を大気方向に切り替えるステップである。 S416: This is a step of switching the three-way valve to the atmospheric direction.
　ポンプ駆動制御部４１１は、三方弁２５の内部の切替弁を配管１６と一端が大気側に開放されている配管５０が連通するように切り替える。このことにより、マイクロチップ１の流路に加わっている気体の圧力を大気中に開放し、液体が移動しないようにすることができる。 The pump drive control unit 411 switches the switching valve inside the three-way valve 25 so that the pipe 16 communicates with the pipe 50 whose one end is open to the atmosphere side. As a result, the pressure of the gas applied to the flow path of the microchip 1 can be released to the atmosphere, and the liquid can be prevented from moving.
　Ｓ４１７：微小時間待つステップである。 S417: This is a step of waiting for a minute time.
　ポンプ駆動制御部４１１は、微小時間待機する。 The pump drive control unit 411 waits for a minute time.
　Ｓ４１８：三方弁２５を配管１５と配管１６が連通するように切り替えるステップである。 S418: This is a step of switching the three-way valve 25 so that the pipe 15 and the pipe 16 communicate with each other.
　ポンプ駆動制御部４１１は、三方弁２５の内部の切替弁を配管１５と配管１６が連通するように切り替える。 The pump drive control unit 411 switches the switching valve inside the three-way valve 25 so that the pipe 15 and the pipe 16 communicate with each other.
　Ｓ４１９：増幅反応の処理を開始するステップである。 S419: This is a step for starting the amplification reaction process.
　ＣＰＵ９８は、温度調節ユニット１５２に所定の温度に加熱するように指令する。 CPU 98 instructs temperature adjustment unit 152 to heat to a predetermined temperature.
　Ｓ４２０：液溜部１４１の反射光を測定するステップである。 S420: This is a step of measuring the reflected light of the liquid reservoir 141.
　液体検知部２８は液溜部１４１の反射光を測定する。ステップＳ４１９で温度調節ユニット１５２によって加熱が開始されると、液体を駆動する気体が膨張し液体の先頭部分が液溜部１４１より下流に押し出されることがある。これを防止するため本ステップで液溜部１４１の反射光を測定し、以下のステップにより液体の先頭部分を液溜部１４１で検知できなくなるまで後退させる。 The liquid detector 28 measures the reflected light of the liquid reservoir 141. When heating is started by the temperature adjustment unit 152 in step S419, the gas that drives the liquid may expand, and the leading portion of the liquid may be pushed downstream from the liquid reservoir 141. In order to prevent this, the reflected light of the liquid reservoir 141 is measured in this step, and the head portion of the liquid is moved backward until it cannot be detected by the liquid reservoir 141 in the following steps.
　Ｓ４２１：受光レベルと閾値とを比較するステップである。 S421: This is a step of comparing the received light level with a threshold value.
　到達判定部４１２は、液体検知部２８の受光レベルに比例する出力信号レベルと、ステップＳ２０１でキャリブレーションを行ったときに求めた閾値と比較し、受光レベル＜閾値か、否か、を判定する。 The arrival determination unit 412 compares the output signal level proportional to the light reception level of the liquid detection unit 28 with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level <the threshold. .
　受光レベル≧閾値の場合、（ステップＳ４２１；Ｎｏ）、ステップＳ４２５に進む。 If received light level ≧ threshold (step S421; No), the process proceeds to step S425.
　受光レベル＜閾値の場合、（ステップＳ４２１；Ｙｅｓ）、ステップＳ４２２に進む。 If the light reception level <the threshold value (step S421; Yes), the process proceeds to step S422.
　Ｓ４２２：ポンプを速度Ｅで吸引方向に駆動するステップである。 S422: This is a step of driving the pump in the suction direction at a speed E.
　ポンプ駆動制御部４１１はドライバ１１に指令し、駆動パルスレートＥで吸引方向にシリンジポンプ１０を駆動する。 The pump drive control unit 411 instructs the driver 11 to drive the syringe pump 10 in the suction direction at the drive pulse rate E.
　Ｓ４２３：所定時間待つステップである。 S423: This is a step of waiting for a predetermined time.
　ポンプ駆動制御部４１１は、所定時間待機する。 The pump drive control unit 411 waits for a predetermined time.
　Ｓ４２４：ポンプを停止するステップである。 S424: This is a step of stopping the pump.
　ポンプ駆動制御部４１１は、シリンジポンプ１０を停止する。 The pump drive control unit 411 stops the syringe pump 10.
　Ｓ４２５：増幅反応の時間が終了したか、否か、を判定するステップである。 S425: This is a step of determining whether or not the amplification reaction time has ended.
　ＣＰＵ９８は、所定の増幅反応の時間が終了したか、否か、を判定する。 CPU 98 determines whether or not the predetermined amplification reaction time has ended.
　増幅反応の時間が終了していない場合、（ステップＳ４２５；Ｎｏ）、ステップＳ４２０に戻る。増幅反応の間、図１４の例では図１４（ａ）のｔ７、ｔ８、ｔ９で示すタイミングで所定時間シリンジポンプ１０を吸引方向に駆動し、図１４（ｄ）のように液溜部１４１で液体が検知できなくなるまで液体の先頭位置を後退させている。 If the amplification reaction time has not ended (step S425; No), the process returns to step S420. During the amplification reaction, in the example of FIG. 14, the syringe pump 10 is driven in the suction direction for a predetermined time at timings indicated by t7, t8, and t9 in FIG. The leading position of the liquid is retracted until the liquid can no longer be detected.
　増幅反応の時間が終了した場合、（ステップＳ４２５；Ｙｅｓ）、ステップＳ２１３に進む。 If the amplification reaction time has ended (step S425; Yes), the process proceeds to step S213.
　Ｓ２１３：反応結果を測定するステップである。 S213: This is a step of measuring the reaction result.
　所定の時間経過後、ＣＰＵ９８は反応測定ルーチンをコールし、検出部１１１ａ、検出部１１１ｂから反応結果を測定する。 After a predetermined time has elapsed, the CPU 98 calls a reaction measurement routine and measures the reaction result from the detection unit 111a and the detection unit 111b.
　第２の実施形態のメインルーチンの説明は以上である。 This completes the description of the main routine of the second embodiment.
　次に、本発明の第３の実施形態に係わるマイクロチップ１の一例について、図１５を用いて説明する。 Next, an example of the microchip 1 according to the third embodiment of the present invention will be described with reference to FIG.
　図１５は本発明の第３の実施形態におけるマイクロチップ１の外観図である。 FIG. 15 is an external view of the microchip 1 according to the third embodiment of the present invention.
　第３の実施形態で用いるマイクロチップ１は、検体を注入する検体注入口１５６と検体を分割定量する分割定量部１５１を有し、検体注入口１５６から注入した検体を分割定量して検査を行うことができる。それ以外の構成は、第１の実施形態、第２の実施形態で説明したマイクロチップ１とほとんど同じであり、同じ構成要素には同番号を付し説明を省略する。 The microchip 1 used in the third embodiment has a sample injection port 156 for injecting a sample and a division quantification unit 151 for dividing and quantifying the sample, and performs a test by dividing and quantifying the sample injected from the sample injection port 156. be able to. Other configurations are almost the same as those of the microchip 1 described in the first embodiment and the second embodiment, and the same components are denoted by the same reference numerals and description thereof is omitted.
　図１５はマイクロチップ１の平面図であり、透明な被覆基板１０９を通して見える溝形成基板１０８の溝を図示している。 FIG. 15 is a plan view of the microchip 1, and illustrates the grooves of the groove forming substrate 108 that can be seen through the transparent coated substrate 109.
　図１５の４１０ｅ、４１０ｆ、４１０ｇ、４１０ｈはマイクロチップ１内部の流路に連通する吸引口であり、各吸引口４１０から空気を吸入し内部の検体や試薬等を駆動する。本実施形態のマイクロチップ１では図１５に示すように注入口４１０ｆから始まる流路の構成と、吸入口４１０ｇから始まる流路の構成は全く同じであり、以降ｆチャンネル、ｇチャンネルと呼び区別する。また、各構成要素にはｆ、ｇを付けて区別する。吸引口４１０ｅから始まる流路は余分な検体を流すダミー流路２５１ｅである。また、吸引口４１０ｈから始まる流路も検体を吸引するために設けられたダミー流路２５１ｈである。ダミー流路２５１ｈと分割定量部１５１の間に液溜部１４４が設けられている。 In FIG. 15, 410e, 410f, 410g, and 410h are suction ports that communicate with the flow path inside the microchip 1, and inhale air from each suction port 410 to drive the specimens, reagents, and the like inside. In the microchip 1 of the present embodiment, as shown in FIG. 15, the configuration of the flow path starting from the injection port 410f and the configuration of the flow path starting from the suction port 410g are exactly the same, and are hereinafter referred to as f channel and g channel. . Each component is distinguished by adding f and g. A flow path starting from the suction port 410e is a dummy flow path 251e through which an extra specimen flows. The flow path starting from the suction port 410h is also a dummy flow path 251h provided for sucking the specimen. A liquid reservoir 144 is provided between the dummy channel 251h and the divided quantification unit 151.
　１５５ｆ、１５５ｇは分割定量部１５１から検体を分割して送る分割流路である。分割流路１５５ｆ、１５５ｇの下流には液溜部１４７ｆ、１４７ｇ設けられている。 155f and 155g are divided flow paths for dividing and sending the sample from the divided quantification unit 151. Liquid reservoirs 147f and 147g are provided downstream of the divided flow paths 155f and 155g.
　１２０ｆ、１２０ｇは第１の試薬を収容する試薬収容部、１２２ｆ、１２２ｇは第２の試薬を収容する試薬収容部、１２３ｆ、１２３ｇは第３の試薬を収容する試薬収容部である。試薬収容部１２３ｆ、１２３ｇの下流には混合部１３０ｆ、混合部１３０ｇと混合部１３１ｆ、混合部１３１ｇが設けられており、検体、第１の試薬、第２の試薬、第３の試薬は各混合部で混合される。 120f and 120g are reagent storage units for storing the first reagent, 122f and 122g are reagent storage units for storing the second reagent, and 123f and 123g are reagent storage units for storing the third reagent. A mixing unit 130f, a mixing unit 130g, a mixing unit 131f, and a mixing unit 131g are provided downstream of the reagent storage units 123f and 123g, and the sample, the first reagent, the second reagent, and the third reagent are mixed. Mixed in parts.
　混合部１３０ｆ、混合部１３０ｇと混合部１３１ｆ、混合部１３１ｇで混合された検体、第１の試薬、第２の試薬、第３の試薬は検出部１１１ｆ、１１１ｇに注入される。第１、第２の実施形態と同様の手順で、検査装置８０の内部で検出部１１１ｆ、１１１ｇを加熱して所定の温度で検体と試薬とを所定の時間反応させる。 The mixing unit 130f, the mixing unit 130g and the mixing unit 131f, and the specimen, the first reagent, the second reagent, and the third reagent mixed in the mixing unit 131g are injected into the detection units 111f and 111g. In the same procedure as in the first and second embodiments, the detection units 111f and 111g are heated inside the inspection apparatus 80, and the specimen and the reagent are reacted at a predetermined temperature for a predetermined time.
　検出部１１１ｆ、１１１ｇの下流には液溜部１４１ｆ、１４１ｇが設けられており、検出部１１１ｆ、１１１ｇが試薬や検体などの液体で充填されたことを検出できるようになっている。 Liquid reservoirs 141f and 141g are provided downstream of the detection units 111f and 111g so that it can be detected that the detection units 111f and 111g are filled with a liquid such as a reagent or a specimen.
　図１６は本発明の第３の実施形態における検出装置８０のブロック図である。図１６では第１の実施形態と異なる点を中心に図示し、図を簡略化している。第２の実施形態における検出装置８０のブロック図と同様の構成であるが、三方弁２５の一方の流路は分岐配管１７により４つに分岐し、バルブ５８ｅ、５８ｆ、５８ｇ、５８ｈと接続されている。バルブ５８ｅ、５８ｆ、５８ｇ、５８ｈは配管１８ｅ、１８ｆ、１８ｇ、１８ｈと接続されており、吸引口４１０ｅ、４１０ｆ、４１０ｇ、４１０ｈと連通している。バルブ５８ｅ、５８ｆ、５８ｇ、５８ｈは制御部９９からの制御信号によりシリンジポンプ１０と吸引口４１０ｅ、４１０ｆ、４１０ｇ、４１０ｈとの流路をそれぞれ開閉する。 FIG. 16 is a block diagram of a detection apparatus 80 according to the third embodiment of the present invention. In FIG. 16, the difference from the first embodiment is mainly shown, and the drawing is simplified. Although it is the same structure as the block diagram of the detection apparatus 80 in 2nd Embodiment, one flow path of the three-way valve 25 branches into four by the branch piping 17, and is connected with valve 58e, 58f, 58g, 58h. ing. The valves 58e, 58f, 58g, and 58h are connected to the pipes 18e, 18f, 18g, and 18h, and communicate with the suction ports 410e, 410f, 410g, and 410h. The valves 58e, 58f, 58g, and 58h open and close the flow paths between the syringe pump 10 and the suction ports 410e, 410f, 410g, and 410h, respectively, according to a control signal from the control unit 99.
　１０はシリンジポンプ、１１はシリンジポンプ１０を駆動するドライバである。三方弁２５は制御部９９からの制御信号により、配管１５と分岐配管１７とを連通させるか、または配管１５と一端が大気側に開放されている配管５０に連通させる切替弁を有している。 10 is a syringe pump, and 11 is a driver for driving the syringe pump 10. The three-way valve 25 has a switching valve that allows the pipe 15 and the branch pipe 17 to communicate with each other according to a control signal from the control unit 99, or allows the pipe 15 and one end to communicate with the pipe 50 that is open to the atmosphere side. .
　第３の実施形態では、液体検知部２８、２９、３０が検査装置８０の各液溜部に対応する位置に配置されている例を説明する。液体検知部３０は液溜部１４４に対応する位置に、液体検知部２９は液溜部１４７に対応する位置に、液体検知部２８は液溜部１４１に対応する位置にそれぞれ配置されている。液体検知部２８、液体検知部２９もｆ、ｇチャンネルにそれぞれ配置されている。 In the third embodiment, an example in which the liquid detection units 28, 29, and 30 are arranged at positions corresponding to the respective liquid reservoirs of the inspection apparatus 80 will be described. The liquid detector 30 is disposed at a position corresponding to the liquid reservoir 144, the liquid detector 29 is disposed at a position corresponding to the liquid reservoir 147, and the liquid detector 28 is disposed at a position corresponding to the liquid reservoir 141. The liquid detection unit 28 and the liquid detection unit 29 are also arranged in the f and g channels, respectively.
　次に、本発明の第３の実施形態の検査装置８０が検査を行う手順を図１７、図１８、図１９、図２０を用いて説明する。 Next, the procedure in which the inspection apparatus 80 according to the third embodiment of the present invention performs an inspection will be described with reference to FIGS. 17, 18, 19, and 20.
　図１７、図１８、図１９は第３の実施形態の検査装置８０が検査を行うメインルーチンを説明するフローチャートである。本実施形態では図１５で説明したマイクロチップ１を用いて検査を行う。図２０は送液制御のステップ毎の送液状態を図示したマイクロチップ１の平面図である。 FIGS. 17, 18, and 19 are flowcharts illustrating a main routine in which the inspection apparatus 80 according to the third embodiment performs an inspection. In this embodiment, the inspection is performed using the microchip 1 described with reference to FIG. FIG. 20 is a plan view of the microchip 1 illustrating the liquid feeding state for each step of liquid feeding control.
　図１７のフローチャートから順に手順を説明する。 The procedure will be described in order from the flowchart of FIG.
　なお、マイクロチップ１には予め検体注入口１５６から検体３５が注入されているものとする。また、バルブ５８は初期状態では全て閉じているものとする。三方弁２５は初期状態では分岐配管１７と配管５０が連通している。 It is assumed that the sample 35 has been injected into the microchip 1 from the sample injection port 156 in advance. In addition, all the valves 58 are closed in the initial state. In the initial state of the three-way valve 25, the branch pipe 17 and the pipe 50 communicate with each other.
　Ｓ２０１：キャリブレーションを行うステップである。 S201: This is a step for performing calibration.
　到達判定部４１２は、液体検知部２８、液体検知部２９、液体検知部３０を発光させ、液溜部１４４、液溜部１４７、液溜部１４１から反射した光を液体検知部２８、液体検知部２９、液体検知部３０がそれぞれ検出した出力信号を、所定の信号レベルと比較する。所定の信号レベルの範囲で無い場合、到達判定部４１２は液体検知部２８、液体検知部２９、液体検知部３０の発光部に流す電流を増加または減少させて所定の信号レベルの範囲になるようキャリブレーションを行う。到達判定部４１２は、液体検知部２８、液体検知部２９、液体検知部３０の出力信号がそれぞれ所定の信号レベルの範囲になると、そのときの出力電圧を基に液体の到達を判定する閾値を決定しＲＡＭ９７に記憶する。また、エラーフラッグを初期化し値を０にする。 The arrival determination unit 412 causes the liquid detection unit 28, the liquid detection unit 29, and the liquid detection unit 30 to emit light, and the light reflected from the liquid storage unit 144, the liquid storage unit 147, and the liquid storage unit 141. The output signals detected by the unit 29 and the liquid detection unit 30 are compared with predetermined signal levels. When it is not within the predetermined signal level range, the arrival determination unit 412 increases or decreases the current flowing through the light emitting units of the liquid detection unit 28, the liquid detection unit 29, and the liquid detection unit 30 so as to be within the predetermined signal level range. Perform calibration. When the output signals of the liquid detection unit 28, the liquid detection unit 29, and the liquid detection unit 30 are in a predetermined signal level range, the arrival determination unit 412 sets a threshold value for determining the arrival of the liquid based on the output voltage at that time. Determine and store in RAM 97. Also, the error flag is initialized and the value is set to zero.
　Ｓ５０１：三方弁をポンプ側に切り替えてバルブ５８ｈを開くステップである。 S501: This is a step of opening the valve 58h by switching the three-way valve to the pump side.
　ポンプ駆動制御部４１１は、三方弁２５を分岐配管１７と配管１５が連通するように切り替えるとともに、バルブ５８ｈを開く。 The pump drive control unit 411 switches the three-way valve 25 so that the branch pipe 17 and the pipe 15 communicate with each other, and opens the valve 58h.
　Ｓ５０２：ポンプを吸引方向に駆動するステップである。 S502: This is a step of driving the pump in the suction direction.
　ポンプ駆動制御部４１１はドライバ１１に指令し、吸引方向にシリンジポンプ１０を駆動する。 The pump drive control unit 411 instructs the driver 11 to drive the syringe pump 10 in the suction direction.
　Ｓ５０３：液溜部１４４の反射光を測定するステップである。 S503: This is a step of measuring the reflected light of the liquid reservoir 144.
　液体検知部３０は液溜部１４４の反射光を測定する。 The liquid detection unit 30 measures the reflected light from the liquid reservoir 144.
　Ｓ５０４：受光レベルと閾値とを比較するステップである。 S504: This is a step of comparing the light reception level with the threshold value.
　到達判定部４１２は、液体検知部３０の受光レベルに比例する出力信号レベルと、ステップＳ２０１でキャリブレーションを行ったときに求めた閾値と比較し、受光レベル＜閾値か、否か、を判定する。 The arrival determination unit 412 compares the output signal level proportional to the light reception level of the liquid detection unit 30 with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level <the threshold. .
　受光レベル≧閾値の場合、（ステップＳ５０４；Ｎｏ）、ステップＳ５０３に戻る。 If the received light level ≧ the threshold (step S504; No), the process returns to step S503.
　受光レベル＜閾値の場合、（ステップＳ５０４；Ｙｅｓ）、ステップＳ５０５に進む。 If the received light level <the threshold value (step S504; Yes), the process proceeds to step S505.
　Ｓ５０５：三方弁を大気開放し、ポンプを停止するステップである。 S505: This is a step of opening the three-way valve to the atmosphere and stopping the pump.
　ポンプ駆動制御部４１１は、三方弁２５を分岐配管１７と配管５０が連通するようにするとともに、シリンジポンプ１０を停止する。図２０（ａ）のように液溜部１４４に検体３５の先頭部分が到達すると液溜部１４４には検体３５が充填され受光レベル＜閾値になる。この状態を検出するとポンプ駆動制御部４１１は、シリンジポンプ１０を停止する。 The pump drive controller 411 causes the three-way valve 25 to communicate with the branch pipe 17 and the pipe 50 and stops the syringe pump 10. As shown in FIG. 20A, when the leading portion of the specimen 35 reaches the liquid reservoir 144, the liquid reservoir 144 is filled with the specimen 35, and the light receiving level <threshold. When this state is detected, the pump drive control unit 411 stops the syringe pump 10.
　Ｓ５０６：バルブ５８ｈを閉じるステップである。 S506: This is a step of closing the valve 58h.
　ポンプ駆動制御部４１１は、バルブ５８ｈを閉じる。 The pump drive control unit 411 closes the valve 58h.
　Ｓ５０７：バルブ５８ｅを開くステップである。 S507: This is a step of opening the valve 58e.
　ポンプ駆動制御部４１１は、バルブ５８ｅを開く。 The pump drive control unit 411 opens the valve 58e.
　Ｓ５０８：ポンプを吸引方向に駆動するステップである。 S508: This is a step of driving the pump in the suction direction.
　ポンプ駆動制御部４１１はドライバ１１に指令し、所定時間吸引方向にシリンジポンプ１０を駆動する。 The pump drive control unit 411 instructs the driver 11 to drive the syringe pump 10 in the suction direction for a predetermined time.
　Ｓ５０９：バルブ５８ｅを閉じるステップである。 S509: This is a step of closing the valve 58e.
　ポンプ駆動制御部４１１は、バルブ５８ｅを閉じる。図２０（ｂ）に示すように、余分な検体３５をダミー流路２５１ｅに流すと、分割定量部１５１には所定の量の検体３５が残る。 The pump drive control unit 411 closes the valve 58e. As shown in FIG. 20B, when an extra sample 35 is caused to flow through the dummy channel 251e, a predetermined amount of the sample 35 remains in the divided quantification unit 151.
　Ｓ５１０：バルブ５８ｆを開くステップである。 S510: This is a step of opening the valve 58f.
　ポンプ駆動制御部４１１は、バルブ５８ｆを開く。 The pump drive control unit 411 opens the valve 58f.
　Ｓ５１１：液溜部１４７ｆの反射光を測定するステップである。 S511: This is a step of measuring the reflected light of the liquid reservoir 147f.
　液体検知部３０は液溜部１４７ｆの反射光を測定する。 The liquid detector 30 measures the reflected light of the liquid reservoir 147f.
　Ｓ５１２：受光レベルと閾値とを比較するステップである。 S512: This is a step of comparing the received light level with a threshold value.
　到達判定部４１２は、液体検知部２９ｆの受光レベルに比例する出力信号レベルと、ステップＳ２０１でキャリブレーションを行ったときに求めた閾値と比較し、受光レベル＜閾値か、否か、を判定する。 The arrival determination unit 412 compares the output signal level proportional to the light reception level of the liquid detection unit 29f with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level <the threshold. .
　受光レベル≧閾値の場合、（ステップＳ５１２；Ｎｏ）、ステップＳ５１２に戻る。 If the received light level ≧ the threshold value (step S512; No), the process returns to step S512.
　受光レベル＜閾値の場合、（ステップＳ５１２；Ｙｅｓ）、ステップＳ５１３に進む。 If received light level <threshold (step S512; Yes), the process proceeds to step S513.
　Ｓ５１３：三方弁を大気開放し、ポンプを停止するステップである。 S513: This is a step of opening the three-way valve to the atmosphere and stopping the pump.
　ポンプ駆動制御部４１１は、三方弁２５を分岐配管１７と配管５０が連通するようにするとともに、シリンジポンプ１０を停止する。図２０（ｃ）のように液溜部１４７ｆに検体３５が到達すると液溜部１４７ｆには検体３５が充填され受光レベル＜閾値になる。この状態を検出するとポンプ駆動制御部４１１は、シリンジポンプ１０を停止する。このようにして分割流路１５５ｆには所定量の検体３５ｆが充填される。 The pump drive controller 411 causes the three-way valve 25 to communicate with the branch pipe 17 and the pipe 50 and stops the syringe pump 10. When the specimen 35 reaches the liquid reservoir 147f as shown in FIG. 20C, the liquid reservoir 147f is filled with the specimen 35, and the light receiving level <threshold. When this state is detected, the pump drive control unit 411 stops the syringe pump 10. In this way, a predetermined amount of the specimen 35f is filled in the divided flow path 155f.
　Ｓ５１４：バルブ５８ｆを閉じるステップである。 S514: This is a step of closing the valve 58f.
　ポンプ駆動制御部４１１は、バルブ５８ｆを閉じる。 The pump drive control unit 411 closes the valve 58f.
　Ｓ５１５：バルブ５８ｇを開くステップである。 S515: This is a step of opening the valve 58g.
　ポンプ駆動制御部４１１は、バルブ５８ｇを開く。 The pump drive control unit 411 opens the valve 58g.
　Ｓ５１６：ポンプを吸引方向に駆動するステップである。 S516: This is a step of driving the pump in the suction direction.
　ポンプ駆動制御部４１１はドライバ１１に指令し、所定時間吸引方向にシリンジポンプ１０を駆動する。 The pump drive control unit 411 instructs the driver 11 to drive the syringe pump 10 in the suction direction for a predetermined time.
　Ｓ５１７：液溜部１４７ｇの反射光を測定するステップである。 S517: This is a step of measuring the reflected light of the liquid reservoir 147g.
　液体検知部３０は液溜部１４７ｇの反射光を測定する。 The liquid detector 30 measures the reflected light of the liquid reservoir 147g.
　Ｓ５１８：受光レベルと閾値とを比較するステップである。 S518: This is a step of comparing the light reception level with the threshold value.
　到達判定部４１２は、液体検知部２９ｇの受光レベルに比例する出力信号レベルと、ステップＳ２０１でキャリブレーションを行ったときに求めた閾値と比較し、受光レベル＜閾値か、否か、を判定する。 The arrival determination unit 412 compares the output signal level proportional to the light reception level of the liquid detection unit 29g with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level <the threshold. .
　受光レベル≧閾値の場合、（ステップＳ５１８；Ｎｏ）、ステップＳ５１８に戻る。 If the light reception level ≧ the threshold value (step S518; No), the process returns to step S518.
　受光レベル＜閾値の場合、（ステップＳ５１８；Ｙｅｓ）、ステップＳ５１９に進む。 If received light level <threshold (step S518; Yes), the process proceeds to step S519.
　Ｓ５１９：三方弁を大気開放し、ポンプを停止するステップである。 S519: This is a step of opening the three-way valve to the atmosphere and stopping the pump.
　ポンプ駆動制御部４１１は、三方弁２５を分岐配管１７と配管５０が連通するようにするとともに、シリンジポンプ１０を停止する。図２０（ｄ）のように液溜部１４７ｇに検体３５が到達すると液溜部１４７ｇには検体３５ｇが充填され受光レベル＜閾値になる。この状態を検出するとポンプ駆動制御部４１１は、シリンジポンプ１０を停止する。このようにして分割流路１５５ｇには所定量の検体３５が充填される。 The pump drive controller 411 causes the three-way valve 25 to communicate with the branch pipe 17 and the pipe 50 and stops the syringe pump 10. When the specimen 35 reaches the liquid reservoir 147g as shown in FIG. 20D, the specimen 35g is filled in the liquid reservoir 147g, and the light receiving level <threshold. When this state is detected, the pump drive control unit 411 stops the syringe pump 10. In this way, a predetermined amount of the specimen 35 is filled in the divided flow path 155g.
　本ステップを終えると図２０（ｄ）のように検体３５は検体３５ｆと検体３５ｇに等量に分割されて分割流路１５５ｆ、分割流路１５５ｇに充填されている。 When this step is completed, as shown in FIG. 20D, the sample 35 is divided into the sample 35f and the sample 35g in equal amounts and filled in the divided flow path 155f and the divided flow path 155g.
　Ｓ５２０：バルブ５８ｇを閉じるステップである。 S520: This is a step of closing the valve 58g.
　ポンプ駆動制御部４１１は、バルブ５８ｇを閉じる。 The pump drive control unit 411 closes the valve 58g.
　Ｓ５２１：温度調整を行うステップである。 S521: Step for adjusting temperature.
　ＣＰＵ９８は、温度調節ユニット１５２に所定の温度に加熱するように指令し、所定の温度になるまで待機する。 The CPU 98 instructs the temperature adjustment unit 152 to heat to a predetermined temperature, and waits until the temperature reaches the predetermined temperature.
　Ｓ５２２：バルブ５８ｆを開くステップである。 S522: This is a step of opening the valve 58f.
　ポンプ駆動制御部４１１は、バルブ５８ｆを開く。 The pump drive control unit 411 opens the valve 58f.
　Ｓ５２３：ポンプを吸引方向に駆動するステップである。 S523: This is a step of driving the pump in the suction direction.
　ポンプ駆動制御部４１１はドライバ１１に指令し、所定時間吸引方向にシリンジポンプ１０を駆動する。 The pump drive control unit 411 instructs the driver 11 to drive the syringe pump 10 in the suction direction for a predetermined time.
　Ｓ５２４：液溜部１４１ｆの反射光を測定するステップである。 S524: This is a step of measuring the reflected light of the liquid reservoir 141f.
　液体検知部２８は液溜部１４１の反射光を測定する。 The liquid detector 28 measures the reflected light of the liquid reservoir 141.
　Ｓ５２５：受光レベルと閾値とを比較するステップである。 S525: This is a step of comparing the received light level with a threshold value.
　到達判定部４１２は、液体検知部２８の受光レベルに比例する出力信号レベルと、ステップＳ２０１でキャリブレーションを行ったときに求めた閾値と比較し、受光レベル＜閾値か、否か、を判定する。 The arrival determination unit 412 compares the output signal level proportional to the light reception level of the liquid detection unit 28 with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level <the threshold. .
　受光レベル≧閾値の場合、（ステップＳ５２５；Ｎｏ）、ステップＳ５２５に戻る。 If the received light level ≧ the threshold value (step S525; No), the process returns to step S525.
　受光レベル＜閾値の場合、（ステップＳ５２５；Ｙｅｓ）、ステップＳ５２６に進む。 If the received light level <the threshold value (step S525; Yes), the process proceeds to step S526.
　Ｓ５２６：三方弁を大気開放し、ポンプを停止するステップである。 S526: A step of opening the three-way valve to the atmosphere and stopping the pump.
　ポンプ駆動制御部４１１は、三方弁２５を分岐配管１７と配管５０が連通するようにするとともに、シリンジポンプ１０を停止する。このステップでは図２０（ｅ）に示すように検体３５ｆと第１の試薬、第２の試薬、第３の試薬とが混合部１３０ｆ、１３１ｆを通過する際に混合された液体５７ｆが検出部１１１ｆに充填されている。 The pump drive controller 411 causes the three-way valve 25 to communicate with the branch pipe 17 and the pipe 50 and stops the syringe pump 10. In this step, as shown in FIG. 20 (e), the liquid 57f mixed when the specimen 35f and the first reagent, the second reagent, and the third reagent pass through the mixing sections 130f and 131f is detected by the detection section 111f. Is filled.
　Ｓ５２７：バルブ５８ｆを閉じるステップである。 S527: This is a step of closing the valve 58f.
　ポンプ駆動制御部４１１は、バルブ５８ｆを閉じる。 The pump drive control unit 411 closes the valve 58f.
　Ｓ５２８：バルブ５８ｇを開くステップである。 S528: This is a step of opening the valve 58g.
　ポンプ駆動制御部４１１は、バルブ５８ｇを開く。 The pump drive control unit 411 opens the valve 58g.
　Ｓ５２９：ポンプを吸引方向に駆動するステップである。 S529: This is a step of driving the pump in the suction direction.
　ポンプ駆動制御部４１１はドライバ１１に指令し、所定時間吸引方向にシリンジポンプ１０を駆動する。 The pump drive control unit 411 instructs the driver 11 to drive the syringe pump 10 in the suction direction for a predetermined time.
　Ｓ５３０：液溜部１４１ｇの反射光を測定するステップである。 S530: This is a step of measuring the reflected light of the liquid reservoir 141g.
　液体検知部２８は液溜部１４１ｇの反射光を測定する。 The liquid detector 28 measures the reflected light of the liquid reservoir 141g.
　Ｓ５３１：受光レベルと閾値とを比較するステップである。 S531: A step of comparing the light reception level with the threshold value.
　到達判定部４１２は、液体検知部２８の受光レベルに比例する出力信号レベルと、ステップＳ２０１でキャリブレーションを行ったときに求めた閾値と比較し、受光レベル＜閾値か、否か、を判定する。 The arrival determination unit 412 compares the output signal level proportional to the light reception level of the liquid detection unit 28 with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level <the threshold. .
　受光レベル≧閾値の場合、（ステップＳ５３１；Ｎｏ）、ステップＳ５３１に戻る。 If the light reception level ≧ the threshold value (step S531; No), the process returns to step S531.
　受光レベル＜閾値の場合、（ステップＳ５３１；Ｙｅｓ）、ステップＳ５３２に進む。 If the received light level <the threshold value (step S531; Yes), the process proceeds to step S532.
　Ｓ５３２：三方弁を大気開放し、ポンプを停止するステップである。 S532: This is a step of opening the three-way valve to the atmosphere and stopping the pump.
　ポンプ駆動制御部４１１は、三方弁２５を分岐配管１７と配管５０が連通するようにするとともに、シリンジポンプ１０を停止する。このステップでは図２０（ｆ）に示すように検体３５ｇと第１の試薬、第２の試薬、第３の試薬とが混合部１３０ｇ、１３１ｇを通過する際に混合された液体５７ｇが検出部１１１ｇに充填されている。 The pump drive controller 411 causes the three-way valve 25 to communicate with the branch pipe 17 and the pipe 50 and stops the syringe pump 10. In this step, as shown in FIG. 20 (f), the liquid 57g mixed when the specimen 35g and the first reagent, the second reagent, and the third reagent pass through the mixing sections 130g and 131g is detected by the detection section 111g. Is filled.
　Ｓ５３３：バルブ５８ｇを閉じるステップである。 S533: This is a step of closing the valve 58g.
　ポンプ駆動制御部４１１は、バルブ５８ｇを閉じる。 The pump drive control unit 411 closes the valve 58g.
　Ｓ５３４：増幅反応の時間が終了したか、否か、を判定するステップである。 S534: This is a step of determining whether or not the time for the amplification reaction has ended.
　ＣＰＵ９８は、所定の増幅反応の時間が終了したか、否か、を判定する。 CPU 98 determines whether or not the predetermined amplification reaction time has ended.
　増幅反応の時間が終了していない場合、（ステップＳ５３４；Ｎｏ）、ステップＳ５３４に戻る。 If the amplification reaction time has not ended (step S534; No), the process returns to step S534.
　増幅反応の時間が終了した場合、（ステップＳ５３４；Ｙｅｓ）、ステップＳ２１３に進む。 If the amplification reaction time has ended (step S534; Yes), the process proceeds to step S213.
　Ｓ２１３：反応結果を測定するステップである。 S213: This is a step of measuring the reaction result.
　所定の時間経過後、ＣＰＵ９８は反応測定ルーチンをコールし、検出部１１１ｇ、検出部１１１ｈから反応結果を測定する。 After a predetermined time has elapsed, the CPU 98 calls a reaction measurement routine and measures the reaction result from the detection unit 111g and the detection unit 111h.
　第３の実施形態のメインルーチンの説明は以上である。 This completes the description of the main routine of the third embodiment.
　以上このように、本発明によれば、流路内の液体の先頭を所望の位置に移動させることができる検査システムを提供することができる。 As described above, according to the present invention, it is possible to provide an inspection system capable of moving the head of the liquid in the flow path to a desired position.

Claims (10)

  1. ポンプを用いて流体をマイクロチップの流路に注入または吸引し、該流路に貯蔵された液体である検体と試薬とを移動させて検出部に充填し、反応させた結果を測定する検査システムにおいて、
    前記流路を流れる液体を溜める液溜部と、
    前記液溜部に溜まった前記液体を検知する液体検知手段と、
    前記ポンプの駆動を制御するポンプ駆動制御手段と、
    前記液体検知手段の検知出力に基づいて前記液体の有無を判定する到達判定手段と、
    を有し、
    前記ポンプ駆動制御手段は、前記到達判定手段の判定に基づいて前記ポンプの駆動を制御することを特徴とする検査システム。     An inspection system that measures the result of injecting or aspirating a fluid into a microchip channel using a pump, moving a sample and a reagent stored in the channel to fill a detection unit, and reacting them. In
    A liquid reservoir for storing liquid flowing in the flow path;
    Liquid detecting means for detecting the liquid accumulated in the liquid reservoir,
    Pump drive control means for controlling the drive of the pump;
    Arrival determination means for determining the presence or absence of the liquid based on the detection output of the liquid detection means;
    Have
    The pump drive control means controls the drive of the pump based on the determination of the arrival determination means.
  2. 前記液溜部は、
    前記検出部の下流側の流路に設けられていることを特徴とする請求の範囲第１項に記載の検査システム。     The liquid reservoir is
    The inspection system according to claim 1, wherein the inspection system is provided in a flow path on a downstream side of the detection unit.
  3. 前記マイクロチップは、
    前記検出部の上流側の流路に前記検体と前記試薬とを混合する混合部を有し、
    前記液溜部は、
    前記混合部に近い上流側の流路に設けられていることを特徴とする請求の範囲第１項または第２項に記載の検査システム。     The microchip is
    A mixing unit that mixes the sample and the reagent in a flow channel upstream of the detection unit;
    The liquid reservoir is
    3. The inspection system according to claim 1, wherein the inspection system is provided in a flow path on an upstream side close to the mixing unit.
  4. 前記液溜部は、
    前記検体または前記試薬が貯蔵された流路に近い下流側の流路に設けられていることを特徴とする請求の範囲第１項から第３項の何れか１項に記載の検査システム。     The liquid reservoir is
    The inspection system according to any one of claims 1 to 3, wherein the inspection system is provided in a flow channel on a downstream side close to a flow channel in which the specimen or the reagent is stored.
  5. 前記マイクロチップの一部を外側から加熱して前記流路の内部にある前記液体を加熱する加熱手段を有し、
    前記液溜部は、
    前記流路の前記加熱手段により加熱可能な先頭の位置に設けられていることを特徴とする請求の範囲第１項から第４項の何れか１項に記載の検査システム。     Heating means for heating a part of the microchip from the outside to heat the liquid in the flow path;
    The liquid reservoir is
    The inspection system according to any one of claims 1 to 4, wherein the inspection system is provided at a leading position of the flow path that can be heated by the heating unit.
  6. 前記マイクロチップは、
    前記試薬または前記検体を分割する分割流路を有し、
    前記液溜部は、
    前記分割流路の下流の流路に設けられていることを特徴とする請求の範囲第１項から第５項の何れか１項に記載の検査システム。     The microchip is
    A divided flow path for dividing the reagent or the specimen;
    The liquid reservoir is
    The inspection system according to any one of claims 1 to 5, wherein the inspection system is provided in a flow path downstream of the divided flow path.
  7. 前記ポンプ駆動制御手段は、
    前記到達判定手段の判定に基づいて前記ポンプの駆動を停止することを特徴とする請求の範囲第１項から第６項の何れか１項に記載の検査システム。     The pump drive control means includes
    The inspection system according to any one of claims 1 to 6, wherein driving of the pump is stopped based on determination by the arrival determination means.
  8. 前記ポンプ駆動制御手段は、
    前記到達判定手段の判定に基づいて前記ポンプから前記マイクロチップの流路に注入または吸引する流体の流量を変更することを特徴とする請求の範囲第１項から第７項の何れか１項に記載の検査システム。     The pump drive control means includes
    The flow rate of the fluid that is injected or sucked into the flow path of the microchip from the pump is changed based on the determination of the arrival determining means, according to any one of claims 1 to 7. The inspection system described.
  9. 前記ポンプ駆動制御手段は、
    前記到達判定手段の判定に基づいてそれまで前記ポンプから注入または吸引している方向と逆方向に前記流体を吸引または注入することを特徴とする請求の範囲第１項から第８項の何れか１項に記載の検査システム。     The pump drive control means includes
    The fluid according to any one of claims 1 to 8, wherein the fluid is sucked or injected in a direction opposite to the direction in which the pump has been infused or sucked until then based on the determination of the arrival judging means. The inspection system according to item 1.
  10. 前記流体は気体であり、前記マイクロチップの前記流路に加わっている前記気体の圧力を大気側に開放する弁を有し、
    前記ポンプ駆動制御手段は、
    前記到達判定手段の判定に基づいて前記弁を大気側に開放することを特徴とする請求の範囲第１項から第９項の何れか１項に記載の検査システム。     The fluid is a gas, and has a valve that opens the pressure of the gas applied to the flow path of the microchip to the atmosphere side,
    The pump drive control means includes
    The inspection system according to any one of claims 1 to 9, wherein the valve is opened to the atmosphere side based on the determination of the arrival determination means.
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