JPWO2009125676A1 - Inspection system - Google Patents

Abstract

A liquid reservoir that accumulates liquid flowing in the flow path, a liquid detector that detects the liquid accumulated in the liquid reservoir, a pump driver that drives the pump, a pump drive controller that controls the pump driver, and a liquid detector And an arrival determination means for determining the presence or absence of liquid based on the detection output of the means, and the pump drive control means controls the drive of the pump based on the determination of the arrival determination means.

Description

  The present invention relates to an inspection system.

  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 examination / 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 techniques, and operation of equipment are required, the cost, required sample amount, and required time can be reduced by using μ-TAS.

  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).

  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.

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

  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.

  This invention is made | formed 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.

  The object of the present invention can be achieved by the following constitution.

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.
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.
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).
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.
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).
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).
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).
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.
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.
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.

  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.

It is an external view of the test | inspection apparatus 80 in embodiment of this invention. It is explanatory drawing of the microchip 1 concerning the 1st Embodiment of this invention. It is an enlarged view of the periphery of the detection part 111. FIG. 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. 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. It is explanatory drawing explaining the liquid with which the detection part 111 was filled. It is a circuit block diagram of the inspection apparatus 80 in the 1st Embodiment of this invention. It is a flowchart explaining the main routine which the test | inspection apparatus 80 of 1st Embodiment performs a test | inspection. 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. It is a flowchart explaining the subroutine with which the test | inspection apparatus 80 of 1st Embodiment performs reaction measurement. It is an external view of the microchip 1 in the 2nd Embodiment of this invention. It is a block diagram of the detection apparatus 80 in the 2nd Embodiment of this invention. It is a flowchart explaining the main routine which the test | inspection apparatus 80 of 2nd Embodiment performs a test | inspection. It is a time chart for demonstrating the liquid feeding control of 2nd Embodiment. It is an external view of the microchip 1 in the 3rd Embodiment of this invention. It is a block diagram of the detection apparatus 80 in the 3rd Embodiment of this invention. It is the flowchart 1 explaining the main routine which the test | inspection apparatus 80 of 3rd Embodiment performs a test | inspection. It is the flowchart 2 explaining the main routine which the test | inspection apparatus 80 of 3rd Embodiment performs a test | inspection. It is the flowchart 3 explaining the main routine which the test | inspection apparatus 80 of 3rd Embodiment performs a test | inspection. It is a top view of the microchip 1 which illustrated the liquid feeding state for every step of liquid feeding control.

Explanation of symbols

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

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

  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 sample 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, and 89 denotes a power switch.

  After the inspection person turns on the power switch 89, the microchip 1 is inserted in the direction of the arrow in FIG. 1, and the operation panel 87 is operated 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.

  The inspection person takes out the microchip 1 from the insertion port 83 after the inspection is completed.

  Next, an example of the microchip 1 according to the first embodiment of the present invention will be described with reference to FIG.

  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.

  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.

  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 on the order of micrometers, and 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.

  In the present embodiment, a microchip 1 used for a process of performing amplification and detection of a specific gene will be described as an example.

  Reference numerals 110a and 110b in FIG. 2B denote injection ports that communicate with the flow path inside the microchip 1. The driving liquid is injected from each of the injection ports 110 to drive the internal specimen, reagent, and the like. 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.

  Reference numerals 121a and 121b denote 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.

  Reference numerals 120a and 120b denote reagent storage parts that store the first reagent, 122a and 122b denote reagent storage parts that store the second reagent, and 123a and 123b denote reagent storage parts that store the third reagent.

  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. 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 sample, the first reagent, and the second reagent pass through the flow path 250 and are injected into the downstream reagent storage units 123a and 123b, respectively, 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 are shallower than the mixing part 130 a and mixing part 130 b and deeper 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.

  The sample, the first reagent, the second reagent, and the third reagent mixed in the mixing unit 130a, the mixing unit 130b and the mixing unit 131a, and 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.

  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.

  An example of the shapes of the detection unit 111 and the liquid reservoir 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.

  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.

  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.

  Next, materials used for the groove forming substrate 108 and the covering substrate 109 constituting the microchip 1 will be described.

  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.

  In particular, it is desirable that a chip intended for a large number of measurement specimens, particularly 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.

  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.

  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.

  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.

  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.

  Hereinafter, an example of the internal configuration of the inspection apparatus 80 will be described with reference to FIGS. 4, 5, and 6.

  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.

  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.

  In the present embodiment, the range that can be heated by the temperature adjustment unit 152 is 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.

  In the cross-sectional view of FIG. 5, 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 is illustrated.

  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.

  The liquid detection unit 20 illustrated in FIG. 5 is a photo reflector including, for example, a light emitting unit and a light receiving unit, and the liquid detection unit 20 is mounted on the 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.

  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.

  Note that the number of the 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.

  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.

  As shown in FIG. 4, one end of the detection substrate 21 is supported by a guide member 354 having a screw portion that is 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.

  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.

  After moving to a predetermined position, the liquid detectors 20a and 20b sequentially irradiate the liquid reservoirs 140a and 140b or the liquid reservoirs 141a and 141b, receive the reflected light, and output an electrical signal.

  The feed screw 351 is driven by the detection board driving 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. 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.

  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 passes through the guide hole. The guide bar is disposed in parallel with the feed screw 301.

  In this embodiment, the case where two detection units 111a and 111b are provided on the microchip 1 has been described. However, the number of 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 inlet 110 of the microchip 1 is provided at a position where it communicates with a corresponding opening provided in the packing 90b when the microchip 1 is brought into close contact with the micropump 75 via the packing 90b.

  A driving liquid tank 91 is connected to the suction port 145 of the micro pump unit 75 via a packing 90a, and the driving liquid filled in the driving liquid tank 91 is sucked 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.

  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.

  The micropump unit 75 is provided with at least one micropump. 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 as 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.

  Hereinafter, functional blocks having the same functions as those described so far are denoted by the same reference numerals, and description thereof is omitted.

  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.

  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.

  The detection unit drive control unit 413 instructs the detection unit drive detection unit drive motor 61 to move the detection unit 22.

  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.

  The pump driving 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 inspections in a predetermined sequence and stores the inspection results 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.

  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.

  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.

  First, an outline procedure of inspection will be described in the order of the flowchart of FIG.

  Assume 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: 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. 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: 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.

  S203: This is a step of detecting the arrival of the liquid.

  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: This is a step of determining an error flag.

  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.

  When the error flag is 1 (step S204; Yes), the process proceeds to step S205.

  S205: This is a step of displaying a warning.

  The control unit 99 displays an error warning on the display unit 84 and stops the inspection apparatus 80.

  When the error flag is 0 (step S204; No), the process proceeds to step S206.

  S206: This is a step of moving the liquid detection unit 20.

  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: 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 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: 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.

  S209: This is a step of detecting the arrival of the liquid.

  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: This is a step of determining an error flag.

  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.

  When the error flag is 1 (step S210; Yes), the process proceeds to step S211.

  S211: A step of displaying a warning.

  The control unit 99 displays an error warning on the display unit 84 and stops the inspection apparatus 80.

  When the error flag is 0 (step S210; No), the process proceeds to step S212.

  S212: This is a step of moving the liquid detection unit 20.

  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: This is a step of measuring the reaction result.

  After a predetermined time has elapsed, the CPU 98 calls a reaction measurement routine and measures the reaction results from the detection unit 111a and the detection unit 111b.

  This is the end of the description of the main routine.

  Next, the liquid arrival detection routine will be described with reference to the flowchart of FIG.

  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: This is a step of measuring the reflected light from the liquid reservoir of the a channel.

  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: A step of comparing the light reception 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 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.

  If the light reception level <the threshold value (step S102; Yes), the process proceeds to step S103.

  S103: It is a step which stops the pump of a channel.

  The pump drive control unit 411 stops the a-channel pump. 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.

  When the received light signal level ≧ the threshold value (step S102; No), the process proceeds to step S104.

  S104: A step of measuring the reflected light from the liquid reservoir of the b channel.

  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: A step of comparing the light reception 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 20b with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level <the threshold. .

  If the received light signal level <the threshold value (step S105; Yes), the process proceeds to step S106.

  S106: This is a step of stopping the pump of the b channel.

  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.

  When the output signal level ≧ the threshold value (step S105; No), the process proceeds to step S107.

  S107: This is a step of determining whether or not the pumps of both channels a and b are stopped.

  The pump drive control unit 411 determines whether or not the pumps of both channels a and b are stopped.

  If 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.

  When the a or b channel pump is not stopped (step S107; No), the process proceeds to step S108.

  S108: This is a step for determining whether it is time-out or not.

  The CPU 98 reads the elapsed time from the internal timer and determines whether or not the timeout time has elapsed.

  In the case of time-out (step S108; Yes), the process proceeds to step S109.

  S109: This is a step of setting the error flag to 1.

  The CPU 98 sets the error flag to 1 and returns to the original routine.

  When it is not time-out (step S108; No), it returns to step S101.

  If not timed out, the process is continued and the liquid is waited for to reach the liquid reservoir.

  This is the end of the description of the liquid arrival routine.

  Next, the reaction measurement routine will be described in the order of the flowchart of FIG.

  S301: This is a step of moving the detection unit 22.

  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: It is a step which measures a reaction result.

  After a predetermined time has elapsed, the CPU 98 causes the light emitting section 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: This is a step of moving the detection unit 22.

  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: It is a step which measures a reaction result.

  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.

  The inspection is finished as described above, and the detection unit drive control unit 413 returns the detection unit 22 to the initial position.

  This completes the description of the procedure of the reaction measurement routine.

  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.

  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.

  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.

  FIG. 12 is a block diagram of a detection device 80 according to the second embodiment of the present invention. In FIG. 12, the difference from the first embodiment is mainly illustrated, and the drawing is simplified.

  Reference numeral 10 denotes a syringe pump, and 11 denotes 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.

  In the second embodiment, an example in which the liquid detection unit is disposed at a position corresponding to each liquid reservoir of the inspection apparatus 80 will be described. 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.

  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.

  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 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.

  A schematic procedure of the inspection will be described in the order of the flowchart of FIG. 13 with reference to the time chart of FIG.

  Assume that the microchip 1 is set at a position where inspection can be performed as shown in FIG. 12, and the CPU is instructed to start inspection by operating the operation unit 87.

  S201: This is a step for performing calibration.

  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: 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.

  S402: This is a step of measuring the reflected light of the liquid reservoir 142.

  The liquid detector 26 measures the reflected light from the liquid reservoir 142.

  S403: A step of comparing the light reception 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 26 with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level <the threshold. .

  When the light reception level ≧ the threshold value (step S403; No), the process returns to step S402.

  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: This is 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.

  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.

  S407: This is a step of waiting for a predetermined time.

  The pump drive controller 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.

  S408: A step of driving the pump in the discharge direction at a speed C.

  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: 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 a 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. .

  If the light reception level ≧ the threshold value (step S410; No), the process returns to step S409.

  If the light reception level <the threshold value (step S410; Yes), the process proceeds to step S411.

  S411: This is a step of driving the pump at the speed D in the discharge direction.

  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: A step of measuring the reflected light of the liquid reservoir 141.

  The liquid detector 28 measures the reflected light from the liquid reservoir 141.

  S413: 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. .

  When the light reception level ≧ the threshold value (step S413; No), the process proceeds to step S414.

  S414: This is a step of determining time over.

  If 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.

  If the time is over (step S414; Yes), the process ends.

  When it is not time over (step S414; No), it returns to step S412.

  If the light reception level <the threshold value (step S413; Yes), the process proceeds to step S415.

  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.

  S416: This is a step of switching the three-way valve to the atmospheric direction.

  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.

  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: This is a step for starting amplification reaction processing.

  The CPU 98 instructs the 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 from 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: a step of comparing the light reception 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. .

  When the light reception level ≧ the threshold value (step S421; No), the process proceeds to step S425.

  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.

  The pump drive controller 411 instructs the driver 11 to drive the syringe pump 10 in the suction direction at the drive pulse rate 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 time for the amplification reaction has ended.

  The CPU 98 determines whether or not the predetermined amplification reaction time has ended.

  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 the timings indicated by t7, t8, and t9 in FIG. 14 (a), and the liquid reservoir 141 as shown in FIG. 14 (d). The leading position of the liquid is retracted until the liquid can no longer be detected.

  When the amplification reaction time is over (step S425; Yes), the process proceeds to step S213.

  S213: This is a step of measuring the reaction result.

  After a predetermined time has elapsed, the CPU 98 calls a reaction measurement routine and measures the reaction results from the detection unit 111a and the detection unit 111b.

  This is the end of the description of the main routine of the second embodiment.

  Next, an example of the microchip 1 according to the third embodiment of the present invention will be described with reference to FIG.

  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 includes a sample injection port 156 for injecting a sample and a division quantification unit 151 for dividing and quantifying the sample. The sample injected from the sample injection port 156 is divided and quantified for testing. 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.

  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.

  Reference numerals 410e, 410f, 410g, and 410h in FIG. 15 denote suction ports that communicate with the flow paths inside the microchip 1, and drive the samples, reagents, and the like inside by sucking air from the suction ports 410. 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.

  Reference numerals 155f and 155g denote 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.

  Reference numerals 120f and 120g denote reagent storage parts that store the first reagent, 122f and 122g denote reagent storage parts that store the second reagent, and 123f and 123g denote reagent storage parts that store 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 sample, the first reagent, the second reagent, and the third reagent mixed in the mixing unit 130f, the mixing unit 130g and the mixing unit 131f, and 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.

  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 device 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.

  Reference numeral 10 denotes a syringe pump, and 11 denotes 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. .

  In the third embodiment, an example will be described in which the liquid detection units 28, 29, and 30 are arranged at positions corresponding to the respective liquid reservoirs of the inspection device 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, 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.

  Next, the procedure in which the inspection apparatus 80 according to the third embodiment of the present invention performs inspection will be described with reference to FIGS. 17, 18, 19, and 20.

  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.

  The procedure will be described in order from the flowchart of FIG.

  It is assumed that the sample 35 is 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: 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. 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: A step of switching the three-way valve to the pump side and opening the valve 58h.

  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 detector 30 measures the reflected light from the liquid reservoir 144.

  S504: 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 30 with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level <the threshold. .

  When the light reception level ≧ the threshold value (step S504; No), the process returns to step S503.

  If the light reception 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 control unit 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 from 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. .

  When the light reception level ≧ the threshold value (step S512; No), the process returns to step S512.

  If the light reception level <the threshold value (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 control unit 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: This is a step of closing the valve 58f.

  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 from the liquid reservoir 147g.

  S518: 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 29g with the threshold obtained when the calibration is performed in step S201, and determines whether the light reception level <the threshold. .

  When the light reception level ≧ the threshold value (step S518; No), the process returns to step S518.

  If the light reception level <the threshold value (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 control unit 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.

  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 channel 155f and the divided channel 155g.

  S520: This is a step of closing the valve 58g.

  The pump drive control unit 411 closes the valve 58g.

  S521: This is a step for adjusting the temperature.

  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 from 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. .

  When the light reception level ≧ the threshold value (step S525; No), the process returns to step S525.

  If the light reception level <the threshold value (step S525; Yes), the process proceeds to step S526.

  S526: This is a step of opening the three-way valve to the atmosphere and stopping the pump.

  The pump drive control unit 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: This is a step of closing the valve 58f.

  The pump drive control unit 411 closes the valve 58f.

  S528: This is a step of opening the valve 58g.

  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 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. .

  When the light reception level ≧ the threshold value (step S531; No), the process returns to step S531.

  If the light reception level <the threshold value (step S531; Yes), the process proceeds to step S532.

  S532: A step of opening the three-way valve to the atmosphere and stopping the pump.

  The pump drive control unit 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: 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 amplification reaction time has ended.

  The CPU 98 determines whether or not the predetermined amplification reaction time has ended.

  If the amplification reaction time has not ended (step S534; No), the process returns to step S534.

  When the amplification reaction time is over (step S534; Yes), the process proceeds to step S213.

  S213: This is a step of measuring the reaction result.

  After a predetermined time elapses, the CPU 98 calls a reaction measurement routine and measures the reaction result from the detection unit 111g and the detection unit 111h.

  This is the end of the description of the main routine of the third embodiment.

  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)

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. 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. 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. 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. 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. 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. 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. 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. 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. 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.