JP2009128277A - Inspection apparatus and inspection system - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an inspection apparatus and an inspection system monitoring liquid dispense states of a plurality of channels according to a microchip by one imaging means. <P>SOLUTION: The inspection apparatus for measuring a result obtained by allowing a specimen that has moved in a microchip channel to react with a reagent includes: an imaging means for acquiring image data by photographing the channel; an image processing means for performing image processing to the image data photographed by the imaging means; and a monitoring region recording means for recording information on a plurality of monitoring regions for monitoring a channel state. The image processing means performs image processing based on information. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an inspection apparatus and 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 test / 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 applicant encloses a reagent or the like in a microchannel of a microchip (microreactor), injects a driving liquid into the microchannel by a micropump, and moves a liquid such as a specimen and a reagent, and then detects the reaction part and then the detection An examination apparatus has been proposed that can measure the reaction result with a specimen such as blood by flowing it to a section (see, for example, Patent Document 2). Patent Document 2 discloses a microchip that divides a reagent and a sample into two or more, sends them to an analysis channel, performs amplification reaction and detection, and performs multi-item analysis for one sample. In such an inspection apparatus, various inspections can be performed by using microchips having different flow paths.

By the way, the viscosity of specimens such as blood, urine, saliva and sputum is not necessarily uniform and may vary greatly. Therefore, a sample injection device that takes a sample of the diffusion state of a sample on a biochip on which a plurality of probes are arranged as a moving image, calculates the diffusion rate from the captured image, and changes the injection rate of the sample according to the result. It has been proposed (see, for example, Patent Document 3).
JP 2004-28589 A JP 2006-149379 A JP-A-2005-214797

  As described above, due to variations in the viscosity of the specimen, the movement of the specimen may stop in the flow path even in the microchip disclosed in Patent Document 2, and the subsequent processing may not be performed normally.

  In the case where the specimen is divided and moved in different flow paths, it is necessary to monitor and respond to the liquid feeding states of the specimens flowing in the plurality of flow paths in order to solve such problems. In addition, since the inspection apparatus disclosed in Patent Document 2 performs a plurality of inspections using microchips having different flow paths, it is necessary to monitor the liquid feeding state at different locations for each microchip.

  However, the method disclosed in Patent Document 3 is applied to a sample injection device that injects a sample between a biochip and a cover that covers the biochip. A method for monitoring with a single imaging means is not disclosed. Also, there is no disclosure of a method for monitoring the liquid feeding state of different flow paths for each microchip.

  The present invention has been made in view of the above problems, and an object of the present invention is to provide an inspection apparatus and an inspection system that can monitor liquid feeding states of a plurality of flow paths corresponding to a microchip with a single imaging unit. .

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

1.
In an inspection device that measures the result of reacting a sample and a reagent that have moved through the flow path of a microchip,
Imaging means for capturing the flow path and acquiring image data;
Image processing means for performing image processing on image data captured by the imaging means;
Monitoring area recording means for recording information of a plurality of monitoring areas for monitoring the state of the flow path;
Have
The image processing means includes
An inspection apparatus that performs image processing based on the information.

2.
Control means for controlling each part of the inspection apparatus;
2. The inspection apparatus according to 1, wherein the control unit performs control based on a result of image processing performed on the image data by the image processing unit.

3.
Display means for displaying warning information;
3. The inspection apparatus according to 2, wherein the control unit causes the display unit to display the warning information based on a result of image processing performed on the image data by the image processing unit.

4).
In an inspection system that measures the result of reacting a sample and a reagent that have moved through the flow path of a microchip,
Imaging means for capturing the flow path and acquiring image data;
Image processing means for performing image processing on image data captured by the imaging means;
Monitoring area recording means for recording information of a plurality of monitoring areas for monitoring the flow path provided in the microchip;
Have
The image processing means includes
An inspection system that performs image processing based on the information.

5).
Control means for controlling each part of the inspection system;
5. The inspection system according to claim 4, wherein the control unit performs control based on a result of image processing performed on the image data by the image processing unit.

6).
Display means for displaying warning information;
6. The inspection system according to 5, wherein the control unit causes the display unit to display the warning information based on a result of image processing performed on the image data by the image processing unit.

7).
The monitoring area recording means is an IC tag,
The inspection system according to any one of 4 to 6, further comprising non-contact reading means capable of reading information written on the IC tag in a non-contact manner.

8).
The inspection system according to any one of claims 4 to 6, wherein the monitoring area recording means is a two-dimensional barcode.

9.
The imaging means includes
Capture the image data by photographing the two-dimensional barcode,
The image processing means includes
9. The inspection system according to 8, wherein the information is acquired by performing image processing on the image data.

  According to the present invention, an image obtained by photographing the flow path of the microchip is image-processed based on the information of the monitoring region, so that the liquid feeding state of the plurality of flow paths corresponding to the microchip can be monitored by one imaging unit. An apparatus and an inspection system can be provided.

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

  FIG. 1 is an external view of an inspection system 80 according to an embodiment of the present invention.

  The inspection device 82 is a device that automatically detects the reaction between the specimen previously injected into the microchip 1 and the reagent and displays the result on the display unit 84. The inspection system 80 includes an inspection device 82 and the microchip 1.

  The inspection device 82 has an insertion port 83, and the microchip 1 is inserted into the insertion port 83 and set inside the inspection device 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 82, the reaction in the microchip 1 is automatically inspected, and when the inspection is completed, the result is displayed on the display unit 84 composed of 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.

  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 device 82.

  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.

  The grooves formed in the groove forming substrate 108 are formed with reference to the center of the marker 71.

  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.

  2B, reference numerals 110a, 110b, and 110c denote driving liquid injection units that communicate with the flow paths inside the microchip 1. The driving liquid injection units 110 inject driving liquids to drive the internal specimens, reagents, and the like. . Reference numeral 113 denotes a sample injection unit for injecting a sample into the microchip 1 and injects a sample such as blood from the sample injection unit 113 using a syringe or the like.

  In the microchip 1 of the present embodiment, the flow channel 250 downstream of the sample injection unit 113 is configured to branch in two directions and divide the sample into two. When the driving liquid is injected from the driving liquid injection unit 110b, the sample injected into the sample injection unit 113 is stored in the sample storage units 121a and 121b through the channel 250aa and the channel 250ab communicating with the sample injection unit 113, respectively. Is done. The sample storage units 121a and 121b have deeper grooves than other flow paths in order to store a predetermined amount of sample.

  When the specimen storage units 121a and 121b are filled with the specimen, the specimen is pushed out by the driving liquid into the channels 250ba and 250bb downstream of the sample storage units 121a and 121b, and the liquid reservoirs provided in the respective channels. 140a and 140b are filled. The liquid reservoirs 140a and 140b are provided to detect that the specimen storage parts 121a and 121b are filled, and the grooves are shallower than the specimen storage parts 121a and 121b and deeper than the other flow paths 250. ing.

  The depth of the grooves of the specimen storage parts 121a and 121b is 1.5 μm, for example, the depth of the grooves of the liquid reservoirs 140a and 140b is 1 μm, and the depth of the grooves of the other flow paths is 0.25 μm, for example.

  120a and 120b are reagent storage units for storing reagents. When the driving liquid is injected from the driving liquid injection sections 110a and 110c, the reagent stored in the reagent storage sections 120a and 120b is pushed out into the flow path 250 and is injected into the downstream sample storage sections 121a and 121b, respectively. The liquid in which the sample and the reagent are mixed is accommodated in the downstream detection units 111a and 111b through the flow channel 250ca and the flow channel 250cb, respectively.

  As will be described later, the detection units 111a and 111b are heated or absorbed in the inspection apparatus 82 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 for accommodating 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.

  The depth of the grooves of the detection units 111a and 111b is 1.5 μm, for example, the depth of the grooves of the liquid reservoirs 141a and 141b is 1 μm, for example, and the depth of the grooves of the other channels is 0.25 μm. It is desirable to provide the liquid reservoirs 141a and 141b as close as possible to 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.

  When the detectors 111a and 111b are irradiated with light, the reagent that has reacted with the specimen emits fluorescence, for example, and thus the reaction result is measured by measuring the amount of fluorescence.

  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 disposed of 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.

  In this embodiment, since the liquid stored in the liquid reservoirs 140a and 140b and the liquid reservoirs 141a and 141b is optically detected, at least the liquid reservoirs 140a and 140b and the liquid reservoirs 141a and 141b of the coated substrate 109 are detected. It is necessary to configure the portion covering the transparent member with a transparent member such as glass or resin.

  FIG. 3 is a perspective view for explaining an example of the internal configuration of the inspection apparatus 82 in the embodiment of the present invention, and FIG. 4 is a cross-sectional view showing an example of the internal configuration of the inspection apparatus 82 in the embodiment of the present invention. is there. Each part will be described with reference to the coordinate axes of X, Y, and Z shown in FIGS.

  The inspection device 82 includes a temperature adjustment unit 152, a detection unit 22, a micro pump unit 75, a packing 90, a driving liquid tank 91, an imaging unit 24, a lens 25, an illumination unit 26, a feed screw 301, a joint 302, and a detection unit drive motor 61. Etc. 3 and 4 show a state in which the microchip 1 is in close contact with the packing 90b. The imaging unit 24 is an imaging unit of the present invention.

  Hereinafter, an example of the internal configuration of the inspection system 80 will be described with reference to FIGS. 3 and 4.

  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. 3 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 is a unit that incorporates a Peltier element, a power supply device, a temperature control device, and the like and adjusts the surface of the microchip 1 to a predetermined temperature by generating heat or absorbing heat.

  Next, 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 imaging unit 24 illustrated in FIG. 4 is, for example, a video camera including a lens 25 and an illumination unit 26, and images the flow path of the microchip 1 illustrated in FIG. 2B and outputs image data. The imaging unit 24 is an imaging unit of the present invention.

  The light flux that has passed through the lens 25 is arranged so as to form an image on a CCD (charge coupled device) that is an example of an image sensor provided in the image pickup unit 24. Note that the image sensor may be a solid-state image sensor such as a MOS sensor or a CID sensor instead of the CCD.

  The CCD is an image pickup element composed of a group of fine pixels, and photoelectrically converts a light image of a subject (subject image) formed by the lens 25 into an image signal at a constant period. The image signal is converted into a digital signal by a signal processing circuit (not shown), and then gamma correction is performed to sequentially obtain image data. The image data is sequentially transmitted to a control unit 99 (not shown in FIG. 4).

  In the present embodiment, an example in which the imaging unit 24 outputs black and white image data will be described. However, when analyzing the liquid feeding state of the flow channel from the color information of the specimen, the imaging unit 24 that outputs color image data. Can be used. The imaging unit 24 is not limited to a video camera that outputs a moving image, and may be a digital still camera that outputs an image taken in response to a command from the control unit 99.

  The illumination unit 26 is an illumination unit such as an LED or a lamp, and is provided to illuminate the surface of the microchip 1 taken by the imaging unit 24.

  In the present embodiment, an example will be described in which liquid stored in the liquid reservoirs 140a and 140b and the liquid reservoirs 141a and 141b of the microchip 1 are detected by image processing.

  As shown in FIG. 4, the range indicated by the dotted line from the lens 25 is the imaging range of the imaging unit 24, and the imaging unit 24 is configured so that the entire flow path of the microchip 1 shown in FIG. Yes. In this embodiment, the image data of the liquid reservoir 140 is cut out from the data obtained by photographing the state in which the liquid is stored in the liquid reservoir 140 (any one of the liquid reservoirs 140a and 140b) in the procedure described in detail later. Process.

  The detection unit 22 includes a light emitting unit and a light receiving unit (not shown), 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. ing. 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 position sensor 41 is a sensor such as a photo reflector or a mechanical switch provided for detecting the initial position of the detection unit 22.

  The detection unit 22 is provided with a guide hole (not shown in FIG. 3) 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.

  FIG. 4 illustrates a case where the detection unit 22 is in a position where the reaction result of the reagent generated by the detection unit 111 (any one of the detection units 111a and 111b) can be optically detected.

  When the microchip 1 is brought into close contact with the micropump 75 via the packing 90b, the driving liquid injection port 110 of the microchip 1 is provided at a position that communicates with a corresponding opening provided in 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 driving liquid 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 driving liquid inlet 110 of the microchip 1 into the flow path 250 formed in the microchip 1. In this way, the driving liquid is injected from the micropump unit 75 into the driving liquid injection port 110.

  The micropump unit 75 is provided with at least one micropump. When the microchip 1 illustrated in FIG. 2 is driven, three micropumps corresponding to the three driving liquid injection ports 110a, 110b, and 110c are necessary.

  FIG. 5 is a circuit block diagram of the detection device 82 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.

  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 an image processing unit 410, a pump drive control unit 411, a detection unit drive control unit 413, and an imaging control unit 414. The image processing unit 410 is an image processing unit of the present invention.

  In the present embodiment, an example in which information of a plurality of monitoring areas 70 for monitoring the state of the flow path is stored in the ROM 96 will be described. The monitoring area recording unit 910 is monitoring area recording means of the present invention. Note that the information of the monitoring area 70 may be stored in the RAM 97, in which case the RAM 97 is the monitoring area recording unit 910.

  The image processing unit 410 reads image data stored in the RAM 97 based on a program and performs predetermined image processing.

  The flow path determination unit 412 determines whether or not the evaluation value calculated by the image processing unit 410 is equal to or higher than a predetermined level based on the program.

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

  The imaging control unit 414 instructs the illumination unit 26 based on a program to turn on / off illumination, and instructs the imaging unit 24 to start or end imaging.

  The pump drive unit 500 is a drive unit that 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.

  FIG. 6 is an explanatory diagram for explaining the monitoring area 70 in the embodiment of the present invention.

  In this embodiment, an example will be described in which the liquid reservoirs 140a and 140b and the liquid reservoirs 141a and 141b of the microchip 1 are monitored to be filled with liquid.

  The information of the monitoring area 70 recorded in the monitoring area recording unit 910 is, for example, the coordinates X and Y and the width l of the monitoring area, and the n monitoring areas 70 are recorded as (Xn, Yn, ln), respectively. With respect to the coordinates of the monitoring area 70, the center of the marker 71 is the origin, the right-hand direction in FIG. 6 is the X-axis positive direction, and the upward direction is the Y-axis positive direction.

  In the present embodiment, the central coordinates of the monitoring areas 70a, 70b, 70c, and 70d are the central coordinates of the liquid reservoirs 140a and 140b and the liquid reservoirs 141a and 141b. The widths of the monitoring areas 70a, 70b, 70c, and 70d are L in both the X direction and the Y axis direction, and are distributed from the center coordinates.

  As shown in FIG. 6, the central coordinates of the monitoring area 70a are (−x1, y2), the central coordinates of the monitoring area 70b are (x1, y2), the central coordinates of the monitoring area 70c are (−x1, y1), and the monitoring area The center coordinates of 70d are (x1, y1). Therefore, the monitoring area 70a is (-x1, y2, L), the monitoring area 70b is (x1, y2, L), the monitoring area 70c is (-x1, y1, L), and the monitoring area 70d is (x1, y1, L). ) Is recorded as information of the monitoring area 70.

  In addition, processing and control performed based on the number of monitoring areas 70 and the state of the monitoring areas 70 are recorded as information on the monitoring areas 70. Control performed based on the state of the monitoring region 70 is, for example, liquid feeding control, temperature control, detection control, and the like.

  Information on the monitoring areas 70 of the plurality of microchips 1 is recorded in advance in the monitoring area recording unit 910. For example, when the type of the microchip 1 to be used is specified by operating the operation unit 87, the information on the corresponding monitoring area 70 is displayed. It has come to be obtained. In this way, even when an inspection is performed using various types of microchips 1 having different external shapes and channel shapes, monitoring according to the microchip 1 can be performed with a simple operation.

  In the present embodiment, control for detecting that the monitoring area 70 is filled with liquid will be described as an example.

  Next, the procedure in which the inspection apparatus 82 according to the embodiment of the present invention performs an inspection will be described with reference to FIGS.

  FIG. 7 is a flowchart for explaining a procedure for performing image processing by the image processing unit 410 according to the embodiment of the present invention. FIG. 8 is a flowchart for explaining a procedure for performing the inspection according to the embodiment of the present invention.

  Hereinafter, description will be made in the order of the flowchart of FIG.

  The image processing routine obtains information about the coordinates X and Y of the monitoring area 70, the width l (Xn, Yn, ln) of the monitoring area 70, and the image processing performed on the state of the monitoring area 70 from the main routine. Execute.

  S10: This is a step of photographing.

  The imaging control unit 414 instructs the illumination unit 26 and the imaging unit 24 to capture images at predetermined time intervals for a predetermined time specified from the main routine, and cause the control unit 99 to transmit image data. The image data received by the control unit 99 is sequentially stored in the RAM 97.

  S11: This is a step of extracting image data of the monitoring area 70.

  The image processing unit 410 extracts image data of an area corresponding to the monitoring area 70 from the image data stored in the RAM 97 based on the information of the monitoring area 70.

  S12: This is a step of analyzing the image.

  The image processing unit 410 analyzes the extracted image data. For example, the difference between the image data of the monitoring area 70a captured first and the image data of the monitoring area 70a captured after a certain time is extracted.

  S13: This is a step of calculating an evaluation value.

  The image processing unit 410 calculates an evaluation value from the analyzed result. For example, the area of the level difference portion of a predetermined level or more is calculated from the difference data of the image data extracted in S12.

  As described above, since the image data of the portion corresponding to the monitoring area 70 is extracted and the predetermined processing is performed, the processing time can be shortened.

  This is the end of the description of the image processing routine.

  Hereinafter, description will be made 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. Further, it is assumed that the type of the microchip 1 used for the inspection is specified by the operation of the operation unit 87.

  S101: This is a step of acquiring information on the monitoring area.

  The image processing unit 410 reads information from the monitoring area recording unit 910, coordinates X and Y of the monitoring area 70 of the corresponding microchip 1, the width L (Xn, Yn, Ln) of the monitoring area, and the state of the monitoring area 70 Information about image processing to be performed is obtained.

  In the present embodiment, control for detecting that the liquid reservoirs 140a and 140b and the liquid reservoirs 141a and 141b of the microchip 1 are sequentially filled with liquid will be described.

  S102: It is a step which starts liquid feeding.

  The pump drive control unit 411 instructs the pump drive unit 500 to send liquid from the micropump unit 75 to the microchip 1 in a predetermined order.

  S103: This is a step of calling an image processing routine.

  In this embodiment, in this step, the states of the monitoring area 70a and the monitoring area 70b are monitored for a predetermined time, and respective evaluation values are obtained. The information given as arguments includes information (−X1, Y2, L) of the monitoring area 70a, information (X1, Y2, L) of the monitoring area 70b, shooting time and time interval, evaluation value calculation parameters, and the like.

  S104: This is a step of confirming that the sample is divided into two.

  The flow path determination unit 412 determines whether or not the evaluation value calculated by the image processing routine is equal to or higher than a predetermined level. As the determination level, for example, a value obtained by actually measuring in advance an evaluation value when the amount of the sample is 90% of the prescribed amount is stored in the ROM 96.

  When it is below the predetermined level (step S104; No), the process proceeds to step S120.

  S120: This is a step of displaying a warning.

  The control unit 99 displays a warning that the amount of the sample is insufficient on the display unit 84 and stops the examination system 80.

  If the level is equal to or higher than the predetermined level (step S104; Yes), the process proceeds to step S105.

  S105: This is a step of calling an image processing routine.

  In this embodiment, in this step, the states of the monitoring area 70c and the monitoring area 70d are monitored for a predetermined time, and respective evaluation values are obtained. The information given as arguments includes the information (−X1, Y1, L) of the monitoring area 70c, the information (X1, Y1, L) of the monitoring area 70d, the shooting time and time interval, the calculation parameter of the evaluation value, and the like.

  S106: It is a step which confirms that the detection parts 111a and 111b are filled.

  The flow path determination unit 412 determines whether or not the evaluation value calculated by the image processing routine is equal to or higher than a predetermined level. As the determination level, for example, a value obtained by actually measuring the output signal level when the amount of the sample is 90% of the prescribed amount is stored in the ROM 96.

  If it is below the predetermined level (step S106; No), the process proceeds to step S120.

  S120: This is a step of displaying a warning.

  The control unit 99 displays a warning that the amount of the sample is insufficient on the display unit 84 and stops the examination system 80.

  If the level is equal to or higher than the predetermined level (step S106; Yes), the process proceeds to step S107.

  S107: 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 move the detection unit 22 in the direction of arrow S2 in FIG. 3, and the detection unit 22 detects the reaction result of the detection unit 111a. Stop at the position you want.

  S108: This is a step of measuring the 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.

  S108: 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. 8, and to a position where the detection result of the detection unit 111b is detected. Stop.

  S109: This is a step of measuring the 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 completed 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 for performing the inspection.

  In the present embodiment, an example in which a warning is displayed based on the result of image processing performed by the image processing unit 410 is described. However, the present invention is not limited to this control, and the result of image processing is used. Based on this, control such as increasing the pressure of the driving liquid discharged from the micropump unit 75 may be performed.

  Next, a second embodiment of the present invention will be described.

  FIG. 9 is an external view of the microchip 1 in the second embodiment of the present invention, and FIG. 10 is a circuit block diagram of a detection system 80 in the second embodiment of the present invention.

  In the second embodiment, a monitoring area recording unit 910 is provided in the microchip 1 as illustrated in FIG. 9, and a reading unit that reads the monitoring area recording unit 910 in the inspection apparatus 82 as illustrated in FIG. The difference from the first embodiment is that 27 is provided. Other configurations are the same as those of the first embodiment, and the same components are denoted by the same reference numerals and description thereof is omitted.

  The monitoring area recording unit 910 embedded in the microchip 1 may be a ROM or a flash memory, but the mechanism is simple if the reading unit 27 can read information in a non-contact manner using an information recording unit such as an IC tag. It is more preferable because the degree of freedom of arrangement increases. The IC tag is composed of an IC chip, and information on a recording medium in the IC can be read out from the reading unit 27 by radio waves.

  The IC tag embedded in the microchip 1 does not require a power source when using a passive system that receives the power wave transmitted from the reading unit 27 and reads and transmits information on the recording medium in the IC using the power obtained from the radio wave. This is more preferable.

  In this way, since the inspection device 82 reads the information on the monitoring area of the microchip 1 used for the inspection every time the inspection is performed, the information on the monitoring area of the microchip 1 used for the inspection need not be stored in the inspection device 82 in advance. Also good. In addition, it is easy to update or add information. Since it is not necessary to designate the type of the microchip 1 in terms of operation, the process can be simplified and an operation error can be prevented.

  The procedure in which the inspection apparatus 82 performs the inspection is in the order of the flowchart described with reference to FIG. 8. The difference is that information is acquired. The other procedures are the same and will not be described.

  Next, a third embodiment of the present invention will be described.

  FIG. 11 is an external view of a microchip 1 according to the third embodiment of the present invention.

  In the third embodiment, as shown in FIG. 11, the monitoring area recording unit 910 is, for example, a QR (Quick Response) code, and a QR code is printed at a predetermined position on the microchip 1 or a sheet on which the QR code is printed. Is affixed. The QR code specifications are standardized in JIS X 0510 and ISO / IEC 18004, and the information in the monitoring area 70 of the microchip 1 is converted into a QR code based on the standard.

  In this embodiment, a QR code is described as an example of a two-dimensional barcode, but any two-dimensional barcode can be used as long as it is a two-dimensional barcode that can record information of the monitoring area 70 such as Data Matrix, PDF417, and Maxi Code. May be used.

  In the third embodiment, as will be described later, the image processing unit 410 cuts out the monitoring area recording unit 910 (QR code) from the image data obtained by the imaging unit 24 capturing the microchip 1, and decodes the QR code based on the standard. is doing. Therefore, it is not necessary to provide the reading unit 27 as in the second embodiment. Other configurations are the same as those of the second embodiment, and a description thereof will be omitted.

  In the third embodiment, as in the second embodiment, the inspection device 82 reads the information on the monitoring area of the microchip 1 used for the inspection every time the inspection is performed. The inspection device 82 may not be stored. In addition, it is easy to update or add information. Since it is not necessary to designate the type of the microchip 1 in terms of operation, the process can be simplified and an operation error can be prevented.

  FIG. 12 is a flowchart for explaining the procedure of QR code analysis performed by the image processing unit 410 in the third embodiment of the present invention.

  S20: This is a step of photographing.

  The imaging control unit 414 instructs the illumination unit 26 and the imaging unit 24 to capture and transmit image data at predetermined time intervals for a predetermined time specified from the main routine. The received image data is sequentially stored in the RAM 97.

  S21: A step of extracting a QR code.

  The image processing unit 410 extracts image data corresponding to the QR code from the image data stored in the RAM 97.

  S22: This is a step of decoding the QR code.

  The image processing unit 410 decodes the extracted QR code based on the standard.

  S23: This is a step of acquiring information of the microchip 1.

  The image processing unit 410 acquires information on the monitoring area 70 from the decoded result, and passes the information to the main routine.

  As described above, since the information of the monitoring area of the microchip 1 can be acquired by the imaging unit 24 and the image processing unit 410, the reading unit 27 and the IC tag are unnecessary, and the inspection system 80 can be configured simply.

  This completes the description of the QR code analysis routine.

  The procedure of the inspection performed by the inspection apparatus 82 is in the order of the flowchart described with reference to FIG. 8. In the step of acquiring the monitoring area information in S101, the QR code analysis routine described in FIG. The difference is that information is read from 910 (QR code). The other procedures are the same and will not be described.

  As described above, according to the present invention, it is possible to provide an inspection apparatus and an inspection system that can monitor the liquid feeding states of a plurality of flow paths corresponding to microchips with a single imaging means.

It is an external view of the test | inspection system 80 in embodiment of this invention. It is explanatory drawing of the microchip 1 concerning the 1st Embodiment of this invention. It is a perspective view which shows an example of the internal structure of the test | inspection system 80 of embodiment of this invention. It is sectional drawing which shows an example of the internal structure of the test | inspection system 80 of embodiment of this invention. It is a circuit block diagram of inspection system 80 in a 1st embodiment of the present invention. It is explanatory drawing for demonstrating the monitoring area | region 70 in embodiment of this invention. It is a flowchart explaining the procedure in which the image process part 410 of embodiment of this invention performs an image process. It is a flowchart explaining the procedure of the test | inspection of embodiment of this invention. It is an external view of the microchip 1 in the 2nd Embodiment of this invention. It is a circuit block diagram of the detection system 80 in the 2nd Embodiment of this invention. It is an external view of the microchip 1 in the 3rd Embodiment of this invention. It is a flowchart for demonstrating the procedure of the QR code analysis which the image process part 410 performs in the 3rd Embodiment of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Microchip 22 Detection unit 24 Image pick-up part 25 Lens 26 Illumination part 27 Reading part 61 Detection unit drive motor 75 Micro pump unit 80 Inspection system 82 Inspection apparatus 83 Insertion port 84 Display part 87 Operation button 90 Packing 110 Drive liquid injection port 111 Detection Unit 113 Sample injection unit 121 Sample storage unit 141 Liquid reservoir unit 152 Temperature adjustment unit 250 Flow path 910 Monitoring area recording unit

Claims (9)

In an inspection device that measures the result of reacting a sample and a reagent that have moved through the flow path of a microchip,
Imaging means for capturing the flow path and acquiring image data;
Image processing means for performing image processing on image data captured by the imaging means;
Monitoring area recording means for recording information of a plurality of monitoring areas for monitoring the state of the flow path;
Have
The image processing means includes
An inspection apparatus that performs image processing based on the information. Control means for controlling each part of the inspection apparatus;
The inspection apparatus according to claim 1, wherein the control unit performs control based on a result of image processing performed on the image data by the image processing unit. Display means for displaying warning information;
The inspection apparatus according to claim 2, wherein the control unit causes the display unit to display the warning information based on a result of image processing performed on the image data by the image processing unit. In an inspection system that measures the result of reacting a sample and a reagent that have moved through the flow path of a microchip,
Imaging means for capturing the flow path and acquiring image data;
Image processing means for performing image processing on image data captured by the imaging means;
Monitoring area recording means for recording information of a plurality of monitoring areas for monitoring the flow path provided in the microchip;
Have
The image processing means includes
An inspection system that performs image processing based on the information. Control means for controlling each part of the inspection system;
The inspection system according to claim 4, wherein the control unit performs control based on a result of image processing performed on the image data by the image processing unit. Display means for displaying warning information;
6. The inspection system according to claim 5, wherein the control unit causes the display unit to display the warning information based on a result of image processing performed on the image data by the image processing unit. The monitoring area recording means is an IC tag,
The inspection system according to claim 4, further comprising non-contact reading means capable of reading information written on the IC tag in a non-contact manner. The inspection system according to claim 4, wherein the monitoring area recording unit is a two-dimensional barcode. The imaging means includes
Capture the image data by photographing the two-dimensional barcode,
The image processing means includes
The inspection system according to claim 8, wherein the information is acquired by performing image processing on the image data.

Images