JPWO2007097257A1 - Inspection device using microchip - Google Patents

Abstract

The present invention provides an inspection apparatus using a microchip that can obtain a high detection accuracy when detecting a plurality of detected parts on the microchip. Light is emitted from a light source at different timings to each detected part of the plurality of detected parts, and light received by the light receiving part is detected based on the irradiation timing of the light source.

Description

  The present invention relates to an inspection apparatus using a microchip.

  In recent years, a micro total analysis system (μTAS) that performs analysis by mixing and reacting a plurality of solutions on a microchip in which microchannels are integrated and processed is drawing attention. Has been.

  μTAS has advantages such as a small amount of sample, a short reaction time, and a small amount of waste. When used in the medical field, the burden on the patient can be reduced by reducing the amount of specimen (blood, urine, wiping liquid, etc.), and the cost of the test can be reduced by reducing the amount of reagent. In addition, since the amount of sample and reagent is small, the reaction time is greatly shortened, and the efficiency of the test can be improved. Furthermore, since the device is small, it can be installed in a small medical institution, and a test can be performed quickly regardless of location.

Patent Document 1 discloses a reaction state of a plurality of reaction detection channels by irradiating light to a plurality of reaction detection channels (detected parts) on a microchip and receiving light from the plurality of reaction detection channels. An inspection apparatus for detecting the above is described.
JP 2003-4752 A

  When the intervals between the detected parts in the plurality of detected parts are close to each other, if a plurality of detected parts are detected at the same time, the light from the adjacent light source is also received, which may reduce the detection accuracy. is there.

  Patent Document 1 does not describe the detection timing of the detected part.

  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 using a microchip that can obtain a high detection accuracy when detecting a plurality of detected parts on the microchip. It is said.

  An inspection apparatus using a microchip according to the present invention includes: a microchip housing portion that can accommodate a microchip having a plurality of detection portions; and a plurality of detection portions of the microchip that are accommodated in the microchip storage portion. A light source that receives light from the light source via the plurality of detected portions of the microchip housed in the microchip housing portion, and each detected portion of the plurality of detected portions And a control unit that irradiates light from the light source at different timings and detects light received by the light receiving unit based on irradiation timing of the light source.

  According to the present invention, even when the intervals between the detected parts in the plurality of detected parts are close to each other, the light for detecting the other detected part is detected at the detection timing of the detected part. And high detection accuracy is obtained.

It is an external view of the test | inspection apparatus using the microchip which concerns on this embodiment. It is a block diagram of the test | inspection apparatus using the microchip which concerns on this embodiment. It is a block diagram of the microchip which concerns on this embodiment. It is a principal part block diagram of the test | inspection apparatus using the microchip which concerns on this embodiment. It is a control block diagram of the photon detection part which concerns on this embodiment. It is a flowchart of the light detection control which concerns on this embodiment. It is a timing chart which showed the light emission timing of each light emission part in the light detection control concerning this embodiment, and the detection timing of each light reception part.

Explanation of symbols

1 Microchip 4a Light emitting unit 4b Light receiving unit 80 Inspection device 90 CPU
92 ROM
111a, 111b, 111c, 111d Detected part

  In the present embodiment, as an example, a case where a specimen and a reagent are reacted on a microchip is shown, but the present invention is not limited to this, and can be applied to a case where at least two types of fluids are mixed on a microchip.

(Basic configuration)
FIG. 1 is an external view of an inspection apparatus 80 using the microchip according to the present embodiment. The inspection device 80 is a device that automatically reacts a sample and a reagent previously injected into the microchip 1 and automatically outputs a reaction result.

  The casing 82 of the inspection device 80 is provided with an insertion port 83 for inserting the microchip 1 into the device, a display unit 84, a memory card slot 85, a print output port 86, an operation panel 87, and an external input / output terminal 88. It has been.

  The person in charge of inspection inserts the microchip 1 in the direction of the arrow in FIG. 1 and operates the operation panel 87 to start the inspection. Inside the inspection device 80, the reaction in the microchip 1 is automatically inspected, and when the inspection is completed, the result is displayed on the display unit 84. 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. After completion of the inspection, the inspection person takes out the microchip 1 from the insertion port 83.

  FIG. 2 is a configuration diagram of an inspection apparatus 80 using the microchip according to the present embodiment. FIG. 2 shows a state where the microchip is inserted from the insertion port 83 shown in FIG. 1 and the setting is completed.

  The inspection apparatus 80 includes a driving liquid tank 10 that stores a driving liquid 11 for feeding a sample and a reagent previously injected into the microchip 1, a pump 5 for supplying the driving liquid 11 to the microchip 1, and a pump 5. Packing 6 that connects the microchip 1 and the microchip 1 without leakage, a temperature control unit 3 that controls the temperature of a necessary portion of the microchip 1, a chip pressing plate 2 that is in close contact with the packing 6 so that the microchip 1 is not displaced, and chip pressing A pressing plate drive unit 32 for raising and lowering the plate 2, a regulating member 31 for accurately positioning the microchip 1 with respect to the pump 5, and a light detection unit 4 for detecting a reaction state between the specimen and the reagent in the microchip 1. (Light emitting unit 4a, light receiving unit 4b) and the like. The light receiving portion 4b is provided inside the chip pressing plate 2 and has an integral structure.

  In the initial state, the chip pressing plate 2 is retracted upward from the state of FIG. Thereby, the microchip 1 can be inserted / removed in the direction of the arrow X, and the person inspecting inserts the microchip 1 from the insertion port 83 (see FIG. 1) until it comes into contact with the regulating member 31. Thereafter, the chip pressing plate 2 is moved downward by the pressing plate driving unit 32 and comes into contact with the microchip 1, and the lower surface of the microchip 1 is in close contact with the temperature control unit 3 and the packing 6.

  The temperature control unit 3 controls the temperature of a necessary part of the microchip 1. For example, the part containing the reagent is cooled so that the reagent is not denatured, or the part where the sample and the reagent react is heated. And has a function of promoting the reaction.

  The pump 5 includes a pump chamber 52, a piezoelectric element 51 that changes the volume of the pump chamber 52, a first throttle channel 53 that is located on the microchip 1 side of the pump chamber 52, and a first that is located on the drive fluid tank 10 side of the pump chamber. It is composed of two throttle channels 54 and the like. The first throttle channel 53 and the second throttle channel 54 are narrow and narrow channels, and the first throttle channel 53 is longer than the second throttle channel 54.

  In the case where the driving liquid 11 is fed in the forward direction (direction toward the microchip 1), first, the piezoelectric element 51 is driven so as to rapidly reduce the volume of the pump chamber 52. Then, a turbulent flow is generated in the second throttle channel 54 that is a short throttle channel, and the channel resistance in the second throttle channel 54 is relatively larger than that of the first throttle channel 53 that is a throttle channel. growing. As a result, the driving liquid 11 in the pump chamber 52 is predominantly pushed toward the first throttle channel 53 and fed. Next, the piezoelectric element 51 is driven so that the volume of the pump chamber 52 is gradually increased. Then, the driving liquid 11 flows from the first throttle channel 53 and the second throttle channel 54 as the volume in the pump chamber 52 increases. At this time, since the length of the second throttle channel 54 is shorter than that of the first throttle channel 53, the channel resistance of the second throttle channel 54 is smaller than that of the first throttle channel 53. Thus, the driving liquid 11 flows predominantly from the second throttle channel 54 into the pump chamber 52. When the piezoelectric element 51 repeats the above operation, the driving liquid 11 is fed in the forward direction.

  On the other hand, when the driving liquid 11 is fed in the reverse direction (direction toward the driving liquid tank 10), first, the piezoelectric element 51 is driven so that the volume of the pump chamber 52 is gradually reduced. Then, since the length of the second throttle channel 54 is shorter than that of the first throttle channel 53, the channel resistance of the second throttle channel 54 is smaller than that of the first throttle channel 53. . As a result, the driving liquid 11 in the pump chamber 52 is predominantly pushed out toward the second throttle channel 54 and fed. Next, the piezoelectric element 51 is driven so that the volume of the pump chamber 52 is rapidly increased. Then, the driving liquid 11 flows from the first throttle channel 53 and the second throttle channel 54 as the volume in the pump chamber 52 increases. At this time, turbulent flow is generated in the second throttle channel 54, which is a short throttle channel, and the channel resistance in the second throttle channel 54 is relatively larger than that of the first throttle channel 53, which is a throttle channel. Become bigger. As a result, the driving liquid 11 flows into the pump chamber 52 predominantly from the first throttle channel 53. When the piezoelectric element 51 repeats the above operation, the driving liquid 11 is fed in the reverse direction.

  FIG. 3 is a configuration diagram of the microchip 1 according to the present embodiment. An example configuration is shown, and the present invention is not limited to this.

  In FIG. 3A, an arrow indicates an insertion direction in which the microchip 1 is inserted into an inspection apparatus 80 to be described later, and FIG. 3A illustrates a surface that becomes the lower surface of the microchip 1 at the time of insertion. FIG. 3B is a side view of the microchip 1.

  As shown in FIG. 3B, the microchip 1 includes a groove forming substrate 108 and a covering substrate 109 that covers the groove forming substrate 108.

  The microchip 1 according to the present embodiment includes a minute groove-like channel (microchannel) and a functional component (channel element) for performing chemical analysis, various inspections, sample processing / separation, chemical synthesis, and the like. ) Are arranged in an appropriate manner according to the application. An example of processing performed in the microchip 1 by these fine flow paths and flow path elements will be described with reference to FIG. FIG. 3C shows a state where the coated substrate 109 is removed in FIG.

  The fine flow path is provided with a sample storage unit 121 that stores a sample liquid, a reagent storage unit 120 that stores a reagent, a positive control storage unit 122 that stores a positive control, a negative control storage unit 123 that stores a negative control, and the like. ing. Reagents, positive controls, and negative controls are stored in advance in the storage units. The positive control reacts with the reagent and shows positive, and the negative control reacts with the reagent and shows negative, and is used to confirm whether or not an accurate test has been performed.

  The sample injection unit 113 is an injection unit for injecting the sample into the microchip 1, and the driving liquid injection units 110 a to 110 d are injection units for injecting the driving liquid 11 into the microchip 1.

  First, prior to performing a test using the microchip 1, the person in charge of the test injects a sample from the sample injection unit 113 using a syringe or the like. As shown in FIG. 3C, the sample injected from the sample injection unit 113 is stored in the sample storage unit 121 through the communicating fine channel.

  Next, the microchip 1 into which the sample is injected is inserted into the insertion port 83 of the inspection apparatus 80 shown in FIG. 1 by the inspection person, and set as shown in FIG.

  Next, the pump 5 shown in FIG. 2 is driven in the forward direction, and the driving liquid 11 is injected from the driving liquid injection units 110a to 110d. The driving liquid 11 injected from the driving liquid injection unit 110 a pushes out the sample stored in the sample storage unit 121 through the communicating fine flow path, and sends the sample to the junction unit 124. The driving liquid 11 injected from the driving liquid injection section 110 b pushes out the positive control stored in the positive control storage section 122 through the communicating fine flow path, and sends the positive control to the junction section 125. The driving liquid 11 injected from the driving liquid injection section 110 c pushes out the negative control stored in the negative control storage section 123 through the communicating fine flow path, and sends the negative control to the junction section 126. The driving liquid 11 injected from the driving liquid injection part 110d pushes out the reagent stored in the reagent storage part 120 through the communicating fine flow path, and sends the reagent into the merging parts 124 to 126.

  In this way, the sample and the reagent merge at the junction 124, the positive control and the reagent merge at the junction 125, and the negative control and the reagent merge at the junction 126.

  Thereafter, a part of the mixed liquid of the specimen and the reagent merged at the merging portion 124 is sent to the detected portion 111a. A part of the mixed liquid of the specimen and the reagent joined at the joining part 124 and a part of the mixed liquid of the positive control and the reagent joined at the joining part 125 are sent to the detected part 111b. A part of the mixed liquid of the positive control and the reagent merged in the merge unit 125 is sent to the detected unit 111c. The liquid mixture of the negative control and the reagent merged at the merge unit 126 is sent to the detected unit 111d.

  The detected part window 111e and the detected parts 111a to 111d are provided for optically detecting the reaction of each liquid mixture, and are made of a transparent member such as glass or resin.

(Configuration of light detection unit)
FIG. 4 is a configuration diagram of the light detection unit 4 according to the present embodiment. In FIG. 2, the microchip 1, the light emitting unit 4 a, and the light receiving unit 4 b correspond to a view seen from the right side in the X direction.

  The light emitting unit 4a is composed of four light emitting units 4a1, 4a2, 4a3, 4a4, and each light emitting unit is provided so as to face the detected portions 111a, 111b, 111c, 111d of the microchip 1, respectively. . As the light source of the light emitting unit 4a, an LED, a laser diode, or the like can be used.

  The light receiving unit 4b is composed of four light receiving units 4b1, 4b2, 4b3, 4b4, and each light receiving unit is provided to face the four light emitting units 4a1, 4a2, 4a3, 4a4 through the microchip 1, respectively. It has been. A photodiode or the like can be used as the light receiving element of the light receiving unit 4b.

  The light emitted from the four light emitting units 4a1, 4a2, 4a3, 4a4 is transmitted through the detected portions 111a, 111b, 111c, 111d of the microchip 1, respectively, and the four light receiving units 4b1, 4b2, 4b3, 4b4. Are received by each.

(Light detection control)
FIG. 5 is a control configuration diagram of the light detection unit 4 according to the present embodiment. A ROM 92, a RAM 93, a nonvolatile memory 94, a light emitting unit 4a, and a light receiving unit 4b are connected to each other by a bus 91, with a CPU 90 executing control of the light detecting unit 4 according to a program. Normally, device components other than the light detection unit 4 are also connected to the CPU 90 via the bus 91, but are omitted here because they are not directly related to this control.

  The ROM 92 stores a light detection control program and data necessary for control, and the CPU 90 executes control of the light detection unit 4 using these programs and data.

  The RAM 93 is used as a work area by the CPU 90 and temporarily stores programs and data necessary for the CPU 90 to execute control.

  The nonvolatile memory 94 stores the detection result in association with the detected units 111a, 111b, 111c, and 111d.

  FIG. 6 is a flowchart of light detection control according to the present embodiment, and FIG. 7 is a timing chart showing the light emission timing of each light emitting unit and the detection timing of each light receiving unit in the light detection control. Hereinafter, the light detection control will be described with reference to FIGS. 6 and 7. The light detection control is performed by the CPU 90 executing a process based on a light detection control program stored in the ROM 92.

  First, at a predetermined timing (time t1 in FIG. 7), the CPU 90 drives the light emitting unit 4a1 to emit light (step S1). The light emission time is set to T1.

  Next, the CPU 90 delays T2 time from the light emission start time t1 of the light emitting unit 4a1 to detect the light receiving unit 4b1 (step S2). The detection time T3 of the light receiving unit 4b1 is set to (T1-T2) or less, and the detection of the light receiving unit 4b1 ends before the light emission of the light emitting unit 4a1 ends. Thereby, the detected part 111a is detected.

  Next, when T4 time (T4> T1) elapses from the light emission start time t1 of the light emitting unit 4a1, the CPU 90 drives the light emitting unit 4a2 to emit light (step S3). The light emission time of the light emitting unit 4a2 is set to T1 as in the case of the light emitting unit 4a1.

  Next, the CPU 90 delays T2 time from the light emission start time t2 of the light emitting unit 4a2 to detect the light receiving unit 4b2 (step S4). The detection time T3 of the light receiving unit 4b2 is set to (T1-T2) or less as in the case of the light receiving unit 4b1, and the detection of the light receiving unit 4b2 ends before the light emission of the light emitting unit 4a2 ends. ing. Thereby, the detected part 111b is detected.

  Next, when the T4 time (T4> T1) has elapsed from the light emission start time t2 of the light emitting unit 4a2, the CPU 90 drives the light emitting unit 4a3 to emit light (step S5). The light emission time of the light emitting unit 4a3 is set to T1 as in the case of the light emitting unit 4a1 and the light emitting unit 4a2.

  Next, the CPU 90 detects the light receiving unit 4b3 with a delay of T2 time from the light emission start time t3 of the light emitting unit 4a3 (step S6). The detection time T3 of the light receiving unit 4b3 is set to (T1-T2) or less as in the case of the light receiving unit 4b1 and the light receiving unit 4b2, and the detection of the light receiving unit 4b3 is completed before the light emission of the light emitting unit 4a3 is completed. It is supposed to be. Thereby, the detected part 111c is detected.

  Next, when the T4 time (T4> T1) has elapsed from the light emission start time t3 of the light emitting unit 4a3, the CPU 90 drives the light emitting unit 4a4 to emit light (step S7). The light emission time of the light emitting unit 4a4 is set to T1 as in the case of the light emitting unit 4a1, the light emitting unit 4a2, and the light emitting unit 4a3.

  Next, the CPU 90 delays T2 time from the light emission start time t4 of the light emitting unit 4a4 to detect the light receiving unit 4b4 (step S8). The detection time T3 of the light receiving unit 4b4 is set to (T1-T2) or less as in the case of the light receiving unit 4b1, the light receiving unit 4b2, and the light receiving unit 4b3, and before the light emission of the light emitting unit 4a4 ends, the light receiving unit 4b4. Detection ends. Thereby, the detected part 111d is detected.

  Finally, the CPU 90 stores each detection result obtained in steps S2, S4, S6, and S8 in the nonvolatile memory 94 in association with the corresponding detected part (step S9).

  As described above, in the light detection control, the four light emitting units 4a1, 4a2, 4a3, 4a4 are caused to emit light at different times, and the signals from the four light receiving units 4b1, 4b2, 4b3, 4b4 are synchronized with the light emission timing. Is detected, and each detected portion is detected.

  As a result, even when the intervals between the detected parts in the plurality of detected parts are close to each other, light for detecting another detected part is incident on the light receiving part at the detection timing of the detected part. And high detection accuracy can be obtained.

  In the present embodiment, detection of the light receiving parts 4b1, 4b2, 4b3, 4b4 is performed with a delay of T2 hours from the light emission start time of the light emitting parts 4a1, 4a2, 4a3, 4a4. Thereby, it can detect after the light quantity of LED and a laser diode used for a light emission part is stabilized, and high detection accuracy is obtained.

  In the present embodiment, the four light emitting units 4a1, 4a2, 4a3, 4a4 are provided. However, only one light emitting unit is provided, and the one light emitting unit is provided at a position facing each detected unit at the time of detection. You may make it move. The light receiving unit 4b also includes four light receiving units 4b1, 4b2, 4b3, and 4b4. However, only one light receiving unit is provided, and the one light receiving unit is provided at a position facing each detected unit at the time of detection. May be moved.

Claims (5)

A microchip accommodating portion capable of accommodating a microchip having a plurality of detected portions;
A light source for irradiating light to the plurality of detected parts of the microchip housed in the microchip housing part;
A light receiving unit that receives light from the light source via the plurality of detected portions of the microchip housed in the microchip housing unit;
A control unit that irradiates light from the light source with different timings to the detected parts of the plurality of detected parts, and detects light received by the light receiving part based on irradiation timings of the light sources;
An inspection apparatus using a microchip, comprising: The light source includes a plurality of light sources provided corresponding to each of the plurality of detection units, and the control unit causes the plurality of light sources to emit light at different timings. An inspection apparatus using the microchip according to item 1. The light source is a single light source, and is movably provided at a position facing the plurality of detected parts of a microchip accommodated in the microchip accommodating part. An inspection apparatus using the microchip according to item 1. The light receiving unit is a single light receiving unit, and is provided so as to be movable to a position facing the plurality of detected portions of a microchip housed in the microchip housing section. 4. An inspection apparatus using the microchip according to any one of items 1 to 3. The inspection using the microchip according to any one of claims 1 to 4, wherein the control unit starts detection of the light receiving unit with a delay from the start of light emission of the light source. apparatus.