JPWO2008093523A1 - Microchip inspection device - Google Patents

Abstract

In the present invention, there is a problem in that bubbles are generated when air is drawn into the micropump, or dust or the like enters, so that accurate liquid feeding cannot be performed. Therefore, by providing suction means, bubbles and dust are sucked into the flow path for supplying the driving liquid, so that a microchip inspection apparatus with high measurement accuracy can be provided.

Description

The present invention relates to a microchip inspection apparatus.

  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 using a microchip integrated on a chip has attracted attention. This is also referred to as μ-TAS (Micro Total Analysis System), and a reagent and a sample (for example, a urine, saliva, blood extracted from a subject subjected to a test, and a DNA-treated extraction solution extracted from the microchip) ) And the characteristics of the sample are examined by detecting the reaction.

When examining the characteristics of the sample using the microchip, the microchip is set in the inspection apparatus, and the driving liquid is supplied to the microchannel of the microchip by the liquid supply pump provided in the inspection apparatus. As a result, the reagent or sample stored in the microchip is pushed out by the driving liquid, and the reagent and the sample react to be guided to the detected part. In the detected portion, the target substance is detected by, for example, an optical detection method (see, for example, Patent Document 1).
JP 2006-266925 A

  However, the microchip is inserted into and removed from the inspection apparatus for each specimen inspection, and dust or the like floating in the work environment at that time adheres to the connection portion of the inspection apparatus with the microchip. Alternatively, when the microchip is pulled out while the inside of the micropump is in a negative pressure state, air is drawn into the micropump and bubbles are generated. Further, even when the inspection device is not used for a certain period, bubbles, dust, etc. enter the micro pump from the connection portion. If this happens, the micropump may not be able to perform accurate liquid feeding, or bubbles or dust may be sent into the microchip and detection may not be performed with high accuracy.

  An object of the present invention is to provide a microchip inspection apparatus that can remove bubbles and dust and perform accurate liquid feeding and accurate detection even if bubbles and dust are mixed into a flow path for driving liquid. Is to provide.

  The above object can be achieved by the following configuration.

1. A microchip housing portion capable of housing a microchip having a flow path through which a sample flows and an injection port into which a driving liquid for flowing the sample is injected;
A liquid feed pump for feeding the driving liquid toward the inlet of the microchip housed in the microchip housing section;
A connection portion having a supply port that contacts the injection port of the microchip stored in the microchip storage unit and supplies the driving liquid supplied by the liquid supply pump to the injection port;
A suction means capable of sucking the driving liquid from a supply port of the connection portion when a microchip is not housed in the microchip housing portion;
A microchip inspection apparatus comprising:

2. Having a liquid detection sensor for detecting the liquid feeding state of the driving liquid;
2. The microchip inspection apparatus according to 1, wherein the suction unit performs a suction operation based on a detection result of the liquid detection sensor.

  3. 3. The microchip inspection apparatus according to 1 or 2, wherein a suction operation by the suction means is performed before the start of inspection.

  4). 4. The microchip inspection apparatus according to any one of 1 to 3, wherein the suction unit covers a supply port of the connection part during standby.

  According to the present invention, even if air bubbles or dust are mixed in the flow path for supplying the driving liquid, the air bubbles or dust can be removed by sucking with the suction means, and accurate liquid feeding or high accuracy can be achieved. Detection can be performed.

It is an external view of the microchip inspection apparatus 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 sectional drawing which shows the form of 1st suction. It is the arrow view seen from the A direction of FIG. It is a perspective view which shows the form of 2nd suction.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Microchip 2 Chip press plate 4 Optical detection part 5 Micropump 6 Pump connection part 7 Suction means 8 Drive liquid on-off valve 10 Drive liquid tank 11 Drive liquid 71 Suction pump

  An embodiment of the present invention will be described. In addition, although this invention is demonstrated based on embodiment of illustration, this invention is not restricted to this embodiment. In addition, the following assertive description in the embodiment of the present invention shows the best mode, and does not limit the meaning or technical scope of the terms of the present invention.

Hereinafter, embodiments of the present invention will be described with reference to the drawings.
(Device 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 serves as a driving liquid tank 10 that stores a driving liquid 11 for feeding a sample and a reagent previously injected into the microchip 1 and a liquid feeding pump for supplying the driving liquid 11 to the microchip 1. A micropump 5 is provided. Further, there is a pump connection portion 6 as a connection portion provided with a supply port 61 for connecting the micropump 5 and the microchip 1 so that the driving liquid 11 does not leak. A temperature adjusting unit 3 for adjusting the temperature of a necessary part of the microchip 1 and a chip pressing plate 2 for bringing the microchip 1 into close contact with the temperature adjusting unit 3 and the pump connection portion 6 so as not to be displaced. Further, a pressing plate driving unit 21 for moving the chip pressing plate 2 up and down, a regulating member 22 for positioning the microchip 1 with respect to the micropump 5 with high accuracy, a reaction state between the specimen and the reagent in the microchip 1 and the like. A light detection unit 4 for detection is provided.

  The chip pressing plate 2 is retracted upward from the position shown in FIG. 2 in the initial state. 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 22. Thereafter, the chip pressing plate 2 is lowered by the pressing plate driving unit 21 and comes into contact with the microchip 1, and the lower surface of the microchip 1 is in close contact with the temperature adjustment unit 3 and the pump connection unit 6. As a result, the supply port 61 of the pump connection unit 6 and the injection port 13 of the microchip 1 are set in a matched state. In addition, the microchip accommodating part of this invention is comprised by the control member 22, the press plate 2, the temperature control unit 3, the pump connection part 6, etc. FIG.

  The temperature control unit 3 includes a Peltier element 31 and a heater 32 on a surface facing the microchip 1. When the microchip 1 is set in the inspection device 80, the Peltier element 31 and the heater 32 are in close contact with the microchip 1. It is like that. A part containing the reagent is cooled by the Peltier element 31 so that the reagent is not denatured, or a part where the specimen and the reagent react is heated by the heater 32 to promote the reaction.

The light detection unit 4 includes a light emitting unit 4a and a light receiving unit 4b. The light detecting unit 4 irradiates the microchip 1 with light from the light emitting unit 4a, and the light receiving unit 4b detects light transmitted through the microchip 1. The light receiving portion 4b is integrally provided inside the chip pressing plate 2. The light emitting part 4a and the light receiving part 4b are provided so as to face the detected part of the microchip 1.
(Micro pump)
Next, the micropump 5 will be described.

  The micropump 5 is located on the pump chamber 52, the piezoelectric element 51 that changes the volume of the pump chamber 52, the first throttle channel 53 located on the microchip 1 side of the pump chamber 52, and the driving fluid tank 10 side of the pump chamber. The second throttle channel 54 is formed. 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.
(Suction part)
Next, the suction means 7 according to the present invention will be described.
<First form>
FIG. 3 is a cross-sectional view showing a first suction mode. 4 is a view as seen from the direction of the arrow A in FIG. FIG. 3 shows that the microchip 1 is retracted from the pump connection portion 6 and the suction connection portion 70 is connected to the pump connection portion 6.

  The suction connection portion 70 is formed of, for example, a resin having flexibility (elasticity, shape followability) such as polytetrafluoroethylene or silicone resin in order to ensure necessary sealing performance and prevent leakage of driving liquid. It is preferable.

  Reference numeral 71 denotes a suction pump that sucks the driving liquid, and is illustrated with the sealing lid removed in order to make the structure easy to understand. The suction pump 71 includes a tube 73 provided along the inner wall 72 and a rotor 74 that rotates while pressing the tube 73 in a squeezed manner. When the rotor 74 rotates in the direction shown in the drawing, the tube 73 is pressed against the inner wall 72, the space in the tube 73 moves gradually, and the liquid and air in the micropump 5 are sucked. The sucked liquid is discharged into the liquid reservoir 75. Here, the suction pump 71 has been described by taking a tube pump using a tube as an example. However, the suction pump 71 is not necessarily a tube pump system, and any system can be used as long as it is a pump capable of suction.

  As shown in FIG. 4, the micropump 5 has a plurality of independent flow paths, and a pump connection portion 6 is provided corresponding to each flow path. A suction connection portion 70 is provided for each pump connection portion 6.

  Above the micropump 5, a liquid detection sensor 76 that includes a light-emitting unit and a light-receiving unit that detect a liquid-feeding state of the driving liquid 11 corresponding to a plurality of flow paths is provided. The substrate of the micropump 5 is made of, for example, a transparent material such as PDMS (polydimethylsiloxane) or polymethylmethacrylate (PMMA), which is an elastomer type silicone resin. The presence or absence of the driving liquid can be detected. Thereby, the liquid feeding state of each flow path of the micropump 5 can be grasped.

  If the presence of the driving liquid in the flow path is not detected by the liquid detection sensor 76 even though the micropump 5 is performing liquid feeding, the inspection device 80 determines that a liquid feeding failure has occurred, The suction means 7 provided in the flow path where the defect has occurred is driven. As a result, it is possible to remove bubbles and dust that cause liquid feeding failure.

  Further, for example, by performing suction by the suction means 7 before the start of the inspection, it is possible to remove the driving liquid 11 that has been deteriorated by being exposed to the air at the head portion or the driving liquid 11 in which the air is dissolved. Further, even when the driving liquid 11 evaporates and the driving liquid 11 is not filled up to the tip of the supply port 61 of the pump connection portion 6, the driving liquid 11 can be filled up to the tip of the supplying port 61. It is suppressed that air is sent to. Suction may be performed only when the inspection apparatus 80 has not been operated for a long time.

  Further, when the inspection device 80 is on standby (including when the power is turned off), it is preferable to place the suction connection portion 70 on the pump connection portion 6 and perform capping. Thereby, it is suppressed that refuse and air penetrate | invade from the pump connection part 6. FIG.

Therefore, in this embodiment, accurate liquid feeding can be performed, and accurate detection can be performed.
<Second form>
FIG. 5 shows a second suction configuration. A part different from the first suction mode will be described. As shown in FIG. 5, one suction connection portion 70 is provided so as to cover the entire plurality of pump connection portions 6, and one suction pump 71 is connected to the suction connection portion 700. If such a suction connection part 700 is used, the structure becomes simple.
(Summary)
As described above, according to the above-described embodiment, even if bubbles or dust is mixed in the flow path for supplying the driving liquid, the bubbles or dust can be removed by suction by the suction means 7. .

  Further, by sucking with the suction means 7, it is possible to remove the driving liquid that has been deteriorated by being exposed to the air in the head portion or the driving liquid in which the air is dissolved.

  In addition, by sucking with the suction means 7, even when the driving liquid evaporates and the driving liquid is not filled up to the tip of the supply port 61 of the pump connection portion 6, the driving liquid can be filled up to the tip of the supply port 61. It is possible to prevent air from being sent into the microchip 1.

  Further, when the inspection device 80 is on standby, the suction connection unit 70 is positioned on the pump connection unit 6 and is capped, so that intrusion of dust and air from the pump connection unit 6 can be suppressed.

  As a result, accurate liquid feeding can be performed, and accurate detection can be performed.

Claims (4)

A microchip housing portion capable of housing a microchip having a flow path through which a sample flows and an injection port into which a driving liquid for flowing the sample is injected;
A liquid feed pump for feeding the driving liquid toward the inlet of the microchip housed in the microchip housing section;
A connection portion having a supply port that contacts the injection port of the microchip stored in the microchip storage unit and supplies the driving liquid supplied by the liquid supply pump to the injection port;
A suction means capable of sucking the driving liquid from a supply port of the connection portion when a microchip is not housed in the microchip housing portion;
A microchip inspection apparatus comprising: Having a liquid detection sensor for detecting the liquid feeding state of the driving liquid;
The microchip inspection apparatus according to claim 1, wherein the suction unit performs a suction operation based on a detection result of the liquid detection sensor. 3. The microchip inspection apparatus according to claim 1, wherein a suction operation by the suction means is performed before the start of inspection. 4. The microchip inspection apparatus according to claim 1, wherein the suction unit covers a supply port of the connection portion during standby. 5.