JP5545233B2 - Inspection system - Google Patents

Description

The present invention relates to inspection systems for use in inspection and analysis of such analytes contained in the test liquid, particularly, it relates to an inspection system for use in biochemical inspection.

  As an inspection system used for gene analysis, biochemical inspection, and the like, the one described in Patent Document 1 is known. In this inspection system, as shown in FIGS. 13A and 13B, an inspection chip 100 in which a plurality of inspection liquids are accommodated, and a liquid feeding apparatus that moves each inspection liquid by a nozzle member 102. 104.

  Specifically, the test chip 100 includes a plurality of chemical solution storage units 106, 106,... For storing each test liquid, and a reaction storage unit 108 into which each test liquid is injected. The reaction storage unit 108 includes a liquid injection unit 110 into which the nozzle member 102 is inserted, and a liquid storage unit 112 in which a biochemical reaction is caused by storing and mixing each test liquid injected from the liquid injection unit 110. It consists of. The liquid injection part 110 has an inner peripheral surface 110b having a shape corresponding to the outer peripheral surface 102a at the tip of the nozzle member 102 and extending downward from the opening 110a at the upper end. Thus, when the tip of the nozzle member 102 is inserted into the liquid injection part 110, the outer peripheral surface 102a of the tip of the nozzle member 102 and the inner peripheral surface 110b of the liquid injection part 110 are brought into close contact with each other. When the inspection liquid is injected, it is possible to prevent the liquid from leaking between them.

  The liquid feeding device 104 includes a nozzle driving unit 120 that moves the nozzle member 102 up and down and moves it in the horizontal direction, and a pump that draws the inspection liquid from the nozzle member 102 and discharges the inspection liquid from the nozzle member 102 (not shown). And a control unit (not shown) for controlling the nozzle driving unit 120 and the pump.

  In this inspection system, the control unit lowers the nozzle member 102 after moving the nozzle member 102 above the predetermined chemical solution storage unit 106 by the nozzle driving unit 120. When the tip of the nozzle member 102 is inserted into the chemical solution storage unit 106, the control unit controls the pump so that the nozzle member 102 sucks the test liquid in the chemical solution storage unit 106. When the inspection liquid is sucked into the nozzle member 102, the control unit raises the nozzle member 102 by the nozzle driving unit 120 and then moves the nozzle member 102 onto the liquid injection unit 110 of the reaction storage unit 108. Let The control unit lowers the nozzle member 102 by the nozzle driving unit 120 and inserts the tip of the nozzle member 102 into the liquid injection unit 110. When the nozzle member 102 is lowered until the outer peripheral surface 102a of the tip end portion of the nozzle member 102 and the inner peripheral surface 110b of the liquid injection unit 110 are in close contact with each other, the control unit pumps the inspection liquid from the nozzle member 102. To control. As a result, the inspection liquid is injected into the liquid container 112.

  By repeating a series of operations for moving the test liquid from the chemical solution storage unit 106 to the liquid storage unit 112 and injecting the test liquid in each chemical solution storage unit 106 into the liquid storage unit 112, the liquid storage unit 112. A biochemical reaction occurs at, and the result of the biochemical test is derived based on the result.

JP 2007-275005 A

  However, in the above inspection system, when the tip of the nozzle member 102 is inserted into the liquid injection unit 110 in order to inject the inspection liquid into the liquid storage unit 112, the operation of the liquid feeding device 104 (nozzle drive unit 120) is activated. The horizontal position of the tip of the nozzle member 102 may be slightly shifted due to an error or the like. In this case, when the nozzle member 102 is lowered, the tip end portion is inserted into the liquid injection portion 110 such that the tip end thereof rubs against the inner peripheral surface 110b of the liquid injection portion 110 (see FIG. 14).

  At this time, the test liquid inside the nozzle member 102 may be accumulated like a ridge at the tip of the nozzle member 102 (see FIG. 5). This is due to the wettability of the nozzle member 102 and the gravity applied to the inspection liquid. Thus, when the tip of the nozzle member 102 is inserted into the liquid injection part 110, the inspection liquid collected like a spear at the tip adheres to the inner peripheral surface 110b. Therefore, when performing a biochemical test or the like using a plurality of test liquids, a plurality of test liquids adhere to the inner peripheral surface 110b of the liquid injection unit 110, and a mixture of these is used in the biochemical reaction. May be a chemical noise factor.

  In order to ensure sufficient accuracy in biochemical reactions, it is necessary to reduce the chemical noise factor as much as possible. Therefore, when the chemical noise factor as described above is generated in the inspection process, it is difficult to ensure sufficient accuracy in biochemical inspection or the like.

Therefore, in view of the above problems, the present invention attaches the inspection liquid to a portion other than the liquid storage portion of the inspection chip when the inspection member is injected and sucked into the liquid storage portion of the inspection chip by the nozzle member. It is an object of the present invention to provide an inspection system that can prevent the above-described problem.

As a result of various studies, the present inventor has found that the above object is achieved by the present invention described below. That is, an inspection system according to an aspect of the present invention is an inspection system that performs inspection of a specimen using a plurality of different inspection liquids, and includes a liquid storage portion that can store the inspection liquid therein. An inspection chip having an insertion opening for communicating the inside and the outside of the liquid storage portion formed on the surface thereof, and a nozzle having a leading end opened, and a nozzle for injecting and sucking the inspection liquid from the opening into the liquid storage portion A nozzle drive unit that lifts and lowers the member, inserts the tip of the nozzle member into the liquid container through the insertion opening, or discharges the inspection liquid from the opening of the nozzle member. And a pump for sucking, and a liquid feeding device having a control unit for controlling the nozzle driving unit and the pump, respectively, and the nozzle member includes the nozzle member therein. A liquid storage section that extends upward from the opening of the end and can store the inspection liquid; and the control section raises and lowers the nozzle member by the nozzle driving section, and a tip of the liquid storage section passes through the insertion opening. Sometimes, the inspection liquid in the liquid storage part is caused to be sucked into the pump so that the inspection liquid is rising in the liquid storage part, and the inspection chip has the liquid storage part. A chip body in which a chip opening that communicates the inside and the outside of the part is formed on the surface thereof, and a sheet-like elastic member that covers the chip opening leaving the insertion opening having a smaller diameter than the chip opening. The tip portion of the nozzle member has a tapered outer peripheral surface whose diameter decreases toward the tip, and the elastic member is configured such that the tip portion of the nozzle member passes through the insertion opening and the liquid. A first sheet having elasticity and ductility so that a peripheral edge of an insertion opening of the elastic member comes into close contact with the outer peripheral surface of the nozzle member when inserted into the container, and is bonded to the first sheet. And a multilayer sheet having a second sheet having a ductility smaller than that of the first sheet .

According to the inspection system of the present invention, when the nozzle member is moved up and down and the tip of the nozzle member passes through the insertion opening, the inspection liquid stored in the nozzle member adheres to the peripheral edge of the insertion opening in the inspection chip. Can be prevented. This is because when the nozzle member moves up and down, the tip of the nozzle member is inserted by allowing the inspection liquid to rise in the liquid reservoir inside the nozzle member when the tip of the nozzle member passes through the insertion opening. This is because the liquid for inspection can be prevented from accumulating like a ridge from the tip while passing through the opening.
Further, since the outer peripheral surface of the tip of the nozzle member and the peripheral edge of the insertion opening of the elastic member are brought into close contact with each other by inserting the tip of the nozzle member into the liquid container, the nozzle can be used even if the pressure in the liquid container varies. Liquid leakage from the insertion opening into which the member is inserted can be prevented. In addition, since the diameter of the opening into which the nozzle member is inserted (insertion opening) is smaller than that of the opening (chip opening) when no elastic member is provided, the inspection liquid adheres to the peripheral edge of the insertion opening of the inspection chip. This can be prevented more effectively.
In this case, the elastic member is a sheet-like member that seals the chip opening, and the insertion opening has a tip end portion of the nozzle member in the liquid storage portion from the chip opening sealed by the elastic member. Since the liquid container is sealed until the inspection is performed by the inspection system (until the insertion opening is formed in the elastic member), the liquid container is sealed. It is possible to reliably prevent evaporation of each inspection liquid stored in the storage portion and mixing of other substances into the inspection liquid. Or it becomes possible to maintain the state (for example, humidity etc.) in a flow path.

  In addition, the control unit uses the pump so that when the tip of the nozzle member passes through the insertion opening, the inspection liquid is positioned above the opening of the tip in the liquid reservoir. By aspirating the inspection liquid in the liquid storage part, the inspection liquid is located inside the nozzle member, so that the inspection liquid stored in the nozzle member is placed in the peripheral edge of the insertion opening of the inspection chip. Adhesion can be reliably prevented.

  If the nozzle member is a pipette tip that is detachably attached to the nozzle drive unit or the pump, the dirty pipette tip after being used a predetermined number of times or in a predetermined step can be easily replaced with a clean pipette tip. This makes it easier to maintain the accuracy of the inspection. Further, if an inexpensive pipette tip such as a general-purpose product is used, an increase in cost can be suppressed even if the replacement frequency of the pipette tip is high.

As described above, according to the present invention, when the inspection liquid is injected and sucked into the liquid storage part of the inspection chip by the nozzle member, the adhesion of the inspection liquid to the part other than the liquid storage part of the inspection chip is prevented. An inspection system can be provided.

It is a mimetic diagram of an inspection system concerning this embodiment. (A) is a schematic longitudinal cross-sectional view of the test | inspection chip used for the said test | inspection system, (B) is a schematic longitudinal cross-sectional view of the prism main-body part in the test | inspection chip concerning other embodiment. It is a schematic block diagram of the liquid feeding part and control part of the state by which the test | inspection chip of the said test | inspection system is arrange | positioned. It is a functional block diagram of the said control part. It is a figure which shows the state in which the test liquid accumulated in the front-end | tip of a nozzle member. It is a figure for demonstrating the formation method of the air hole to the said test | inspection chip. It is a figure for demonstrating injection | pouring and suction | inhalation of the liquid for a test | inspection to the flow path of the said test | inspection chip, Comprising: (A) shows the state before drilling a sealing member, (B) is test | inspected in a flow path. The state in which the liquid for inspection is being injected is shown, and (C) shows the state in which the inspection liquid is being sucked from the flow path. It is a figure for demonstrating the state of each sheet | seat when an insertion opening is formed in the sealing member of the said test | inspection chip, (A) shows the state before all the sheets reach | attain a fracture | rupture limit, B) shows a state where the second sheet has reached the breaking limit, and (C) shows a state where all the sheets have reached the breaking limit and an insertion opening has been formed. It is a figure for demonstrating the pressure in the flow path and peeling moment which are added to an insertion opening peripheral part. It is a schematic block diagram of the detection part in the inspection apparatus of the said inspection system. It is a figure for demonstrating the elastic member for filling the clearance gap between the nozzle member which concerns on other embodiment, and a flow-path opening peripheral part. It is a figure for demonstrating the sealing member which concerns on other embodiment. It is a figure for demonstrating the conventional test | inspection system. It is a figure which shows the insertion state of the nozzle member to the liquid injection | pouring part of a test | inspection chip in the conventional test | inspection system.

  Hereinafter, an embodiment of the present invention will be described with reference to the accompanying drawings.

  The test system according to the present embodiment is used for a biochemical test for detecting and analyzing a specimen such as an antigen using a plurality of test liquids. As shown in FIG. 1, the inspection system includes an inspection chip 10 and an inspection device 2. The inspection device 2 is a device that generates a biochemical reaction in the inspection chip 10 and measures and analyzes the result. A liquid feed that generates a biochemical reaction by injecting and sucking the inspection liquid L into the inspection chip 10. Unit (liquid feeding device) 30, holding / carrying unit 57 that can hold test chip 10 in a predetermined position and transport the test chip 10 to a predetermined position, detection unit 60 that detects a sample or the like, and test apparatus 2 And a control unit 70 for controlling the respective units.

  Here, as the plurality of test liquids L in the present embodiment, a sample solution containing a specimen to be detected, a cleaning liquid used when cleaning the flow path 22 of the test chip 10, a buffer liquid, or the like is used. However, the present invention is not limited to these, and includes an antibody solution, a labeled antibody solution, a reaction inhibiting solution, and other chemical solutions used in biochemical examinations.

  The inspection chip 10 is a chip used for inspection and analysis of biological materials by antigen-antibody reaction or the like. The test chip 10 according to the present embodiment is an analyzer that analyzes a specimen based on a change in the resonance angle of surface plasmon resonance, or a specimen or a fluorescent substance labeled on the specimen is excited by an enhanced electric field based on surface plasmon resonance. This is a so-called Kretschmann-arranged sensor chip used in an analyzer for measuring emitted fluorescence.

  Specifically, as shown in FIG. 2A, the inspection chip 10 includes an inspection chip main body (chip main body) 11 and end openings (flow container portions) 22 provided in the inspection chip 10 ( And a sealing member (elastic member) 12 for sealing the channel opening) 25.

  The inspection chip body 11 has a metal film 13, and the prism portion 14 in which surface plasmon resonance occurs in the metal film 13 when the excitation light α (see FIGS. 1 and 10) incident on the inspection chip body is reflected by the metal film 13. And a flow path member 15 that forms a flow path 22 through which the inspection liquid L flows in cooperation with the prism portion 14.

  The prism portion 14 includes a prism main body portion into which excitation light α for generating surface plasmons is incident and a metal film 13 formed on a specific surface 17 of the prism main body portion 16.

  The prism main body 16 has an incident surface 18 on which the excitation light α from the excitation light source 61 of the detection unit 60 is incident when the inspection chip 10 is installed in the detection unit 60 of the inspection apparatus 2 and analyzes the specimen. And a film-forming surface 17 that reflects the excitation light α incident on the inside by the metal film 13 formed on the surface, and the excitation light α that is reflected by the metal film 13 on the film-forming surface 17 16 includes a light exit surface 19 that emits light to the outside. The prism main body 16 is made of transparent glass or resin.

  In addition, although the prism main-body part 16 of this embodiment is comprised only with the prism, it is not limited to this. For example, as shown in FIG. 2B, the prism main body 16A may include a prism 161 and a substrate 162 on which the metal film 13 is provided. That is, the prism portion 14 </ b> A includes a substrate portion 162 having a substrate 163 and a metal film 13 formed on the substrate 163, and a prism 161. Specifically, the substrate 163 has the same refractive index as the prism 161, and has the metal film 13 on the surface (one surface in the thickness direction) 163a. The substrate 163 is disposed via a matching oil 164 on the surface of the predetermined surface 161 a of the prism 161 with the back surface (the other surface in the thickness direction) 163 b facing the prism 161. Since the prism portion 14A includes the prism 161 and the substrate portion 162 including the metal film 13 as described above, when the metal film 13 needs to be replaced due to peeling, dirt, damage, or the like, only the substrate portion 162 is replaced. Since the prism 161 can be used continuously by exchanging, the cost can be reduced.

  Returning to FIG. 2B, the metal film 13 is a metal thin film formed (formed) on the film formation surface 17 of the prism body 16. The metal film 13 of this embodiment is made of gold. The metal film 13 is a member for amplifying an evanescent wave generated when the excitation light α from the prism main body 16 side is totally reflected by the metal film 13 in the prism section 14. The metal film 13 is a thin film having a film thickness of 100 nm or less so that surface plasmon resonance can be generated, and is preferably formed on the film formation surface 17 so as to have a film thickness of 30 to 70 nm. .

  A reaction film 20 is provided on the surface of the metal film 13 (the surface opposite to the prism body 16) 13a. The reaction film 20 is formed by fixing on the metal film 13 a physiologically active substance 21 for capturing a specimen (specific antigen or the like) contained in a sample solution (test liquid). In the present embodiment, an antibody is used as the physiologically active substance 21. This physiologically active substance 21 is fixed to the surface 13a of the metal film 13 by surface treatment. Specifically, the physiologically active substance 21 is a region on the surface 13 a of the metal film 13 that is in contact with the sample solution flowing through the flow path 22 when the prism main body 16 forms the flow path 22 in cooperation with the flow path member 15. Fixed to. Note that the physiologically active substance (antibody) 21 in FIG. 2A is schematically shown and is different from the actual form.

  The flow path member 15 is provided on the film formation surface 17 (specifically, on the metal film 13) of the prism main body 16, and forms the flow path 22 in cooperation with the prism section 14. The flow path member 15 is formed of a transparent resin. The flow path member 15 of the present embodiment is a plate-like member that expands in the horizontal direction. The flow path 22 has a plurality of (two in this embodiment) communication portions that communicate the reaction portion 23 in which a biochemical reaction (for example, an antigen-antibody reaction or the like) is performed and the reaction portion 23 and the outside of the test chip 10. 24.

  The reaction portion 23 is surrounded by a groove provided on the back surface (the lower surface in FIG. 2A) 15b of the flow path member 15 and the prism portion 14 (specifically, the metal film 13 on the prism main body portion 16). It is. That is, in the reaction part 23, the sample solution flows while contacting the surface of the metal film 13 (region where the physiologically active substance 21 is fixed) 13a. Therefore, by flowing the sample solution through the flow path 22, the sample solution flows while being in contact with the physiologically active substance 21. In the test chip 10 of the present embodiment, the reaction in the reaction unit 23 is promoted, stopped, washed, etc. by the test liquid L such as a sample solution or a chemical solution group including a specimen discharged from the nozzle member 31 of the liquid feeding unit 30. Thereafter, the specimen or the like in the sample solution captured by the physiologically active substance 21 is optically inspected. The reaction part 23 has an inner diameter smaller than that of the communication part 24. Specifically, the inner diameter of the reaction unit 23 is large enough to cause capillary action (for example, about 30 to 200 μm).

  As for each communicating part 24, one edge part opens in the surface (upper surface in FIG. 2 (A)) 15a of the flow-path member 15, and the other edge part (edge part on the opposite side to said one edge part) Is connected to the reaction section 23. In the present embodiment, the pair of communication portions 24, 24 extend from both ends of the reaction portion 23 toward the upper surface of the inspection chip body 11, that is, the upper surface 15 a of the flow path member 15, and the upper surface (surface) of the inspection chip body 11. By opening at 15 a, a single flow path 22 is formed by the reaction part 23 and the pair of communication parts 24, 24.

  The sealing member 12 is a sheet-like member that covers the flow path opening 25 and seals the flow path 22 on the surface of the test chip body 11. In the present embodiment, the sealing member 12 is provided so as to cover the entire area of the upper surface 15a of the test chip body 11, but is provided at least in a region where the flow path opening 25 can be sealed. Just do it. By providing the sealing member 12 in such a region, the inside of the flow path 22 can be sealed.

  The sealing member 12 is a multilayer sheet in which a plurality of sheets are laminated. In this sealing member 12, the sheets adjacent in the stacking direction are bonded with an adhesive or a pressure-sensitive adhesive. The sealing member 12 of this embodiment has a three-layer structure in which a first sheet (first sheet) 26, a second sheet (second sheet) 27, and a third sheet 28 are laminated in order.

  The first sheet 26 has a predetermined ductility that can be pierced by pressing the nozzle member 31 of the liquid feeding unit 30 from the front end side, and the sealing member 12 when the nozzle member penetrates the sealing member 12. A portion surrounding the hole (insertion opening 29) formed in the inner surface (that is, the insertion opening peripheral edge portion 290 of the sealing member 12) is in close contact with the outer peripheral surface 37 a of the nozzle member 31, and between the sealing member 12 and the nozzle member 31. It is the polymer film which has the predetermined elasticity which can ensure the adhesiveness (sealing property) in (refer FIG. 3). Specifically, the first sheet 26 is a sheet having low elasticity and high ductility (for example, a break elongation of 200 to 720% and an elastic modulus of 0.05 to 0.5 GPA). The first sheet 26 of the present embodiment is made of low density polyethylene (LDPE) and has a thickness of 30 to 70 μm. In the first sheet formed by this LDPE, for example, the elongation at break is 480 to 720% and the elastic modulus is 0.19 to 0.4 GPA.

  The material of the first sheet 26 is not limited to LDPE. For example, the first sheet 26 has high ductility such as linear low density polyethylene (LLDPE), ethylene vinyl acetate copolymer (EVA), aliphatic aromatic copolyester, and the like. Any elastic polymer film may be used. In the first sheet 26 formed of these materials, when the material is LLDPE, for example, the elongation at break is 230 to 690%, the elastic modulus is 0.17 to 0.39 GPA, and the material is EVA, for example, The elongation at break is 550% and the elastic modulus is 0.05 to 0.14 GPA.

  The second sheet 27 is formed of a material having lower ductility than the first sheet 26 (breaking elongation is 50% or less), and is inside the first sheet 26 (on the inspection chip body 11 side) in the sealing member 12. positioned. The second sheet 27 of the present embodiment is made of aluminum (AL) and has a thickness of 3 to 10 μm. In the second sheet 27 composed of this AL, for example, the breaking elongation is 20 to 25% and the elastic modulus is 70 GPA.

  The material of the second sheet 27 is not limited to AL, and may be, for example, copper (Cu), tin (Sn), gold (Au), or the like. When the material is Cu, the second sheet 27 formed of these materials has, for example, a breaking elongation of 7 to 13%, an elastic modulus of 130 GPA, and a material of Sn, for example, a breaking elongation of 20%, When the elastic modulus is 50 GPA and the material is Au, for example, the elongation at break is 42%.

  By forming the second sheet 27 from aluminum, a sufficient moisture blocking property and a light shielding property between the inside of the flow path 22 and the outside of the inspection chip 10 are ensured. Note that the second sheet 27 may be disposed outside the first sheet 26.

  The 3rd sheet | seat 28 is an adhesive film comprised with an adhesive, and has a thickness of 20-100 micrometers. With the third sheet 28, the sealing member 12 is firmly bonded to the inspection chip body 11.

  The liquid feeding unit (liquid feeding device) 30 includes a nozzle member 31, a pump 32, and a nozzle driving unit 33 (see FIG. 3). The liquid feeding unit 30 includes a plurality of chemical liquid containers and chemical liquid chips (not shown) in which various chemical liquids (test liquids) are stored, and a waste liquid container (not shown) for discarding the used test liquid L. ) And a pipette disposal container (not shown) for discarding the used nozzle member 31.

  The nozzle member 31 has an opening 35 at the tip, and discharges (injects) and sucks the inspection liquid L from the opening 35 into the flow path 22 of the inspection chip 10. In this embodiment, a pipette tip that is detachably attached to the pump 32 is used as the nozzle member 31.

  The pipette tip 31 has a liquid storage portion 36 that extends upward from the opening 35 at the tip and can store the inspection liquid L therein. The pipette tip 31 of the present embodiment is a nozzle member that is long in the vertical direction, and a through-hole penetrating along the axial direction (vertical direction in FIG. 3) of the pipette tip 31 is provided therein. The portion of the through hole on the side of the opening 35 of the pipette tip 31 (from the opening 35 to the tip of the pump nozzle 41 inserted into the through hole) constitutes the liquid storage portion 36. That is, the liquid storage part 36 of this embodiment is a part surrounding a columnar space that communicates from the opening 35 at the tip of the pipette tip 31 to the pump nozzle 41 to which the pipette tip 31 is connected.

  The tip portion 37 of the pipette tip 31 has a so-called tapered outer peripheral surface 37a whose outer diameter (diameter) gradually decreases toward the tip.

  Specifically, the pipette tip 31 is formed of an elastic member such as polypropylene in order to improve the adhesion with the sealing member 12, and the tip side is formed in a tapered shape. The tapered portion is reduced in diameter toward the tip at a constant rate, that is, the inclination angle is constant, and the inclination angle is 1 ° to 15 ° with respect to the axial direction of the pipette tip 31. Is formed. The tip surface 38 surrounding the opening 35 at the tip of the pipette tip 31 is orthogonal or substantially orthogonal to the axis of the pipette tip 31.

  The pump 32 includes a pump main body 40 that sucks and discharges fluid, and a pump nozzle 41 for connecting the pipette tip 31 to the pump main body 40. The pump body 40 is connected to and controlled by the control unit 70. The pump nozzle 41 has an outer peripheral surface 41 a having a shape corresponding to the inner peripheral surface of the through hole of the pipette tip 31. Thus, the pipette tip 31 is fitted into the pump nozzle 41 by inserting the pump nozzle 41 into the through hole of the pipette tip 31 from the base side of the pipette tip 31. In the present embodiment, in the axial direction of the pipette tip 31, the pipette tip 31 can be removed from the pump 32 by applying a force to the pipette tip 31 in the direction of separating the pipette tip 31 from the pump nozzle 41. it can.

  The nozzle drive unit 33 can raise and lower the pipette tip 31 connected to the pump 32 by raising and lowering the pump 32. Specifically, the nozzle drive unit 33 includes an elevating unit 45 and a horizontal moving unit 51.

  The elevating unit 45 holds the pump 32 and raises / lowers the pump 32 so that the tip of the pipette tip 31 faces downward (that is, the upper surface of the inspection chip 10 held by the holding and conveying unit 57). The pipette tip 31 is moved up and down (reciprocated in the Z-axis direction). Specifically, the elevating unit 45 includes a linear stage 46 and a Z-axis motor 50. The linear stage 46 engages with a feed screw 47, a guide member 48 extending in the vertical direction, and the feed screw 47 and the guide member 48, respectively, and a moving base 49 that holds the pump 32 in a predetermined range so as to be movable up and down. With. The Z-axis motor 50 rotates the feed screw 47 of the linear stage 46 to move the moving base 49 in the Z-axis direction along the guide member 48 (that is, move up and down). The Z-axis motor 50 is connected to the control unit 70 and controlled by the control unit 70.

  The horizontal movement unit 51 moves the pump 32 in the horizontal direction (in this embodiment, the X-axis direction: the left-right direction in FIG. 3), that is, the direction orthogonal to the Z-axis direction. The horizontal direction moving part 51 of this embodiment moves the pump 32 and the raising / lowering part 45 with the pipette tip 31 attached together in the X-axis direction. Specifically, the horizontal movement unit 51 includes a linear stage 52 and an X-axis motor 53. The linear stage 52 includes a feed screw 54, a guide member 55 extending in the X-axis direction, and a moving platform 56 that engages with the feed screw 54 and the guide member 55 and holds the elevating unit 45. The X-axis motor 53 moves the moving base 56 in the X-axis direction along the guide member 55 by rotating the feed screw 54 of the linear stage 52. The X-axis motor 53 is connected to the control unit 70 and is controlled by the control unit 70.

  The holding and conveying unit 57 holds the inspection chip 10 inserted into the inspection apparatus 2 from a chip insertion port (not shown) or the like, conveys it to a predetermined position of the liquid feeding unit 30, and holds it at this position. And the holding conveyance part 57 capture | acquires the biochemical reaction in the flow path 22 of the test | inspection chip 10 in the liquid delivery part 30 (in this embodiment, the capture | acquisition of the specimen etc. by the bioactive substance 21, and the fluorescent substance to the captured specimen The inspection chip 10 is transported to a predetermined position of the detection unit 60 and held at this position.

  Specifically, the holding and conveying unit 57 is in the posture (shown in FIG. 3) in which the flow path member 15 is on the upper side and the prism unit 14 is on the lower side in the liquid feeding unit 30, and on the upper surface 15 a of the inspection chip body 11. The inspection chip 10 is held so that the two flow path openings 25 that are opened are positioned under the orbit of the pipette tip 31 in the X-axis direction. Further, the holding and conveying unit 57 is configured so that, in the detection unit 60, the flow path member 15 is on the upper side and the prism unit 14 is on the lower side, and the excitation light α emitted from the excitation light source 61 is incident on the incident surface 18 of the prism unit 14. The inspection chip 10 is held at a position where it enters the prism portion 14.

  The detection unit 60 includes an excitation light source 61 that emits excitation light α and an excitation fluorescence measurement unit 62 that measures excitation fluorescence. The excitation light source 61 causes excitation light α to be incident on the prism portion 14 of the inspection chip 10 from the incident surface 18 and reflected by the metal film 13, thereby causing plasmon resonance in the metal film 13. At this time, the excitation light source 61 is arranged so that the excitation light α is incident on the metal film 13 from the back side of the area where the physiologically active substance 21 is fixed in the metal film 13 (area corresponding to the reaction part 23 of the flow path 22). The excitation light α is emitted. As a result, the specimen captured by the physiologically active substance 21 or the fluorescent substance labeled on the specimen emits light by the enhanced electric field caused by the plasmon resonance generated in the metal film 13. The excitation fluorescence measuring unit 62 is positioned above the inspection chip 10 held in the detection unit 60 by the holding and conveying unit 57 (see FIGS. 1 and 10), and excited fluorescence excited by the enhanced electric field. And the measurement result is output to the controller 70.

  The chemical solution container, the waste liquid container, and the pipette disposal container are containers whose upper ends are open or can be opened so that the pipette tip 31 can be inserted from above, and are respectively disposed under the X-axis direction of the pipette tip 31. Has been.

  The control unit 70 is a circuit that controls each unit of the inspection apparatus 2 according to the function. For example, a control program for controlling each unit of the inspection apparatus 2 according to the function or an output from the excitation fluorescence measurement unit 62 Non-volatile storage element for storing various predetermined programs such as a calculation program for detecting and analyzing a sample or the like based on the data, and various predetermined data such as data necessary for executing the predetermined program ROM (Read Only Memory), EEPROM (Electrically Erasable Programmable Read Only Memory) which is a rewritable nonvolatile memory element, CPU which performs predetermined arithmetic processing and control processing by reading and executing the predetermined program (Central Processing Unit), a so-called CPU working memory for storing data generated during execution of the predetermined program, and the like That RAM (Random Access Memory), and constituted by a microcomputer or the like provided with these peripheral circuits. As shown in FIG. 4, the control unit 70 functionally includes a liquid feeding control unit 71, a conveyance control unit 72, and an inspection control unit 73.

  The liquid feeding control unit 71 controls each part of the liquid feeding unit 30 and has a nozzle position control unit 74 and a pump control unit 75.

  The nozzle position control unit 74 controls the position of the pipette tip 31, specifically the relative position of the pipette tip 31 with respect to the inspection tip 10 held by the holding and conveying unit 57, and controls the horizontal moving unit 51. An X-axis direction control unit 76 that controls the position of the pipette tip 31 in the X-axis direction, and a Z-axis direction control unit 77 that controls the position of the pipette tip 31 in the Z-axis direction by controlling the elevating unit 45.

  The X-axis direction control unit 76 controls the X-axis motor 53 of the horizontal direction moving unit 51 to move the moving table 56 along the guide member 55 in the X-axis direction. Specifically, the X-axis direction control unit 76 includes the upper positions of the openings of the chemical liquid containers (not shown), the waste liquid containers (not shown), and the pipette disposal containers (not shown), and the upper surface 15a of the inspection chip body 11. The X-axis motor 53 is controlled so that the pipette tip 31 moves to a position above each flow path opening 25.

  The Z-axis direction control unit 77 controls the Z-axis motor 50 of the elevating unit 45 after the pipette tip 31 has been moved to a predetermined position in the X-axis direction by the X-axis direction control unit 76, and moves the moving table 49 to the guide member 48. Along the Z axis. Thereby, the pipette tip 31 can be moved up and down. Specifically, the Z-axis direction control unit 77 has a height position where the pipette tip 31 does not interfere with the inspection tip 10, the chemical solution container, the waste solution container, and the pipette disposal container when the pipette tip 31 moves in the X-axis direction ( When the pipette tip 31 is moved up to the retreat position, and the pipette tip 31 moves along the X-axis direction to a position above the opening of the chemical liquid container, the waste liquid container, or the like, or a position above the flow path opening 25 of the inspection chip body 11. The pipette tip 31 is lowered.

  Specifically, the Z-axis direction control unit 77 lowers the pipette tip 31 to a predetermined height position when the pipette tip 31 moves to a position above the opening of the chemical solution container along the X-axis direction. Is inserted into a test liquid (sample solution, cleaning liquid, buffer liquid, etc.) stored in the chemical container. Then, after the pump 32 is controlled by the pump control unit 75 and the test liquid L is sucked into the pipette tip 31, the Z-axis direction control unit 77 raises the pipette tip 31 to the retracted position.

  Further, the Z-axis direction control unit 77 lowers the pipette tip 31 when the pipette tip 31 moves to the position above the opening of the waste liquid container along the X-axis direction, and the tip side thereof is inserted into the waste liquid container from the opening. The pipette tip 31 is stopped from descending when it is in the closed state. After the pump 32 is controlled by the pump control unit 75 and the inspection liquid L in the pipette tip 31 is discharged, the Z-axis direction control unit 77 raises the pipette tip 31 to the retracted position.

  Further, the Z-axis direction control unit 77 lowers the pipette tip 31 when the pipette tip 31 moves to the position above the opening of the pipette disposal container along the X-axis direction, and the pipette tip 31 is pipetted from the opening. When the pipette tip 31 is inserted into the disposal container, the descent of the pipette tip 31 is stopped. Then, the Z-axis direction control unit 77 removes the pipette tip 31 from the pump 32 using a pipette attachment / detachment device (not shown), and discards the pipette tip 31. Thereafter, the Z-axis direction control unit 77 raises the pipette tip 31 to the retracted position, and attaches a new pipette tip 31 to the pump 32 by the pipette attachment / detachment device.

  Further, the Z-axis direction control unit 77 is used to inject and suck the inspection liquid L into the flow path 22 of the inspection chip 10 or to pierce the sealing member 12 with an air hole 29A. Moves along the X-axis direction to a position above the flow path opening 25, the pipette tip 31 is lowered to a predetermined position, and its tip 37 is inserted into the flow path 22 through the flow path opening 25. At this time, if the channel opening 25 is covered with the sealing member 12, the tip of the pipette tip 31 is pressed against the sealing member 12, so that the tip 37 of the pipette tip 31 is connected to the channel 22. Plugged in. On the other hand, when the sealing member 12 has already been perforated by the pipette tip 31, the tip portion 37 of the pipette tip 31 is inserted into the flow path 22 through the formed opening (insertion opening 29). Then, after the pump 32 is controlled by the pump control unit 75 and the inspection liquid L is discharged and sucked by the pipette tip 31, the Z-axis direction control unit 77 raises the pipette tip 31 to the retracted position.

  The pump control unit 75 operates the pump 32 when the pipette tip 31 is moved to a predetermined position by the nozzle position control unit 74 or while the pipette tip 31 is moving at the predetermined position.

  Specifically, when the pipette tip 31 descends toward the flow path opening 25 of the flow path 22 with the test liquid L stored in the liquid storage section 36, the pump control section 75 When the front end surface 38 approaches the surface of the sealing member 12 (the upper surface in FIG. 3) (see FIG. 7A), the pump 32 is driven to suck the inspection liquid L in the liquid reservoir 36. . As a result, the inspection liquid L begins to slowly rise in the liquid storage portion 36. When the tip 37 is inserted into the flow path 22 until the pipette tip 31 passes through the sealing member 12 and the tip surface 38 of the pipette tip 31 is not in contact with the sealing member 12 (FIG. 8 ( C)), the pump control unit 75 stops the pump 32 and stops the suction of the inspection liquid L in the liquid storage unit 36. Thereby, when the pipette tip 31 descends, the tip (tip surface 38) of the pipette tip 31 passes through the insertion opening peripheral portion (cylindrical portion) 290 of the sealing member 12 in the vertical direction. Since the inside of the liquid storage part 36 is rising, the pipette tip 31 passes through the insertion opening peripheral part (cylindrical part) 290 of the sealing member 12 in the vertical direction during this period. In addition, it is possible to prevent the inspection liquid L from accumulating like a spear from the tip of the pipette tip 31 (see FIG. 5). The pump control unit 75 raises the test liquid L in the liquid storage unit 36 at a speed at which the test liquid L does not enter the pump 32 while the tip of the pipette tip 31 passes through the sealing member 12. . Further, the pump control unit 75 determines the timing of starting and stopping the suction of the inspection liquid L in the pipette tip 31 based on the position of the pipette tip in the Z-axis direction. The position of the pipette tip 31 in the Z-axis direction may be determined based on the amount of descent from the retracted position of the pipette tip 31, and the position of the tip of the pipette tip 31 is measured by a position sensor or the like. Also good.

  Similarly, when the pipette tip 31 is lifted from the state in which the tip portion 37 is inserted into the flow path 22 with the test liquid L stored in the liquid storage unit 36, the pump control unit 75. When the tip surface 38 of the pipette tip 31 approaches the insertion opening peripheral portion 290 of the sealing member 12, the pump 32 is driven to suck the inspection liquid L in the liquid storage portion 36. As a result, the inspection liquid L begins to slowly rise in the liquid storage portion 36. When the pipette tip 31 is pulled out from the insertion opening 29 of the sealing member 12 and the tip end surface 38 of the pipette tip 31 is raised to a position above the surface of the sealing member 12, the pump controller 75. Stops the suction of the liquid L for inspection in the liquid reservoir 36 by stopping the pump 32. Thus, when the pipette tip 31 is raised, the inspection liquid L rises in the liquid reservoir 36 when the tip (tip surface 38) of the pipette tip 31 passes through the insertion opening peripheral edge 290 of the sealing member 12. Therefore, during this period (that is, while the tip of the pipette tip 31 passes through the insertion opening peripheral edge portion 290 of the sealing member 12 in the vertical direction), the inspection liquid L flows like a ridge from the tip of the pipette tip 31. Accumulation (see FIG. 5) can be prevented. In this case as well, as in the case where the pipette tip 31 is lowered, the pump control unit 75 does not allow the inspection liquid L to enter the pump 32 while the tip of the pipette tip 31 passes through the sealing member 12. Thus, the inspection liquid L is raised in the liquid reservoir 36. In addition, the pump control unit 75 starts the suction of the inspection liquid L in the pipette tip 31 based on the position of the pipette tip 31 in the Z-axis direction even when the pipette tip 31 is lowered, as in the case where the pipette tip 31 is lowered. And determine when to stop.

  As described above, the inspection liquid L rises in the liquid reservoir 36 when the tip of the pipette tip 31 passes through the insertion opening peripheral edge 290 of the sealing member 12 when the pipette tip 31 moves up and down. By doing so, it is effectively prevented that the inspection liquid L accumulates like a spear from the tip of the pipette tip 31 during this period, and as a result, the inspection stored in the pipette tip 31 when the pipette tip 31 is raised and lowered The liquid L can be reliably prevented from adhering to the insertion opening peripheral edge portion 290 (sealing member 12).

  Further, the pump control unit 75 appropriately drives the pump 32 when the distal end portion 37 of the pipette tip 31 is inserted into the flow channel 22 through the insertion opening 29, so that the inspection liquid into the flow channel 22 is obtained. By injecting L, sucking the inspection liquid L from the flow path 22, repeating injection and suction of the inspection liquid L into the flow path 22, and the like, the test liquids L are mixed or biochemical. Promote the reaction.

  Further, the pump control unit 75 drives the pump 32 when the tip 37 of the pipette tip 31 is inserted into the waste liquid container to check the inspection liquid L in the liquid storage unit 36 (specifically, a used inspection). The liquid L for inspection) is discharged from the pipette tip 31, and the liquid L for inspection is discarded in the waste liquid container.

  The conveyance control unit 72 controls the holding conveyance unit 57. Specifically, when the inspection chip 10 is installed in the holding and conveying unit 57, the conveyance control unit 72 drives the holding and conveying unit 57 to convey the inspection chip 10 to a predetermined position of the liquid feeding unit 30. Hold in position. When the process in the liquid feeding unit 30 is completed, the transport control unit 72 causes the holding transport unit 57 to position the test chip 10 in the liquid feeding unit 30 (the flow path member 15 is on the upper side and the prism unit 14 is on the lower side. The inspection chip 10 is transported to a predetermined position of the detection unit 60 and held at the predetermined position.

  The inspection control unit 73 controls each unit of the detection unit 60 and processes the measurement result of the excitation fluorescence. Specifically, when the inspection chip 10 is conveyed to the detection unit 60, the inspection control unit 73 irradiates the excitation light α from the excitation light source 61 toward the inspection chip 10. Further, the inspection control unit 73 causes the excitation fluorescence measurement unit 62 to measure the amount of excitation fluorescence generated by the enhanced electric field caused by the plasmon resonance generated in the vicinity of the metal film 13 of the inspection chip 10 by the irradiation of the excitation light α. Then, the examination control unit 73 analyzes the sample based on the output from the excitation fluorescence measuring unit 62, and the result is displayed outside the examination apparatus 2 (for example, a display device such as a monitor or a printer) or the examination. The data is output to storage means (not shown) of the device 2.

  In such an inspection system 1, a biochemical inspection is performed as follows.

<Inspection chip installation and air hole formation process>
When the inspection chip 10 is inserted into the inspection apparatus 2 from a chip insertion port (not shown) or the like, the control unit 70 moves the inspection chip 10 to the predetermined position of the liquid feeding unit 30 by the holding and conveying unit 57. At this time, the two flow path openings 25, 25 of the test chip 10 are both covered with the sealing member 12, whereby the flow path 22 is hermetically sealed (see FIG. 2A). When the inspection chip 10 is disposed at a predetermined position in the liquid feeding unit 30, the control unit 70 uses the nozzle position control unit 74 to pipet the portion of the sealing member 12 that seals one flow path opening 25. A hole (air hole) 29A that communicates the inside of the flow path 22 and the outside of the test chip 10 is formed by lowering 31 and penetrating the tip 37 (see FIG. 6). By forming the air hole 29A, the inspection liquid L can be easily injected from the other flow path opening 25.

<Liquid feeding process>
Next, the control unit 70 uses the nozzle position control unit 74 and the pump control unit 75 to perform a test liquid L (a sample solution containing a sample or the like in the present embodiment) necessary for the biochemical sequence in the test apparatus 2 from the chemical solution container. ) In a pipette tip 31 (that is, a predetermined amount of sample solution is sucked into the liquid reservoir 36), and the pipette tip 31 is connected to the other channel opening 25 (the side sealed by the sealing member 12). (See FIG. 7A). Then, the control unit 70 causes the nozzle position control unit 74 to lower the pipette tip 31 in a state where the sample solution is stored in the liquid storage unit 36, and seals the flow path opening 25 with the tip 37 of the pipette tip 31. The stopped sealing member 12 is drilled.

  Specifically, the control unit 70 lowers the pipette tip 31 and operates the pump 32 when the tip approaches the sealing member 12 to suck the sample solution in the liquid storage unit 36. As a result, the sample solution slowly rises in the liquid reservoir 36 (see arrow A in FIG. 7A). The controller 70 further lowers the pipette tip 31, so that the tip surface 38 comes into contact with the sealing member 12. Thereby, the site | part of the sealing member 12 which covers the other flow-path opening 25 is pushed by the front end surface 38 of the pipette tip 31, and begins to extend gradually (refer FIG. 8 (A)). At this time, the sample solution does not come into contact with the sealing member 12 because the sample solution is slowly rising in the liquid reservoir 36. And the 2nd sheet | seat 27 with low ductility reaches the limit in the sealing member 12, and it begins to fracture | rupture from the corner | angular part of the pipette tip 31 tip where the force from the pipette tip 31 concentrates (refer FIG.8 (B)). Further, when the control unit 70 lowers the pipette tip 31 and pushes the tip 37 of the pipette tip 31 into the flow path 22, the first sheet 26 corresponding to the region where the second sheet 27 in the sealing member 12 is broken is formed. The pipette tip 31 extends so as to be in close contact with the outer peripheral surface 37a of the tip 37, and a cylindrical portion (insertion opening peripheral portion) 290 is formed along the outer peripheral surface 37a. When the control unit 70 further lowers the pipette tip 31, the first sheet 26 also extends and reaches the limit and breaks (see FIG. 8C). Thereby, the insertion opening 29 is formed in the sealing member 12.

  As described above, when the tip of the pipette tip 31 passes through the sealing member 12, the control unit 70 stops the suction of the sample solution in the liquid storage unit 36 by the pump 32. Thereby, when the tip of the pipette tip 31 passes through the insertion opening 29 when the pipette tip 31 is lowered, the sample solution (inspection liquid L) rises in the liquid reservoir 36 in the pipette tip 31. (See FIGS. 8A to 8C), that is, when the tip of the pipette tip 31 passes through the insertion opening 29, the sample solution is positioned above the opening 35 at the tip in the liquid reservoir 36. Therefore, the sample solution can be prevented from accumulating like a spear from the tip of the pipette tip 31 during this period. As a result, when the pipette tip 31 is lowered and its tip passes through the insertion opening 29, the sample solution stored in the pipette tip 31 is inserted into the peripheral edge of the insertion opening (cylindrical part) in the sealing member 12 of the inspection chip 10. ) Can be reliably prevented from adhering to 290.

  Then, when the tip of the pipette tip 31 is inserted to the vicinity of the reaction portion 23 of the flow path 22 (position shown in FIG. 7B), the controller 70 stops the drop of the pipette tip 31. At this time, a cylindrical portion (insertion opening peripheral portion) 290 that is in close contact with the outer peripheral surface 37a of the tip portion 37 of the pipette tip 31 is formed by the first sheet 26 having a predetermined elasticity in the sealing member 12. Adequate adhesion is ensured between the pipette tip 31 and the sealing member 12.

  Next, the controller 70 causes the pump controller 75 to discharge the sample solution in the pipette tip 31 into the flow path 22 (see FIG. 7B). At this time, in order to prevent the generation of bubbles in the flow path 22, the control unit 70 first performs slow liquid feeding, and after the flow path 22 (specifically, the reaction unit 23) is filled with the sample solution. Then, the flow rate of the sample solution flowing through the reaction unit 23 is increased to promote the biochemical reaction between the physiologically active substance 21 and the specimen contained in the sample solution (capture of the specimen or the like by the physiologically active substance 21). In the present embodiment, the control unit 70 increases the flow rate to about 10,000 to 20000 uL / min. When the flow velocity is increased in this way, the pressure in the flow path 22 applied to the portion of the sealing member 12 through which the pipette tip 31 penetrates increases, but a cylindrical portion (insertion opening peripheral portion) 290 is formed. Therefore, liquid leakage from between the pipette tip 31 and the sealing member 12 is effectively suppressed. This is because the pressure in the flow path 22 is applied in a direction perpendicular to the surface surrounding the flow path 22, and therefore, if the internal pressure of the flow path becomes high, there is no insertion opening peripheral portion (cylindrical portion) 290. Although the opening peripheral edge of the stopper member 12 tends to extend due to the internal pressure of the flow path and easily leaks (see FIG. 9A), when the insertion opening peripheral edge 290 is formed, this portion is connected to the pipette tip 31. This is because the pressure (flow path internal pressure) is applied in the direction of pressing against the outer peripheral surface 37a, so that liquid leakage is difficult (see FIG. 9B). Further, by forming the insertion opening peripheral portion 290, as shown in FIG. 9A and FIG. 9B, as compared with the case where there is no portion of the insertion opening peripheral portion (tubular portion) 290. The force acting in the direction in which the sealing member 12 is peeled from the inspection chip body 11 (the peeling moment shown in FIGS. 9A and 9B) can also be reduced. Liquid leakage caused by peeling of the stop member 12 can also be effectively prevented.

  In this embodiment, since the inner diameter of the reaction part 23 (height from the metal film surface 13a in FIG. 2A) is about 30 to 200 μm, the channel resistance when the sample solution flows through the reaction part 23 As a result, the pressure in the flow path 22 is about +0.1 MPA higher in relative pressure than the atmospheric pressure (0.1 MPA). Specifically, the flow path resistance is defined by the shape of the flow path 22, the length of the flow path 22, the liquid feeding speed, the viscosity of the inspection liquid L, and the like. The reaction rate of the biochemical reaction in the reaction unit 23 depends on the shape of the flow path 22 and the velocity (flow velocity) of the test liquid L. In the biochemical test as in this embodiment, the inner diameter of the flow path 22 (the surface of the metal film on which the reaction film 20 is formed) so that the test liquid L flows only in the vicinity of the reaction film 20 formed on the metal film 13. 13a) and the flow rate of the biochemical reaction is preferably increased by increasing the flow rate of the test liquid L in the reaction unit 23, so that the flow resistance of the sample solution flowing through the reaction unit 23 is reduced. As a result, the pressure in the flow path 22 (specifically, the pressure in the vicinity of the insertion opening 29 into which the tip 37 of the pipette tip 31 is inserted) increases.

  The controller 70 causes the pump controller 75 to repeatedly inject and suck the sample solution into the flow path 22 a predetermined number of times, and then sucks all the sample solution in the flow path 22 into the pipette tip 31 (FIG. 7 ( C)). This suction is performed slowly so that no liquid remains in the flow path 22. When the sample solution in the flow path 22 is aspirated, the pressure in the flow path 22 decreases, but the insertion opening peripheral edge 290 and the pipette tip 31 are in close contact with each other. Air can be prevented from entering the flow path, and thus the sample solution can be efficiently sucked by the pipette tip 31.

  When the sample solution in the channel 22 is all sucked, the control unit 70 raises the pipette tip 31 by the nozzle position control unit 74 and pulls the tip of the pipette tip 31 out of the channel 22 (insertion opening 29). At this time, when the tip of the pipette tip 31 inserted into the flow path 22 approaches the lower end of the opening peripheral portion (cylindrical portion) 290 of the sealing member 12, the control unit 70 is controlled by the pump control unit 75. The sample solution in the pipette tip 31 is sucked and the sample solution is slowly raised in the liquid reservoir 36. When the tip of the pipette tip 31 passes through the insertion opening peripheral edge 290 and the entire tip 37 of the pipette tip 31 is pulled out from the flow path 22, the control unit 70 stops the suction of the sample solution by the pump 32. As a result, when the tip of the pipette tip 31 when the pipette tip 31 is raised passes through the insertion opening 29, the sample solution is raised in the liquid reservoir 36 in the pipette tip 31, The sample solution can be prevented from accumulating like a spear from the tip of the pipette tip 31. As a result, when the pipette tip 31 is raised and its tip passes through the insertion opening 29, the sample solution stored in the pipette tip 31 adheres to the insertion opening peripheral portion (cylindrical portion) 290 in the inspection tip 10. This can be surely prevented.

  The controller 70 causes the nozzle position controller 74 to move the pipette tip 31 to a waste liquid container (not shown), and then causes the pump controller 75 to discharge the used sample solution from the pipette chip 31 into the waste liquid container.

  Next, the control unit 70 repeatedly injects and sucks another inspection liquid (in this embodiment, a cleaning liquid) sucked from the chemical solution storage unit (not shown) by the pipette tip 31 into the flow path 22 and repeats the flow path 22. After cleaning the inside, all the cleaning liquid used for the cleaning is sucked from the flow path 22 and discarded in a waste liquid container (not shown).

  This liquid feeding (reaction and washing in the reaction unit 23) process is repeated a predetermined number of times. In this repetition, injection or the like of the same sample solution L (a sample solution containing a specimen or the like in the present embodiment) may be performed, and other test liquids (for example, the physiologically active substance 21 constituting the reaction membrane 20) Injection and aspiration of a solution containing a fluorescent substance that labels the captured specimen or the like may be performed.

  In this repetition, the insertion and withdrawal of the tip 37 of the pipette tip 31 from the insertion opening 29 formed in the sealing member 12 is repeated. At this time, in the sealing member 12, the insertion opening peripheral edge portion 290 (first sheet 26) in contact with the outer peripheral surface 37a of the tip portion 37 of the pipette tip 31 inserted into the insertion opening 29 has a predetermined elasticity. Even when the insertion and withdrawal of the tip 37 of the pipette tip 31 into and from the insertion opening 29 is repeated, the adhesion between the peripheral edge portion 290 of the insertion opening and the outer peripheral surface 37a of the tip 37 of the pipette tip 31 is maintained each time it is inserted. Secured. As a result, liquid leakage from between the pipette tip 31 and the sealing member 12 is suppressed during the injection and suction of the inspection liquid L from the pipette tip 31 into the flow path 22. Further, by forming the insertion opening peripheral portion 290, the sealing member from the inspection chip body 11 can be obtained even when pressure fluctuations due to repeated injection and suction of the inspection liquid L in the flow path 22 are repeated. 12 peeling is also effectively suppressed.

  When a predetermined number of liquid feeding steps are completed, the control unit 70 causes the pipette tip 31 to flow the buffer liquid (other test liquid) sucked from the chemical liquid container (not shown) from the distal end portion 37 inserted through the insertion opening 29. Inject into the channel 22. Then, the controller 70 raises the pipette tip 31 and pulls the tip 37 out of the insertion opening 29 while the buffer solution is being injected into the flow path 22. In this extraction, when the tip of the pipette tip 31 passes through the insertion opening 29, suction by the pump 32 is not performed. Since the step of injecting the inspection liquid L into the flow path 22 is not performed after the step of injecting the buffer solution, the contamination due to the mixing of the inspection liquids L adhering to the insertion opening peripheral portion 290 does not occur. Because.

  After the injection of the buffer solution, the control unit 70 moves the pipette tip 31 to a pipette disposal container (not shown), removes the pipette tip 31 from the pump 32 by a pipette attachment / detachment device (not shown), and uses it. The used pipette tip 31 is discarded in a pipette disposal container. Thereafter, the controller 70 raises the pipette tip 31 to the retracted position by the Z-axis direction controller 77 and attaches a new pipette tip 31 to the pump 32 by the pipette attachment / detachment device.

<Inspection process>
Next, the control unit 70 causes the holding and conveying unit 57 to convey the test chip 10 from the liquid feeding unit 30 to the detecting unit 60. When the inspection chip 10 is conveyed to the detection unit 60 and held at a predetermined position, the control unit 70 causes the inspection control unit 73 to irradiate the excitation light α from the excitation light source 61 toward the inspection chip 10. At this time, the excitation light α incident on the prism portion 14 from the incident surface 18 of the test chip 10 is totally reflected on the back side of the site where the reaction film 20 of the metal film 13 is provided (the physiologically active substance 21 is fixed). Then, the excitation light α is irradiated to the inspection chip 10 at such an angle that plasmon resonance occurs in the metal film 13 by this total reflection (see FIG. 10). By the enhanced electric field formed by this plasmon resonance, the fluorescent substance labeled on the specimen (antigen) or the like captured by the physiologically active substance 21 is excited and emits fluorescence. The control unit 70 measures the amount of excitation fluorescence by the excitation fluorescence measurement unit 62 and derives, for example, the amount of excitation fluorescence per unit area in the inspection control unit 73 based on the measurement result. Then, the control unit 70 outputs the derived result to the outside (for example, a display device such as a monitor or a printing device such as a printer), a storage unit (not shown) or the like of the inspection device 2, and ends the measurement.

  According to the above inspection system 1, when the pipette tip 31 is moved up and down and the tip passes through the insertion opening 29, the inspection liquid (for example, sample solution) L stored in the pipette tip is inserted into the inspection tip 10. Adhesion to the peripheral edge portion 290 of the opening 29 can be prevented. This is because when the pipette tip 31 moves up and down, the inspection liquid L rises in the liquid reservoir 36 of the pipette tip 31 when the tip of the pipette tip 31 passes through the insertion opening 29. This is because the inspection liquid L can be prevented from accumulating like a spear from the tip of the pipette tip 31 during this period.

  Further, according to the present embodiment, by inserting the tip portion 37 of the pipette tip 31 into the flow path 22, the outer peripheral surface 37 a of the tip portion 37 of the pipette tip 31 and the insertion opening peripheral portion 290 of the sealing member 12 are formed. Due to the close contact, even if the pressure in the flow path 22 fluctuates, liquid leakage from the insertion opening 29 into which the tip 37 of the pipette tip 31 is inserted can be prevented. In addition, since the diameter of the opening (insertion opening) 29 into which the pipette tip 31 is inserted is smaller than the flow path opening (tip opening) 25 when the sealing member 12 is not provided, the inspection liquid L is inspected. It can prevent more effectively adhering to the 10 insertion opening peripheral part 290. FIG. That is, when the pipette tip 31 is inserted into and removed from the insertion opening 29, the tip thereof is easy to come into contact with the insertion opening peripheral edge 290, but the pipette tip 31 is stored in the liquid storage portion 36 when the tip passes through the insertion opening 29. By sucking the inspection liquid L so as to rise, it is possible to effectively prevent the inspection liquid L from adhering to the peripheral edge portion 290 of the insertion opening. Thereby, when a plurality of inspection liquids L are injected and sucked into the flow path 22, contamination due to mixing of different inspection liquids L adhering to the insertion opening peripheral edge 290 can be prevented.

  Further, according to the present embodiment, the flow path 22 is sealed (sealed) until the inspection is performed by the inspection system 1 (that is, until the insertion opening 29 is formed in the sealing member 12). Therefore, it is possible to reliably prevent evaporation of the liquid stored in the flow path 22 and mixing of other substances into the liquid. Or it becomes possible to maintain the state (for example, humidity etc.) in the flow path 22, and the bioactive substance 21 in the flow path 22 can be prevented from being contaminated or dried.

  Further, according to the present embodiment, since the pipette tip 31 is detachably attached to the pump 32, the dirty pipette tip 31 after being used at a predetermined number of times or in a predetermined step can be easily converted into a clean pipette tip 31. It can be exchanged, which makes it easier to maintain the accuracy of the inspection. Further, if an inexpensive pipette tip 31 such as a general-purpose product is used, an increase in cost can be suppressed even if the pipette tip 31 is exchanged frequently.

  According to the present embodiment, when the pipette tip 31 is pierced into the sealing member 12, the adhesiveness (sealability) between the pipette tip 31 and the sealing member 12 is sufficiently ensured, and the pipette tip 31. Even if the insertion / extraction of pressure and the pressure fluctuation in the flow path 22 are repeated, peeling between the sheets 26 and 27 constituting the sealing member 12 is difficult to occur, and thus liquid leakage can be effectively prevented.

  In addition, according to the present embodiment, the adjacent sheets 26 and 27 are bonded to each other with an adhesive or a pressure-sensitive adhesive, so that the respective sheets 26 and 27 are compared with the case where the adjacent sheets are bonded only by thermal welding. Since 27 are firmly bonded to each other, even if pressure fluctuation in the flow path 22 and insertion / extraction of the pipette tip 31 are repeated, peeling between the sheets 26 and 27 constituting the sealing member 12 hardly occurs.

  Further, according to the present embodiment, since the first sheet 26 is positioned on the outermost side in the sealing member 12, the pipette tip 31 is pierced into the sealing member 12 and the insertion opening peripheral portion (cylindrical portion) 290 is formed. Since the first sheet 26 having elasticity when formed is in contact with the peripheral surface 37a of the pipette tip 31, the peripheral edge portion 290 of the insertion opening and the outer peripheral surface 37a of the pipette tip 31 are more closely attached, and the adhesion between them is improved. More improved.

  Further, according to the present embodiment, since the breaking elongation of the first sheet 26 is 200% or more and 720% or less and the breaking elongation of the second sheet 27 is 50% or less, the pipette tip 31 is sealed. When the stop member 12 is pierced, the insertion opening peripheral portion (cylindrical portion) 290 is suitably formed.

  Moreover, according to this embodiment, since the 2nd sheet | seat 27 is formed with aluminum, the interruption | blocking property of the moisture between the inside of the flow path 22 and the exterior (external of the test | inspection chip 10) and light-shielding property are fully ensured. Is done. Thereby, the physiologically active substance 21 provided in the flow path 22 can be protected from drying and light.

  Further, in the channel 22 of the present embodiment, since the inner diameter of the intermediate part (reaction part 23) is smaller than the inner diameter of the end part (communication part 24), the sample solution L is injected from the channel opening 25 by the pipette tip 31. When the flow rate of the sample solution L flowing through the reaction unit 23 is increased, the flow path resistance increases, and thereby the pressure around the opening 25 in the flow path 22 becomes higher than the atmospheric pressure. By using the sealing member 12 of the present embodiment in the inspection chip 10 provided with such a flow path 22, when the pipette tip 31 is pierced into the sealing member 12, the pipette tip 31 and the sealing member 12 are used. Is sufficiently secured, and even when the pipette tip 31 is inserted and removed and the pressure fluctuation in the flow path 22 is repeated, separation between the sheets 26 and 27 hardly occurs. Can be prevented.

  The inspection system of the present invention is not limited to the above-described embodiment, and it is needless to say that various modifications can be made without departing from the gist of the present invention.

  The specific configuration of the liquid storage unit 22 provided in the inspection chip 10 is not limited. For example, in the present embodiment, the liquid storage portion is configured by a single flow path, but the flow path is branched into a plurality of branch flow paths, and the end of each branch flow path is the inspection chip body 11. You may open each on the surface. Further, the liquid storage portion may be a concave portion (so-called well) that is formed on the upper surface of the inspection chip body and is recessed downward.

  Moreover, although the nozzle member of the said embodiment is the pipette tip 31 detachably attached to the pump 32 etc., it is not limited to this, The nozzle member fixed to the pump etc. may be sufficient. That is, it may not be a disposable nozzle member as in the above embodiment.

  Further, in the above-described embodiment, the insertion opening peripheral portion 290 formed by penetrating the tip portion 37 of the nozzle member 31 so that liquid leakage does not occur between the nozzle member (pipette tip 31) and the inspection tip 10. However, the present invention is not limited to this. For example, as shown in FIG. 11, an elastic member 12B such as rubber having a shape corresponding to the flow path opening 25 is provided on the outer peripheral surface 37a of the tip portion 37 of the nozzle member, and the outer peripheral surface 37a of the nozzle member is provided by this elastic member 12B. And the periphery of the flow path opening 25 of the inspection chip body 11 may be sealed. In this case, while the tip of the nozzle member passes through the flow path opening 25 in the test chip body 11, the control unit sucks the test liquid L by the pump so that the test liquid L rises slowly in the liquid storage unit.

  The elastic member 12B may be configured to be fixed to the peripheral edge portion of the flow path opening 25 and to insert the tip portion 37 of the nozzle member into the through hole of the elastic member 12B. In this case, while the tip of the nozzle member passes through the through hole of the elastic member 12B, the control unit sucks the inspection liquid L by the pump so that the inspection liquid L rises slowly in the liquid storage unit.

  The specific configuration of the sealing member provided in the inspection chip 10 is not limited. In the embodiment described above, the first sheet 26 having a predetermined ductility and a predetermined elasticity, the second sheet 27 having a smaller ductility than the first sheet 26, and the third sheet, which is a third sheet that is an adhesive layer, are sequentially stacked. Although it consists of a structure, it is not limited to this, If a 1st sheet | seat and a 2nd sheet | seat are included and each layer adjacent to the upper and lower sides is adhere | attached with the adhesive agent or the adhesive, 2 layers or 4 layers or more It may be a sheet-like member. For example, specifically, as illustrated in FIG. 12, the sealing member 12 </ b> A includes a first sheet 26, a second sheet 27, a first sheet 26, and a third sheet 27 that are sequentially stacked. May be formed. Even in such a sealing member 12 </ b> A, when the insertion opening 29 is formed by the nozzle member, the second sheet 27 starts to break and the uppermost first sheet 26 starts based on the difference in ductility of each layer. A cylindrical part (insertion opening peripheral part) 290 having predetermined elasticity is formed.

1 Inspection System 10 Inspection Chip 11 Inspection Chip Body (Chip Body)
12, 12A, 12B Sealing member (elastic member)
22 Channel (Liquid container)
25 Channel opening (chip opening)
26 First sheet (first sheet)
27 Second sheet (second sheet)
29 Insertion opening 30 Liquid feeding part (Liquid feeding device)
31 Pipette tip (nozzle member)
32 Pump 33 Nozzle driving part 35 Opening 36 at the tip 36 Liquid storage part 37 Tip of the pipette tip (tip of the nozzle member)
37a The outer peripheral surface of the tip of the pipette tip (the outer peripheral surface of the tip of the nozzle member)
38 Tip surface of pipette tip (tip surface of nozzle member)
57 Holding / conveying section 60 Detection section 70 Control section 290 Insertion opening peripheral edge L Inspection liquid

Claims (4)

An inspection system for inspecting a specimen using a plurality of different test liquids,
An inspection chip having a liquid storage portion capable of storing the inspection liquid therein, and having an insertion opening formed on the surface thereof for communicating the inside and the outside of the liquid storage portion;
A front end is opened, a nozzle member that injects and sucks the inspection liquid into the liquid storage portion from the opening, the nozzle member is moved up and down, and the front end portion is inserted into the liquid storage portion through the insertion opening, or the A liquid feeding device having a nozzle driving unit that is pulled out from the liquid storage unit, a pump that discharges and sucks the inspection liquid from the opening at the tip of the nozzle member, and a control unit that controls the nozzle driving unit and the pump, respectively. And comprising
The nozzle member has a liquid storage portion extending upward from the opening at the tip and capable of storing the inspection liquid therein.
The control unit is configured to store the liquid in the pump so that the inspection liquid ascends in the liquid storage unit when the nozzle member is moved up and down by the nozzle driving unit and a tip of the nozzle member passes through the insertion opening. Aspirating the inspection liquid inside the unit ,
The inspection chip includes the liquid storage portion, the chip main body in which a chip opening communicating the inside and the outside of the liquid storage portion is formed on the surface, and the insertion opening having a smaller diameter than the chip opening. A sheet-like elastic member that covers the chip opening and leaves
The tip portion of the nozzle member has a tapered outer peripheral surface whose diameter decreases toward the tip,
The elastic member has such an elasticity that the peripheral edge of the insertion opening of the elastic member is in close contact with the outer peripheral surface of the nozzle member when the tip of the nozzle member is inserted into the liquid container through the insertion opening. An inspection system comprising a first sheet having ductility and a second sheet bonded to the first sheet and having a lower ductility than the first sheet .   The controller stores the liquid by the pump so that the inspection liquid is located above the opening of the tip in the liquid reservoir when the tip of the nozzle member passes through the insertion opening. The inspection system according to claim 1, wherein the inspection liquid in the section is aspirated. The inspection according to claim 1 , wherein the insertion opening is formed by inserting a tip end portion of the nozzle member into the liquid storage portion from a chip opening sealed by the elastic member. system. The inspection system according to any one of claims 1 to 3 , wherein the nozzle member is a pipette tip that is detachably attached to the nozzle driving unit or the pump .

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