Chamber device, hybridization reaction system, nucleic acid analysis system, sealing member, resin chamber device, and sample placement method for resin chamber device
The chamber unit composed of a transparent component, a sealing component and a substrate, combined with a hinge and a locking mechanism, solves the assembly and operability problems of the chamber device, and realizes an airtight and disposable chamber device.
Patent Information
- Application Number
- CN202510283956.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2024-03-15
- Filing Date
- 2025-03-11
- Publication Date
- 2025-09-16
AI Technical Summary
Existing chamber devices have deficiencies in assembly and operability, and are difficult to achieve disposable use. In particular, biochemical reaction boxes made of glass and resin frames need to be sorted and processed when discarded.
The chamber unit consists of a transparent component, a sealing component and a substrate. The detachable connection of the chamber frame is achieved through a hinge mechanism and a locking mechanism. The annular protrusion and the snap-fit groove are combined to improve the airtightness, and steps and holes are set in the groove forming part to ensure the sealing.
The assembly and operability of the chamber device are improved, the airtightness of the chamber is achieved, and at the same time, it supports disposable use and avoids complicated disassembly and cleaning processes.
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Figure CN120648550A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to a chamber device, a hybridization reaction system, a nucleic acid analysis system, a sealing member, a resin chamber device, and a sample setting method for a resin chamber device. This application claims the benefit of Japanese Patent Application No. 2024-039115 filed on March 13, 2024, and Japanese Patent Application No. 2024-040909 filed on March 15, 2024, the contents of which are incorporated herein by reference. Background Art
[0002] Japanese Patent Application Publication No. 2009-542222 discloses a chamber apparatus including a chamber frame having an upper integrated gasket and a lower integrated gasket, a substrate, and a substrate frame for positioning and capturing the substrate.
[0003] Japanese Patent Application Laid-Open No. 2009-082084 discloses a target substance detection device. The target substance detection device includes a sealing portion capable of sealing a first flow path and a pressure relief member for maintaining the pressure within a reaction chamber at a substantially constant level in a biochemical reaction cartridge. The biochemical reaction cartridge includes a reaction chamber, a first flow path, and a second flow path. The reaction chamber has an area for fixing a probe for target substance detection and allowing a material to react in the fixed area. The first flow path and the second flow path connect the reaction chamber to the outside.
[0004] The above-mentioned prior art has room for improvement in terms of the assembling and operability of the chamber device. In addition, since the above-mentioned biochemical reaction box is made by joining glass and a resin frame, it must be sorted for disposal and is difficult to be disposable. Summary of the Invention
[0005] The first object of the present invention is to improve the assembly and operability of the chamber device. In addition, the second object of the present invention is to ensure the airtightness of the chamber while enabling disposable use.
[0006] Technical means for solving technical problems
[0007] In order to solve the above technical problems, a first embodiment of the chamber device of the present invention comprises: a chamber unit, wherein the chamber unit comprises a sealing component, a transparent component and a substrate, wherein the sealing component is formed with a plurality of slot forming portions extending in the thickness direction, the transparent component is mounted on a first surface side of the sealing component at one end of the slot forming portion to block one end of the slot forming portion, and the substrate is mounted on a second surface side of the sealing component at the other end of the slot forming portion to block the other end of the slot forming portion; and a chamber frame, wherein the chamber frame can be loaded and unloaded and clamped into the chamber unit in a direction in which the transparent component, the sealing component and the substrate overlap.
[0008] The second embodiment of the chamber device of the present invention In the first embodiment of the chamber device of the present invention, the chamber frame includes: a first frame, the first frame abuts against the first surface side of the chamber unit; a second frame, the second frame abuts against the second surface side of the chamber unit; a hinge mechanism, the hinge mechanism connects the first frame and the second frame so as to be rotatable; and a locking mechanism, the locking mechanism locks the two frames when the first frame and the second frame are folded.
[0009] The third-type chamber device of the present invention In the second-type chamber device of the present invention, the locking mechanism includes: a latch, which is rotatably arranged on one side of the first frame and the second frame; and a locked part, which is arranged on the other side of the first frame and the second frame and is locked with the latch.
[0010] A chamber device according to a fourth aspect of the present invention is the chamber device according to the third aspect of the present invention, wherein a surface of at least one of the latch and the locked portion is plated.
[0011] The chamber device of the fifth embodiment of the present invention is a chamber device of any one of the first to fourth embodiments of the present invention, wherein an annular protrusion is formed on the peripheral edge of the opening of the slot forming portion, and the annular protrusion abuts against the substrate and the transparent component in a compressed state when the chamber unit is clamped by the chamber frame.
[0012] A sixth aspect of the present invention provides the chamber device according to any one of the first to fifth aspects of the present invention, wherein the sealing member includes a first hole and a second hole extending from an inner wall surface to an outer side surface of the slot forming portion.
[0013] A chamber device according to a seventh aspect of the present invention is the chamber device according to the sixth aspect of the present invention, wherein a step or a wall is formed on the inner wall surface of the slot forming portion between the first hole portion and the second hole portion.
[0014] A chamber device according to an eighth aspect of the present invention is the chamber device according to the sixth or seventh aspect of the present invention, further comprising a cover member attached to the sealing member to close the first hole and the second hole.
[0015] The ninth aspect of the chamber device of the present invention is a chamber device of any one of the first to eighth aspects of the present invention, wherein the sealing component comprises: a first engaging groove, the first engaging groove being formed on the first surface side and engaging with the peripheral portion of the transparent component; and a second engaging groove being formed on the second surface side and engaging with the peripheral portion of the substrate.
[0016] A hybridization reaction system according to a tenth aspect of the present invention performs a hybridization reaction using the chamber device according to any one of the first to ninth aspects of the present invention.
[0017] The nucleic acid analysis system according to the eleventh aspect of the present invention analyzes nucleic acid extracted using the hybridization reaction system according to the tenth aspect of the present invention.
[0018] The sealing component of the twelfth embodiment of the present invention comprises: a plurality of slot forming portions, which penetrate in the thickness direction; a first hole portion and a second hole portion, which extend from the inner wall surface of the slot forming portion to the outer side surface; and a step or wall, which is arranged between the first hole portion and the second hole portion on the inner wall surface of the slot forming portion.
[0019] The resin chamber device of the thirteenth embodiment of the present invention comprises: a sealing component, which is formed with a groove forming portion that penetrates in the thickness direction; a transparent component, which is arranged on the first surface side of the sealing component at one end of the groove forming portion, and blocks one end of the groove forming portion; a substrate, which is arranged on the second surface side of the sealing component at the other end of the groove forming portion, and blocks the other end of the groove forming portion; a first frame, which abuts against the transparent component; a second frame, which abuts against the substrate; and a clamping component, which clamps the peripheral edges of the first frame and the second frame.
[0020] The fourteenth embodiment of the resin chamber device of the present invention is the resin chamber device of the thirteenth embodiment of the present invention, wherein the first frame and the second frame are formed into a rectangle when viewed from above, and are formed with a plurality of sliding grooves, which extend from the four corners along the long side direction and engage with the clamping part.
[0021] The resin chamber device of the fifteenth embodiment of the present invention In the resin chamber device of the fourteenth embodiment of the present invention, the sliding groove has a first inclined shape that becomes shallower as it moves toward the middle position in the long side direction of the first frame and the second frame, and the clamping part has an engaging claw portion that engages with the sliding groove and has a second inclined shape corresponding to the first inclined shape.
[0022] The resin chamber device of the sixteenth aspect of the present invention is the resin chamber device of any one of the thirteenth to fifteenth aspects of the present invention, wherein the surface of the first frame is covered with a resin black plating layer, and a window portion is formed for observing the slot forming portion through the transparent component.
[0023] The seventeenth embodiment of the resin chamber device of the present invention is a resin chamber device of any one of the thirteenth to fifteenth embodiments of the present invention, wherein a positioning pin protruding toward the other side is formed on one side of the first frame and the second frame, and a positioning hole engaged with the positioning pin is formed on the other side of the first frame and the second frame.
[0024] The hybridization reaction system according to the eighteenth aspect of the present invention performs a hybridization reaction using the resin chamber device according to any one of the thirteenth to fifteenth aspects of the present invention.
[0025] The nucleic acid analysis system according to the nineteenth aspect of the present invention analyzes nucleic acid extracted using the hybridization reaction system according to the eighteenth aspect of the present invention.
[0026] The sample setting method of the resin chamber device according to the twentieth aspect of the present invention comprises: a first step, in which a sealing member is superimposed on a first frame to form a first chamber unit, wherein the sealing member uses a transparent member to seal one end of a slot forming portion penetrating in the thickness direction; a second step, in which, after the first step, a sample is dripped into the slot forming portion from the other end thereof; a third step, in which, after the second step, a second chamber unit formed by superimposing a substrate on a second frame is superimposed on the first chamber unit, and the other end of the slot forming portion is sealed using the substrate; and a fourth step, in which, after the third step, the peripheral edges of the first and second frames are clamped by a clamping member.
[0027] According to one embodiment of the present invention, the chamber device can be improved in terms of assembly and operability. In addition, according to one embodiment of the present invention, the chamber device can be used once while ensuring airtightness.
[0028] Further features and aspects of the present invention will become apparent from the detailed description of the embodiments described below with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS
[0029] Figure 1 It is a perspective view of a chamber device according to the first embodiment of the present invention.
[0030] Figure 2 It is a right side view of the chamber device according to the first embodiment of the present invention.
[0031] Figure 3 This is a perspective view showing a state where the chamber frame according to the first embodiment of the present invention is opened and the cover is removed.
[0032] Figure 4It is a perspective view showing a state where a chamber unit is attached to a chamber frame according to the first embodiment of the present invention.
[0033] Figure 5 This is an exploded perspective view of the chamber unit according to the first embodiment of the present invention.
[0034] Figure 6 It is a plan view of the chamber unit according to the first embodiment of the present invention.
[0035] Figure 7 It is a bottom view of the chamber unit according to the first embodiment of the present invention.
[0036] Figure 8 yes Figure 6 The cross-sectional view shown is taken along arrow VIII-VIII.
[0037] Figure 9 This is a flow chart of assembling the chamber device according to the first embodiment of the present invention.
[0038] Figure 10 This is a schematic diagram of a nucleic acid analysis system according to a first embodiment of the present invention.
[0039] Figure 11 It is a perspective view of a slot forming portion according to a second embodiment of the present invention.
[0040] Figure 12 It is a top view of a chamber device according to a third embodiment of the present invention.
[0041] Figure 13 It is a bottom view of a chamber device according to a third embodiment of the present invention.
[0042] Figure 14 It is a perspective view of a chamber device according to a fourth embodiment of the present invention.
[0043] Figure 15 It is an exploded perspective view of a chamber device according to a fourth embodiment of the present invention.
[0044] Figure 16 It is a cross-sectional view of a chamber device according to a fourth embodiment of the present invention.
[0045] Figure 17 yes Figure 16 An enlarged view of area A is shown.
[0046] Figure 18 It is a perspective view of a resin chamber device according to a fifth embodiment of the present invention.
[0047] Figure 19 It is a front view of a resin chamber device according to a fifth embodiment of the present invention.
[0048] Figure 20 It is an exploded perspective view of a resin chamber device according to a fifth embodiment of the present invention.
[0049] Figure 21 It is a cross-sectional view of a resin chamber device according to a fifth embodiment of the present invention.
[0050] Figure 22 This is a flowchart of a sample setting method of a resin chamber device according to a fifth embodiment of the present invention.
[0051] Figure 23 It is along Figure 22 The assembly diagram of the resin chamber device shown in the flowchart.
[0052] Figure 24 It is along Figure 22 The assembly diagram of the resin chamber device shown in the flowchart.
[0053] Figure 25 It is along Figure 22 The assembly diagram of the resin chamber device shown in the flowchart.
[0054] Figure 26 It is along Figure 22 The assembly diagram of the resin chamber device shown in the flowchart.
[0055] Figure 27 This is a schematic diagram of a nucleic acid analysis system using a resin chamber device according to a fifth embodiment of the present invention.
[0056] Figure 28 It is a side view of a resin chamber device according to a sixth embodiment of the present invention.
[0057] Figure 29 It is an exploded perspective view of a resin chamber device according to a seventh embodiment of the present invention.
[0058] Figure 30 It is a cross-sectional view of a resin chamber device according to a seventh embodiment of the present invention. DETAILED DESCRIPTION
[0059] The following describes in detail the chamber devices, hybridization reaction systems, nucleic acid analysis systems, and sealing components of the first to fourth embodiments of the present invention with reference to the accompanying drawings. The following first provides an overview of the embodiments of the present invention, followed by a detailed description of each embodiment.
[0060] 〔summary〕
[0061] Japanese Unexamined Patent Publication No. 2009-542222 discloses a method for sealing the upper and lower mixing chamber components by fastening them around their entire perimeter with snaps. Japanese Unexamined Patent Publication No. 2009-082084 discloses a mixing chamber technology that provides sample injection channels at two locations, stirs the sample to improve reaction efficiency, and maintains a substantially constant pressure within the reaction chamber through the effect of a pressure relief member, thereby preventing obstruction of sample flow.
[0062] However, in the structure described in Japanese Unexamined Patent Publication No. 2009-542222, since each compartment is secured around its entire circumference after the sample is injected, assembly must be performed in a manner that prevents the injected sample from overflowing or contaminating other compartments. Furthermore, if disassembly is required after assembly, the mixing chamber components may be difficult to disassemble due to the circumferential securing with clips. Furthermore, when disassembling the mixing chamber components, the enclosed sample and the like may be scattered, requiring cleaning. Furthermore, in the structure described in Japanese Unexamined Patent Publication No. 2009-082084, since the glass is joined to the frame, manufacturing costs may be high.
[0063] In an embodiment of the present invention, a chamber unit is assembled by overlapping a transparent component, a sealing component, and a substrate, and this chamber unit is detachably clamped into a chamber frame. This structure allows the chamber device to be constructed from components that do not require joints, improving the assembly and operability of the chamber device. Furthermore, after use, the chamber unit can be removed and replaced, allowing the chamber frame to be reused without cleaning. Furthermore, by directly discarding the replaced chamber unit, the enclosed sample can be prevented from scattering.
[0064] [First embodiment]
[0065] Figure 1 It is a perspective view of the chamber device 1 according to the first embodiment of the present invention. Figure 2 It is a right side view of the chamber apparatus 1 according to the first embodiment of the present invention.
[0066] As shown in these figures, the chamber apparatus 1 includes a chamber unit 2, a chamber frame 3, and a cover 4 (cover member). The chamber apparatus 1 has a flat, substantially rectangular parallelepiped shape.
[0067] It should be noted that in the following description, an XYZ orthogonal coordinate system is sometimes set, and the positional relationship of each component is described with reference to this XYZ orthogonal coordinate system. The X-axis direction is the width direction (left-right direction) of the chamber device 1. The Y-axis direction is the depth direction (front-back direction) of the chamber device 1. The Z-axis direction is the thickness direction (up-down direction) of the chamber device 1. It should be noted that the front and back, up and down, and left and right of the chamber device 1 are defined by taking the side of the chamber frame 3 where the locking mechanism 60 is configured as the front side and the side where the hinge mechanism 50 is configured as the rear side.
[0068] Figure 3 This is a perspective view showing a state in which the chamber frame 3 according to the first embodiment of the present invention is opened and the cover 4 is removed. Figure 4 It is a perspective view showing a state where the chamber unit 2 is attached to the chamber frame 3 according to the first embodiment of the present invention.
[0069] As shown in these figures, the chamber apparatus 1 includes a chamber unit 2 detachably sandwiched between a chamber frame 3. The chamber unit 2 is provided with a plurality of well-forming portions 20 for storing samples.
[0070] Figure 5 It is an exploded perspective view of the chamber unit 2 according to the first embodiment of the present invention. Figure 6 It is a plan view of the chamber unit 2 according to the first embodiment of the present invention. Figure 7 It is a bottom view of the chamber unit 2 according to the first embodiment of the present invention. Figure 8 yes Figure 6 The cross-sectional view shown is taken along arrow VIII-VIII.
[0071] like Figure 5 As shown, the chamber unit 2 includes a sealing member 10 , a slide glass 11 (transparent member), and a DNA array substrate 12 (substrate).
[0072] The sealing member 10 has a flat rectangular shape when viewed from above. The sealing member 10 is formed of, for example, elastic silicone rubber. The sealing member 10 includes a first surface 10A facing upward, a second surface 10B facing downward, a third surface 10C facing forward, a fourth surface 10D facing rightward, a fifth surface 10E facing rearward, and a sixth surface 10F facing leftward.
[0073] The sealing member 10 is formed with a plurality of slot-forming portions 20 extending through the sealing member 10 in the thickness direction (Z-axis direction). The slot-forming portions 20 are arranged in a row in the depth direction (Y-axis direction) and in two rows spaced apart in the width direction (X-axis direction). It should be noted that the number, arrangement, and shape of the slot-forming portions 20 are not limited to those shown in the figure.
[0074] The slide glass 11 is mounted on the first surface 10A side of the sealing member 10 at the opening at one end (upper end) of the slot forming portion 20. When mounted on the sealing member 10, the slide glass 11 blocks the opening at one end (upper end) of the slot forming portion 20. As the slide glass 11, a commercially available standard part can be used. It should be noted that any transparent part that is rectangular when viewed from above is not limited to the slide glass 11, and a transparent acrylic plate or the like can also be used.
[0075] The DNA array substrate 12 includes a plurality of DNA microarrays 12a in which probe carriers for performing hybridization reactions are arranged in an array. The DNA microarrays 12a are formed in an arrangement corresponding to the slot-forming portions 20. It should be noted that the number of DNA microarrays 12a does not necessarily have to be the same as the number of slot-forming portions 20. In addition, when performing reactions other than hybridization reactions, a substrate having corresponding reaction portions may also be used.
[0076] The DNA array substrate 12 is mounted on the second surface 10B side of the sealing member 10, where the other end (lower end) of the slot-forming portion 20 is open. When mounted on the sealing member 10, the DNA array substrate 12 blocks the other end (lower end) of the slot-forming portion 20. A cutout 12b is formed on the DNA array substrate 12 to prevent incorrect assembly (orientation) relative to the sealing member 10. The cutout 12b is formed at one of the four corners of the DNA array substrate 12.
[0077] like Figure 6 As shown, an annular convex portion 21A that contacts the slide glass 11 is formed at the peripheral edge of the opening of the groove forming portion 20 on the first surface 10A side of the sealing member 10. Figure 8 The annular protrusion 21A has a semicircular convex shape in cross section and abuts against the slide glass 11 attached to the sealing member 10 in a compressed state in the vertical direction (Z-axis direction), thereby improving the sealing performance of the groove forming portion 20.
[0078] Furthermore, a first engaging groove 22 is formed on the first surface 10A side of the sealing member 10 to engage with the peripheral edge portion of the slide glass 11. Figure 6 As shown, the first engagement groove 22 is engaged with the peripheral edge portion of the slide glass 11 over the entire circumference. When the slide glass 11 is engaged with the first engagement groove 22, the sealing member 10 is elastically deformed.
[0079] like Figure 5As shown, the first surface 10A of the sealing member 10 is formed with an engaging recess 23 extending in the front-to-back direction (Y-axis direction). A pair of engaging recesses 23 are formed along the fourth surface 10D and the sixth surface 10F. Furthermore, the second surface 10B of the sealing member 10 is also formed with an engaging recess 23 extending in the front-to-back direction (Y-axis direction). A pair of engaging recesses 23 are also formed along the fourth surface 10D and the sixth surface 10F.
[0080] like Figure 6 As shown, the sealing member 10 is formed with an inlet 25 (first hole) and an outlet 24 (second hole) extending from the inner wall surface of the slot-forming portion 20 in the width direction (X-axis direction) to the outer side surfaces (fourth surface 10D and sixth surface 10F) of the sealing member 10. An injection needle such as a pipette is inserted into the inlet 25 to inject the sample into the slot-forming portion 20. Air, sample, etc. are exhausted from the slot-forming portion 20 through the outlet 24.
[0081] A step 28 is formed on the inner wall of the slot-forming portion 20 between the injection port 25 and the discharge port 24. In other words, a recessed portion is provided on the inner wall of the slot-forming portion 20, and the discharge port 24 is formed in this recessed portion. This prevents the reagent injected into the slot-forming portion 20 from short-circuiting to the discharge port 24 immediately after injection and being discharged. Consequently, a predetermined amount of reagent can be efficiently injected into the slot-forming portion 20.
[0082] The outlet side (outer side) of the injection port 25 is formed into a tapered portion 25a with an expanded diameter. A plate portion 26 is formed on the outer side surfaces (fourth surface 10D and sixth surface 10F) of the sealing member 10, protruding laterally. To prevent contamination of the sample between the slot-forming sections 20, the plate portion 26 is provided to separate the injection port 25 and discharge port 24 connected to the same slot-forming section 20 from the injection port 25 and discharge port 24 connected to other slot-forming sections 20.
[0083] Figure 1 as well as Figure 2 The cap 4 shown is attached to the outer side surfaces (fourth surface 10D and sixth surface 10F) of the sealing member 10 to block the inlet 25 and the outlet 24. The cap 4 includes two protrusions (not shown) into which the inlet 25 and the outlet 24 can be inserted, and a receiving groove (not shown) for receiving the plate portion 26.
[0084] like Figure 8As shown, an annular protrusion 21B is formed around the opening of the slot-forming portion 20 on the second surface 10B side of the sealing member 10, which contacts the DNA array substrate 12. The annular protrusion 21B has a semicircular convex shape when viewed in cross-section. The annular protrusion 21B contacts the DNA array substrate 12 attached to the sealing member 10 in a compressed state in the vertical direction (Z-axis direction), thereby improving the sealing performance of the slot-forming portion 20.
[0085] In addition, a second engagement groove 29 is formed on the second surface 10B side of the sealing member 10 to engage with the peripheral edge portion of the DNA array substrate 12. Figure 7 As shown, the second engagement groove 29 is engaged with the peripheral edge portion of the DNA array substrate 12 over substantially the entire circumference. Note that when the DNA array substrate 12 is engaged with the second engagement groove 29, the sealing member 10 is elastically deformed.
[0086] Positioning recesses 27a to 27d are formed on the second surface 10B of the sealing member 10 at positions corresponding to the four corners of the DNA array substrate 12. Positioning recesses 27a and 27b are formed at positions corresponding to the two front corners of the DNA array substrate 12. Positioning recesses 27c and 27d are formed at positions corresponding to the two rear corners of the DNA array substrate 12.
[0087] Positioning recesses 27c and 27d are connected to second engagement groove 29. Therefore, the corners at two locations on the rear of DNA array substrate 12 extend from second engagement groove 29 into positioning recesses 27c and 27d. It should be noted that positioning recesses 27a and 27b are not connected to second engagement groove 29, but they can be connected.
[0088] like Figure 4 As shown, the chamber frame 3 includes: a first frame 30 abutting against the first surface 10A side of the chamber unit 2, a second frame 40 abutting against the second surface 10B side of the chamber unit 2, a hinge mechanism 50 rotatably connecting the first frame 30 and the second frame 40, and a locking mechanism 60 locking the two frames when the first frame 30 and the second frame 40 are folded.
[0089] The second frame 40 is formed with a support base 41 for supporting the DNA array substrate 12 from below and positioning protrusions 42a to 42d provided at four locations around the support base 41. The support base 41 has a rectangular shape when viewed from above and has a structure that can be inserted into the support base 41. Figure 7 The size of the second engaging groove 29 is shown.
[0090] The positioning protrusions 42a to 42d have a structure that can be inserted into Figure 7By inserting the positioning protrusions 42a to 42d into the positioning recesses 27a to 27d, the DNA array substrate 12 (chamber unit 2) is positioned relative to the second frame 40. Figure 4 As shown, each of the positioning protrusions 42 a to 42 d is formed with a recessed portion to avoid interference with the corners of the DNA array substrate 12 .
[0091] A pair of engaging ribs 43 extending parallel to the front-to-back direction (Y-axis direction) are formed on the left and right sides of the support base 41. The pair of engaging ribs 43 engage with a pair of engaging recesses 23 provided on the second surface 10B side of the sealing member 10. The engagement of the pair of engaging ribs 43 with the pair of engaging recesses 23 positions the sealing member 10 (chamber unit 2) relative to the second frame 40.
[0092] A pair of clamping protrusions 44 extending parallel to the front-back direction (Y-axis direction) are formed on both left and right sides of the pair of engaging ribs 43. Figure 1 as well as Figure 2 The convex portion of the cover 4 is shown. This makes it difficult for the cover 4 to be separated from the sealing member 10 (chamber unit 2).
[0093] like Figure 4 As shown, a plurality of windows 31 for observing the slot forming portion 20 and a pair of slits 32 arranged on the left and right sides of the plurality of windows 31 are formed on the first frame 30. Figure 1 As shown, in a state where the chamber apparatus 1 is assembled, the plurality of windows 31 are formed at positions overlapping with the slot forming portion 20 in the Z-axis direction.
[0094] The windows 31 extend through the first frame 30 in the thickness direction (Z-axis direction). The windows 31 are arranged in a row in the depth direction (Y-axis direction) and in two rows spaced apart in the width direction (X-axis direction). It should be noted that the number, arrangement, and shape of the windows 31 are not limited to those shown in the figure. In this embodiment, two slot-forming portions 20 can be observed from a single window 31.
[0095] The slit 32 penetrates the first frame 30 along the thickness direction (Z-axis direction). Figure 6 As shown, the slit 32 is formed at a position overlapping the middle portion of the injection port 25 and the discharge port 24 of the sealing member 10 when viewed from above. This allows confirmation that the injection needle is securely inserted into the injection port 25 when injecting a sample into the slot-forming portion 20. It should be noted that the sealing member 10 only needs to be light-transmissive, and can be, for example, transparent or translucent.
[0096] like Figure 4As shown, a pair of engaging ribs 33 extending parallel to the front-to-back direction (Y-axis direction) are formed on the left and right sides of the pair of slits 32. The pair of engaging ribs 33 engage with the pair of engaging recesses 23 provided on the first surface 10A side of the sealing member 10. The engagement of the pair of engaging ribs 33 with the pair of engaging recesses 23 positions the sealing member 10 (chamber unit 2) relative to the first frame 30.
[0097] A pair of clamping protrusions 34 extending parallel to the front-back direction (Y-axis direction) are formed on both left and right sides of the pair of engaging ribs 33. Figure 1 as well as Figure 2 The convex portion of the cover 4 is shown. This makes it difficult for the cover 4 to be separated from the sealing member 10 (chamber unit 2).
[0098] like Figure 3 as well as Figure 4 As shown, the hinge mechanism 50 connects rear end portions of the first frame 30 and the second frame 40 to each other so as to be rotatable around an axis extending in the width direction (X-axis direction).
[0099] like Figure 1 As shown, the locking mechanism 60 releasably fixes the front ends of the first frame 30 and the second frame 40 to each other.
[0100] The locking mechanism 60 includes a latch 61 rotatably mounted on the first frame 30 and a locked portion 62 mounted on the second frame 40 and locked with the latch 61. Alternatively, the latch 61 may be rotatably mounted on the second frame 40, and the locked portion 62 may be mounted on the first frame 30.
[0101] like Figure 3 As shown, the latch 61 is rotatably coupled to the front end of the first frame 30 about an axis extending in the width direction (X-axis direction). The latch 61 has an elongated hole 61a extending in the width direction. A claw 61b protrudes from the inside of the elongated hole 61a. The claw 61b is formed on the inner wall surface of the elongated hole 61a, on the side (lower side) of the latch 61's rotation end, and extends in the width direction.
[0102] The locked portion 62 is formed at the front end of the second frame 40. The locked portion 62 is formed in a plate-like shape extending in the width direction. A step portion 62a is provided protruding from the lower surface of the locked portion 62. When the locked portion 62 is inserted into the elongated hole 61a of the latch 61, the claw portion 61b passes over the step portion 62a and engages with the step portion 62a in the depth direction (Y-axis direction), thereby locking the first frame 30 and the second frame 40.
[0103] The securing force of the locking mechanism 60 is preferably within the range of 20N to 40N, equivalent to the force of a typical human finger. In this embodiment, the securing force is designed to be 20N, for example. Furthermore, to improve slidability and durability, the surfaces of the latch 61 and the latched portion 62 are preferably plated. This allows for smooth opening and closing of the chamber frame 3.
[0104] Figure 9 This is a flowchart of assembling the chamber apparatus 1 according to the first embodiment of the present invention. When assembling the chamber apparatus 1, first, the first frame 30 and the second frame 40 connected by the hinge mechanism 50 are opened and set (set to rest) (step S1).
[0105] Next, the glass slide 11 and the DNA array substrate 12 are placed around the first engagement groove 22 and the second engagement groove 29 of the sealing member 10 (step S2). Annular protrusions 21A and 21B are formed around the opening of the slot-forming portion 20 on the first and second surfaces 10A, 10B of the sealing member 10. By placing the glass slide 11 and the DNA array substrate 12, a sealed space, i.e., a reaction space for the DNA microarray 12a and the reagents, is formed in the slot-forming portion 20.
[0106] Next, the chamber unit 2, which is assembled with the sealing member 10, the slide glass 11, and the DNA array substrate 12, is placed on the second frame 40 (step S3). The second frame 40 is provided with a positioning structure (positioning protrusions 42a to 42d, engaging ribs 33, etc.) for placing the chamber unit 2 in a predetermined position, making it easy to place the chamber unit 2.
[0107] Next, the first frame 30 connected to the second frame 40 is closed, and with the first and second frames 30 and 40 folded, the latch 61 is hooked onto the latched portion 62 to secure them (step S4). After holding the chamber frame 3 by hand or placing it on a dedicated jig, etc., a test reagent is injected from the injection port 25 into the slot-forming portion 20 using a pipette or the like (step S5).
[0108] After the reagent is injected into the slot-forming portion 20 on one side (e.g., the right side), the injection port 25 and the discharge port 24 on one side are sealed with the lid 4, so that the slot-forming portion 20 on one side becomes a sealed state (step S6). The same operation is performed on the slot-forming portion 20 on the opposite side (e.g., the left side) (step S7). Once the above steps are all completed, the next step is transferred to (step S8).
[0109] After completing the next step, the latch 61 is removed from the locked portion 62, and the chamber frame 3 is opened (step S9). Then, the chamber unit 2, which is assembled with the sealing component 10, the glass slide 11, and the DNA array substrate 12, is removed from the chamber frame 3 with the lid 4 attached and directly discarded (step S10). The glass slide 11 and the DNA array substrate 12 are completely or substantially completely enclosed in the sealing component 10, and the reagent inside can be retained without leakage for only tens of seconds, so the reagent will not be scattered into the chamber frame 3. Therefore, the chamber frame 3 can be reused without cleaning.
[0110] Figure 10 This is a schematic diagram of a nucleic acid analysis system 600 using the chamber device 1 according to the first embodiment of the present invention.
[0111] like Figure 10 As shown, the nucleic acid analysis system 600 includes a bacteria recovery system 200 , a nucleic acid extraction system 300 , a hybridization reaction system 400 , and a detection system 500 .
[0112] The bacteria recovery system 200 is a system for recovering bacteria (such as bacteria or fungi) contained in the sample 100. For example, when testing a beverage, the sample 100 may be the manufactured beverage, the water used to make the beverage, or a liquid used in the beverage manufacturing process. Alternatively, to examine the presence and extent of bacterial contamination in the manufacturing environment, the sample 100 may also be a liquid from which bacteria have been recovered, such as from a cotton swab used to wipe the inspection environment.
[0113] Bacteria can be recovered, for example, by pressurizing or depressurizing the recovered liquid and filtering it with a filter. For example, in the case of recovering bacteria or fungi, the pore size of the filter can be 0.22μm to 0.45μm. After the bacteria are recovered with the filter, the filter is placed in a culture container described later and immersed in a culture solution for culturing the bacteria to culture the bacteria. In the culture of bacteria, for example, there are static culture in which the culture container is placed stationary for cultivation and shaking culture in which the culture container is shaken for cultivation. The culture solution in which the bacteria are cultured is transferred to the next process (nucleic acid extraction system 300). It should be noted that the bacteria can be collected by centrifugation and transferred to the next process, or the liquid placed in the filter can be vibrated to transfer the liquid in which the bacteria are suspended to the next process.
[0114] The nucleic acid extraction system 300 is a system that destroys (dissolves) the membrane structure of cells in a liquid and extracts nucleic acids from bacterial cells. It should be noted that a liquid containing other nucleic acids that react with the extracted nucleic acids can also be mixed into the sample 100 from which nucleic acids have been extracted. In addition, in order to detect in the detection process (detection system 500) described later, the other nucleic acids can also be nucleic acids that are given sites that have fluorescence, luminescence, or extinction under specific conditions. These can be mixed into the sample 100 before being processed using the nucleic acid extraction system 300, or mixed into the sample 100 after being processed using the nucleic acid extraction system 300.
[0115] The hybridization reaction system 400 performs a hybridization reaction on nucleic acids in the sample 100. The aforementioned chamber device 1 is used in this process. During the hybridization reaction, the sample 100 is heated to, for example, 60°C and stirred in the well-forming portion 20, thereby performing a hybridization reaction with the aforementioned other nucleic acids. During this reaction, for example, sites on the aforementioned other nucleic acids that exhibit fluorescence, luminescence, or quenching properties under specific conditions react with the nucleic acids in the sample 100, thereby producing fluorescence, luminescence, or quenching properties.
[0116] It should be noted that by designing the structure of the aforementioned other nucleic acid to react with a specific nucleic acid, for example, it is possible to make it react only with nucleic acids contained in specific bacteria in the sample 100. That is, by using other nucleic acids that react with the specific nucleic acid in the process of the hybridization reaction system 400, the fluorescence, luminescence, or quenching effect imparted to the other nucleic acid can be exhibited only when the sample 100 contains the specific bacteria.
[0117] The detection system 500 detects the presence, extent, etc. of fluorescence, luminescence, or quenching effects expressed in the sample 100 processed by the hybridization reaction system 400. For example, the detection system 500 excites fluorescence expressed in nucleic acids in the sample 100 using an excitation laser and detects the excited fluorescence using a highly sensitive camera.
[0118] Alternatively, the detection system 500 uses a highly sensitive camera to detect the luminescence effect manifested in the nucleic acid of the sample 100. Alternatively, the detection system 500 uses a highly sensitive camera to detect the degree of extinction of the fluorescence or luminescence imparted near the site where the extinction effect is imparted. Regarding this detection method, for example, the method described in Japanese Patent Application Laid-Open No. 2020-74726 can also be used.
[0119] The nucleic acid analysis system 600 can analyze whether specific bacteria (such as bacteria or fungi) are contained in the sample 100 or the concentration thereof by using the series of systems described above.
[0120] As described above, the chamber device 1 of this embodiment includes: a chamber unit 2 including a sealing member 10, a glass slide 11 (transparent member), and a DNA array substrate 12 (substrate). The sealing member 10 is formed with a plurality of slot-forming portions 20 extending through the sealing member 10 in the thickness direction. The glass slide 11 (transparent member) is attached to the first surface 10A of the sealing member 10, where one end of the slot-forming portion 20 is open, thereby blocking the slot-forming portion 20. The DNA array substrate 12 (substrate) is attached to the second surface 10B of the sealing member 10, where the other end of the slot-forming portion 20 is open, thereby blocking the other end of the slot-forming portion 20. Furthermore, a chamber frame 3 is provided to detachably sandwich the chamber unit 2 in a direction in which the glass slide 11, the sealing member 10, and the DNA array substrate 12 overlap. This configuration allows the chamber device 1 to be constructed from components that do not require joints, thereby improving the ease of assembly and operability of the chamber device 1. Furthermore, after use, the chamber unit 2 can be removed and replaced, and the chamber frame 3 can be reused without cleaning. Furthermore, by directly discarding the replaced chamber unit 2, the sealed sample can be prevented from scattering.
[0121] Furthermore, in the chamber apparatus 1 of this embodiment, the chamber frame 3 includes a first frame 30 that abuts the first surface 10A side of the chamber unit 2, a second frame 40 that abuts the second surface 10B side of the chamber unit 2, a hinge mechanism 50 that rotatably connects the first frame 30 and the second frame 40, and a locking mechanism 60 that locks the first frame 30 and the second frame 40 when the two frames are folded. With this structure, since the first frame 30 and the second frame 40 are connected by the hinge mechanism 50, the two frames only need to be fixed at a single location, simplifying the assembly of the chamber apparatus 1.
[0122] Furthermore, in the chamber apparatus 1 of this embodiment, the locking mechanism 60 includes a latch 61 rotatably provided on one of the first frame 30 and the second frame 40, and a latched portion 62 provided on the other of the first frame 30 and the second frame 40 and latched with the latch 61. With this structure, the chamber frame 3 can be secured simply by hooking the latch 61 with the latched portion 62.
[0123] In the chamber apparatus 1 of this embodiment, at least one of the latch 61 and the engaged portion 62 is plated. This configuration improves the slidability and durability of the latch 61 and the engaged portion 62, enabling smoother opening and closing of the chamber frame 3.
[0124] Furthermore, in the chamber device 1 of this embodiment, annular protrusions 21A and 21B are formed around the periphery of the opening of the slot-forming portion 20. These annular protrusions 21A and 21B abut against the DNA array substrate 12 and the glass slide 11 in a compressed state when the chamber unit 2 is sandwiched between the chamber frame 3. With this structure, the annular protrusions 21A and 21B abut against the glass slide 11 and the DNA array substrate 12 in a compressed state, thereby forming a sealed space within the slot-forming portion 20, i.e., a reaction space for the DNA microarray 12a and the reagents.
[0125] Furthermore, in the chamber device 1 of this embodiment, an injection port 25 (first hole) and an exhaust port 24 (second hole) are formed in the sealing member 10, extending from the inner wall surface of the slot-forming portion 20 to the outer side surfaces (fourth surface 10D and sixth surface 10F). This configuration allows the reagent to be injected from the outer side while forming a sealed space in the slot-forming portion 20.
[0126] Furthermore, in the chamber device 1 of this embodiment, a step 28 is formed on the inner wall surface of the slot-forming portion 20 between the injection port 25 and the discharge port 24. This configuration prevents the reagent injected from the injection port 25 into the slot-forming portion 20 from short-circuiting to the discharge port 24 immediately after injection and being discharged.
[0127] The chamber device 1 of this embodiment further includes a cover 4 (cover member) attached to the sealing member 10 to close the injection port 25 and the discharge port 24. This structure can prevent the reagent injected into the groove forming portion 20 from leaking from the injection port 25 or the discharge port 24.
[0128] Furthermore, in the chamber device 1 of this embodiment, the sealing member 10 includes a first engaging groove 22 formed on the first surface 10A side and engaging with the peripheral edge of the slide glass 11, and a second engaging groove 29 formed on the second surface 10B side and engaging with the peripheral edge of the DNA array substrate 12. With this structure, the slide glass 11 and the DNA array substrate 12 are fully inserted around the sealing member 10, and the reagent inside can be retained for only tens of seconds without leakage. Therefore, when the chamber frame 3 is discarded, the reagent can be prevented from scattering onto the chamber frame 3.
[0129] Furthermore, the hybridization reaction system 400 of this embodiment performs a hybridization reaction using the chamber device 1. According to this configuration, the operability of the hybridization reaction can be improved by improving the assemblability and operability of the chamber device 1.
[0130] Furthermore, the nucleic acid analysis system 600 of this embodiment analyzes nucleic acids extracted using the hybridization reaction system 400. According to this configuration, the assemblability and operability of the chamber device 1 are improved, thereby improving the workability of nucleic acid analysis.
[0131] [Second embodiment]
[0132] Next, a second embodiment of the present invention will be described. In the following description, the same or equivalent components as those in the above embodiment are denoted by the same reference numerals, and their descriptions will be simplified or omitted.
[0133] Figure 11 It is a perspective view of a slot forming portion 20 according to a second embodiment of the present invention.
[0134] like Figure 11 As shown, a wall 28 a is formed on the inner wall surface of the slot forming portion 20 of the second embodiment between the injection port 25 and the discharge port 24 .
[0135] Wall 28a extends obliquely from injection port 25 toward discharge port 24. Wall 28a is formed into a generally triangular tongue-like shape when viewed from above. Discharge port 24 is located closer to the outer side of sealing member 10 than the top end of wall 28a. This configuration, similar to step 28 of the first embodiment, prevents reagent injected from injection port 25 into slot-forming portion 20 from short-circuiting to discharge port 24 immediately after injection and being discharged.
[0136] [Third embodiment]
[0137] Next, a third embodiment of the present invention will be described. In the following description, the same or equivalent components as those in the above embodiment are denoted by the same reference numerals, and their descriptions will be simplified or omitted.
[0138] Figure 12 It is a plan view of a chamber apparatus 1 according to a third embodiment of the present invention. Figure 13 It is a bottom view of the chamber apparatus 1 according to the third embodiment of the present invention.
[0139] As shown in these drawings, the lock mechanism 60 of the third embodiment has a bayonet structure.
[0140] The locking mechanism 60 of the third embodiment includes a pair of fixing pieces 63 rotatably mounted on the first frame 30, and a pair of through-holes 64 provided in the second frame 40 and locked by rotating the pair of fixing pieces 63. It should be noted that the pair of fixing pieces 63 may be rotatably mounted on the second frame 40, while the pair of through-holes 64 may be provided in the first frame 30.
[0141] like Figure 12 As shown, the fixing piece 63 is rotatably mounted on the front end portion of the first frame 30 around a rotation axis 63a extending in the thickness direction (Z-axis direction). Figure 13 As shown, the fixing piece 63 includes an insertion end 63b that can be inserted into the through hole 64. The insertion end 63b has a substantially rectangular shape when viewed from below.
[0142] The through hole 64 extends through the front end of the second frame 40 in the thickness direction (Z-axis direction). When viewed from above, the through hole 64 has a roughly rectangular shape extending in the front-to-back direction (Y-axis direction). The lower end of the fixing plate 63 is inserted into the through hole 64. By rotating the fixing plate 63, the insertion end 63b is locked to the opening edge of the through hole 64, thereby locking the first frame 30 and the second frame 40. With the above structure, the chamber device 1 can also be composed of components that do not have joints, thereby improving the assembly and operability of the chamber device 1.
[0143] [Fourth embodiment]
[0144] Next, a fourth embodiment of the present invention will be described. In the following description, the same or equivalent components as those in the above-described embodiment are denoted by the same reference numerals, and their descriptions will be simplified or omitted.
[0145] In each of the above embodiments, the chamber frame 3 includes a first frame 30 that abuts the first surface 10A of the chamber unit 2, a second frame 40 that abuts the second surface 10B of the chamber unit 2, and a hinge mechanism 50 that rotatably connects the first frame 30 and the second frame 40. The chamber frames 3 in each of the above embodiments are designed for repeated use, and the hinge mechanism 50 is made of metal. In contrast, the fourth embodiment aims to provide a disposable chamber device 1 including a chamber frame 3.
[0146] Figure 14 It is a perspective view of a chamber device 1 according to a fourth embodiment of the present invention. Figure 15 It is an exploded perspective view of a chamber device 1 according to a fourth embodiment of the present invention.
[0147] As shown in these drawings, the chamber apparatus 1 of the fourth embodiment includes resin-made clamping members 70 that clamp the short sides of the first frame 30 and the second frame 40 on both sides in the Y-axis direction.
[0148] The clamping member 70 is formed in a U-shape when viewed from the X-axis direction. Sliding grooves 35 extending in the X-axis direction are formed along the short sides of the first and second frames 30 and 40 in the Y-axis direction. A protrusion that engages with the sliding grooves 35 is formed at the top of the U-shape of the clamping member 70. The clamping member 70 engages with the first and second frames 30 and 40 by sliding along the sliding grooves 35 in the X-axis direction, and clamps the first and second frames 30 and 40 in the Z-axis direction.
[0149] like Figure 15As shown, in the fourth embodiment, a transparent resin member 11A is used as a transparent member instead of the slide glass 11. Examples of the transparent resin member 11A include acrylic, polyethylene terephthalate, polycarbonate, and polyvinyl chloride. The transparent resin member 11A has a plurality of protrusions 11a formed thereon, which are arranged in the plurality of windows 31.
[0150] This transparent resin member 11A is integrated with the first frame 30 (high-strength resin member) by, for example, two-color molding. Protrusions 11a are provided in the window portion 31 to enhance the strength of the portion that serves as the cavity in the aforementioned embodiments. It should be noted that by integrating the transparent resin member 11A with the first frame 30, the chamber unit 2 consists of the sealing member 10 and the DNA array substrate 12, excluding the transparent member.
[0151] Figure 16 It is a cross-sectional view of a chamber device 1 according to a fourth embodiment of the present invention. Figure 17 yes Figure 16 An enlarged view of area A is shown.
[0152] like Figure 16 As shown, an annular protrusion 21B is formed around the opening of the slot-forming portion 20 on the second surface 10B side (-Z side) of the sealing member 10, which contacts the DNA array substrate 12. On the other hand, the annular protrusion 21A of the above-described embodiments is not formed around the opening of the slot-forming portion 20 on the first surface 10A side (+Z side) of the sealing member 10.
[0153] like Figure 17 As shown, the sealing performance of the slotted hole forming portion 20 on the first surface 10A side (+Z side) of the sealing member 10 is ensured by the flange portion 11b formed on the transparent resin member 11A. The flange portion 11b abuts against the inner wall surface of the slotted hole forming portion 20 formed in the sealing member 10 over the entire circumference. As a result, the inner wall surface of the slotted hole forming portion 20 is compressed, which can improve the sealing performance of the slotted hole forming portion 20 on the first surface 10A side (+Z side) of the sealing member 10.
[0154] This structure replaces the annular protrusion 21A with the flange 11b, compressing the sealing member 10 in the transverse direction (along the XY plane). This reduces the force exerted on the sealing member 10 in the Z-axis direction by half compared to the aforementioned embodiments. Consequently, even when the metal hinge mechanism 50 is replaced with the resin clamping member 70, sufficient sealing of the slotted portion 20 can be ensured. Consequently, the entire chamber apparatus 1, including the chamber frame 3, can be used once.
[0155] While preferred embodiments of the present invention have been described above with reference to the accompanying drawings, the present invention is not limited to the aforementioned embodiments. The various shapes and combinations of the components shown in the aforementioned embodiments are merely examples, and various modifications may be made based on design requirements, etc., without departing from the spirit of the present invention.
[0156] For example, in the above embodiment, the first frame 30 and the second frame 40 are rotatably connected by the hinge mechanism 50, but the hinge mechanism 50 may be omitted. In this case, the locking mechanism 60 may be provided at the portion where the hinge mechanism 50 was originally located, thereby locking the first frame 30 and the second frame 40 at two locations.
[0157] Next, the resin chamber devices, hybridization reaction systems, nucleic acid analysis systems, and sample placement methods for resin chamber devices according to the fifth to seventh embodiments of the present invention will be described in detail with reference to the accompanying drawings. Below, an overview of the embodiments of the present invention will be first described, followed by a detailed description of each embodiment.
[0158] 〔summary〕
[0159] In Japanese Patent Application Laid-Open No. 2009-082084, disclose the flow path of injecting sample at two positions, carry out the mixing chamber of stirring of sample in order to improve reaction efficiency.This mixing chamber can not hinder the flow of sample by keeping the pressure in the reaction chamber as the effect of roughly constant pressure relief member.But, in the structure that Japanese Patent Application Laid-Open No. 2009-082084 is put down in writing, owing to glass and resin frame are joined, therefore, manufacturing cost is likely to become expensive.In addition, in order to discard, glass and resin frame must be classified, be difficult to disposable (disposable).
[0160] To address these issues, the inventors of this application proposed a structure in which a chamber unit is sandwiched between chamber frames that are openably and closably connected by a hinge mechanism, and the chamber frames are secured by a latch mechanism to prevent them from opening. This structure allows the chamber unit to be removed from the chamber frame by releasing the latch mechanism, making it disposable, thus preventing sample scattering and allowing for repeated use without requiring cleaning. However, the chamber frame is made of metal to ensure strength, preventing the entire device from being disposable.
[0161] In an embodiment of the present invention, a transparent member, a sealing member, and a substrate are sandwiched between a first frame and a second frame, and the peripheral edges of the first and second frames are clamped by a clamping member. This structure allows various components to be made of resin, while ensuring the tightness of the slots formed in the sealing member. Consequently, a used resin chamber device can be directly discarded.
[0162] [Fifth embodiment]
[0163] Figure 18 It is a perspective view of a resin chamber device 101 according to a fifth embodiment of the present invention. Figure 19 It is a front view of a resin chamber device 101 according to a fifth embodiment of the present invention. Figure 20 It is an exploded perspective view of a resin chamber device 101 according to a fifth embodiment of the present invention. Figure 21 It is a cross-sectional view of a resin chamber device 101 according to a fifth embodiment of the present invention.
[0164] like Figure 20 as well as Figure 21 As shown, the resin chamber device 101 includes a sealing member 110 , a transparent member 111 , a DNA array substrate 112 (substrate), a first frame 130 , a second frame 140 , and a clamping member 150 .
[0165] The sealing member 110, the transparent member 111, the DNA array substrate 112, the first frame 130, the second frame 140, and the clamping member 150 are formed of a resin material. In order to ensure the airtightness of the slot forming portion 120, the sealing member 110 can be formed of, for example, an elastic silicone resin. In order to maintain the shape, the first frame 130, the second frame 140, and the clamping member 150 are formed of a high-strength resin material having a higher strength than the sealing member 110. As a high-strength resin material, the elastic modulus is preferably above 10 GPa. Unless otherwise specified, a known resin material can be used. It should be noted that the transparent member 111 and the DNA array substrate 112 can also be formed of a high-strength resin material, but can also be formed of a resin material having an elastic modulus of about 2 GPa (e.g., cycloolefin polymer (COP) resin).
[0166] like Figure 18 As shown, the resin chamber device 101 has a rectangular shape when viewed from above. It should be noted that in the following description, an XYZ orthogonal coordinate system is sometimes used, and the positional relationships of the various components are described with reference to this XYZ orthogonal coordinate system. The X-axis direction is the short side direction (left-right direction) of the resin chamber device 101. The Y-axis direction is the long side direction (front-back direction) of the resin chamber device 101. The Z-axis direction is the thickness direction (up-down direction) of the resin chamber device 101.
[0167] like Figure 20As shown, the sealing member 110 has a rectangular flat shape when viewed from above. A plurality of slot-forming portions 120 are formed on the sealing member 110, extending through the sealing member 110 in the thickness direction (Z-axis direction). The slot-forming portions 120 are arranged in a row in the longitudinal direction (Y-axis direction) and in two rows spaced apart in the transverse direction (X-axis direction). It should be noted that the number, arrangement, and shape of the slot-forming portions 120 are not limited to those shown in the figure.
[0168] like Figure 21 As shown, the transparent component 111 is arranged on the first surface 110A side of the sealing component 110 at the opening of one end (upper end) of the slot forming portion 120. The transparent component 111 blocks the opening of one end (upper end) of the slot forming portion 120 when the resin chamber device 101 is assembled. As the transparent component 111, for example, cycloolefin polymer (COP) resin can be preferably used. It should be noted that the sealing component 110 can also be pre-formed on a single side of the transparent component 111. Thereby, the sealing performance between the transparent component 111 and the sealing component 110 can be improved.
[0169] like Figure 20 As shown, the DNA array substrate 112 includes a plurality of DNA microarrays 112a in which probe carriers for hybridization reactions are arranged in an array. The DNA microarrays 112a are arranged to correspond to the slot-forming portions 120. It should be noted that the number of DNA microarrays 112a does not necessarily have to be the same as the number of slot-forming portions 120. Furthermore, when performing reactions other than hybridization, a substrate having corresponding reaction portions may also be used.
[0170] like Figure 21 As shown, the DNA array substrate 112 is arranged on the second surface 110B side of the sealing component 110 where the other end (lower end) of the slot forming portion 120 is open. When the resin chamber device 101 is assembled, the DNA array substrate 112 blocks the opening of the other end (lower end) of the slot forming portion 120. An annular protrusion 121B is formed around the opening of the slot forming portion 120 on the second surface 110B side of the sealing component 110, which abuts the DNA array substrate 112. The annular protrusion 121B has a convex shape that is semicircular when viewed in cross section. The annular protrusion 121B abuts the DNA array substrate 112 mounted on the sealing component 110 in a compressed state in the vertical direction (Z-axis direction), thereby improving the sealing performance of the slot forming portion 120.
[0171] like Figure 20As shown, a plurality of window portions 131 for observing the slot forming portion 120 are formed on the first frame 130. When the resin chamber device 101 is assembled, the plurality of window portions 131 are formed at positions overlapping with the slot forming portion 120 in the Z-axis direction. The window portions 131 pass through the first frame 130 in the thickness direction (Z-axis direction). The window portions 131 form a row in the long side direction (Y-axis direction) and are formed into two rows at intervals in the short side direction (X-axis direction). It should be noted that the number, configuration and shape of the window portions 131 are not limited to those shown in the figure. As shown in FIG. Figure 21 As shown, a groove 134 is formed on the lower side (-Z side) of the first frame 130 , in which the transparent member 111 is arranged to close the window 131 .
[0172] The surface of the first frame 130 is covered with a black coating made of resin. When the first frame 130 is formed of a conventional high-strength resin material, the first frame 130 generates autofluorescence, which sometimes obstructs the fluorescence observation of the slot forming portion 120. Therefore, by covering the surface of the first frame 130 with a black coating made of resin, it is possible to prevent the autofluorescence of the first frame 130 from obstructing the fluorescence observation. It should be noted that, in addition to the first frame 130, the sealing component 110, the transparent component 111, and the DNA array substrate 112 forming the slot forming portion 120 can also be made of, for example, 5 uW / m 2 The following low autofluorescence resin material is formed.
[0173] like Figure 19 as well as Figure 20 As shown, a positioning pin 133 is formed on the first frame 130 on the side (-Z side) facing the second frame 140. A positioning hole 141 is formed on the second frame 140 on the side (+Z side) facing the first frame 130 to engage with the positioning pin 133. Figure 20 As shown, the positioning pins 133 and the positioning holes 141 are provided at two locations on one side (-Y side) in the longitudinal direction and one location on the other side (+Y side) in the longitudinal direction, and cannot be combined when the first frame 130 and the second frame 140 are facing opposite directions in the longitudinal direction.
[0174] like Figure 20 As shown, a receiving groove 142 for accommodating the DNA array substrate 112 is formed on the second frame 140. Receiving groove 142 has a rectangular shape when viewed from above. A plurality of protrusions 141a are formed on the side surfaces of receiving groove 142 for positioning the DNA array substrate 112. Furthermore, a recessed recess 141b is formed on the bottom surface of receiving groove 142. A double-sided adhesive tape (not shown) is disposed in recess 141b to secure the DNA array substrate 112.
[0175] like Figure 20As shown, the first frame 130 and the second frame 140 are formed in a rectangular shape when viewed from above. Sliding grooves 132 extending along the longitudinal direction (Y-axis direction) are formed on the periphery of the first frame 130 and the second frame 140. The sliding grooves 132 are formed from the four corners of the first frame 130 and the second frame 140 along a pair of long sides of the first frame 130 and the second frame 140. The sliding grooves 132 are formed in a straight line with a certain depth relative to the upper surface of the first frame 130 and the lower surface of the second frame 140.
[0176] like Figure 18 as well as Figure 19 As shown, the clamping members 150 engage with the sliding grooves 132. The clamping members 150 engage with the sliding grooves 132 from the four corners of the first frame 130 and the second frame 140. Therefore, in this embodiment, the peripheral edges of the first frame 130 and the second frame 140 are clamped by the four clamping members 150.
[0177] like Figure 19 As shown, the clamping member 150 is formed into a U-shape when viewed from the longitudinal direction (Y-axis direction). An engaging claw 151 is formed at the top end of the U-shape of the clamping member 150, which engages with the sliding groove 132. The clamping member 150 engages with the first frame 130 and the second frame 140 by sliding along the sliding groove 132 in the Y-axis direction, thereby clamping the first frame 130 and the second frame 140 in the thickness direction.
[0178] Figure 22 This is a flowchart of a sample setting method in the resin chamber device 101 according to the fifth embodiment of the present invention. Figures 23 to 26 It is along Figure 22 The flowchart shown is an assembly diagram of the resin chamber device 101.
[0179] When the sample is placed in the resin chamber device 101, first, Figure 23 As shown, the first chamber unit 102 is formed (first process). Specifically, the first frame 130 is turned over, and the transparent member 111 and the sealing member 110 are superimposed on the first frame 130 to form the first chamber unit 102 (step S1).
[0180] Then, if Figure 24 As shown, the second chamber unit 103 is formed. Specifically, the DNA array substrate 112 is stacked on the second frame 140 to form the second chamber unit 103 (step S2). It should be noted that a double-sided adhesive tape (not shown) can also be placed in the storage groove 142 of the second frame 140 to fix the DNA array substrate 112.
[0181] Next, the Figure 23A certain amount of sample is placed in the slot forming portion 120 of the first chamber unit 102 shown (step S3). Specifically, a pipette or the like is used to drop the sample into the slot forming portion 120 from the other end side (-Z side) of the opening of the slot forming portion 120 (second step). In this way, since the sample can be dropped from directly above the slot forming portion 120, the operator does not need special skills to operate. In addition, since the annular protrusion 121B is formed on the peripheral edge of the opening of the slot forming portion 120, the possibility of contamination between adjacent slot forming portions 120 is extremely low.
[0182] Then, if Figure 25 As shown, the second chamber unit 103 is turned over and superimposed on the first chamber unit 102 (step S4). Specifically, the positioning pins 133 of the first frame 130 are aligned with the positioning holes 141 of the second frame 140, and the second chamber unit is superimposed on the first chamber unit. At this time, although the second chamber unit 103 is turned over, the DNA array substrate 112 is fixed to the second frame 140, so the DNA array substrate 112 does not fall. In this way, by superimposing the second chamber unit 103 on the first chamber unit 102, the other end of the slot forming portion 120 is sealed by the DNA array substrate 112 (third step).
[0183] In this way, since the DNA array substrate 112 is assembled after the sample is dripped, there is no contact between the DNA array substrate 112 and the pipette, and no damage is caused to the DNA microarray 112a located on the DNA array substrate 112. In addition, during the assembly of the DNA array substrate 112, the positioning pins 133 of the first frame 130 are aligned with the positioning holes 141 of the second frame 140, enabling high-precision assembly.
[0184] Then, if Figure 26 As shown, the peripheral edge of the first frame 130 and the second frame 140 are clamped by the clamping member 150 (the fourth step). Specifically, the clamping member 150 is engaged with the sliding grooves 132 at the four corners of the first frame 130 and the second frame 140 (step S5). As a result, the sealing member 110 is compressed between the first frame 130 and the second frame 140. Figure 21 As shown, the slot forming portion 120 is in a sealed state. If all the above steps are completed, the process proceeds to the next step (step S6).
[0185] After completing the next step, the resin chamber device 101 can be directly discarded (step S7). Since the resin chamber device 101 does not contain any metal materials, it can be discarded without classification. It should be noted that if there is no sample leakage, the components of the resin chamber device 101 can be disassembled and partially reused.
[0186] Figure 27 This is a schematic diagram of a nucleic acid analysis system 600 using a resin chamber device 101 according to a fifth embodiment of the present invention.
[0187] like Figure 27 As shown, the nucleic acid analysis system 600 includes a bacteria recovery system 200 , a nucleic acid extraction system 300 , a hybridization reaction system 400 , and a detection system 500 .
[0188] The bacteria recovery system 200 is a system for recovering bacteria (such as bacteria or fungi) contained in the sample 100. For example, when testing a beverage, the sample 100 may be the manufactured beverage, the water used to make the beverage, or a liquid used in the beverage manufacturing process. Alternatively, to examine the presence and extent of bacterial contamination in the manufacturing environment, the sample 100 may also be a liquid from which bacteria have been recovered, such as from a cotton swab used to wipe the inspection environment.
[0189] Bacteria can be recovered, for example, by pressurizing or depressurizing the recovered liquid and filtering it with a filter. For example, in the case of recovering bacteria or fungi, the pore size of the filter can be 0.22μm to 0.45μm. After the bacteria are recovered with the filter, the filter is placed in a culture container described later and immersed in a culture solution for culturing the bacteria to culture the bacteria. In the culture of bacteria, for example, there are static culture in which the culture container is placed stationary for cultivation and shaking culture in which the culture container is shaken for cultivation. The culture solution in which the bacteria are cultured is transferred to the next process (nucleic acid extraction system 300). It should be noted that the bacteria can be collected by centrifugation and transferred to the next process, or the liquid placed in the filter can be vibrated to transfer the liquid in which the bacteria are suspended to the next process.
[0190] The nucleic acid extraction system 300 is a system that destroys (dissolves) the membrane structure of cells in a liquid and extracts nucleic acids from bacterial cells. It should be noted that a liquid containing other nucleic acids that react with the extracted nucleic acids can also be mixed into the sample 100 from which nucleic acids have been extracted. In addition, in order to detect in the detection process (detection system 500) described later, the other nucleic acids can also be nucleic acids that are given sites that have fluorescence, luminescence, or extinction under specific conditions. These can be mixed into the sample 100 before being processed using the nucleic acid extraction system 300, or mixed into the sample 100 after being processed using the nucleic acid extraction system 300.
[0191] The hybridization reaction system 400 performs a hybridization reaction on the nucleic acids in the sample 100. The aforementioned resin chamber device 101 is used in this process. During the hybridization reaction, the sample 100 is heated to, for example, 60°C and stirred in the well-forming portion 120, thereby performing a hybridization reaction with the aforementioned other nucleic acids. During this reaction, for example, sites on the aforementioned other nucleic acids that exhibit fluorescence, luminescence, or quenching properties under specific conditions react with the nucleic acids in the sample 100, thereby producing fluorescence, luminescence, or quenching properties.
[0192] It should be noted that by designing the structure of the aforementioned other nucleic acid to react with a specific nucleic acid, for example, it is possible to make it react only with nucleic acids contained in specific bacteria in the sample 100. That is, by using other nucleic acids that react with the specific nucleic acid in the process of the hybridization reaction system 400, the fluorescence, luminescence, or quenching effect imparted to the other nucleic acid can be exhibited only when the sample 100 contains the specific bacteria.
[0193] The detection system 500 detects the presence, extent, etc. of fluorescence, luminescence, or quenching effects expressed in the sample 100 processed by the hybridization reaction system 400. For example, the detection system 500 excites fluorescence expressed in nucleic acids in the sample 100 using an excitation laser and detects the excited fluorescence using a highly sensitive camera.
[0194] Alternatively, the detection system 500 uses a highly sensitive camera to detect the luminescence effect manifested in the nucleic acid of the sample 100. Alternatively, the detection system 500 uses a highly sensitive camera to detect the degree of extinction of the fluorescence or luminescence imparted near the site where the extinction effect is imparted. Regarding this detection method, for example, the method described in Japanese Patent Application Laid-Open No. 2020-74726 can also be used.
[0195] The nucleic acid analysis system 600 can analyze whether specific bacteria (such as bacteria or fungi) are contained in the sample 100 or the concentration thereof by using the series of systems described above.
[0196] As described above, the resin chamber device 101 of this embodiment includes: a sealing member 110 having a slot forming portion 120 extending through the sealing member 110 in the thickness direction; a transparent member 111 disposed on the first surface 110A of the sealing member 110, where one end of the slot forming portion 120 is open, to close the one end of the slot forming portion 120; a DNA array substrate 112 disposed on the second surface 110B of the sealing member 110, where the other end of the slot forming portion 120 is open, to close the other end of the slot forming portion 120; a first frame 130 abutting against the transparent member 111; a second frame 140 abutting against the DNA array substrate 112; and a clamping member 150 for clamping the peripheral edges of the first frame 130 and the second frame 140. According to this structure, the sealing property of the slotted hole forming portion 120 can be ensured, and the entire resin chamber device 101 can be used once.
[0197] Furthermore, in the resin chamber apparatus 101 of this embodiment, the first frame 130 and the second frame 140 are rectangular in plan view and have a plurality of sliding grooves 132 extending longitudinally from the four corners and engaging with the clamping member 150. This structure ensures the tightness of the slot-forming portion 120 by clamping the four corners of the first and second frames 130, 140, even without the use of metal. Leakage testing confirmed that the tightness of the slot-forming portion 120 in the resin chamber apparatus 101 is comparable to that of the chamber frame structure using metal materials described in [Overview].
[0198] In the resin chamber device 101 of this embodiment, the surface of the first frame 130 is covered with a black resin coating, and a window 131 is formed to allow viewing of the slotted portion 120 through the transparent member 111. This configuration prevents autofluorescence of the first frame 130 from obstructing fluorescence observation.
[0199] Furthermore, in the resin chamber device 101 of this embodiment, a positioning pin 133 is formed on one side of the first frame 130 and the second frame 140, protruding toward the other side, and a positioning hole 141 is formed on the other side of the first frame 130 and the second frame 140, which engages with the positioning pin 133. This structure allows the first frame 130 and the second frame 140 to be assembled with high precision.
[0200] Furthermore, the hybridization reaction system 400 of this embodiment uses a resin chamber device to perform hybridization reactions. According to this configuration, the entire resin chamber device 101 can be used once, thereby improving the efficiency of hybridization reaction operations.
[0201] Furthermore, the nucleic acid analysis system 600 of this embodiment analyzes nucleic acids extracted using the hybridization reaction system 400. According to this configuration, since the entire resin chamber device 101 can be used once, the efficiency of nucleic acid analysis can be improved.
[0202] The sample setting method of the resin chamber device 101 of the present embodiment includes: a first step in which a sealing member 110 is superimposed on a first frame 130 to form a first chamber unit, wherein the sealing member 110 seals one end of a slot-forming portion 120 extending through the first frame 130 in the thickness direction with a transparent member 111; a second step in which, after the first step, a sample is dropped from the other end of the slot-forming portion 120 into the slot-forming portion 120; a third step in which, after the second step, a second chamber unit formed by superimposing a DNA array substrate 112 on a second frame 140 is superimposed on the first chamber unit, and the other end of the slot-forming portion 120 is sealed with the DNA array substrate 112; and a fourth step in which, after the third step, the peripheral edges of the first frame 130 and the second frame 140 are clamped with a clamping member 150. According to this structure, since the DNA array substrate 112 is assembled after the sample is dropped, there is no contact between the DNA array substrate 112 and the pipette, and no damage is caused to the DNA microarray 112a located on the DNA array substrate 112. In addition, since the sample can be dropped from directly above the groove forming portion 120, the operator does not need special skills to operate.
[0203] [Sixth embodiment]
[0204] Next, a sixth embodiment of the present invention will be described. In the following description, the same or equivalent components as those in the above-described embodiment are denoted by the same reference numerals, and their descriptions will be simplified or omitted.
[0205] Figure 28 It is a side view of a resin chamber device 101 according to a sixth embodiment of the present invention.
[0206] like Figure 28 Specifically, the sliding groove 132 has a first inclined shape 132a whose depth in the thickness direction (Z-axis direction) decreases toward the middle position in the longitudinal direction (Y-axis direction) of the first frame 130 and the second frame 140 .
[0207] The first inclined shape 132a is formed at an inclination of approximately 0.5° relative to the XY plane. That is, when the first frame 130 and the second frame 140 are assembled, the Z-axis entrance dimensions of the upper and lower sliding grooves 132 are small, and the Z-axis dimensions increase as they move toward the inner side. The clamping member 150 includes an engaging claw portion 151 having a second inclined shape 151a corresponding to the first inclined shape 132a. That is, the second inclined shape 151a is also formed at an inclination of approximately 0.5° relative to the XY plane.
[0208] According to this structure, since the sliding groove 132 and the engaging claw portion 151 have the same inclined shape, dimensional variations of the resin material components can be accommodated. Specifically, since the entrance dimension of the sliding groove 132 is small when the first frame 130 and the second frame 140 are combined, the entrance dimension of the clamping member 150 is larger, thereby allowing the clamping member 150 to smoothly engage with the sliding groove 132. Furthermore, when the clamping member 150 is inserted into the inner side of the sliding groove 132, the inclination of the first inclined shape 132a and the second inclined shape 151a ensures close contact between the two. Therefore, even if there are dimensional variations of the resin material components, it is unlikely that a gap will form between the clamping member 150 and the sliding groove 132.
[0209] [Seventh embodiment]
[0210] Next, a seventh embodiment of the present invention will be described. In the following description, the same or equivalent components as those in the above-described embodiment are denoted by the same reference numerals, and their descriptions will be simplified or omitted.
[0211] Figure 29 It is an exploded perspective view of a resin chamber device 101 according to a seventh embodiment of the present invention. Figure 30 It is a cross-sectional view of a resin chamber device 101 according to a seventh embodiment of the present invention.
[0212] As shown in these figures, the resin chamber device 101 of the seventh embodiment includes, in addition to the aforementioned sealing member 110, transparent member 111, DNA array substrate 112, first frame 130, second frame 140, and clamping member 150, a sample receiving member 113 and a gasket 114. It should be noted that the sample receiving member 113 and the gasket 114 are also formed of a resin material.
[0213] like Figure 30As shown, the sample receiving member 113 has a disk-like shape that accommodates the DNA array substrate 112. The entire disk-shaped edge of the sample receiving member 113 is bonded to the outer periphery of the transparent member 111 via adhesive tape or adhesive (not shown). The gasket 114 is formed into a rectangular ring shape and is positioned on the -Z side of the disk-shaped edge of the sample receiving member 113. The gasket 114 is compressed between the first frame 130 and the second frame 140, and its reaction force presses the disk-shaped edge (adhesive portion) of the sample receiving member 113 against the transparent member 111.
[0214] With this structure, when the resin chamber device 101 is disassembled, the sample overflowing from the groove forming portion 120 can be received by the sample receiving member 113. Therefore, the first frame 130, the second frame 140, and the clamping member 150 can be reused without cleaning.
[0215] While preferred embodiments of the present invention have been described above with reference to the accompanying drawings, the present invention is not limited to the aforementioned embodiments. The various shapes and combinations of the components shown in the aforementioned embodiments are merely examples, and various modifications may be made based on design requirements, etc., without departing from the spirit of the present invention.
Claims
1. A resin chamber device, wherein: The resin chamber device comprises: a sealing member having a slot-forming portion extending therethrough in a thickness direction; a transparent member disposed on the first surface side of the sealing member where one end of the slot forming portion is open, and blocking the one end of the slot forming portion; a substrate, the substrate being arranged on the second surface side of the sealing member where the other end of the slot forming portion is open, and blocking the other end of the slot forming portion; a first frame, the first frame abutting against the transparent component; a second frame, the second frame abutting against the substrate; A clamping member clamps the peripheral edges of the first frame and the second frame.
2. The resin chamber device according to claim 1, wherein The first frame and the second frame are formed in a rectangular shape in a plan view and are formed with a plurality of sliding grooves extending from four corners along the longitudinal direction and engaging with the clamping member.
3. The resin chamber device according to claim 2, wherein: The sliding groove has a first inclined shape that becomes shallower toward a middle position in the longitudinal direction of the first frame and the second frame. The clamping member includes an engaging claw portion that engages with the slide groove and has a second inclined shape corresponding to the first inclined shape.
4. The resin chamber device according to any one of claims 1 to 3, wherein The surface of the first frame is covered with a black resin plating layer, and a window portion is formed thereon for observing the slot forming portion through the transparent member.
5. The resin chamber device according to any one of claims 1 to 3, wherein A positioning pin protruding toward the other is formed on one of the first frame and the second frame. A positioning hole that engages with the positioning pin is formed in the other of the first frame and the second frame.
6. A hybridization reaction system, wherein: The hybridization reaction system uses the resin chamber device according to any one of claims 1 to 3 to perform a hybridization reaction.
7. A nucleic acid analysis system, wherein: The nucleic acid analysis system analyzes nucleic acids extracted using the hybridization reaction system according to claim 6.
8. A method for setting a sample in a resin chamber device, wherein: A first step, in which a sealing member is superimposed on a first frame to form a first chamber unit, wherein the sealing member uses a transparent member to seal one end of a slot-forming portion penetrating in a thickness direction; a second step, after the first step, in which a sample is dripped from the other end of the slot forming portion into the slot forming portion; a third step, after the second step, in which a second chamber unit formed by stacking a substrate on a second frame is stacked on the first chamber unit, and the other end of the slot forming portion is sealed with the substrate; A fourth step is performed after the third step, in which peripheral edges of the first frame and the second frame are clamped by a clamping member.
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