CN113174307B - Upper cover based on nucleic acid detection chip installation bin - Google Patents

Upper cover based on nucleic acid detection chip installation bin Download PDF

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Publication number
CN113174307B
CN113174307B CN202110055530.6A CN202110055530A CN113174307B CN 113174307 B CN113174307 B CN 113174307B CN 202110055530 A CN202110055530 A CN 202110055530A CN 113174307 B CN113174307 B CN 113174307B
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China
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layer
boss
straight arm
sample adding
sample
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CN113174307A (en
Inventor
范东雨
王宏伟
任玮鹏
吴世超
蔡亦梅
高静
任鲁风
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Beijing Integrated Biosystems Co ltd
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Beijing Integrated Biosystems Co ltd
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Publication of CN113174307A publication Critical patent/CN113174307A/en
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813—Hybridisation assays
    • C12Q1/6834—Enzymatic or biochemical coupling of nucleic acids to a solid phase
    • C12Q1/6837—Enzymatic or biochemical coupling of nucleic acids to a solid phase using probe arrays or probe chips

Abstract

The invention relates to an upper cover based on a nucleic acid detection chip mounting bin, which comprises a top cover and side plates, wherein the top cover is in a long-strip plate shape, and the side plates are arranged on the long side of the top cover and are fixedly connected with the top cover to be integrally formed; one end of the side plate is provided with a connecting hole which is used for being detachably connected with the connecting lug of the upper shell, and one end of the top cover, which is far away from the connecting hole, is provided with a first bulge which is used for being clamped with the connecting groove of the upper shell; the inner side of the top cover comprises a first boss, a second boss and a third boss, the second boss is arranged between the first boss and the third boss, and the number of the second bosses is two, and the second bosses are symmetrically arranged along the center line of the top cover; the inner side of the second boss is provided with a positioning column which is used for matching with a positioning hole on the chip. The positioning column is arranged on the inner side of the top cover, and the positioning column is matched with the positioning hole formed in the chip, so that the relative position of the upper cover and the chip is fixed, and the device is convenient and simple, easy to realize and simple in structure.

Description

Upper cover based on nucleic acid detection chip installation bin
Technical Field
The invention relates to the field of nucleic acid detection, in particular to an upper cover based on a nucleic acid detection chip mounting bin.
Background
In the process of nucleic acid detection, a sample needs to be extracted, purified and amplified, so as to obtain the specificity of nucleic acid substances in the sample. Generally, the extraction process of nucleic acid is to mix a sample and a lysis solution to separate nucleic acid substances and impurities such as protein in the sample to obtain a mixture of the nucleic acid substances and the protein, then wash the mixture, adsorb the nucleic acid substances on the surface of magnetic beads by utilizing the molecular bond effect between the magnetic beads and the nucleic acid substances, wash after adsorption, wash and flush the impurities such as the protein, and only retain the nucleic acid substances. And finally, separating the nucleic acid substances from the magnetic beads by using the eluent, and allowing the nucleic acid substances to enter an amplification bin so as to perform amplification reaction.
The chip locking device provided by the embodiment of the invention can further comprise a chip positioning sheet, the chip positioning sheet is in a polygon shape with multiple symmetry, the side surface of the chip positioning sheet is provided with a lug, the chip to be detected is arranged on the chip positioning sheet, and the chip positioning sheet can fix the position of the chip to be detected and prevent the chip to be detected from moving in the through hole.
However, with the increase of the service time, the number of structural members in the structure is large, and the temperature control adapter plate, the chip positioning plate and the like are easy to be lost, so that the structural members need to be replaced, which is time-consuming and tedious.
Disclosure of Invention
Therefore, the invention provides the upper cover based on the nucleic acid detection chip mounting bin, which can improve the replacement efficiency of the detection chip.
In order to achieve the above object, the present invention provides an upper cover of a nucleic acid detecting chip-mounting chamber, comprising:
the top cover is in a long-strip plate shape, and the side plate is arranged on the long side of the top cover and is fixedly connected with the top cover to be integrally formed;
one end of the side plate is provided with a connecting hole which is used for being detachably connected with a connecting lug of the upper shell, one end of the top cover, which is far away from the connecting hole, is provided with a first bulge, and the first bulge is used for being clamped with a connecting groove of the upper shell;
the inner side of the top cover comprises a first boss, a second boss and a third boss, the second boss is arranged between the first boss and the third boss, the height of the second boss is higher than that of the third boss, the height of the third boss is higher than that of the first boss, the first boss is close to the boss, and the second boss is adjacent to the third boss; the number of the second bosses is two, and the second bosses are symmetrically arranged along the central line of the top cover; the third boss is far away from the bulge, and the third boss is positioned between the two second bosses;
a positioning column is arranged on the inner side of the second boss and is used for matching with a positioning hole in the chip to be detected;
the chip to be detected comprises a sample adding layer arranged at the uppermost end, a gasket arranged on the lower side of the sample adding layer and a pipeline layer arranged on the lower side of the gasket;
wherein the content of the first and second substances,
the upper side of the sample adding layer is provided with a sample adding hole for adding a sample into the chip, and the sample injected into the chip is subjected to nucleic acid extraction, purification and amplification reaction in sequence;
the sample adding layer and the pipeline layer are movably connected with a limiting frame arranged on the side part of the pipeline layer through clamping strips, correspondingly, a first clamping groove is arranged on the inner side of the limiting frame and is mutually matched and connected through the clamping strips, so that the relative position switching and fixing of the sample adding layer and the pipeline layer are realized;
the second clamping groove is arranged on the inner side of the limiting frame and is positioned below the first clamping groove;
when in transportation or storage, the sample adding layer is connected with the first clamping groove;
when the sample injection device is used, the gasket is pulled out, the sample injection layer is pressed downwards to be connected with the second clamping groove, and meanwhile, the puncture needle is arranged on the upright column on the pipeline layer and is used for puncturing the reagent arranged in the sample injection layer so as to enable the reagent and the sample to be mixed and reacted;
after the sample adding layer and the pipeline layer are pressed, a first strain gauge arranged at the bottom of the sample adding layer detects the extrusion force between the sample adding layer and the pipeline layer so as to determine the stress uniformity of the sample adding layer and the pipeline layer in the pressing process;
the positioning device is characterized by further comprising a control unit, wherein the control unit determines the depth of the positioning column inserted into the positioning hole according to the stress of the first strain gauge, so that the thickness of the chip to be detected and the upper cover after installation is within a preset range.
Furthermore, a second boss is arranged on the third boss, a through hole is arranged on the second boss, the through hole is a circular through hole, and the second boss is a cube;
the second boss comprises a first reinforcing rib and a second reinforcing rib, the first reinforcing rib and the second reinforcing rib are symmetrically arranged, the first reinforcing rib and the second reinforcing rib are symmetrical in structure, and the first reinforcing rib comprises a first straight arm, a second straight arm and a third straight arm; the second reinforcing rib comprises a fourth straight arm, a fifth straight arm and a sixth straight arm, the second straight arm is arranged between the first straight arm and the second straight arm, the first straight arm is vertical to the second straight arm, the second straight arm is vertical to the third straight arm, and the second straight arm is in smooth transition connection with the third straight arm; the fifth straight arm is arranged between the fourth straight arm and the sixth straight arm, the fourth straight arm is perpendicular to the fifth straight arm, the fifth straight arm is perpendicular to the sixth straight arm, the positioning column comprises a first positioning column and a second positioning column, the first positioning column is arranged on the side face of the third straight arm, and the second positioning column is arranged on the side face of the sixth straight arm.
Furthermore, the chip to be detected further comprises a sealing film and a second strain gauge, the sealing film is arranged on the lower side of the pipeline layer and used for realizing sealing, and the second strain gauge is respectively arranged in the first clamping groove and the second clamping groove; taking M positions in the first card slot transversely, detecting the stress at the M positions by the second strain gauge, marking as a first stress function F (F1, F2 … … fm), wherein the selected positions in the second card slot correspond to the positions in the first card slot one by one, and the second stress function of the second card slot is F '(F1', F2 ', … … fm'), and judging the position of the sample adding layer according to the first stress function and the second stress function.
Further, when the sample adding layer is connected with the first card slot, firstly, f1 and fm are compared to obtain a first positive difference value, and if the first positive difference value is higher than a first preset difference value f0, the sample adding layer is readjusted; if the first positive difference is lower than a first preset difference f0, performing subsequent operation;
when the sample adding layer is connected with the second clamping groove, f1 ' and fm ' are compared to obtain a second positive difference value, and if the second positive difference value is higher than a second preset difference value f0 ', the sample adding layer is readjusted; if the second positive difference is lower than a second predetermined difference f 0', the subsequent operation is performed.
Furthermore, the first positioning column and the second positioning column are arranged in a staggered mode, the distance between the first positioning column and the second boss is smaller than the distance between the second positioning column and the second boss, the first boss is provided with a square notch, a notch is formed in the notch, and the top cover is trapezoidal.
Furthermore, the lower side of the gasket is also provided with a slide rail, correspondingly, the upper side surface of the pipeline layer is provided with a slide groove, and the slide rail is connected with the slide groove in a matching way so as to realize the sliding connection between the gasket and the pipeline layer;
the sliding groove is arranged on the inner side of the limiting frame on the pipeline layer;
the end part of the gasket is provided with a plurality of notches and bulges which are arranged at intervals, wherein the slide rail is arranged on the bottom surface of the bulge at the outermost side.
Further, the application of sample layer with the pipeline layer still sets up buckle structure, is provided with first buckle in one side of application of sample layer, and the downside of first buckle stretches out the end and stretches out the bottom of application of sample layer after installing application of sample layer and pipeline layer cooperation together, through first buckle joint on the side of pipeline layer to prevent application of sample layer and pipeline layer separation.
Furthermore, a plurality of ribs arranged at intervals are arranged on the outer side wall of the reinforcing rib, three first ribs are arranged on the outer side of the first straight arm, two second ribs are arranged on the outer side of the second straight arm, and two third ribs are arranged on the outer side of the third straight arm; three fourth convex edges are arranged on the outer side of the fourth straight arm; two fifth convex edges are arranged on the outer side of the fifth straight arm; and two sixth convex ridges are arranged on the outer side of the sixth straight arm.
Further, arc-shaped transition pieces are arranged on the inner sides of the first straight arm and the fourth straight arm and used for enabling the upper cover to be in smooth contact with the chip in the clamping process;
the first protrusion comprises a clamping portion and a connecting portion, the connecting portion is fixedly connected with the clamping portion, the connecting portion is fixedly connected with the upper cover, the clamping portion is used for extending into the connecting groove of the upper shell, and the clamping portion is an irregular prism with opposite sides.
Furthermore, a plurality of sample adding bins are arranged at intervals below the sample adding hole, a reagent outlet is arranged at the end part of each sample adding bin, and a sealing structure is arranged between each reagent outlet and each sample adding bin and used for sealing;
a pressurizing structure is arranged on one side of the sample adding bin and comprises a tube wall, a piston is arranged in the tube wall, and the piston moves back and forth along the tube wall to push the reagent in the piston to flow out or be drawn back to a reagent outlet; a sealing ring is arranged at the end part of a piston rod of the piston and used for sealing;
when the sample adding layer is connected with the second card slot, comparing absolute values of stress difference values at positions corresponding to one another in a first stress function F (F1, F2 … … fm) and a second stress function F '(F1', F2 ', … … fm'), wherein the first stress function F (F1, F2 … … fm) is a function generated when the sample adding layer is connected with the first card slot, judging whether the absolute value of each stress difference value is smaller than a preset standard error F0, if so, continuing to operate, and if not, determining the corresponding position of the absolute value of a certain group of corresponding stress difference values so as to determine the damage of the sample adding layer or the pipeline layer;
the piston rod is also provided with a nut which is in threaded connection with the nut, a guide sleeve is sleeved outside the nut, a corresponding shaft shoulder is arranged inside the pipe wall and used for positioning and fixing the guide sleeve, and clamping rings are arranged outside two ends of the guide sleeve and used for clamping the corresponding guide sleeve; and a sheath is arranged on the outer side of the guide sleeve and used for protecting the piston rod, the screw cap and the guide sleeve.
Compared with the prior art, the invention has the beneficial effects that the two side plates are arranged on the long side edge of the top cover, the side plates and the top cover are integrally formed, and the upper cover needs to cover a chip placed in the chip bin in practical application.
Particularly, in the upper cover based on the nucleic acid detecting chip mounting bin, the control unit is arranged, and the depth of the positioning column inserted into the positioning hole is determined according to the stress of the first strain gauge in the chip to be detected, so that the thickness of the upper cover and the chip to be detected after mounting is within a preset range, and the upper cover and the chip to be detected are accurately matched.
Furthermore, the upper cover based on the nucleic acid detecting chip mounting bin provided by the embodiment of the invention realizes the relative fixation of the upper cover and the chip in the vertical direction through the arrangement of the first boss, the second boss and the third boss which are staggered, and the relative fixation of the upper cover and the chip in the horizontal direction is realized through the positioning column arranged on the upper cover.
Furthermore, corresponding bulges are arranged on the corresponding chips, the fixing is realized again through the matching of the through holes and the bulges, and the circular through holes are adopted, so that the structure is simple and convenient to process.
Further, through setting up first strengthening rib and second strengthening rib for the application of sample layer butt on first upper cover and the chip is more firm, and first strengthening rib and second strengthening rib have constituted the space of placing the chip, make the overall structure of chip and upper cover more compact, practice thrift the space, increase the utilization ratio to the space.
Drawings
FIG. 1 is a schematic structural diagram of an upper cover of a nucleic acid detecting chip-based mounting chamber according to an embodiment of the present invention;
FIG. 2 is a schematic side view of an upper cover of a nucleic acid detecting chip-based mounting chamber according to an embodiment of the present invention;
FIG. 3 is a schematic perspective view of an upper cover of a nucleic acid detecting chip-mounting chamber according to an embodiment of the present invention;
FIG. 4 is a schematic diagram of an inner side structure of an upper cover of a nucleic acid detecting chip-based mounting chamber according to an embodiment of the present invention;
FIG. 5 is a top view of a chip structure mated with an upper cover of a nucleic acid detecting chip-based mounting chamber provided in an embodiment of the present invention;
FIG. 6 is an exploded view of a detection chip according to an embodiment of the present invention;
FIG. 7 is a schematic structural diagram of a sample addition layer in an embodiment of the present invention.
Detailed Description
In order that the objects and advantages of the invention will be more clearly understood, the invention is further described below with reference to examples; it should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Preferred embodiments of the present invention are described below with reference to the accompanying drawings. It should be understood by those skilled in the art that these embodiments are only for explaining the technical principle of the present invention, and do not limit the scope of the present invention.
It should be noted that in the description of the present invention, the terms of direction or positional relationship indicated by the terms "upper", "lower", "left", "right", "inner", "outer", etc. are based on the directions or positional relationships shown in the drawings, which are only for convenience of description, and do not indicate or imply that the device or element must have a specific orientation, be constructed in a specific orientation, and be operated, and thus, should not be construed as limiting the present invention.
Furthermore, it should be noted that, in the description of the present invention, unless otherwise explicitly specified or limited, the terms "mounted," "connected," and "connected" are to be construed broadly, and may be, for example, fixedly connected, detachably connected, or integrally connected; can be mechanically or electrically connected; they may be connected directly or indirectly through intervening media, or they may be interconnected between two elements. The specific meanings of the above terms in the present invention can be understood by those skilled in the art according to specific situations.
Referring to fig. 1 to 4, an upper cover of a nucleic acid detecting chip mounting chamber according to an embodiment of the present invention includes: the top cover 10 is in a long plate shape, and the side plate 20 is arranged on the long side of the top cover 10 and is fixedly connected with the top cover 10 to be integrally formed; one end of the side plate 20 is provided with a connecting hole 30, the connecting hole 30 is used for being detachably connected with a connecting lug of an upper shell, one end of the top cover 10, which is far away from the connecting hole 30, is provided with a first bulge 40, and the first bulge 40 is used for being clamped with a connecting groove of the upper shell; the inner side of the top cover 10 comprises a first boss 11, a second boss 12 and a third boss 13, the second boss 12 is arranged between the first boss 11 and the third boss 13, the height of the second boss 12 is higher than that of the third boss 13, the height of the third boss 13 is higher than that of the first boss 11, the first boss 11 is close to the boss, and the second boss 12 is adjacent to the third boss 13; two second bosses 12 are arranged and symmetrically arranged along the central line of the top cover 10; the third boss 13 is far away from the protrusion, and the third boss 13 is located between the two second bosses 12; the inner side of the second boss 12 is provided with a positioning column, and the positioning column is used for matching with a positioning hole on a chip to be detected.
Specifically, according to the upper cover of the nucleic acid detecting chip mounting bin provided by the embodiment of the invention, the two side plates 20 are arranged on the long side edge of the top cover 10, the side plates 20 and the top cover 10 are integrally formed, and in practical application, the upper cover needs to cover a chip to be detected placed in the chip bin.
In order to further fix the chip to be detected and the upper cover as a whole, a connecting hole 30 is formed in one end of the side plate 20, the connecting hole 30 is used for being detachably connected with a connecting lug of the upper shell, a first protrusion 40 is arranged at one end, away from the connecting hole 30, of the top cover 10, the first protrusion 40 is used for being clamped with a connecting groove of the upper shell, the upper cover and the upper shell are completely fixed through clamping, the chip to be detected arranged inside the chip to be detected is fixed again, and the chip to be detected is prevented from being subjected to position deviation to influence the experiment progress.
Specifically, the inner side of the top cover 10 includes a first boss 11, a second boss 12 and a third boss 13, the second boss 12 is disposed between the first boss 11 and the third boss 13, the height of the second boss 12 is higher than the height of the third boss 13, the height of the third boss 13 is higher than the first boss 11, the first boss 11 is close to the boss, and the second boss 12 is adjacent to the third boss 13; two second bosses 12 are arranged and symmetrically arranged along the central line of the top cover 10; the third boss 13 is far away from the protrusion, the third boss 13 is located between the two second bosses 12, the first bosses 11, the second bosses 12 and the third bosses 13 with different heights are arranged to be matched with the sizes of all structures on the chip to be detected, so that the upper cover and the chip to be detected are more compact in matching, the chip to be detected is prevented from moving in the vertical direction, and the chip to be detected and the upper cover are relatively fixed in the horizontal position through the matching of the positioning columns and the positioning holes.
Therefore, the upper cover based on the nucleic acid detecting chip mounting bin provided by the embodiment of the invention realizes the relative fixation of the upper cover and the chip to be detected in the vertical direction through the arrangement of the first boss 11, the second boss 12 and the third boss 13 which are staggered, and the relative fixation of the upper cover and the chip to be detected in the horizontal direction is realized through the positioning column arranged on the upper cover.
Specifically, in order to further realize the fixation of the upper cover, a second protrusion 130 is disposed on the third boss 13, and a through hole is disposed on the second protrusion 130, and the through hole is a circular through hole. The corresponding protrusion is arranged on the corresponding chip to be detected, the fixing is realized again through the matching of the through hole and the protrusion, and the circular through hole is adopted, so that the structure is simple and convenient to process.
Specifically, the second boss 12 includes a first reinforcing rib and a second reinforcing rib, the first reinforcing rib and the second reinforcing rib are symmetrically arranged, the first reinforcing rib and the second reinforcing rib are symmetrical in structure, and the first reinforcing rib includes a first straight arm 121, a second straight arm 122 and a third straight arm 123; the second reinforcing rib comprises a fourth straight arm 124, a fifth straight arm 125 and a sixth straight arm 126, the second straight arm 122 is arranged between the first straight arm 121 and the second straight arm 122, the first straight arm 121 is vertical to the second straight arm 122, the second straight arm 122 is vertical to the third straight arm 123, and the second straight arm 122 and the third straight arm 123 are in smooth transition connection; the fifth straight arm 125 is disposed between the fourth straight arm 124 and the sixth straight arm 126, the fourth straight arm 124 is perpendicular to the fifth straight arm 125, the fifth straight arm 125 is perpendicular to the sixth straight arm 126, the positioning column includes a first positioning column 14 and a second positioning column 15, the first positioning column 14 is disposed on the side of the third straight arm 123, and the second positioning column 15 is disposed on the side of the sixth straight arm 126. The inner side wall of the third straight arm 123 is provided with a notch, the first positioning column 14 is arranged at the notch, the inner side wall of the sixth straight arm 126 is also provided with a notch, and the second positioning column 15 is arranged at the notch.
In practical application, first strengthening rib is by first straight arm 121, the straight arm of second 122 and the straight arm of third 123 are connected in order and are constituteed, first strengthening rib is integrated into one piece, the second strengthening rib is integrated into one piece also, first strengthening rib and second strengthening rib are used for with wait to detect the upside butt of chip, through the perpendicular first straight arm 121 of connecting in order, the straight arm of second 122 and the straight arm of three and the perpendicular fourth straight arm 124 of connecting in order, the straight arm of fifth 125 and the straight arm of sixth 126 constitute first strengthening rib and second strengthening rib, the space that first strengthening rib and second strengthening rib are constituteed is used for the holding to wait to detect the application of sample layer structure that sets up on the chip pipeline layer. Through setting up first strengthening rib and second strengthening rib for first upper cover and wait to detect the more firm of application of sample layer butt on the chip, and first strengthening rib and second strengthening rib have constituted and have placed the space of waiting to detect the chip, make the overall structure who waits to detect chip and upper cover more compact, practice thrift the space, increase the utilization ratio to the space.
Particularly, the injection molding processing is convenient, and the second boss 12 is a cube. It can be understood by those skilled in the art that the second boss 12 may be a rectangular parallelepiped or other polygonal cylinder as long as the second boss 12 can abut against the corresponding structure on the chip to be detected.
Specifically, in the actual use process, the first positioning column 14 is disposed at the notch of the third straight arm 123, the second positioning column 15 is disposed at the notch of the sixth straight arm 126, the positions of the third straight arm 123 and the sixth straight arm 126 are opposite, and the lengths are the same, but the positions of the notches of the third straight arm 123 and the sixth straight arm 126 are not opposite, so that the advantage of this arrangement is that the relative position of the chip to be detected is fixed through two positions, so that the first positioning column 14 and the second positioning column 15 can correct the positions with each other, the positioning effect is better, the positioning accuracy is higher, the first positioning column 14 and the second positioning column 15 are arranged in a staggered manner, and the distance from the first positioning column 14 to the second boss 12 is smaller than the distance from the second positioning column 15 to the second boss 12. Those skilled in the art can understand that the arrangement positions of the first positioning column 14 and the second positioning column 15 may be arranged oppositely or in a staggered manner, the distance between the first positioning column 14 and the second boss 12 and the distance between the second positioning column 15 and the second boss 12 may be the same or different, and the arrangement of the first positioning column 14 and the second positioning column 15 is performed in a manner that the distances are different, so that the position positioning is more accurate, convenient and fast.
Specifically, the first boss 11 is provided with a square notch at which a notch 110 is provided. First boss 11 is irregular square, is provided with a square breach, first boss 11 with wait to detect the chip butt for the upper cover with wait to detect more fastening of chip joint, in order to strengthen the fastness, be provided with notch 110 in its breach department, the corresponding arch that is provided with the correspondence on waiting to detect the chip, arch and notch 110 cooperation realize the further fixed of upper cover, simple structure easily realizes.
Particularly, the structure on pipeline layer is that one end is provided with a plurality of pipelines and purification storehouse etc. in practical application, needs more space, and the other end is provided with the amplification storehouse, and it is complicated to belong to one end structure, one end simple structure's structure for the chip storehouse also belongs to one section broad, the narrower structure of one end, thereby in order to cooperate the actual size in chip storehouse, will top cap 10 sets up to trapezoidal, not only can satisfy the fixing of waiting to detect the chip in the chip storehouse, can effectively protect the various structures of waiting to detect in the chip storehouse in addition, prevent to damage.
Specifically, a plurality of ribs are arranged at intervals on the outer side wall of the reinforcing rib, three first ribs 1210 are arranged on the outer side of the first straight arm 121, two second ribs 1220 are arranged on the outer side of the second straight arm 122, and two third ribs 1230 are arranged on the outer side of the third straight arm 123; three fourth ribs 1240 are arranged on the outer side of the fourth straight arm 124; two fifth protruding ribs 1250 are arranged on the outer side of the fifth straight arm 125; two sixth protruding ribs 1260 are arranged on the outer side of the sixth straight arm 126. The intensity of first strengthening rib and second strengthening rib is because the block is too firm in actual quoting, easily damage, in order to prevent the damage of first strengthening rib and second strengthening rib, still be provided with first bead 1210 in the outside of first straight arm 121, all be provided with corresponding bead on each straight arm that corresponds, increase the intensity of first strengthening rib and second strengthening rib, prevent that it from producing crackle or breach after bearing great effort, the influence waits to detect the integrality of the overall structure and the upper cover of chip.
Specifically, an arc-shaped transition piece 127 is further disposed on the second boss 12, an arc-shaped transition piece 127 is disposed on the inner sides of the first straight arm 121 and the fourth straight arm 124, and the arc-shaped transition piece 127 is used for enabling the upper cover to be in smooth contact with the chip to be detected in the clamping process. Adopt arc transition 127, make the upper cover more gentle with the block of waiting to detect the chip, prevent to produce hard damage at the block in-process, in practical application, need open the upper cover many times and wait to detect the change of chip etc, need open the upper cover many times, it waits to detect the chip structure to change many times, consequently, in order to make the upper cover with wait to detect the chip and produce too big impact force at the block in-process and cause the damage to the upper cover or wait to detect the chip, consequently, arc transition has been set up on the second boss 12 of upper cover, make at the block in-process, realize soft contact, prevent to damage the upper cover or wait to detect the structure of chip.
Specifically, the first protrusion 40 includes a fastening portion and a connecting portion, the connecting portion is fixedly connected with the fastening portion, the connecting portion is fixedly connected with the upper cover, the fastening portion is used for extending into a connecting groove of the upper housing, and the fastening portion is an irregular polygonal prism. First arch 40's effect carries out the block with upper cover and epitheca, and it is convenient when the mode that adopts the block is opened in practical application, is convenient for change and waits to detect the chip, and first arch 40 includes block portion and connecting portion, and block portion is irregular polygon prism, adopts irregular polygon prism card on the epitheca, and its and epitheca contact's point is more, and the block is more firm, the chucking of being convenient for, difficult pine takes off.
Referring to fig. 5, fig. 5 shows an upper structure of a chip to be detected, which is matched with the upper cover, where a positioning hole is formed in the chip to be detected, and the positioning hole is matched with a positioning column of the upper cover to position the chip to be detected, so as to clamp the chip to be detected at a correct position of the upper cover.
Referring to fig. 6, which is a schematic diagram illustrating an explosion structure of a chip device for nucleic acid detection according to an embodiment of the present invention, the chip device for nucleic acid detection according to the embodiment of the present invention includes a sample addition layer 3 disposed at the uppermost end, a gasket 2 disposed at the lower side of the sample addition layer 3, a pipeline layer 101 disposed at the lower side of the gasket 2, and a sealing film 104 disposed at the lowermost side, wherein a sample addition hole 302 is disposed at the upper side of the sample addition layer 3 for adding a sample into a chip, and the sample injected into the chip undergoes a reaction of nucleic acid extraction, purification, and amplification. The sample adding layer 3 and the pipeline layer 101 of the present embodiment are movably connected to the limiting frame 106 disposed at the side of the pipeline layer 101 through the clamping strip 304, correspondingly, the inner side of the limiting frame 106 is provided with the first clamping groove 107, and the first clamping groove 107 is connected to each other through the clamping strip 304 in a matching manner, so as to realize the switching and fixing of the relative positions of the sample adding layer 3 and the pipeline layer 101. The switching of relative position indicates the change of the relative distance of application of sample layer 3 and pipeline layer 101 exactly, application of sample layer 3 is by the process of first draw-in groove 107 switching second draw-in groove for the distance between application of sample layer 3 and pipeline layer 101 has become nearly, take out gasket 2 after, application of sample layer 3 and pipeline layer 101 communicate, specifically speaking, gasket 2's primary function is protection application of sample layer 3 and pipeline layer 101 do not communicate, take out the gasket during the use again, wherein, seal membrane 104 is pasted in the downside of pipeline layer 101, in order to realize sealed. The assembled sample adding layer 3, the gasket 2, the pipeline layer 101 and the sealing film 104 form a completely closed whole, and viruses in the sample cannot leak. As shown in fig. 6, in the embodiment, a second engaging groove is further disposed on a side surface of the limiting frame 106 at the lower side of the first engaging groove 107, the second engaging groove is located at the lower side of the first engaging groove 107, when the sample adding layer 3 is transported or stored, the first card slot 107 is connected with the sample adding layer 3, when the reagent reaction is carried out, the gasket 3 is drawn out, the sample adding layer 3 is pressed downwards, so that the sample adding layer 3 is connected with the second card slot, at the same time, the pricking pin disposed on the pipeline layer 101 punctures the reagent disposed in the sample addition layer 3, so that the reagent and the sample can be mixed and reacted, and the puncture needle is arranged on the pipeline layer 101, and in the practical application process, the pipeline layer 101 is provided with an upright post, the puncture needle is arranged at the circle center of the upright post, the upper end surface of the upright post is oval, and the end surface of the upright post is inclined, so that the puncture needle on the upright post can be conveniently matched with the tail end of the reagent tube, the reagent tube can be smoothly punctured, and the reagent can be filled. According to the chip device for nucleic acid detection provided by the embodiment of the invention, the first clamping groove 107 and the second clamping groove are arranged, so that the sample adding layer 3 and the pipeline layer 101 can be pressed to generate relative position change after the gasket 2 is extracted, and meanwhile, the pricker punctures the reagent in the sample adding layer 3 to realize sample adding, so that a sample and the reagent perform a series of reactions.
In order to monitor the real-time state of the sample adding layer 3, a second strain gauge (not shown in the figure) is arranged in the first card slot 107 and the second card slot, and the second strain gauge is used for testing the stress change of each part when the first card slot 107 or the second card slot is connected with the sample adding layer 3. In the practical application process, M points are transversely taken from the first card slot 107, wherein the M points are arranged at intervals, the state of the sample adding layer 3 is judged by detecting the stress change of the M points, when the sample adding layer 3 is stored or transported, the sample adding layer 3 is connected with the first card slot 107, the first stress function in the first card slot 107 is F (F1, F2 … … fm), wherein F1 and F2 … … fm represent the stress condition of each point, and the stress conditions of all the points are approximately the same because the sample adding layer 3 is uniformly stressed; at this time, stress detection is also performed at a corresponding position in the second card slot, and since the second card slot is not connected with the sample adding layer 3, a second stress function in the second card slot is F ' (F1 ', F2 ', … … fm '), wherein F1 ', F2 ', … … fm ' are all 0; when the sample adding layer 3 is connected with the second card slot, both F1 and F2 … … fm of the first stress function F (F1 and F2 … … fm) in the first card slot are 0, so that the current position of the sample adding layer 3 can be judged according to the first stress function and the second stress function, the problem that the experimenters leave midway and cannot continue to complete subsequent experiments is solved, and other experimenters can continue to complete subsequent experiments according to the experiment progress of the previous experimenters.
Furthermore, when the stress values at the positions in the second stress function are all 0, that is, the sample-adding layer 3 is connected to the first card slot 107, a first stress function F (F1, F2 … … fm) is obtained, the stress value F1 at the first position in the first stress function is compared with the stress value fm at the mth position in the first stress function, a first positive difference value is obtained, if the first positive difference value is lower than a first preset difference value, it indicates that the sample-adding layer 3 is uniformly stressed in the first card slot 107, and then the subsequent operations of pulling out the gasket 2 to press and the like can be performed; if the first positive difference is higher than the first predetermined difference, the difference between the stress value at the first position and the stress value at the mth position is larger, and it may be that the clip strip 304 of the sample-adding layer 3 or the first clip groove 107 on the limiting frame 106 has a defect or has impurities, etc., and the sample-adding layer 3 needs to be checked and adjusted, so that the first positive difference is lower than the first predetermined difference. And when the first positive difference value is lower than the first preset difference value, the back gasket 2 is output, the sample adding layer 3 is pressed, so that the sample adding layer 3 enters the second card slot under the action of external force, when the sample adding layer 3 is connected with the second card slot, a second stress function F ' (F1 ', F2 ', … … fm ') is obtained, the stress value F1 ' of the first position in the second card slot and the stress value fm ' of the M position are compared, a second positive difference value is obtained, and if the second positive difference value is lower than the second preset difference value F0 ', the situation that the sample adding layer 3 is pressed to the second card slot is shown, the stress is uniform, and no matter whether the card strip 304 or the second card slot has no obvious abnormality. If the second positive difference is higher than the second preset difference f 0', the sample addition layer 3 needs to be adjusted, which specifically refers to the adjustment when the stress value in the first slot 107 is abnormal, and is not described again.
In the practical application process, the stress response difference value between the first position and the mth position can be selected, and the positive difference value comparison can be performed on the positions of any two other points, so that the positions of all points in the first clamping groove 101 and the second clamping groove can be analyzed and checked, and the accuracy of the detection result can be further ensured.
When the sample adding layer 3 is connected with the first card slot 107, the stress difference value of the first position and the Mth position in the first stress function is detected, so that the state of the sample adding layer 3 in the first card slot 107 is checked and judged, the uniform stress of the sample adding layer in the first card slot 107 is ensured, and the states of all parts of the chip device are in normal states; correspondingly, when the sample adding layer 3 is connected with the second clamping groove, the stress difference value of the first position and the Mth position in the second stress function is detected, so that the state of the sample adding layer 3 in the second clamping groove is checked and judged, the uniform stress of the sample adding layer in the second clamping groove is ensured, and the states of all parts of the chip device are in normal states. In the practical application process, the sample adding layer 3 is physically pressed in the process of being pressed from the first card slot 107 to the second card slot, and abrasion to each structural component of the chip device easily occurs in the process, so that the first card slot 107, the second card slot, the card strip 304 and other related components need to be checked to ensure the accuracy of the mixed reaction result of the sample and the reagent.
Further, when the sample adding layer 3 is connected to the second card slot, a second stress function F '(F1', F2 ', … … fm') is obtained, and then absolute values of stress difference values at positions corresponding to one another in the first stress function F (F1, F2 … … fm) and the second stress function F '(F1', F2 ', … … fm') are compared, where the first stress function F (F1, F2 … … fm) is a first stress function generated when the sample adding layer 3 and the first card slot 107 are connected, and whether the absolute value of each stress difference value is smaller than a preset standard error F0 is determined, that is, the absolute values of standard errors of | 1 '-F1 |, | F2' -F2|, | F3 '-F9 |, | F4' -F4|, … … and | fm '-fm | and F0 | and the size of the standard error F | F1| F874F 7' -F8672 |, respectively are determined, If | F3 '-F3 |, | F4' -F4|, … … and | fm '-fm | are all smaller than F0, it indicates that the stress difference values at all positions are within the error range, it indicates that no error or obvious difference occurs in the process of the sample-adding layer 3 reaching the second card slot from the first card slot 107, and a subsequent related operation of adding a reagent for reaction can be performed, but in the actual comparison process, if | F1' -F1| is greater than the standard error F0, it is necessary to detect the card strip of the sample-adding layer 3 at the first position or the card slot of the pipeline layer, the comparison methods from other second positions to the M-th position are similar, and if the absolute value of the stress difference value at a certain position is found to be greater than the standard error F0, it is necessary to search for the cause of data abnormality until the related abnormality is eliminated, and the detection is performed again.
In practical application, in order to determine whether the chip device is abnormal or not according to the stress values at the respective positions, rough estimation may be performed, for example, absolute values of stress differences at the M positions are obtained, and if the absolute values of stress differences at more than half of the M positions are smaller than the standard difference F0, that is, if the stress at most of the M positions is uniform, the subsequent operations may be performed; of course, the user can also select the judgment criteria to be M/2 positions or 4M/5 positions or the number of other position points according to actual needs, which are not listed here.
In practical application process, probably because the pressing power degree is inhomogeneous for some of application of sample layer 3 has pressed the second draw-in groove, and some has remained in first draw-in groove or because press and lead to application of sample layer 3 to incline, detect f1 ' and fm ' in the second draw-in groove this moment, the stress of first two positions at the end must be different very greatly, not in presetting the difference within range, just need readjust application of sample layer 3 ' this moment. In practical application, the stress difference of any two points in the M points can be detected, so that the position of the sample adding layer 3 is ensured to be accurate and stable. In addition, the stress value of the first position in the first card slot 107 and the stress value of the first position in the second card slot can be detected, when the stress on the sample adding layer 3 is not uniform, f1 and f 1' have slight difference, and it can be understood that, besides the stress difference of the first position, the stress difference of other M-1 positions can be detected, which is not described one by one here. In this embodiment, the second strain gauge provides multiple modes for detecting the stress uniformity of the sample adding layer 3 in the chip device, thereby ensuring the accuracy of subsequent nucleic acid detection.
In the practical application process, possible factors causing slight changes of stress values of the second strain gauges in the first clamping groove 107 and the second clamping groove include abrasion of the sample adding layer 3, inclination, external impurities, abrasion of the second strain gauge and the like, and the examination needs to be carried out according to data of the first stress function and the second stress function to ensure that the sample adding layer 3 and the pipeline layer 101 are stably butted to ensure that subsequent fluid enters a preset liquid injection port and a preset pipeline.
Particularly, through setting up the second foil gage, make in the pressfitting process, can assess the steady of pressfitting in-process, so that confirm the unstable factor in the pressfitting process, and after the block, through first foil gage, through the stress variation of first foil gage, make in the experimentation, add the sample and extract the purification and amplify the reaction process, carry out real-time supervision to the block condition of the two, prevent in the reaction process because stress variation leads to the problem of leakproofness, influence the experiment progress, through the stress variation who sets up first foil gage, can in time discover abnormal conditions, in time adjust. The sealing condition of the sample adding layer and the pipeline layer can affect the efficiency of the amplification reaction, so that the arrangement of the first strain gauge is necessary.
Specifically, the depth of the positioning column inserted into the positioning hole is determined according to the stress of the first strain gauge.
Specifically, the mean value of the first strain gauge is set, and if the stress of the first strain gauge is higher than the mean value of the first strain gauge, the positioning column is inserted into the positioning hole to a certain depth, so that the chip device can be better matched with the mounting bin.
Specifically, if the stress of the first strain gauge is lower than the average value of the first strain gauge, the depth of the positioning column inserted into the positioning hole is shallow, so that the chip device can be better matched with the mounting bin.
Specifically, the insertion depth of the positioning column and the positioning hole determines the thickness of the chip device and the upper cover, the thickness is thinner if the insertion depth is deep, the thickness is thicker if the insertion depth is shallow, and the arrangement of the chip layer and the pipeline layer in the chip device also affects the actual thickness of the chip device within an error allowable range.
As shown in fig. 6, the lower side of the gasket 2 according to the embodiment of the present invention is further provided with a slide rail 202, and correspondingly, the upper side of the pipeline layer 101 is provided with a slide groove 108, and the slide rail 202 is connected with the slide groove 108 in a matching manner, so as to realize the sliding connection between the gasket 2 and the pipeline layer 101. The slide groove 108 of the present embodiment is provided inside the stopper 106 on the pipe layer 101. The end of the gasket 2 is provided with a plurality of notches and protrusions arranged at intervals, wherein the slide rail 202 is arranged on the bottom surface of the outermost protrusion.
As shown in fig. 6, the sample application hole 302 of the present embodiment is provided with a sample application hole cover 303 for sealing. Still set up buckle structure at application of sample layer 3 and pipeline layer 101, be provided with first buckle 301 in one side of application of sample layer 3, the downside of first buckle 301 stretches out the end and stretches out application of sample layer 3's bottom is installing application of sample layer 3 and pipeline layer 101 cooperation back together, through first buckle 301 joint on the side of pipeline layer 101 to prevent application of sample layer 3 and pipeline layer 101 separation.
As shown in fig. 6, the pipeline layer 101 of the present embodiment is provided with two first single valves 102 for controlling the stopping or flowing of the liquid in the pipeline layer 101 during the reaction process; the pipeline layer 101 is further provided with a double valve 103 for cutting off a road for fluid in the pipeline or allowing the fluid to pass through, the double valve 103 is communicated with the amplification bin through the pipeline, and the double valve 103 is used for controlling two ends of the amplification bin to be closed or opened simultaneously so that a closed cavity is formed inside the amplification bin. In fig. 6, handles 201 are further provided on both sides of the gasket 2 to facilitate extraction of the chip device for nucleic acid detection. In the embodiment of the invention, the amplification bin is arranged at the edge of the pipeline layer 101, and the amplification bin is of a semi-elliptical structure, so that not only can the reaction of the reaction reagent be realized, but also the convenient positioning and installation can be realized through the convex semi-elliptical structure when in use.
Continuing to refer to fig. 6, in the present embodiment, a row of pricker 105 is disposed on the pipeline layer 101, after the sample-adding layer 3 and the gasket 2 are clamped together, the handle 201 is operated to slide the gasket 2 along the sliding groove 108, when the gasket 2 is pulled out when the gasket slides to a position where the gasket cannot advance, the sample-adding layer 3 is pressed into the second clamping groove from the first clamping groove 107, so that the pricker 105 can prick a reagent tube in the sample-adding layer 3, and further the pricker 105 is communicated with a reagent in the sample-adding layer 3, and when a fluorescence sequence marked in the reagent is complementarily matched with a nucleic acid pricker at a corresponding position, a group of probe sequences with completely complementary sequences is obtained by determining a probe position with the strongest fluorescence intensity. A baffle is disposed outside the needle 105, and it acts as a stop and a positioning function when the sample injection layer 3 is matched with the pipeline layer 101.
Specifically, in the embodiment of the present invention, in the sample loading state, referring to fig. 5, a plurality of sets of reagent tubes 100 are disposed in the sample loading layer 3, the sample loading layer 3 is clamped with the first clamping groove 107 through the clamping strip 304 thereon, in the initial installation state, the sample loading layer 3 is matched with the pipeline layer 101 from top to bottom, and the gasket 2 isolates the lancet from the reagent in the reagent tube, so as to prevent the lancet from being mixed with the reagent due to vibration during transportation, protect the sample loading layer from being disconnected from the pipeline layer, and avoid puncturing. When needs are tested, outwards take gasket 2 out along spout 108, outwards take back along spout 108 for gasket 2 presses application of sample layer 3 downwards for card strip 304 and the second draw-in groove joint on application of sample layer 3, and at this moment, felting needle 105 on setting up on pipeline layer 101 mixes with application of sample layer 3's reagent, introduces reagent into pipeline layer 101 and tests.
Specifically, the gasket structure is arranged, so that the chip device for nucleic acid detection can be stored perfectly in the processes of reagent storage and transportation, and when the chip device is used, the reagent can be introduced into the pipeline layer only by drawing out the gasket and pressing the sample adding layer downwards.
FIG. 7 is a schematic view of a sample-adding layer according to an embodiment of the present invention; in this embodiment, a sample loading chamber is located below the sample loading hole 302, the sample loading chamber can be connected to a reagent tube for loading a reagent or a sample, a reagent outlet 312 is located at the lower portion of the sample loading chamber, a sealing structure 313 is located between the reagent outlet 312 and the sample loading chamber for sealing, and when a reagent needs to be loaded, the spike 105 can puncture 313 to allow the reagent to enter the fluid pipeline along the reagent outlet 312. A pressurizing structure is arranged on one side of the sample adding bin and comprises a tube wall 305, a piston 308 is arranged in the tube wall 305, and the piston 308 moves towards the sample adding bin to push the reagent in the sample adding bin to flow out to a reagent outlet 312; of course, when the reagent is required to be withdrawn, the piston 308 may also withdraw the reagent or other waste liquid, and a sealing ring 311 is provided at the end of the piston rod of the piston 308 for sealing.
Continuing to refer to fig. 7, the piston rod of this embodiment is further provided with a nut 307, which is in threaded connection with the nut 307 to realize relative rotation, and correspondingly, an output structure, such as an air cylinder and an oil cylinder, is provided at one end of the piston rod, or connected to the piston rod by rotating the output structure, such as a motor and a lead screw, at this time, the piston rod rotates, and only the reagent needs to be pushed to flow out of the reagent outlet. Correspondingly, a guide sleeve 306 is sleeved outside the nut 307, and a corresponding shaft shoulder is arranged inside the pipe wall 305 to position and fix the guide sleeve 306; snap rings 314 are further provided at the outer sides of both ends of the guide sleeve 306 to catch the corresponding guide sleeve 306. A sheath 309 is also provided outside the guide sleeve 306 to protect the piston rod, the nut 307 and the guide sleeve 306. When reagent is injected into the pipeline layer 101, the piston moves toward the sample loading bin to increase the pressure therein, so as to push the reagent to flow toward the reagent outlet 312, thereby realizing reagent injection. Referring to fig. 5, in the embodiment of the present invention, a plurality of sets of reagent tubes 100 are provided, and in the embodiment, five sets of reagent tubes are provided, and different or the same reagents are sequentially applied to the pipeline layer according to the experiment requirement, so that the use efficiency can be greatly improved.
As shown in fig. 3, a second buckle 310 is disposed below the sample adding layer 3, and the second buckle 310 is disposed on a side surface opposite to the first buckle 301 to prevent the sample adding layer 3 from sliding.
It can be seen that this embodiment is integrated at chip pipeline layer to complicated experimentation, can control the liquid trend to can improve work efficiency effectively.
The specific structures and the arrangement of the pipeline layer 101 and the sample adding layer 3 in the chip device for nucleic acid detection provided in the embodiment of the present invention will be further described in detail.
As can be understood by those skilled in the art, the tube structure disposed on the tube layer is unable to perform related nucleic acid detection tests when the sample adding layer is not connected to the tube layer, so that it is necessary to perform nucleic acid extraction, purification and amplification reactions when the tube layer is in contact with the sample adding layer.
Specifically, the pipeline layer comprises a first sample inlet, a first reagent port, a second reagent port, a third reagent port, a fourth reagent port, a purification bin and an amplification bin, the first sample inlet is connected with the first reagent port through a first pipeline, a first single valve is arranged on the first pipeline, the purification bin comprises an inlet and an outlet, the first sample inlet is connected with the inlet through a second pipeline, the first reagent port is connected with the outlet through a third pipeline, and the second reagent port, the third reagent port and the fourth reagent port are all connected with the inlet through a fourth pipeline; the first end of the amplification bin is provided with a first part of the double valve, the second end of the amplification bin is provided with a second part of the double valve, the first part of the double valve is connected with another single valve through a fifth pipeline, the other single valve is connected with the outlet through a sixth pipeline, and the first double valve and the second double valve are opened and closed simultaneously.
The specific working process is further described below, the first sample inlet, the first reagent port, the second reagent port, the third reagent port, the fourth reagent port, the purification bin and the PCR amplification bin are connected through a first pipeline, a second single valve is arranged on the first pipeline, the purification bin comprises an inlet and an outlet, the first sample inlet is connected with the inlet through a second pipeline, the first reagent port and the outlet are sequentially connected through a seventh pipeline, a first buffer bin, a first single valve and a third pipeline, and the second reagent port, the third reagent port and the fourth reagent port are all connected with the inlet through a fourth pipeline; the first portion of bivalve is connected to the first end in PCR amplifys the storehouse, the second portion of bivalve is connected to the second end in PCR amplifys the storehouse, and the exit linkage of eighth pipeline and purification storehouse is passed through to the second portion in bivalve, the first portion of bivalve is connected to first reagent mouth through second surge bin, surge bin pipeline, first surge bin, and the mode of action of the first portion of bivalve and the second portion of bivalve is for closing simultaneously or opening simultaneously.
Specifically, the purification amplification device provided by the embodiment of the invention further comprises a first buffer bin, which can be called a waste liquid bin, and the first buffer bin is internally provided with high water absorption sponge, and mainly has the advantages that after the lysate in the first reagent port is injected, a small amount of liquid remains in the lysate bin, the first reagent port is used as a matched driven bin and is matched with other reagents to enter the purification bin, in the process, a piston structure connected with the first reagent port can perform suction movement, so that the small amount of overflowing waste liquid is prevented from mixing into the whole liquid path system, the first buffer bin is arranged for absorbing a small amount of waste liquid, one end of the first buffer bin is connected with the first reagent port through a seventh pipeline, the other end of the first buffer bin is connected to a fifth pipeline to form a three-way pipeline, and a second buffer bin is arranged between the three-way pipeline and the PCR amplification bin, the sponge is arranged in the second buffer bin and used for strengthening and protecting the PCR amplification bin, the second part of the double valve is connected with the outlet through an eighth pipeline, the first pipeline is provided with a second single valve, one end of the second single valve is connected with the first sample inlet through a ninth pipeline, and the other end of the second single valve is connected with the first reagent inlet through a tenth pipeline.
When amplification reaction is carried out, firstly, a sample is injected into the first sample injection port, the sample can be blood or a swab, etc., and a first reagent is injected into the first reagent port, the first reagent is lysate, a second single valve is opened to mix the sample and the first reagent through the first pipeline, so as to obtain a first product, the first product comprises liquid, the liquid enters the purification bin through the second pipeline, magnetic beads are arranged in the purification bin, after the sample is decomposed through the lysate, nucleic acid substances and proteins are separated, the purification bin is a reaction bin for nucleic acid extraction and purification, the extraction is to extract the nucleic acid substances from the mixture of the nucleic acid substances and the proteins, the purification is to clean the extracted nucleic acid substances, then the second single valve is closed, the first single valve is opened, a second reagent is injected into the second reagent port, and the second reagent is a cleaning solution, and the second reagent enters the purification bin through the fourth pipeline and reacts with the liquid to obtain a second product, a third reagent is injected into a third reagent port, the third reagent is a cleaning solution, the third reagent enters the purification bin through the fourth pipeline and reacts with the second product to obtain a third product, a fourth reagent is injected into a fourth reagent port, the fourth reagent is an eluent, so that the nucleic acid substance is separated from the magnetic beads, the fourth reagent enters the purification bin through the fourth pipeline and reacts with the third product to obtain a fourth product, and the fourth product is introduced into the PCR amplification bin through the sixth pipeline, the first single valve and the fifth pipeline to perform amplification reaction.
Adding a sample into the first sample port, closing the first single valve, the first part of the double valve and the second part of the double valve, opening the second single valve, then pushing the first reagent into the first reagent port, wherein the sample can be blood, a nasopharyngeal swab, the sample is along the ninth pipeline, the first reagent is along the tenth pipeline, and mixing is carried out in the first pipeline, in order to ensure that the sample and the first reagent are mixed more fully, in the practical application process, a push-suction device, specifically a piston structure, can be added at the first reagent port and the first sample port, so as to accelerate micro flow of the sample or the reagent in the ninth pipeline and the tenth pipeline, fully mix and react, obtain a first product in the first pipeline, and the first product is filled in the first pipeline.
The second single valve, the first portion of the double valve and the second portion of the double valve are closed, and the first single valve is opened. At the moment, the first product is respectively reserved in the ninth pipeline and the tenth pipeline, the first product comprises liquid and gas, the liquid enters the purification bin from the first sample inlet through the second pipeline, the liquid is filled in the purification bin and overflows into the sixth pipeline, meanwhile, under the buffering action of the second buffer bin, the gas of the first product enters the sixth pipeline through the seventh pipeline and the first single valve, and the liquid and the gas are converged in the sixth pipeline. Then when a second reagent is added, the second reagent is pushed into the second reagent port, the second reagent actually enters the purification bin from the inlet along the fourth pipeline, in order to enable the second reagent to enter the purification bin which is filled with liquid, magnetic beads are arranged in the purification bin, the magnetic beads in the purification bin are scattered under the action of ultrasonic waves, so that nucleic acid in the liquid in the purification bin is fully contacted and adsorbed with the magnetic beads, the first reagent port needs to be sucked when the second reagent is pushed in, the first product is sucked into the first reagent port, so that the second reagent smoothly enters the purification bin, the second product is obtained after the second reagent reacts with the first product, and the purification bin is filled with the second product. And generating a second product and simultaneously generating a waste liquid, wherein the waste liquid can be discharged to the first reagent port and/or the first sample injection port, and optionally, the waste liquid is discharged to the first reagent port or the waste liquid is discharged to the first sample injection port.
When the third reagent and the second product are mixed, the second reagent and the third reagent clean the liquid in the purification bin to realize the extraction and purification of nucleic acid, when the third reagent port is pushed into the third reagent through a fourth pipeline, the second reagent port sucks part of the second product, then when the second reagent port is pushed into the second product, the third reagent port sucks the third reagent, and finally the waste liquid of the reaction is sucked into the second reagent port and/or the first sample port; when the fourth reagent and the third product are mixed and the fourth reagent port is pushed in the fourth reagent, the third reagent port sucks part of the third product, then when the third reagent port is pushed in the third product, the fourth reagent port sucks the fourth reagent, the fourth reagent is eluent, at this time, the purifying bin is filled with the fourth product after the third reagent and the third reactant react, the first single valve and the second single valve are closed, the first part of the double valve and the second part of the double valve are opened, the fourth product is filled in the PCR amplifying bin from the outlet along the eighth pipeline, and the first part of the double valve and the second part of the double valve are closed. Compared with the previous embodiment of the invention, the fourth product is introduced into the PCR amplification bin through the eighth pipeline, and compared with the PCR amplification bin introduced through the sixth pipeline and the fifth pipeline, the eighth pipeline is not polluted by other liquid or gas in the reaction process, is clean, and can ensure the purity of substances entering the PCR amplification bin.
So far, the technical solutions of the present invention have been described in connection with the preferred embodiments shown in the drawings, but it is easily understood by those skilled in the art that the scope of the present invention is obviously not limited to these specific embodiments. Equivalent changes or substitutions of related technical features can be made by those skilled in the art without departing from the principle of the invention, and the technical scheme after the changes or substitutions can fall into the protection scope of the invention.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention; various modifications and alterations to this invention will become apparent to those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (10)

1. An upper cover based on a nucleic acid detecting chip mounting bin, comprising: the top cover is in a long-strip plate shape, and the side plate is arranged on the long side of the top cover and is fixedly connected with the top cover to be integrally formed;
one end of the side plate is provided with a connecting hole which is used for being detachably connected with a connecting lug of the upper shell, one end of the top cover, which is far away from the connecting hole, is provided with a first bulge, and the first bulge is used for being clamped with a connecting groove of the upper shell;
the inner side of the top cover comprises a first boss, a second boss and a third boss, the second boss is arranged between the first boss and the third boss, the height of the second boss is higher than that of the third boss, the height of the third boss is higher than that of the first boss, the first boss is close to the first boss, and the second boss is adjacent to the third boss; the number of the second bosses is two, and the second bosses are symmetrically arranged along the central line of the top cover; the third boss is far away from the first boss, and the third boss is positioned between the two second bosses;
a positioning column is arranged on the inner side of the second boss and is used for matching with a positioning hole in the chip to be detected;
the chip to be detected comprises a sample adding layer arranged at the uppermost end, a gasket arranged on the lower side of the sample adding layer and a pipeline layer arranged on the lower side of the gasket;
wherein the content of the first and second substances,
the upper side of the sample adding layer is provided with a sample adding hole for adding a sample into the chip, and the sample injected into the chip is subjected to nucleic acid extraction, purification and amplification reaction in sequence;
the sample adding layer and the pipeline layer are movably connected with a limiting frame arranged on the side part of the pipeline layer through clamping strips, correspondingly, a first clamping groove is arranged on the inner side of the limiting frame and is mutually matched and connected through the clamping strips, so that the relative position switching and fixing of the sample adding layer and the pipeline layer are realized;
the second clamping groove is arranged on the inner side of the limiting frame and is positioned below the first clamping groove;
when in transportation or storage, the sample adding layer is connected with the first clamping groove;
when the sample injection device is used, the gasket is pulled out, the sample injection layer is pressed downwards to be connected with the second clamping groove, and meanwhile, the puncture needle is arranged on the upright column on the pipeline layer and is used for puncturing the reagent arranged in the sample injection layer so as to enable the reagent and the sample to be mixed and reacted;
after the sample adding layer and the pipeline layer are pressed, a first strain gauge arranged at the bottom of the sample adding layer detects the extrusion force between the sample adding layer and the pipeline layer so as to determine the stress uniformity of the sample adding layer and the pipeline layer in the pressing process;
the positioning device is characterized by further comprising a control unit, wherein the control unit determines the depth of the positioning column inserted into the positioning hole according to the stress of the first strain gauge, so that the thickness of the chip to be detected and the upper cover after installation is within a preset range.
2. The nucleic acid detecting chip mounting bin-based upper cover according to claim 1, wherein a second protrusion is arranged on the third boss, a through hole is arranged on the second protrusion, the through hole is a circular through hole, and the second boss is a cube;
the second boss comprises a first reinforcing rib and a second reinforcing rib, the first reinforcing rib and the second reinforcing rib are symmetrically arranged, the first reinforcing rib and the second reinforcing rib are symmetrical in structure, and the first reinforcing rib comprises a first straight arm, a second straight arm and a third straight arm; the second reinforcing rib comprises a fourth straight arm, a fifth straight arm and a sixth straight arm, the second straight arm is arranged between the first straight arm and the third straight arm, the first straight arm is vertical to the second straight arm, the second straight arm is vertical to the third straight arm, and the second straight arm is in smooth transition connection with the third straight arm; the fifth straight arm is arranged between the fourth straight arm and the sixth straight arm, the fourth straight arm is perpendicular to the fifth straight arm, the fifth straight arm is perpendicular to the sixth straight arm, the positioning column comprises a first positioning column and a second positioning column, the first positioning column is arranged on the side face of the third straight arm, and the second positioning column is arranged on the side face of the sixth straight arm.
3. The upper cover based on the nucleic acid detecting chip mounting bin is characterized in that the chip to be detected further comprises a sealing film and a second strain gauge, the sealing film is arranged on the lower side of the pipeline layer and used for realizing sealing, and the second strain gauge is respectively arranged in the first clamping groove and the second clamping groove; taking M positions in the first card slot transversely, detecting the stress at the M positions by the second strain gauge, marking as a first stress function F, wherein the first stress function specifically comprises F1, F2 … … and fm, the selected positions in the second card slot correspond to the positions in the first card slot one by one, the second stress function of the second card slot is F ', and the second stress function specifically comprises F1', F2 ', … … and fm', and judging the position of the sample adding layer according to the first stress function and the second stress function.
4. The nucleic acid detecting chip mounting cartridge based on upper cover of claim 3, wherein when the sample adding layer is connected to the first card slot, f1 and fm are compared first to obtain a first positive difference value, and if the first positive difference value is higher than a first preset difference value f0, the sample adding layer is readjusted; if the first positive difference is lower than a first preset difference f0, performing subsequent operation;
when the sample adding layer is connected with the second clamping groove, f1 ' and fm ' are compared to obtain a second positive difference value, and if the second positive difference value is higher than a second preset difference value f0 ', the sample adding layer is readjusted; if the second positive difference is lower than a second predetermined difference f 0', the subsequent operation is performed.
5. The nucleic acid detecting chip mounting bin-based upper cover according to claim 4, wherein the first positioning column and the second positioning column are arranged in a staggered manner, the distance from the first positioning column to the second boss is smaller than the distance from the second positioning column to the second boss, the first boss is provided with a square notch, a notch is arranged at the notch, and the top cover is trapezoidal.
6. The nucleic acid based detection chip mounting cartridge cover according to claim 5,
the lower side of the gasket is also provided with a sliding rail, correspondingly, the upper side surface of the pipeline layer is provided with a sliding groove, and the sliding rail is connected with the sliding groove in a matching way so as to realize the sliding connection between the gasket and the pipeline layer;
the sliding groove is arranged on the inner side of the limiting frame on the pipeline layer;
the end part of the gasket is provided with a plurality of notches and bulges which are arranged at intervals, wherein the slide rail is arranged on the bottom surface of the bulge at the outermost side.
7. The upper cover of the nucleic acid detecting chip mounting bin according to claim 1, wherein a buckle structure is further disposed on the sample adding layer and the pipeline layer, a first buckle is disposed on one side of the sample adding layer, a lower side extending end of the first buckle extends out of a bottom end of the sample adding layer, and after the sample adding layer and the pipeline layer are fitted together, the first buckle is clamped on a side surface of the pipeline layer to prevent the sample adding layer and the pipeline layer from separating.
8. The nucleic acid detecting chip mounting cartridge-based cover according to claim 6, wherein a plurality of ribs are disposed at intervals on the outer side wall of the rib, three first ribs are disposed on the outer side of the first straight arm, two second ribs are disposed on the outer side of the second straight arm, and two third ribs are disposed on the outer side of the third straight arm; three fourth convex edges are arranged on the outer side of the fourth straight arm; two fifth convex edges are arranged on the outer side of the fifth straight arm; and two sixth convex ridges are arranged on the outer side of the sixth straight arm.
9. The nucleic acid detecting chip mounting cartridge-based upper cover according to claim 3, wherein the inner sides of the first straight arm and the fourth straight arm are provided with arc-shaped transition pieces for smoothly contacting the upper cover with the chip during the clamping process;
the first protrusion comprises a clamping portion and a connecting portion, the connecting portion is fixedly connected with the clamping portion, the connecting portion is fixedly connected with the upper cover, the clamping portion is used for extending into the connecting groove of the upper shell, and the clamping portion is an irregular prism with opposite sides.
10. The nucleic acid based detection chip mounting cartridge cover according to claim 9,
a plurality of sample adding bins which are arranged at intervals are arranged below the sample adding holes, a reagent outlet is arranged at the end part of each sample adding bin, and a sealing structure is arranged between each reagent outlet and each sample adding bin and used for sealing;
a pressurizing structure is arranged on one side of the sample adding bin and comprises a tube wall, a piston is arranged in the tube wall, and the piston moves back and forth along the tube wall to push the reagent in the piston to flow out or be drawn back to a reagent outlet; a sealing ring is arranged at the end part of a piston rod of the piston and used for sealing;
when the sample adding layer is connected with the second card slot, comparing absolute values of all stress difference values at positions corresponding to one another in a first stress function F and a second stress function F', wherein the first stress function F is a function generated when the sample adding layer is connected with the first card slot, judging whether the absolute value of each stress difference value is smaller than a preset standard error F0, if so, continuing to operate, and if not, determining the corresponding position of the absolute value of the corresponding group of stress difference values so as to determine the damage of the sample adding layer or the pipeline layer;
the piston rod is also provided with a nut which is in threaded connection with the nut, a guide sleeve is sleeved outside the nut, a corresponding shaft shoulder is arranged inside the pipe wall and used for positioning and fixing the guide sleeve, and clamping rings are arranged outside two ends of the guide sleeve and used for clamping the corresponding guide sleeve; and a sheath is arranged on the outer side of the guide sleeve and used for protecting the piston rod, the screw cap and the guide sleeve.
CN202110055530.6A 2021-01-15 2021-01-15 Upper cover based on nucleic acid detection chip installation bin Active CN113174307B (en)

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Application publication date: 20210727

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