CN116515617A - Centrifugal PCR-fluorescence multi-target detection chip - Google Patents
Centrifugal PCR-fluorescence multi-target detection chip Download PDFInfo
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- CN116515617A CN116515617A CN202310800190.4A CN202310800190A CN116515617A CN 116515617 A CN116515617 A CN 116515617A CN 202310800190 A CN202310800190 A CN 202310800190A CN 116515617 A CN116515617 A CN 116515617A
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- 238000009413 insulation Methods 0.000 claims description 3
- 238000003825 pressing Methods 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 6
- 238000001917 fluorescence detection Methods 0.000 abstract description 4
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- 150000007523 nucleic acids Chemical group 0.000 description 2
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- 238000012360 testing method Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
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- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
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- 238000009434 installation Methods 0.000 description 1
- 238000002032 lab-on-a-chip Methods 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 description 1
- 238000001259 photo etching Methods 0.000 description 1
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Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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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
- C12Q1/6844—Nucleic acid amplification reactions
- C12Q1/686—Polymerase chain reaction [PCR]
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0689—Sealing
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/14—Process control and prevention of errors
- B01L2200/141—Preventing contamination, tampering
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/04—Closures and closing means
- B01L2300/046—Function or devices integrated in the closure
- B01L2300/049—Valves integrated in closure
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The centrifugal PCR-fluorescence multi-target detection chip comprises a chip base, a chip cover plate and a chip valve body, wherein a detection flow channel for detecting targets is arranged on the chip base, the chip cover plate is arranged on the chip base in a covering mode, the chip valve body is assembled between the chip base and the chip cover plate and is assembled on the detection flow channel, and the on-off of the detection flow channel is controlled through the chip valve body; the detection flow channel is covered by the chip cover plate, so that the requirement of the whole chip on tightness is met, and meanwhile, target pre-packaging can be carried out according to actual detection requirements; the PCR reaction is sealed in a sealed space through the arrangement of the chip valve body, so that the evaporation loss and aerosol pollution are reduced; through the design of the detection reaction chamber and the control flow channel, the whole flow of PCR and multi-target fluorescence detection is realized in a whole-process closed environment after one sample addition.
Description
Technical Field
The invention belongs to the technical field of laboratory ware, and particularly relates to a centrifugal PCR-fluorescence multi-target detection chip.
Background
In the existing PCR detection experiment, pollution mainly occurs in the link of adding fluorescent dye after the end of the PCR reaction and after the secondary cover opening. Because the concentration of a specific nucleic acid fragment is very high after the PCR reaction, the risk of sample addition by secondary uncapping is very high. At present, the problem is not well solved in the commercial PCR fluorescent detection products.
In recent years, based on continuous innovation in the field of lab-on-a-chip research, chips on the market at present mainly have the following defects that (1) the chip detection mostly adopts mechanical driving such as pneumatic micropumps, piezoelectric micropumps and reciprocating micropumps or non-mechanical driving principles such as electroosmosis driving and gravity driving, and the driving mode is complex and has higher requirements; (2) The chip mostly adopts capillary action for controlling the fluid, and controls the fluid system through the surface tension, the power consumption and the flow resistance of the fluid, but the chip can not meet the requirement of PCR reaction on tightness; or a mode of adding a plurality of layers of materials and films is adopted, the films are deformed by controlling the gas in the film flow channels so as to block the liquid flow channels, and active control is realized on the liquid flow channels, but the chip manufacturing process is difficult and the control system is complex.
Disclosure of Invention
Aiming at the defects, the invention aims to provide a centrifugal PCR-fluorescence multi-target detection chip, which ensures the tightness of PCR reaction and is convenient for controlling micro-liquid of the detection chip.
In order to solve the technical problems, the invention adopts the technical proposal that,
a centrifugal PCR fluorescent multi-target detection chip comprises
The chip base is provided with a detection flow channel for detecting a target, a control flow channel is arranged in the detection flow channel, and the flow resistance of the mixed liquid in the control flow channel area of the detection flow channel is increased through the control flow channel so as to control the flow position of the liquid;
the chip cover plate is fixed on the chip base and covers the detection flow channel below the chip cover plate;
the chip valve body is assembled on the detection flow channel and controls the on-off of the detection flow channel through the chip valve body.
As a preferable scheme of the invention, the control flow channel comprises a plurality of flow channel units, adjacent flow channel units are in transitional connection through arc-shaped flow channels, and the flow resistance of liquid in the detection flow channel is increased through the flow channel units so as to control the position of the liquid flow.
As a preferable scheme of the invention, the flow channel units are transversely arranged on the chip base, and the flow channel units are arranged in a manner of vertical detection of the whole flow direction of the flow channel.
As a preferred scheme of the invention, the detection flow channel comprises a plurality of PCR reaction chambers for placing targets and a plurality of detection reaction chambers for detecting targets, and the control flow channel is arranged between the PCR reaction chambers and the detection reaction chambers so as to control the flow position through the control flow channel.
As a preferable scheme of the invention, the rear end of the control flow channel is provided with the vein flow channel, the vein flow channel is connected with the detection reaction chamber through the connecting flow channel, and the detection reaction chamber is uniformly distributed on the vein flow channel.
As a preferable scheme of the invention, the detection flow channel further comprises a mixing chamber, and the mixing chamber is arranged between the PCR reaction chamber and the control flow channel.
As a preferable scheme of the invention, the detection flow channel further comprises a feeding flow channel, the feeding flow channel comprises a feeding main flow channel and a feeding branch flow channel, the plurality of PCR reaction chambers are connected with the feeding main flow channel through the feeding branch flow channel, the tail end of the feeding main flow channel is connected with the mixing chamber, and the chip valve body is arranged at the joint of the feeding branch flow channel and the feeding main flow channel.
As a preferable scheme of the invention, a thermal insulation hole is arranged between the PCR reaction chamber and the mixing chamber.
As a preferable scheme of the invention, the upper end of the chip valve body extends out of the chip cover plate, the chip valve body is provided with a valve body bulge which extends into the detection flow channel, and the relative position of the valve body bulge and the detection flow channel is changed by pressing the chip valve body so as to control the on-off of the detection flow channel.
As a preferred scheme of the invention, the chip cover plate comprises a sealing cover plate and a detection cover plate, wherein the sealing cover plate is fixed on the chip base, and the detection cover plate is detachably assembled on the chip base.
As a preferable scheme of the invention, the chip valve body is provided with a static sealing ring for improving the tightness of the chip valve body, and the static sealing ring is arranged between the chip base and the chip cover plate.
As a preferable scheme of the invention, one side of the PCR reaction chamber is provided with a dislocation groove, the chip cover plate is provided with a sample adding hole, and the sample adding hole is connected with the dislocation groove.
The invention has the beneficial effects that the detection flow channel is covered by the chip cover plate, so that the requirement of the PCR reaction on the tightness is met; the PCR reaction is sealed in a sealed space through the arrangement of the chip valve body, so that the evaporation loss and aerosol pollution are reduced; through the design of the detection reaction chamber and the control flow channel, the whole flow of PCR and multi-target fluorescence detection is realized in a whole-process closed environment after one sample addition.
Drawings
Fig. 1 is a schematic diagram of the structure of the chip.
Fig. 2 is a rear view of a chip substrate.
Fig. 3 is a schematic front-end view of a chip substrate.
Fig. 4 is a schematic half-section of the present chip.
Reference numerals: chip base 1, control runner 1-1, runner unit 1-2, arc runner 1-3, PCR reaction chamber 1-4, detection reaction chamber 1-5, vein runner 1-6, connecting runner 1-7, mixing chamber 1-8, feeding dry flow runner 1-9, feeding tributary runner 1-10, heat insulation hole 1-11, dislocation groove 1-12, chip base plate 1-13, chip bottom plate 1-14, shutoff through hole 1-15, shutoff taper hole 1-16, chip cover plate 2, sealing cover plate 2-1, detection cover plate 2-2, sample adding hole 2-3, chip valve body 3, valve body protrusion 3-1, static sealing ring 3-2.
Detailed Description
The invention is further described below with reference to the accompanying drawings.
The existing microfluidic chip is mostly manufactured by adopting technologies such as PMMA or PDMS material ion deep etching method, photoetching chemical candling method, soft candling technology and the like, micro liquid driving and controlling are mostly based on principles such as pneumatic micropump, piezoelectric micropump, electroosmosis driving or capillary action, and the like, so that the surface hydrophilic and hydrophobic modification is required to be carried out on the flow channel, and the manufacturing process is complex and the cost is high. Meanwhile, the control mode can not meet the requirements of the PCR-fluorescence detection integrated flow operation in molecular diagnosis. The invention relates to a centrifugal PCR-fluorescence multi-target detection chip, which comprises a chip base 1, a chip cover plate 2 and a chip valve body 3, wherein a detection flow channel for detecting targets is arranged on the chip base 1, the chip cover plate 2 is arranged on the chip base 1 in a covering manner, the chip valve body 3 is assembled between the chip base 1 and the chip cover plate 2, the chip valve body 3 is assembled on the detection flow channel, and the on-off of the detection flow channel is controlled through the chip valve body 3; the detection flow channel is covered by the chip cover plate 2, so that the requirement of the PCR reaction on the tightness is met; and the PCR reaction is sealed in a sealed space through the arrangement of the chip valve body 3, so that the evaporation loss and aerosol pollution are reduced, and the whole flow of PCR and multi-target fluorescence detection is realized in a whole-process sealed environment after one sample addition is achieved.
The chip cover plate 2 comprises a sealing cover plate 2-1 and a detection cover plate 2-2, the sealing cover plate 2-1 is fixed on the chip base 1, the detection cover plate 2-2 is detachably assembled on the chip base 1, the chip is adhered and sealed after targets are added according to requirements in actual tests, and the sealing performance of the chip is ensured by sealing the sample adding holes 2-3 through the sealing cover plate 2-1 and the sealing film.
The chip base 1 comprises a chip substrate 1-13 and a chip base plate 1-14, wherein the chip substrate 1-13 is used for a detection flow channel required by a processing test flow, the chip valve body 3 is installed, the chip valve body 3 is integrally formed with the chip substrate 1-13 through hot press bonding or laser bonding after the installation, the chip base plate 1-14 is integrally formed with the chip substrate through hot press bonding or laser bonding, and the detection cover plate 2-2 is adhered to the chip substrate through PSA after the chip substrate 1-13 is filled with a required target, so that the chip is integrally formed.
The detection flow channel on the chip substrate 1-13 comprises a PCR reaction chamber 1-4, a feeding flow channel, a mixing chamber 1-8, a control flow channel 1-1, a leaf vein flow channel 1-6 and a detection reaction chamber 1-5 which are connected in sequence; the PCR reaction chambers 1-4 are used for accommodating nucleic acid and PCR reaction reagents; the feeding flow channel is used for guiding the reagent in each PCR reaction chamber 1-4 to the mixing chamber 1-8; the control flow channel 1-1 is used for increasing the flow resistance of the mixed liquid in the area of the control flow channel 1-1, namely, the flow resistance of the liquid in the control flow channel 1-1 is larger than the flow resistance of the flow channel formed by the feeding flow channels 1-9 and 1-10, when the liquid in the detection flow channel is driven by the centrifugal machine to flow, the centrifugal machine is at a fixed rotating speed, the position where the liquid can flow into the mixing chamber 1-8 or the detection chamber 1-5 is fixed, and the position where the liquid can flow into the mixing chamber 1-8 or the detection reaction chamber 1-5 is regulated by changing the rotating speed (increasing centrifugal force) of the centrifugal machine; the vein flow channel 1-6 is used for flowing liquid into the detection reaction chamber 1-5. The feeding flow channel comprises a feeding main flow channel 1-9 and a feeding branch flow channel 1-10, the plurality of PCR reaction chambers 1-4 are connected with the feeding main flow channel 1-9 through the feeding branch flow channel 1-10, the tail end of the feeding main flow channel 1-9 is connected with the mixing chamber 1-8, the chip valve body 3 is arranged at the joint of the feeding branch flow channel 1-10 and the feeding main flow channel 1-9, and the chip valve body 3 separates each feeding branch flow channel 1-10, so that the PCR reaction step is isolated from the mixing step and the detection step; in this embodiment, three PCR reaction chambers 1-4 flow into the feed dry flow channel 1-9 through the feed branch flow channel 1-10, and then flow into the mixing chamber 1-8 through the feed dry flow channel 1-9.
The control flow channel 1-1 comprises a plurality of flow channel units 1-2, adjacent flow channel units 1-2 are in transitional connection through arc-shaped flow channels 1-3, in the embodiment, the flow channel units 1-2 are horizontally arranged flat flow channels, the flow channel units 1-2 are arranged relative to the whole flow direction of the vertical detection flow channel, namely, the flow channel units 1-2 are arranged in a manner of being perpendicular to connecting lines of the PCR reaction chamber 1-4 and the detection reaction chamber 1-5, so that the flow resistance of liquid in the area of the control flow channel 1-1 is increased through the flow channel units 1-2, and the position of the liquid flowing into the detection reaction chamber 1-5 is conveniently controlled through the rotating speed of the centrifugal machine; in some other embodiments, the control flow passage 1-1 may have an S-shaped flow passage structure.
Fifty detection reaction chambers 1-5 are arranged on the chip substrate 1-13 of the embodiment, in order to facilitate the liquid to flow into the detection reaction chambers 1-5, a vein runner 1-6 is arranged at the rear end of the control runner 1-1, the vein runner 1-6 comprises a main runner and a plurality of parallel sub-runners, the main runner of the vein runner 1-6 is connected with the control runner 1-1, the main runner is arranged along the length direction of the chip substrate 1-13, the sub-runners are obliquely arranged relative to the main runner, in the embodiment, the sub-runners are obliquely arranged towards the tail ends of the main runners, so that the detection liquid can flow into the detection reaction chambers 1-5 through the sub-runners in the use process of the chip on one hand; on the other hand, more detection reaction chambers 1-5 can be additionally arranged on the chip substrate 1-13, the detection reaction chambers 1-5 are uniformly distributed on the sub-channels of the leaf vein flow channels 1-6, the leaf vein flow channels 1-6 are connected with the detection reaction chambers 1-5 through the connecting flow channels 1-7, preferably, the connecting flow channels 1-7 are arranged in parallel with the main flow channels, the leaf vein flow channels 1-6 enable mixed liquid to enter a plurality of detection reaction chambers 1-5, and diffusion pollution among targets in each target detection reaction chamber is prevented through the connecting flow channels 1-7; in some preferred modes, the connecting flow channels 1-7 are arranged along the whole flow direction of the detecting flow channels, and liquid is always remained in the detecting reaction chambers 1-5 under the action of centrifugal force, so that diffusion pollution caused by backflow of the liquid through the connecting flow channels 1-7 is prevented.
The temperature separation holes 1-11 are arranged between the PCR reaction chamber 1-4 and the mixing chamber 1-8, and the temperature of the PCR reaction chamber 1-4 and the temperature of the mixing chamber 1-8 are distinguished through the temperature separation holes 1-11, so that the influence of the PCR reaction temperature on the mixed reagent and the detection reagent is effectively isolated, and the detection accuracy is ensured.
The PCR reaction chamber 1-4, the mixing chamber 1-8 and the detection reaction chamber 1-5 are all through groove structures on the chip substrate 1-13, the feeding flow channel, the control flow channel 1-1 and the leaf vein flow channel 1-6 are all groove structures on one side end surface of the chip substrate 1-13, and the chip cover plate 2 is arranged on the feeding flow channel, the control flow channel 1-1 and the leaf vein flow channel 1-6 in a covering manner to form a sealed flow channel structure; the other side end face of the chip substrate 1-13 is provided with a dislocation groove 1-12, the dislocation groove 1-12 is communicated with the PCR reaction chamber 1-4, the sealing cover plate 2-1 is provided with a sample adding hole 2-3, the sample adding hole 2-3 is connected with the dislocation groove 1-12, and the sample adding hole is sealed by a sealing film, so that the chip structure has good sealing performance; during PCR reaction, liquid is influenced by temperature to expand with heat and contract with cold and evaporate, and the liquid and the evaporant thereof are sealed in the PCR reaction chamber 1-4 through the sealing film on the sample adding hole 2-3 and the chip valve body 3; when the centrifugal machine works, the chip valve body 3 keeps an open state, liquid flows out of the PCR reaction chamber 1-4 to the mixing chamber 1-8 under the action of centrifugal force, and after the mixing is finished, the liquid is centrifuged to the detection chamber 1-5 again and reacts with a target pre-packaged in the detection chamber.
The sealing cover plate 2-1 is provided with a through hole, the upper end of the chip valve body 3 extends out of the chip cover plate 2 through the through hole, so that the chip valve body 3 is conveniently pressed outside the chip, the lower end surface of the chip valve body 3 is provided with a valve body bulge 3-1, the valve body bulge 3-1 extends into the joint of the feeding branch flow channel 1-10 and the feeding main flow channel 1-9, and the depth of the valve body bulge 3-1 extending into the feeding flow channel is changed by pressing the chip valve body 3, so that the feeding flow channel is blocked; after the pressure is removed, the feeding flow channel is opened, so that the liquid can flow in the detection flow channel conveniently; the pressure of the chip valve body 3 is actively controlled, so that the PCR reaction chamber is actively sealed during the PCR reaction, and the quality of the PCR reaction is effectively ensured.
In order to ensure the sealing performance of the mounting position of the chip valve body 3, a static sealing ring 3-2 is arranged on the chip valve body 3, the static sealing ring 3-2 is fixed between the chip base 1 and the chip cover plate 2, and the static sealing ring 3-2 is welded with the chip base plate 1-13 through hot-press bonding or laser bonding, so that the connection tightness of the chip valve body 3 and the chip base plate 1-13 is ensured.
The upper end face of the chip substrate 1-13 is provided with a plugging through hole 1-15, the valve body bulge 3-1 stretches into the liquid inlet flow channel through the plugging through hole 1-15, the upper end face of the plugging through hole 1-15 is provided with a plugging conical hole 1-16, and the descending stroke of the chip valve body 3 is conveniently increased through the setting of the plugging conical hole 1-16, so that the liquid inlet flow channel is conveniently plugged through the valve body bulge 3-1.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention; thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Although the terms corresponding to the reference numerals in the drawings are used more herein, the possibility of using other terms is not excluded; these terms are used merely for convenience in describing and explaining the nature of the invention; they are to be interpreted as any additional limitation that is not inconsistent with the spirit of the present invention.
Claims (9)
1. A centrifugal PCR-fluorescence multi-target detection chip is characterized by comprising
The chip base (1) is provided with a detection flow channel for detecting a target, a control flow channel (1-1) is arranged in the detection flow channel, and the flow resistance of mixed liquid in the area of the control flow channel (1-1) of the detection flow channel is increased through the control flow channel (1-1) so as to control the flow position of the liquid;
the chip cover plate (2) is fixed on the chip base (1) and covers the detection flow channel below the chip cover plate (2);
the chip valve body (3), the chip valve body (3) is assembled on the detection flow channel, and the on-off of the detection flow channel is controlled through the chip valve body (3);
the upper end of the chip valve body (3) extends out of the chip cover plate (2), the chip valve body (3) is provided with a valve body protrusion (3-1) which extends into the detection flow channel, and the relative position of the valve body protrusion (3-1) and the detection flow channel is changed by pressing the chip valve body (3) so as to control the on-off of the detection flow channel.
2. The centrifugal PCR-fluorescence multi-target detection chip according to claim 1, wherein the control flow channel (1-1) comprises a plurality of flow channel units (1-2), adjacent flow channel units (1-2) are in transitional connection through an arc-shaped flow channel (1-3), and the flow resistance of liquid in the detection flow channel is increased through the flow channel units (1-2) for controlling the position of the liquid flow.
3. The centrifugal PCR-fluorescence multi-target detection chip according to claim 2, wherein the flow channel units (1-2) are horizontally arranged on the chip base (1) and are arranged perpendicular to the whole flow direction of the detection flow channel.
4. The centrifugal PCR-fluorescence multi-target detection chip according to claim 1, wherein the detection flow channel comprises a plurality of PCR reaction chambers (1-4) for placing targets and a plurality of detection reaction chambers (1-5) for detecting targets, and the control flow channel (1-1) is arranged between the PCR reaction chambers (1-4) and the detection reaction chambers (1-5) so as to control the flow position through the control flow channel (1-1).
5. The centrifugal PCR-fluorescence multi-target detection chip according to claim 4, wherein a leaf vein runner (1-6) is arranged at the rear end of the control runner (1-1), the leaf vein runner (1-6) is connected with the detection reaction chamber (1-5) through a connecting runner (1-7), and the detection reaction chamber (1-5) is uniformly distributed on the leaf vein runner (1-6).
6. The centrifugal PCR-fluorescence multi-target detection chip according to claim 4, wherein the detection flow channel further comprises a mixing chamber (1-8), and the mixing chamber (1-8) is arranged between the PCR reaction chamber (1-4) and the control flow channel (1-1).
7. The centrifugal PCR-fluorescence multi-target detection chip according to claim 6, wherein the detection flow channel further comprises a feeding flow channel, the feeding flow channel comprises a feeding main flow channel (1-9) and a feeding branch flow channel (1-10), the plurality of PCR reaction chambers (1-4) are connected with the feeding main flow channel (1-9) through the feeding branch flow channel (1-10), the tail end of the feeding main flow channel (1-9) is connected with the mixing chamber (1-8), and the chip valve body (3) is arranged at the joint of the feeding branch flow channel (1-10) and the feeding main flow channel (1-9).
8. The centrifugal PCR-fluorescence multi-target detection chip according to claim 6, wherein a thermal insulation hole (1-11) is arranged between the PCR reaction chamber (1-4) and the mixing chamber (1-8).
9. The centrifugal PCR-fluorescence multi-target detection chip according to claim 1, wherein the chip cover plate (2) comprises a sealing cover plate (2-1) and a detection cover plate (2-2), the sealing cover plate (2-1) is fixed on the chip base (1), and the detection cover plate (2-2) is detachably assembled on the chip base (1).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310800190.4A CN116515617B (en) | 2023-07-03 | 2023-07-03 | Centrifugal PCR-fluorescence multi-target detection chip |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310800190.4A CN116515617B (en) | 2023-07-03 | 2023-07-03 | Centrifugal PCR-fluorescence multi-target detection chip |
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| CN116515617A true CN116515617A (en) | 2023-08-01 |
| CN116515617B CN116515617B (en) | 2023-10-20 |
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Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090191618A1 (en) * | 2004-11-18 | 2009-07-30 | Remacle Jose | Reaction chamber for real time pcr comprising capture probes and permitting detection of the pcr product by hybridisation without opening the pcr vessel |
| CN109499634A (en) * | 2018-12-13 | 2019-03-22 | 迪亚莱博（张家港）生物科技有限公司 | A kind of micro-fluidic chip and preparation method thereof and detection method |
| CN209307400U (en) * | 2018-11-06 | 2019-08-27 | 苏州璞瑞卓越生物科技有限公司 | A kind of micro-fluidic digital pcr detection chip |
| US20190351412A1 (en) * | 2017-09-26 | 2019-11-21 | Nanjing Lansion Biotechnology Co., Ltd. | Multi-flux microfluidic chip for nucleic acid detection and capable of actively controlling flow path, and use method thereof |
| CN111088161A (en) * | 2019-12-19 | 2020-05-01 | 深圳市华迈生物医疗科技有限公司 | Micro-fluidic chip for nucleic acid amplification detection and detection method |
| CN213761867U (en) * | 2020-10-13 | 2021-07-23 | 重庆市公共卫生医疗救治中心 | Centrifugal urine routine detection micro-fluidic chip |
| CN217499275U (en) * | 2022-05-19 | 2022-09-27 | 北京中科生仪科技有限公司 | Totally-enclosed nucleic acid detection chip |
| CN115678771A (en) * | 2022-11-07 | 2023-02-03 | 苏州思迈德生物科技有限公司 | Multi-channel molecular diagnosis micro-fluidic chip |
| CN116103139A (en) * | 2023-04-14 | 2023-05-12 | 杭州霆科生物科技有限公司 | Totally enclosed full-integrated nucleating acid detection micro-fluidic chip |
-
2023
- 2023-07-03 CN CN202310800190.4A patent/CN116515617B/en active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090191618A1 (en) * | 2004-11-18 | 2009-07-30 | Remacle Jose | Reaction chamber for real time pcr comprising capture probes and permitting detection of the pcr product by hybridisation without opening the pcr vessel |
| US20190351412A1 (en) * | 2017-09-26 | 2019-11-21 | Nanjing Lansion Biotechnology Co., Ltd. | Multi-flux microfluidic chip for nucleic acid detection and capable of actively controlling flow path, and use method thereof |
| CN209307400U (en) * | 2018-11-06 | 2019-08-27 | 苏州璞瑞卓越生物科技有限公司 | A kind of micro-fluidic digital pcr detection chip |
| CN109499634A (en) * | 2018-12-13 | 2019-03-22 | 迪亚莱博（张家港）生物科技有限公司 | A kind of micro-fluidic chip and preparation method thereof and detection method |
| CN111088161A (en) * | 2019-12-19 | 2020-05-01 | 深圳市华迈生物医疗科技有限公司 | Micro-fluidic chip for nucleic acid amplification detection and detection method |
| CN213761867U (en) * | 2020-10-13 | 2021-07-23 | 重庆市公共卫生医疗救治中心 | Centrifugal urine routine detection micro-fluidic chip |
| CN217499275U (en) * | 2022-05-19 | 2022-09-27 | 北京中科生仪科技有限公司 | Totally-enclosed nucleic acid detection chip |
| CN115678771A (en) * | 2022-11-07 | 2023-02-03 | 苏州思迈德生物科技有限公司 | Multi-channel molecular diagnosis micro-fluidic chip |
| CN116103139A (en) * | 2023-04-14 | 2023-05-12 | 杭州霆科生物科技有限公司 | Totally enclosed full-integrated nucleating acid detection micro-fluidic chip |
Non-Patent Citations (1)
| Title |
|---|
| 吴李刚等: "基于离心微流技术的阵列化检测芯片", 微纳电子技术, vol. 53, no. 10, pages 658 - 662 * |
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