WO2022174472A1 - Puce microfluidique multi-index entièrement intégrée pour le test d'acide nucléique - Google Patents
Puce microfluidique multi-index entièrement intégrée pour le test d'acide nucléique Download PDFInfo
- Publication number
- WO2022174472A1 WO2022174472A1 PCT/CN2021/078004 CN2021078004W WO2022174472A1 WO 2022174472 A1 WO2022174472 A1 WO 2022174472A1 CN 2021078004 W CN2021078004 W CN 2021078004W WO 2022174472 A1 WO2022174472 A1 WO 2022174472A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- nucleic acid
- pool
- liquid
- amplification
- tube
- Prior art date
Links
- 238000011330 nucleic acid test Methods 0.000 title abstract 2
- 239000007788 liquid Substances 0.000 claims abstract description 168
- 230000003321 amplification Effects 0.000 claims abstract description 80
- 238000003199 nucleic acid amplification method Methods 0.000 claims abstract description 80
- 239000006185 dispersion Substances 0.000 claims abstract description 57
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 55
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 55
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 55
- 238000001514 detection method Methods 0.000 claims description 54
- 239000002699 waste material Substances 0.000 claims description 21
- 239000003153 chemical reaction reagent Substances 0.000 claims description 19
- 238000005406 washing Methods 0.000 claims description 17
- 239000003480 eluent Substances 0.000 claims description 15
- 239000006166 lysate Substances 0.000 claims description 13
- 239000012528 membrane Substances 0.000 claims description 11
- 238000007789 sealing Methods 0.000 claims description 10
- 230000009471 action Effects 0.000 claims description 6
- 238000003825 pressing Methods 0.000 claims description 2
- 238000009423 ventilation Methods 0.000 claims description 2
- 239000000758 substrate Substances 0.000 abstract description 5
- 238000002955 isolation Methods 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 17
- 238000000034 method Methods 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 238000003752 polymerase chain reaction Methods 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 230000009089 cytolysis Effects 0.000 description 4
- 238000000605 extraction Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 238000011901 isothermal amplification Methods 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 230000002934 lysing effect Effects 0.000 description 2
- 201000001178 Bacterial Pneumonia Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000010876 biochemical test Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000005382 thermal cycling Methods 0.000 description 1
Images
Classifications
-
- 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
-
- 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
- B01L3/502738—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 characterised by integrated valves
-
- 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
Definitions
- the invention belongs to the field of life medical detection, and in particular relates to a fully integrated multi-index nucleic acid detection microfluidic chip.
- nucleic acid Since the 1990s, as one of the most basic substances in organisms, nucleic acid has played an increasingly important role in modern biomedicine. It is characterized by strong detection specificity, very easy operation, and technological development. It is mature and has a very short detection time, so it is of great significance in the fields of infectious disease detection, food safety monitoring, and environmental protection. Therefore, rapid detection based on nucleic acid has been recognized as one of the important molecular detection methods.
- nucleic acid-based rapid detection mainly includes the following two methods: polymerase chain reaction (PCR) and isothermal amplification technology.
- PCR polymerase chain reaction
- isothermal amplification technology As a mature nucleic acid amplification technology, PCR has become a technology that cannot be ignored in the field of life medical detection and disease diagnosis after decades of development.
- the temperature cycler performs precise temperature control of each thermal cycling step.
- Nucleic acid isothermal amplification technology only needs a single reaction temperature in the whole process, and has simpler reaction temperature conditions. It is simpler and more convenient than PCR technology in terms of actual operation and instrument requirements, and can get rid of the need for sophisticated equipment. It has shown its good application prospects in clinical and field rapid diagnosis.
- the current nucleic acid detection is mainly based on traditional methods, that is, the first step is to manually extract the nucleic acid in the sample. This step is generally to purchase a commercial nucleic acid extraction kit, and then operate according to the product instructions. A series of complex biochemical tests are carried out in test tubes.
- the following amplification process takes the commonly used polymerase chain reaction amplification as an example. The amplification needs to be manually added to the reaction mixture and then used for the final detection by a commercial instrument. The whole process is time-consuming and labor-intensive, and also requires professional laboratories and professional operators.
- nucleic acid detection methods can no longer meet the needs of the growing business volume of nucleic acid detection.
- some companies have launched commercial fully integrated nucleic acid analyzers, their detection throughput is low.
- high-throughput detection is achieved by stacking multiple control and detection instruments, such as the FilmArray 2.0 system.
- the fully integrated microfluidic system still needs to be improved in the adjustability of the flux.
- the purpose of the present invention is to overcome the defects in the prior art, to solve the complex and precise fluid operations such as sample pretreatment, nucleic acid extraction, amplification and detection in nucleic acid detection based on microfluidic chips, and at the same time use an independent chamber as a reaction area Complete multi-index, high-throughput detection.
- the present invention provides a multi-index nucleic acid detection microfluidic chip, comprising:
- nucleic acid sample pretreatment assembly includes a base plate, an elastic mold and a guide plate, the base plate is provided with a plurality of liquid storage tubes for liquid storage, and the baffle plate is provided with a storage tube and a storage tube.
- the liquid storage tank corresponding to the liquid pipe and the flow channel used to communicate with the liquid storage tank, an elastic mold is sandwiched between the bottom of the base plate and the top of the guide plate, and the elastic mold is deformed between the liquid storage pipe and the liquid storage tank.
- the guide plate is provided with a sample pool for storing processed nucleic acid samples;
- a multi-index nucleic acid amplification assembly includes a main channel and a plurality of amplification chambers, and each amplification chamber and the main channel are used to achieve isolation between different amplification chambers
- the dispersing pipeline is communicated; the main channel is communicated with the sample pool.
- a shunt column is arranged between the main channel and the amplification chamber, and the shunt column divides the space between the main channel and the amplification chamber into three dispersed flow channels, along the direction of the flow of the main channel liquid.
- the dispersion flow channel between the shunt column and the outer wall of the amplification chamber is the first dispersion flow channel and the third dispersion flow channel
- the second dispersion flow channel is between the shunt column and the main channel
- the dispersion flow channel The relationship of the cross-sectional area is the first dispersion flow channel > the second dispersion flow channel > the third dispersion flow channel.
- the cross-sectional area ratio of the first dispersion channel, the second dispersion channel, and the third dispersion channel is 7-12:3-5:1.
- the cross-sectional area ratio of the first dispersion flow channel, the second dispersion flow channel, and the third dispersion flow channel is 10:4:1.
- the shunt column 43 may be a column with a trapezoidal cross-section, the shorter base of the trapezoid faces the direction of liquid flow, and the distance between the side wall of the amplification chamber near the flow direction and the column is greater than The distance between the sidewall of the amplification chamber away from the flow direction and the column.
- the liquid flow direction refers to the direction shown by the arrow in Fig. 2a.
- the baffle plate is correspondingly provided with a lysis solution pool, a ventilation pool, a washing solution pool, an eluent pool, a first waste solution pool, a flow channel, a collection pool, an amplification reagent pool, and a sealing oil Pool and sample pool; wherein, the lysate tube and the lysate pool, the washing solution tube and the washing solution pool, the eluent tube and the eluent pool, the amplification reagent tube and the amplification reagent pool, the sealing oil tube and the sealing oil There is a liquid inlet one-way valve that flows from top to bottom between the pools; the first waste liquid pipe and the first waste liquid pool, the second waste liquid pipe and the sample pool are provided with a bottom
- the liquid inlet check valve, the liquid outlet check valve and the liquid inlet and outlet check valve are realized by the deformation on the elastic film, and the function of the check valve is realized by applying pressure to control the deformation direction of the elastic film.
- the liquid inlet check valve forms a downward one-way valve under the action of pressure;
- the valve forms an upward one-way valve under the action of pressure; under the action of no external pressure, due to the elastic properties of the elastic membrane itself, it is in the state of a closed valve.
- liquid inlet one-way valve and the liquid outlet one-way valve are both sheet-shaped elastic diaphragms including a unilateral fixed part and a first elastic movable part;
- one end of the unilateral fixed part of the liquid inlet check valve is fixedly connected with the outer wall of the liquid storage pipe, and the other end of the unilateral fixed part is fixedly connected with the first elastic movable part.
- the first elastic movable part moves downward and is separated from the liquid outlet of the liquid storage pipe, so that the liquid outlet and the flow channel on the guide plate are in a conducting state, that is, the The liquid inlet check valve is in the open state.
- the first elastic movable part is attached to the liquid outlet, so that the liquid outlet is sealed and isolated. state, that is, the liquid inlet check valve is in a closed state;
- One end of the unilateral fixed part of the liquid outlet check valve is fixedly connected to the outer wall of the liquid storage pipe, and the other end of the unilateral fixed part is fixedly connected to the first elastic movable part.
- the first elastic movable part moves upward and is separated from the liquid inlet of the liquid storage tube, so that the liquid inlet and the flow channel on the baffle plate are in a conductive state , that is, the liquid outlet one-way valve is in an open state, and when the pressure in the liquid storage pipe is positive pressure, the first elastic movable part is attached to the liquid inlet, so that the liquid inlet is in a closed state. , the liquid outlet one-way valve is closed.
- the liquid inlet and outlet check valve includes a liquid inlet check valve, a liquid outlet check valve and a fixing piece located between the liquid outlet and the liquid inlet, and the unilateral fixing part of the liquid inlet check valve is in phase with the fixing piece.
- the unilateral fixed part of the liquid outlet check valve is fixedly connected to the side wall of the liquid storage pipe, and the liquid inlet check valve and the liquid outlet check valve are closed and opened in the same state as above.
- the on-off valve includes a fixed block connected with the flow channel and a second elastic movable part, the second elastic movable part is a part of the elastic mold, and the edge of the second elastic movable part is fixedly connected with the side outer wall of the on-off valve tube;
- the switch valve tube When there is negative pressure in the switch valve tube, the upward protrusion of the second elastic movable part is separated from the fixed block, and the flow passages on both sides of the fixed block are connected; The runners on both sides of the fixed block are closed.
- a guide groove is provided on the surface where the guide plate is attached to the elastic film, and the guide groove is used to communicate with each liquid storage tank on the guide plate.
- the upper part of the liquid storage pipe is provided with a push rod; the bottom of the guide plate is also provided with a detection device.
- each reaction chamber is provided with different primers in advance, so as to realize multi-index amplification.
- the present invention also provides a multi-index nucleic acid amplification detection system, comprising the multi-index nucleic acid detection microfluidic chip.
- the invention proposes a new rapid and automatic multi-index nucleic acid detection device based on a microfluidic chip, which is a rapid detection tool with simple operation and low cost, and is suitable for the detection of various types of detection samples in various detection occasions. Fast multi-index detection.
- FIG. 1 is a schematic structural diagram of a multi-index nucleic acid detection microfluidic chip of the present invention, wherein Figure a is a schematic structural diagram, and Figure b is an exploded view;
- Figure 2 is a schematic diagram of the principle structure of a multi-index amplification chip, wherein Figure a is a schematic diagram of a partial structure, and Figure b is a schematic diagram of the flow direction of the liquid over time;
- Figure 3 is a schematic diagram of some valves, in which a is a liquid inlet check valve, b is a liquid outlet check valve, c is a liquid inlet and outlet check valve, and d is an on-off valve.
- a microfluidic chip for multi-index nucleic acid detection based on a microfluidic chip proposed by the present invention includes:
- the nucleic acid sample pretreatment assembly includes a substrate 1, an elastic mold 2 and a guide plate 3, the substrate 1 is provided with a plurality of liquid storage tubes for liquid storage, the guide plate 2 There is a liquid storage tank corresponding to the liquid storage pipe and a flow channel for connecting the liquid storage tank, an elastic mold 2 is sandwiched between the bottom of the base plate 1 and the top of the guide plate 3, and the liquid storage pipe is connected to the storage tank.
- the liquid pools are connected or closed by the deformation of the elastic mold 2, and the guide plate 3 is provided with a sample pool for storing the processed nucleic acid samples.
- the liquid storage pipes there are a plurality of the liquid storage pipes, as shown in FIG. 1 , along the direction from left to right are the lysing liquid pipe 11 , the vent pipe 12 , the washing liquid pipe 13 , the eluent pipe 14 , and the first waste liquid pipe. 15.
- On-off valve pipe 16 collecting pipe 17, amplification reagent pipe 18, sealing oil pipe 19 and second waste liquid pipe 10; the baffle 2 is provided with a lysing solution pool 21, aeration pool 22, washing solution pool correspondingly 23.
- a guide groove is provided on the surface where the guide plate is attached to the elastic film, the position of the guide groove corresponds to the through hole, and the guide groove is used to control the microfluid flowing out of the through hole.
- Conduct drainage The upper part of the liquid storage pipe is provided with a push rod, which is used to adjust the pressure in the liquid storage tank and provide fluid forward power.
- a detection device is also provided at the bottom of the deflector.
- the liquid inlet check valve 5 and the liquid outlet check valve 6 are both sheet-shaped elastic diaphragms including a unilateral fixed portion and a first elastic movable portion.
- One end of the unilateral fixed portion 51 of the liquid inlet check valve is fixedly connected to the outer wall of the liquid storage pipe, and the other end of the unilateral fixed portion is connected to the first elastic movable portion 52 of the liquid inlet check valve.
- Fixed connection when there is a positive pressure in the liquid storage tube, the first elastic movable part moves downward and is separated from the liquid outlet of the liquid storage tube, so that the liquid outlet and the flow channel on the baffle plate are in a guiding position.
- the liquid inlet one-way valve In the open state, that is, the liquid inlet one-way valve is in the open state, when the pressure in the liquid storage pipe is less than the flow channel pressure or negative pressure, the first elastic movable part is in contact with the liquid outlet, so that the The liquid outlet is in a closed and isolated state, that is, the liquid inlet check valve is in a closed state.
- One end of the unilateral fixed part of the liquid outlet one-way valve 6 is fixedly connected to the outer wall of the liquid storage pipe, and the other end is fixedly connected to the first elastic movable part of the liquid outlet one-way valve.
- the first elastic movable part moves upward and separates from the liquid inlet of the liquid storage pipe, so that the liquid inlet and the flow channel on the baffle plate are in a conducting state, that is, The liquid outlet one-way valve is in the open state
- the first elastic movable part is attached to the liquid inlet, so that the liquid inlet is in a closed and isolated state, so The liquid one-way valve is closed.
- the liquid inlet and outlet check valve 7 includes a liquid inlet check valve, a liquid outlet check valve and a fixing piece located between the liquid outlet and the liquid inlet.
- the unilateral fixing part of the liquid inlet check valve is connected to the fixing piece.
- the unilateral fixed part of the liquid outlet one-way valve is fixedly connected to the side wall of the liquid storage pipe, and the closing and opening states of the liquid inlet one-way valve and the liquid outlet one-way valve are the same as above.
- the on-off valve 8 includes a fixed block 81 connected to the flow channel and a second elastic movable portion 82, the second elastic movable portion is a part of the elastic mold 2, and the edge of the second elastic movable portion is connected to the side of the on-off valve tube.
- the outer wall is fixedly connected; when the inside of the switch valve tube is under negative pressure, the second elastic movable part protrudes upwards and separates from the fixed block, and the flow channels on both sides of the fixed block are connected; when the inside of the switch valve tube is under positive pressure, the second elastic movable part protrudes upwards It is in close contact with the fixed block, and the flow channels on both sides of the fixed block are closed.
- the first waste liquid pool is provided with a silica gel membrane for collecting DNA; the silica gel membrane can realize the capture of nucleic acid in the sample, and after the capture, the elution of DNA can be realized by adding an eluent.
- a multi-index nucleic acid amplification assembly 4 the multi-index nucleic acid amplification assembly 4 includes a main channel 41 and a plurality of amplification chambers 42, and each amplification chamber 42 and the main channel 41 pass through to achieve different amplifications
- the isolated dispersion pipes between the chambers 42 communicate; the main channel 41 communicates with the sample cell.
- a shunt column 43 is arranged between the main channel 41 and the amplification chamber 42 , and the shunt column divides the space between the main channel and the amplification chamber into three scattered channels, along the The flow direction of the main channel liquid, the dispersion channel between the distribution column 43 and the outer wall of the amplification chamber 42 is the first dispersion channel 44 and the third dispersion channel 46, between the distribution column 43 and the main channel 41 is the second dispersion flow channel 45, and the relationship of the cross-sectional area of the dispersion flow channel is the first dispersion flow channel>the second dispersion flow channel>the third dispersion flow channel.
- cross-sectional area ratio of the first dispersion channel, the second dispersion channel, and the third dispersion channel may be 7-12:3-5:1, specifically 10:4:1.
- the shunt column 43 can be a column with a trapezoidal cross-section, and the shorter side of the trapezoid faces the direction of liquid flow. As shown in FIG. 2a, the direction of the arrow indicates the flow direction of the liquid.
- v1/v2/v3 represent the cross-sections of the first dispersion channel, the second dispersion channel, and the third dispersion channel, respectively.
- the process of dispersing the sample liquid in the sample pool to each amplification chamber through the main channel is as follows, as shown in Figure 2b: S1.
- S2. Since the resistance faced by the second dispersion channel > the resistance faced by the first dispersion channel, the sample liquid enters the amplification chamber along the first dispersion channel; S3.
- S3. When After the amplification chamber is full, the sample liquid encounters the third dispersion flow channel. At this time, since the resistance faced by the third dispersion flow channel > the resistance faced by the second dispersion flow channel, the sample liquid will pass through the second dispersion flow channel along the way.
- the channel flows forward; S4.
- a section of air column is left at the third dispersion flow channel of the amplification chamber, and the existence of the air column makes the samples in different amplification chambers stably separated; S5.
- Pressure is applied to the sealed oil pool 29 for The oil separating the samples flows into the main channel. Due to the good wettability between the oil and the chip, the oil can drive out the air column stored in the third dispersion flow and realize the isolation between different amplification chambers.
- step (3) Apply positive pressure to the vent pipe while keeping the on-off valve v6 closed, and introduce air into the pipe for 40s to completely remove the residual liquid on the silica gel membrane, and the residual liquid flows to the first waste liquid pipe along the same path in step (2);
- Multi-index amplification can be achieved by pre-spotting different primers in each amplification chamber.
- different primers can be pre-spotted in each amplification chamber. Since each amplification chamber does not interfere with each other, after nucleic acid amplification, it is possible to accurately determine which bacteria caused pneumonia; the judgment is marked as if it is pre-pointed with the amplification chamber. If the primers can be amplified, it means that it contains the pathogenic bacteria corresponding to the primers. If the primers on the amplification chamber cannot be amplified, it means that it does not contain the pathogenic bacteria corresponding to the primers. bacteria.
- the invention proposes a new rapid and automatic multi-index nucleic acid detection device based on a microfluidic chip, which is a rapid detection tool with simple operation and low cost, and is suitable for the detection of various types of detection samples in various detection occasions.
- Fast multi-index detection Multi-target amplification can be achieved by pre-spotting different primers in each amplification chamber.
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Analytical Chemistry (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Immunology (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Genetics & Genomics (AREA)
- Dispersion Chemistry (AREA)
- Hematology (AREA)
- Clinical Laboratory Science (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
La présente invention concerne une puce microfluidique multi index entièrement intégrée pour le test d'acide nucléique, comprenant les éléments suivants : un ensemble de prétraitement d'échantillon d'acide nucléique, l'ensemble de prétraitement d'échantillon d'acide nucléique comprenant un substrat, un moule élastique et un plateau de guidage d'écoulement, une pluralité de tubes de stockage de liquide pour stocker du liquide étant disposés sur le substrat, des réservoirs de stockage de liquide correspondant aux tubes de stockage de liquide et des canaux d'écoulement pour communiquer avec les réservoirs de stockage de liquide sont disposés sur le plateau de guidage d'écoulement, le moule élastique est intercalé entre le fond du substrat et le haut du plateau de guidage d'écoulement, les tubes de stockage de liquide et les réservoirs de stockage de liquide sont en communication ou fermés par la déformation du moule élastique, et le plateau de guidage d'écoulement est muni d'un réservoir d'échantillon pour stocker un échantillon d'acide nucléique traité ; et un ensemble multi-index d'amplification d'acide nucléique, comprenant un canal d'écoulement principal et une pluralité de chambres d'amplification, chacune des chambres d'amplification étant en communication avec le canal d'écoulement principal par l'intermédiaire d'un conduit de dispersion pour assurer l'isolation entre différentes chambres d'amplification, et le canal d'écoulement principal étant en communication avec le réservoir d'échantillons.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110188839.2 | 2021-02-19 | ||
CN202110188839.2A CN112795474A (zh) | 2021-02-19 | 2021-02-19 | 一种全集成多指标核酸检测微流控芯片 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2022174472A1 true WO2022174472A1 (fr) | 2022-08-25 |
Family
ID=75815188
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CN2021/078004 WO2022174472A1 (fr) | 2021-02-19 | 2021-02-26 | Puce microfluidique multi-index entièrement intégrée pour le test d'acide nucléique |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN112795474A (fr) |
WO (1) | WO2022174472A1 (fr) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115322888A (zh) * | 2022-09-14 | 2022-11-11 | 翊新诊断技术(苏州)有限公司 | 微流控囊袋式循环pcr芯片及其应用 |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023206096A1 (fr) * | 2022-04-26 | 2023-11-02 | 广州国家实验室 | Dispositif de transfert de liquide et dispositif de transfert de liquide parallèle à trajets multiples |
CN114570449B (zh) * | 2022-04-26 | 2022-08-16 | 广州国家实验室 | 液体转移装置及多路并联的液体转移装置 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN208649284U (zh) * | 2018-05-23 | 2019-03-26 | 博奥生物集团有限公司 | 一种基于微流控的全自动dna提取扩增模块 |
CN110616138A (zh) * | 2019-10-09 | 2019-12-27 | 山东百骏生物科技有限公司 | 一种分腔室多指标核酸扩增微流控芯片 |
CN110841730A (zh) * | 2019-10-21 | 2020-02-28 | 清华大学 | 一种微流控芯片及肿瘤dna检测芯片 |
CN111389474A (zh) * | 2020-04-09 | 2020-07-10 | 清华大学 | 一种用于样本分散的微流控芯片及其制备方法与应用 |
CN111644213A (zh) * | 2020-05-25 | 2020-09-11 | 清华大学 | 一种流体操控装置及流体控制方法 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2394152B1 (fr) * | 2009-02-03 | 2019-05-01 | ANDE Corporation | Purification d'acide nucléique |
US8720036B2 (en) * | 2010-03-09 | 2014-05-13 | Netbio, Inc. | Unitary biochip providing sample-in to results-out processing and methods of manufacture |
CN207552287U (zh) * | 2017-09-20 | 2018-06-29 | 清华大学 | 一种微流控芯片及芯片组件 |
CN107502544B (zh) * | 2017-09-20 | 2023-12-15 | 杭州梓晶生物有限公司 | 一种微流控芯片检测控制系统 |
CN111647498B (zh) * | 2020-05-25 | 2022-03-22 | 杭州梓晶生物有限公司 | 一种一体化自助式核酸检测装置及其使用方法 |
-
2021
- 2021-02-19 CN CN202110188839.2A patent/CN112795474A/zh active Pending
- 2021-02-26 WO PCT/CN2021/078004 patent/WO2022174472A1/fr active Application Filing
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN208649284U (zh) * | 2018-05-23 | 2019-03-26 | 博奥生物集团有限公司 | 一种基于微流控的全自动dna提取扩增模块 |
CN110616138A (zh) * | 2019-10-09 | 2019-12-27 | 山东百骏生物科技有限公司 | 一种分腔室多指标核酸扩增微流控芯片 |
CN110841730A (zh) * | 2019-10-21 | 2020-02-28 | 清华大学 | 一种微流控芯片及肿瘤dna检测芯片 |
CN111389474A (zh) * | 2020-04-09 | 2020-07-10 | 清华大学 | 一种用于样本分散的微流控芯片及其制备方法与应用 |
CN111644213A (zh) * | 2020-05-25 | 2020-09-11 | 清华大学 | 一种流体操控装置及流体控制方法 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115322888A (zh) * | 2022-09-14 | 2022-11-11 | 翊新诊断技术(苏州)有限公司 | 微流控囊袋式循环pcr芯片及其应用 |
CN115322888B (zh) * | 2022-09-14 | 2024-01-19 | 翊新诊断技术(苏州)有限公司 | 微流控囊袋式循环pcr芯片及其应用 |
Also Published As
Publication number | Publication date |
---|---|
CN112795474A (zh) | 2021-05-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2022174472A1 (fr) | Puce microfluidique multi-index entièrement intégrée pour le test d'acide nucléique | |
CN111647498B (zh) | 一种一体化自助式核酸检测装置及其使用方法 | |
CN107723210B (zh) | 新型核酸检测微流控芯片装置 | |
CN204727866U (zh) | 一种集核酸扩增和微阵列检测于一体的微流控装置 | |
WO2021237396A1 (fr) | Dispositif intégré de détection d'acides nucléiques en libre-service et son procédé d'utilisation | |
WO2022174471A1 (fr) | Puce microfluidique entièrement intégrée pour le test d'acide nucléique des agents pathogènes | |
CN109852530A (zh) | 一种集循环肿瘤细胞捕获、裂解与核酸检测于一体的微流控芯片及其装置以及方法 | |
CN111909835A (zh) | 一种封闭式微流控核酸检测卡盒 | |
CN101813695B (zh) | 用于微囊藻毒素快速检测的微流控芯片及其制备方法 | |
CN108300640B (zh) | 一种用于核酸自动化提取和检测的微流控芯片 | |
CN111621417B (zh) | 一种用于生物样本处理的微流控芯片及其使用方法 | |
CN213012800U (zh) | 一种防止交叉污染的核酸扩增微流控芯片 | |
CN111760601A (zh) | 一种集成液路切换阀的微流控芯片及核酸检测方法 | |
CN210522535U (zh) | 一种微流控芯片 | |
CN217499275U (zh) | 一种全封闭核酸检测芯片 | |
CN104946505B (zh) | 实现pcr的微流控芯片及实时pcr的病毒快速检测装置 | |
WO2022152244A1 (fr) | Puce d'amplification isotherme à médiation par les boucles | |
CN115651807B (zh) | 核酸检测芯片和核酸检测方法 | |
CN115400806A (zh) | 一体化核酸提取微流控芯片盒和核酸提取及检测方法 | |
CN211620516U (zh) | 一种核酸微流控制检测系统 | |
CN216808819U (zh) | 基于移动柱塞的气动一体式pcr检测试剂盒 | |
CN211035866U (zh) | 一种柱塞式核酸检测一体化卡盒 | |
CN107216998B (zh) | 迅速测量油田污水和成品油中细菌含量的自动化装置 | |
CN212560268U (zh) | 一种双层微流控芯片 | |
CN103055984B (zh) | 一种微流管道内驱动装置 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 21926189 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 21926189 Country of ref document: EP Kind code of ref document: A1 |