Micro-fluidic chip and kit suitable for comparative genome hybridization pretreatment
By designing an integrated microfluidic chip, the problems of cumbersome manual operations and large space requirements in comparative genomics hybridization preprocessing were solved, enabling automated operation and efficient construction of labeled product libraries.
Patent Information
- Application Number
- CN202422610887.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-28
- Publication Date
- 2025-12-02
- Estimated Expiration
- 2034-10-28
AI Technical Summary
The construction of marker product libraries for pre-hybridization of comparative genomes in existing technologies is cumbersome, requires manual operation, demands large experimental space, and lacks automated tools and integrated equipment.
A microfluidic chip was designed, which includes modules for digestion and ligation, polymerase chain reaction, purification and fragmentation, and labeling. It integrates a reagent pre-loading area and a reaction area, and uses electromagnetic microvalve and pneumatic microvalve to achieve automated operation, reducing manual steps and saving experimental space.
It automates the construction of labeled product libraries, reduces manual operations, improves experimental efficiency and stability, and saves experimental space and equipment usage.
Smart Images
Figure CN223620383U_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of detection technology, specifically relating to a microfluidic chip and reagent kit suitable for preprocessing comparative genomic hybridization. Background Technology
[0002] The basic principle of comparative genomics is to specifically hybridize high-density deoxyribonucleic acid probes on a fixed matrix with fluorescently labeled sample deoxyribonucleic acid, scan to obtain the fluorescence signal value of the corresponding probe, and analyze the copy number abnormality of the sample under test based on the fluorescence signal value.
[0003] Amniotic fluid contains fetal cells, from which fetal genomic DNA can be extracted. Comparative genomics involves digesting the extracted genomic DNA with Nsp I (viral non-structural protein type I) enzymes to obtain genomic DNA fragments with sticky ends. Adapters specifically recognizing these sticky ends are then added to both ends of the digested product. Using primers specifically recognizing these adapters, polymerase chain reaction (PCR) amplification is performed to obtain high-abundance genomic DNA. This is purified using magnetic beads, and washing removes enzymes, deoxyribonucleotide triphosphates, primers, etc., yielding purified PCR amplification products. Fragmentation enzymes are used to further break the genomic DNA into smaller fragments, and terminal deoxynucleotidyl transferases are used to label the ends of these small fragments, constructing a labeled product library. The labeled product library is added to a microarray for hybridization, followed by washing and staining to remove unhybridized DNA. Finally, it is scanned using a microarray scanner, and analysis software is used to analyze chromosome copy number variations.
[0004] The construction of labeled product libraries is a cumbersome process. Current library construction methods based on comparative genomics are still purely manual, lacking automated tools or equipment. The drawbacks of existing technologies include tedious manual operations and processing, resulting in complex procedures and a high workload. Furthermore, there is currently no microfluidic chip and supporting device that can integrate prehybridization library construction using comparative genomics technology in a step-by-step manner. Microfluidic chips capable of integrating operations such as shaking and mixing, and polymerase chain reaction (PCR), require only centimeter-level experimental space. The disadvantages of existing technologies include large experimental space requirements and the need for instruments such as shaking and mixing equipment and polymerase chain reaction apparatus. Summary of the Invention
[0005] The purpose of this invention is to overcome the shortcomings of the prior art and provide a microfluidic chip and reagent kit suitable for preprocessing comparative genomic hybridization.
[0006] In order to achieve the purpose of this utility model, the following technical solutions will be adopted.
[0007] A microfluidic chip suitable for preprocessing comparative genomic hybridization, the microfluidic chip comprising a digestion and ligation and polymerase chain reaction (PCR) module substrate (28) and a purification and fragmentation and labeling module substrate (29), a digestion and ligation and PCR module cover plate (30) and a purification and fragmentation and labeling module cover plate (31), an electromagnetic microvalve layer (32) and a thin film layer disposed between the digestion and ligation and PCR module substrate (28) and the digestion and ligation and PCR module cover plate (30), and an electromagnetic microvalve layer (33) and a thin film layer disposed between the purification and fragmentation and labeling module substrate (29) and the purification and fragmentation and labeling module cover plate (31); the digestion and ligation and PCR module substrate (28) and the purification and fragmentation and labeling module substrate (29) are provided with a reagent pre-loading area and a reaction area, the reagent pre-loading area and the reaction area being interconnected, wherein:
[0008] The reagent pre-loading area includes a digestion reservoir, a connection reservoir, a polymerase chain reaction amplification and detection reservoir, a purification reservoir, a fragmentation reservoir, and a labeling reservoir.
[0009] The digestion reservoir includes a nuclease-free water reservoir (1), a viral non-structural protein type I buffer reservoir (2), a bovine serum albumin reservoir (3), and a viral non-structural protein type I enzyme reservoir (4).
[0010] The ligation reservoir includes a phage T4 genome deoxyribonucleic acid ligation buffer reservoir or primer adapter reservoir (6) and a phage T4 genome deoxyribonucleic acid ligase reservoir (11).
[0011] The polymerase chain reaction amplification and detection reservoir includes a nuclease-free water reservoir, a deoxyribonucleic acid polymerase buffer reservoir, a guanine-cytosine fusion reagent reservoir, a deoxyribonucleoside triphosphate reservoir, a polymerase chain reaction primer reservoir, or a deoxyribonucleic acid polymerase reservoir (9).
[0012] The purification storage tank includes a purification magnetic bead storage tank (13), a purification washing solution storage tank (14), an elution solution storage tank (15), and a nuclease-free water storage tank (22);
[0013] The fragmented storage tank includes a fragmented buffer solution storage tank (16) and a fragmented reagent storage tank (25);
[0014] The labeling reservoir includes a deoxynucleotide terminal transferase buffer reservoir (18), a deoxyribonucleic acid labeling reagent reservoir (26), and a deoxynucleotide terminal transferase reservoir (27);
[0015] The reaction zone includes a digestion reaction pool (5), a connection reaction pool (7), polymerase chain reaction (PCR) reaction pools 1-4 (12), a purification reaction pool (24), a fragmentation reaction pool (17), a labeling reaction pool (20), a PCR product mixing pool (10), a prehybridization library pool (21), a PCR reagent mixing pool (8), a labeling reagent mixing pool (19), and a purified product pool (23).
[0016] in:
[0017] The digestion reaction tank (5) is connected to the bovine serum albumin storage tank (3) through a microchannel, and a pneumatic microvalve or an electromagnetic microvalve is provided on the microchannel.
[0018] The nuclease-free water storage tank (1), the viral non-structural protein type I buffer storage tank (2), and the viral non-structural protein type I enzyme storage tank (4) are respectively connected to the bovine serum albumin storage tank (3) through microchannels, and electromagnetic microvalve is provided on the microchannels;
[0019] The connecting reaction tank (7) is connected to the digestion reaction tank (5) through a microchannel, and a pneumatic microvalve or an electromagnetic microvalve is provided on the microchannel;
[0020] The genomic DNA ligation buffer reservoir or primer adapter reservoir (6) of phage T4 and the genomic DNA ligase reservoir (11) of phage T4 are respectively connected to the ligation reaction pool (7) through microchannels, and electromagnetic microvalve is provided on the microchannels;
[0021] The polymerase chain reaction reagent mixing tank (8) is connected to the connecting reaction tank (7) through a microchannel, and a pneumatic microvalve or electromagnetic microvalve is provided on the microchannel;
[0022] The nuclease-free water storage tank (1) is connected to the nuclease-free water storage tank, the deoxyribonucleic acid polymerase buffer storage tank, the guanine-cytosine fusion reagent storage tank, the deoxyribonucleoside triphosphate storage tank, the polymerase chain reaction primer storage tank, or the deoxyribonucleic acid polymerase storage tank (9) through microchannels, and electromagnetic microvalve is provided on the microchannels;
[0023] The polymerase chain reaction reagent mixing pool (8) is connected to the polymerase chain reaction reaction pool 1-4 (12) through a microchannel, and the polymerase chain reaction reaction pool 1-4 (12) is connected to the polymerase chain reaction product mixing pool (10) through a microchannel. A pneumatic microvalve or an electromagnetic microvalve is provided on the microchannel.
[0024] The purification storage tank includes a purification magnetic bead storage tank (13), a purification washing solution storage tank (14), an elution solution storage tank (15), and a nuclease-free water storage tank (22), which are connected to the purification reaction tank (24) through microchannels, and electromagnetic microvalve is provided on the microchannels;
[0025] The purification reaction pool (24) is connected to the purification product pool (23) through a microchannel. The purification product pool (23) is connected to the fragmentation reaction pool (17) through a microchannel. The fragmentation reaction pool (17) is connected to the labeling reagent mixing pool (19) through a microchannel. The labeling reagent mixing pool (19) is connected to the labeling reaction pool (20) through a microchannel. The labeling reaction pool (20) is connected to the prehybridization library pool (21) through a microchannel. A pneumatic microvalve or an electromagnetic microvalve is provided on the microchannel.
[0026] The fragmented buffer solution reservoir (16) and the fragmented reagent reservoir (25) are respectively connected to the microchannel between the purified product reservoir (23) and the fragmented reaction reservoir (17) via a pneumatic microvalve or an electromagnetic microvalve. The microchannel connecting the fragmented buffer solution reservoir (16) to the pneumatic microvalve or electromagnetic microvalve to the fragmented reaction reservoir (17) and the microchannel connecting the fragmented reagent reservoir (25) to the pneumatic microvalve or electromagnetic microvalve to the fragmented reaction reservoir (17) are provided with electromagnetic microvalve.
[0027] The labeling reservoir includes a deoxynucleotide terminal transferase buffer reservoir (18), a deoxyribonucleic acid labeling reagent reservoir (26), and a deoxynucleotide terminal transferase reservoir (27), which are respectively connected to the labeling reagent mixing pool (19) through microchannels, and electromagnetic microvalve is provided on the microchannels;
[0028] The polymerase chain reaction product mixture (10) in the digestion and ligation and polymerase chain reaction module substrate (28) is transferred manually to the purification magnetic bead reservoir (13) in the purification and fragmentation and labeling module substrate (29).
[0029] As a preferred embodiment of this utility model, both the pneumatic microvalve and the electromagnetic microvalve are disposed in the electromagnetic microvalve layer.
[0030] As a preferred embodiment of the present invention, the purification reaction tank (24) has magnetic microspheres.
[0031] As a preferred embodiment of the present invention, the reaction zone is provided with a temperature control device (34), which includes a temperature control device 1 (34-1), a temperature control device 2 (34-2), a temperature control device 3 (34-3), and a temperature control device 4 (34-4). The temperature control device 1 is responsible for controlling the temperature of the digestion reaction tank (5) and the connecting reaction tank (7); the temperature control device 2 is responsible for controlling the temperature of the polymerase chain reaction tanks 1-4 (12); the temperature control device 3 is responsible for controlling the temperature of the fragmentation reaction tank (17); and the temperature control device 4 is responsible for controlling the temperature of the labeling reaction tank (20).
[0032] As a preferred embodiment of this utility model, the temperature control device 1 (34-1) is located at the bottom of the digestion and ligation and polymerase chain reaction module cover (30) and at a position corresponding to the digestion reaction pool (5) and ligation reaction pool (7) in the digestion and ligation and polymerase chain reaction module substrate (28); the temperature control device 2 (34-2) is located at the bottom of the digestion and ligation and polymerase chain reaction module cover (30) and at a position corresponding to the polymerase chain reaction pools 1-4 (12) in the digestion and ligation and polymerase chain reaction module substrate (28); the temperature control device 3 (34-3) is located at the bottom of the purification and fragmentation and labeling module cover (31) and at a position corresponding to the fragmentation reaction pool (17) in the purification and fragmentation and labeling module substrate (29); the temperature control device 4 (34-4) is located at the bottom of the purification and fragmentation and labeling module cover (31) and at a position corresponding to the labeling reaction pool (20) in the purification and fragmentation and labeling module substrate (29).
[0033] A reagent kit includes the aforementioned microfluidic chip.
[0034] Beneficial effects:
[0035] 1) It provides an automated tool that greatly reduces manual operation steps. Operations such as solution preparation, shaking and mixing, and polymerase chain reaction can all be completed by microfluidic chip, which improves experimental efficiency and experimental stability.
[0036] 2) Saves experimental space. Due to the integrated operation of the microfluidic chip, the use of instruments such as shaking instruments, mixing instruments and polymerase chain reaction instruments is reduced. Attached Figure Description
[0037] Figure 1 This is a schematic diagram of the layer structure of the microfluidic chip described in this utility model;
[0038] Figure 2 This is a schematic diagram of the substrate structure in this utility model;
[0039] Figure 3This is a schematic diagram of the cover plate in this utility model. Detailed Implementation
[0040] To facilitate understanding by those skilled in the art, the present invention will be further described below with reference to embodiments and accompanying drawings. The content mentioned in the embodiments is not intended to limit the present invention.
[0041] As an embodiment of this utility model, such as Figures 1 to 3 As shown, a microfluidic chip suitable for preprocessing comparative genomic hybridization includes a digestion and ligation and polymerase chain reaction (PCR) module substrate (28) and a purification and fragmentation and labeling module substrate (29); a digestion and ligation and PCR module cover plate (30) and a purification and fragmentation and labeling module cover plate (31); an electromagnetic microvalve layer (32) and a thin film layer disposed between the digestion and ligation and PCR module substrate (28) and the digestion and ligation and PCR module cover plate (30); and an electromagnetic microvalve layer (33) and a thin film layer disposed between the purification and fragmentation and labeling module substrate (29) and the purification and fragmentation and labeling module cover plate (31); the digestion and ligation and PCR module substrate (28) and the purification and fragmentation and labeling module substrate (29) are provided with a reagent pre-loading area and a reaction area, which are connected to each other, wherein:
[0042] The reagent pre-loading area includes a digestion reservoir, a connection reservoir, a polymerase chain reaction amplification and detection reservoir, a purification reservoir, a fragmentation reservoir, and a labeling reservoir.
[0043] The digestion reservoir includes a nuclease-free water reservoir (1), a viral non-structural protein type I buffer reservoir (2), a bovine serum albumin reservoir (3), and a viral non-structural protein type I enzyme reservoir (4).
[0044] The ligation reservoir includes a phage T4 genome deoxyribonucleic acid ligation buffer reservoir or primer adapter reservoir (6) and a phage T4 genome deoxyribonucleic acid ligase reservoir (11).
[0045] The polymerase chain reaction amplification and detection reservoir includes a nuclease-free water reservoir, a deoxyribonucleic acid polymerase buffer reservoir, a guanine-cytosine fusion reagent reservoir, a deoxyribonucleoside triphosphate reservoir, a polymerase chain reaction primer reservoir, or a deoxyribonucleic acid polymerase reservoir (9).
[0046] The purification storage tank includes a purification magnetic bead storage tank (13), a purification washing solution storage tank (14), an elution solution storage tank (15), and a nuclease-free water storage tank (22);
[0047] The fragmented storage tank includes a fragmented buffer solution storage tank (16) and a fragmented reagent storage tank (25);
[0048] The labeling reservoir includes a deoxynucleotide terminal transferase buffer reservoir (18), a deoxyribonucleic acid labeling reagent reservoir (26), and a deoxynucleotide terminal transferase reservoir (27);
[0049] The reaction zone includes a digestion reaction pool (5), a connection reaction pool (7), polymerase chain reaction (PCR) reaction pools 1-4 (12), a purification reaction pool (24), a fragmentation reaction pool (17), a labeling reaction pool (20), a PCR product mixing pool (10), a prehybridization library pool (21), a PCR reagent mixing pool (8), a labeling reagent mixing pool (19), and a purified product pool (23).
[0050] in:
[0051] The digestion reaction tank (5) is connected to the bovine serum albumin storage tank (3) through a microchannel, and a pneumatic microvalve or an electromagnetic microvalve is provided on the microchannel.
[0052] The nuclease-free water storage tank (1), the viral non-structural protein type I buffer storage tank (2), and the viral non-structural protein type I enzyme storage tank (4) are respectively connected to the bovine serum albumin storage tank (3) through microchannels, and electromagnetic microvalve is provided on the microchannels;
[0053] The connecting reaction tank (7) is connected to the digestion reaction tank (5) through a microchannel, and a pneumatic microvalve or an electromagnetic microvalve is provided on the microchannel;
[0054] The genomic DNA ligation buffer reservoir or primer adapter reservoir (6) of phage T4 and the genomic DNA ligase reservoir (11) of phage T4 are respectively connected to the ligation reaction pool (7) through microchannels, and electromagnetic microvalve is provided on the microchannels;
[0055] The polymerase chain reaction reagent mixing tank (8) is connected to the connecting reaction tank (7) through a microchannel, and a pneumatic microvalve or electromagnetic microvalve is provided on the microchannel;
[0056] The nuclease-free water storage tank (1) is connected to the nuclease-free water storage tank, the deoxyribonucleic acid polymerase buffer storage tank, the guanine-cytosine fusion reagent storage tank, the deoxyribonucleoside triphosphate storage tank, the polymerase chain reaction primer storage tank, or the deoxyribonucleic acid polymerase storage tank (9) through microchannels, and electromagnetic microvalve is provided on the microchannels;
[0057] The polymerase chain reaction reagent mixing pool (8) is connected to the polymerase chain reaction reaction pool 1-4 (12) through a microchannel, and the polymerase chain reaction reaction pool 1-4 (12) is connected to the polymerase chain reaction product mixing pool (10) through a microchannel. A pneumatic microvalve or an electromagnetic microvalve is provided on the microchannel.
[0058] The purification storage tank includes a purification magnetic bead storage tank (13), a purification washing solution storage tank (14), an elution solution storage tank (15), and a nuclease-free water storage tank (22), which are connected to the purification reaction tank (24) through microchannels, and electromagnetic microvalve is provided on the microchannels;
[0059] The purification reaction pool (24) is connected to the purification product pool (23) through a microchannel. The purification product pool (23) is connected to the fragmentation reaction pool (17) through a microchannel. The fragmentation reaction pool (17) is connected to the labeling reagent mixing pool (19) through a microchannel. The labeling reagent mixing pool (19) is connected to the labeling reaction pool (20) through a microchannel. The labeling reaction pool (20) is connected to the prehybridization library pool (21) through a microchannel. A pneumatic microvalve or an electromagnetic microvalve is provided on the microchannel.
[0060] The fragmented buffer solution reservoir (16) and the fragmented reagent reservoir (25) are respectively connected to the microchannel between the purified product reservoir (23) and the fragmented reaction reservoir (17) via a pneumatic microvalve or an electromagnetic microvalve. The microchannel connecting the fragmented buffer solution reservoir (16) to the pneumatic microvalve or electromagnetic microvalve to the fragmented reaction reservoir (17) and the microchannel connecting the fragmented reagent reservoir (25) to the pneumatic microvalve or electromagnetic microvalve to the fragmented reaction reservoir (17) are provided with electromagnetic microvalve.
[0061] The labeling reservoir includes a deoxynucleotide terminal transferase buffer reservoir (18), a deoxyribonucleic acid labeling reagent reservoir (26), and a deoxynucleotide terminal transferase reservoir (27), which are respectively connected to the labeling reagent mixing pool (19) through microchannels, and electromagnetic microvalve is provided on the microchannels;
[0062] The polymerase chain reaction product mixture (10) in the digestion and ligation and polymerase chain reaction module substrate (28) is transferred manually to the purification magnetic bead reservoir (13) in the purification and fragmentation and labeling module substrate (29).
[0063] As an embodiment of this utility model, such as Figure 1 As shown, both the pneumatic microvalve and the electromagnetic microvalve are disposed in the electromagnetic microvalve layer (32).
[0064] As an embodiment of this utility model, such as Figure 2 As shown, the purification reaction cell (24) has magnetic microspheres.
[0065] As an embodiment of this utility model, such as Figure 2 and Figure 3 As shown, the reaction zone is equipped with a temperature control device (34), which includes temperature control device 1 (34-1), temperature control device 2 (34-2), temperature control device 3 (34-3), and temperature control device 4 (34-4). Temperature control device 1 is responsible for controlling the temperature of the digestion reaction tank (5) and the connecting reaction tank (7); temperature control device 2 is responsible for controlling the temperature of polymerase chain reaction tanks 1-4 (12); temperature control device 3 is responsible for controlling the temperature of the fragmentation reaction tank (17); and temperature control device 4 is responsible for controlling the temperature of the labeling reaction tank (20).
[0066] As an embodiment of this utility model, such as Figure 2 and Figure 3 As shown, the temperature control device 1 (34-1) is located at the bottom of the digestion and ligation and polymerase chain reaction module cover (30) and at a position corresponding to the digestion reaction pool (5) and ligation reaction pool (7) in the digestion and ligation and polymerase chain reaction module substrate (28); the temperature control device 2 (34-2) is located at the bottom of the digestion and ligation and polymerase chain reaction module cover (30) and at a position corresponding to the polymerase chain reaction reaction pools 1-4 (12) in the digestion and ligation and polymerase chain reaction module substrate (28); the temperature control device 3 (34-3) is located at the bottom of the purification and fragmentation and labeling module cover (31) and at a position corresponding to the fragmentation reaction pool (17) in the purification and fragmentation and labeling module substrate (29); the temperature control device 4 (34-4) is located at the bottom of the purification and fragmentation and labeling module cover (31) and at a position corresponding to the labeling reaction pool (20) in the purification and fragmentation and labeling module substrate (29).
[0067] As an embodiment of this utility model, such as Figures 1 to 3 As shown, a reagent kit includes the aforementioned microfluidic chip.
[0068] As an embodiment of this utility model, such as Figures 1 to 3 As shown, the running conditions of each program in the process of building the labeled product library by the microfluidic chip are as follows:
[0069] 1. Digestion
[0070] Run the digestion program:
[0071]
[0072] 2. Connection
[0073] Run the connection program;
[0074]
[0075] 3. Polymerase chain reaction amplification and detection
[0076] Running the polymerase chain reaction amplification program:
[0077]
[0078]
[0079] 4. Purification
[0080] 5. Quantitative
[0081] 6. Fragmentation and electrophoretic detection after fragmentation
[0082] Run the fragmentation program:
[0083]
[0084] 7. Mark
[0085] Run the marking program;
[0086]
[0087] The preferred embodiments of the present application have been described above with reference to the accompanying drawings, but this does not limit the scope of the claims of the present application. Any modifications, equivalent substitutions, and improvements made by those skilled in the art without departing from the scope and substance of the embodiments of the present application shall be within the scope of the claims of the present application.
Claims
1. A microfluidic chip suitable for preprocessing comparative genomic hybridization, the microfluidic chip comprising a digestion and ligation and polymerase chain reaction (PCR) module substrate and a purification and fragmentation and labeling module substrate, a digestion and ligation and PCR module cover plate and a purification and fragmentation and labeling module cover plate, an electromagnetic microvalve layer and a thin film layer disposed between the digestion and ligation and PCR module substrate and the digestion and ligation and PCR module cover plate, and an electromagnetic microvalve layer and a thin film layer disposed between the purification and fragmentation and labeling module substrate and the purification and fragmentation and labeling module cover plate; characterized in that: The digestion and ligation module substrate and the purification and fragmentation module substrate are provided with a reagent pre-loading area and a reaction area, which are connected to each other, wherein: The reagent pre-loading area includes a digestion reservoir, a connection reservoir, a polymerase chain reaction amplification and detection reservoir, a purification reservoir, a fragmentation reservoir, and a labeling reservoir. The digestion storage tank includes a nuclease-free water storage tank, a viral non-structural protein type I buffer storage tank, a bovine serum albumin storage tank, and a viral non-structural protein type I enzyme storage tank. The ligation reservoir includes a phage T4 genome deoxyribonucleic acid ligation buffer reservoir or a primer adapter reservoir, and a phage T4 genome deoxyribonucleic acid ligase reservoir. The polymerase chain reaction (PCR) amplification and detection reservoir includes a nuclease-free water reservoir, a deoxyribonucleic acid (DNA) polymerase buffer reservoir, a guanine-cytosine fusion reagent reservoir, a deoxyribonucleoside triphosphate reservoir, a PCR primer reservoir, or a DNA polymerase reservoir. The purification storage tank includes a purification magnetic bead storage tank, a purification washing solution storage tank, an elution solution storage tank, and a nuclease-free water storage tank. The fragmented storage tank includes a fragmented buffer solution storage tank and a fragmented reagent storage tank; The labeling reservoir includes a deoxynucleotide terminal transferase buffer reservoir, a deoxyribonucleic acid labeling reagent reservoir, and a deoxynucleotide terminal transferase reservoir; The reaction zone includes a digestion reaction tank, a ligation reaction tank, polymerase chain reaction tanks 1-4, a purification reaction tank, a fragmentation reaction tank, a labeling reaction tank, a polymerase chain reaction product mixing tank, a prehybridization library tank, a polymerase chain reaction reagent mixing tank, a labeling reagent mixing tank, and a purified product tank. in: The digestion reaction tank is connected to the bovine serum albumin storage tank through a microchannel, and the microchannel is equipped with a pneumatic microvalve or an electromagnetic microvalve. The nuclease-free water storage tank, the viral non-structural protein type I buffer storage tank, and the viral non-structural protein type I enzyme storage tank are respectively connected to the bovine serum albumin storage tank through microchannels, and electromagnetic microvalve is provided on the microchannels. The connecting reaction tank is connected to the digestion reaction tank through a microchannel, and a pneumatic microvalve or an electromagnetic microvalve is provided on the microchannel. The genomic DNA ligation buffer reservoir or primer adapter reservoir of phage T4 and the genomic DNA ligase reservoir of phage T4 are respectively connected to the ligation reaction pool through microchannels, and electromagnetic microvalve is provided on the microchannels. The polymerase chain reaction reagent mixing cell is connected to the connecting reaction cell via a microchannel, and the microchannel is equipped with a pneumatic microvalve or an electromagnetic microvalve. The nuclease-free water storage tank is connected to the nuclease-free water storage tank, the deoxyribonucleic acid polymerase buffer storage tank, the guanine-cytosine fusion reagent storage tank, the deoxyribonucleoside triphosphate storage tank, the polymerase chain reaction primer storage tank, or the deoxyribonucleic acid polymerase storage tank via microchannels, and electromagnetic microvalve is provided on the microchannels; The polymerase chain reaction reagent mixing pool is connected to the polymerase chain reaction reaction pool 1-4 through a microchannel, and the polymerase chain reaction reaction pool 1-4 is connected to the polymerase chain reaction product mixing pool through a microchannel, and a pneumatic microvalve or electromagnetic microvalve is provided on the microchannel. The purification storage tank includes a purification magnetic bead storage tank, a purification washing solution storage tank, an elution solution storage tank, and a nuclease-free water storage tank, which are respectively connected to the purification reaction tank through microchannels, and electromagnetic microvalve is provided on the microchannels. The purification reaction pool is connected to the purification product pool via a microchannel, the purification product pool is connected to the fragmentation reaction pool via a microchannel, the fragmentation reaction pool is connected to the labeling reagent mixing pool via a microchannel, the labeling reagent mixing pool is connected to the labeling reaction pool via a microchannel, and the labeling reaction pool is connected to the prehybridization library pool via a microchannel. A pneumatic microvalve or an electromagnetic microvalve is provided on the microchannel. The fragmented buffer solution reservoir and the fragmented reagent reservoir are respectively connected to the microchannel between the purified product reservoir and the fragmented reaction reservoir via a pneumatic microvalve or an electromagnetic microvalve on the microchannel. Electromagnetic microvalve is provided on the microchannel connecting the fragmented buffer solution reservoir to the microchannel between the pneumatic microvalve or electromagnetic microvalve and the fragmented reaction reservoir, and on the microchannel connecting the fragmented reagent reservoir to the microchannel between the pneumatic microvalve or electromagnetic microvalve and the fragmented reaction reservoir. The labeling reservoir includes a deoxynucleotide terminal transferase buffer reservoir, a deoxyribonucleic acid labeling reagent reservoir, and a deoxynucleotide terminal transferase reservoir, which are respectively connected to the labeling reagent mixing reservoir through microchannels, and electromagnetic microvalve is provided on the microchannels; The polymerase chain reaction product mixing pool in the digestion and ligation and polymerase chain reaction module substrate is transferred manually to the purification magnetic bead reservoir in the purification and fragmentation and labeling module substrate.
2. A microfluidic chip suitable for preprocessing comparative genomic hybridization according to claim 1, characterized in that, Both the pneumatic microvalve and the electromagnetic microvalve are disposed in the electromagnetic microvalve layer.
3. A microfluidic chip suitable for preprocessing comparative genomic hybridization according to claim 1, characterized in that, The purification reaction tank contains magnetic microspheres.
4. A microfluidic chip suitable for preprocessing comparative genomic hybridization according to claim 1, characterized in that, The reaction zone is equipped with a temperature control device, which includes temperature control device 1, temperature control device 2, temperature control device 3 and temperature control device 4. Temperature control device 1 is responsible for controlling the temperature of the digestion reaction tank and the connecting reaction tank; temperature control device 2 is responsible for controlling the temperature of polymerase chain reaction tanks 1-4; temperature control device 3 is responsible for controlling the temperature of the fragmentation reaction tank; and temperature control device 4 is responsible for controlling the temperature of the labeling reaction tank.
5. A microfluidic chip suitable for preprocessing comparative genomic hybridization according to claim 4, characterized in that, The temperature control device 1 is located at the bottom of the cover plate of the digestion and ligation module and at a position corresponding to the digestion reaction pool and ligation reaction pool in the substrate of the digestion and ligation module; the temperature control device 2 is located at the bottom of the cover plate of the digestion and ligation module and at a position corresponding to the polymerase chain reaction reaction pools 1-4 in the substrate of the digestion and ligation module; the temperature control device 3 is located at the bottom of the cover plate of the purification and fragmentation and labeling module and at a position corresponding to the fragmentation reaction pool in the substrate of the purification and fragmentation and labeling module; the temperature control device 4 is located at the bottom of the cover plate of the purification and fragmentation and labeling module and at a position corresponding to the labeling reaction pool in the substrate of the purification and fragmentation and labeling module.
6. A reagent kit, characterized in that, The kit includes the microfluidic chip as described in claim 1.