Oligonucleotide synthesis device
By designing an oligonucleotide synthesis device including chip module, rotary cutting valve module and high-pressure gas source module, the problems of complex equipment, high investment and inconvenient operation in the prior art are solved, and the efficiency of oligonucleotide synthesis has been improved.
Patent Information
- Application Number
- CN202421969983.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2024-08-14
- Publication Date
- 2025-06-10
- Estimated Expiration
- 2034-08-14
AI Technical Summary
In the existing oligonucleotide synthesis technology, the liquid structure of column synthesis technology is difficult to ensure that the residual reagents are cleaned, resulting in complex equipment, high investment cost and inconvenient operation, which affects the efficiency of oligonucleotide synthesis.
An oligonucleotide synthesis device was designed, using chip module, rotary cutting valve module and high-pressure gas source module. The high-pressure gas is used as both a purge gas source for the sheet-shaped chip reaction chamber and a power source for passing the reaction reagent into the reaction chamber, simplifying the device structure and operation process.
The overall structure of the oligonucleotide synthesis device is simplified, the equipment investment is reduced, the operation process is simplified, and the synthesis efficiency of oligonucleotide chains is improved.
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Figure CN222961346U_ABST
Abstract
Description
Technical Field
[0001] The utility model relates to the technical field of oligonucleotide synthesis, in particular to an oligonucleotide synthesis device. Background Technique
[0002] At present, the commercial oligonucleotide synthesis technology is the column synthesis technology. Its principle is to fill the powder of Controlled Pore Glass (abbreviated as CPG) into a filling column. Since there are upper and lower sieve plates in the filling column, the CPG powder can be sealed in the filling column. Then the filling column sealed with CPG powder is placed in a column synthesizer. Finally, the corresponding computer program is started to synthesize oligonucleotides. Among them, the liquid path of the column synthesis technology adopts the positive pressure liquid supply method. Due to its structural characteristics, it is difficult to ensure that the residual reagent is cleaned up.
[0003] It has been found through research that the surface of the sheet-like chip reaction chamber is a monolayer, which is easy to clean and can synthesize longer oligonucleotide chains. However, the liquid supply and cleaning of the traditional sheet-like chip reaction chamber are controlled by different positive pressure modules, resulting in a more complex synthesis device, higher input costs, inconvenient operation, and affecting the oligonucleotide synthesis efficiency. Content of the Utility Model
[0004] The purpose of the utility model is to provide an oligonucleotide synthesis device to solve the problems existing in the above-mentioned prior art, making the overall structure of the oligonucleotide synthesis device simpler, reducing the equipment input, and also facilitating the simplification of the operation process of oligonucleotide chain synthesis and improving the synthesis efficiency of oligonucleotide chains.
[0005] To achieve the above purpose, the utility model provides the following scheme:
[0006] An oligonucleotide synthesis device includes a chip module, a rotary valve module, and a high-pressure gas source module. The chip module includes a sheet-like chip reaction chamber for synthesizing oligonucleotide chains. Reaction chamber inlets and reaction chamber outlets are respectively arranged at both ends of the sheet-like chip reaction chamber. The medium inlets of the rotary valve module are provided with a plurality of inlets, which are respectively used to connect the high-pressure gas source with the reaction reagent bottles. The reaction reagent bottles are communicated with the high-pressure gas source module. The reagent in the reaction reagent bottles is sent into the rotary valve by using high-pressure gas, and the medium outlet of the rotary valve is connected with the reaction chamber inlet.
[0007] Preferably, the rotary cutting valve module includes a first rotary cutting valve and a second rotary cutting valve. The medium inlet of the first rotary cutting valve includes a first high-pressure gas connection port, an OXI reagent connection port, a first ACN reagent connection port, a CAPA reagent connection port, an ACT reagent connection port, and a TCA reagent connection port. The medium outlet of the first rotary cutting valve is connected to the first end of a first three-way connector through a first stop valve; the medium inlet of the second rotary cutting valve includes a second high-pressure gas connection port, a second ACN reagent connection port, a CAPB reagent connection port, an A reagent connection port, a T reagent connection port, a C reagent connection port, and a G reagent connection port. The medium outlet of the second rotary cutting valve is connected to the second end of the first three-way connector through a second stop valve, and the third end of the first three-way connector is connected to the reaction chamber inlet.
[0008] Preferably, it further includes a second three-way connector. The first end of the second three-way connector is connected to the high-pressure gas source module, the second end is connected to a plurality of the reaction reagent bottles, and the third end is connected to the first high-pressure gas connection port and the second high-pressure gas connection port.
[0009] Preferably, the first end of the second three-way connector is connected to the high-pressure gas source module through a first pressure reducing valve.
[0010] Preferably, the second end of the second three-way connector is connected to a plurality of the reaction reagent bottles through a second pressure reducing valve.
[0011] Preferably, it further includes a third three-way connector. The first end of the third three-way connector is connected to the third end of the second three-way connector, and the second end and the third end are respectively connected to the first high-pressure gas connection port and the second high-pressure gas connection port.
[0012] Preferably, it further includes a gas distributor. The gas inlet of the gas distributor is communicated with the high-pressure gas source module, and a plurality of gas outlets are respectively communicated with a plurality of the reaction reagent bottles.
[0013] Preferably, the high-pressure gas source module includes a high-pressure argon gas source.
[0014] Preferably, both the first stop valve and the second stop valve are solenoid valves.
[0015] The utility model has the following technical effects compared with the prior art:
[0016] The high-pressure gas source module in the present utility model provides high-pressure gas, which serves both as the purging gas source for the sheet chip reaction chamber and as the power source for introducing reaction reagents into the sheet chip reaction chamber. Thus, there is no need to separately set up a power element for the reaction reagents, making the overall structure of the oligonucleotide synthesis device simpler, reducing equipment investment, and also facilitating the simplification of the operation process for oligonucleotide chain synthesis and improving the synthesis efficiency of oligonucleotide chains. BRIEF DESCRIPTION OF THE DRAWINGS
[0017] In order to more clearly illustrate the technical solutions in the embodiments of the present utility model or the prior art, the following will briefly introduce the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present utility model. For those of ordinary skill in the art, without creative efforts, other drawings can be obtained based on these drawings.
[0018] Figure 1 It is a schematic structural diagram of the oligonucleotide synthesis device in the present utility model;
[0019] Description of the reference numerals:
[0020] 1. Sheet chip reaction chamber; 2. Reaction reagent bottle; 3. First rotary cutting valve; 4. Second rotary cutting valve; 5. First three-way connector; 6. Second three-way connector; 7. Third three-way connector; 8. First pressure reducing valve; 9. Second pressure reducing valve; 10. First solenoid valve; 11. Second solenoid valve. DETAILED DESCRIPTION OF THE EMBODIMENTS
[0021] The following will clearly and completely describe the technical solutions in the embodiments of the present utility model with reference to the drawings in the embodiments of the present utility model. Obviously, the described embodiments are only some, rather than all, of the embodiments of the present utility model. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present utility model without creative efforts shall fall within the protection scope of the present utility model.
[0022] The purpose of the present utility model is to provide an oligonucleotide synthesis device to solve the problems existing in the above-mentioned prior art, making the overall structure of the oligonucleotide synthesis device simpler, reducing equipment investment, and also facilitating the simplification of the operation process for oligonucleotide chain synthesis and improving the synthesis efficiency of oligonucleotide chains.
[0023] To make the above-mentioned objects, features, and advantages of the present utility model more obvious and understandable, the present utility model will be further described in detail below with reference to the drawings and specific embodiments.
[0024] As Figure 1As shown in the figure, this embodiment provides an oligonucleotide synthesis device, which includes a chip module, a rotary valve module, and a high-pressure gas source module. The chip module includes a sheet-shaped chip reaction chamber 1 for synthesizing oligonucleotide chains. A reaction chamber inlet and a reaction chamber outlet are respectively arranged at the front end and the rear end of the sheet-shaped chip reaction chamber 1. The medium inlet of the rotary valve module is provided with a plurality of inlets, which are respectively used to connect the high-pressure gas source and the reaction reagent bottles 2. A plurality of reaction reagent bottles 2 are provided, and different reagents for synthesizing oligonucleotide chains or for cleaning are respectively stored in them. The reaction reagent bottles 2 are communicated with the high-pressure gas source module, and the reagents in the reaction reagent bottles 2 are sent into the rotary valve by using high-pressure gas. The medium outlet of the rotary valve is connected to the reaction chamber inlet.
[0025] During use, the high-pressure gas source module introduces high-pressure gas into the reaction reagent bottles 2, and the reaction reagents in the reaction reagent bottles 2 are introduced into the rotary valve module by using the high-pressure gas. By adjusting the rotary valve module, the required reaction reagents can be selected to be introduced into the sheet-shaped chip reaction chamber 1 for reaction or the reacted sheet-shaped chip reaction chamber 1 can be cleaned. At the same time, the high-pressure gas source module is directly connected to the sheet-shaped chip reaction chamber 1 through the rotary valve module, and the reacted sheet-shaped chip reaction chamber 1 can be purged by using high-pressure gas. Thus, the high-pressure gas provided by the high-pressure gas source module in this embodiment serves both as the purging gas source of the sheet-shaped chip reaction chamber 1 and as the power source for introducing the reaction reagents into the sheet-shaped chip reaction chamber 1, so that there is no need to separately set up a power element acting on the reaction reagents, making the overall structure of the oligonucleotide synthesis device simpler, reducing the equipment investment, and also being beneficial to simplifying the operation process of oligonucleotide chain synthesis and improving the synthesis efficiency of oligonucleotide chains.
[0026] Further, in this embodiment, the rotary cutting valve module includes a first rotary cutting valve 3 and a second rotary cutting valve 4. The medium inlet of the first rotary cutting valve 3 includes a first high-pressure gas connection port, an OXI (iodine solution) reagent connection port, a first ACN (acetonitrile) reagent connection port, a CAPA (capping agent A) reagent connection port, an ACT (4,5-dicyanoimidazole) reagent connection port, and a TCA (trichloroacetic acid) reagent connection port. The medium outlet of the first rotary cutting valve 3 is connected to the first end of a first three-way connector 5 through a first stop valve; the medium inlet of the second rotary cutting valve 4 includes a second high-pressure gas connection port, a second ACN reagent connection port, a CAPB (capping agent B) reagent connection port, an A (5'-O-(4,4'-dimethoxytriphenyl)-N6-benzoyl-2'-deoxyadenosine-3'-(2-cyanoethyl-N,N-diisopropyl) phosphoramidite) reagent connection port, a T (5'-(4,4'-dimethoxytriphenyl)-3'-deoxythymidine 2'-(2-cyanoethyl-N,N-diisopropyl) phosphoramidite) reagent connection port, a C (5'-O-(4,4'-dimethoxytriphenyl)-N4-benzoyl-2'-deoxycytidine-3'-(2-cyanoethyl-N,N-diisopropyl) phosphoramidite) reagent connection port, and a G (DMF-DG-CE phosphoramidite monomer) reagent connection port. The medium outlet of the second rotary cutting valve 4 is connected to the second end of the first three-way connector 5 through a second stop valve. The third end of the first three-way connector 5 is connected to the reaction chamber inlet. The first high-pressure gas connection port and the second high-pressure gas connection port on the first rotary cutting valve 3 are both connected to the high-pressure gas module, and the multiple reagent connection ports are respectively connected to reaction reagent bottles 2 storing corresponding reagents.
[0027] The rotary cutting valve is a common structure in the art. By adjusting the rotary cutting valve, it is possible to adjust the connection between a certain medium inlet and the medium outlet, thereby realizing the introduction of reaction reagents, cleaning reagents, or purging high-pressure gas into the sheet chip reaction chamber 1 at different stages.
[0028] For the convenience of control, the first stop valve and the second stop valve in this embodiment are both solenoid valves.
[0029] Further, this embodiment further includes a second three-way connector 6. The first end of the second three-way connector 6 is connected to the high-pressure gas source module, the second end is connected to the multiple reaction reagent bottles 2, and the third end is connected to the first high-pressure gas connection port and the second high-pressure gas connection port.
[0030] The first end of the second three-way connector 6 is connected to the high-pressure gas source module through a first pressure reducing valve 8. The second end of the second three-way connector 6 is connected to the multiple reaction reagent bottles 2 through a second pressure reducing valve 9. By adjusting the first pressure reducing valve 8 and the second pressure reducing valve 9, the pressure of the high-pressure gas can be adjusted, thereby adjusting the flow rate of the reaction reagent and the purging pressure of the high-pressure gas. Usually, the flow rate of the reaction reagent is maintained at 1 ml / s.
[0031] Further, this embodiment further includes a third three-way connector 7. The first end of the third three-way connector 7 is connected to the third end of the second three-way connector 6, and the second end and the third end are respectively connected to the first high-pressure gas connection port and the second high-pressure gas connection port.
[0032] Further, this embodiment further includes a gas distributor. The gas inlet of the gas distributor is communicated with the high-pressure gas source module, and a plurality of gas outlets are respectively communicated with a plurality of reaction reagent bottles 2. The gas distributor can be provided with one or two. In this embodiment, two are provided, namely a first gas distributor and a second gas distributor. The gas inlet of the first gas distributor is connected to the second pressure reducing valve 9, and the six exhaust ports of the first gas distributor are respectively connected to the first ACN reagent bottle, the second ACN reagent bottle, the CAPA reagent bottle, the CAPB reagent bottle, the OXI reagent bottle and the gas inlet of the second gas distributor. The six gas outlets of the second gas distributor are respectively connected to the TCA reagent bottle, the ACT reagent bottle, the A reagent bottle, the T reagent bottle, the C reagent bottle and the G reagent bottle, and each reagent bottle has a gas inlet and a liquid discharge port. The gas inlet is connected to the exhaust ports of the first gas distributor and the second gas distributor, and the liquid discharge port is connected to the first rotary cutting valve 3 or the second rotary cutting valve 4.
[0033] Further, the high-pressure gas source module in this embodiment includes a high-pressure argon gas source, which uses high-pressure argon gas as the purge gas for the flake chip reaction chamber 1 and also as the power for the reaction reagent to enter the first rotary cutting valve 3 and the second rotary cutting valve 4.
[0034] The methods for synthesizing oligonucleotide chains and cleaning are well-known to those skilled in the art. For the convenience of understanding, examples of the method for synthesizing oligonucleotide chains are listed in this embodiment for illustration.
[0035] The method for synthesizing oligonucleotide chains includes:
[0036] Step 1: TCA deprotection step; In the TCA deprotection step, TCA reagent is added to the flake chip reaction chamber 1 for deprotection reaction, and after the reaction is completed, ACN reagent is added for cleaning.
[0037] Step 2: Mononucleotide reagent coupling step; In the mononucleotide reagent coupling step, the required mononucleotide reagent and ACT reagent are simultaneously added to the flake chip reaction chamber 1 for coupling reaction, and after the reaction is completed, ACN reagent is added for cleaning.
[0038] Step 3: Capping reaction step; In the capping reaction step, CAPA reagent and CAPB reagent are simultaneously added to the flake chip reaction chamber 1 for capping reaction, and after the reaction is completed, ACN reagent is added for cleaning.
[0039] Step 4: Oxidation reaction step; In the oxidation reaction step, an OXI reagent is added to the flake chip reaction chamber 1 for oxidation reaction, and after the reaction is completed, an ACN reagent is added for cleaning.
[0040] Step 5: Repeat steps 1 to 4 to obtain an oligonucleotide chain; wherein, the number of repetitions is determined by the length of the oligonucleotide chain.
[0041] The specific operation procedures of steps 1 to 4 are as follows:
[0042] a. Removal of the DMT protecting group
[0043] After resetting the first rotary valve 3 and the second rotary valve 4, the switching end of the first rotary valve 3 rotates to the TCA reagent connection port. At this time, under the positive pressure of high-pressure argon gas, the TCA reagent is pushed into the first rotary valve 3. Open the first solenoid valve 10, so that the TCA reagent enters from the reaction chamber inlet at the front end of the flake chip reaction chamber 1 through the first solenoid valve 10. After the flake chip reaction chamber 1 is filled with the TCA reagent, close the first solenoid valve 10, and use the TCA reagent to remove the DMT on the nucleoside connected to the chip to expose the 5'-end hydroxyl group. Rotate the switching end of the first rotary valve 3 to the first high-pressure gas connection port and open the first solenoid valve 10, so that argon gas enters from the reaction chamber inlet at the front end of the flake chip reaction chamber 1 through the first solenoid valve 10. The argon gas discharges the residual reagent through the reaction chamber outlet at the rear end of the flake chip reaction chamber 1 and then closes the first solenoid valve 10. Rotate the switching end of the first rotary valve 3 to the first ACN reagent connection port, and rotate the switching end of the second rotary valve 4 to the second ACN reagent connection port. Open the first solenoid valve 10 and the second solenoid valve 11 to make the ACN reagent enter from the reaction chamber inlet at the front end of the flake chip reaction chamber 1, and discharge the residual reagent in the flake chip reaction chamber 1 and the pipeline from the rear end. After cleaning three times, close the first solenoid valve 10 and the second solenoid valve 11. Rotate the switching end of the first rotary valve 3 to the first high-pressure gas connection port, and rotate the switching end of the second rotary valve 4 to the second high-pressure gas connection port. Open the first solenoid valve 10 and the second solenoid valve 11, so that argon gas enters from the reaction chamber inlet at the front end of the flake chip reaction chamber 1. The argon gas discharges the residual reagent through the reaction chamber outlet at the rear end of the flake chip reaction chamber 1 and dries the chip, and then closes the first solenoid valve 10 and the second solenoid valve 11.
[0044] b. Condensation reaction
[0045] Rotate the switching end of the first rotary valve 3 to the ATC reagent connection port, and rotate the switching end of the second rotary valve 4 to the single nucleotide connection port (one of the A reagent connection port, T reagent connection port, C reagent connection port, and G reagent connection ports). At this time, under the action of positive pressure, the ACT reagent and the single nucleotide reagent are simultaneously pushed into the first rotary valve 3 and the second rotary valve 4. Open the first solenoid valve 10 and the second solenoid valve 11 to allow the ACT reagent and the single nucleotide reagent to enter from the reaction chamber inlet at the front end of the sheet-like chip reaction chamber 1. After filling with the reagent, close the first solenoid valve 10 and the second solenoid valve 11. When the ACT reagent collides with the single nucleotide reagent, a nucleophilic reaction occurs with the 5'-hydroxyl group, resulting in coupling and the removal of tetrazole, and the synthesized oligonucleotide chain is extended by one. Rotate the switching end of the first rotary valve 3 to the first high-pressure gas connection port, open the first solenoid valve 10, rotate the switching end of the second rotary valve 4 to the second high-pressure gas connection port, and open the first solenoid valve 10. Argon enters from the reaction chamber inlet at the front end of the sheet-like chip reaction chamber 1. After the argon discharges the residual reagent through the reaction chamber outlet at the rear end of the sheet-like chip reaction chamber 1, close the first solenoid valve 10 and the second solenoid valve 11. Rotate the switching end of the first rotary valve 3 to the first ACN reagent connection port, rotate the switching end of the second rotary valve 4 to the second ACN reagent connection port, open the first solenoid valve 10 and the second solenoid valve 11 to allow the ACN reagent to enter from the reaction chamber inlet at the front end of the sheet-like chip reaction chamber 1, and discharge the residual reagent from the rear end. After cleaning three times, close the solenoid valves. Rotate the switching end of the first rotary valve 3 to the first high-pressure gas connection port, rotate the switching end of the first rotary valve 3 to the second high-pressure gas connection port, open the first solenoid valve 10 and the second solenoid valve 11, allow argon to enter from the reaction chamber inlet at the front end of the sheet-like chip reaction chamber 1, discharge the residual reagent through the reaction chamber outlet at the rear end of the sheet-like chip reaction chamber 1, and dry the chip, then close the first solenoid valve 10 and the second solenoid valve 11.
[0046] c. Cap
[0047] Rotate the switching end of the first rotary valve 3 to the CAPA reagent connection port, and rotate the switching end of the second rotary valve 4 to the CAPB reagent connection port. At this time, the CAPA reagent and the CAPB reagent are simultaneously pushed into the first rotary valve 3 and the second rotary valve 4 under positive pressure. Open the first solenoid valve 10 and the second solenoid valve 11 to allow the CAPA reagent and the CAPB reagent to enter from the reaction chamber inlet at the front end of the sheet-like chip reaction chamber 1. After filling with the reagent, close the first solenoid valve 10 and the second solenoid valve 11. To prevent the 5'-hydroxyl group of the unreacted mononucleotide connected to the chip from being extended in the subsequent cycle, it is necessary to block it after the condensation reaction is sufficient. Rotate the switching end of the first rotary valve 3 to the first high-pressure gas connection port, open the first solenoid valve 10, rotate the switching end of the second rotary valve 4 to the second high-pressure gas connection port, open the second solenoid valve 11, and allow argon to enter from the reaction chamber inlet at the front end of the sheet-like chip reaction chamber 1. After the argon discharges the residual reagent through the reaction chamber outlet at the rear end of the sheet-like chip reaction chamber 1, close the first solenoid valve 10. Rotate the switching end of the first rotary valve 3 to the first ACN reagent connection port, rotate the switching end of the second rotary valve 4 to the second ACN reagent connection port, open the first solenoid valve 10 and the second solenoid valve 11 to allow the ACN reagent to enter from the reaction chamber inlet at the front end of the sheet-like chip reaction chamber 1, and discharge the residual reagent from the reaction chamber outlet. After cleaning three times, close the solenoid valves. Rotate the switching end of the first rotary valve 3 to the first high-pressure gas connection port, rotate the switching end of the second rotary valve 4 to the second high-pressure gas connection port, open the first solenoid valve 10 and the second solenoid valve 11, and allow argon to enter from the reaction chamber inlet at the front end of the sheet-like chip reaction chamber 1. After the argon discharges the residual reagent through the reaction chamber outlet at the rear end of the sheet-like chip reaction chamber 1 and dries the chip, close the first solenoid valve 10 and the second solenoid valve 11.
[0048] d. Oxidation:
[0049] The switching end of the first rotary cutting valve 3 rotates to the OXI reagent connection port. At this time, the OXI reagent is pushed into the first rotary cutting valve 3. The first electromagnetic valve 10 is opened to allow the OXI reagent to enter from the reaction chamber inlet at the front end of the chip reaction chamber 1 of the sheet. After the reagent is filled, the first electromagnetic valve 10 is closed. The newly added nucleotide after the condensation reaction is connected to the oligonucleotide chain on the chip through a phosphite bond. This phosphite bond is unstable and is easily hydrolyzed by acids and alkalis. Therefore, the trivalent phosphorus here needs to be oxidized to pentavalent phosphorus. The switching end of the first rotary cutting valve 3 is rotated to the first high-pressure gas connection port to open the first electromagnetic valve 10, allowing argon to enter from the reaction chamber inlet at the front end of the chip reaction chamber 1 of the sheet. After the argon discharges the residual reagent through the reaction chamber outlet at the rear end of the chip reaction chamber 1, the first electromagnetic valve 10 is closed. The switching end of the first rotary cutting valve 3 is rotated to the first ACN reagent connection port, and the switching end of the second rotary cutting valve 4 is rotated to the second ACN reagent connection port. The first electromagnetic valve 10 and the second electromagnetic valve 11 are opened to allow the ACN reagent to enter from the reaction chamber inlet at the front end of the chip reaction chamber 1 of the sheet, and the residual reagent is discharged from the reaction chamber outlet. After cleaning three times, the first electromagnetic valve 10 and the second electromagnetic valve 11 are closed. The switching end of the first rotary cutting valve 3 is rotated to the first high-pressure gas connection port, and the switching end of the second rotary cutting valve 4 is rotated to the second high-pressure gas connection port. The first electromagnetic valve 10 and the second electromagnetic valve 11 are opened to allow argon to enter from the reaction chamber inlet at the front end of the chip reaction chamber 1 of the sheet. After the argon discharges the residual reagent through the reaction chamber outlet at the rear end of the chip reaction chamber 1 and dries the chip, the first electromagnetic valve 10 and the second electromagnetic valve 11 are closed.
[0050] n. The full cycle process is the repeated cycle of a - d. Only in step b, select the current cycle single nucleotide reagent path.
[0051] Adaptations made according to actual needs are within the protection scope of the present utility model.
[0052] Specific examples are used in the present utility model to elaborate on the principle and implementation manner of the present utility model. The description of the above embodiments is only used to help understand the method and its core idea of the present utility model; at the same time, for those of ordinary skill in the art, based on the idea of the present utility model, there will be changes in the specific implementation manner and application scope. In summary, the content of this specification should not be construed as a limitation to the present utility model.
Claims
1. An oligonucleotide synthesis device, characterized in that: It comprises a chip module, a rotary cutting valve module and a high-pressure gas source module, wherein the chip module comprises a sheet-shaped chip reaction chamber for synthesizing oligonucleotide chains, and a reaction chamber inlet and a reaction chamber outlet are respectively arranged at both ends of the sheet-shaped chip reaction chamber; the rotary cutting valve module is provided with a plurality of medium inlets, which are respectively used to connect the high-pressure gas source and a reaction reagent bottle, the reaction reagent bottle is connected to the high-pressure gas source module, and the reagent in the reaction reagent bottle is delivered into the rotary cutting valve by using high-pressure gas, and the medium outlet of the rotary cutting valve is connected to the reaction chamber inlet.
2. The oligonucleotide synthesis device according to claim 1, characterized in that: The rotary cutting valve module includes a first rotary cutting valve and a second rotary cutting valve, the medium inlet of the first rotary cutting valve includes a first high-pressure gas connection port, an OXI reagent connection port, a first ACN reagent connection port, a CAPA reagent connection port, an ACT reagent connection port and a TCA reagent connection port, and the medium outlet of the first rotary cutting valve is connected to the first end of the first three-way connector through a first stop valve; the medium inlet of the second rotary cutting valve includes a second high-pressure gas connection port, a second ACN reagent connection port, a CAPB reagent connection port, an A reagent connection port, a T reagent connection port, a C reagent connection port and a G reagent connection port, the medium outlet of the second rotary cutting valve is connected to the second end of the first three-way connector through a second stop valve, and the third end of the first three-way connector is connected to the reaction chamber inlet.
3. The oligonucleotide synthesis device according to claim 2, characterized in that: It also includes a second three-way connector, a first end of which is connected to the high-pressure gas source module, a second end is connected to the plurality of reaction reagent bottles, and a third end is connected to the first high-pressure gas connection port and the second high-pressure gas connection port.
4. The oligonucleotide synthesis device according to claim 3, characterized in that: The first end of the second three-way connector is connected to the high-pressure gas source module through a first pressure reducing valve.
5. The oligonucleotide synthesis device according to claim 4, characterized in that: The second end of the second three-way connector is connected to the plurality of reaction reagent bottles through a second pressure reducing valve.
6. The oligonucleotide synthesis device according to claim 5, characterized in that: It also includes a third three-way connector, a first end of which is connected to the third end of the second three-way connector, and a second end and a third end of which are respectively connected to the first high-pressure gas connection port and the second high-pressure gas connection port.
7. The oligonucleotide synthesis device according to claim 1, characterized in that: It also includes a gas distributor, the gas inlet of the gas distributor is connected to the high-pressure gas source module, and the multiple gas outlets are respectively connected to the multiple reaction reagent bottles.
8. The oligonucleotide synthesis device according to claim 1, characterized in that: The high-pressure gas source module includes a high-pressure argon gas source.
9. The oligonucleotide synthesis device according to claim 2, characterized in that: The first stop valve and the second stop valve are both solenoid valves.