Nucleic acid synthesis equipment
By using gas drainage and pressure-drying reagent technology in nucleic acid synthesis equipment, the problems of reagent residue and high cost in existing equipment are solved, and more efficient nucleic acid synthesis and lower production costs are achieved.
Patent Information
- Application Number
- CN202311701118.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-12-12
- Publication Date
- 2025-06-13
AI Technical Summary
The existing nucleic acid synthesis equipment is difficult to completely drain the reagent during the synthesis reaction, resulting in residual effects on the synthesis performance. The use of a large amount of acetonitrile as a replacement reagent is high cost and cannot guarantee the dryness of the synthesis environment.
The gas drainage and pressure-drying reagent is used to inject compatible gas into the nucleic acid synthesis chamber through the gas-channel pressure-drying assembly, drain the synthesis reaction reagent and pressure-drying cleaning reagent, and combine the reagent switching and transportation assembly to achieve efficient switching and cleaning of reagents.
It effectively reduces the chance of reagent residue, ensures dryness of the synthesis environment, improves synthesis efficiency, and reduces synthesis cost.
Smart Images
Figure CN120132737A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of medical devices, and in particular to a nucleic acid synthesis device. Background Art
[0002] Artificial synthesis of nucleic acids refers to the synthesis of oligonucleotides or nucleic acid (DNA and RNA) macromolecules using nucleosides or mononucleotides as raw materials through organic synthesis reactions or enzymatic synthesis reactions. Currently, there are devices for nucleic acid synthesis. Existing nucleic acid synthesis devices generally use reagent acetonitrile (ACN) as a displacement reagent to complete the displacement reaction of the synthesis reaction reagent.
[0003] However, the method of using acetonitrile to displace the synthesis reaction reagent not only cannot completely drain the previous synthesis reaction reagent in the synthesis environment online, and the residual reagent that is not completely displaced poses a risk of affecting the nucleic acid synthesis performance. Moreover, a large amount of acetonitrile is required as a displacement reagent during nucleic acid synthesis, resulting in very high costs. At the same time, it cannot well ensure a dry synthesis environment without water vapor, seriously affecting the synthesis efficiency. Summary of the Invention
[0004] The purpose of the present invention is to provide a nucleic acid synthesis device. The nucleic acid synthesis device adopts a gas drainage and pressing method for reagents, reducing the probability of reagent residue, ensuring a dry synthesis environment without water vapor in the synthesis device, improving the synthesis efficiency, and reducing the synthesis cost.
[0005] To achieve this purpose, the present invention adopts the following technical solutions:
[0006] A nucleic acid synthesis device, comprising: a synthesis device, the synthesis device having a nucleic acid synthesis chamber, the nucleic acid synthesis chamber having a drain port that can be selectively opened and closed; a gas path pressing and drying assembly, the gas path pressing and drying assembly including a gas source and a gas path, the gas source being used to provide a gas that is compatible with the cleaning reagent and the synthesis reaction reagent, the gas source being selectively communicable with the nucleic acid synthesis chamber through the gas path to drain the synthesis reaction reagent in the nucleic acid synthesis chamber and press dry the cleaning reagent; a reagent switching and transporting assembly, the reagent switching and transporting assembly including a switching valve and a liquid path, the reagent ports of the switching valve being used to communicate with a plurality of reagent sources one by one, the reagent sources including a cleaning reagent source and a reaction reagent source, and the outlet of the switching valve being communicated with the nucleic acid synthesis chamber through the liquid path.
[0007] Preferably, the gas path drying and pressing assembly includes a first gas source and a first gas path. The first gas source is used to provide a protective gas. The first gas source is connected to the nucleic acid synthesis chamber through the first gas path and is used to introduce the protective gas into the nucleic acid synthesis chamber to drain the residual synthesis reaction reagent in the nucleic acid synthesis chamber. The gas path drying and pressing assembly includes a second gas source and a second gas path. The second gas source is used to provide air. The second gas source is connected to the nucleic acid synthesis chamber through the second gas path and is used to introduce air into the nucleic acid synthesis chamber to press-dry the residual cleaning reagent in the nucleic acid synthesis chamber. Wherein, both the first gas path and the second gas path can be selectively switched on and off.
[0008] Preferably, the nucleic acid synthesis device further includes a waste liquid discharging assembly. The waste liquid discharging assembly includes a waste liquid pipe and a waste liquid collection container. The waste liquid collection container is connected to the liquid discharging port through the waste liquid pipe, and a waste liquid discharging switch valve is arranged on the waste liquid pipe; and / or, a metering pump is arranged on the liquid path.
[0009] Preferably, a gas path cut-off switch valve is arranged on the first gas path.
[0010] Preferably, a first pressure relief valve is arranged on the first gas path; and / or, a first pressure gauge is arranged on the first gas path; and / or, a first pressure regulating valve is arranged on the first gas path; and / or, a second pressure relief valve is arranged on the second gas path; and / or, a second pressure gauge is arranged on the second gas path; and / or, a second pressure regulating valve is arranged on the second gas path.
[0011] Preferably, a dry filter is arranged on the second gas path.
[0012] Preferably, the first gas source is an inert gas cylinder and the protective gas is an inert gas; or, the first gas source is a nitrogen cylinder and the protective gas is nitrogen.
[0013] Preferably, the gas path drying and pressing assembly further includes a main gas path. One end of the first gas path is connected to the first gas source, and the other end is connected to the intake end of the main gas path. One end of the second gas path is connected to the second gas source, and the other end is connected to the intake end of the main gas path. The outlet end of the main gas path is connected to the intake port of the nucleic acid synthesis chamber.
[0014] Preferably, a third pressure gauge is arranged on the main gas path; and / or, a pressure reducing valve is arranged on the main gas path.
[0015] Preferably, a gas path switching valve is arranged at the connection of the main gas path, the first gas path and the second gas path.
[0016] Advantages of the present invention:
[0017] The nucleic acid synthesis equipment provided by the present invention includes a synthesis device, a gas circuit drying component, and a reagent switching and transportation component. The nucleic acid synthesis chamber of the synthesis device has a drain port that can be selectively opened and closed. The gas circuit drying component includes a gas source and a gas circuit. The gas source is used to provide a gas that is compatible with the cleaning reagent and the synthesis reaction reagent. The gas source is selectively connected to the nucleic acid synthesis chamber through the gas circuit to drain the synthesis reaction reagent in the nucleic acid synthesis chamber and dry the cleaning reagent. The reagent switching and transportation component includes a switching valve and a liquid circuit. The reagent ports of the switching valve are used to communicate with multiple reagent sources one by one. The reagent sources include a cleaning reagent source and a reaction reagent source. The outlet of the switching valve is connected to the nucleic acid synthesis chamber through the liquid circuit. The gas source of this nucleic acid synthesis equipment can fill the nucleic acid synthesis chamber with gas through the gas circuit to drain the residual synthesis reaction reagent in the chamber or dry the cleaning reagent, and a small amount of cleaning reagent can be injected into the nucleic acid synthesis chamber through the reagent switching and transportation component to clean the nucleic acid synthesis chamber. In this way, not only the synthesis efficiency is improved, but also the synthesis cost is reduced. Description of the Drawings
[0018] Figure 1 is a schematic diagram of the nucleic acid synthesis equipment provided by an embodiment of the present invention.
[0019] In the figure:
[0020] 100, synthesis device; 101, nucleic acid synthesis chamber;
[0021] 200, gas circuit drying component; 201, first gas source; 202, second gas source; 203, first gas circuit; 204, second gas circuit; 205, gas circuit cut-off switch valve; 206, first pressure relief valve; 207, first pressure gauge; 208, first pressure regulating valve; 209, drying filter; 210, second pressure relief valve; 211, second pressure gauge; 212, second pressure regulating valve; 213, main gas circuit; 214, third pressure gauge; 215, pressure reducing valve; 216, gas circuit switching valve;
[0022] 300, reagent switching and transportation component; 301, switching valve; 302, metering pump; 303, liquid circuit;
[0023] 400, waste liquid discharging component; 401, waste liquid pipe; 402, waste liquid collection container; 403, waste liquid discharging switch valve. Detailed Embodiments
[0024] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are some, but not all, of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.
[0025] In the description of the present invention, it should be noted that the orientation or positional relationship indicated by the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. is based on the orientation or positional relationship shown in the drawings. These are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation. Therefore, it should not be construed as a limitation to the present invention. In addition, the terms "first" and "second" are only used for descriptive purposes and cannot be construed as indicating or implying relative importance. Among them, the terms "first position" and "second position" are two different positions.
[0026] In the description of the present invention, it should be noted that unless otherwise clearly specified and limited, the terms "installation", "connection", and "coupling" should be understood in a broad sense. For example, it can be a fixed connection or a detachable connection; it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium, and it can be the communication inside two elements. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.
[0027] Next, refer to Figure 1 to describe the specific structure of the nucleic acid synthesis device according to the embodiments of the present invention.
[0028] The nucleic acid synthesis device provided by the embodiments of the present invention includes a synthesis device 100, a gas path drying component 200, and a reagent switching and transportation component 300. Among them, the synthesis device 100 has a nucleic acid synthesis chamber 101. The nucleic acid synthesis chamber 101 is a closed reaction space for the synthesis carrier and the synthesis reaction reagent. The nucleic acid synthesis chamber 101 has a drain port that can be selectively opened and closed, and has an air inlet and a liquid inlet. The gas path drying component 200 includes a gas source and a gas path. The gas source is used to provide a gas that is compatible with the cleaning reagent and the synthesis reaction reagent. The gas source is selectively connected to the nucleic acid synthesis chamber 101 through the gas path to drain the synthesis reaction reagent in the nucleic acid synthesis chamber 101 and dry the cleaning reagent in the nucleic acid synthesis chamber 101. The reagent switching and transportation component 300 is used to sequentially add the same or different reagents to the nucleic acid synthesis chamber 101. Specifically, the reagent switching and transportation component 300 includes a switching valve 301 and a liquid path 303. The switching valve 301 has a plurality of reagent ports and an outlet, thereby forming a plurality of channels for the reagent to flow through. The reagent ports of the switching valve 301 are used to connect to a plurality of reagent sources one by one. The reagent sources include a cleaning reagent source and a reaction reagent source. The cleaning reagent source is used to store the cleaning reagent, such as acetonitrile, and the reaction reagent source is used to store the reagent participating in the nucleic acid synthesis reaction. The outlet of the switching valve 301 is connected to the nucleic acid synthesis chamber 101 through the liquid path 303.
[0029] Compared with the method of replacing the synthesis reaction reagent with a replacement reagent in the prior art, the gas source of the nucleic acid synthesis device provided in the embodiment of the present invention can inject a gas that does not react with the synthesis reaction reagent or the cleaning reagent into the nucleic acid synthesis chamber 101 through the gas path, so as to be able to drain the residual synthesis reaction reagent in the nucleic acid reaction chamber 101 with gas and press-dry the residual cleaning reagent in the nucleic acid reaction chamber 101. This not only reduces the residue of the reagent in the synthesis reaction environment and on the synthesis carrier, ensures that the synthesis environment in the synthesis device 100 is dry without water vapor, thus avoiding the influence of the residual synthesis reaction reagent on the synthesis performance and improving the synthesis efficiency. Moreover, compared with the method of using a large amount of cleaning reagent to replace the synthesis reaction reagent in the prior art, the nucleic acid synthesis device provided in the embodiment of the present invention can inject a small amount of cleaning reagent into the nucleic acid reaction chamber 101 through the liquid path, greatly reducing the amount of cleaning reagent used, and thus reducing the cost of nucleic acid synthesis.
[0030] In some embodiments, the gas path press-drying component 200 has only one gas source and one gas path, and uses the same gas to drain the residual synthesis reaction reagent in the nucleic acid reaction chamber 101 and press-dry the cleaning reagent.
[0031] In some embodiments, the gas path press-drying component 200 has two gas sources and two gas paths, and uses different gases to drain the residual synthesis reaction reagent in the nucleic acid reaction chamber 101 and press-dry the cleaning reagent. Specifically, the gas path press-drying component 200 includes a first gas source 201, a second gas source 202, a first gas path 203 and a second gas path 204. The first gas source 201 is used to store a protective gas. One end of the first gas path 203 is connected to the outlet of the first gas source 201, and the other end of the first gas path 203 is connected to the inlet of the nucleic acid synthesis chamber 101. The first gas source 201 is connected to the nucleic acid synthesis chamber 101 through the first gas path 203. When the first gas path 203 is turned on, the protective gas in the first gas source 201 can enter the nucleic acid synthesis chamber 101 through the first gas path 203 to drain the residual synthesis reaction reagent in the nucleic acid synthesis chamber 101. One end of the second gas path 204 is connected to the outlet of the second gas source 202, and the other end is connected to the inlet of the nucleic acid synthesis chamber 101. The second gas source 202 is connected to the nucleic acid synthesis chamber 101 through the second gas path 204. When the second gas path 204 is turned on, the second gas source 202 can pass air into the nucleic acid synthesis chamber 101 through the second gas path 204 to press-dry the residual cleaning reagent in the nucleic acid synthesis chamber 101. Both the first gas path 203 and the second gas path 204 can be selectively turned on and off, and in the actual working process, the first gas path 203 and the second gas path 204 generally only conduct selectively, that is, the first gas path 203 and the second gas path 204 do not conduct simultaneously.
[0032] In some embodiments, the first gas source 201 is an inert gas bottle, and the protective gas is a high-pressure inert gas. Alternatively, the first gas source is an argon gas bottle, and the inert gas is argon. In some other embodiments, the first gas source 201 is a nitrogen gas bottle, and the protective gas is high-pressure nitrogen. High-pressure argon or nitrogen is used as the motive force to drain the residual synthesis reaction reagents in the nucleic acid reaction chamber.
[0033] In some embodiments, the second gas source 202 is used to generate high-pressure air, because the time for drying is much longer than the time for draining, and argon is relatively expensive, and air does not need to be purchased, so it is more economical to use air as the motive force for drying the reaction environment in the synthesis device 100. Of course, in other embodiments, the second gas source 202 can also be a gas cylinder containing high-pressure argon or nitrogen.
[0034] Taking the gas path pressing and drying component having two gas sources and two gas paths as an example, the synthesis reaction reagent adding process and the synthesis reaction reagent draining process of the nucleic acid synthesis process of the nucleic acid synthesis device provided by the present invention are introduced: during the synthesis reaction reagent adding process, the first gas path 203 and the second gas path 204 are both in a blocked state, and the switching valve 301 is rotated to make the reagent port connected to the reaction reagent source containing the target synthesis reaction reagent connected to the outlet, so that the target synthesis reaction reagent can enter the nucleic acid synthesis chamber 101 of the synthesis device 100 through the liquid path 303 for reaction; after the synthesis reaction reagent located in the nucleic acid synthesis chamber 101 completes the reaction, it needs to be drained to facilitate the addition of another synthesis reaction reagent. At this time, the liquid path 303 is disconnected, and the first gas path 203 is controlled to be connected, and the first gas path 204 is opened. The protective gas in the source 201 is filled into the nucleic acid synthesis chamber 101 through the first gas path 203, so that the residual synthesis reaction reagent in the chamber is discharged; thereafter, the first gas path 203 is disconnected, and the reagent port of the cleaning reagent source containing the cleaning reagent is connected to the outlet by rotating the switching valve 301, so that the cleaning reagent can enter the nucleic acid synthesis chamber 101 of the synthesizer 100 through the liquid path 303 to complete the cleaning; finally, the second gas path 204 is connected, the first gas path 203 remains disconnected, and the second gas source 202 can fill air into the nucleic acid synthesis chamber 101 through the second gas path 204 to discharge the cleaning agent, so that the nucleic acid synthesis chamber 101 has a dry synthesis environment; thereafter, the synthesis reaction reagent adding process can be performed again, and this cycle is repeated until the synthesis reaction is completed.
[0035] Continue to refer to Figure 1As shown, in some embodiments, the synthesis device 100 is a columnar synthesis column, which serves as a closed reaction environment for a synthesis carrier such as a chip carrier and synthesis reaction reagents, isolating external environmental influencing factors. A nucleic acid synthesis chamber 101 is formed inside the synthesis column. A liquid discharge port communicating with the nucleic acid synthesis chamber 101 is formed at the bottom end of the synthesis column. An air inlet communicating with the first gas path 203 and the second gas path 204 is formed at the top end of the synthesis column, and a liquid inlet communicating with the liquid path 303 is formed. Of course, in other embodiments, the synthesis device 100 can also be of other shapes, and the synthesis carrier can also be of other types, which can be flexibly selected according to requirements.
[0036] In some embodiments, the first gas path 203 and the second gas path 204 are independent gas paths. The synthesis device 100 has two air inlets. The first gas path 203 communicates with one of the air inlets, and the second gas path 204 communicates with the other air inlet.
[0037] To control the on / off of the first gas path 203, in some embodiments, a gas path cut-off switch valve 205 is provided on the first gas path 203. The gas path cut-off switch valve 205 is used to switch and cut off the protective gas. When the gas path cut-off switch valve 205 is powered on, the gas path cut-off switch valve 205 opens, and the protective gas can enter the nucleic acid synthesis chamber 101 through the first gas path 203. When the gas path cut-off switch valve 205 is powered off, the gas path cut-off switch valve 205 closes, and the protective gas cannot enter the nucleic acid synthesis chamber 101 through the first gas path 203. Optionally, the gas path cut-off switch valve 205 is a solenoid valve.
[0038] Continue to refer to Figure 1 As shown, in some embodiments, a first pressure relief valve 206 is provided on the first gas path 203. The first pressure relief valve 206 enables the gas system pressure of the protective gas to be within a preset pressure range. If the pressure in the first gas path 203 exceeds the set pressure of the first pressure relief valve 206, the gas will flow out from the first pressure relief valve 206 to achieve the purpose of pressure relief. Optionally, the first pressure relief valve 206 is a solenoid valve.
[0039] In some embodiments, a first pressure gauge 207 is further provided on the first gas path 203, and the first pressure gauge 207 is used to display the gas path pressure of the first gas path 203.
[0040] In some embodiments, a first pressure regulating valve 208 is further provided on the first gas path 203, and the first pressure regulating valve 208 is used to adjust the pressure in the first gas path 203 to within a preset pressure range. Optionally, the first pressure regulating valve 208 is a solenoid valve.
[0041] In order to control the on / off of the second gas path 204, in some embodiments, a switching valve (not shown in the figure) is provided on the second gas path 204. The switching valve is used to switch and cut off the air. When the switching valve is powered on, the switching valve opens, and air can enter the nucleic acid synthesis chamber 101 through the second gas path 204; when the switching valve is powered off, the switching valve closes, and air cannot enter the nucleic acid synthesis chamber 101 through the second gas path 204.
[0042] Continue to refer to Figure 1 As shown, in some embodiments, a second pressure relief valve 210 is provided on the second gas path 204. The second pressure relief valve 210 enables the gas system pressure of the air to be within a preset pressure range. If the pressure in the second gas path 204 exceeds the set pressure of the second pressure relief valve 210, the gas will flow out from the second pressure relief valve 210 to achieve the purpose of pressure relief. Optionally, the second pressure relief valve 210 is an electromagnetic valve.
[0043] In some embodiments, a second pressure gauge 211 is further provided on the second gas path 204, and the second pressure gauge 211 is used to display the gas path pressure of the second gas path 204.
[0044] In some embodiments, a second pressure regulating valve 212 is further provided on the second gas path 204, and the second pressure regulating valve 212 is used to adjust the pressure in the second gas path 204 to be within a preset pressure range. Optionally, the second pressure regulating valve 212 is an electromagnetic valve.
[0045] In order to keep the air flowing out of the second gas source 202 in a dry state, continue to refer to Figure 1 As shown, in some embodiments, a dry filter 209 is provided on the second gas path 204. The dry filter 209 is mainly used to filter the water vapor in the air produced by the second gas source 202 to form dry air. The use of dry air avoids the influence of water vapor in the air on the synthesis performance. The specific structure of the dry filter 209 is prior art and will not be described in detail here. The types of the dry filter 209 can be flexibly limited according to requirements and will not be limited here.
[0046] In order to shorten the extension lengths of the first gas path 203 and the second gas path 204 and reduce the gas path material consumption, in some embodiments, the gas path drying assembly 200 further includes a main gas path 213. One end of the first gas path 203 is connected to the first gas source 201, and the other end is connected to the intake end of the main gas path 213. One end of the second gas path 204 is connected to the second gas source 202, and the other end is connected to the intake end of the main gas path 213. The outlet end of the main gas path 213 is connected to the intake port of the nucleic acid synthesis chamber 101. The first gas path 203, the second gas path 204, and the main gas path 213 are connected to form a tee. Such a setting enables only one intake port to be provided in the synthesis device 100.
[0047] Further, in some embodiments, a third pressure gauge 214 is provided on the main gas path 213. In some embodiments, a pressure reducing valve 215 is provided on the main gas path 213. The third pressure gauge 214 is used to display the gas path pressure of the main gas path 213, and the pressure reducing valve 215 is used to accurately reduce the pressure of the protective gas or air in the main gas path 213 to the required pressure value, such as 100 Kpa.
[0048] In some embodiments, a gas path switching valve 216 is provided at the connection of the main gas path 213, the first gas path 203 and the second gas path 204. For example, the gas path switching valve 216 can be a solenoid valve. The gas path switching valve 216 is used to control which one of the first gas path 203 and the second gas path 204 is connected to the main gas path 213, so as to control whether the protective gas or the dry gas enters the main gas path 213. Optionally, the gas path switching solenoid valve 216 is a two-position three-way valve, which includes a NO port connected to the first gas path 203 and a NC port connected to the second gas path 204. When the gas path switching valve 216 is de-energized, the NO port is opened and the NC port is closed. At this time, the first gas path 203 is connected to the main gas path 213, and the protective gas can enter the main gas path 213 through the first gas path 203; when the gas path switching valve 216 is energized, the NO port is closed and the NC port is opened. At this time, the second gas path 204 is connected to the main gas path 213, and the dry gas can enter the main gas path 213 through the second gas path 204. It should be noted that when a gas path switching valve 216 is provided at the connection of the main gas path 213, the first gas path 203 and the second gas path 204, a switching valve may not be provided on the second gas path 204 any more.
[0049] Continue to refer to Figure 1 As shown, in order to avoid the waste liquid discharged from the liquid discharge port of the synthesis device 100 from polluting the environment, in some embodiments, the nucleic acid synthesis equipment further includes a waste liquid discharging assembly 400. The waste liquid discharging assembly 400 includes a waste liquid pipe 401 and a waste liquid collection container 402. The waste liquid collection container 402 is communicated with the liquid discharge port through the waste liquid pipe 401, and a waste liquid discharge switching valve 403 is provided on the waste liquid pipe 401.
[0050] The waste liquid discharge switching valve 403 is used to assist the synthesis device 100 in storing the synthesis reaction reagent and discharging the waste liquid to the waste liquid collection container 402. When the waste liquid discharge switching valve 403 is energized, the waste liquid pipe 401 is conducted, the liquid discharge port is automatically opened, and the residual synthesis reaction reagent in the nucleic acid synthesis chamber 101 flows into the waste liquid collection container 402 through the liquid discharge port and via the waste liquid pipe 401; when the waste liquid discharge switching valve 403 is de-energized, the waste liquid pipe 401 is blocked, and the liquid discharge port is forced to close, so as to ensure that the newly added synthesis reaction reagent in the nucleic acid synthesis chamber 101 cannot be discharged.
[0051] In some embodiments, the reagent switching and transporting assembly 300 further includes a metering pump 302. The metering pump 302 is disposed on the liquid path 303 and is used to meter the synthesis reaction reagent or the cleaning reagent in the liquid path 303.
[0052] Continuing to refer to Figure 1 As shown, in some embodiments, the switching valve 301 is a rotary switching valve. The rotary switching valve can access more than ten kinds of synthesis reaction reagents. Different synthesis reaction reagents are used for different reaction steps of nucleic acid synthesis reactions, such as deprotection, activation coupling, oxidation, capping and other reaction steps. It should be noted that the steps of nucleic acid synthesis reactions are prior art, and the synthesis reaction reagents used in each step are also prior art, so they will not be described in detail here.
[0053] In some embodiments, the switching valve 301 is used to switch the connection between different reagent ports and the synthesis device 100, so as to form a fluid path for different synthesis reaction reagents to flow into the liquid path 303. For example, when the channel of the switching valve 301 is switched to the 10th position, at this time, acetonitrile can flow through the liquid path 303 into the synthesis device 100 under the drive of the metering pump 302.
[0054] In some embodiments, the metering pump 302 is a rotary metering pump, which is used as the driving force for reagent transportation and can also meter the reagent injected into the synthesis device 100. The reagent input into the synthesis device 100 per revolution of the rotary metering pump is 0.2 ml. For example, if 1 mL of synthesis reaction reagent needs to be input into the synthesis device 100, controlling the rotary metering pump 302 to rotate five circles is sufficient.
[0055] In summary, this nucleic acid synthesis equipment is used in nucleic acid synthesis reactions. After a synthesis reaction reagent reacts with the synthesis carrier, we need to introduce a protective gas into the synthesis column to drain the residual reagent in the synthesis column after the reaction, and then inject a cleaning reagent into the synthesis column to clean the reaction environment in the synthesis column. Then, dry air is introduced into the synthesis column to press-dry the residual cleaning reagent, so as to provide a dry and reagent-free residual environment for the next injection of a new synthesis reaction reagent.
[0056] Taking the need to drain, clean, and press-dry the deprotection reagent TCA (trichloroacetic acid) after the reaction in the synthesis column as an example, the steps of using argon to drain the synthesis reagent, acetonitrile to clean the residual synthesis reagent, and air to press-dry the cleaning reagent acetonitrile are as follows:
[0057] 1. Draining the synthesis reaction reagent TCA with argon:
[0058] The air circuit cut-off switch valve 205 is powered on → the air circuit switching valve 216 is powered off → the waste liquid discharge switch valve 403 is powered on → the residual reagent TCA in the synthesis column is discharged into the waste liquid collection container 402, and wait for 10 seconds → the air circuit cut-off switch valve 205 is powered off and the waste liquid discharge switch valve 403 is powered off, and the argon discharge procedure ends;
[0059] 2. Acetonitrile is used to clean the residual synthesis reaction reagent TCA:
[0060] The switching valve 301 is switched to the 10th acetonitrile port position → the metering pump 302 is powered on and rotated 25 turns to inject 5 ml of acetonitrile into the synthesis column → the metering pump 302 is powered off → the residual TCA reagent is cleaned with acetonitrile, and the cleaning procedure ends;
[0061] 3. Air is used to dry the cleaning reagent acetonitrile:
[0062] The air circuit switching valve 216 is powered on → the waste liquid discharge switch valve 403 is powered on → the cleaning reagent acetonitrile in the synthesis column is dried and discharged into the waste liquid collection container 402, wait for 15 seconds, and there is no reagent residue in the synthesis column → the air circuit switching valve 216 is powered off and the waste liquid discharge switch valve 403 is powered off, and the air drying procedure ends.
[0063] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, rather than limiting the implementation manners of the present invention. For those of ordinary skill in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all implementation manners here. Any modifications, equivalent replacements, and improvements made within the spirit and principle of the present invention shall be included within the protection scope of the claims of the present invention.
Claims
1. A nucleic acid synthesis device, characterized in that, it includes: a synthesis device (100), the synthesis device (100) having a nucleic acid synthesis chamber (101), the nucleic acid synthesis chamber (101) having a drain port that can be selectively opened and closed; a gas path drying component (200), the gas path drying component (200) including a gas source and a gas path, the gas source being used to provide a gas that is compatible with cleaning reagents and synthesis reaction reagents, the gas source being selectively communicable with the nucleic acid synthesis chamber (101) through the gas path to drain the synthesis reaction reagents in the nucleic acid synthesis chamber (101) and dry the cleaning reagents; a reagent switching and transporting component (300), the reagent switching and transporting component (300) including a switching valve (301) and a liquid path (303), the reagent ports of the switching valve (301) being used to communicate with a plurality of reagent sources one by one, the reagent sources including a cleaning reagent source and a reaction reagent source, the outlet of the switching valve (301) being communicated with the nucleic acid synthesis chamber (101) through the liquid path (303).
2. The nucleic acid synthesis device according to claim 1, characterized in that, the gas path drying component (200) includes a first gas source (201) and a first gas path (203), the first gas source (201) being used to provide a protective gas, the first gas source (201) being communicated with the nucleic acid synthesis chamber (101) through the first gas path (203) and being used to introduce the protective gas into the nucleic acid synthesis chamber (101) to drain the residual synthesis reaction reagents in the nucleic acid synthesis chamber (101); the gas path drying component (200) includes a second gas source (202) and a second gas path (204), the second gas source (202) being used to provide air, the second gas source (202) being communicated with the nucleic acid synthesis chamber (101) through the second gas path (204) and being used to introduce air into the nucleic acid synthesis chamber (101) to dry the residual cleaning reagents in the nucleic acid synthesis chamber (101); wherein, both the first gas path (203) and the second gas path (204) can be selectively opened and closed.
3. The nucleic acid synthesis device according to claim 1, characterized in that, the nucleic acid synthesis device further includes a waste liquid discharging component (400), the waste liquid discharging component (400) including a waste liquid pipe (401) and a waste liquid collection container (402), the waste liquid collection container (402) being communicated with the drain port through the waste liquid pipe (401), a waste liquid discharging switch valve (403) being provided on the waste liquid pipe (401); and / or, a metering pump (302) is provided on the liquid path (303).
4. The nucleic acid synthesis device according to claim 2, characterized in that, a gas path cut-off switch valve (205) is provided on the first gas path (203).
5. The nucleic acid synthesis device according to claim 2, characterized in that, a first pressure relief valve (206) is provided on the first gas path (203); and / or, a first pressure gauge (207) is provided on the first gas path (203); And / or, a first pressure regulating valve (208) is provided on the first gas path (203); And / or, a second pressure relief valve (210) is provided on the second gas path (204); And / or, a second pressure gauge (211) is provided on the second gas path (204); And / or, a second pressure regulating valve (212) is provided on the second gas path (204).
6. The nucleic acid synthesis device according to claim 2, wherein, a dry filter (209) is provided on the second gas path (204).
7. The nucleic acid synthesis device according to claim 2, wherein, the first gas source (201) is an inert gas cylinder, and the protective gas is an inert gas; or, the first gas source (201) is a nitrogen cylinder, and the protective gas is nitrogen.
8. The nucleic acid synthesis device according to claim 2, wherein, the gas path drying assembly (200) further includes a main gas path (213), one end of the first gas path (203) is communicated with the first gas source (201), the other end is communicated with the inlet end of the main gas path (213), one end of the second gas path (204) is communicated with the second gas source (202), the other end is communicated with the inlet end of the main gas path (213), and the outlet end of the main gas path (213) is communicated with the inlet port of the nucleic acid synthesis chamber (101).
9. The nucleic acid synthesis device according to claim 8, wherein, a third pressure gauge (214) is provided on the main gas path (213); And / or, a pressure reducing valve (215) is provided on the main gas path (213).
10. The nucleic acid synthesis device according to claim 8, wherein, a gas path switching valve (216) is provided at the connection of the main gas path (213), the first gas path (203) and the second gas path (204).