Nucleic acid synthesis equipment

Abstract

The invention discloses nucleic acid synthesis equipment. The nucleic acid synthesis equipment comprises a synthesis assembly, a gas supply assembly, a liquid supply assembly, a dry pressing gas path pipe, a gas-liquid switching valve and a gas-liquid supply pipe, before a synthesis reaction is started, a gas source injects a certain amount of gas into a synthesis cavity of a synthesis device through a gas path, the synthesis cavity forms a sealing cavity with a certain pressure, and the pressure in the sealing cavity is detected by a pressure detection mechanism; the air tightness of the synthetic assembly can be judged by judging whether the pressure change of the sealing cavity in a period of time exceeds the expectation or not, manual detection is not needed in the process, and the labor cost is reduced. Moreover, after the synthesis reaction in the synthesis device is completed, the working state of the gas-liquid switching valve is switched, so that gas in the gas source can enter the synthesis cavity through the gas-liquid supply pipe, the gas-liquid supply pipe is dried, then liquid in the synthesis cavity can be pressed to be dry, the problem that the synthesis carrier cannot be completely poured out due to vibration liquid dropping is solved, and the synthesis efficiency is improved. The synthesis accuracy of the synthesis carrier is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of nucleic acid synthesis, and in particular to a nucleic acid synthesis device. Background Art

[0002] Nucleic acid synthesis reactions must be carried out in a sealed environment (i.e., isolated from water, steam and other media in the air). Nucleic acid synthesis equipment is a device for carrying out nucleic acid synthesis reactions. Based on the airtightness requirements for nucleic acid synthesis reactions, nucleic acid synthesis equipment will install sealing devices in the synthesis reaction system to achieve sealed protection during the synthesis process.

[0003] During the nucleic acid synthesis process of the nucleic acid synthesis equipment, if the sealing device has a reduced airtightness due to various reasons (such as failure of the sealing ring, low assembly accuracy, etc.), the synthetic material will come into contact with water, oxygen and other substances in the air, which will affect the synthesis efficiency and even cause synthesis failure, thereby leading to an increase in production costs. In addition, in the nucleic acid synthesis equipment, since the injection pipeline is injected from the upper end of the synthesis column gland, if the lid is opened after the synthesis reaction is completed, the vibration of the synthesis column gland causes the liquid retained in the injection pipeline to drip into the synthesis column. Due to the viscosity of the liquid, if the liquid drips on the synthesis carrier, it will stick to the wall, which will eventually cause the synthesis carrier to be unable to be automatically poured out of the synthesis column for subsequent automated processing, which seriously reduces the synthesis accuracy of the synthesis carrier.

[0004] Currently, the nucleic acid synthesis equipment on the market lacks a system for real-time monitoring of the sealing device, so it is impossible to monitor the sealing effect of the sealing device during the entire synthesis process. Therefore, how to propose a nucleic acid synthesis equipment that can detect air tightness during the synthesis process and enable the synthesis carrier to be smoothly poured out of the synthesis column is a technical problem that needs to be solved urgently. Summary of the invention

[0005] The object of the present invention is to provide a nucleic acid synthesis device, which is not only simple in structure and has an airtightness detection function, but also can smoothly and thoroughly pour out the synthesis carrier.

[0006] To achieve this object, the present invention adopts the following technical solutions:

[0007] A nucleic acid synthesis device comprises: a synthesis component, the synthesis component comprises a synthesis device and a sealing gland, the synthesis device has a synthesis chamber, and the sealing gland is detachably mounted at the opening of the synthesis chamber; an air supply component, the air supply component comprises an air source, an air path and a pressure detection mechanism, the air source is selectively connected to the synthesis chamber through the air path, and the pressure detection mechanism is arranged on the air path; a liquid supply component, the liquid supply component comprises a liquid source and a liquid path, one end of the liquid path is connected to the liquid source; a compressed air path pipe, a gas-liquid switching valve and a gas-liquid supply pipe, the gas-liquid switching valve has a first inlet, a second inlet and an outlet, the other end of the liquid path is connected to the first inlet, one end of the compressed air path pipe is connected to the air path, and the other end is connected to the second inlet, the gas-liquid supply pipe is connected to the gas path, and the gas-liquid supply pipe is connected to the gas path. One end of the tube is connected to the synthesis chamber, and the other end is connected to the outlet. The gas-liquid switching valve has a first state in which the first inlet is connected to the outlet and a second state in which the second inlet is connected to the outlet. The liquid source supplies liquid to the synthesis chamber through the liquid circuit, the gas-liquid switching valve in the first state, and the gas-liquid supply pipe. The gas source supplies gas to the synthesis chamber through part of the gas circuit, the squeezed gas circuit pipe, the gas-liquid switching valve in the second state, and the gas-liquid supply pipe to dry the gas-liquid supply pipe. The gas source can supply the gas to the synthesis chamber through the complete gas circuit to squeeze the synthesis carrier in the synthesis chamber dry, and the synthesis chamber can form a sealed chamber, and the pressure detection mechanism is used to detect the gas pressure in the sealed chamber.

[0008] Preferably, the pressure detecting mechanism is a pressure sensor; and / or, the gas supply assembly also includes a first switch valve, which is arranged on the gas path, along the direction of the gas input into the synthesis chamber, the pressure detecting mechanism is arranged downstream of the first switch valve, and one end of the compressed air path pipe is connected between the pressure detecting mechanism and the first switch valve.

[0009] Preferably, the gas supply component further includes a pressure regulating valve, which is arranged on the gas line, and is used to adjust the pressure of the gas output by the gas source to a first target value; and / or, the gas supply component further includes a pressure relief valve, which is arranged on the gas line, and is used to relieve pressure when the pressure of the gas exceeds a first target value; and / or, the gas supply component further includes a pressure reducing valve, which is arranged on the gas line, and is used to reduce the pressure of the gas to a second target value.

[0010] Preferably, the gas supply assembly further comprises a first pressure gauge, which is disposed upstream or downstream of the pressure regulating valve along the direction in which the gas is input into the synthesis chamber; and / or, the gas supply assembly further comprises a second pressure gauge, which is disposed downstream of the pressure reducing valve along the direction in which the gas is input into the synthesis chamber.

[0011] Preferably, the nucleic acid synthesis device further comprises a second switch valve, and the second switch valve is arranged on the liquid path.

[0012] Preferably, the nucleic acid synthesis device further comprises a waste discharge component, which comprises a waste collection container and a waste discharge pipeline, and the synthesis chamber has a waste discharge port, which is selectively connected to the waste collection container through the waste discharge pipeline.

[0013] Preferably, the waste collecting container includes a waste liquid barrel and an exhaust hood, the waste discharge pipeline includes a waste liquid pipe and an exhaust gas pipe, the waste liquid barrel is connected to the waste discharge port through the waste liquid pipe, a third switch valve is provided on the waste liquid pipe, and the exhaust hood is connected to the waste liquid barrel through the exhaust gas pipe.

[0014] Preferably, the gas source is an inert gas bottle, and the gas is an inert gas.

[0015] Preferably, the gas source is an argon gas cylinder, and the gas is argon gas; or, the gas source is a nitrogen gas cylinder, and the gas is nitrogen gas.

[0016] Preferably, the sealing gland includes a cover body and a sealing ring, and the sealing ring is clamped between the cover body and the synthesis device; or, the sealing gland includes a cover body, the gas path is connected to the side of the cover body and connected to the upper space of the synthesis chamber, and the gas-liquid supply pipe passes through the cover body from top to bottom and penetrates into the lower space of the synthesis chamber.

[0017] Beneficial effects of the present invention:

[0018] Before the synthesis reaction of the nucleic acid synthesis device provided by the present invention begins, the gas source can inject a certain amount of gas into the synthesis cavity of the synthesis device through the gas path, so that the synthesis cavity can form a sealed cavity with a certain pressure, and the pressure in the sealed cavity is detected by the pressure detection mechanism. By judging whether the pressure change in the sealed cavity exceeds the expectation within a period of time, the air tightness of the synthesis component can be judged. After the synthesis reaction in the synthesis device is completed, by switching the working state of the gas-liquid switching valve, the gas in the gas source can enter the synthesis cavity through the gas-liquid supply pipe, and the drying of the gas-liquid supply pipe can be achieved in this process. After that, the gas in the gas source can enter the synthesis cavity through the gas path to press the liquid in the synthesis cavity dry, thereby solving the problem that the synthetic carrier cannot be completely poured out due to vibration dripping. In addition, while pressing the synthetic carrier dry, the nucleic acid synthesis device is not only simple in structure, but also has an airtightness detection function, reduces production costs, does not require manual participation in detection, reduces labor costs, and the synthetic carrier can be completely poured out of the synthesis device for the next round of reaction, which improves the synthesis accuracy of the synthetic carrier. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 It is a schematic diagram of the nucleic acid synthesis device provided by the present invention.

[0020] In the figure:

[0021] 100, synthesis component; 110, synthesis device; 120, sealing gland; 101, synthesis chamber;

[0022] 200, gas supply assembly; 201, gas source; 202, gas circuit; 203, pressure detection mechanism; 204, first switch valve; 205, first pressure gauge; 206, pressure relief valve; 207, pressure reducing valve; 208, pressure regulating valve; 209, second pressure gauge;

[0023] 300, liquid supply component; 301, liquid circuit; 302, second switch valve;

[0024] 400, waste discharge assembly; 401, waste liquid barrel; 402, exhaust hood; 403, waste liquid pipe; 404, waste gas pipe; 405, third switch valve;

[0025] 500. Press the air pipe dry; 600. Gas-liquid switching valve; 700. Gas-liquid supply pipe. DETAILED DESCRIPTION

[0026] The present invention will be further described in detail below in conjunction with the accompanying drawings and embodiments. It is to be understood that the specific embodiments described herein are only used to explain the present invention, rather than to limit the present invention. It should also be noted that, for ease of description, only parts related to the present invention, rather than all structures, are shown in the accompanying drawings.

[0027] In the description of the present invention, unless otherwise clearly specified and limited, the terms "connected", "connected", and "fixed" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0028] In the present invention, unless otherwise clearly specified and limited, a first feature being "above" or "below" a second feature may include that the first and second features are in direct contact, or may include that the first and second features are not in direct contact but are in contact through another feature between them. Moreover, a first feature being "above", "above" and "above" a second feature includes that the first feature is directly above and obliquely above the second feature, or simply indicates that the first feature is higher in level than the second feature. A first feature being "below", "below" and "below" a second feature includes that the first feature is directly below and obliquely below the second feature, or simply indicates that the first feature is lower in level than the second feature.

[0029] In the description of this embodiment, the terms "upper", "lower", "right", etc., directions or positional relationships are based on the directions or positional relationships shown in the drawings, and are only for the convenience of description and simplification of operation, rather than indicating or implying that the device or element referred to must have a specific direction, be constructed and operated in a specific direction, and therefore cannot be understood as limiting the present invention. In addition, the terms "first" and "second" are only used to distinguish in the description and have no special meaning.

[0030] The present invention provides a nucleic acid synthesis device, which can perform nucleic acid synthesis reactions. Specifically, Figure 1As shown, the nucleic acid synthesis device includes a synthesis component 100 and a gas supply component 200. The synthesis component 100 provides a reaction environment for the occurrence of nucleic acid synthesis reaction. The synthesis component 100 includes a synthesis device 110 and a sealing gland 120. The synthesis device 110 has a synthesis chamber 101, and the synthesis chamber 101 has an opening. The sealing gland 120 is detachably installed at the opening of the synthesis chamber 101. After the sealing gland 120 is installed at the opening of the synthesis chamber 101, it can seal the opening of the synthesis chamber 101. The gas supply component 200 is used to supply gas into the synthesis chamber 101. The gas supply component 200 includes a gas source 201, a gas circuit 202 and a pressure detection mechanism 203. The gas circuit 202 is a pipeline capable of conveying gas. The gas source 201 is selectively connected to the synthesis chamber 101 through the gas circuit 202. The gas source 201 is used to pass gas into the synthesis chamber 101. The pressure detection mechanism 203 is arranged on the gas circuit 202. The synthesis cavity 101 can form a sealed cavity. After a certain amount of gas is injected into the synthesis cavity 101, the sealed cavity forms a chamber with a certain pressure. The pressure detection mechanism 203 is used to detect the gas pressure in the sealed cavity.

[0031] It should be noted that the gas injected into the synthesis chamber 101 by the gas source 201 through the gas path 202 can be used as a detection gas as well as a gas for draining synthesis reaction reagents or cleaning reagents, as long as the gas is compatible with the synthesis reaction reagents and the cleaning reagents. Compatibility here means that it does not affect the performance of the synthesis reaction reagents and the cleaning reagents.

[0032] Compared with the nucleic acid synthesis equipment without air tightness detection in the prior art, in the nucleic acid synthesis equipment provided by the present invention, before the air tightness detection is performed, the synthesis carrier is first placed in the synthesis device 110, and then the synthesis device 110 is covered and closed. When the air tightness detection is performed, the gas source 201 can inject a certain amount of gas into the synthesis chamber 101 of the synthesis device 110 through the gas path 202. The injection of gas increases the air pressure in the synthesis chamber 101. After the air pressure increases to the expected value, the synthesis chamber 101 is switched to a sealed state, so that the synthesis chamber 101 is formed into a sealed chamber with a certain pressure. The nucleic acid synthesis equipment is left to stand for a period of time. During this process, the pressure in the sealed chamber is detected in real time by the pressure detection mechanism 203. By judging whether the pressure change in the sealed chamber during this period exceeds expectations, the air tightness of the synthesis component 100 and whether leakage occurs can be judged. If the air tightness decreases, the nucleic acid synthesis equipment can give an alarm in time and suspend nucleic acid synthesis, so that the production personnel can effectively maintain the synthesis component 100 immediately. The nucleic acid synthesis equipment not only has a simple structure and an airtightness detection function, but can also effectively avoid significant losses of reagents and materials required for production, thereby reducing production costs and improving production efficiency. It also does not require manual participation in detection, thereby reducing labor costs.

[0033] In some embodiments, the synthesis device 110 is a synthesis reaction column, and the top of the synthesis reaction column forms an opening. Optionally, the synthesis reaction column includes a flange portion, a cylindrical portion and a tapered portion connected sequentially from top to bottom, and the top of the synthesis reaction column forms a circular opening. Of course, in other embodiments, the synthesis reaction column can also be set to other shapes according to needs.

[0034] In one embodiment, the sealing gland 120 includes a plate-shaped cover body and a sealing ring, and the sealing ring is sandwiched between the cover body and the composite device 110. When the cover body carrying the sealing ring is pressed into the opening of the composite device 110, an effective seal can be formed. The provision of the sealing ring can improve the airtightness between the composite device 110 and the sealing gland 120. Optionally, the plate-shaped cover body is covered on the flange portion, and can be fixed to the flange portion. The fixing method is not limited, and can be connected by a connector, magnetic attraction, etc. Optionally, the sealing ring is an O-shaped rubber ring. Of course, in other embodiments, the sealing gland 120 can also include a columnar cover body and a sealing ring, and the columnar cover body is inserted into the opening of the composite device 110, and the sealing ring is sleeved outside the cover body and sandwiched between the outer wall surface of the cover body and the inner wall surface of the composite device 110.

[0035] In some embodiments, the pressure detection mechanism 203 is a pressure sensor. Of course, in other embodiments, the pressure detection mechanism 203 can also be a pressure gauge or other mechanism that can detect pressure and display pressure values.

[0036] Continue to refer to Figure 1 As shown, the gas supply assembly 200 also includes a first switch valve 204, which is arranged on the gas path 202, along the direction of gas input into the synthesis chamber 101, and the pressure detection mechanism 203 is arranged downstream of the first switch valve 204. The first switch valve 204 is used to control the on-off of the gas path 202, and does not affect the detection of the pressure in the synthesis chamber 101 by the pressure detection mechanism 203. Optionally, the first switch valve 204 is a solenoid valve. Further optionally, the first switch valve 204 is a liquid path direct solenoid valve, the liquid path direct solenoid valve is powered on and opened, at this time the gas path 202 is in a conducting state, and the gas source 201 can transport gas into the synthesis chamber 101; the liquid path direct solenoid valve is powered off and closed, at this time the gas path 202 is in a blocked state, and the gas source 201 stops transporting gas into the synthesis chamber 101.

[0037] In some embodiments, the gas source 201 is an inert gas bottle, and the gas is an inert gas. The properties of inert gas are stable, and the use of inert gas as a detection gas is highly safe. In one embodiment, the inert gas bottle is an argon gas bottle, and the gas is argon; in another embodiment, the inert gas bottle is a nitrogen gas bottle, and the gas is nitrogen.

[0038] In order to store as much gas as possible, the gas is generally stored in a high-pressure state in the gas cylinder, which results in a higher pressure of the gas discharged from the gas cylinder. In order to roughly adjust the gas to a usable range, continue to refer to Figure 1 As shown, in some embodiments, the gas supply assembly 200 further includes a pressure regulating valve 208, which is disposed on the gas circuit 202, and the pressure regulating valve 208 is used to adjust the pressure of the gas output by the gas source 201 to a first target value. Optionally, the first target value is 200 KPa. Of course, in other embodiments, the first target value can also be set to other values ​​according to requirements.

[0039] In order to protect the entire air supply assembly 200, continue to refer to Figure 1 As shown, in some embodiments, the gas supply assembly 200 further includes a pressure relief valve 206, which is disposed on the gas circuit 202. The pressure relief valve 206 is used to relieve pressure when the pressure of the gas exceeds the first target value. In one embodiment, when the pressure in the gas circuit 202 exceeds the 200KPa pressure set by the pressure relief valve 206, the gas will be relieved from the pressure relief valve 206.

[0040] To fine-tune the pressure in the gas circuit 202, continue to refer to Figure 1 As shown, in some embodiments, the gas supply assembly 200 further includes a pressure reducing valve 207, which is disposed on the gas circuit 202 and is used to reduce the pressure of the gas to a second target value. Optionally, the second target value is 100 KPa.

[0041] It should be noted that the pressure regulating valve 208, the pressure relief valve 206 and the pressure reducing valve 207 are sequentially arranged along the direction of gas input into the synthesis chamber 101. In addition, the pressure regulating valve 208, the pressure relief valve 206 and the pressure reducing valve 207 are all electromagnetic valves for easy control.

[0042] Continue to refer to Figure 1 As shown, in some embodiments, the gas supply assembly 200 further includes a first pressure gauge 205, which is disposed upstream of the pressure regulating valve 208 along the direction of gas input into the synthesis chamber 101. The first pressure gauge 205 is used to display the pressure in the gas circuit 202 before the pressure regulating valve 208 regulates the pressure. If the pressure exceeds the expected value, the pressure regulating valve 208 is used to adjust the pressure. In some embodiments, the first pressure gauge 205 can also be disposed downstream of the pressure regulating valve 208 to display the pressure in the gas circuit 202 after the pressure regulating valve 208 regulates the pressure. Specifically, it can be disposed between the pressure regulating valve 208 and the pressure relief valve 206.

[0043] Continue to refer to Figure 1As shown, in some embodiments, the gas supply assembly 200 further includes a second pressure gauge 209, which is disposed downstream of the pressure reducing valve 207 along the direction of gas input into the synthesis chamber 101. The second pressure gauge 209 is used to display the pressure in the gas circuit 202 after the pressure is reduced by the pressure reducing valve 207.

[0044] The forward flow route of the gas is as follows: the gas source 201 provides gas → the pressure regulating valve 208 roughly reduces the pressure → the pressure reducing valve 207 accurately reduces the pressure → the second pressure gauge 209 displays the pressure → the first switch valve 204 → the pressure detection mechanism 203 → the synthesis component 100.

[0045] Continue to refer to Figure 1 As shown, the nucleic acid synthesis device further includes a liquid supply component 300. Specifically, the liquid supply component 300 includes a liquid source (not shown in the figure), a liquid path 301, and a second switch valve 302. The liquid path 301 is a pipeline capable of conveying reagents. One end of the liquid path 301 is connected to the liquid source. The liquid source can inject liquid into the synthesis chamber 101 through the liquid path 301. The second switch valve 302 is arranged on the liquid path 301. In some embodiments, the liquid source is used to provide a reagent. Optionally, the reagent is a synthesis reaction reagent or a cleaning reagent.

[0046] Optionally, the second switch valve 302 is a solenoid valve. Further optionally, the second switch valve 302 is a liquid path direct solenoid valve, which is opened when the second switch valve 302 is powered on, the liquid path 301 is in a conducting state, and the liquid source transports the synthesis reaction reagent or the cleaning reagent into the synthesis chamber 101 through the liquid path 301; the second switch valve 302 is closed when the power is off, the liquid path 301 is in a blocked state, and the liquid source stops transporting the synthesis reaction reagent or the cleaning reagent into the synthesis chamber 101.

[0047] Continue to refer to Figure 1 As shown, the nucleic acid synthesis device also includes a compressed air pipe 500, a gas-liquid switching valve 600 and a gas-liquid supply pipe 700. Among them, the gas-liquid switching valve 600 is a three-way valve, which has a first inlet, a second inlet and an outlet, and the gas-liquid switching valve 600 has a first state in which the first inlet is connected to the outlet and a second state in which the second inlet is connected to the outlet. The gas-liquid switching valve 600 is used to connect the compressed air pipe 500, the gas-liquid supply pipe 700 and the liquid circuit 301. Specifically, the other end of the liquid circuit 301 away from the liquid source is connected to the first inlet, one end of the compressed air pipe 500 is connected to the air circuit 202, and the other end is connected to the second inlet, and one end of the gas-liquid supply pipe 700 is connected to the synthesis chamber 101, and the other end is connected to the outlet.

[0048] When the gas-liquid switching valve 600 is switched to the first state, the liquid source supplies liquid to the synthesis chamber 101 through the liquid path 301, the gas-liquid switching valve 600 in the first state, and the gas-liquid supply pipe 700. When the gas-liquid switching valve 600 is switched to the second state, the gas source 201 supplies gas to the synthesis chamber 101 through a part of the gas path 202, the compressed gas path pipe 500, the gas-liquid switching valve 600 in the second state, and the gas-liquid supply pipe 700. In this process, the gas can dry the liquid remaining in the gas-liquid supply pipe 700, so that no liquid remains in the gas-liquid supply pipe 700. In addition, after drying the gas-liquid supply pipe 700, the gas-liquid switching valve 600 is switched to the first state again. At this time, the gas source 201 can supply gas to the synthesis chamber 101 through the complete gas path 202 to perform a compression operation on the synthetic carrier in the synthesis chamber 101.

[0049] After the above operation, if the synthetic carrier needs to be poured out of the synthesis device 110 later, the sealing gland 120 needs to be removed from the synthesis device 110 first. During this process, the vibration of the sealing gland 120 will not cause the gas-liquid supply pipe 700 to drip, which will affect the thoroughness and smoothness of the subsequent pouring of the synthetic carrier out of the synthesis device 110. When the next round of synthesis is required, the synthetic carrier in the synthesis device 110 can be poured out smoothly and thoroughly, and no base deletion will occur in the next round of synthesis, thereby improving the accuracy of synthesis and reducing the synthesis cost.

[0050] In some embodiments, the gas-liquid switching valve 600 is a three-way solenoid valve having a common end, an NC end and an NO end. The common end forms an outlet, the NO end forms a first inlet, and the NC end forms a second opening. When the gas-liquid switching valve 600 is powered on, the common end of the gas-liquid switching valve 600 is switched to connect to the NC end, and the gas-liquid switching valve 600 is switched to the second state. When the gas-liquid switching valve 600 is powered off, the common end of the gas-liquid switching valve 600 is switched to connect to the NO end, and the gas-liquid switching valve 600 is switched to the first state.

[0051] In some embodiments, one end of the compressed air pipe 500 is connected between the pressure detection mechanism 203 and the first switch valve 204 .

[0052] In some embodiments, the gas-liquid supply pipe 700 passes through the cover from top to bottom and extends into the lower space of the synthesis chamber 101 , while the gas path 202 is connected to the side of the cover and connected to the upper space of the synthesis chamber 101 .

[0053] When draining the reagent from the gas-liquid switching valve 600 to the gas-liquid supply pipe 700 at the synthesis device 110 end, the forward flow route of the gas is as follows: the gas source 201 provides gas → the pressure regulating valve 208 roughly reduces the pressure → the pressure reducing valve 207 accurately reduces the pressure → the second pressure gauge 209 displays the pressure → the first switch valve 204 is powered on and opened → the gas-liquid switching valve 600 is powered on and opened → the synthesis component 100.

[0054] When performing the gas operation of pressing the synthesis device 110 and detecting the air tightness of the synthesis device 110, the forward flow route of the gas is as follows: the gas source 201 provides gas → the pressure regulating valve 208 roughly reduces the pressure → the pressure reducing valve 207 accurately reduces the pressure → the second pressure gauge 209 displays the pressure → the pressure detection mechanism 203 → the synthesis component 100. The gas enters the synthesis device 110 through this path, and through the control of the device, the reaction reagent in the synthesis device 110 is pressed dry by the gas, and the gas pressure in the synthesis device 110 is collected by the pressure detection mechanism 203 to detect the air tightness in the synthesis device 110.

[0055] Continue to refer to Figure 1 As shown, the nucleic acid synthesis device also includes a waste discharge component 400, which is used to discharge waste liquid or waste gas in the synthesis chamber 101. Specifically, the waste discharge component 400 includes a waste collection container and a waste discharge pipeline, and the synthesis chamber 101 has a waste discharge port, which can be selectively connected to the waste collection container through the waste discharge pipeline. In one embodiment, the waste discharge port is formed at the bottom of the synthesis reaction column.

[0056] In some embodiments, the waste collecting container includes a waste liquid barrel 401 and an exhaust hood 402, the waste discharge pipeline includes a waste liquid pipe 403 and an exhaust gas pipe 404, the waste liquid barrel 401 is connected to the waste discharge port through the waste liquid pipe 403, a third switch valve 405 is provided on the waste liquid pipe 403, and the exhaust hood 402 is connected to the waste liquid barrel 401 through the exhaust gas pipe 404.

[0057] The waste liquid barrel 401 is used to collect waste liquid, which can be liquid in the synthesis reaction process or liquid after cleaning, and is used as a transfer station for waste gas recovery. The exhaust hood 402 is used to discharge the waste gas in the waste liquid barrel 401. The waste liquid pipe 403 is used to transport the liquid that has completed the operation in the synthesis chamber 101 to the waste liquid barrel 401 or to transport the compressed gas to the waste liquid barrel 401. The waste gas pipe 404 is used to transport the waste gas in the waste liquid barrel 401 to the exhaust hood 402 to prevent the waste liquid from overflowing from the waste liquid barrel 401 due to excessive pressure in the waste liquid barrel 401.

[0058] Optionally, the third switch valve 405 is a solenoid valve. Further optionally, the third switch valve 405 is a liquid path direct solenoid valve, which is opened when powered on, the waste liquid pipe 403 is in a conducting state, and the reagent or gas in the synthesis chamber 101 is discharged into the waste liquid barrel 401 through the waste liquid pipe 403; the liquid path direct solenoid valve is closed when powered off, the waste liquid pipe 403 is in a blocked state, and the synthesis chamber 101 can store reagents and gases.

[0059] In this embodiment, the nucleic acid synthesis device also includes a control mechanism, which can be a centralized or distributed controller. For example, the controller can be a single single-chip microcomputer or a distributed plurality of single-chip microcomputers. The control program can be run in the single-chip microcomputer to control the aforementioned valve bodies and the pressure detection mechanism 203 to realize their functions respectively.

[0060] The nucleic acid synthesis equipment can complete the following actions:

[0061] The action of storing reagents in the synthesis component 100 is as follows: the second switch valve 302 is opened, the third switch valve 405 is closed, and the gas-liquid switching valve 600 is in the first state. According to the requirements of the synthesis reaction, the liquid source injects a certain amount of reagents into the synthesis chamber 101 through the liquid path 301 and the gas-liquid supply pipe 700 for reaction.

[0062] The action of the synthesis component 100 to discharge the reagent is as follows: the second switch valve 302 is closed, the gas-liquid switching valve 600 is in the first state, the third switch valve 405 and the first switch valve 204 are opened, and the gas source 201 injects gas into the synthesis chamber 101 through the gas path 202. The gas squeezes the reagent, and the reagent is discharged to the waste liquid barrel 401 through the waste liquid pipe 403, thereby completing the discharge of the reagent from the synthesis chamber 101.

[0063] The synthesis component 100 stores gas by closing the second switch valve 302 and the third switch valve 405, making the gas-liquid switching valve 600 in the first state, opening the first switch valve 204, and injecting a certain amount of gas into the synthesis chamber 101 through the gas path 202 according to the air tightness detection requirements for air tightness detection;

[0064] The action of exhausting the gas from the synthesis component 100 is as follows: close the second switch valve 302 and the first switch valve 204, put the gas-liquid switching valve 600 in the first state, open the third switch valve 405 to exhaust the gas from the synthesis chamber 101, and the gas enters the waste liquid barrel 401 through the waste liquid pipe 403, and enters the exhaust hood 402 through the waste gas pipe 404.

[0065] The following is a detailed introduction to the process of airtightness testing of nucleic acid synthesis equipment:

[0066] Step 1: Inject gas into the synthesis chamber 101 to form a sealed chamber.

[0067] In one embodiment, step one specifically includes the following steps: press the sealing cover 120 into the synthesis device 110 → close the second switch valve 302 → put the gas-liquid switching valve 600 in the first state → close the third switch valve 405 → open the first switch valve 204, and input 100 kPa argon gas into the synthesis chamber 101 for 5 seconds → close the first switch valve 204, so that the synthesis chamber 101 forms a sealed chamber.

[0068] Step 2: Start the pressure detection mechanism 203 to detect the pressure in the sealed cavity.

[0069] In one embodiment, step 2 is specifically as follows: within 15 seconds, the pressure sensor automatically reads the pressure value in the sealing cavity twice, and determines whether the sealing of the sealing gland 120 to the composite device 110 fails according to the change in the pressure value. The qualified standard is specifically as follows: the pressure difference before and after the two pressure measurements does not exceed 15%, and the absolute value of the pressure difference is not less than 60KPa.

[0070] Step 3: If it is determined that the seal fails, the nucleic acid synthesis device suspends the synthesis reaction and manual maintenance of the nucleic acid synthesis device is performed.

[0071] If the sealing is determined to be successful, the synthesis chamber 101 is deflated and opened for nucleic acid synthesis reaction.

[0072] In one embodiment, the specific operation for determining whether the sealing is successful is as follows: open the third switch valve 405 for one second to release part of the pressure in the synthesis device 110 to the waste liquid bucket 401 to avoid excessive pressure in the synthesis chamber 101 caused by subsequent injection and damage to the synthesis component 100 → close the third switch valve 405 → start the current synthesis base injection file to start nucleic acid synthesis.

[0073] It should be added that, for high-throughput nucleic acid synthesis equipment, having an airtightness detection function is particularly important and has even greater significance.

[0074] High-throughput nucleic acid synthesis is a technology that can synthesize a large number of DNA fragments at the same time. It greatly improves the efficiency and accuracy of nucleic acid synthesis through automation and high-throughput methods. For high-throughput nucleic acid synthesis equipment, each synthetic carrier is transported and sorted into different bases (such as conventional A, T, C, G bases, but not limited to these bases) in the synthesis device 110 for synthesis. Each synthetic carrier will be sent to a different base synthesis device 110 for synthesis according to each round of sorting until each carrier synthesizes a complete sequence (this sequence is composed of bases such as A, T, C, G, etc.). Therefore, during the operation of the high-throughput nucleic acid synthesis equipment, the synthesis device 110 must be frequently opened and capped to realize the pouring out and putting in of the synthetic carrier. However, as the use time of the high-throughput nucleic acid synthesis device increases, frequent capping and uncapping operations will inevitably cause the O-ring provided at the sealing gland 120 to wear, and due to the phenomenon of non-concentricity between the sealing gland 120 and the synthesis device 110, the sealing between the sealing gland 120 and the synthesis device 110 will also fail, thereby affecting the instrument performance and synthesis quality of the high-throughput nucleic acid synthesis device. Therefore, in the high-throughput nucleic acid synthesis device, after the synthetic carrier is divided into the synthesis device 110 and the sealing gland 120 is pressed, and before the chemical reagent synthesis begins, the pressure detection mechanism 203 is first used to detect whether the sealing conditions at the synthesis device 110 and the sealing gland 120 meet the synthesis requirements. Specifically, the nucleic acid synthesis device with airtightness detection function proposed by the present invention delivers argon gas of a certain pressure into the synthesis device 110 before the synthesis begins, and uses a pressure sensor to monitor whether the pressure of the argon gas in the synthesis device 110 will be greatly reduced within 15 seconds, and the sealing failure phenomenon such as leakage is judged in turn, which is conducive to ensuring the instrument performance and synthesis quality of the high-throughput nucleic acid synthesis device, and has important economic significance.

[0075] The process of draining the reagents in the gas-liquid supply pipe 700 at the upper end of the synthesis device 110 is described in detail below:

[0076] Step 1: drain the reagent from the gas-liquid switching valve 600 to the gas-liquid supply pipe 700 at the upper end of the synthesis device 110.

[0077] In one embodiment, step one specifically includes the following steps: the first switch valve 204 is powered on and opened → the gas-liquid switching valve 600 is powered on and the NC end is opened → 100 kPa argon is input for 5 seconds → argon flows through the gas-liquid supply pipe 700 to drain the reagents in the gas-liquid supply pipe 700 from the gas-liquid switching valve 600 to the upper end of the synthesis device 110.

[0078] Step 2: squeeze out the reagents discharged into the synthesis device 110.

[0079] In one embodiment, step two specifically includes the following steps: the second switch valve 302 is powered off and closed → the gas-liquid switching valve 600 is powered off and the NC end is closed → the third switch valve 405 is powered on and opened → the first switch valve 204 is powered on and opened → 100 kPa argon gas is input for 50 seconds, and the argon gas flows through the gas path 202 and the synthesis device 110, and presses the reagents on the synthesis device 110 and the synthesis carrier into the waste liquid barrel 401, so that the synthesis carrier and the synthesis device 110 remain dry to avoid adhesion.

[0080] It should be added that, for high-throughput nucleic acid synthesis equipment, avoiding adhesion of synthetic carriers is particularly important and has even greater significance.

[0081] Since the nucleic acid synthesis device injects liquid from the upper end of the synthesis device 110, the gas-liquid supply pipe 700 installed on the sealing cover 120 of the synthesis device 110 will be vibrated by external force when the cover is opened, and there is a risk of liquid dripping from the gas-liquid supply pipe 700. Since the dripping reagent is viscous, the synthetic carrier will adhere to the inner wall of the synthesis device 110 and cannot be poured out of the synthesis device 110. The high-throughput nucleic acid synthesis device transports and sorts each synthetic carrier into different bases (such as conventional A, T, C, G bases, but not limited to these bases) in the synthesis device 110 for synthesis. Each carrier will be sent to a different base synthesis device 110 for synthesis according to each round of sorting until each carrier synthesizes a complete sequence (the sequence is composed of bases such as A, T, C, G, etc.). To achieve this, the synthesis carriers in the synthesis device 110 must be poured out of the synthesis device 110 each time after synthesis is completed to enter the next round of sorting. Otherwise, the synthesis carriers that are not poured out of the synthesis device 110 will miss the next round of synthesis, resulting in the bases that should have been synthesized not being synthesized, causing the bases in a synthesis sequence to be missing (a synthesis carrier represents a sequence, and a sequence is composed of preset bases). This means that the sequence has not been accurately synthesized, which not only reduces the accuracy of the synthesis, but also increases the synthesis cost.

[0082] The nucleic acid synthesis device provided by the present invention has an added function of draining the reagents in the gas-liquid supply pipe 700 at the upper end of the synthesis device 110. After the synthesis carrier completes the synthesis of one base and before pouring out the synthesis device 110, the gas source 201 is used to input argon gas through the gas path 202, and by controlling the gas-liquid switching valve 600, the argon gas is used to drain the reagents in the gas-liquid supply pipe 700 at the upper end of the synthesis device 110 into the synthesis device 110 to solve the dripping problem, and then the pressing function of the nucleic acid synthesis device is used to press the reagents on the synthesis carrier, so that the synthesis carrier and the synthesis device 110 are kept dry, so that the synthesis carrier can be smoothly poured out of the synthesis device 110.

[0083] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. For those skilled in the art, various obvious changes, readjustments and substitutions can be made without departing from the protection scope of the present invention. It is not necessary and impossible to list all the embodiments here. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. A nucleic acid synthesis device, characterized in that: include: A synthesis component (100), the synthesis component (100) comprising a synthesis device (110) and a sealing gland (120), the synthesis device (110) having a synthesis cavity (101), the sealing gland (120) being detachably mounted at an opening of the synthesis cavity (101); An air supply component (200), the air supply component (200) comprising an air source (201), an air path (202), and a pressure detection mechanism (203), the air source (201) being selectively connected to the synthesis chamber (101) via the air path (202), and the pressure detection mechanism (203) being arranged on the air path (202); A liquid supply component (300), the liquid supply component (300) comprising a liquid source and a liquid path (301), one end of the liquid path (301) being in communication with the liquid source; A compressed air path tube (500), a gas-liquid switching valve (600) and a gas-liquid supply pipe (700), wherein the gas-liquid switching valve (600) has a first inlet, a second inlet and an outlet, the other end of the liquid path (301) is connected to the first inlet, one end of the compressed air path tube (500) is connected to the gas path (202), and the other end is connected to the second inlet, one end of the compressed air path tube (500) is connected to the synthesis chamber (101), and the other end is connected to the outlet, and the gas-liquid switching valve (600) has a first state in which the first inlet is connected to the outlet, and a second state in which the second inlet is connected to the outlet; The liquid source supplies liquid to the synthesis chamber (101) through the liquid circuit (301), the gas-liquid switching valve (600) in the first state, and the gas-liquid supply pipe (700); the gas source (201) supplies gas to the synthesis chamber (101) through part of the gas circuit (202), the squeeze-dry gas circuit pipe (500), the gas-liquid switching valve (600) in the second state, and the gas-liquid supply pipe (700), so as to dry the gas-liquid supply pipe (700); the gas source (201) can supply the gas to the synthesis chamber (101) through the complete gas circuit (202), so as to squeeze the synthesis carrier in the synthesis chamber (101) dry, and the synthesis chamber (101) can form a sealed chamber, and the pressure detection mechanism (203) is used to detect the gas pressure in the sealed chamber.

2. The nucleic acid synthesis device according to claim 1, characterized in that: The pressure detection mechanism (203) is a pressure sensor; And / or, the gas supply component (200) further comprises a first switch valve (204), the first switch valve (204) being arranged on the gas path (202), along the direction in which the gas is input into the synthesis chamber (101), the pressure detection mechanism (203) being arranged downstream of the first switch valve (204), and one end of the compressed air path pipe (500) being connected between the pressure detection mechanism (203) and the first switch valve (204).

3. The nucleic acid synthesis device according to claim 1, characterized in that: The gas supply assembly (200) further comprises a pressure regulating valve (208), wherein the pressure regulating valve (208) is arranged on the gas path (202), and the pressure regulating valve (208) is used to regulate the pressure of the gas output by the gas source (201) to a first target value; And / or, the gas supply assembly (200) further comprises a pressure relief valve (206), the pressure relief valve (206) being arranged on the gas path (202), the pressure relief valve (206) being used to relieve pressure when the pressure of the gas exceeds a first target value; And / or, the gas supply assembly (200) further comprises a pressure reducing valve (207), wherein the pressure reducing valve (207) is arranged on the gas path (202), and the pressure reducing valve (207) is used to reduce the pressure of the gas to a second target value.

4. The nucleic acid synthesis device according to claim 3, characterized in that: The gas supply assembly (200) further comprises a first pressure gauge (205), and along the direction in which the gas is input into the synthesis chamber (101), the first pressure gauge (205) is arranged upstream or downstream of the pressure regulating valve (208); And / or, the gas supply assembly (200) further comprises a second pressure gauge (209), and along the direction of the gas input into the synthesis chamber (101), the second pressure gauge (209) is arranged downstream of the pressure reducing valve (207).

5. The nucleic acid synthesis device according to claim 1, characterized in that: The nucleic acid synthesis device further comprises a second switch valve (302), wherein the second switch valve (302) is arranged on the liquid path (301).

6. The nucleic acid synthesis device according to claim 1, characterized in that: The nucleic acid synthesis device further comprises a waste discharge component (400), the waste discharge component (400) comprising a waste collection container and a waste discharge pipeline, the synthesis chamber (101) having a waste discharge port, the waste discharge port being selectively connected to the waste collection container via the waste discharge pipeline.

7. The nucleic acid synthesis device according to claim 6, characterized in that: The waste collection container comprises a waste liquid barrel (401) and an exhaust hood (402); the waste discharge pipeline comprises a waste liquid pipe (403) and an exhaust gas pipe (404); the waste liquid barrel (401) is connected to the waste discharge port via the waste liquid pipe (403); a third switch valve (405) is provided on the waste liquid pipe (403); and the exhaust hood (402) is connected to the waste liquid barrel (401) via the exhaust gas pipe (404).

8. The nucleic acid synthesis device according to claim 1, characterized in that: The gas source (201) is an inert gas bottle, and the gas is an inert gas.

9. The nucleic acid synthesis device according to claim 1, characterized in that: The gas source (201) is an argon gas cylinder, and the gas is argon gas; Alternatively, the gas source (201) is a nitrogen cylinder, and the gas is nitrogen.

10. The nucleic acid synthesis device according to claim 1, characterized in that: The sealing gland (120) comprises a cover body and a sealing ring, wherein the sealing ring is sandwiched between the cover body and the synthesis device (110); Alternatively, the sealing gland (120) comprises a cover body, the gas path (202) is connected to the side of the cover body and to the upper space of the synthesis chamber (101), and the gas-liquid supply pipe (700) passes through the cover body from top to bottom and penetrates into the lower space of the synthesis chamber (101).

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