A nucleic acid synthesis device

Abstract

The present invention discloses a nucleic acid synthesis device. The nucleic acid synthesis device includes a synthesis component, a gas supply component, a liquid supply component, a dry gas pipeline, a gas-liquid switching valve and a gas-liquid supply pipe. Before the synthesis reaction starts, a certain amount of gas is injected into the synthesis cavity of the synthesis device through the gas pipeline by the gas source, and the synthesis cavity forms a sealed cavity with a certain pressure. The pressure detection mechanism is used to detect the pressure in the sealed cavity, and the airtightness of the synthesis component can be judged by determining whether the pressure change in the sealed cavity exceeds the expected value within a certain period of time. This process does not require manual participation in detection, reducing the labor cost. Moreover, 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 to achieve the drying of the gas-liquid supply pipe. Thereafter, the liquid in the synthesis cavity can be dried, solving the problem that the synthesis carrier cannot be completely poured out due to vibration and dripping, and improving the synthesis accuracy of the synthesis carrier.

Description

Technical Field

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

[0002] The nucleic acid synthesis reaction must be carried out in a sealed environment (i.e., under the condition of isolating media such as water and steam in the air). A nucleic acid synthesis device is a device for carrying out the nucleic acid synthesis reaction. Based on the airtightness requirement for the nucleic acid synthesis reaction, a sealing device will be installed in the synthesis reaction system part of the nucleic acid synthesis device, so as to achieve the sealing protection during the synthesis process.

[0003] During the process of nucleic acid synthesis by the nucleic acid synthesis device, if the sealing device has a decrease in airtightness due to various reasons (such as seal ring failure, low assembly accuracy, etc.), it will cause the synthesis materials to come into contact with substances such as water and oxygen in the air, which will affect the synthesis efficiency and even lead to the failure of synthesis, and further lead to an increase in production costs. Moreover, in the nucleic acid synthesis device, since the liquid injection pipeline injects liquid from the upper end of the synthesis column gland, if the cover is opened after the synthesis reaction, the vibration of the synthesis column gland will cause the liquid remaining in the liquid injection pipeline to drip into the synthesis column. Due to the viscosity of the liquid, if the liquid drips on the synthesis carrier, there will be adhesion and sticking to the wall, and finally the synthesis carrier cannot be completely automatically poured out of the synthesis column for subsequent automated processing, resulting in a serious reduction in the synthesis accuracy of the synthesis carrier.

[0004] At present, 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 whole synthesis process. Therefore, how to propose a nucleic acid synthesis device that can detect airtightness during the synthesis process and the synthesis carrier can be smoothly poured out of the synthesis column is a technical problem that needs to be solved urgently now. Summary of the Invention

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

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

[0007] A nucleic acid synthesis device, comprising: a synthesis component, the synthesis component includes a synthesis device and a sealing gland, the synthesis device has a synthesis cavity, and the sealing gland is detachably installed at the opening of the synthesis cavity; a gas supply component, the gas supply component includes a gas source, a gas path and a pressure detection mechanism, the gas source is selectively communicated with the synthesis cavity through the gas path, and the pressure detection mechanism is arranged on the gas path; a liquid supply component, the liquid supply component includes a liquid source and a liquid path, one end of the liquid path is communicated with the liquid source; a dry gas 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 communicated with the first inlet, one end of the dry gas path pipe is communicated with the gas path, and the other end is communicated with the second inlet, one end of the gas-liquid supply pipe is communicated with the synthesis cavity, and the other end is communicated with the outlet, the gas-liquid switching valve has a first state in which the first inlet is communicated with the outlet and a second state in which the second inlet is communicated with the outlet; the liquid source supplies liquid to the synthesis cavity through the liquid path, the gas-liquid switching valve in the first state, and the gas-liquid supply pipe; the gas source supplies gas to the synthesis cavity through a part of the gas path, the dry gas path 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 cavity through the complete gas path to perform a drying operation on the synthesis carrier in the synthesis cavity, and the synthesis cavity can form a sealed cavity, and the pressure detection mechanism is used to detect the air pressure in the sealed cavity.

[0008] Preferably, the pressure detection mechanism is a pressure sensor; and / or, the gas supply component further includes a first switching valve, the first switching valve is arranged on the gas path, along the direction of the gas input into the synthesis cavity, the pressure detection mechanism is arranged downstream of the first switching valve, and one end of the dry gas path pipe is communicated between the pressure detection mechanism and the first switching valve.

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

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

[0011] Preferably, the nucleic acid synthesis device further includes a second switching valve, which is arranged on the liquid path.

[0012] Preferably, the nucleic acid synthesis device further includes a waste discharging assembly, which includes a waste collecting container and a waste discharging pipeline. The synthesis chamber has a waste discharging port, and the waste discharging port is selectively communicated with the waste collecting container through the waste discharging pipeline.

[0013] Preferably, the waste collecting container includes a waste liquid barrel and an exhaust hood, the waste discharging pipeline includes a waste liquid pipe and a waste gas pipe, the waste liquid barrel is communicated with the waste discharging port through the waste liquid pipe, a third switching valve is arranged on the waste liquid pipe, and the exhaust hood is communicated with the waste liquid barrel through the waste gas pipe.

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

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

[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 communicated on the side of the cover body and communicates with the upper space of the synthesis chamber, and the gas-liquid supply pipe passes through the cover body from top to bottom and extends into the lower space of the synthesis chamber.

[0017] Advantages of the present invention:

[0018] Before the nucleic acid synthesis device provided by the present invention starts the synthesis reaction, the gas source can inject a certain amount of gas into the synthesis chamber of the synthesis device through the gas path, so that the synthesis chamber can form a sealed chamber with a certain pressure. The pressure detection mechanism is used to detect the pressure in the sealed chamber, and by judging whether the pressure change in the sealed chamber exceeds the expected value within a certain period of time, the airtightness 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 chamber through the gas-liquid supply pipe. During this process, the gas-liquid supply pipe can be dried. After that, the gas in the gas source can enter the synthesis chamber through the gas path to press-dry the liquid in the synthesis chamber, thereby solving the problem that the synthesis carrier cannot be completely poured out due to vibration dripping. Moreover, while pressing-drying the synthesis carrier, the nucleic acid synthesis device not only has a simple structure, has an airtightness detection function, reduces the production cost, does not require manual participation in detection, reduces the labor cost, but also the synthesis carrier can be completely poured out of the synthesis device for the next round of reaction, improving the synthesis accuracy of the synthesis carrier. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 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 component; 201, gas source; 202, gas path; 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 path; 302, second switch valve;

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

[0025] 500, press-drying gas path pipe; 600, gas-liquid switching valve; 700, gas-liquid supply pipe. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0026] The present invention will be further described in detail below with reference to the drawings and embodiments. It can be understood that the specific embodiments described herein are only used to explain the present invention, rather than limiting the present invention. In addition, it should be noted that for the sake of description, only some parts related to the present invention are shown in the drawings, not all structures.

[0027] In the description of the present invention, unless otherwise clearly defined and limited, the terms "connected", "connected to", and "fixed" shall be understood in a broad sense. For example, it may be a fixed connection, a detachable connection, or integrated; it may be a mechanical connection or an electrical connection; it may be directly connected or indirectly connected through an intermediate medium, and it may be the communication inside two elements or the interaction relationship between 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 situations.

[0028] In the present invention, unless otherwise clearly defined and limited, the first feature being "above" or "below" the second feature may include the direct contact between the first and second features, or may include the situation where the first and second features are not in direct contact but in contact through other features therebetween. Moreover, the first feature being "above", "over", and "on" the second feature includes that the first feature is directly above and obliquely above the second feature, or merely means that the horizontal height of the first feature is higher than that of the second feature. The first feature being "below", "under", and "beneath" the second feature includes that the first feature is directly below and obliquely below the second feature, or merely means that the horizontal height of the first feature is lower than that of the second feature.

[0029] In the description of this embodiment, the orientation or positional relationships such as "above", "below", "right", etc. are based on the orientation or positional relationship shown in the drawings, and are only for the convenience of description and simplifying the operation, 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 distinction in description and have no special meaning.

[0030] The present invention provides a nucleic acid synthesis device that is capable of performing nucleic acid synthesis reactions. Specifically, as Figure 1As shown in the figure, 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 reactions. 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 path 202, and a pressure detection mechanism 203. The gas path 202 is a pipeline capable of transporting gas. The gas source 201 is selectively connected to the synthesis chamber 101 through the gas path 202. The gas source 201 is used to introduce gas into the synthesis chamber 101. The pressure detection mechanism 203 is arranged on the gas path 202. The synthesis chamber 101 can form a sealed chamber. After injecting a certain amount of gas into the synthesis chamber 101, the sealed chamber forms a chamber with a certain pressure. The pressure detection mechanism 203 is used to detect the air pressure in the sealed chamber.

[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 not only as a detection gas but also as a gas for draining the synthesis reaction reagent or the cleaning reagent, as long as the gas is compatible with the synthesis reaction reagent and the cleaning reagent. Here, "compatible" means that it does not affect the performance of the synthesis reaction reagent and the cleaning reagent.

[0032] Compared with the nucleic acid synthesis device without airtightness detection in the prior art, in the nucleic acid synthesis device provided by the present invention, before performing airtightness detection, first place the synthesis carrier into the synthesis device 110, and then close the gland of the synthesis device 110. When performing airtightness detection, 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 the gas increases the air pressure in the synthesis chamber 101. After the air pressure increases to the expected value, switch the synthesis chamber 101 to a sealed state, so that the synthesis chamber 101 forms a sealed chamber with a certain pressure. The nucleic acid synthesis device is left standing for a period of time. During this process, the pressure detection mechanism 203 is used to detect the pressure in the sealed chamber in real time. By judging whether the pressure change in the sealed chamber during this period exceeds the expected value, it is possible to judge the airtightness of the synthesis component 100 and whether there is a leakage phenomenon. If the airtightness decreases, the nucleic acid synthesis device can give an alarm in time and suspend nucleic acid synthesis, so that production personnel can immediately perform effective maintenance on the synthesis component 100. This nucleic acid synthesis device not only has a simple structure, has an airtightness detection function, can effectively avoid major losses of reagent materials required for production, can reduce production costs, improve production efficiency, but also does not require manual participation in detection, and can reduce labor costs.

[0033] In some embodiments, the synthesis device 110 is a synthesis reaction column, and an opening is formed at the top of the synthesis reaction column. Optionally, the synthesis reaction column includes a flanging portion, a cylindrical portion, and a conical portion that are sequentially connected from top to bottom, and a circular opening is formed at the top of the synthesis reaction column. Of course, in other embodiments, the synthesis reaction column can also be set to other shapes according to requirements.

[0034] In one embodiment, the sealing gland 120 includes a plate-shaped cover body and a sealing ring. The sealing ring is clamped between the cover body and the synthesis device 110. When the cover body carrying the sealing ring is pressed into the opening of the synthesis device 110, an effective seal can be formed. The setting of the sealing ring can improve the airtightness between the synthesis device 110 and the sealing gland 120. Optionally, the plate-shaped cover body is disposed on the flanging portion and can be fixed to the flanging portion. The fixing method is not limited and can be connection by a connecting member, 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. The columnar cover body is inserted into the opening of the synthesis device 110, and the sealing ring is sleeved outside the cover body and clamped between the outer wall surface of the cover body and the inner wall surface of the synthesis 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 other mechanisms such as a pressure gauge that can detect pressure and display the pressure value.

[0036] Continue to refer to Figure 1 As shown, the gas supply assembly 200 further includes a first switching valve 204. The first switching valve 204 is disposed on the gas path 202. Along the direction of gas input into the synthesis chamber 101, the pressure detection mechanism 203 is disposed downstream of the first switching valve 204. The first switching 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 switching valve 204 is an electromagnetic valve. Further optionally, the first switching valve 204 is a direct liquid path electromagnetic valve. The direct liquid path electromagnetic valve is opened when powered on. At this time, the gas path 202 is in a conductive state, and the gas source 201 can deliver gas into the synthesis chamber 101; the direct liquid path electromagnetic valve is closed when powered off. At this time, the gas path 202 is in a blocked state, and the gas source 201 stops delivering gas into the synthesis chamber 101.

[0037] In some embodiments, the gas source 201 is an inert gas cylinder, and the gas is an inert gas. The properties of inert gas are stable. Using inert gas as the detection gas has high safety. In one embodiment, the inert gas cylinder is an argon cylinder, and the gas is argon; in another embodiment, the inert gas cylinder is a nitrogen cylinder, and the gas is nitrogen.

[0038] In order to store as much gas as possible, the gas is generally stored in a gas cylinder under high pressure, so the pressure of the gas discharged from the gas cylinder is relatively high. 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. The pressure regulating valve 208 is provided on the gas path 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] To protect the entire gas 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. The pressure relief valve 206 is provided on the gas path 202, and 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 path 202 exceeds the 200 KPa pressure set by the pressure relief valve 206, the gas will be relieved from the pressure relief valve 206.

[0040] To finely adjust the pressure in the gas path 202, continue to refer to Figure 1 As shown, in some embodiments, the gas supply assembly 200 further includes a pressure reducing valve 207. The pressure reducing valve 207 is provided 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. Optionally, the second target value is 100 Kpa.

[0041] It should be noted that along the direction of the gas input into the synthesis chamber 101, the pressure regulating valve 208, the pressure relief valve 206, and the pressure reducing valve 207 are arranged in sequence. In addition, the pressure regulating valve 208, the pressure relief valve 206, and the pressure reducing valve 207 are all solenoid 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. Along the direction of the gas input into the synthesis chamber 101, the first pressure gauge 205 is provided upstream of the pressure regulating valve 208. The first pressure gauge 205 is used to display the pressure in the gas path 202 before the pressure regulating valve 208 adjusts the pressure. If the pressure exceeds the expected value, the pressure regulating valve 208 is used for adjustment. In some embodiments, the first pressure gauge 205 can also be provided downstream of the pressure regulating valve 208 to display the pressure in the gas path 202 after the pressure regulating valve 208 adjusts the pressure. Specifically, it can be set 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. Along the direction of gas input into the synthesis chamber 101, the second pressure gauge 209 is disposed downstream of the pressure reducing valve 207. The second pressure gauge 209 is used to display the pressure in the gas path 202 after being reduced by the pressure reducing valve 207.

[0044] The forward flow path of the gas is as follows: the gas source 201 supplies gas → the pressure regulating valve 208 roughly reduces the pressure → the pressure reducing valve 207 precisely reduces the pressure → the second pressure gauge 209 displays the pressure → the first switching valve 204 → the pressure detection mechanism 203 → the synthesis assembly 100.

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

[0046] Optionally, the second switching valve 302 is a solenoid valve. Further optionally, the second switching valve 302 is a direct-through solenoid valve for the liquid path. When the second switching valve 302 is energized, it opens, and the liquid path 301 is in a conducting state. The liquid source transports synthesis reaction reagents or cleaning reagents into the synthesis chamber 101 through the liquid path 301. When the second switching valve 302 is de-energized, it closes, and the liquid path 301 is in a blocked state, and the liquid source stops transporting synthesis reaction reagents or cleaning reagents into the synthesis chamber 101.

[0047] Continue to refer to Figure 1 As shown, the nucleic acid synthesis device further includes a dry compressed gas pipeline 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. 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 dry compressed gas pipeline 500, the gas-liquid supply pipe 700, and the liquid path 301. Specifically, the other end of the liquid path 301 away from the liquid source is connected to the first inlet, one end of the dry compressed gas pipeline 500 is connected to the gas path 202, and the other end is connected to the second inlet. 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 switches 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 switches to the second state, the gas source 201 supplies gas to the synthesis chamber 101 through part of the gas path 202, the dry gas pressure pipe 500, the gas-liquid switching valve 600 in the second state, and the gas-liquid supply pipe 700. During this process, the gas can dry the residual liquid in the gas-liquid supply pipe 700 so that there is no liquid residue in the gas-liquid supply pipe 700. And 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 inside of the synthesis chamber 101 through the complete gas path 202 to perform a drying operation on the synthesis carrier in the synthesis chamber 101.

[0049] After the above operations, if it is necessary to pour out the synthesis carrier from the synthesis device 110 subsequently, the sealing gland 120 needs to be removed from the synthesis device 110 first. During this process, the dripping of the gas-liquid supply pipe 700 caused by the vibration of the sealing gland 120 will not affect the thoroughness and smoothness of pouring out the synthesis carrier from the synthesis device 110 subsequently. When the next round of synthesis is required, the synthesis carrier in the synthesis device 110 can be poured out smoothly and thoroughly, and there will be no base deletion during the next round of synthesis, improving the synthesis accuracy and reducing the synthesis cost.

[0050] In some embodiments, the gas-liquid switching valve 600 is a three-way solenoid valve, which has 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 switches to communicate with the NC end, and the gas-liquid switching valve 600 switches to the second state. When the gas-liquid switching valve 600 is powered off, the common end of the gas-liquid switching valve 600 switches to communicate with the NO end, and the gas-liquid switching valve 600 switches to the first state.

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

[0052] In some embodiments, the gas-liquid supply pipe 700 passes through the cover body 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 body and communicates with the upper space of the synthesis chamber 101.

[0053] When performing the operation of draining the reagent in the gas-liquid supply pipe 700 from the gas-liquid switching valve 600 to the synthesis device 110 end, the forward flow path 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 precisely reduces the pressure → the second pressure gauge 209 displays the pressure → the first switching valve 204 is powered on and opened → the gas-liquid switching valve 600 is powered on and opened → the synthesis assembly 100.

[0054] When drying the synthesis device 110 by pressing and detecting the airtightness of the synthesis device 110 with gas, the forward flow path of the gas is as follows: The gas source 201 supplies gas → the pressure regulating valve 208 roughly reduces the pressure → the pressure reducing valve 207 precisely reduces the pressure → the second pressure gauge 209 displays the pressure → the pressure detection mechanism 203 → the synthesis assembly 100. The gas enters the synthesis device 110 through this path. Through equipment control, the reaction reagent in the synthesis device 110 is dried by the gas, and the pressure detection mechanism 203 collects the gas pressure in the synthesis device 110 to detect the airtightness in the synthesis device 110.

[0055] Continue to refer to Figure 1 As shown, the nucleic acid synthesis equipment further includes a waste discharge assembly 400, and the waste discharge assembly 400 is used to discharge the waste liquid or waste gas in the synthesis chamber 101. Specifically, the waste discharge assembly 400 includes a waste collection container and a waste discharge pipeline. The synthesis chamber 101 has a waste discharge port, and the waste discharge port is selectively communicated with the waste collection container through the waste discharge pipeline. In one embodiment, the bottom of the synthesis reaction column forms a waste discharge port.

[0056] In some embodiments, the waste collection container includes a waste liquid bucket 401 and an exhaust hood 402, the waste discharge pipeline includes a waste liquid pipe 403 and a waste gas pipe 404, the waste liquid bucket 401 is communicated with the waste discharge port through the waste liquid pipe 403, and a third switching valve 405 is provided on the waste liquid pipe 403. The exhaust hood 402 is communicated with the waste liquid bucket 401 through the waste gas pipe 404.

[0057] The waste liquid bucket 401 is used to collect waste liquid. The waste liquid here can be the liquid during the synthesis reaction or the liquid after cleaning, and it 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 bucket 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 bucket 401 or to transport the dried gas to the waste liquid bucket 401. The waste gas pipe 404 is used to transport the waste gas in the waste liquid bucket 401 to the exhaust hood 402 to prevent the phenomenon that the waste liquid overflows from the waste liquid bucket 401 due to excessive pressure in the waste liquid bucket 401.

[0058] Optionally, the third switching valve 405 is a solenoid valve. Further optionally, the third switching valve 405 is a direct-flow liquid path solenoid valve. When the direct-flow liquid path solenoid valve is powered on, it opens, and the waste liquid pipe 403 is in a conducting state. The reagent or gas in the synthesis chamber 101 is discharged into the waste liquid bucket 401 through the waste liquid pipe 403. When the direct-flow liquid path solenoid valve is powered off, it closes, and the waste liquid pipe 403 is in a blocked state. The reagent and gas can be stored in the synthesis chamber 101.

[0059] In this embodiment, the nucleic acid synthesis device further includes a control mechanism, which can be a centralized or distributed controller. For example, the controller can be a single microcontroller or composed of multiple distributed microcontrollers. A control program can run in the microcontroller to control the above-mentioned valve bodies and the pressure detection mechanism 203 to perform their respective functions.

[0060] The nucleic acid synthesis device can perform the following actions:

[0061] Action of the synthesis component 100 for storing reagents: Open the second switching valve 302, close the third switching valve 405, make the gas-liquid switching valve 600 in the first state, and 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] Action of the synthesis component 100 for discharging reagents: Close the second switching valve 302, make the gas-liquid switching valve 600 in the first state, open the third switching valve 405 and the first switching valve 204, the gas source 201 injects gas into the synthesis chamber 101 through the gas path 202, the gas squeezes the reagents, and the reagents are discharged into the waste liquid bucket 401 through the waste liquid pipe 403, thereby completing the discharge of the reagents in the synthesis chamber 101.

[0063] Action of the synthesis component 100 for storing gas: Close the second switching valve 302 and the third switching valve 405, make the gas-liquid switching valve 600 in the first state, open the first switching valve 204, and according to the requirements of the airtightness detection, the gas source 201 injects a certain amount of gas into the synthesis chamber 101 through the gas path 202 for airtightness detection;

[0064] Action of the synthesis component 100 for discharging gas: Close the second switching valve 302 and the first switching valve 204, make the gas-liquid switching valve 600 in the first state, open the third switching valve 405 to discharge the gas in the synthesis chamber 101, and the gas enters the waste liquid bucket 401 through the waste liquid pipe 403 and enters the exhaust hood 402 through the waste gas pipe 404.

[0065] The following details the process of airtightness detection of the nucleic acid synthesis device:

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

[0067] In one embodiment, step 1 specifically includes the following steps: Press the sealing gland 120 into the synthesis device 110 → Close the second switching valve 302 → Make the gas-liquid switching valve 600 in the first state → Close the third switching valve 405 → Open the first switching valve 204, and continuously input argon gas at 100 kPa into the synthesis chamber 101 for 5 seconds → Close the first switching valve 204 to make the synthesis chamber 101 form a sealed chamber.

[0068] Step 2: Activate the pressure detection mechanism 203, and the pressure detection mechanism 203 detects the pressure in the sealing 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 seal of the sealing gland 120 on the synthesis device 110 fails according to the change of the pressure value. The specific qualified standard for determination is that 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 60 KPa.

[0070] Step 3: If it is determined that the seal fails, the nucleic acid synthesis equipment pauses the synthesis reaction, and manual intervention is required to maintain the nucleic acid synthesis equipment.

[0071] If it is determined that the seal is successful, the synthesis chamber 101 is depressurized, and the nucleic acid synthesis reaction is started.

[0072] In one embodiment, the specific operation for determining that the seal is successful is: open the third switching 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 later liquid injection and damage to the synthesis component 100 → close the third switching valve 405 → activate the current synthetic base injection file to start nucleic acid synthesis.

[0073] It should be added that for high-throughput nucleic acid synthesis equipment, it is particularly important to have an airtightness detection function, which has even more important significance.

[0074] High-throughput nucleic acid synthesis is a technology capable of simultaneously synthesizing a large number of DNA fragments. Through an automated and high-throughput approach, it greatly improves the efficiency and accuracy of nucleic acid synthesis. For high-throughput nucleic acid synthesis equipment, it transports and sorts each synthesis carrier into different base (such as conventional A, T, C, G bases, but not limited to these bases) synthesis devices 110 for synthesis. Each synthesis carrier will be sent into 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). Therefore, during the operation of high-throughput nucleic acid synthesis equipment, the synthesis device 110 must frequently open and close the lid to pour out and put in the synthesis carrier. However, as the usage time of high-throughput nucleic acid synthesis equipment increases, the frequent lid-opening and lid-closing operations will inevitably cause wear of the O-ring provided at the sealed lid 120, and the sealing failure between the sealed lid 120 and the synthesis device 110 will also occur due to phenomena such as the non-concentricity of the sealed lid 120 and the synthesis device 110, thus affecting the instrument performance and synthesis quality of high-throughput nucleic acid synthesis equipment. Therefore, in high-throughput nucleic acid synthesis equipment, after the synthesis carrier is sorted into the synthesis device 110 and the sealed lid 120 is pressed on, and before the chemical reagent synthesis starts, first use the above pressure detection mechanism 203 to detect whether the sealing condition at the synthesis device 110 and the sealed lid 120 meets the synthesis requirements. Specifically, through the nucleic acid synthesis equipment with an airtightness detection function proposed by the present invention, before the synthesis starts, argon gas with a certain pressure is transported into the synthesis device 110, and a pressure sensor is used to monitor whether the pressure of the argon gas in the synthesis device 110 will drop significantly within 15 seconds, and then judge whether there are sealing failure phenomena such as air leakage, which is beneficial to ensuring the instrument performance and synthesis quality of high-throughput nucleic acid synthesis equipment and has important economic significance.

[0075] The following details the process of draining the reagent in the gas-liquid supply pipe 700 at the upper end of the synthesis device 110:

[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 1 specifically includes the following steps: The first switching valve 204 is powered on and opened → The NC end of the gas-liquid switching valve 600 is powered on and opened → 100 kPa of argon gas is input for 5 seconds → The argon gas flows through the gas-liquid supply pipe 700 to 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.

[0078] Step 2: Press and drain the reagent drained into the synthesis device 110.

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

[0080] It should be added that for high-throughput nucleic acid synthesis equipment, it is particularly important to avoid the adhesion of the synthesis carrier, which has even more important significance.

[0081] Since the nucleic acid synthesis equipment injects liquid from the upper end of the synthesis device 110, the gas-liquid supply pipe 700 installed on the sealing gland 120 of the synthesis device 110 will be subject to external vibration when the cover is opened, and there is a risk of dripping of the gas-liquid supply pipe 700. Since the dripping reagent is viscous, it will cause the synthesis carrier to adhere to the inner wall of the synthesis device 110 and the synthesis device 110 cannot be emptied. The high-throughput nucleic acid synthesis equipment transports and sorts each synthesis carrier into different base (such as conventional A, T, C, G bases, but not limited to these bases) synthesis devices 110 for synthesis. Each carrier will be sent into different base synthesis devices 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). To achieve this, the synthesis carrier in the synthesis device 110 must be completely emptied from the synthesis device 110 into the next round of sorting every time. Otherwise, the synthesis carrier that has not been emptied from 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 on a synthesis sequence to be missing (one synthesis carrier represents one sequence, and one sequence is composed of preset bases). This sequence is equivalent to not being accurately synthesized, which not only reduces the synthesis accuracy but also increases the synthesis cost.

[0082] The nucleic acid synthesis equipment provided by the present invention adds the function of draining the reagent in the gas-liquid supply pipe 700 at the upper end of the synthesis device 110. Before the synthesis carrier finishes synthesizing one base and is emptied from the synthesis device 110, argon gas is input through the gas path 202 by the gas source 201, and by controlling the gas-liquid switching valve 600, the reagent in the gas-liquid supply pipe 700 at the upper end of the synthesis device 110 is drained into the synthesis device 110 by argon gas to solve the dripping problem, and then the pressing and drying function of the nucleic acid synthesis equipment is used to press and dry the reagent on the synthesis carrier, so as to keep the synthesis carrier and the synthesis device 110 dry, enabling the synthesis carrier to be smoothly emptied from the synthesis device 110.

[0083] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, rather than limitations on the implementation manners of the present invention. For those of ordinary skill in the art, various obvious changes, re-adjustments and substitutions can be made without departing from the protection scope of the present invention. It is not necessary and impossible to enumerate all the implementation manners here. Any modifications, equivalent substitutions and improvements made within the spirit and principle of the present invention shall 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 chamber (101), the sealing gland (120) being detachably mounted at the opening of the synthesis chamber (101), the synthesis device (110) being frequently opened and capped to pour out and put in synthesis carriers, and the synthesis carriers being transported and sorted into synthesis devices (110) of different bases for synthesis; 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 path (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 path (202), the squeeze-dry gas path pipe (500), the gas-liquid switching valve (600) in the second state, and the gas-liquid supply pipe (700) 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 path (202) to squeeze the synthesis carrier in the synthesis chamber (101) to enable the synthesis carrier in the synthesis device (110) to be poured out smoothly and thoroughly, 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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