A nucleic acid synthesizer

Abstract

The invention discloses a nucleic acid synthesizer, which relates to the technical field of nucleic acid synthesis, and comprises a chassis, a monomer bottle, a reagent bottle, an inlet valve, an infusion pump, a pressure sensor, a circulation valve, a column position switching valve, a synthesis column, a conductivity detector, an ultraviolet detector, a back pressure valve and a waste valve; the chassis is a box structure with a bottle body installation panel and a control component panel on the outside and a control component accommodating cavity arranged inside; multiple monomer bottles, reagent bottles and synthesis columns are arranged and installed on the bottle body installation panel; the inlet valve, the waste valve, the infusion pump, the pressure sensor, the circulation valve and the column position switching valve are installed in the chassis; the nucleic acid synthesizer of the invention delivers reagents or monomers into the synthesis column through the infusion pump in cooperation with various valves, the delivered liquid flow is more accurate, the consumption of reaction reagents is reduced, and the entire chassis has a simple structure, a high degree of automation, and a high efficiency of nucleic acid synthesis.

Description

Technical Field

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

[0002] With the rapid development of oligonucleotide chain synthesis technology, the synthesis cost has continued to decline, and the synthesis length and accuracy have continued to increase, making large-scale DNA and RNA synthesis starting with oligonucleotide chains possible, thus resulting in the emergence of nucleic acid synthesizers.

[0003] Currently, there are only a few foreign companies (such as Germany's K&A Labor Geraete, the United States' GE and the United States' Biolytic, Russia's BIOSSET'S, etc.) producing industrialized nucleic acid synthesizers on the market. However, the reagent delivery of current nucleic acid synthesizers is not accurate enough, the reaction reagents are seriously wasted, the air tightness is not good enough, the price is high, the maintenance cycle is too long, and the repair is relatively cumbersome. In view of the above defects in the existing technology, it is necessary to develop a new synthesizer to make it more practical to meet the needs of actual applications. Summary of the invention

[0004] The purpose of the present invention is to provide a nucleic acid synthesizer to solve the problems existing in the above-mentioned prior art. The liquid flow rate delivered is more accurate, the consumption of reaction reagents is reduced, and the entire chassis structure is simple and the degree of automation is high. The number of monomer bottles can be set according to process requirements, and the nucleic acid synthesis efficiency is high.

[0005] To achieve the above object, the present invention provides the following solutions:

[0006] The present invention provides a nucleic acid synthesizer, comprising a chassis, a monomer bottle, a reagent bottle, an inlet valve, an infusion pump, a pressure sensor, a circulation valve, a column position switching valve and a synthesis column; the chassis is a box structure with a bottle body installation panel and a control component panel on the outside and a control element accommodating cavity provided inside; the monomer bottle, the reagent bottle and the synthesis column are all provided in plurality and installed on the bottle body installation panel; the inlet valve, the infusion pump, the pressure sensor, the circulation valve and the column position switching valve are installed in the chassis, and the channel interfaces of the inlet valve, the infusion pump, the circulation valve and the column position switching valve all protrude from the outside of the control component panel;

[0007] The inlet valve comprises inlet valve 1, inlet valve 2, inlet valve 3 and inlet valve 4, and the inlet valve 1 and inlet valve 2 are both provided with a plurality of them, and the plurality of inlet valves 1 and inlet valves 2 are respectively connected to different monomer bottles or reagent bottles through infusion pipelines, and each of the inlet valves 1 and 2 is also connected to the inlet valve 3 through an infusion pipeline, and the inlet valve 3 is also connected to the reagent bottle through an infusion pipeline; the infusion pump comprises infusion pump 1 and infusion pump 2, the inlet valve 3 is connected to the inlet of the infusion pump 1 through an infusion pipeline, and the inlet valve 4 is connected to the inlet of the infusion pump 1 through an infusion pipeline. The column position switching valve comprises a column position switching valve 1 and a column position switching valve 2, and the two ends of the synthetic column are respectively connected to the column position switching valve 1 and the column position switching valve 2 by an infusion pipeline. The infusion pump 1 and the infusion pump 2 are connected to the column position switching valve 1 by an infusion pipeline and a three-way joint. A pressure sensor 1 is arranged on the infusion pipeline between the three-way joint and the column position switching valve 1. The column position switching valve 2 is connected to the circulation valve by an infusion pipeline, and a conductivity detection device is arranged on the infusion pipeline.

[0008] Preferably, an inert gas protection device is also included, and the inert gas protection device includes an inert gas source, a second pressure sensor, a third pressure sensor, a first pressure regulating valve, a second pressure regulating valve, a first gas source distributor and a second gas source distributor. The inert gas source is distributed to the first gas source distributor and the second gas source distributor through a three-way connector. The first gas source distributor and the second gas source distributor are respectively used to distribute inert gas to the monomer bottle and the reagent bottle. The second pressure sensor and the third pressure sensor are respectively arranged on the two gas pipes. The second pressure sensor is connected to the first pressure regulating valve, and the third pressure sensor is connected to the second pressure regulating valve. The first pressure regulating valve and the second pressure regulating valve are used to adjust the pressure in the monomer bottle or the reagent bottle according to process requirements.

[0009] Preferably, the trachea is a polytetrafluoro tube or a PEEK tube; the infusion pipeline is a PEEK tube or a polytetrafluoro tube or a stainless steel tube.

[0010] Preferably, the circulation valve is also connected to a waste valve for discharging waste liquid through a discharge pipeline, the channel interface of the waste valve protrudes from the outside of the bottle body mounting panel, and an ultraviolet detector and a back pressure valve are arranged on the discharge pipeline, and the back pressure valve is located at the tail end of the ultraviolet detector.

[0011] Preferably, the drainage pipeline is a polytetrafluoroethylene tube or a PEEK tube.

[0012] Preferably, the reagent bottle and the monomer bottle are both mounted on the bottle body mounting panel by means of a clamp, the clamp comprising an upper clamp and a lower clamp, the upper clamp is connected to the bottle body mounting plate, the upper clamp is a door-shaped plate, the bottom outer sides of the two vertical plates of the upper clamp are provided with transversely arranged clamping parts, the top two sides of the lower clamp are provided with clamping grooves for clamping the clamping parts, a sealing gasket is provided at the bottle mouth of the monomer bottle or the reagent bottle, the bottle mouth of the monomer bottle or the reagent bottle is clamped into the bottle mouth clamping groove on the lower clamp through a notch provided in the middle part of the lower clamp, and the clamping groove of the lower clamp pushes toward each other along the clamping part of the upper clamp to clamp the monomer bottle or the reagent bottle between the upper clamp and the lower clamp.

[0013] Preferably, the synthetic column is mounted on the bottle body mounting panel via a bracket.

[0014] Preferably, the inlet valve, circulation valve, column position switching valve and waste valve are all multi-channel switching valves, and each valve body is a motor-driven rotating shaft, which drives the rotor fixed at the shaft end to rotate and switch to the required channel on the valve head.

[0015] Preferably, the inlet valve, circulation valve, column position switching valve and waste valve are all valve group structures composed of multiple diaphragm valves, and the diaphragm of a single diaphragm in each valve group is controlled on and off by an actuator, thereby controlling the on and off of the pipeline connected to the single valve body.

[0016] Preferably, the chassis is an explosion-proof chassis or a non-explosion-proof chassis.

[0017] Compared with the prior art, the present invention has achieved the following beneficial technical effects:

[0018] The nucleic acid synthesizer provided by the present invention delivers reagents or monomers into the synthesis column through an infusion pump in cooperation with various valves. The delivered liquid flow is more accurate, reducing the consumption of reaction reagents. The entire chassis structure is simple and the degree of automation is high. The number of monomer bottles can be set according to process requirements, and the nucleic acid synthesis efficiency is high. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0020] Figure 1 is a schematic diagram of the three-dimensional structure of the nucleic acid synthesizer of the present invention;

[0021] Figure 2 It is a schematic diagram of the forward structure of the nucleic acid synthesizer in the present invention;

[0022] Figure 3 is a process flow chart of the nucleic acid synthesizer of the present invention;

[0023] Figure 4 is a flow chart of the inert gas protection device in the present invention;

[0024] Figure 5 It is a schematic diagram of the installation of reagent bottles or monomer bottles;

[0025] Figure 6 It is a schematic diagram of the structure of a bracket with a synthetic column installed;

[0026] In the figure: 1-chassis, 2-monomer bottle, 3-reagent bottle, 4-inlet valve 1, 5-inlet valve 2, 6-inlet valve 3, 7-inlet valve 4, 8-infusion pump 1, 9-infusion pump 2, 10-pressure sensor 1, 11-pressure sensor 2, 12-pressure sensor 3, 13-circulation valve, 14-column position switching valve 1, 15-column position switching valve 2, 16-synthesis column, 17-bottle body installation panel, 18-control Control component panel, 19- three-way connector, 20- conductivity detection device, 21- inert gas source, 22- gas source distributor 1, 23- gas source distributor 2, 24- pressure regulating valve 1, 25- pressure regulating valve 2, 26- bottle mouth, 27- bracket, 28- waste valve, 29- ultraviolet detector, 30- back pressure valve, 31- upper splint, 32- lower splint, 33- clamping part, 34- slot, 35- bottle mouth slot. DETAILED DESCRIPTION

[0027] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0028] The purpose of the present invention is to provide a nucleic acid synthesizer to solve the problems existing in the prior art.

[0029] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.

[0030] The nucleic acid synthesizer in this embodiment is as follows Figure 1-3As shown, it includes a chassis 1, a monomer bottle 2, a reagent bottle 3, an inlet valve, an infusion pump, a pressure sensor, a circulation valve 13, a column position switching valve and a synthesis column 16; the chassis 1 is a box structure with a bottle body installation panel 17 and a control component panel 18 on the outside, and a control element accommodating cavity is arranged inside; the monomer bottle 2, the reagent bottle 3 and the synthesis column 16 are each provided with multiple and installed on the bottle body installation panel 17; the inlet valve, the waste valve 28, the infusion pump, the pressure sensor, the circulation valve 13 and the column position switching valve are installed in the chassis 1, and the channel interfaces of the inlet valve, the infusion pump, the circulation valve 13 and the column position switching valve are all outside the control component panel 18, and the channel interfaces are used to connect different pipelines according to process requirements;

[0031] The inlet valve includes an inlet valve 1 4, an inlet valve 2 5, an inlet valve 3 6 and an inlet valve 4 7. There are multiple inlet valves 1 4 and 2 5. In the present embodiment, there are 8 inlet valves 1 4 and 2 5. The multiple inlet valves 1 4 and 2 5 are connected to different monomer bottles 2 or reagent bottles 3 through infusion pipelines according to process requirements. Each inlet valve 1 4 and inlet valve 2 5 is connected to the inlet valve 3 6 through an infusion pipeline, and the inlet valve 3 6 is also connected to the reagent bottle 3 through an infusion pipeline; the infusion pump includes an infusion pump 1 8 and an infusion pump 2 9. The inlet valve 3 6 is connected to the inlet of the infusion pump 1 8 through an infusion pipeline. The inlet valve 4 7 is connected to the circulation valve 13 through the infusion pipeline, and the circulation valve 13 is connected to the infusion pump 29 through the infusion pipeline; the column position switching valve includes a column position switching valve 14 and a column position switching valve 2 15, and the two ends of the synthesis column 16 are respectively connected to the column position switching valve 14 and the column position switching valve 2 15 by the infusion pipeline, and the infusion pump 18 and the infusion pump 29 are connected to the column position switching valve 14 through the infusion pipeline and the three-way joint 19, and the pressure sensor 10 is set on the infusion pipeline between the three-way joint 19 and the column position switching valve 14, and the column position switching valve 2 15 is connected to the circulation valve 13 through the infusion pipeline, and the conductivity detection device 20 is set on the infusion pipeline. Among them, the infusion pipeline is a PEEK tube or a tetrafluoro tube or a stainless steel tube.

[0032] In this specific embodiment, the circulation valve 13 is also connected to a waste valve 28 for discharging waste liquid through a discharge pipeline. The discharge pipeline is a polytetrafluoroethylene tube or a PEEK tube. The channel interface of the waste valve 28 protrudes from the outside of the bottle body mounting panel 17. The channel interface is used to connect different pipelines according to process requirements. An ultraviolet detector 29 and a back pressure valve 30 are arranged on the discharge pipeline. The back pressure valve 30 is located at the tail end of the ultraviolet detector 29. The purpose of setting the back pressure valve 30 is to provide appropriate back pressure to prevent bubbles from being generated in the front end flow path and affecting the detection data.

[0033] like Figure 4As shown, it also includes an inert gas protection device, which includes an inert gas source 21, a pressure sensor 2 11, a pressure sensor 3 12, a pressure regulating valve 1 24, a pressure regulating valve 2 25, a gas source distributor 1 22 and a gas source distributor 2 23. The inert gas source 21 is connected to the gas source distributor 1 22 and the gas source distributor 2 23 respectively through a three-way joint and two air pipes. The gas source distributor 1 22 and the gas source distributor 2 23 are provided with multiple gas ports, each of which is connected to a different monomer bottle 2 or reagent bottle 3, so as to distribute the inert gas to each monomer bottle 2 and reagent bottle 3. The pressure sensor 2 11 and the pressure sensor 3 12 are respectively arranged on the two air pipes between the three-way joint and the gas source distributor 1 22 and the gas source distributor 2 23. The pressure sensor 2 11 is connected to the pressure regulating valve 1 24, the pressure sensor 3 12 is connected to the pressure regulating valve 2 25, and the control terminals of the pressure regulating valve 1 24 and the pressure regulating valve 2 25 are arranged on the control component panel 18. The monomer bottle 2 and the reagent bottle 3 need to be protected by inert gas, and the pressure is set at 0.3-0.35Bar. The inert gas source 21 enters the gas source distributor 1 22 and the gas source distributor 2 23 through the gas pipe behind the chassis 1 respectively. The pressure sensor 2 11 and the pressure sensor 3 12 cooperate with the pressure regulating valve 1 24 and the pressure regulating valve 2 25 to adjust the pressure in the bottle in time. The gas source distributor can distribute several gas pipes to connect to the monomer bottle 2 or the reagent bottle 3. The monomer bottle 2 and the reagent bottle 3 are both provided with sealing devices to ensure the internal pressure of the gas cylinder; the pressure sensor 2 11 and the pressure sensor 3 12 are arranged on the control component panel 18; the gas pipe is a polytetrafluoro tube or a PEEK tube.

[0034] like Figure 5 As shown, the monomer bottle 2 and the reagent bottle 3 are both installed on the bottle body mounting panel 17 through a clamping plate, and the clamping plate includes an upper clamping plate 31 and a lower clamping plate 32. The upper clamping plate 31 is connected to the bottle body mounting panel 17, and the upper clamping plate 31 is a door-shaped plate. The bottom outer side of the two vertical plates of the upper clamping plate 31 is provided with a horizontally arranged clamping portion 33, and the top two sides of the lower clamping plate 32 are provided with a clamping groove 34 for clamping the clamping portion 33. A sealing gasket is provided at the bottle mouth of the monomer bottle 2 or the reagent bottle 3, and the bottle mouth 26 of the monomer bottle 2 or the reagent bottle 3 is clamped into the bottle mouth clamping groove 35 on the lower clamping plate 32 through a notch provided in the middle part of the lower clamping plate 32. The clamping groove 34 of the lower clamping plate 32 is pushed toward each other along the clamping portion 33 of the upper clamping plate 31 to clamp the monomer bottle 2 or the reagent bottle 3 between the upper clamping plate 31 and the lower clamping plate 32.

[0035] like Figure 6 As shown, the synthetic column 16 is mounted on the bottle body mounting panel 17 via a bracket 27 .

[0036] In this embodiment, each inlet valve, circulation valve 13, column position switching valve, and waste valve 28 are multi-channel switching valves. Each channel of the valve body is connected to different pipelines according to process requirements. When the valve body is working, the motor drives the rotating shaft to drive the rotor fixed at the end of the shaft to rotate, switch to the required channel on the valve head, and then open the corresponding pipeline.

[0037] In another embodiment, each inlet valve, circulation valve 13, column position switching valve, and waste valve 28 are valve group structures composed of multiple diaphragm valves. The diaphragm of a single diaphragm in each valve group is controlled by an actuator to control the on-off of the pipeline connected to the single valve body, and each single diaphragm valve is connected to different pipelines according to process requirements.

[0038] In this embodiment, the chassis 1 can be made into an explosion-proof chassis or a non-explosion-proof chassis according to needs; the synthesis column 16 can be configured in various specifications according to process requirements.

[0039] Specific process implementation steps:

[0040] 1. The first step of the synthesis is deblocking, using trichloroacetic acid to remove the DMT on the nucleoside linked to CPG to expose the 5' hydroxyl group for the next coupling step.

[0041] Workflow: trichloroacetic acid in the reagent bottle 3 enters through the trichloroacetic acid port of the inlet valve 36, and enters the synthesis column 16 through the infusion pump 8, the pressure sensor 10, and the column position switching valve 14. After the reaction is completed, acetonitrile enters the system through the acetonitrile port of the inlet valve 36, cleans the above flow path, and is discharged through the waste valve 288.

[0042] 2. The second step - activation. Before coupling, the monomer is mixed with tetrazole and enters the synthesis column 16. At this time, tetrazole provides a proton to the N atom of the diisopropylamine group on the 3' phosphate. The protonated diisopropylamine is a good free group and forms an active intermediate, phosphoramidite tetrazole, with tetrazole.

[0043] Working process: the monomer in the monomer bottle 2 enters through the required ports of inlet valve 14, inlet valve 25, and inlet valve 36, and enters the synthesis column 16 through infusion pump 18, pressure sensor 10, and column position switching valve 14; the tetrazole in the reagent bottle 3 enters the circulation valve 13, infusion pump 29, pressure sensor 10, and column position switching valve 14 through the tetrazole port of inlet valve 47 to enter the synthesis column 16. After the reaction is completed, acetonitrile enters the system through the acetonitrile ports of inlet valve 14, inlet valve 25, and inlet valve 36, and at the same time, it also enters the system through the acetonitrile port of inlet valve 47. The above-mentioned flow path is cleaned and discharged through the waste valve 28.

[0044] 3. The third step - coupling. When the phosphoramidite tetrazole collides with the nucleotide connected to CPG, it undergoes a nucleophilic reaction with its 5' hydroxyl group, coupling occurs and the tetrazole is removed, and the synthesized oligonucleotide chain is extended by one.

[0045] Workflow: the circulation valve 13 is switched to the circulation state, the infusion pump 29 is started, the flow rate is set, the infusion pump 29 provides power, and the infusion pump 29, the pressure sensor 10, the column position switching valve 14, the column position switching valve 215, the conductivity detection device 20, and the circulation valve 13 form a closed loop operation. After the reaction is completed, acetonitrile enters the system through the acetonitrile port of the inlet valve 297, the above-mentioned flow path is cleaned, and it is discharged through the waste valve 28.

[0046] 4. The fourth step - capping. In order to prevent the unreacted 5' hydroxyl group connected to CPG from being extended in subsequent cycles, it is necessary to cap it after the coupling reaction is fully carried out.

[0047] Workflow: the capping agent (the capping agent is acetylated) enters the infusion pump 8 through the capping agent port of the inlet valve 3 6, passes through the pressure sensor 10, and enters the synthesis column 16 through the column position switching valve 14. After the reaction is completed, acetonitrile enters the system through the acetonitrile port of the inlet valve 3 6, and the above-mentioned flow path is cleaned and discharged through the waste valve 28.

[0048] 5. The fifth step - oxidation. After the coupling reaction, the newly added nucleotides are connected to the oligonucleotide chain on the CPG through a phosphite bond (phosphorus is trivalent). This phosphite bond is unstable and easily hydrolyzed by acid and alkali, so the trivalent phosphorus here needs to be oxidized to pentavalent phosphorus.

[0049] Working process: the oxidant (the oxidant is tetrahydrofuran) enters the synthesis column 16 through the oxidant port of the inlet valve 47, the circulation valve 13, the infusion pump 29, the pressure sensor 10, and the column position switching valve 14. After the reaction is completed, acetonitrile enters the system through the acetonitrile port of the inlet valve 47, and the above-mentioned flow path is cleaned and discharged through the waste valve 28.

[0050] 6. Repeat steps 1 to 5 above until the oligonucleotide chain is extended to the desired length.

[0051] During the entire reaction process, the monomer bottle 2 and the reagent bottle 3 need to be pressurized with argon or nitrogen to achieve the purpose of isolating the air.

[0052] After each of the above process steps is executed, the pipeline needs to be flushed to ensure cleanliness. The monomers perform the above cycle steps in sequence according to needs.

[0053] The present invention uses specific examples to illustrate the principles and implementation methods of the present invention. The above examples are only used to help understand the method and core ideas of the present invention. At the same time, for those skilled in the art, according to the ideas of the present invention, there will be changes in the specific implementation methods and application scopes. In summary, the content of this specification should not be understood as limiting the present invention.

Claims

1. A nucleic acid synthesizer, characterized in that: It comprises a chassis, a monomer bottle, a reagent bottle, an inlet valve, an infusion pump, a pressure sensor, a circulation valve, a column position switching valve and a synthesis column; the chassis is a box structure with a bottle body installation panel and a control component panel on the outside and a control element accommodating cavity provided inside; the monomer bottle, the reagent bottle and the synthesis column are provided with a plurality of them and installed on the bottle body installation panel; the inlet valve, the infusion pump, the pressure sensor, the circulation valve and the column position switching valve are installed in the chassis, and the channel interfaces of the inlet valve, the infusion pump, the circulation valve and the column position switching valve are all protruding from the outside of the control component panel; The inlet valve comprises inlet valve 1, inlet valve 2, inlet valve 3 and inlet valve 4, and the inlet valve 1 and inlet valve 2 are both provided with a plurality of them, and the plurality of inlet valves 1 and inlet valves 2 are respectively connected to different monomer bottles or reagent bottles through infusion pipelines, and each of the inlet valves 1 and 2 is also connected to the inlet valve 3 through an infusion pipeline, and the inlet valve 3 is also connected to the reagent bottle through an infusion pipeline; the infusion pump comprises infusion pump 1 and infusion pump 2, the inlet valve 3 is connected to the inlet of the infusion pump 1 through an infusion pipeline, and the inlet valve 4 is connected to the inlet of the infusion pump 1 through an infusion pipeline. The column position switching valve comprises a column position switching valve 1 and a column position switching valve 2, and the two ends of the synthetic column are respectively connected to the column position switching valve 1 and the column position switching valve 2 by an infusion pipeline. The infusion pump 1 and the infusion pump 2 are connected to the column position switching valve 1 by an infusion pipeline and a three-way joint. A pressure sensor 1 is arranged on the infusion pipeline between the three-way joint and the column position switching valve 1. The column position switching valve 2 is connected to the circulation valve by an infusion pipeline, and a conductivity detection device is arranged on the infusion pipeline.

2. The nucleic acid synthesizer according to claim 1, characterized in that: It also includes an inert gas protection device, which includes an inert gas source, a second pressure sensor, a third pressure sensor, a first pressure regulating valve, a second pressure regulating valve, a first gas source distributor and a second gas source distributor. The inert gas source is connected to the first gas source distributor and the second gas source distributor through a three-way joint and two gas pipes, respectively. The first gas source distributor and the second gas source distributor are used to distribute inert gas to the monomer bottle and the reagent bottle, respectively. The second pressure sensor and the third pressure sensor are respectively arranged on the two gas pipes. The second pressure sensor is connected to the first pressure regulating valve, and the third pressure sensor is connected to the second pressure regulating valve. The first pressure regulating valve and the second pressure regulating valve are used to adjust the pressure in the monomer bottle or the reagent bottle according to process requirements.

3. The nucleic acid synthesizer according to claim 2, characterized in that: The trachea is a PTFE tube or a PEEK tube; the infusion pipeline is a PEEK tube or a PTFE tube or a stainless steel tube.

4. The nucleic acid synthesizer according to claim 1, characterized in that: The circulation valve is also connected to a waste valve for discharging waste liquid through a discharge pipeline. The channel interface of the waste valve protrudes from the outside of the bottle body mounting panel. An ultraviolet detector and a back pressure valve are arranged on the discharge pipeline. The back pressure valve is located at the tail end of the ultraviolet detector.

5. The nucleic acid synthesizer according to claim 4, characterized in that: The liquid discharge pipeline is a polytetrafluoroethylene tube or a PEEK tube.

6. The nucleic acid synthesizer according to claim 1, characterized in that: The reagent bottle and the monomer bottle are both mounted on the bottle body mounting panel through a clamp, the clamp comprising an upper clamp and a lower clamp, the upper clamp is connected to the bottle body mounting plate, the upper clamp is a door-shaped plate, and the bottom outer sides of the two vertical plates of the upper clamp are provided with transversely arranged clamping parts, and the top two sides of the lower clamp are provided with clamping grooves for clamping the clamping parts, a sealing gasket is provided at the bottle mouth of the monomer bottle or the reagent bottle, and the bottle mouth of the monomer bottle or the reagent bottle is clamped into the bottle mouth clamping groove on the lower clamp through a notch provided in the middle part of the lower clamp, and the clamping groove of the lower clamp pushes toward each other along the clamping part of the upper clamp to clamp the monomer bottle or the reagent bottle between the upper clamp and the lower clamp.

7. The nucleic acid synthesizer according to claim 1, characterized in that: The synthetic column is mounted on the bottle body mounting panel via a bracket.

8. The nucleic acid synthesizer according to claim 4, characterized in that: The inlet valve, circulation valve, column position switching valve and waste valve are all multi-channel switching valves, and each valve body is a motor-driven rotating shaft, which drives the rotor fixed on the shaft end to rotate and switch to the required channel on the valve head.

9. The nucleic acid synthesizer according to claim 1, characterized in that: The inlet valve, circulation valve, column position switching valve and waste valve are all valve group structures composed of multiple diaphragm valves. The diaphragm of a single diaphragm in each valve group is controlled on and off by an actuator, thereby controlling the on and off of the pipeline connected to the single valve body.

10. The nucleic acid synthesizer according to claim 1, characterized in that: The chassis is an explosion-proof chassis or a non-explosion-proof chassis.

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