Fluid circulation synthesis system and synthesis method for synthesizing biochemical substances

Abstract

The invention relates to a fluid circulation synthesis system and a synthesis method for synthesizing biochemical substances. The system comprises a pipeline system, a valve assembly and a synthesis container. The valve assembly includes a first control valve. The pipeline system comprises a fluid input pipeline, an output pipeline, a first fluid afflux pipeline and a fluid circulation pipeline. The first end of the fluid input pipeline is connected with the inlet of the synthesis container; the first end of the output pipeline is connected with the outlet of the synthesis container; the first end of the first fluid afflux pipeline is used for injecting first fluid. The second end of the first fluid afflux pipeline and the first end of the fluid circulation pipeline are connected with the second end of the output pipeline through the first control valve, and the second end of the fluid circulation pipeline is connected with the second end of the fluid input pipeline. The first control valve selectively communicates the fluid circulation pipeline to the first fluid afflux pipeline or the first fluid output pipeline so as to switch to the first fluid injection path or the first fluid circulation path. The problem of insufficient reaction between the fluid and the synthetic carrier can be improved.

Description

Technical Field

[0001] The present application relates to biochemical substance synthesis, and in particular to a fluid circulation synthesis system and a synthesis method for synthesizing biochemical substances. Background Art

[0002] Common biological macromolecules include proteins, nucleic acids (DNA, RNA), sugars, etc. Biological macromolecules are usually polymerized from simple components. Taking nucleic acids as an example, the component unit of nucleic acids is nucleotides. If biological macromolecules need to be artificially synthesized, it is usually necessary to use a nucleic acid synthesizer, by injecting different reagents into the synthesis container in sequence, so that the reagents and the synthetic carrier are immersed in reaction.

[0003] However, the reaction speed of the above reaction is relatively slow, resulting in a long synthesis time. If multiple reagents are injected at the same time, the reagents cannot be fully mixed due to the different densities of the reagents, thereby reducing the synthesis efficiency. Summary of the invention

[0004] In order to solve the above shortcomings, it is necessary to provide a fluid circulation synthesis system and method for synthesizing biochemical substances.

[0005] The first aspect of the present application provides a fluid circulation synthesis system, including a pipeline system, a valve assembly and a synthesis container. The valve assembly includes a first control valve, and the pipeline system includes a fluid input pipeline, an output pipeline, a first fluid confluence pipeline and a fluid circulation pipeline. The first end of the fluid input pipeline is connected to the inlet of the synthesis container, and the first end of the output pipeline is connected to the outlet of the synthesis container. The first end of the first fluid confluence pipeline is used to inject a first fluid. The second end of the first fluid confluence pipeline and the first end of the fluid circulation pipeline are connected to the second end of the output pipeline through the first control valve, and the second end of the fluid circulation pipeline is connected to the second end of the fluid input pipeline. The first control valve is used to connect the fluid circulation pipeline to the first fluid confluence pipeline, so that the first fluid confluence pipeline, the fluid circulation pipeline and the fluid input pipeline are connected in sequence, thereby switching the fluid circulation synthesis system to the first fluid injection path, so that the first fluid is loaded into the first fluid injection path. The first control valve is also used to connect the fluid circulation pipeline to the output pipeline, so that the fluid circulation pipeline, the fluid input pipeline and the output pipeline are connected in sequence, thereby switching the fluid circulation synthesis system to a circulation path and allowing the first fluid to circulate in the circulation path.

[0006] Based on the first aspect, in some possible implementations, the fluid circulation synthesis system further includes a fluid loading mechanism, the fluid loading mechanism includes a first fluid loading component for storing the first fluid, the pipeline system further includes a first fluid loading pipeline connected to the first fluid loading component, and the first end of the first fluid confluence pipeline is connected to the first fluid loading pipeline, so that the first fluid stored in the first fluid loading component is loaded into the first fluid injection path.

[0007] Based on the first aspect, in some possible implementations, the number of the first fluid loading pipeline and the number of the first fluid loading member are respectively multiple. The valve assembly further includes a first switching valve, and the first end of the first fluid confluence pipeline is connected to multiple first fluid loading pipelines through the first switching valve. The first switching valve is used to selectively connect the first fluid confluence pipeline to at least one first fluid loading pipeline.

[0008] Based on the first aspect, in some possible implementations, the pipeline system further includes a second fluid inlet pipeline, a first end of the second fluid inlet pipeline is used to inject a second fluid, and a second end of the second fluid inlet pipeline is connected to a second end of the fluid input pipeline. The second fluid inlet pipeline and the fluid input pipeline are used to be connected in sequence, so as to switch the fluid circulation synthesis system to the second fluid injection path, so that the second fluid is loaded into the second fluid injection path.

[0009] Based on the first aspect, in some possible implementations, the fluid loading mechanism further includes a second fluid loading component for storing a second fluid, the pipeline system further includes a second fluid loading pipeline connected to the second fluid loading component, and the first end of the second fluid confluence pipeline is connected to the second fluid loading pipeline, so that the second fluid stored in the second fluid loading component is loaded into the second fluid injection path.

[0010] Based on the first aspect, in some possible implementations, the number of the second fluid loading pipelines and the number of the second fluid loading members are respectively multiple, the valve assembly further includes a second switching valve, the first end of the second fluid confluence pipeline is connected to multiple second fluid loading pipelines through the second switching valve, and the second switching valve is used to selectively connect the second fluid confluence pipeline to at least one second fluid loading pipeline.

[0011] Based on the first aspect, in some possible implementations, the pipeline system further includes a gas input pipeline and a waste liquid pipeline, the first end of the gas input pipeline is connected to another inlet of the synthesis container, and the second end of the gas input pipeline is used to connect to a gas source. The fluid circulation synthesis system also includes a waste liquid collection piece, the first end of the waste liquid pipeline is connected to the second end of the output pipeline, and the second end of the waste liquid pipeline is connected to the waste liquid collection piece. The gas input pipeline, the output pipeline and the waste liquid pipeline are used to be connected in sequence, so that the fluid circulation synthesis system is switched to an exhaust path, so that the gas source loads gas into the exhaust path.

[0012] Based on the first aspect, in some possible implementations, the fluid circulation synthesis system also includes a first power component, which is arranged in the fluid circulation pipeline and is used to provide power to the first fluid flowing through the first fluid injection path and the circulation path respectively.

[0013] Based on the first aspect, in some possible implementations, the first power member is a metering pump, which is used to provide power to the first fluid and to measure whether the amount of the first fluid injected into the synthesis container reaches a predetermined amount.

[0014] Based on the first aspect, in some possible implementations, the first control valve is a solenoid valve, and when the first control valve is powered off, the fluid flow pipeline is connected to the output pipeline. When the first control valve is powered on, the fluid flow pipeline is connected to the first fluid inlet pipeline.

[0015] The second aspect of the present application provides a synthesis method applied to the above-mentioned fluid circulation synthesis system, comprising the following steps: controlling the first control valve to connect the fluid circulation pipeline to the first fluid inlet pipeline, so that the first fluid inlet pipeline, the fluid circulation pipeline and the fluid input pipeline are connected in sequence, thereby switching the fluid circulation synthesis system to the first fluid injection path; loading the first fluid into the first fluid inlet pipeline; controlling the first control valve to connect the fluid circulation pipeline to the output pipeline, so that the fluid circulation pipeline, the fluid input pipeline and the output pipeline are connected in sequence, thereby switching the fluid circulation synthesis system to the circulation path, and allowing the first fluid to circulate in the circulation path.

[0016] Based on the second aspect, in some possible implementations, the fluid circulation synthesis system further includes a fluid loading mechanism, the fluid loading mechanism includes a first fluid loading component for storing the first fluid, the pipeline system further includes a first fluid loading pipeline connected to the first fluid loading component, and the first end of the first fluid inlet pipeline is connected to the first fluid loading pipeline. "Loading the first fluid into the first fluid inlet pipeline" specifically includes: connecting the first fluid inlet pipeline and the first fluid loading pipeline, so that the first fluid stored in the first fluid loading component is loaded into the first fluid injection path.

[0017] Based on the second aspect, in some possible implementations, the number of the first fluid loading pipeline and the number of the first fluid loading element are respectively multiple, the valve assembly further includes a first switching valve, the first end of the first fluid inlet pipeline is connected to multiple first fluid loading pipelines through the first switching valve, and the multiple first fluid loading pipelines are further connected to multiple first fluid loading elements through multiple second control valves. "Connecting the first fluid inlet pipeline and the first fluid loading pipeline" specifically includes: selectively connecting the first fluid inlet pipeline to at least one first fluid loading pipeline through the first switching valve; opening at least one second control valve corresponding to at least one first fluid loading pipeline, so that the first fluid stored in at least one first fluid loading element connected to at least one first fluid loading pipeline is loaded into the first fluid inlet pipeline.

[0018] Based on the second aspect, in some possible implementations, the fluid circulation synthesis system further includes a first power member disposed in the fluid circulation pipeline, the first power member is a metering pump, and when the first fluid is loaded into the first fluid confluence pipeline. The synthesis method further includes: controlling the first power member to open, thereby providing power to the first fluid flowing through the first fluid injection path, and measuring whether the amount of the first fluid injected into the synthesis container reaches a predetermined amount; when the amount of the first fluid injected into the synthesis container reaches the predetermined amount, controlling the second control valve to close.

[0019] Based on the second aspect, in some possible implementations, the pipeline system further includes a second fluid inlet pipeline, the first end of the second fluid inlet pipeline is used to inject the second fluid, and the second end of the second fluid inlet pipeline is connected to the second end of the fluid input pipeline. The synthesis method further includes: connecting the second fluid inlet pipeline and the fluid input pipeline in sequence, thereby switching the fluid circulation synthesis system to the second fluid injection path; loading the stored second fluid into the second fluid injection path by the second fluid loading member; and controlling the first control valve to connect the fluid circulation pipeline to the output pipeline, thereby switching the fluid circulation synthesis system to the circulation path, so that the second fluid circulates in the circulation path.

[0020] Based on the second aspect, in some possible implementations, the fluid loading mechanism further includes a second fluid loading member for storing a second fluid, the pipeline system further includes a second fluid loading pipeline connected to the second fluid loading member, and the first end of the second fluid inlet pipeline is connected to the second fluid loading pipeline. "Loading the second fluid into the second fluid injection path" specifically includes: connecting the second fluid inlet pipeline and the second fluid loading pipeline, so that the second fluid stored in the second fluid loading member is loaded into the second fluid injection path.

[0021] Based on the second aspect, in some possible implementations, the first fluid is loaded into the first fluid inlet pipeline and the second fluid is loaded into the second fluid inlet pipeline simultaneously, so that the first fluid and the second fluid are mixed in the fluid input pipeline.

[0022] Based on the second aspect, in some possible implementations, the valve assembly further includes a fourth control valve and a fifth control valve, the pipeline system further includes a gas input pipeline and a waste liquid pipeline, the first end of the gas input pipeline is connected to another inlet of the synthesis container, the second end of the gas input pipeline is used to connect to a gas source, and the fourth control valve is arranged on the gas input pipeline; the fluid circulation synthesis system further includes a waste liquid collection piece, the first end of the waste liquid pipeline is connected to the second end of the output pipeline through the fifth control valve, and the second end of the waste liquid pipeline is connected to the waste liquid collection piece. The synthesis method further includes: opening the fourth control valve and the fifth control valve to connect the gas input pipeline, the output pipeline and the waste liquid pipeline in sequence, thereby switching the fluid circulation synthesis system to an exhaust path; opening the gas source so that the gas from the gas source is loaded into the exhaust path and the remaining first fluid in the synthesis container is transferred to the waste liquid collection piece.

[0023] In the present application, the fluid circulation synthesis system is switched to the first fluid injection path through the valve assembly, so that the first fluid can be injected. By switching the fluid circulation synthesis system to the circulation path through the valve assembly, a closed-loop circulation space can be formed, so that the first fluid can be continuously circulated in the circulation path, so that the first fluid can fully react chemically in the synthesis container, improve the reaction efficiency, improve the problem of insufficient reaction, and also help to shorten the synthesis reaction time. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 A schematic diagram of a fluid circulation synthesis system provided in accordance with one embodiment of the present application.

[0025] Figure 2 for Figure 1 A schematic diagram of the first fluid injection path of the fluid circulation synthesis system.

[0026] Figure 3 for Figure 1 A schematic diagram of the second fluid injection path of the fluid circulation synthesis system.

[0027] Figure 4 for Figure 1 A schematic diagram of the circulation path of the fluid circulation synthesis system.

[0028] Figure 5 for Figure 1 Schematic diagram of the exhaust path of the fluid circulation synthesis system.

[0029] Figure 6 A flow chart of a synthesis method provided in one embodiment of the present application.

[0030] Main component symbols

[0031] Fluid loading mechanism 10

[0032] First fluid loading element 11

[0033] Second fluid loading element 12

[0034] Pipeline system 20

[0035] Fluid input pipeline 21

[0036] Output pipeline 22

[0037] First fluid loading pipeline 23

[0038] Second fluid loading pipeline 24

[0039] The first fluid enters the pipeline 25

[0040] The second fluid enters the pipeline 26

[0041] Fluid flow pipeline 27

[0042] Gas input pipeline 28

[0043] Waste liquid pipeline 29

[0044] First ends 21a, 22a, 25a, 26a, 27a, 28a, 29a

[0045] Second ends 21b, 22b, 25b, 26b, 27b, 28b, 29b

[0046] Valve assembly 30

[0047] First control valve 31

[0048] First switching valve 32

[0049] Second switching valve 33

[0050] Second control valve 34

[0051] The third control valve 35

[0052] Fourth control valve 36

[0053] Fifth control valve 37

[0054] Crafting container 40

[0055] Waste liquid collection unit 50

[0056] The first power member 60

[0057] The second power member 70

[0058] Fluid Circulation Synthesis System 100

[0059] Connecting pipe 291

[0060] NC Port 311

[0061] NO Port 312

[0062] First connector A

[0063] Second connector B

[0064] First fluid injection path P1

[0065] Second fluid injection path P2

[0066] Cycle path P3

[0067] Exhaust path P4

[0068] Steps S1-S8

[0069] The following specific implementation methods will further illustrate the present application in conjunction with the above-mentioned drawings. DETAILED DESCRIPTION

[0070] In order to more clearly understand the above-mentioned purpose, features and advantages of the present application, the present application is described in detail below in conjunction with the accompanying drawings and specific embodiments. It should be noted that, in the case of no conflict, the embodiments of the present application and the features in the embodiments can be combined with each other. In the following description, many specific details are set forth to facilitate a full understanding of the present application, and the described embodiments are only a part of the embodiments of the present application, rather than all of the embodiments.

[0071] It should be noted that when a component is referred to as being "fixed to" or "mounted on" another component, it may be directly on the other component or there may be a central component. When a component is considered to be "set on" another component, it may be directly set on the other component or there may be a central component at the same time. The term "and / or" as used herein includes all and any combinations of one or more of the relevant listed items.

[0072] It should be noted that, although a logical order is shown in the flowchart, in some cases, the steps shown or described may be performed in an order different from that in the flowchart. The method disclosed in the embodiment of the present application includes one or more steps or actions for implementing the method. The method steps and / or actions may be interchangeable with each other without departing from the scope of the claims. Unless a specific order of steps or actions is specified, the order and / or use of specific steps and / or actions may be modified without departing from the scope of the claims.

[0073] See also Figure 1 In one embodiment of the present application, a fluid circulation synthesis system 100 is provided, which can be used to synthesize biochemical substances. For example, the fluid circulation synthesis system 100 can be used to synthesize nucleic acids.

[0074] In some embodiments, the fluid circulation synthesis system 100 includes a fluid loading mechanism 10, a pipeline system 20, a valve assembly 30 and a synthesis container 40. The fluid loading mechanism 10, the valve assembly 30 and the synthesis container 40 are all connected to the pipeline system 20. The fluid loading mechanism 10 includes a first fluid loading member 11 for storing a first fluid and a second fluid loading member 12 for storing a second fluid. The first fluid loading member 11 is used to load the first fluid into the synthesis container 40 through the pipeline system 20. The second fluid loading member 12 is used to load the second fluid into the synthesis container 40 through the pipeline system 20. The synthesis container 40 is used to accommodate a synthesis carrier. Therefore, the first fluid and the second fluid can react with the synthesis carrier separately or simultaneously in the synthesis container 40 to finally generate biochemical substances. The valve assembly 30 can include a control valve installed at each position of the pipeline system 20 and used to control the on-off, and the corresponding operation of each control valve can realize the switching of different paths. In other embodiments, the fluid loading mechanism 10 may also be a component independent of the fluid circulation synthesis system 100 . When in use, the fluid loading mechanism 10 is connected to the pipeline system 20 of the fluid circulation synthesis system 100 .

[0075] In some embodiments, the fluid circulation synthesis system 100 may further include a processor (not shown). The processor is used to control the corresponding operation of each control valve, so as to switch the fluid circulation synthesis system 100 to the desired path. The processor can be a central processing unit (CPU), or other general-purpose processors, digital signal processors (DSP), application-specific integrated circuits (ASIC), field-programmable gate arrays (FPGA) or other programmable logic devices, discrete gates or transistor logic devices, discrete hardware components, etc. The general-purpose processor can be a microprocessor or the processor can also be any conventional processor, etc.

[0076] Among them, Figure 1 As shown, the valve assembly 30 includes a first control valve 31. The pipeline system 20 includes a fluid input pipeline 21, an output pipeline 22, a first fluid loading pipeline 23, a second fluid loading pipeline 24, a first fluid confluence pipeline 25, a second fluid confluence pipeline 26 and a fluid flow pipeline 27.

[0077] The first end 21 a of the fluid input pipeline 21 is connected to the inlet of the synthesis container 40 , and the first end 22 a of the output pipeline 22 is connected to the outlet of the synthesis container 40 .

[0078] The first end 25a of the first fluid inlet pipeline 25 is connected to the first fluid loading pipeline 23, and the first fluid loading pipeline 23 is also connected to the first fluid loading element 11. Therefore, the first fluid stored in the first fluid loading element 11 can be loaded into the first fluid inlet pipeline 25 through the first fluid loading pipeline 23. In some embodiments, the number of the first fluid loading pipelines 23 is multiple, and the number of the first fluid loading elements 11 is also multiple. At this time, the valve assembly 30 further includes a first switching valve 32, and the first end 25a of the first fluid inlet pipeline 25 is connected to multiple first fluid loading pipelines 23 through the first switching valve 32, and the multiple first fluid loading pipelines 23 are also connected to multiple first fluid loading elements 11 through multiple second control valves 34. The first switching valve 32 is used to selectively connect the first fluid inlet pipeline 25 to at least one first fluid loading pipeline 23, so that the first fluid stored in the first fluid loading element 11 connected to the first fluid loading pipeline 23 can be loaded into the first fluid inlet pipeline 25 through the first switching valve 32. The first switching valve 32 may be a rotary switching valve, which can connect the first fluid inlet pipeline 25 and at least one first fluid loading pipeline 23 when rotating. The second control valve 34 may be a solenoid valve, which connects the first fluid loading pipeline 23 and the corresponding first fluid loading member 11 when opened.

[0079] The first end 26a of the second fluid inlet pipeline 26 is connected to the second fluid loading pipeline 24, and the second fluid loading pipeline 24 is also connected to the second fluid loading element 12. Therefore, the second fluid stored in the second fluid loading element 12 can be loaded into the second fluid inlet pipeline 26 through the second fluid loading pipeline 24. In some embodiments, the number of the second fluid loading pipelines 24 is multiple, and the number of the second fluid loading elements 12 is also multiple. The first end 26a of the second fluid inlet pipeline 26 is connected to multiple second fluid loading pipelines 24 through the second switching valve 33, and the multiple second fluid loading pipelines 24 are also connected to multiple second fluid loading elements 12 through multiple third control valves 35. At this time, the valve assembly 30 further includes a second switching valve 33, and the second switching valve 33 is used to selectively connect the second fluid inlet pipeline 26 to at least one second fluid loading pipeline 24, so that the second fluid stored in the second fluid loading element 12 connected to the second fluid loading pipeline 24 can be loaded into the second fluid inlet pipeline 26 through the second switching valve 33. The second switching valve 33 may be a rotary switching valve, which can connect the second fluid inlet pipeline 26 and at least one second fluid loading pipeline 24 when rotating. The third control valve 35 may be a solenoid valve, which connects the second fluid loading pipeline 24 and the corresponding second fluid loading member 12 when opened.

[0080] The second end 25b of the first fluid inlet pipeline 25 and the first end 27a of the fluid circulation pipeline 27 are connected to the second end 22b of the output pipeline 22 through the first control valve 31. The first control valve 31 is used to selectively connect the fluid circulation pipeline 27 to the first fluid inlet pipeline 25 or the output pipeline 22. The second end 26b of the second fluid inlet pipeline 26 and the second end 27b of the fluid circulation pipeline 27 are both connected to the second end 21b of the fluid input pipeline 21. In some embodiments, the first control valve 31 is a solenoid valve, which may include a COM port 310, an NC port 311 and a NO port 312. The COM port 310 is connected to the fluid circulation pipeline 27, the NC port 311 is connected to the first fluid inlet pipeline 25, and the NO port 312 is connected to the output pipeline 22. When the first control valve 31 is not energized, the NO port 312 is opened and the NC port 311 is closed, so the fluid flow pipeline 27 is connected to the output pipeline 22; when the first control valve 31 is energized, the NO port 312 is closed and the NC port 311 is opened, so the fluid flow pipeline 27 is connected to the first fluid inlet pipeline 25.

[0081] In some embodiments, the fluid circulation synthesis system 100 further includes a first power member 60. The first power member 60 is disposed in the fluid circulation pipeline 27, and is used to provide power to the first fluid. Further, the fluid circulation synthesis system 100 further includes a second power member 70. The second power member 70 is disposed in the second fluid confluence pipeline 26, and is used to provide power to the second fluid. The specific functions of the first power member 60 and the second power member 70 will be described in the following section in conjunction with the working principle of the fluid circulation synthesis system 100 of the present application.

[0082] In some embodiments, the valve assembly 30 further includes a fourth control valve 36 and a fifth control valve 37, and the pipeline system 20 further includes a gas input pipeline 28 and a waste liquid pipeline 29. The first end 28a of the gas input pipeline 28 is connected to another inlet of the synthesis container 40, the second end 28b of the gas input pipeline 28 is connected to a gas source (not shown), and the fourth control valve 36 is arranged on the gas input pipeline 28. The fluid circulation synthesis system 100 further includes a waste liquid collection member 50, the first end 29a of the waste liquid pipeline 29 is connected to the second end 22b of the output pipeline 22 through the fifth control valve 37, and the second end 29b of the waste liquid pipeline 29 is connected to the waste liquid collection member 50. Among them, the fourth control valve 36 can be a solenoid valve, which connects the gas input pipeline 28 and the synthesis container 40 when it is opened. The fifth control valve 37 can be a solenoid valve, which connects the output pipeline 22 and the waste liquid pipeline 29 when it is opened. The gas source can input argon or other inert gases into the synthesis container, but the present application is not limited thereto. Each of the first fluid loading member 11 , the second fluid loading member 12 , and the waste liquid collecting member 50 may be a bottle-shaped or barrel-shaped container.

[0083] In some embodiments, the pipeline system 20 further includes a first connector A and a connecting pipeline 291. The first end of the connecting pipeline 291 is directly connected to the NO port 312 of the first control valve 31, and the second end of the connecting pipeline 291, the second end 22b of the output pipeline 22, and the first end 29a of the waste liquid pipeline 29 are connected through the first connector A. Specifically, the first connector A can be a three-way connector. In some embodiments, the pipeline system 20 further includes a second connector B. The second end 27b of the fluid circulation pipeline 27, the second end 26b of the second fluid confluence pipeline 26, and the second end 21b of the fluid input pipeline 21 are connected through the second connector B. Specifically, the second connector B can be a three-way connector.

[0084] The following is an example of a biochemical substance being a nucleic acid, a synthesis container 40 being a synthesis column, a first fluid being various reaction reagents required for nucleic acid synthesis, and a second fluid being various monomer reagents required for nucleic acid synthesis, to explain the working principle of the fluid circulation synthesis system 100 of the present application. Among them, the reaction reagents required for nucleic acid synthesis are related to the specific process of the nucleic acid synthesis process. The nucleic acid synthesis process includes steps such as deprotection, activation coupling, oxidation, and capping. Among them, deprotection is to remove the DMT group from the end of the synthesis carrier by a deprotection reagent (such as TCA) to expose the 5' hydroxyl group for subsequent coupling with the monomer; activation coupling is to convert the added free monomer into a tetrazole derivative by an activation reagent (such as ACT), and then react with the exposed 5' hydroxyl group on the synthesis carrier to form a 3'-5' phosphite triester, oxidation is to oxidize the phosphite triester to a phosphate triester by an oxidizing reagent (such as OX iodine solution), and capping is to seal the unreacted 5' hydroxyl group by a capping reagent (such as CAPA or CAPB) to form an acylate. Therefore, the reaction reagents required for nucleic acid synthesis may include a variety of synthesis reagents such as deprotection reagents, activation reagents, oxidation reagents, and capping reagents. Further, the first fluid may also include a cleaning reagent, which is used to remove the remaining reaction reagents after the reaction of the reaction reagents with the synthesis carrier, thereby avoiding the generation of impurities by the reaction reagent residues. The monomer reagents required for nucleic acid synthesis include adenine (A), thymine (T), cytosine (C), and guanine (G) and other base monomers, and of course, other special modified bases, such as AC, TT and other double bases, and the above monomers can be injected into the synthesis column in sequence according to the sequence required for the nucleic acid for synthesis reaction.

[0085] like Figure 2As shown, when the first control valve 31 connects the fluid circulation pipeline 27 to the first fluid inlet pipeline 25 (e.g., the first control valve 31 is energized, so that the NO port 312 is closed and the NC port 311 is opened), the first fluid loading pipeline 23, the first fluid inlet pipeline 25, the fluid circulation pipeline 27, and the fluid input pipeline 21 are connected in sequence, so that the fluid circulation synthesis system 100 is switched to the first fluid injection path P1. Therefore, the first fluid (such as a reaction reagent or a cleaning reagent) stored in the first fluid loading member 11 connected to the first fluid loading pipeline 23 can be loaded into the first fluid inlet pipeline 25 through the first switching valve 32, and enter the synthesis container 40 through the fluid circulation pipeline 27 and the fluid input pipeline 21. In some embodiments, according to the specific position of the fifth control valve 37, the first fluid injection path P1 can also include the output pipeline 22. The first power member 60 is used to provide power to the first fluid flowing through the first fluid injection path P1. Further, the first power member 60 can be a metering pump (e.g., a plunger metering pump). When turned on, the metering pump can provide power to the first fluid flowing through the first fluid injection path P1 (e.g., providing power through the reciprocating plunger movement), and can also be used as a metering tool for the injection amount of the first fluid injected into the synthetic column. That is, the setting of the metering pump facilitates the injection of a predetermined amount of the first fluid into the synthetic column, thereby achieving precise injection. After the predetermined amount of the first fluid is injected into the synthetic column, the second control valve 34 is closed to cut off the source of the first fluid.

[0086] like Figure 3 As shown, when the first control valve 31 connects the fluid circulation pipeline 27 to the output pipeline 22 (for example, when the first control valve 31 is powered off, the NO port 312 is opened and the NC port 311 is closed; for example, when the first control valve 31 is powered on, the NO port 312 is closed and the NC port 311 is opened), the second fluid loading pipeline 24, the second fluid inlet pipeline 26, and the fluid input pipeline 21 are connected in sequence, so that the fluid circulation synthesis system 100 is switched to the second fluid injection path P2. Therefore, the second fluid stored in the second fluid loading element 12 connected to the second fluid loading pipeline 24 can be loaded into the second fluid inlet pipeline 26 through the second switching valve 33, and enter the synthesis container 40 through the fluid circulation pipeline 27 and the fluid input pipeline 21. Therefore, the second fluid (such as a monomer reagent) stored in the second fluid loading element 12 connected to the second fluid loading pipeline 24 can be loaded into the second fluid inlet pipeline 26 through the second switching valve 33, and enter the synthesis container 40 through the fluid input pipeline 21. Combined with reference Figure 1It can be understood that although the first control valve 31 is powered off so that the NO port 312 is opened so that the fluid circulation pipeline 27 is connected to the output pipeline 22, at this time, since the first power member 60 is closed, there is no power for the fluid to flow in the fluid circulation pipeline 27. After the second fluid flows out of the output pipeline 22 from the synthesis container 40, it will not flow further into the fluid circulation pipeline 27. Therefore, the second fluid injection path P2 does not include the fluid circulation pipeline 27. In some embodiments, according to the specific position of the fifth control valve 37, the second fluid injection path P2 may also include the output pipeline 22. The second power member 70 is used to provide power to the second fluid flowing through the second fluid injection path P2. Further, the second power member 70 can be a metering pump (such as a plunger metering pump). When it is turned on, the metering pump can provide power to the second fluid flowing through the second fluid injection path P2 (such as providing power through the reciprocating plunger movement), and can also be used as a metering tool for the injection amount of the second fluid injected into the synthesis column. That is, the setting of the metering pump facilitates the injection of a predetermined amount of the second fluid into the synthesis column. After a predetermined amount of the second fluid is injected into the synthesis column, the third control valve 35 is closed to cut off the source of the second fluid.

[0087] In some embodiments, the second switching valve 33 is further connected to a first fluid loading pipeline 23, and the first fluid loading pipeline 23 is in communication with the first fluid loading part 11 storing the cleaning reagent. Therefore, the second switching valve 33 can also selectively connect the second fluid inlet pipeline 26 to the first fluid loading pipeline 23 in communication with the first fluid loading part 11 storing the cleaning reagent, so that the cleaning fluid stored in the first fluid loading part 11 can be loaded into the second fluid injection path P2 through the second switching valve 33, thereby cleaning the corresponding pipeline.

[0088] In some embodiments, the injection of the first fluid and the injection of the second fluid are performed simultaneously, so that the first fluid and the second fluid can be fully mixed in the fluid input pipeline 21 before entering the synthesis container 40, thereby improving the reaction efficiency. Specifically, the first control valve 31 is energized, so that the NO port 312 is closed and the NC port 311 is opened, so that the first control valve 31 connects the fluid flow pipeline 27 to the first fluid inlet pipeline 25. At the same time, the first power member 60 and the second power member 70 are opened, and the first fluid enters the first fluid injection path P1 under the action of the first power member 60, and the second fluid enters the second fluid injection path P2 under the action of the second power member 70, so that the first fluid and the second fluid can be fully mixed in the fluid input pipeline 21 before entering the synthesis container 40.

[0089] like Figure 4As shown, when the first control valve 31 connects the fluid circulation pipeline 27 to the output pipeline 22 (e.g., the first control valve 31 is powered off, so that the NO port 312 is opened and the NC port 311 is closed), the fluid circulation pipeline 27, the fluid input pipeline 21 and the output pipeline 22 are connected in sequence, thereby switching the fluid circulation synthesis system 100 to the circulation path P3. Thus, the first fluid and / or the second fluid can be continuously circulated in the circulation path P3. When the first fluid is a reaction reagent and the second fluid is a monomer reagent, the continuous circulation in the circulation path P3 enables the first fluid and / or the second fluid to continuously flush with the synthesis carrier, thereby facilitating a more sufficient chemical reaction, improving the reaction efficiency, and also facilitating shortening the synthesis reaction time; when the first fluid is a cleaning reagent, the continuous circulation in the circulation path P3 enables the cleaning reagent to fully remove the remaining reaction reagent or monomer reagent, thereby avoiding the generation of impurities by the reaction reagent or monomer reagent residue. When the fluid circulation synthesis system 100 is switched to the circulation path P3, the first power element 60 works to provide power for the first fluid and / or the second fluid circulating in the circulation path P3.

[0090] like Figure 5 As shown, when the fourth control valve 36 connects the gas input pipeline 28 and the synthesis container 40, and the fifth control valve 37 connects the output pipeline 22 and the waste liquid pipeline 29, the gas input pipeline 28, the output pipeline 22 and the waste liquid pipeline 29 are connected in sequence, so that the fluid circulation synthesis system 100 is switched to the exhaust path P4. Thus, the gas provided by the gas source of the gas input pipeline 28 can be loaded into the synthesis container 40 through the gas input pipeline 28, and drive the waste liquid in the synthesis container 40 (such as the reaction reagent / monomer reagent that has completed the reaction, or the excess reaction reagent / monomer reagent) to flow out of the synthesis container 40, and further flow into the waste liquid collection part 50 through the waste liquid pipeline 29. Combined with reference Figure 1 At this time, the first control valve 31 can be de-energized, and the NO port 312 is opened so that the fluid flow pipeline 27 is connected to the output pipeline 22. However, it can be understood that since the first power member 60 is closed, the waste liquid will not flow further into the fluid flow pipeline 27 after flowing out of the output pipeline 22 from the synthesis container 40. Therefore, the exhaust path P4 does not include the fluid flow pipeline 27.

[0091] In other embodiments, the first fluid loading pipeline 23 and the second fluid loading pipeline 24 may also be omitted. In this case, the first fluid may be directly injected through the first fluid inlet pipeline 25 , and the second fluid may be directly injected through the second fluid inlet pipeline 26 .

[0092] In the present application, the fluid circulation synthesis system 100 is switched to the first fluid injection path P1 by the valve assembly 30, so that the injection of the first fluid can be achieved. The fluid circulation synthesis system 100 is switched to the second fluid injection path P2 by the valve assembly 30, so that the injection of the second fluid can be achieved. By switching the fluid circulation synthesis system 100 to the circulation path P3 by the valve assembly 30, a closed-loop circulation space can be formed, so that the first fluid and / or the second fluid can be continuously circulated in the circulation path P3, so that the first fluid and / or the second fluid can be fully chemically reacted with the synthetic carrier, improve the reaction efficiency, improve the problem of insufficient reaction between the fluid and the synthetic carrier, and also help to shorten the synthesis reaction time. When the first fluid and the second fluid are injected at the same time, the first fluid and the second fluid can be mixed in advance in the fluid input pipeline 21 in advance, so as to further improve the reaction efficiency. When the fluid circulation synthesis system 100 is switched to the exhaust path P4 through the valve assembly 30, the gas can be loaded into the synthesis container 40 through the gas input pipeline 28, so that the waste liquid in the synthesis container 40 that has completed the reaction flows into the waste liquid collection part 50, and the synthesis carrier is fully pressed dry to improve the synthesis efficiency. Among them, when the cleaning reagent is injected through the first fluid injection path P1 and the fluid circulation synthesis system 100 is switched to the circulation path P3 through the valve assembly 30, the synthesis carrier can also be fully cleaned.

[0093] The following will be combined Figure 6 The specific functions of each component of the fluid circulation synthesis system 100 are further described. Figure 6 In one embodiment of the present application, a synthesis method for the fluid circulation synthesis system 100 is provided. According to different requirements, the order of the steps of the above method can be changed, and some steps can be omitted or combined. The above synthesis method includes the following steps:

[0094] In step S1, the first control valve 31 connects the fluid circulation pipeline 27 to the first fluid inlet pipeline 25 (e.g., the first control valve 31 is energized so that the NO port 312 is closed and the NC port 311 is opened), so that the first fluid loading pipeline 23, the first fluid inlet pipeline 25, the fluid circulation pipeline 27, and the fluid input pipeline 21 are connected in sequence, thereby switching the fluid circulation synthesis system 100 to the first fluid injection path P1.

[0095] In some other embodiments, the first fluid loading pipeline 23 may also be omitted. In this case, the first fluid may be directly injected through the first fluid inlet pipeline 25 , that is, the first fluid injection path P1 does not include the first fluid loading pipeline 23 .

[0096] Step S2, the first switching valve 32 is rotated to connect the first fluid inlet pipeline 25 and the first fluid loading pipeline 23, and the second control valve 34 is opened, so that the first fluid (e.g., TCA reagent) stored in the first fluid loading member 11 connected to the first fluid loading pipeline 23 is loaded into the first fluid inlet pipeline 25 through the first switching valve 32, and the first power member 60 is opened, so that the first fluid enters the synthesis container 40 through the fluid circulation pipeline 27 and the fluid input pipeline 21. Then, the second control valve 34 is closed.

[0097] In step S3, the first control valve 31 connects the fluid circulation pipeline 27 to the output pipeline 22 (e.g., the first control valve 31 is powered off, so that the NO port 312 is opened and the NC port 311 is closed), so that the fluid circulation pipeline 27, the fluid input pipeline 21 and the output pipeline 22 are connected in sequence, thereby switching the fluid circulation synthesis system 100 to the circulation path P3. The first power member 60 continues to work. Thus, the first fluid circulates continuously in the circulation path P3, so that the first fluid and the synthesis carrier undergo a continuous flushing reaction.

[0098] Step S4, the first power member 60 is closed. The fourth control valve 36 and the fifth control valve 37 are energized, so that the gas input pipeline 28, the output pipeline 22 and the waste liquid pipeline 29 are connected in sequence, thereby switching the fluid circulation synthesis system 100 to the exhaust path P4. Thus, the gas provided by the gas source of the gas input pipeline 28 is loaded into the synthesis container 40 through the gas input pipeline 28, so that the waste liquid (such as the reagent that has completed the reaction) in the synthesis container 40 flows out of the synthesis container 40, and further flows into the waste liquid collection member 50 through the waste liquid pipeline 29.

[0099] In step S5, the first control valve 31 connects the fluid circulation pipeline 27 to the first fluid inlet pipeline 25 (e.g., the first control valve 31 is energized so that the NO port 312 is closed and the NC port 311 is opened), so that the first fluid loading pipeline 23, the first fluid inlet pipeline 25, the fluid circulation pipeline 27, and the fluid input pipeline 21 are connected in sequence, thereby switching the fluid circulation synthesis system 100 to the first fluid injection path P1.

[0100] Step S6, the first switching valve 32 is rotated to connect the first fluid inlet pipeline 25 and another first fluid loading pipeline 23, and the second control valve 34 is opened, so that the first fluid (such as ACN cleaning reagent) stored in the first fluid loading component 11 connected to the first fluid loading pipeline 23 is loaded into the first fluid inlet pipeline 25 through the first switching valve 32, and the first power component 60 is opened, so that the first fluid enters the synthesis container 40 through the fluid circulation pipeline 27 and the fluid input pipeline 21. Then, the second control valve 34 is closed.

[0101] In step S7, the first control valve 31 connects the fluid circulation pipeline 27 to the output pipeline 22 (e.g., the first control valve 31 is powered off, so that the NO port 312 is opened and the NC port 311 is closed), so that the fluid circulation pipeline 27, the fluid input pipeline 21 and the output pipeline 22 are connected in sequence, thereby switching the fluid circulation synthesis system 100 to the circulation path P3. The first power member 60 continues to work. Thus, the first fluid circulates continuously in the circulation path P3, so that the first fluid fully cleans the synthesis carrier.

[0102] Step S8, the first power member 60 is closed. The fourth control valve 36 and the fifth control valve 37 are energized, so that the gas input pipeline 28, the output pipeline 22 and the waste liquid pipeline 29 are connected in sequence, thereby switching the fluid circulation synthesis system 100 to the exhaust path P4. Thus, the gas provided by the gas source of the gas input pipeline 28 is loaded into the synthesis container 40 through the gas input pipeline 28, and drives the waste liquid (such as the reagent that has been cleaned) in the synthesis container 40 to flow out of the synthesis container 40, and further flows into the waste liquid collection member 50 through the waste liquid pipeline 29.

[0103] In some embodiments, the above steps may be repeated to inject other types of first fluids. Optionally, for some reaction reagents, step S3 or step S7 may be omitted, that is, the reaction reagents do not need to circulate in the circulation path P3, but directly flow into the waste liquid collection member 50 later.

[0104] In some embodiments, the fluid circulation synthesis system 100 can be subsequently switched to the second fluid injection path P2, the circulation path P3, the exhaust path P4, etc., so as to inject the second fluid and allow the second fluid to undergo a chemical synthesis reaction with the synthesis carrier. In other embodiments, the injection of the first fluid and the injection of the second fluid can also be performed simultaneously, so that the first fluid and the second fluid can be fully mixed in the fluid input pipeline 21, and then enter the synthesis container 40 to undergo a chemical synthesis reaction with the synthesis carrier, thereby improving the reaction efficiency.

[0105] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present application and are not intended to limit it. Although the present application has been described in detail with reference to the preferred embodiments, a person of ordinary skill in the art should understand that the technical solution of the present application may be modified or replaced by equivalents without departing from the spirit and scope of the technical solution of the present application.

Claims

1. A fluid circulation synthesis system, characterized in that: Including piping systems, valve components and synthetic containers; The valve assembly includes a first control valve, and the pipeline system includes a fluid input pipeline, an output pipeline, a first fluid confluence pipeline, and a fluid circulation pipeline; The first end of the fluid input pipeline is connected to the inlet of the synthesis container, and the first end of the output pipeline is connected to the outlet of the synthesis container; the first end of the first fluid inlet pipeline is used to inject the first fluid, the second end of the first fluid inlet pipeline and the first end of the fluid circulation pipeline are connected to the second end of the output pipeline through the first control valve, and the second end of the fluid circulation pipeline is connected to the second end of the fluid input pipeline; The first control valve is used to connect the fluid circulation pipeline to the first fluid inlet pipeline, so that the first fluid inlet pipeline, the fluid circulation pipeline and the fluid input pipeline are connected in sequence, thereby switching the fluid circulation synthesis system to the first fluid injection path, so that the first fluid is loaded into the first fluid injection path; When the first control valve is also used to connect the fluid circulation pipeline to the output pipeline, the fluid circulation pipeline, the fluid input pipeline and the output pipeline are connected in sequence, thereby switching the fluid circulation synthesis system to the circulation path, allowing the first fluid to circulate in the circulation path.

2. The fluid circulation synthesis system according to claim 1, characterized in that: The fluid circulation synthesis system further includes a fluid loading mechanism, which includes a first fluid loading component for storing the first fluid. The pipeline system further includes a first fluid loading pipeline connected to the first fluid loading component, and the first end of the first fluid confluence pipeline is connected to the first fluid loading pipeline, so that the first fluid stored in the first fluid loading component is loaded into the first fluid injection path.

3. The fluid circulation synthesis system according to claim 2, characterized in that: The number of the first fluid loading pipelines and the first fluid loading members is respectively multiple, and the valve assembly further includes a first switching valve, the first end of the first fluid confluence pipeline is connected to multiple first fluid loading pipelines through the first switching valve, and the first switching valve is used to selectively connect the first fluid confluence pipeline to at least one first fluid loading pipeline.

4. The fluid circulation synthesis system according to claim 2, characterized in that: The pipeline system further includes a second fluid inlet pipeline, a first end of the second fluid inlet pipeline is used to inject a second fluid, and a second end of the second fluid inlet pipeline is connected to a second end of the fluid input pipeline; The second fluid confluence pipeline and the fluid input pipeline are used to be connected in sequence, so as to switch the fluid circulation synthesis system to the second fluid injection path, so that the second fluid is loaded into the second fluid injection path.

5. The fluid circulation synthesis system according to claim 4, characterized in that: The fluid loading mechanism further includes a second fluid loading component for storing a second fluid, and the pipeline system further includes a second fluid loading pipeline connected to the second fluid loading component, and a first end of the second fluid inlet pipeline is connected to the second fluid loading pipeline, so that the second fluid stored in the second fluid loading component is loaded into the second fluid injection path.

6. The fluid circulation synthesis system according to claim 5, characterized in that: The number of the second fluid loading pipelines and the second fluid loading members is respectively multiple, and the valve assembly further includes a second switching valve, the first end of the second fluid inlet pipeline is connected to multiple second fluid loading pipelines through the second switching valve, and the second switching valve is used to selectively connect the second fluid inlet pipeline to at least one second fluid loading pipeline.

7. The fluid circulation synthesis system according to claim 1, characterized in that: The pipeline system further comprises a gas input pipeline and a waste liquid pipeline, wherein the first end of the gas input pipeline is connected to another inlet of the synthesis container, and the second end of the gas input pipeline is used to connect to a gas source; the fluid circulation synthesis system further comprises a waste liquid collection piece, wherein the first end of the waste liquid pipeline is connected to the second end of the output pipeline, and the second end of the waste liquid pipeline is connected to the waste liquid collection piece; The gas input pipeline, the output pipeline and the waste liquid pipeline are used to be connected in sequence, so as to switch the fluid circulation synthesis system to an exhaust path, so that the gas source loads the gas into the exhaust path.

8. The fluid circulation synthesis system according to claim 1, characterized in that: The fluid circulation synthesis system further includes a first power member, which is disposed in the fluid circulation pipeline and is used to provide power to the first fluid flowing through the first fluid injection path and the circulation path respectively.

9. The fluid circulation synthesis system according to claim 8, characterized in that: The first power member is a metering pump, which is used to provide power to the first fluid and to measure whether the amount of the first fluid injected into the synthesis container reaches a predetermined amount.

10. The fluid circulation synthesis system according to claim 1, characterized in that: The first control valve is a solenoid valve. When the first control valve is powered off, the fluid flow pipeline is connected to the output pipeline; when the first control valve is powered on, the fluid flow pipeline is connected to the first fluid inlet pipeline.

11. A synthesis method applied to the fluid circulation synthesis system as claimed in claim 1, characterized in that: The steps include: Controlling the first control valve to connect the fluid circulation pipeline to the first fluid inlet pipeline, so that the first fluid inlet pipeline, the fluid circulation pipeline and the fluid input pipeline are connected in sequence, thereby switching the fluid circulation synthesis system to the first fluid injection path; Loading the first fluid into the first fluid inlet pipeline; as well as Control the first control valve to connect the fluid circulation pipeline to the output pipeline, so that the fluid circulation pipeline, the fluid input pipeline and the output pipeline are connected in sequence, thereby switching the fluid circulation synthesis system to the circulation path and allowing the first fluid to circulate in the circulation path.

12. The synthesis method according to claim 11, characterized in that The fluid circulation synthesis system further includes a fluid loading mechanism, the fluid loading mechanism includes a first fluid loading component for storing the first fluid, the pipeline system further includes a first fluid loading pipeline connected to the first fluid loading component, the first end of the first fluid inlet pipeline is connected to the first fluid loading pipeline, and "loading the first fluid into the first fluid inlet pipeline" specifically includes: The first fluid inlet pipeline and the first fluid loading pipeline are connected so that the first fluid stored in the first fluid loading component is loaded into the first fluid injection path.

13. The synthesis method according to claim 12, characterized in that: The number of the first fluid loading pipeline and the number of the first fluid loading components are respectively multiple, the valve assembly further includes a first switching valve, the first end of the first fluid inlet pipeline is connected to the multiple first fluid loading pipelines through the first switching valve, and the multiple first fluid loading pipelines are further connected to the multiple first fluid loading components through multiple second control valves, and "connecting the first fluid inlet pipeline and the first fluid loading pipeline" specifically includes: The first fluid inlet pipeline is selectively connected to at least one first fluid loading pipeline through the first switching valve; At least one second control valve corresponding to at least one first fluid loading pipeline is opened, so that the first fluid stored in at least one first fluid loading component connected to at least one first fluid loading pipeline is loaded into the first fluid inlet pipeline.

14. The synthesis method according to claim 13, characterized in that The fluid circulation synthesis system further includes a first power member disposed in the fluid circulation pipeline, wherein the first power member is a metering pump. When the first fluid is loaded into the first fluid confluence pipeline, the synthesis method further includes: Controlling the first power member to open, thereby providing power to the first fluid flowing through the first fluid injection path, and measuring whether the amount of the first fluid injected into the synthesis container reaches a predetermined amount; When the amount of the first fluid injected into the synthesis container reaches the predetermined amount, the second control valve is controlled to be closed.

15. The synthesis method according to claim 12, characterized in that The pipeline system further includes a second fluid inlet pipeline, a first end of the second fluid inlet pipeline is used to inject a second fluid, and a second end of the second fluid inlet pipeline is connected to a second end of the fluid input pipeline. The synthesis method further includes: The second fluid inlet pipeline and the fluid input pipeline are connected in sequence, so that the fluid circulation synthesis system is switched to the second fluid injection path; loading a second fluid into the second fluid injection path; and The first control valve is controlled to connect the fluid circulation pipeline to the output pipeline, thereby switching the fluid circulation synthesis system to the circulation path, so that the second fluid circulates in the circulation path.

16. The synthesis method according to claim 15, characterized in that The fluid loading mechanism further includes a second fluid loading member for storing the second fluid, the pipeline system further includes a second fluid loading pipeline connected to the second fluid loading member, the first end of the second fluid inlet pipeline is connected to the second fluid loading pipeline, and "loading the second fluid into the second fluid injection path" specifically includes: The second fluid inlet pipeline and the second fluid loading pipeline are connected so that the second fluid stored in the second fluid loading component is loaded into the second fluid injection path.

17. The synthesis method according to claim 15, characterized in that The first fluid is loaded into the first fluid inlet pipeline and the second fluid is loaded into the second fluid inlet pipeline simultaneously, so that the first fluid and the second fluid are mixed in the fluid input pipeline.

18. The synthesis method according to claim 11, characterized in that The valve assembly further includes a fourth control valve and a fifth control valve, the pipeline system further includes a gas input pipeline and a waste liquid pipeline, the first end of the gas input pipeline is connected to another inlet of the synthesis container, the second end of the gas input pipeline is used to connect to a gas source, and the fourth control valve is arranged on the gas input pipeline; the fluid circulation synthesis system further includes a waste liquid collection piece, the first end of the waste liquid pipeline is connected to the second end of the output pipeline through the fifth control valve, and the second end of the waste liquid pipeline is connected to the waste liquid collection piece, and the synthesis method further includes: Opening the fourth control valve and the fifth control valve to connect the gas input pipeline, the output pipeline and the waste liquid pipeline in sequence, thereby switching the fluid circulation synthesis system to an exhaust path; The gas source is turned on, so that the gas from the gas source is loaded into the exhaust path and the remaining first fluid in the synthesis vessel is transferred to the waste collection member.

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