Liquid path system for biochemical synthesis

Abstract

A liquid path system for biochemical synthesis, comprising a gas supply unit, a liquid supply unit, a liquid mixing unit, gas-liquid path switching units, a main flow channel unit, and a waste liquid collection unit. The gas supply unit comprises a gas storage device, a main gas path assembly, a reagent bottle gas path assembly, a liquid mixing bottle gas path assembly, a high-pressure purge gas path assembly, and a low-pressure purge gas path assembly; the liquid supply unit comprises a plurality of main reagent bottles and a plurality of transition bottles; the liquid mixing unit comprises a target liquid mixing bottle connected to the liquid mixing bottle gas path assembly, and a liquid inlet of the target liquid mixing bottle is connected to at least two transition bottles; the gas-liquid path switching units are respectively connected to a liquid outlet of the target liquid mixing bottle, target transition bottles, and the low-pressure purge gas path assembly; and the main flow channel unit comprises a sealed reaction chamber connected to the gas-liquid path switching units by means of multi-path liquid dispensers, and liquid inlets of the sealed reaction chamber are provided with multi-way solenoid valves connected to the high-pressure purge gas path assembly. In the liquid path system, switching of different reagents can be implemented without cross-contamination, and a plurality of areas can be communicated at the same time for chemical reaction.

Description

Fluidic systems for biochemical synthesis Technical Field

[0001] This disclosure relates to the field of biochemical synthesis, and more particularly to a liquid circuit system for biochemical synthesis. Background Technology

[0002] The technology of synthesizing DNA base chains on chip surfaces mainly involves four chemical reactions: coupling, capping, oxidation, and deprotection. Traditional DNA synthesizers face many challenges in the biosynthesis process, such as cross-contamination in liquid channels, inaccurate enzyme dosage, difficult waste liquid treatment, and poor adaptability to complex industrial environments. Although existing chip surface DNA base chain synthesis technologies have solved some of these problems to a certain extent through staged chemical reactions, they still have limitations such as complex reagent switching, low reaction efficiency, high error rate, and the impact of air bubbles in the liquid channels on reaction efficiency. Summary of the Invention

[0003] This disclosure provides a liquid circuit system for biochemical synthesis, which at least partially solves the problems existing in the prior art, such as complex reagent switching, low reaction efficiency, high error rate, and the impact of liquid circuit bubble generation on reaction efficiency.

[0004] In a first aspect, embodiments of this disclosure provide a liquid circuit system for biochemical synthesis, comprising:

[0005] The gas supply unit includes a gas storage device, a main gas path assembly, and a reagent bottle gas path assembly, a mixed liquid bottle gas path assembly, a high-pressure purging gas path assembly, and a low-pressure purging gas path assembly that are connected to the main gas path assembly and are independently set.

[0006] The liquid supply unit includes a plurality of main reagent bottles and a plurality of transition bottles corresponding to the plurality of main reagent bottles; the air inlet of the main reagent bottle is connected to the gas path assembly of the reagent bottle, and the liquid outlet of the main reagent bottle is connected to the transition bottle;

[0007] A mixing unit includes a target mixing bottle connected to the mixing bottle gas path assembly, wherein the inlet of the target mixing bottle is connected to the outlet of at least two of the transition bottles for mixing at least two reagents.

[0008] The gas-liquid path switching unit is connected to the outlet of the target mixing bottle, the target transition bottle, and the low-pressure purge gas path assembly, respectively; the target transition bottle is one of the other transition bottles among the plurality of transition bottles except the one connected to the target mixing bottle;

[0009] The main channel unit includes a sealed reaction chamber connected to the outlet of the gas-liquid switching unit via a multi-channel distributor. The sealed reaction chamber has several reaction zones, each of which has an independently set target inlet, and each of which has a multi-way solenoid valve connected to the high-pressure purging gas path assembly.

[0010] Waste liquid collection unit connected to the sealed reaction chamber.

[0011] In some embodiments, the main air path assembly includes a main air pipeline, a main air path pressure regulating valve, a main air path manual valve, and a four-way air distribution manifold sequentially installed on the main air pipeline, wherein the four-way air distribution manifold has a first air outlet, a second air outlet, a third air outlet, and a fourth air outlet.

[0012] The reagent bottle gas path assembly includes a first pipeline connected to the first gas outlet, a reagent bottle pressure regulating valve, a first gas distribution manual valve, and a reagent bottle gas distribution outlet, which are sequentially installed on the first pipeline.

[0013] The mixing bottle gas circuit assembly includes a second pipeline connected to the second gas outlet, a mixing bottle pressure regulating valve, a second gas distribution manual valve, and a mixing bottle gas distributor installed sequentially on the second pipeline;

[0014] The high-pressure purging air circuit assembly includes a third pipeline connected to the third air outlet, a high-pressure purging pressure regulating valve, a third air distribution manual valve, a pressure relief valve, a high-pressure air storage tank, and a high-pressure air distribution outlet, which are installed sequentially on the third pipeline.

[0015] The low-pressure purging air path assembly includes a fourth pipeline connected to the fourth air outlet, a low-pressure purging pressure regulating valve, a fourth air distribution manual valve, and a low-pressure air distribution outlet, which are sequentially installed on the fourth pipeline.

[0016] In some embodiments, the main reagent bottle and the reagent bottle gas distributor are connected by a pipeline. Under the pressurization of the reagent bottle gas circuit assembly, the main reagent bottle is transferred to the transition bottle through a dual-channel pipeline. Each dual-channel pipeline is equipped with a liquid circuit manual valve.

[0017] The liquid supply unit also includes a weight detection component located at the bottom of the main reagent bottle.

[0018] In some embodiments, the mixing unit further includes a mixing sensor for controlling the mixing process;

[0019] A pressure switching solenoid valve is installed on the connecting pipeline between the target mixing bottle and the gas circuit assembly of the mixing bottle.

[0020] In some embodiments, the gas-liquid path switching unit includes a multi-channel multi-way valve, which includes several inlet channels and a common outlet channel. The several inlet channels are respectively connected to the outlet of the target mixing bottle, several target transition bottles, and the low-pressure gas distributor.

[0021] The common liquid outlet channel is equipped with a flow channel switching solenoid valve and a liquid inlet shut-off valve.

[0022] In some embodiments, the sealed reaction chamber includes several independently set target liquid inlets, several target liquid outlets, and several liquid outlet pipelines, and each target liquid inlet is provided with a three-way solenoid valve between it and the multi-way liquid distributor.

[0023] The number of the three-way solenoid valves and the number of the high-pressure gas distributor ports are set to be the same;

[0024] Each of the aforementioned outlet pipelines is equipped with an outlet solenoid valve and an outlet detection sensor.

[0025] In some embodiments, two sets of the gas-liquid path switching unit are provided. One set of the gas-liquid path switching unit is connected to the target liquid inlet of the sealed reaction chamber through a three-way liquid separator, and the other set of the gas-liquid path switching unit is connected to the target liquid inlet of the sealed reaction chamber through a four-way liquid separator.

[0026] In some embodiments, the waste liquid collection unit includes a waste liquid tank connected to each of the target outlets;

[0027] The waste liquid tank is connected to each of the target outlets via a waste liquid transmission pipeline, and each waste liquid transmission pipeline is equipped with a waste liquid solenoid valve.

[0028] The waste liquid tank is connected to the outlet of the flow channel switching solenoid valve through two target transmission pipelines, and each target transmission pipeline is equipped with a target solenoid valve.

[0029] In some embodiments, the waste liquid tank is further provided with a pipe integration joint, and the waste liquid transmission pipeline and the target transmission pipeline are both connected to the pipe integration joint.

[0030] In some embodiments, the waste liquid collection unit further includes a venting assembly connected to the waste liquid tank for depressurizing the waste liquid tank.

[0031] The liquid circuit system for biochemical synthesis disclosed in this application, through the independent configuration of reagent bottle gas circuit components, mixing bottle gas circuit components, high-pressure purge gas circuit components, and low-pressure purge gas circuit components, enables simple and efficient control of different reagents, while effectively avoiding cross-contamination between different reagents or gases, thus improving reaction efficiency. Specifically, the liquid supply unit and mixing unit can achieve the mixing of preset types of reagents; the gas-liquid circuit switching unit can quickly switch between different reagents and reaction conditions, simplifying the reagent switching process and improving reaction efficiency; the main flow channel unit, matched with the gas-liquid circuit switching unit and high-pressure purge gas circuit components, can accurately distribute different reagents to the corresponding reaction sites in the sealed reaction chamber, reducing reagent mixing in the liquid circuit, lowering the risk of cross-contamination, and simultaneously achieving bubble elimination and waste liquid removal, enabling rapid and precise liquid supply reaction. In summary, this liquid circuit system can deliver different reagents to the sealed reaction chamber for reaction, ensuring that the reaction chamber is bubble-free and reaction waste liquid can be completely removed, guaranteeing that each step of the reaction is completed stably and efficiently.

[0032] The above description is merely an overview of the technical solution disclosed herein. In order to better understand the technical means of this disclosure and to implement it in accordance with the contents of the specification, and to make the above and other objects, features and advantages of this disclosure more apparent and understandable, preferred embodiments are described below in detail with reference to the accompanying drawings. Attached Figure Description

[0033] To more clearly illustrate the technical solutions of the embodiments of this disclosure, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this disclosure. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0034] Figure 1 is a schematic diagram of a liquid circuit system for biochemical synthesis provided in an embodiment of this disclosure.

[0035] Figure 2 is a schematic diagram of the gas supply unit in Figure 1.

[0036] Figure 3 is a schematic diagram of the liquid supply unit in Figure 1.

[0037] Figure 4 is a schematic diagram of the mixing unit in Figure 1.

[0038] Figure 5 is a schematic diagram of the gas-liquid path switching unit in Figure 1.

[0039] Figure 6 is a schematic diagram of the main channel unit in Figure 1.

[0040] Figure 7 is a schematic diagram of the waste liquid collection unit in Figure 1.

[0041] Explanation of reference numerals in the attached figures:

[0042] 100. Gas supply unit; 110. Gas storage tank; 120. Main gas circuit pressure regulating valve; 130. Main gas circuit manual valve; 140. Four-way gas distributor; 151. Reagent bottle pressure regulating valve; 152. First gas distributor manual valve; 153. Reagent bottle gas distributor; 161. Mixing bottle pressure regulating valve; 162. Second gas distributor manual valve; 163. Mixing bottle gas distributor; 171. High-pressure purging pressure regulating valve; 172. Third gas distributor manual valve; 173. Pressure relief valve; 174. High-pressure gas storage tank; 175. High-pressure gas distributor; 181. Low-pressure purging pressure regulating valve; 182. Fourth gas distributor manual valve; 183. Low-pressure gas distributor;

[0043] 200. Liquid supply unit; 211. First main reagent bottle; 212. Second main reagent bottle; 213. Third main reagent bottle; 214. Fourth main reagent bottle; 215. Fifth main reagent bottle; 221. First transition bottle; 222. Second transition bottle; 223. Third transition bottle; 224. Fourth transition bottle; 225. Fifth transition bottle; 230. Weighing sensor; 240. Liquid circuit manual valve;

[0044] 300. Mixing unit; 310. Target mixing bottle; 320. Inlet solenoid valve; 330. Gas pressure switching solenoid valve; 340. Mixing sensor;

[0045] 400. Gas-liquid path switching unit; 410. Ten-channel multi-way valve; 420. Flow channel switching solenoid valve; 430. Liquid inlet shut-off valve;

[0046] 500. Main channel unit; 510. Sealed reaction chamber; 520. Three-way distributor; 530. Four-way distributor; 540. Three-way solenoid valve; 550. Outlet solenoid valve; 560. Discharge detection sensor;

[0047] 600 Waste liquid collection unit; 610 Waste liquid tank; 620 Waste liquid transmission pipeline; 630 Waste liquid solenoid valve; 640 Target transmission pipeline; 650 Pipe integration joint; 660 Exhaust pipe. Detailed Implementation

[0048] The embodiments of this disclosure will now be described in detail with reference to the accompanying drawings.

[0049] It should be understood that the following specific examples illustrate the implementation of this disclosure, and those skilled in the art can easily understand other advantages and effects of this disclosure from the content disclosed in this specification. Obviously, the described embodiments are only a part of the embodiments of this disclosure, and not all of them. This disclosure can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of this disclosure. It should be noted that, in the absence of conflict, the following embodiments and features in the embodiments can be combined with each other. Based on the embodiments in this disclosure, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this disclosure.

[0050] Referring to Figure 1, this application discloses a liquid circuit system for biochemical synthesis, including: a gas supply unit 100, a liquid supply unit 200, a liquid mixing unit 300, a gas-liquid circuit switching unit 400, a main flow channel unit 500, and a waste liquid collection unit 600. The gas supply unit 100 includes a gas storage device, a main gas circuit assembly, and reagent bottle gas circuit assemblies, liquid mixing bottle gas circuit assemblies, high-pressure purging gas circuit assemblies, and low-pressure purging gas circuit assemblies that are connected to the main gas circuit assembly and are independently arranged. The independently arranged reagent bottle gas circuit assembly, liquid mixing bottle gas circuit assembly, high-pressure purging gas circuit assembly, and low-pressure purging gas circuit assembly are used to provide the required pressurized gas for different functional areas.

[0051] The liquid supply unit 200 includes several main reagent bottles and several transition bottles corresponding to the main reagent bottles; the air inlet of the main reagent bottle is connected to the reagent bottle gas path assembly, and the liquid outlet of the main reagent bottle is connected to the transition bottle.

[0052] The mixing unit 300 includes a target mixing bottle 310 connected to the mixing bottle gas path assembly. The inlet of the target mixing bottle 310 is connected to the outlet of at least two transition bottles for mixing at least two reagents.

[0053] The gas-liquid path switching unit 400 is connected to the outlet of the target mixing bottle 310, the target transition bottle, and the low-pressure purge gas path assembly, respectively; the target transition bottle is one of the other transition bottles connected to the target mixing bottle 310.

[0054] The main flow unit 500 includes a sealed reaction chamber 510 connected to the outlet of the gas-liquid switching unit 400 via a multi-channel distributor. The sealed reaction chamber 510 has several reaction zones, each with an independently set target inlet. Each target inlet of the reaction zone is equipped with a multi-port solenoid valve connected to the high-pressure purging gas path assembly. The waste liquid collection unit 600 is connected to the sealed reaction chamber 510 and is used to collect the waste liquid after the reaction.

[0055] The liquid circuit system for biochemical synthesis disclosed in this application significantly improves upon existing technologies through innovative design and modular structure. Specifically, the reagent bottle gas circuit assembly, mixing bottle gas circuit assembly, high-pressure purge gas circuit assembly, and low-pressure purge gas circuit assembly are all independently set, effectively avoiding cross-contamination between different reagents or gases. The liquid supply unit and mixing unit enable the mixing of preset reagent types. The gas-liquid circuit switching unit allows for rapid switching between different reagents and reaction conditions, simplifying the reagent switching process and improving reaction efficiency. The main flow channel unit, matched with the gas-liquid circuit switching unit and high-pressure purge gas circuit assembly, precisely distributes different reagents to corresponding reaction sites in the sealed reaction chamber, reducing reagent mixing in the liquid circuit, lowering the risk of cross-contamination, and simultaneously eliminating bubbles and removing waste liquid, achieving rapid and precise liquid supply and reaction. In summary, this liquid circuit system can deliver different reagents to a sealed reaction chamber for reaction, ensuring a bubble-free reaction chamber and thorough removal of reaction waste liquid, guaranteeing stable and efficient completion of each reaction step.

[0056] Referring to Figure 2, the gas storage device is a gas storage tank 110, which is filled with inert gas at a certain pressure.

[0057] The main gas circuit assembly includes a main gas pipeline connected to the gas storage tank 110, a main gas pressure regulating valve 120, a main gas manual valve 130, and a four-way gas distributor 140 installed sequentially on the main gas pipeline. The main gas pressure regulating valve 120 is used to regulate the output pressure; the main gas manual valve 130 is used to manually control the on / off of the gas source; the four-way gas distributor 140 has a first air inlet, a first air outlet, a second air outlet, a third air outlet, and a fourth air outlet. The first air inlet is connected to the main gas pipeline, and the first, second, third, and fourth air outlets are arranged in parallel.

[0058] The reagent bottle gas circuit assembly includes a first pipeline connected to a first gas outlet, a reagent bottle pressure regulating valve 151, a first gas distribution manual valve 152, and a reagent bottle gas distribution outlet 153, which are sequentially installed on the first pipeline. The reagent bottle pressure regulating valve 151 is used to regulate the pressure on the first pipeline, and the first gas distribution manual valve 152 is used to manually control the gas supply on the first pipeline.

[0059] The mixing bottle gas circuit assembly includes a second pipeline connected to a second gas outlet, a mixing bottle pressure regulating valve 161, a second gas distribution manual valve 162, and a mixing bottle gas distributor 163, which are installed sequentially on the second pipeline. The mixing bottle pressure regulating valve 161 is used to regulate the pressure on the second pipeline, and the second gas distribution manual valve 162 is used to manually control the gas supply on and off the second pipeline.

[0060] The high-pressure purging gas path assembly includes a third pipeline connected to the third gas outlet, and a high-pressure purging pressure regulating valve 171, a third gas distribution manual valve 172, a pressure relief valve 173, a high-pressure gas storage tank 174, and a high-pressure gas distributor 175, which are installed sequentially on the third pipeline. The high-pressure purging pressure regulating valve 171 is used to regulate the pressure on the third pipeline, and the third gas distribution manual valve 172 is used to manually control the gas supply on and off the third pipeline. The high-pressure gas storage tank 174 is used to buffer the gas during high-pressure purging and avoid impact. The pressure relief valve 173 is used to discharge the high-pressure gas in the high-pressure gas storage tank 174 after high-pressure purging, in preparation for the next high-pressure gas buffering.

[0061] The low-pressure purging air circuit assembly includes a fourth pipeline connected to the fourth air outlet, a low-pressure purging pressure regulating valve 181, a fourth air distribution manual valve 182, and a low-pressure air distribution outlet 183 installed sequentially on the fourth pipeline. The low-pressure purging pressure regulating valve 181 is used to regulate the pressure on the fourth pipeline, and the fourth air distribution manual valve 182 is used to manually control the air supply on and off on the fourth pipeline.

[0062] Referring to Figure 3, the liquid supply unit 200 includes a main reagent bottle and a transition bottle corresponding to the main reagent bottle. The air inlet of the main reagent bottle is connected to the gas path assembly of the reagent bottle, and the liquid outlet of the main reagent bottle is connected to the transition bottle.

[0063] Under the pressurization of the reagent bottle gas path assembly, the main reagent bottle is transferred to the transition bottle through a dual-channel pipeline. That is, the reagent bottle gas path assembly is used to provide positive pressure gas to the main reagent bottle so as to force out the liquid from the main reagent bottle.

[0064] Each of the dual-channel pipelines is equipped with a hydraulic manual valve 240 to control the on / off state of the corresponding pipeline.

[0065] The main reagent bottle has a three-channel cap. One channel connects to the reagent bottle gas distributor 153 to pressurize the main reagent bottle. The other two channels are liquid outlets connected to the liquid flow manual valve 240. The liquid flow manual valve 240 is connected to the corresponding transition bottle. The transition bottle cap has four channels: two for liquid inlet and two for liquid outlet.

[0066] The number of transition bottles is the same as the number of main reagent bottles; the transition bottles allow for replacement of main reagent bottles without shutting down the machine, and avoid the influence of air introduced when replacing main reagent bottles.

[0067] The liquid supply unit 200 also includes a weight detection component located at the bottom of the main reagent bottle. Specifically, the weight detection component includes a weighing sensor 230, which can display the weight of the main reagent bottle in real time and convert it into volume for display in the software. This is used to monitor reagent consumption and remaining reagent volume, and can also serve as a basis for judging liquid leakage or liquid circuit component failure.

[0068] In this embodiment, there are five main reagent bottles and five transition bottles, specifically including: a first main reagent bottle 211, a second main reagent bottle 212, a third main reagent bottle 213, a fourth main reagent bottle 214, a fifth main reagent bottle 215, a first transition bottle 221, a second transition bottle 222, a third transition bottle 223, a fourth transition bottle 224, and a fifth transition bottle 225. The first main reagent bottle 211 is connected to the first transition bottle 221, the second main reagent bottle 212 is connected to the second transition bottle 222, the third main reagent bottle 213 is connected to the third transition bottle 223, the fourth main reagent bottle 214 is connected to the fourth transition bottle 224, and the fifth main reagent bottle 215 is connected to the fifth transition bottle 225 through dual-channel pipelines.

[0069] Reagents flow in through a separate main reagent bottle and transition bottle system. The amount of each reagent can be controlled by precisely adjusting the gas pressure and liquid flow rate to ensure the accuracy of reagent dosage.

[0070] Referring to Figure 4, the mixing unit 300 includes a target mixing bottle 310 connected to the mixing bottle gas path assembly. The inlet of the target mixing bottle 310 is connected to the outlet of at least two transition bottles for mixing at least two reagents, and further, to achieve a 1:1 mixing of at least two reagents.

[0071] In this embodiment, it is mainly used to achieve a 1:1 mixing of two reagents. Specifically, the cap of the target mixing bottle 310 has four channels: two channels for liquid inlet, which are connected to two different transition bottles through pipelines, and each pipeline is equipped with a liquid inlet solenoid valve 320; one channel for liquid outlet, and one channel is connected to the mixing bottle gas distributor 163.

[0072] The mixing unit 300 also includes a mixing sensor 340 installed on the side of the target mixing bottle 310, which is used to control the mixing process. When the mixing sensor 340 is triggered, the mixing is terminated, indicating that the reagent injected into the target mixing bottle 310 is sufficient.

[0073] A pressure switching solenoid valve 330 is installed on the connecting pipeline between the target mixing bottle 310 and the mixing bottle gas outlet 163 to switch the gas pressure inside the target mixing bottle 310. The pressure is normal when the liquid is injected and positive when the liquid is discharged. By precisely controlling the opening time of the liquid inlet solenoid valve 320 on the corresponding pipeline and providing algorithm compensation, accurate mixing can be achieved with a mixing ratio error of ≤1%.

[0074] Referring to Figure 5, the gas-liquid path switching unit 400 is connected to the outlet of the target mixing bottle 310, the target transition bottle, and the low-pressure purging gas path assembly, respectively; the target transition bottle is one of the other transition bottles connected to the target mixing bottle 310.

[0075] Specifically, the gas-liquid switching unit 400 includes a multi-channel multi-way valve, which includes several inlet channels and a common outlet channel. The several inlet channels are respectively connected to the outlet of the target mixing bottle 310, several target transition bottles, and the low-pressure gas distributor 183. The common outlet channel is equipped with a flow channel switching solenoid valve 420 and an inlet shut-off valve 430.

[0076] In this embodiment, the multi-channel multi-way valve is preferably a ten-channel multi-way valve 410. The ten-channel multi-way valve 410 has ten inlet channels and one common outlet channel. The inlet channels connect to four reaction reagents and a low-pressure gas distributor 183, while one channel is blocked as a zero position. To avoid contamination during reagent switching, the reagents and gases are connected to the inlet channels of the ten-channel multi-way valve 410 according to the process sequence and the rotation direction of the valve. The outlet of the ten-channel multi-way valve 410 is connected to a flow channel switching solenoid valve 420, which is a three-way solenoid valve 540, enabling switching between the reaction flow channel and the cleaning flow channel. An inlet shut-off valve 430 is installed after the flow channel switching solenoid valve 420 for shutting off the inlet pipeline.

[0077] The 10-channel multi-way valve 410 allows for switching between different reagents and gases, achieving low pollution and high efficiency.

[0078] Furthermore, a bypass can be set after the ten-channel multi-way valve 410 to enable filling and cleaning of the ten-channel multi-way valve 410 and its upstream liquid circuit.

[0079] In this embodiment, two sets of gas-liquid path switching units 400 are provided.

[0080] Referring to Figure 6, the main channel unit 500 includes a sealed reaction chamber 510 connected to the outlet of the gas-liquid switching unit 400 via a multi-channel distributor for reagent reaction.

[0081] The sealed reaction chamber 510 includes several target liquid inlets, several target liquid outlets, and several liquid outlet pipelines. Each target liquid inlet is equipped with a three-way solenoid valve 540 between itself and the multi-way distributor. Each liquid outlet pipeline is equipped with an outlet solenoid valve 550 and a liquid outlet detection sensor 560 for liquid outlet detection.

[0082] In this embodiment, an outlet solenoid valve 550 is installed at the outlet of the sealed reaction chamber 510. By controlling the opening and closing of the outlet solenoid valve 550, the effect of pressurization and degassing can be achieved. Because some organic reagents have low boiling points and are highly volatile, a large number of bubbles are generated during liquid injection due to pipe diameter changes and pressure reduction. These bubbles are detrimental to the reaction, easily causing incomplete or even no reaction. This device eliminates the bubbles by pressurizing the reagent. Specifically, during liquid injection, the outlet solenoid valve 550 of the sealed reaction chamber 510 is first closed. The reagent fills the sealed reaction chamber 510 under positive pressure and reaches the injection pressure. At this point, some bubbles still remain in the sealed reaction chamber 510. Then, the outlet solenoid valve 550 is opened to continue injection until the bubbles disappear.

[0083] The liquid detection sensor 560 can determine whether there is liquid in the liquid tube, and use this as input for related interlocking actions.

[0084] In this embodiment, the main flow channel unit 500 includes a three-way distributor 520 connecting the outlet of the first gas-liquid path switching unit 400 (i.e., the outlet of the corresponding liquid inlet shut-off valve 430) and a four-way distributor 530 connecting the outlet of another gas-liquid path switching unit 400 (i.e., the outlet of the corresponding liquid inlet shut-off valve 430). Through the distributor structure, liquid path changes from one to three or one to four can be achieved, thereby adapting to the seven-zone sealed reaction chamber 510.

[0085] Specifically, the sealed reaction chamber 510 includes seven reaction zones, with seven liquid inlets and seven liquid outlets. Two liquid distributors with a total of seven liquid outlets are connected to the seven liquid inlets of the sealed reaction chamber 510. The outlet solenoid valve 550, the liquid outlet detection sensor 560, and the liquid outlet pipe are all provided with seven.

[0086] Seven three-way solenoid valves 540 are installed on the liquid path connecting the four-way liquid separator 530, the three-way liquid separator 520 and the seven liquid inlets of the sealed reaction chamber 510. When cleaning up waste liquid, the liquid path can be switched to the high-pressure purging gas path through the three-way solenoid valves 540.

[0087] The multi-channel dispenser can distribute reagents to multiple reaction zones, each with tens of thousands of reaction sites. The sealed reaction chamber 510 design ensures that the reaction in each reaction zone proceeds independently.

[0088] Referring to Figure 7, the waste liquid collection unit 600 includes a waste liquid tank 610 connected to each target outlet; the waste liquid tank 610 is connected to each target outlet through a waste liquid transmission pipeline 620, and each waste liquid transmission pipeline 620 is equipped with a waste liquid solenoid valve 630.

[0089] Biosynthesis is generally carried out in a glove box with strictly controlled water and oxygen content. The liquid circuit system can be isolated from the external atmospheric environment of the glove box by the waste liquid solenoid valve 630.

[0090] Waste liquid tank 610 is connected to the outlet of flow channel switching solenoid valve 420 through two target transmission pipelines 640, each of which is equipped with a target solenoid valve.

[0091] The waste liquid tank 610 is also equipped with a pipe integration connector 650. The waste liquid transmission pipeline 620 and the target transmission pipeline 640 are both connected to the pipe integration connector 650. The pipe integration connector 650 can be used for a long time. When there is too much waste liquid, only the waste liquid tank 610 needs to be replaced.

[0092] The waste liquid collection unit 600 also includes an exhaust assembly connected to the waste liquid tank 610 for venting waste gas and relieving pressure from the waste liquid tank 610; in this embodiment, the exhaust assembly includes an exhaust pipe 660.

[0093] A dedicated waste liquid collection unit 600 is directly connected to the sealed reaction chamber 510, which can collect the waste liquid after the reaction in time, reduce the retention of waste liquid in the system, and improve the treatment efficiency.

[0094] In this embodiment, the purging of waste liquid is divided into two types: low-pressure purging and high-pressure purging. The air source path for low-pressure purging is a ten-channel multi-way valve, and the path for high-pressure purging is a three-way solenoid valve at the front end of the sealed reaction chamber. Different purging process combinations can be selected according to different working conditions.

[0095] Specifically, the low-pressure purging gas source is connected to the inlet of the ten-channel multi-way valve. The three-way solenoid valve at the outlet of the ten-channel multi-way valve and the inlet of the reaction chamber forms a common pipeline through which all reagents pass. The low-pressure purging primarily cleans the common pipeline and most of the reagents in the reaction chamber. The high-pressure purging gas source is connected to the three-way solenoid valve at the inlet of the reaction chamber. By switching the three-way solenoid valve on and off, the liquid path can be switched to the high-pressure purging gas path. The main function of high-pressure purging is to completely dry any remaining reagents in the reaction chamber.

[0096] In this application, the reagents are diverse and have varying degrees of corrosivity. Therefore, the fluid circuit components are all made of materials that have good resistance to all reagents.

[0097] The liquid circuit system for biochemical synthesis disclosed in this application allows for flexible combination of process steps by setting different programs and parameters, adapting to different reaction requirements at different stages. The liquid circuit system for biochemical synthesis disclosed in this application adopts a modular design, with each unit operating independently. It can be flexibly adjusted and expanded according to actual needs, enhancing the system's adaptability to complex industrial environments. The sealed reaction chamber design reduces dependence on the external environment, enabling the system to operate stably in various industrial environments.

[0098] The above description of the disclosed aspects is provided to enable any person skilled in the art to make or use this disclosure. Various modifications to these aspects will be readily apparent to those skilled in the art, and the general principles defined herein may be applied to other aspects without departing from the scope of this disclosure. Therefore, this disclosure is not intended to be limited to the aspects shown herein, but rather to be carried out within the widest scope consistent with the principles and novel features disclosed herein.

[0099] The above description has been given for purposes of illustration and description. Furthermore, this description is not intended to limit the embodiments of this disclosure to the forms disclosed herein. Although numerous exemplary aspects and embodiments have been discussed above, those skilled in the art will recognize certain variations, modifications, alterations, additions, and sub-combinations therein.

Claims

1. A liquid circuit system for biochemical synthesis, comprising: The gas supply unit includes a gas storage device, a main gas path assembly, and a reagent bottle gas path assembly, a mixed liquid bottle gas path assembly, a high-pressure purging gas path assembly, and a low-pressure purging gas path assembly that are connected to the main gas path assembly and are independently set. The liquid supply unit includes a plurality of main reagent bottles and a plurality of transition bottles corresponding to the plurality of main reagent bottles; the air inlet of the main reagent bottle is connected to the gas path assembly of the reagent bottle, and the liquid outlet of the main reagent bottle is connected to the transition bottle; A mixing unit includes a target mixing bottle connected to the mixing bottle gas path assembly, wherein the inlet of the target mixing bottle is connected to the outlet of at least two of the transition bottles for mixing at least two reagents. The gas-liquid path switching unit is connected to the outlet of the target mixing bottle, the target transition bottle, and the low-pressure purge gas path assembly, respectively; the target transition bottle is one of the other transition bottles among the plurality of transition bottles except the one connected to the target mixing bottle; The main channel unit includes a sealed reaction chamber connected to the outlet of the gas-liquid switching unit via a multi-channel distributor. The sealed reaction chamber has several reaction zones, each of which has an independently set target liquid inlet, and each target liquid inlet is equipped with a multi-way solenoid valve connected to the high-pressure purging gas path assembly. Waste liquid collection unit connected to the sealed reaction chamber.

2. The liquid circuit system for biochemical synthesis according to claim 1, wherein the main gas circuit assembly includes a main gas pipeline, a main gas circuit pressure regulating valve, a main gas circuit manual valve and a four-way gas distribution manifold installed sequentially on the main gas pipeline, wherein the four-way gas distribution manifold has a first gas outlet, a second gas outlet, a third gas outlet and a fourth gas outlet. The reagent bottle gas path assembly includes a first pipeline connected to the first gas outlet, a reagent bottle pressure regulating valve, a first gas distribution manual valve, and a reagent bottle gas distribution outlet, which are sequentially installed on the first pipeline. The mixing bottle gas circuit assembly includes a second pipeline connected to the second gas outlet, a mixing bottle pressure regulating valve, a second gas distribution manual valve, and a mixing bottle gas distributor installed sequentially on the second pipeline; The high-pressure purging air circuit assembly includes a third pipeline connected to the third air outlet, a high-pressure purging pressure regulating valve, a third air distribution manual valve, a pressure relief valve, a high-pressure air storage tank, and a high-pressure air distribution outlet, which are installed sequentially on the third pipeline. The low-pressure purging air path assembly includes a fourth pipeline connected to the fourth air outlet, a low-pressure purging pressure regulating valve, a fourth air distribution manual valve, and a low-pressure air distribution outlet, which are sequentially installed on the fourth pipeline.

3. The liquid circuit system for biochemical synthesis according to claim 2, characterized in that, The main reagent bottle and the reagent bottle gas distributor are connected by a pipeline. Under the pressure of the reagent bottle gas circuit assembly, the main reagent bottle is transferred to the transition bottle through a dual-channel pipeline. Each dual-channel pipeline is equipped with a liquid circuit manual valve. The liquid supply unit also includes a weight detection component located at the bottom of the main reagent bottle.

4. The liquid circuit system for biochemical synthesis according to claim 2, characterized in that, The mixing unit also includes a mixing sensor for controlling the mixing process; A pressure switching solenoid valve is installed on the connecting pipeline between the target mixing bottle and the gas circuit assembly of the mixing bottle.

5. The liquid circuit system for biochemical synthesis according to claim 2, characterized in that, The gas-liquid switching unit includes a multi-channel multi-way valve, which includes several inlet channels and a common outlet channel. The several inlet channels are respectively connected to the outlet of the target mixing bottle, several target transition bottles, and the low-pressure gas distributor. The common liquid outlet channel is equipped with a flow channel switching solenoid valve and a liquid inlet shut-off valve.

6. The liquid circuit system for biochemical synthesis according to claim 5, characterized in that, The sealed reaction chamber includes several independently set target liquid inlets, several target liquid outlets, and several liquid outlet pipelines. Each target liquid inlet is equipped with a three-way solenoid valve between itself and the multi-way liquid distributor. The number of the three-way solenoid valves and the number of the high-pressure gas distributor ports are set to be the same; Each of the aforementioned outlet pipelines is equipped with an outlet solenoid valve and an outlet detection sensor.

7. The liquid circuit system for biochemical synthesis according to claim 6, characterized in that, Two sets of the gas-liquid path switching unit are provided. One set of the gas-liquid path switching unit is connected to the target liquid inlet of the sealed reaction chamber through a three-way liquid distributor, and the other set of the gas-liquid path switching unit is connected to the target liquid inlet of the sealed reaction chamber through a four-way liquid distributor.

8. The liquid circuit system for biochemical synthesis according to claim 7, characterized in that, The waste liquid collection unit includes a waste liquid tank connected to each of the target outlets; The waste liquid tank is connected to each of the target outlets via a waste liquid transmission pipeline, and each waste liquid transmission pipeline is equipped with a waste liquid solenoid valve. The waste liquid tank is connected to the outlet of the flow channel switching solenoid valve through two target transmission pipelines, and each target transmission pipeline is equipped with a target solenoid valve.

9. The liquid circuit system for biochemical synthesis according to claim 8, characterized in that, The waste liquid tank is also equipped with a pipe integration joint, and the waste liquid transmission pipeline and the target transmission pipeline are both connected to the pipe integration joint.

10. The liquid circuit system for biochemical synthesis according to claim 8, characterized in that, The waste liquid collection unit also includes a venting assembly connected to the waste liquid tank for depressurizing the waste liquid tank.

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