Liquid path system for biochemical synthesis

Abstract

The liquid path system comprises a gas supply unit, a liquid supply unit, a liquid mixing unit, a gas-liquid path switching unit, a main flow channel unit and a waste liquid collecting unit, and 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 purging gas path assembly and a low-pressure purging 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 with the liquid mixing bottle gas path assembly, and a liquid inlet of the target liquid mixing bottle is connected with at least two transition bottles; the gas-liquid path switching unit is connected with a liquid outlet of the target liquid mixing bottle, the target transition bottle and the low-pressure purging gas path assembly. The main flow channel unit comprises a sealed reaction cavity connected with the gas-liquid path switching unit through a multi-path liquid separator, and a liquid inlet of the main flow channel unit is provided with a multi-way electromagnetic valve connected with the high-pressure purging gas path assembly. According to the liquid path system, different reagents can be switched without cross contamination, and a plurality of areas can be communicated at the same time for chemical reaction.

Description

Technical Field

[0001] The present disclosure relates to the field of biochemical synthesis, and in particular to a liquid circuit system for biochemical synthesis. Background Art

[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 process of biosynthesis, such as cross-contamination of liquid circuits, inaccurate enzyme dosage, difficulty in waste liquid treatment, and poor adaptability to complex industrial environments. Although the existing technology of synthesizing DNA base chains on chip surfaces has solved some problems to a certain extent through staged chemical reactions, it still has limitations such as complex reagent switching, low reaction efficiency, high error rate, and liquid circuit bubbles that affect reaction efficiency. Summary of the invention

[0003] In view of this, the embodiments of the present disclosure provide 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 liquid circuit bubble generation affecting reaction efficiency.

[0004] In a first aspect, the present disclosure provides a liquid circuit system for biochemical synthesis, comprising:

[0005] A gas supply unit, comprising a gas storage device, a main gas circuit assembly, and a reagent bottle gas circuit assembly, a mixing bottle gas circuit assembly, a high-pressure purge gas circuit assembly, and a low-pressure purge gas circuit assembly that are connected to the main gas circuit assembly and are independently arranged;

[0006] A liquid supply unit, comprising a plurality of main reagent bottles and a plurality of transition bottles corresponding to the main reagent bottles; the air inlet of the main reagent bottle is connected to the reagent bottle air circuit assembly, and the liquid outlet of the main reagent bottle is connected to the transition bottle;

[0007] A liquid mixing unit, comprising a target liquid mixing bottle connected to the liquid mixing bottle gas path assembly, wherein the liquid inlet of the target liquid mixing bottle is connected to the liquid outlets of at least two of the transition bottles, for mixing at least two reagents;

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

[0009] A main channel unit, comprising a sealed reaction chamber connected to the outlet of the gas-liquid path switching unit through a multi-way liquid distributor, wherein the sealed reaction chamber has a plurality of reaction partitions, each of which has a target liquid inlet independently arranged, and each of which has a multi-way solenoid valve connected to the high-pressure purge gas path assembly;

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

[0011] Optionally, 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 row installed on the main gas pipeline in sequence, and the four-way gas distribution row has a first gas outlet, a second gas outlet, a third gas outlet and a fourth gas outlet;

[0012] The reagent bottle gas circuit assembly comprises a first pipeline connected to the first gas outlet, a reagent bottle pressure regulating valve, a first gas circuit manual valve, and a reagent bottle gas 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 circuit manual valve, and a mixing bottle gas outlet installed in sequence on the second pipeline;

[0014] The high-pressure purge gas circuit assembly includes a third pipeline connected to the third gas outlet, a high-pressure purge pressure regulating valve, a third gas circuit manual valve, a pressure relief valve, a high-pressure gas storage tank, and a high-pressure gas outlet installed in sequence on the third pipeline;

[0015] The low-pressure purge gas circuit assembly includes a fourth pipeline connected to the fourth gas outlet, a low-pressure purge pressure regulating valve, a fourth gas branch manual valve, and a low-pressure gas branch exhaust installed in sequence on the fourth pipeline.

[0016] Optionally, the main reagent bottle is connected to the reagent bottle gas distribution row through a pipeline, and the main reagent bottle is transferred to the transition bottle through a dual-channel pipeline under the pressure of the reagent bottle gas circuit assembly; and a liquid circuit manual valve is installed on both of the dual-channel pipelines;

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

[0018] Optionally, the liquid mixing unit further includes a liquid mixing sensor for controlling the liquid mixing process;

[0019] An air pressure switching solenoid valve is provided on the connecting pipeline between the target mixing bottle and the mixing bottle air circuit assembly.

[0020] Optionally, the gas-liquid path switching unit comprises a multi-channel multi-way valve, the multi-channel multi-way valve comprises a plurality of liquid inlet channels and a common liquid outlet channel, the plurality of liquid inlet channels are respectively connected to the liquid outlet of the target mixed liquid bottle, a plurality of target transition bottles, and the low-pressure gas distribution row;

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

[0022] Optionally, the sealed reaction chamber comprises a plurality of independently arranged target liquid inlets, a plurality of target liquid outlets, and a plurality of liquid outlet pipelines, and a three-way solenoid valve is provided between each of the target liquid inlets and the multi-way liquid distributor;

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

[0024] Each of the liquid outlet pipelines is provided with an outlet solenoid valve and a liquid outlet detection sensor.

[0025] Optionally, two sets of the gas-liquid switching units are provided, one set of the gas-liquid switching units 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 switching units is connected to the target liquid inlet of the sealed reaction chamber through a four-way liquid separator.

[0026] Optionally, the waste liquid collection unit comprises a waste liquid bucket connected to each of the target liquid outlets;

[0027] The waste liquid barrel is connected to each of the target liquid outlets through a waste liquid transmission pipeline, and each of the waste liquid transmission pipelines is provided with a waste liquid solenoid valve;

[0028] The waste liquid barrel is connected to the liquid outlet of the flow channel switching solenoid valve through two target transmission pipelines, and the target transmission pipelines are both provided with target solenoid valves.

[0029] Optionally, a pipe integrated joint is also provided on the waste liquid barrel, and the waste liquid transmission pipeline and the target transmission pipeline are both connected to the pipe integrated joint.

[0030] Optionally, the waste liquid collection unit further comprises an exhaust assembly connected to the waste liquid barrel for relieving pressure on the waste liquid barrel.

[0031] The liquid circuit system for biochemical synthesis disclosed in the present application can realize simple and efficient control of different reagents through the independent setting of the reagent bottle gas circuit assembly, the mixing bottle gas circuit assembly, the high-pressure purge gas circuit assembly, and the low-pressure purge gas circuit assembly, and effectively avoid cross contamination between different reagents or gases, thereby improving reaction efficiency; specifically, the mixing of preset types of reagents can be realized through the liquid supply unit and the mixing liquid unit; different reagents and reaction conditions can be quickly switched through the gas-liquid circuit switching unit, simplifying the reagent switching process and improving reaction efficiency; through the main flow channel unit matched with the gas-liquid circuit switching unit and the high-pressure purge gas circuit assembly, different reagents can be accurately distributed to the corresponding reaction sites in the sealed reaction chamber, reducing the mixing of reagents in the liquid circuit, reducing the risk of cross contamination, and realizing bubble elimination and waste liquid removal at the same time, realizing fast and accurate liquid supply reaction. In summary, this liquid circuit system can realize the transportation of different reagents to the sealed reaction chamber for reaction, there are no bubbles in the reaction chamber, and the reaction waste liquid can be cleaned up, ensuring that each step of the reaction is completed stably and efficiently.

[0032] The above description is only an overview of the technical solution of the present invention. In order to more clearly understand the technical means of the present invention, it can be implemented in accordance with the contents of the specification. In order to make the above and other purposes, features and advantages of the present invention more obvious and easy to understand, the following preferred embodiments are specifically cited and described in detail with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] In order to more clearly illustrate the technical solutions of the embodiments of the present disclosure, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present disclosure. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0034] Figure 1 A schematic diagram of the structure of a liquid system for biochemical synthesis provided in an embodiment of the present disclosure.

[0035] Figure 2 for Figure 1 Schematic diagram of the air supply unit in .

[0036] Figure 3 for Figure 1 Schematic diagram of the liquid supply unit in.

[0037] Figure 4 for Figure 1 Schematic diagram of the mixing unit in .

[0038] Figure 5 for Figure 1 Schematic diagram of the gas-liquid switching unit.

[0039] Figure 6 for Figure 1 Schematic diagram of the main channel unit in .

[0040] Figure 7 for Figure 1 Schematic diagram of the waste collection unit in .

[0041] Description of reference numerals:

[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 distribution bar; 151, reagent bottle pressure regulating valve; 152, first gas circuit manual valve; 153, reagent bottle gas distribution bar; 161, mixing bottle pressure regulating valve; 162, second gas circuit manual valve; 163, mixing bottle gas distribution bar; 171, high-pressure purge pressure regulating valve; 172, third gas circuit manual valve; 173, pressure relief valve; 174, high-pressure gas storage tank; 175, high-pressure gas distribution bar; 181, low-pressure purge pressure regulating valve; 182, fourth gas circuit manual valve; 183, low-pressure gas distribution bar;

[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, liquid mixing unit; 310, target liquid mixing bottle; 320, liquid inlet solenoid valve; 330, air pressure switching solenoid valve; 340, liquid mixing sensor;

[0045] 400, gas-liquid path switching unit; 410, ten-channel multi-way valve; 420, flow path switching solenoid valve; 430, liquid inlet cut-off valve;

[0046] 500, main channel unit; 510, sealed reaction chamber; 520, three-way liquid distributor; 530, four-way liquid distributor; 540, three-way solenoid valve; 550, outlet solenoid valve; 560, liquid outlet detection sensor;

[0047] 600, waste liquid collection unit; 610, waste liquid barrel; 620, waste liquid transmission pipeline; 630, waste liquid solenoid valve; 640, target transmission pipeline; 650, pipe integrated joint; 660, exhaust pipe. DETAILED DESCRIPTION

[0048] The present disclosure is further described in detail below in conjunction with the accompanying drawings and implementations. It is understood that the specific implementations described herein are only used to explain the relevant content, rather than to limit the present disclosure. It should also be noted that, for ease of description, only the parts related to the present disclosure are shown in the accompanying drawings.

[0049] It should be noted that, in the absence of conflict, the embodiments and features of the embodiments in the present disclosure can be combined with each other. The technical solution of the present disclosure will be described in detail below with reference to the accompanying drawings and in combination with the embodiments.

[0050] Unless otherwise specified, the exemplary embodiments / embodiments shown will be understood as providing exemplary features of various details of some ways in which the technical concept of the present disclosure can be implemented in practice. Therefore, unless otherwise specified, the features of the various embodiments / embodiments can be combined, separated, interchanged and / or rearranged without departing from the technical concept of the present disclosure.

[0051] The use of cross-hatching and / or shading in the accompanying drawings is generally used to make the boundaries between adjacent components clear. As such, unless otherwise specified, the presence or absence of cross-hatching or shading does not convey or indicate any preference or requirement for the specific materials, material properties, dimensions, proportions, commonalities between the components shown, and / or any other characteristics, attributes, properties, etc. of the components. In addition, in the accompanying drawings, the sizes and relative sizes of the components may be exaggerated for clarity and / or descriptive purposes. When the exemplary embodiments can be implemented differently, the specific process sequence can be performed in a different order than described. For example, two successively described processes can be performed substantially simultaneously or in an order opposite to the described order. In addition, the same figure numbers represent the same components.

[0052] When a component is referred to as being "on" or "over," "connected to," or "coupled to" another component, the component may be directly on, directly connected to, or directly coupled to the other component, or intervening components may be present. However, when a component is referred to as being "directly on," "directly connected to," or "directly coupled to" another component, there are no intervening components. For this purpose, the term "connected" may refer to a physical connection, an electrical connection, etc., with or without intervening components.

[0053] For descriptive purposes, the present disclosure may use spatially relative terms such as "under," "beneath," "under," "down," "over," "upper," "above," "higher," and "side (e.g., as in "sidewall")," to describe the relationship of one component to another (other) component as shown in the accompanying drawings. The spatially relative terms are intended to encompass different orientations of the device in use, operation, and / or manufacture in addition to the orientation depicted in the accompanying drawings. For example, if the device in the accompanying drawings is turned over, components described as "under" or "beneath" other components or features would subsequently be positioned "over" the other components or features. Thus, the exemplary term "under" can encompass both the "above" and "below" orientations. Furthermore, the device may be otherwise oriented (e.g., rotated 90 degrees or at other orientations), and the spatially relative descriptors used herein should be interpreted accordingly.

[0054] The terms used here are for the purpose of describing specific embodiments, and are not intended to be restrictive. As used here, unless the context clearly indicates otherwise, the singular forms "one (kind, person)" and "said (the)" are also intended to include plural forms. In addition, when the terms "comprise" and / or "include" and their variations are used in this specification, it is explained that there are stated features, integral bodies, steps, operations, parts, assemblies and / or their groups, but it is not excluded that there are or add one or more other features, integral bodies, steps, operations, parts, assemblies and / or their groups. It should also be noted that, as used here, the terms "substantially", "approximately" and other similar terms are used as approximate terms and not as degree terms, so that they are used to explain the inherent deviations of the measured values, calculated values ​​and / or the values ​​provided that will be recognized by those of ordinary skill in the art.

[0055] Reference Figure 1 The present 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 channel unit 500 and a waste liquid collection unit 600, wherein the gas supply unit 100 includes a gas storage device, a main gas circuit assembly, and a reagent bottle gas circuit assembly, a mixing bottle gas circuit assembly, a high-pressure purge gas circuit assembly, and a low-pressure purge gas circuit assembly that are connected to the main gas circuit assembly and independently arranged, and the independently arranged reagent bottle gas circuit assembly, the mixing bottle gas circuit assembly, the high-pressure purge gas circuit assembly, and the low-pressure purge gas circuit assembly are used to provide the required pressure gas for different functional areas.

[0056] The liquid supply unit 200 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 reagent bottle air circuit assembly, and the liquid outlet of the main reagent bottle is connected to the transition bottle;

[0057] The liquid mixing unit 300 includes a target liquid mixing bottle 310 connected to the liquid mixing bottle gas path assembly, and the liquid inlet of the target liquid mixing bottle 310 is connected to the liquid outlets of at least two transition bottles for mixing at least two reagents;

[0058] The gas-liquid path switching unit 400 is connected to the liquid outlet of the target mixed liquid bottle 310, the target transition bottle, and the low-pressure purge gas path assembly respectively; the target transition bottle is the other transition bottles among the plurality of transition bottles except the one connected to the target mixed liquid bottle 310;

[0059] The main channel unit 500 includes a sealed reaction chamber 510 connected to the outlet of the gas-liquid path switching unit 400 through a multi-way liquid divider, the sealed reaction chamber 510 has a plurality of reaction partitions, the target liquid inlet of each reaction partition is independently set, and the target liquid inlet of each reaction partition is provided with a multi-way solenoid valve connected to the high-pressure purge gas path assembly; the waste liquid collection unit 600 is connected to the sealed reaction chamber 510, and is used to collect waste liquid after the reaction.

[0060] The liquid circuit system for biochemical synthesis disclosed in the present application has significantly improved the problems existing in the prior art through innovative design and modular structure. Specifically, the reagent bottle gas circuit assembly, the mixing bottle gas circuit assembly, the high-pressure purge gas circuit assembly, and the low-pressure purge gas circuit assembly are all independently arranged to effectively avoid cross contamination between different reagents or gases; the mixing of preset types of reagents can be achieved through the liquid supply unit and the mixing liquid unit; different reagents and reaction conditions can be quickly switched through the gas-liquid circuit switching unit, simplifying the reagent switching process and improving the reaction efficiency; through the main channel unit matched with the gas-liquid circuit switching unit and the high-pressure purge gas circuit assembly, different reagents can be accurately distributed to the corresponding reaction sites in the sealed reaction chamber, reducing the mixing of reagents in the liquid circuit, reducing the risk of cross contamination, and at the same time, bubble elimination and waste liquid removal can be achieved, realizing fast and accurate liquid supply reaction. In summary, this liquid circuit system can realize the transportation of different reagents to the sealed reaction chamber for reaction, there are no bubbles in the reaction chamber, and the reaction waste liquid can be cleaned up, ensuring that each step of the reaction is stable and efficiently completed.

[0061] Reference Figure 2 The gas storage device is a gas storage tank 110, and the gas storage tank 110 is filled with an inert gas at a certain pressure.

[0062] The main gas circuit assembly includes a main gas pipeline connected to the gas storage tank 110, a main gas circuit pressure regulating valve 120, a main gas circuit manual valve 130 and a four-way gas distribution exhaust 140 which are installed on the main gas pipeline in sequence, wherein the main gas circuit pressure regulating valve 120 is used to adjust the output pressure; the main gas circuit manual valve 130 is used to manually control the on and off of the gas source; the four-way gas distribution exhaust 140 has a first gas inlet, a first gas outlet, a second gas outlet, a third gas outlet and a fourth gas outlet, wherein the first gas inlet is connected to the main gas pipeline, and the first gas outlet, the second gas outlet, the third gas outlet and the fourth gas outlet are arranged in parallel.

[0063] The reagent bottle gas circuit assembly includes a first pipeline connected to the first gas exhaust port, a reagent bottle pressure regulating valve 151, a first gas circuit manual valve 152, and a reagent bottle gas exhaust 153 installed in sequence on the first pipeline, wherein the reagent bottle pressure regulating valve 151 is used to adjust the pressure on the first pipeline, and the first gas circuit manual valve 152 is used to manually control the on and off of the gas source on the first pipeline.

[0064] The mixing bottle gas circuit assembly includes a second pipeline connected to the second gas outlet, a mixing bottle pressure regulating valve 161, a second gas circuit manual valve 162, and a mixing bottle gas outlet 163 installed in sequence on the second pipeline, wherein the mixing bottle pressure regulating valve 161 is used to adjust the pressure on the second pipeline, and the second gas circuit manual valve 162 is used to manually control the on and off of the gas source on the second pipeline.

[0065] The high-pressure purge gas circuit assembly includes a third pipeline connected to the third gas exhaust port, a high-pressure purge pressure regulating valve 171 installed on the third pipeline in sequence, a third gas circuit manual valve 172, a pressure relief valve 173, a high-pressure gas storage tank 174, and a high-pressure gas exhaust 175, wherein the high-pressure purge pressure regulating valve 171 is used to adjust the pressure on the third pipeline, and the third gas circuit manual valve 172 is used to manually control the on and off of the gas source on the third pipeline; the high-pressure gas storage tank 174 is used for gas buffering and avoiding impact during high-pressure purge, and the pressure relief valve 173 is used to discharge the high-pressure gas in the high-pressure gas storage tank 174 after high-pressure purge, in preparation for the next high-pressure gas buffer.

[0066] The low-pressure purge air circuit assembly includes a fourth pipeline connected to the fourth air exhaust port, a low-pressure purge pressure regulating valve 181, a fourth air circuit manual valve 182, and a low-pressure air exhaust 183 installed in sequence on the fourth pipeline, wherein the low-pressure purge pressure regulating valve 181 is used to adjust the pressure on the fourth pipeline, and the fourth air circuit manual valve 182 is used to manually control the on-off of the air source on the fourth pipeline.

[0067] Reference 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 reagent bottle air circuit component, and the liquid outlet of the main reagent bottle is connected to the transition bottle.

[0068] Under the pressurization of the reagent bottle gas circuit assembly, the main reagent bottle is transmitted to the transition bottle through a dual-channel pipeline, that is, the reagent bottle gas circuit assembly is used to provide positive pressure gas to the main reagent bottle to pressurize the liquid supply from the main reagent bottle.

[0069] The dual-channel pipelines are both equipped with hydraulic manual valves 240 for controlling the on-off of the corresponding pipelines.

[0070] The bottle cap of the main reagent bottle is a three-channel bottle cap, one channel is connected to the reagent bottle gas distribution exhaust 153, for pressurizing the main reagent bottle; the other two channels are liquid outlets, connected to the liquid circuit manual valve 240; the liquid pipe behind the liquid circuit manual valve 240 is connected to the transition bottle corresponding to the reagent, and the transition bottle cap has four channels, two channels for liquid inlet and two channels for liquid outlet.

[0071] Among them, the setting number of transition bottles is consistent with the setting number of main reagent bottles; the transition bottles can realize the replacement of main reagent bottles without stopping the machine, and can avoid the influence of introducing air when replacing the main reagent bottles.

[0072] The liquid supply unit 200 also includes a weight detection component arranged at the bottom of the main reagent bottle. Specifically, the weight detection component includes a weighing sensor 230. The weighing sensor 230 can display the weight of the main reagent bottle in real time, convert it into volume and display it in the software. It is used for monitoring the reagent consumption and the remaining reagent amount, and can also be used as a basis for judging liquid leakage or liquid circuit component failure.

[0073] In this embodiment, there are five main reagent bottles and 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 and the first transition bottle 221, the second main reagent bottle 212 and the second transition bottle 222, the third main reagent bottle 213 and the third transition bottle 223, the fourth main reagent bottle 214 and the fourth transition bottle 224, and the fifth main reagent bottle 215 and the fifth transition bottle 225 are respectively connected by dual-channel pipelines.

[0074] Reagents flow in through independent main reagent bottles and transition bottle systems. The amount of each reagent can be controlled by precisely adjusting the air pressure and liquid flow rate to ensure the accuracy of the reagent dosage.

[0075] Reference Figure 4 The liquid mixing unit 300 includes a target liquid mixing bottle 310 connected to the liquid mixing bottle gas path assembly, and the liquid inlet of the target liquid mixing bottle 310 is connected to the liquid outlets of at least two transition bottles for mixing at least two reagents, and further, achieving a 1:1 mixing of at least two reagents.

[0076] In this embodiment, it is mainly used to achieve a 1:1 mixing of two reagents. Specifically, the bottle cap of the target mixing bottle 310 has four channels, two channels for liquid inlet, respectively connected to two different transition bottles through pipelines, and a liquid inlet solenoid valve 320 is provided on the corresponding pipelines; one channel for liquid outlet, and one channel is connected to the mixing bottle gas distribution exhaust 163.

[0077] The liquid mixing unit 300 further includes a liquid mixing sensor 340 installed on the side of the target liquid mixing bottle 310 for controlling the liquid mixing process, that is, when the liquid mixing sensor 340 is triggered, the liquid mixing is terminated, indicating that the reagent injected into the target liquid mixing bottle 310 is sufficient.

[0078] An air pressure switching solenoid valve 330 is provided on the connecting pipeline between the target mixing bottle 310 and the mixing bottle gas outlet 163, which is used to switch the air pressure in the target mixing bottle 310; it is in a normal pressure state when injecting and mixing liquids, and in a positive pressure state when discharging liquids. By accurately controlling the valve opening time of the liquid inlet solenoid valve 320 on the corresponding pipeline and providing algorithm compensation, accurate mixing can be achieved, and the mixing ratio error is ≤1%.

[0079] Reference Figure 5 The gas-liquid circuit switching unit 400 is respectively connected to the liquid outlet of the target mixed liquid bottle 310, the target transition bottle, and the low-pressure purge gas circuit assembly; the target transition bottle is other transition bottles among the plurality of transition bottles except the one connected to the target mixed liquid bottle 310.

[0080] Specifically, the gas-liquid path switching unit 400 includes a multi-channel multi-way valve, which includes several liquid inlet channels and a common liquid outlet channel. The several liquid inlet channels are respectively connected to the liquid outlet of the target mixed liquid bottle 310, several target transition bottles, and the low-pressure gas distribution row 183; the common liquid outlet channel is provided with a flow channel switching solenoid valve 420 and a liquid inlet cut-off valve 430.

[0081] In this embodiment, the multi-channel multi-way valve is preferably a ten-channel multi-way valve 410, which has 10 liquid inlet channels and 1 common liquid outlet channel, wherein the liquid inlet channel connects 4 kinds of reaction reagents and the low-pressure gas distribution row 183, and 1 channel is blocked as the zero position. In order to avoid contamination when the reagents are switched, the reagents and gases are connected to the liquid inlet channel of the ten-channel multi-way valve 410 according to the process sequence and the rotation direction of the ten-channel multi-way valve 410. The outlet of the ten-channel multi-way valve 410 is connected to the flow channel switching solenoid valve 420, which is a three-way solenoid valve 540, which can realize the switching of the reaction flow channel and the cleaning flow channel; the liquid inlet cut-off valve 430 is installed behind the flow channel switching solenoid valve 420, which is used to cut off the liquid inlet pipeline.

[0082] By switching different reagents and gases through the ten-channel multi-way valve 410, low pollution and high efficiency can be achieved.

[0083] Furthermore, a bypass may be provided behind the ten-channel multi-way valve 410 to enable the filling and cleaning of the ten-channel multi-way valve 410 and the front-end liquid circuit.

[0084] In this embodiment, two sets of gas-liquid path switching units 400 are provided.

[0085] Reference Figure 6 The main channel unit 500 includes a sealed reaction chamber 510 connected to the outlet of the gas-liquid path switching unit 400 through a multi-way liquid distributor for performing reagent reactions.

[0086] The sealed reaction chamber 510 includes a plurality of target liquid inlets, a plurality of target liquid outlets, and a plurality of liquid outlet pipelines. A three-way solenoid valve 540 is provided between each target liquid inlet and the multi-way liquid distributor; each liquid outlet pipeline is provided with an outlet solenoid valve 550 and a liquid outlet detection sensor 560 for liquid outlet detection.

[0087] In this embodiment, by setting an outlet electromagnetic valve 550 at the outlet of the sealed reaction chamber 510, the effect of pressurizing and removing bubbles can be achieved by controlling the opening and closing of the outlet electromagnetic valve 550. Because some organic reagents have low boiling points and are very volatile, more bubbles will be generated during liquid injection due to pipe diameter change and pressure reduction. Bubbles are not good for the reaction and are likely to cause insufficient or even no reaction. The device can eliminate bubbles by pressurizing the reagents. The specific process is that when injecting liquid, the outlet electromagnetic valve 550 of the sealed reaction chamber 510 is closed first, and the reagent fills the sealed reaction chamber 510 under positive pressure and reaches the injection pressure. At this time, there are still some bubbles in the sealed reaction chamber 510, and then the outlet electromagnetic valve 550 is opened to continue injecting liquid until the bubbles disappear.

[0088] The liquid outlet detection sensor 560 can be used to determine whether there is liquid in the liquid pipe, which serves as an input for the relevant locking action.

[0089] In this embodiment, the main channel unit 500 includes a connection with the outlet of the first set of gas-liquid path switching unit 400 (i.e., the outlet of the corresponding liquid inlet cut-off valve 430) through a three-way liquid distributor 520, and is connected with the outlet of the other set of gas-liquid path switching unit 400 (i.e., the outlet of the corresponding liquid inlet cut-off valve 430) through a four-way liquid distributor 530. Through the liquid distributor structure, a one-to-three or one-to-four liquid path change can be achieved, thereby adapting to the seven-partition sealed reaction chamber 510.

[0090] Specifically, the sealed reaction chamber 510 includes seven reaction partitions, seven liquid inlets and seven liquid outlets. The two liquid distributors have a total of seven liquid outlets that are correspondingly connected to the seven liquid inlets of the sealed reaction chamber 510; seven outlet solenoid valves 550, seven liquid outlet detection sensors 560, and seven liquid outlet pipelines are each provided.

[0091] Seven three-way solenoid valves 540 are installed on the liquid circuit connecting the four-way liquid distributor 530, the three-way liquid distributor 520 and the seven liquid inlets of the sealed reaction chamber 510. When removing waste liquid, the liquid circuit can be switched to the high-pressure purge gas circuit through the three-way solenoid valve 540.

[0092] The multi-channel dispenser can distribute reagents to multiple reaction partitions, each of which has tens of thousands of reaction sites. The design of the sealed reaction chamber 510 ensures that the reaction in each reaction partition is carried out independently.

[0093] Reference Figure 7 The waste liquid collection unit 600 includes a waste liquid barrel 610 connected to each target liquid outlet; the waste liquid barrel 610 is connected to each target liquid outlet through a waste liquid transmission pipeline 620, and each waste liquid transmission pipeline 620 is provided with a waste liquid solenoid valve 630.

[0094] Biosynthesis is generally carried out in a glove box where the water and oxygen components are strictly controlled. The waste liquid solenoid valve 630 can be set to isolate the liquid system from the atmospheric environment outside the glove box.

[0095] The waste liquid barrel 610 is connected to the liquid outlet of the flow channel switching electromagnetic valve 420 through two target transmission pipelines 640 , and each of the target transmission pipelines 640 is provided with a target electromagnetic valve.

[0096] The waste liquid barrel 610 is also provided with a pipe integrated joint 650, and the waste liquid transmission pipeline 620 and the target transmission pipeline 640 are both connected to the pipe integrated joint 650. The pipe integrated joint 650 can be used for a long time. When there is too much waste liquid, only the waste liquid barrel 610 needs to be replaced.

[0097] The waste liquid collection unit 600 further includes an exhaust assembly connected to the waste liquid barrel 610 for exhausting waste gas and relieving pressure from the waste liquid barrel 610 ; in this embodiment, the exhaust assembly includes an exhaust pipe 660 .

[0098] The dedicated waste liquid collection unit 600 is directly connected to the sealed reaction chamber 510, and can collect the waste liquid after the reaction in real time, thereby reducing the retention of the waste liquid in the system and improving the processing efficiency.

[0099] In this embodiment, the purging of waste liquid is divided into low-pressure purging and high-pressure purging. The gas source path of the low-pressure purging is a ten-channel multi-way valve, and the path of the 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.

[0100] Specifically, the gas source for low-pressure purge is connected to the inlet of the ten-channel multi-way valve. The outlet of the ten-channel multi-way valve to the three-way solenoid valve at the entrance of the reaction chamber is a common pipeline, through which all reagents will pass. The low-pressure purge is mainly used to purge the reagents in the common pipeline and most of the reaction chambers. The gas source for high-pressure purge is connected to the three-way solenoid valve at the entrance of the reaction chamber. By switching the three-way solenoid valve, the liquid circuit can be switched to the high-pressure purge gas circuit. The main function of high-pressure purge is to completely dry the residual reagents in the reaction chamber.

[0101] In this application, there are many different reagents, most of which have different degrees of corrosiveness, so the liquid path components are all made of materials that have good resistance to all reagents.

[0102] The liquid circuit system for biochemical synthesis disclosed in the present application can realize flexible process combination by setting different programs and different parameters, and can adapt to different reaction requirements at different stages. The liquid circuit system for biochemical synthesis disclosed in the present application adopts a modular design, and each unit operates independently, and can be flexibly adjusted and expanded according to actual needs, which enhances the adaptability of the system to complex industrial environments. The design of the sealed reaction chamber reduces dependence on the external environment, so that the system can operate stably in different industrial environments.

[0103] In the description of this specification, the description with reference to the terms "one embodiment / method", "some embodiments / methods", "example", "specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment / method or example are included in at least one embodiment / method or example of the present application. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment / method or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments / methods or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments / methods or examples described in this specification and the features of the different embodiments / methods or examples, unless they are contradictory.

[0104] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include at least one of the features. In the description of this application, the meaning of "plurality" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined.

[0105] Those skilled in the art should understand that the above embodiments are only for the purpose of clearly illustrating the present disclosure, and are not intended to limit the scope of the present disclosure. For those skilled in the art, other changes or modifications may be made based on the above disclosure, and these changes or modifications are still within the scope of the present disclosure.

Claims

1. A liquid circuit system for biochemical synthesis, characterized in that: include: A gas supply unit, comprising a gas storage device, a main gas circuit assembly, and a reagent bottle gas circuit assembly, a mixing bottle gas circuit assembly, a high-pressure purge gas circuit assembly, and a low-pressure purge gas circuit assembly that are connected to the main gas circuit assembly and are independently arranged; A liquid supply unit, comprising a plurality of main reagent bottles and a plurality of transition bottles corresponding to the main reagent bottles; the air inlet of the main reagent bottle is connected to the reagent bottle air circuit assembly, and the liquid outlet of the main reagent bottle is connected to the transition bottle; A liquid mixing unit, comprising a target liquid mixing bottle connected to the liquid mixing bottle gas path assembly, wherein the liquid inlet of the target liquid mixing bottle is connected to the liquid outlets of at least two of the transition bottles, and is used to mix at least two reagents; A gas-liquid circuit switching unit is connected to the liquid outlet of the target mixed liquid bottle, the target transition bottle, and the low-pressure purge gas circuit assembly respectively; the target transition bottle is other transition bottles among the plurality of transition bottles except the one connected to the target mixed liquid bottle; A main channel unit, comprising a sealed reaction chamber connected to the outlet of the gas-liquid path switching unit through a multi-way liquid distributor, wherein the sealed reaction chamber has a plurality of reaction partitions, each of which has a target liquid inlet independently arranged, and each of which has a multi-way solenoid valve connected to the high-pressure purge gas path assembly; A waste liquid collection unit connected to the sealed reaction chamber.

2. The liquid circuit system for biochemical synthesis according to claim 1, characterized in that: 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 row which are sequentially installed on the main gas pipeline, and the four-way gas distribution row has a first gas outlet, a second gas outlet, a third gas outlet and a fourth gas outlet; The reagent bottle gas circuit assembly comprises a first pipeline connected to the first gas outlet, a reagent bottle pressure regulating valve, a first gas circuit manual valve, and a reagent bottle gas 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 circuit manual valve, and a mixing bottle gas outlet installed in sequence on the second pipeline; The high-pressure purge gas circuit assembly includes a third pipeline connected to the third gas outlet, a high-pressure purge pressure regulating valve, a third gas circuit manual valve, a pressure relief valve, a high-pressure gas storage tank, and a high-pressure gas outlet installed in sequence on the third pipeline; The low-pressure purge gas circuit assembly includes a fourth pipeline connected to the fourth gas outlet, a low-pressure purge pressure regulating valve, a fourth gas branch manual valve, and a low-pressure gas branch exhaust installed in sequence on the fourth pipeline.

3. The liquid circuit system for biochemical synthesis according to claim 2, characterized in that: The main reagent bottle is connected to the reagent bottle gas distribution row through a pipeline. Under the pressure of the reagent bottle gas circuit assembly, the main reagent bottle is transmitted to the transition bottle through a double-channel pipeline; a liquid circuit manual valve is installed on both of the double-channel pipelines; The liquid supply unit also includes a weight detection component arranged at the bottom of the main reagent bottle.

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

5. The liquid circuit system for biochemical synthesis according to claim 2, characterized in that: The gas-liquid path switching unit includes a multi-channel multi-way valve, which includes a plurality of liquid inlet channels and a common liquid outlet channel, and the plurality of liquid inlet channels are respectively connected to the liquid outlet of the target mixed liquid bottle, a plurality of target transition bottles, and the low-pressure gas distribution row; The common liquid outlet channel is provided with a flow channel switching solenoid valve and a liquid inlet cut-off valve.

6. The liquid circuit system for biochemical synthesis according to claim 5, characterized in that: The sealed reaction chamber comprises a plurality of independently arranged target liquid inlets, a plurality of target liquid outlets, and a plurality of liquid outlet pipelines, and a three-way solenoid valve is provided between each of the target liquid inlets and the multi-way liquid distributor; The number of the three-way solenoid valves and the number of the gas distribution ports of the high-pressure gas distribution row are set to be consistent; Each of the liquid outlet pipelines is provided with an outlet solenoid valve and a liquid outlet detection sensor.

7. The liquid circuit system for biochemical synthesis according to claim 6, characterized in that: The gas-liquid switching unit is provided with two sets, one set of the gas-liquid 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 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 bucket connected to each of the target liquid outlets; The waste liquid barrel is connected to each of the target liquid outlets through a waste liquid transmission pipeline, and each of the waste liquid transmission pipelines is provided with a waste liquid solenoid valve; The waste liquid barrel is connected to the liquid outlet of the flow channel switching solenoid valve through two target transmission pipelines, and the target transmission pipelines are both provided with target solenoid valves.

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

10. The liquid circuit system for biochemical synthesis according to claim 8, characterized in that: The waste liquid collection unit also includes an exhaust assembly connected to the waste liquid barrel for relieving pressure on the waste liquid barrel.

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