Gene synthesis device and gene synthesis method
By using the air pressure regulation component to control the leakage and reaction time of the reagent on the carrier in the gene synthesis device, the problems of long synthesis time, high cost and large deviation in the result are solved, and efficient and low-cost gene synthesis is achieved.
Patent Information
- Application Number
- CN202410014273.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-01-03
- Publication Date
- 2025-07-04
AI Technical Summary
In the existing gene synthesis devices, the synthesis time is long, the cost is high, and the synthesis results are large, which is mainly due to uneven leakage of preset reagents in the synthesis column.
The air pressure adjustment assembly controlled by the controller is adopted. By setting the air pressure adjustment assembly on both sides of the synthetic plate, the back pressure and positive pressure are formed to control the leakage of the reagent on the carrier and the reaction time to ensure that the reagent and the carrier are fully reacted.
It shortens the synthesis time, reduces the synthesis cost, and improves the accuracy and consistency of synthesis results, reducing the amount of reagents and the possibility of synthesis failure.
Smart Images
Figure CN120242930A_ABST
Abstract
Description
Technical Field
[0001] The present application relates to the technical field of biomedical equipment, and in particular to a gene synthesis device and a gene synthesis method. Background Art
[0002] At present, artificially synthesized DNA is mainly synthesized by gene synthesis devices. The gene synthesis device includes a porous synthesis plate and multiple carriers, and the multiple carriers are arranged in a plurality of synthesis columns of the porous synthesis plate in a one-to-one correspondence. When synthesizing DNA, it is necessary to inject a plurality of preset reagents into each synthesis column of the porous synthesis plate according to a specific chemical reaction step. After the preset reagents are injected, the preset reagents flow to the carrier along the side wall of the synthesis column, so that the multiple preset reagents in each synthesis column react in the carrier in turn to obtain a synthetic product. However, since the preset reagents will have different degrees of downward leakage relative to the carrier when injected into the synthesis column, this results in different drainage speeds in the synthesis columns with different leakage degrees when the preset reagents are injected and positive pressure blowing or negative pressure pumping and draining are performed, so that the entire synthesis process needs to extend the blowing or pumping time to ensure that the preset reagents in all the synthesis columns on the synthesis plate have passed through the carrier and chemical reactions occur, so that the time required for the entire synthesis process increases, the synthesis cost is high, and the synthesis result deviation is large. Summary of the invention
[0003] Based on this, it is necessary to provide a gene synthesis device to address the problems in the existing DNA synthesis process, such as the long synthesis time, high synthesis cost, and large deviation in synthesis results.
[0004] A gene synthesis device, comprising:
[0005] Controller;
[0006] A bearing assembly, wherein the bearing assembly is configured with a first bearing cavity and is used for bearing a composite board;
[0007] a first air pressure regulating component, wherein the first air pressure regulating component is electrically connected to the controller and communicated with the first bearing cavity, and the controller is used to control the first air pressure regulating component to regulate the air pressure in the first bearing cavity;
[0008] An upper cover assembly, wherein the upper cover assembly is configured with a second bearing cavity; the upper cover assembly is disposed on a side of the composite board away from the first bearing cavity; and the first bearing cavity and the second bearing cavity are separated by the composite board;
[0009] The second air pressure regulating component is electrically connected to the controller, and the second air pressure regulating component is communicated with the second bearing cavity, and the controller is used to control the second air pressure regulating component to regulate the air pressure in the second bearing cavity.
[0010] In one embodiment, the first air pressure regulating assembly includes a first air chamber and a first regulating valve;
[0011] A first ventilation pipeline is constructed on the wall of the first bearing cavity. The first regulating valve is arranged between the first air chamber and the first ventilation pipeline. The controller is electrically connected to the first regulating valve, and the controller is configured to control the first regulating valve to regulate the intake air volume of the gas in the first air chamber entering the first ventilation pipeline.
[0012] In one embodiment, a positioning member protruding toward the bearing assembly is constructed on the side wall of the upper cover assembly; the positioning member abuts against the side wall of the bearing assembly.
[0013] In one embodiment, one of the bearing assembly and the upper cover assembly is constructed with a buckle, and the other is constructed with a clamping groove, and the buckle and the clamping groove cooperate.
[0014] In one embodiment, at least one of the bearing assembly and the upper cover assembly is provided with an elastic sealing member at the abutting portion between the two;
[0015] The elastic sealing member can be extruded and deformed to seal and connect the bearing assembly and the upper cover assembly.
[0016] In one embodiment, the second air pressure regulating assembly includes a second air chamber and a second regulating valve;
[0017] A second ventilation pipeline is constructed on the wall of the second bearing cavity. The second regulating valve is arranged between the second air chamber and the second ventilation pipeline. The controller is electrically connected to the second regulating valve, and the controller is configured to control the second regulating valve to regulate the intake air volume of the gas in the second air chamber entering the second ventilation pipeline.
[0018] In one embodiment, the gene synthesis device further includes a waste liquid pipeline assembly; the waste liquid pipeline assembly includes a waste liquid carrier and a third control valve;
[0019] A waste liquid pipeline is further constructed on the side wall of the first bearing cavity. The third control valve is arranged between the waste liquid carrier and the waste liquid pipeline; the third control valve is used to control the on-off of the waste liquid pipeline and the waste liquid carrier.
[0020] This application also provides a gene synthesis method, based on the gene synthesis device according to any one of the above embodiments, which includes:
[0021] Placing the synthesis plate on the bearing assembly;
[0022] Adjust the air pressure in the first bearing cavity through the first air pressure regulating component;
[0023] Inject a preset reagent into the first chambers of a plurality of synthesis columns in the synthesis plate respectively;
[0024] Install the upper cover assembly on one side of the synthesis plate facing away from the first bearing cavity of the bearing assembly;
[0025] Adjust the air pressure in the second bearing cavity through the second air pressure regulating component, so that the preset reagent passes through the carrier in the synthesis column;
[0026] Calculate the mutation rate of the reaction result between the substance carried on the carrier of each synthesis column and the preset reagent;
[0027] Adjust the contact duration between the substance carried on the carrier and the preset reagent according to the maximum difference between multiple mutation rates;
[0028] In one embodiment, the step of adjusting the contact duration between the substance carried on the carrier and the preset reagent according to the maximum difference between multiple mutation rates specifically includes:
[0029] If the maximum difference between multiple mutation rates is greater than a preset value, increase the contact duration between the preset reagent and the carried substance;
[0030] If the maximum difference between multiple mutation rates is less than or equal to a preset value, reduce the contact duration between the preset reagent and the carried substance.
[0031] In one embodiment, the step of increasing the contact duration between the preset reagent and the carried substance if the maximum difference between multiple mutation rates is greater than a preset value specifically includes:
[0032] By controlling the change rate of the air pressure in the first bearing cavity and the air pressure in the second bearing cavity, make the preset reagent pass through the carrier multiple times in the first direction, or reduce the rate at which the preset reagent passes through the carrier.
[0033] When synthesizing genes through the above gene synthesis device, the synthesis board is first carried on the bearing assembly, and then the preset reagents are respectively injected into the first chambers of the multiple synthesis columns of the synthesis board. In the process of injecting the preset reagent, the first air pressure regulating assembly is controlled by the controller to adjust the air pressure in the first bearing chamber, so that the air pressure in the first bearing chamber can form a back pressure greater than the atmospheric pressure, and then the air pressure in the first bearing chamber can apply an upward lifting force to the preset reagent in the first chamber, thereby reducing the possibility of the preset reagent in the first chamber leaking downward relative to the carrier in the synthesis column before the synthesis reaction. After the preset reagent is injected, the upper cover assembly is set on the side of the synthesis board away from the first bearing chamber, and at this time, the second air pressure regulating assembly is controlled by the controller to adjust the air pressure in the second bearing chamber, so that the preset reagent passes through the carrier and reacts chemically with the carrier carried on the carrier. In this process, since the drainage speed of the preset reagents in multiple synthesis columns relative to the carrier is relatively the same, the drainage time required for the entire synthesis process is short, and there is no need to add excess preset reagents to reduce the possibility of synthesis failure, so the overall synthesis cost is low; and by controlling the air pressure in the first chamber and the second chamber, the preset reagents can move up and down multiple times relative to the carrier, so that the preset reagents can react more fully with the carrier carried on the carrier, the synthesis result has a smaller deviation, and the effect is better. BRIEF DESCRIPTION OF THE DRAWINGS
[0034] Figure 1 This is a first connection diagram of a carrier assembly, an upper cover assembly and a snap-on assembly of a gene synthesis device provided in some embodiments of the present application.
[0035] Figure 2 for Figure 1 The second connection schematic diagram of the carrier assembly, the upper cover assembly and the clamping assembly of the gene synthesis device is shown.
[0036] Figure 3 A connection diagram of a gene synthesis device provided in some embodiments of the present application and equipped with a synthesis board.
[0037] Figure 4 for Figure 3 A partial enlarged view of point A shown.
[0038] Figure 5 for Figure 3 A schematic diagram of an air flow adjustment member is shown.
[0039] Figure 6 A flow chart of a gene synthesis method provided for some embodiments of the present application.
[0040] Reference numerals: 100 - bearing assembly; 110 - first bearing cavity; 111 - first ventilation pipeline; 112 - waste liquid pipeline; 113 - viewing window; 200 - upper cover assembly; 210 - second bearing cavity; 211 - second ventilation pipeline; 220 - alignment member; 300 - first air pressure regulating assembly; 310 - first control valve; 320 - first regulating valve; 400 - second air pressure regulating assembly; 410 - second control valve; 420 - second regulating valve; 430 - air flow regulating member; 431 - air flow regulating channel; 500 - clamping assembly; 510 - buckle; 520 - clamping groove; 600 - elastic seal; 700 - waste liquid pipeline assembly; 710 - waste liquid carrier; 720 - third control valve; 800 - synthetic board; 810 - synthetic column; 811 - first chamber; 812 - carrier; 813 - second chamber. Detailed implementation manners
[0041] To make the above objects, features, and advantages of the present application more apparent and understandable, the following describes the detailed implementation manners of the present application with reference to the accompanying drawings. Many specific details are set forth in the following description to fully understand the present application. However, the present application can be implemented in many other ways different from those described herein. Those skilled in the art can make similar improvements without departing from the connotation of the present application. Therefore, the present application is not limited by the specific embodiments disclosed below.
[0042] In the description of the present application, it should be understood that if there are terms such as "center", "longitudinal", "transverse", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", "axial", "radial", "circumferential", etc., the orientation or positional relationship indicated by these terms is based on the orientation or positional relationship shown in the accompanying drawings. These are only for the convenience of describing the present application and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation. Therefore, it should not be construed as a limitation to the present application.
[0043] In addition, if there are terms such as "first" and "second", these terms are only used for descriptive purposes and cannot be understood as indicating or implying relative importance or implicitly specifying the quantity of the indicated technical features. Thus, features defined with "first" and "second" may explicitly or implicitly include at least one of such features. In the description of the present application, if there is a term "plural", the meaning of "plural" is at least two, such as two, three, etc., unless otherwise specifically and clearly defined.
[0044] In this application, unless otherwise clearly defined and limited, if terms such as "installed", "connected", "linked", "fixed", etc. appear, these terms shall be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or integrated; it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium, and it can be the communication inside two elements or the interaction relationship between two elements, unless otherwise clearly defined. For those of ordinary skill in the art, the specific meanings of the above terms in this application can be understood according to specific circumstances.
[0045] In this application, unless otherwise clearly defined and limited, if there is a description such as a first feature being "on" or "under" a second feature, its meaning can be that the first and second features are in direct contact, or the first and second features are in indirect contact through an intermediate medium. Moreover, the first feature being "above", "over" and "on top of" the second feature can mean that the first feature is directly above or obliquely above the second feature, or simply means that the first feature is at a higher horizontal level than the second feature. The first feature being "under", "beneath" and "underneath" the second feature can be that the first feature is directly below or obliquely below the second feature, or simply means that the first feature is at a lower horizontal level than the second feature.
[0046] It should be noted that if an element is referred to as "fixed to" or "disposed on" another element, it can be directly on the other element or there can also be an intermediate element. If an element is considered to be "connected" to another element, it can be directly connected to the other element or there may be an intermediate element at the same time. If so, the terms "vertical", "horizontal", "up", "down", "left", "right" and similar expressions used in this application are only for the purpose of illustration and do not represent the only implementation.
[0047] At present, artificially synthesized DNA is the only known way to directionally modify gene sequences and is widely used in many fields such as protein modification and life sciences, such as nucleic acid drugs, enzyme engineering, gene detection, gene therapy, etc. Artificially synthesized DNA is mainly synthesized using a gene synthesis device, which includes a porous synthesis plate and a plurality of carriers, and the plurality of carriers are correspondingly arranged in a plurality of synthesis columns of the porous synthesis plate. When synthesizing DNA, a variety of preset reagents need to be injected into each synthesis column of the porous synthesis plate according to specific chemical reaction steps. After injecting the preset reagents, the preset reagents flow along the side wall of the synthesis column to the carrier, so that the various preset reagents in each synthesis column react with the load carried by the carrier in sequence to obtain a synthesis product. However, when the preset reagents are injected into the synthesis column, the density of the carrier itself is uneven, which causes the preset reagents to have different degrees of downward leakage relative to the carrier. This results in different drainage speeds in the synthesis columns with different leakage degrees when performing positive pressure blowing or negative pressure pumping after injecting the preset reagents, so that the entire synthesis process requires an extended blowing or pumping time to ensure that the preset reagents in all the synthesis columns on the synthesis plate pass through the carrier and undergo chemical reactions. In this way, the time required for the entire synthesis process increases, the synthesis cost is relatively high, and the synthesis result has a large deviation. Based on the above problems, the present application provides a gene synthesis device.
[0048] It should be noted that the synthesis plate has a plurality of synthesis columns. For example, a 384-well synthesis plate has 384 synthesis columns, and a 192-well synthesis plate has 192 synthesis columns.
[0049] Please refer to Figure 4 , Figure 4 which shows Figure 3 a partial enlarged view of the location A shown in
[0050] Please refer to Figure 3 , Figure 3The figure shows a connection diagram of a gene synthesis device provided by some embodiments of the present application and a synthesis board 800 installed. The gene synthesis device provided by some embodiments of the present application includes a controller (not shown in the figure), a bearing assembly 100, a first air pressure regulating assembly 300, an upper cover assembly 200 and a second air pressure regulating assembly 400. The bearing assembly 100 is constructed with a first bearing cavity 110, and the bearing assembly 100 is used to bear the synthetic board 800; the first air pressure regulating assembly 300 is electrically connected to the controller, and the first air pressure regulating assembly 300 is communicated with the first bearing cavity 110, and the controller is used to control the first air pressure regulating assembly 300 to adjust the air pressure in the first bearing cavity 110; the upper cover assembly 200 is constructed with a second bearing cavity 210; the upper cover assembly 200 is arranged on the side of the synthetic board 800 away from the first bearing cavity 110; and the first bearing cavity 110 and the second bearing cavity 210 are separated by the synthetic board 800; the second air pressure regulating assembly 400 is electrically connected to the controller, and the second air pressure regulating assembly 400 is communicated with the second bearing cavity 210, and the controller is used to control the second air pressure regulating assembly 400 to adjust the air pressure in the second bearing cavity 210.
[0051] When synthesizing genes through the above gene synthesis device, the synthesis plate 800 is first carried on the bearing assembly 100, and then the preset reagents are respectively injected into the first chambers 811 of the multiple synthesis columns 810 of the synthesis plate 800. In the process of injecting the preset reagent, the first air pressure regulating assembly 300 is controlled by the controller to adjust the air pressure in the first bearing cavity 110, so that the air pressure in the first bearing cavity 110 can form a back pressure greater than the atmospheric pressure, and then the air pressure in the first bearing cavity 110 can apply an upward lifting force to the preset reagent in the first cavity 811, thereby reducing the possibility of the preset reagent in the first cavity 811 leaking downward relative to the carrier 812 in the synthesis column 810 before the synthesis reaction. After the preset reagent is injected, the upper cover assembly 200 is set on the side of the synthesis plate 800 away from the first bearing cavity 110, and at this time, the second air pressure regulating assembly 400 is controlled by the controller to adjust the air pressure in the second bearing cavity 210, so that the preset reagent passes through the carrier 812 and reacts chemically with the carrier carried on the carrier 812. In this process, since the drainage speed of the preset reagents in the multiple synthesis columns 810 is relatively the same relative to the carrier 812, the drainage time required for the entire synthesis process is shorter, and there is no need to add excess preset reagents to reduce the possibility of synthesis failure, and the overall synthesis cost is lower; and it is also possible to control the air pressure in the first chamber 811 and the second chamber 813 so that the preset reagents can move up and down multiple times relative to the carrier 812, so that the preset reagents can react more fully with the carrier carried on the carrier 812, the synthesis result has smaller deviation, and the effect is better.
[0052] It should be noted that by controlling the air pressure in the second bearing cavity 210 and the air pressure in the first bearing cavity 110, the preset reagent in the synthesis column 810 can be made to move downward or upward under the action of the pressure difference, thereby enabling the control of the number of times and duration of the mixing reaction between the preset reagent and the carrier 812, and making the reaction between the preset reagent and the carrier 812 more sufficient. When the reaction duration and the expected synthesis effect are reached, the first control valve 310 is closed, so that all the preset reagents are blown away from the synthesis column 810 from the second chamber 813.
[0053] When synthesizing DNA with this gene synthesis device, by precisely controlling the sufficient reaction between the preset reagent and the carrier 812, the amount of the preset reagent is greatly reduced. Specifically, 50% of the preset reagent can be saved; moreover, the synthesis mutation rate can be controlled at about 5%, effectively reducing the cost of gene synthesis.
[0054] When injecting the preset reagent into multiple synthesis columns 810 with this gene synthesis device, after the injection is completed, the heights of the preset reagents in all the synthesis columns 810 can be basically kept the same.
[0055] In one of the embodiments, the upper cover assembly 200 is detachably connected to the bearing assembly 100. By detachably connecting the upper cover assembly 200 to the bearing assembly 100, it is convenient for the user to perform multiple liquid addition operations on the first chamber 811 in the synthesis column 810, and thus the synthesis of multiple base sequences is realized.
[0056] The following specifically describes the structure of the gene synthesis device. Please refer to Figure 1 、 Figure 2 and Figure 5 。 Figure 1 FIG. shows a first connection schematic diagram of the bearing assembly 100, the upper cover assembly 200, and the clamping assembly 500 of the gene synthesis device provided in some embodiments of the present application. Figure 2 FIG. shows Figure 1 a second connection schematic diagram of the bearing assembly 100, the upper cover assembly 200, and the clamping assembly 500 of the gene synthesis device shown in Figure 5 FIG. shows Figure 3 a schematic diagram of the air flow regulating member 430 shown in
[0057] Please refer to Figure 3, in some embodiments, the first air pressure regulating assembly 300 includes a first air chamber and a first regulating valve 320; a first air passage 111 is formed on the wall of the first bearing cavity 110, and the first regulating valve 320 is disposed between the first air chamber and the first air passage 111. The controller is electrically connected to the first regulating valve 320, and the controller is configured to control the first regulating valve 320 to adjust the air intake amount of the gas in the first air chamber entering the first air passage 111. By adjusting the air intake amount of the gas in the first air chamber entering the first air passage 111 through the first regulating valve 320, the air pressure in the first bearing cavity 110 is further adjusted, so that the air pressure in the first bearing cavity 110 can be adjusted according to the weight of the preset reagent added to the first chamber 811 to just lift the preset reagent.
[0058] Please refer to Figure 3 , in some embodiments, the first air pressure regulating assembly 300 further includes a first control valve 310, and the first control valve 310 is installed between the first air chamber and the first regulating valve 320. The first control valve 310 is used to directly control the on-off between the first air chamber and the first air passage 111, which is more convenient.
[0059] Please refer to Figure 2 , in some embodiments, a positioning member 220 protruding toward the bearing assembly 100 is formed on the side wall of the upper cover assembly 200; the positioning member 220 abuts against the side wall of the bearing assembly 100. By providing the positioning member 220, when the upper cover assembly 200 and the bearing assembly 100 are installed, quick positioning can be achieved through the positioning member 220, which is relatively rapid and convenient.
[0060] Please refer to Figure 2 , in some embodiments, the number of the positioning members 220 is at least two, and the at least two positioning members 220 are respectively disposed on different side walls of the upper cover assembly 200. By providing at least two positioning members 220 and disposing the at least two positioning members 220 on different side walls of the upper cover assembly 200, when the upper cover assembly 200 is installed with the bearing assembly 100, quick positioning and installation in different directions can be achieved through the at least two positioning members 220, and the entire installation and connection process is more convenient. In one specific embodiment, the number of the positioning members 220 is two.
[0061] Please refer to Figures 1 - 3, in some embodiments, one of the carrier assembly 100 and the upper cover assembly 200 is configured with a snap 510, and the other is configured with a snap groove 520, and the snap 510 and the snap groove 520 cooperate. Through the cooperation of the snap 510 and the snap groove 520, the carrier assembly 100 and the upper cover assembly 200 are separated or connected. In one embodiment, the snap 510 is a spring snap 510, and the spring snap 510 is rotatably connected to the side wall of the carrier assembly 100, and the spring snap 510 rotates relative to its own rotation axis, so as to realize separation and snap connection with the snap groove 520.
[0062] In one embodiment, the mutually cooperating snap 510 and snap groove 520 together form a snap assembly 500. The gene synthesis device is provided with four groups of snap assemblies 500, and the four groups of snap assemblies 500 are arranged at intervals on the outer periphery of the carrier assembly 100 and the upper cover assembly 200, so that the carrier assembly 100 and the upper cover assembly 200 are more stable in the connected state.
[0063] Please refer to Figure 3 , in some embodiments, at least one of the carrier assembly 100 and the upper cover assembly 200 is provided with an elastic seal 600 at the abutting portion between the two; the elastic seal 600 can be squeezed and deformed to seal and connect the carrier assembly 100 and the upper cover assembly 200. By providing the elastic seal 600, when the upper cover assembly 200 is mounted on the carrier assembly 100, the airtightness of the first carrier cavity 110 and the second carrier cavity 210 is good through the sealing effect of the elastic seal 600, which is convenient for maintaining and adjusting the air pressure in the first carrier cavity 110 and the second carrier cavity 210.
[0064] Please refer to Figure 3 , in some embodiments, both the carrier assembly 100 and the upper cover assembly 200 are provided with an elastic seal 600 at the abutting portion between the two, so that when the upper cover assembly 200 is mounted on the carrier assembly 100, the airtightness in the first carrier cavity 110 and the second carrier cavity 210 is good.
[0065] In one embodiment, the elastic seal 600 is a silicone pad.
[0066] Please refer to Figure 3, in some embodiments, the second air pressure regulating assembly 400 includes a second air chamber and a second regulating valve 420; a second ventilation pipeline 211 is configured on the chamber wall of the second bearing cavity 210, the second regulating valve 420 is disposed between the second air chamber and the second ventilation pipeline 211, the controller is electrically connected to the second regulating valve 420, and the controller is used to control the second regulating valve 420 to regulate the air intake amount of the gas in the second air chamber entering the second ventilation pipeline 211. By controlling the second regulating valve 420 with the controller to regulate the air intake amount entering the second ventilation pipeline 211, the air pressure in the second bearing cavity 210 can be regulated, so that it is possible to control whether the preset reagent in the synthesis column 810 moves downward or upward. For example, when it is necessary for the preset reagent to move downward along the Figure 3 yy' direction in Figure 3 , the second regulating valve 420 is used to allow more gas to enter the second bearing cavity 210, so that the air pressure in the second bearing cavity 210 is greater than the air pressure in the first bearing cavity 110. When it is necessary for the preset reagent to move upward along the
[0067] Please refer to Figure 3 , in some embodiments, the second air pressure regulating assembly 400 further includes a second control valve 410, the second control valve 410 is installed between the second air chamber and the second regulating valve 420, and the second control valve 410 is used to directly control the on-off between the second air chamber and the second ventilation pipeline 211, which is more convenient.
[0068] Please refer to Figure 3 and combine with Figure 5 Figure 5 , in some embodiments, the second air pressure regulating assembly 400 further includes an air flow regulating member 430, the air flow regulating member 430 is accommodated in the second bearing cavity 210, and the air flow regulating member 430 is connected to the side of the second ventilation pipeline 211 away from the second regulating valve 420; an air flow regulating channel 431 is configured on the air flow regulating member 430, and the gas in the second ventilation pipeline 211 can flow into the second bearing cavity 210 along the extending direction of the air flow regulating channel 431. By providing the air flow regulating member 430, the gas in the second ventilation pipeline 211 can flow into the second bearing cavity 210 along the extending direction of the air flow regulating channel 431, that is to say, the flow direction of the gas flowing into the second bearing cavity 210 is controllable and will not directly blow against the preset reagent in the synthesis column 810, so that the synthesis effect is better.
[0069] Please refer to Figure 3, in some embodiments, the gene synthesis device further includes a waste liquid pipeline 112 assembly 700; the waste liquid pipeline 112 assembly 700 includes a waste liquid carrier 710 and a third control valve 720; a waste liquid pipeline 112 is further constructed on the side wall of the first carrier cavity 110, and the third control valve 720 is arranged between the waste liquid carrier 710 and the waste liquid pipeline 112; the third control valve 720 is used to control the on-off of the waste liquid pipeline 112 and the waste liquid carrier 710. By providing the waste liquid pipeline 112 assembly 700, when the synthesis experiment is completed, the preset reagent in the synthesis column 810 can flow into the second carrier cavity 210 through the second chamber 813, and finally flow into the waste liquid carrier 710 through the waste liquid pipeline 112.
[0070] Please refer to Figure 1 and Figure 2 , in some embodiments, at least one side wall of the first carrier cavity 110 is further constructed with a viewing window 113. By providing the viewing window 113 on at least one side wall of the first carrier cavity 110, the user can observe the reaction situation in real time through the viewing window 113. In one embodiment, the number of viewing windows 113 is three, and the three viewing windows 113 are respectively arranged on the three side walls of the first carrier cavity 110.
[0071] This application also provides a gene synthesis method, which is based on the gene synthesis device described in any of the above embodiments. Please refer to Figure 6 , Figure 6 shows a flowchart of the gene synthesis method provided by an embodiment of this application. The gene synthesis method provided by the embodiment of this application includes:
[0072] S10: Place the synthesis plate 800 on the carrier assembly 100.
[0073] S20: Adjust the air pressure in the first carrier cavity 110 of the carrier assembly 100 through the first air pressure adjustment assembly 300.
[0074] S30: Inject the preset reagent into the first chambers 811 of the multiple synthesis columns 810 in the synthesis plate 800 respectively.
[0075] S40: Install the upper cover assembly 200 on one side of the synthesis plate 800 facing away from the first carrier cavity 110 of the carrier assembly 100.
[0076] S50: Adjust the air pressure in the second carrier cavity 210 of the upper cover assembly 200 through the second air pressure adjustment assembly 400, so that the preset reagent passes through the carrier 812 in the synthesis column 810.
[0077] When gene synthesis is required, first place the synthesis plate 800 on the carrier assembly 100; then adjust the air pressure in the first carrier chamber 110 through the first air pressure regulating assembly 300 so that the air pressure in the first carrier chamber 110 can form a back pressure greater than the atmospheric pressure; at this time, inject the preset reagents into the first chambers 811 of the plurality of synthesis columns 810 in the synthesis plate 800 respectively. During the injection of the preset reagents, since the air pressure in the first carrier chamber 110 is greater than the atmospheric pressure, the air pressure in the first carrier chamber 110 can apply an upward lifting force to the preset reagents in the first chambers 811, thereby reducing the possibility of the preset reagents in the first chambers 811 leaking downward relative to the carriers 812 in the synthesis columns 810 before the synthesis reaction. After the preset reagents are injected, install the upper cover assembly 200 on the side of the synthesis plate 800 facing away from the first carrier chamber 110. At this time, adjust the air pressure in the second carrier chamber 210 through the second air pressure regulating assembly 400, so that the preset reagents pass through the carriers 812 in the synthesis columns 810 and chemically react with the substances carried on the carriers 812. During this process, since the drainage speeds of the preset reagents in the plurality of synthesis columns 810 relative to the carriers 812 are relatively the same, the drainage time required for the entire synthesis process is shorter, and there is no need to additionally add an excessive amount of preset reagents to reduce the possibility of synthesis failure, and the overall synthesis cost is lower; moreover, by controlling the air pressure magnitudes in the first chambers 811 and the second chambers 813, the preset reagents can move up and down relative to the carriers 812 multiple times, so that the reaction between the preset reagents and the substances carried on the carriers 812 is more sufficient, the deviation of the synthesis result is smaller, and the effect is better.
[0078] S60: Calculate the mutation rate of the reaction result between the substance carried on the carrier 812 of each synthesis column 810 and the preset reagent.
[0079] S70: Adjust the contact duration between the substance carried on the carrier 812 and the preset reagent according to the maximum difference between multiple mutation rates.
[0080] After the preset reagent reacts with the substance carried on the carrier 812, calculate the mutation rate of the reaction result between the substance carried on the carrier 812 of each synthesis column 810 and the preset reagent, then calculate the maximum difference between multiple mutation rates, and then adjust the contact duration between the substance carried on the carrier 812 and the preset reagent according to the maximum difference between multiple mutation rates, so that when the mutation rate of the reaction result between the substance and the preset reagent is divided by a smaller value, the contact duration between the substance and the preset reagent is more reasonable, neither too long to affect the synthesis efficiency nor too short to cause a large deviation in the synthesis result.
[0081] In some of these embodiments, step S70: adjusting the contact duration between the load on the carrier 812 and the preset reagent according to the maximum difference between multiple mutation rates specifically includes:
[0082] If the maximum difference between multiple mutation rates is greater than a preset value, then increase the contact duration between the preset reagent and the load; if the maximum difference between multiple mutation rates is less than or equal to the preset value, then decrease the contact duration between the preset reagent and the load. When the maximum difference between the mutation rates of the reaction results of the loads on the carriers 812 of multiple synthesis columns 810 is greater than the preset value, it indicates that the error of the gene synthesis result is relatively large, and it is necessary to increase the contact duration between the preset reagent and the load to make the reaction between the load on the carrier 812 and the preset reagent more sufficient and uniform. When the maximum difference between the mutation rates of the reaction results of the loads on the carriers 812 of multiple synthesis columns 810 is less than or equal to the preset value, it indicates that the error of the gene synthesis result is relatively small, and the reaction between the load on the carrier 812 and the preset reagent is relatively sufficient and uniform. At this time, the contact duration between the preset reagent and the load can be selected to be reduced, thereby improving the efficiency of the entire gene synthesis process.
[0083] In one specific embodiment, the preset value is 6%. That is, when the difference between the mutation rates of multiple synthesis columns 810 on the synthesis plate 800 is greater than 6%, it indicates that the error of the synthesis result is relatively large. For example, the synthesis mutation rate in one synthesis column 810 is 10%, and the synthesis mutation rate in another synthesis column 810 is 17%, indicating that the difference between the two is 7%, which is greater than the preset value of 6%. At this time, it is necessary to increase the preset duration of the preset reagent and the load to make the reaction between the load on the carrier 812 and the preset reagent more sufficient and uniform.
[0084] In some specific embodiments, the step: if the maximum difference between multiple mutation rates is greater than the preset value, then increasing the contact duration between the preset reagent and the load specifically includes: by controlling the change rate of the air pressure in the first loading cavity 110 and the air pressure in the second loading cavity 210, making the preset reagent pass through the carrier 812 multiple times in the first direction. Specifically, the first direction is Figure 3 the yy' direction in, or reducing the rate at which the preset reagent passes through the carrier 812.
[0085] When it is necessary to increase the contact duration between the preset reagent and the carrier, the change rate of the air pressure in the first carrier chamber 110 and the air pressure in the second carrier chamber 210 can be controlled, so that the preset reagent passes through the carrier 812 multiple times in the first direction, or the rate at which the preset reagent passes through the carrier 812 is reduced, thereby increasing the contact duration between the carrier 812 and the preset reagent. For example, after adjusting the air pressure in the first carrier chamber 110 to be less than the air pressure in the second carrier chamber 210, the air pressure in the first carrier chamber 110 is adjusted to be greater than the air pressure in the second carrier chamber 210, and such operations are repeated, so that the preset reagent moves up and down in the yy' direction in Figure 3 multiple times, thereby increasing the contact duration between the carrier 812 and the preset reagent. It is also possible to control the difference in the air pressure between the first carrier chamber 110 and the second carrier chamber 210, so that the rate at which the preset reagent moves downward in the yy' direction in Figure 3 becomes slower, thereby increasing the contact duration between the carrier 812 and the preset reagent.
[0086] In some specific embodiments, the step: if the maximum difference between multiple mutation rates is less than or equal to a preset value, reducing the contact duration between the preset reagent and the carrier specifically includes: controlling the change rate of the air pressure in the first carrier chamber 110 and the air pressure in the second carrier chamber 210, so that the number of times the preset reagent passes through the carrier 812 in the first direction is reduced, or the rate at which the preset reagent passes through the carrier 812 is increased.
[0087] When it is necessary to reduce the contact duration between the preset reagent and the carrier, the change rate of the air pressure in the first carrier chamber 110 and the air pressure in the second carrier chamber 210 can be controlled, so that the number of times the preset reagent passes through the carrier 812 in the first direction is reduced, or the rate at which the preset reagent passes through the carrier 812 is increased, thereby reducing the contact duration between the carrier 812 and the preset reagent. For example, after adjusting the air pressure in the first carrier chamber 110 to be less than the air pressure in the second carrier chamber 210, the air pressure in the first carrier chamber 110 is adjusted to be greater than the air pressure in the second carrier chamber 210, and the number of times of such repeated operations is reduced, so that the number of times the preset reagent moves up and down in the yy' direction in Figure 3 is reduced, thereby reducing the contact duration between the carrier 812 and the preset reagent. It is also possible to control the difference in the air pressure between the first carrier chamber 110 and the second carrier chamber 210, so that the rate at which the preset reagent moves downward in the yy' direction in Figure 3 is increased, thereby reducing the contact duration between the carrier 812 and the preset reagent.
[0088] It should be understood that in the embodiments of the present application, at least some of the steps in the preparation method may include multiple steps or multiple stages. These steps or stages are not necessarily executed and completed at the same time, but can be executed at different times. The execution order of these steps or stages is not necessarily sequential, but can be executed alternately or in turn with at least some of the steps or stages in other steps or other steps.
[0089] The technical features of the above-described embodiments can be combined arbitrarily. For the sake of brevity of description, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, it should be considered as the scope described in this specification.
[0090] The above-described embodiments only represent several implementation manners of the present application. The description is relatively specific and detailed, but it should not be construed as a limitation on the scope of the patent application. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present application, several modifications and improvements can still be made, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent of the present application shall be subject to the appended claims.
Claims
1. A gene synthesis device, characterized in that, The gene synthesis device includes: A controller; A carrier assembly (100) configured with a first carrier cavity (110), and the carrier assembly (100) is used to carry a synthesis plate (800); A first air pressure regulating assembly (300) electrically connected to the controller, and the first air pressure regulating assembly (300) is in communication with the first carrier cavity (110), and the controller is used to control the first air pressure regulating assembly (300) to regulate the air pressure in the first carrier cavity (110); An upper cover assembly (200) configured with a second carrier cavity (210); the upper cover assembly (200) is disposed on a side of the synthesis plate (800) away from the first carrier cavity (110); and the first carrier cavity (110) and the second carrier cavity (210) are separated by the synthesis plate (800); A second air pressure regulating assembly (400) electrically connected to the controller, and the second air pressure regulating assembly (400) is in communication with the second carrier cavity (210), and the controller is used to control the second air pressure regulating assembly (400) to regulate the air pressure in the second carrier cavity (210).
2. The gene synthesis device according to claim 1, wherein The first air pressure regulating assembly (300) includes a first air chamber and a first regulating valve (320); A first air pipe path (111) is configured on the wall of the first carrier cavity (110), the first regulating valve (320) is disposed between the first air chamber and the first air pipe path (111), the controller is electrically connected to the first regulating valve (320), and the controller is used to control the first regulating valve (320) to regulate the intake air volume of the gas in the first air chamber entering the first air pipe path (111).
3. The gene synthesis device according to claim 1, characterized in that A positioning member (220) protruding towards the carrier assembly (100) is configured on the side wall of the upper cover assembly (200); the positioning member (220) abuts against the side wall of the carrier assembly (100).
4. The gene synthesis device according to claim 1, wherein One of the carrier assembly (100) and the upper cover assembly (200) is configured with a snap (510), and the other is configured with a snap groove (520), and the snap (510) and the snap groove (520) are matched.
5. The gene synthesis device according to claim 1, characterized in that At least one of the carrier assembly (100) and the upper cover assembly (200) is provided with an elastic sealing member (600) at the abutting portion of the two; The elastic sealing member (600) can be squeezed and deformed to hermetically connect the carrier assembly (100) and the upper cover assembly (200).
6. The gene synthesis device according to claim 1, characterized in that The second air pressure regulating assembly (400) includes a second air chamber and a second regulating valve (420); A second ventilation pipeline (211) is configured on the cavity wall of the second bearing cavity (210). The second regulating valve (420) is arranged between the second air chamber and the second ventilation pipeline (211). The controller is electrically connected to the second regulating valve (420), and the controller is used to control the second regulating valve (420) to regulate the air intake amount of the gas in the second air chamber entering the second ventilation pipeline (211).
7. The gene synthesis device according to claim 1, wherein The gene synthesis device further includes a waste liquid pipeline (112) assembly; the waste liquid pipeline (112) assembly includes a waste liquid carrier (710) and a third control valve (720); A waste liquid pipeline (112) is further configured on the side wall of the first bearing cavity (110). The third control valve (720) is arranged between the waste liquid carrier (710) and the waste liquid pipeline (112); the third control valve (720) is used to control the on-off of the waste liquid pipeline (112) and the waste liquid carrier (710).
8. A gene synthesis method, characterized in that, Based on the gene synthesis device according to any one of claims 1-7, the gene synthesis method includes: Placing the synthesis plate (800) on the bearing assembly (100); Adjusting the air pressure in the first bearing cavity (110) through the first air pressure regulating assembly (300); Respectively injecting a preset reagent into the first chambers (811) of a plurality of synthesis columns (810) in the synthesis plate (800); Installing the upper cover assembly (200) on one side of the synthesis plate (800) facing away from the first bearing cavity (110) of the bearing assembly (100); Adjusting the air pressure in the second bearing cavity (210) through the second air pressure regulating assembly (400) so that the preset reagent passes through the carrier (812) in the synthesis column (810); Calculating the mutation rate of the reaction result of the substance carried on the carrier (812) of each synthesis column (810) and the preset reagent; Adjusting the contact duration between the substance carried on the carrier (812) and the preset reagent according to the maximum difference between a plurality of the mutation rates; 9. The gene synthesis method according to claim 8, wherein The step of adjusting the contact duration between the substance carried on the carrier (812) and the preset reagent according to the maximum difference between a plurality of the mutation rates specifically includes: If the maximum difference between a plurality of the mutation rates is greater than a preset value, increasing the contact duration between the preset reagent and the carried substance; If the maximum difference between a plurality of the mutation rates is less than or equal to the preset value, reducing the contact duration between the preset reagent and the carried substance.
10. The gene synthesis method according to claim 9, characterized in that, The step of if the maximum difference between a plurality of the mutation rates is greater than the preset value, increasing the contact duration between the preset reagent and the carried substance specifically includes: By controlling the change rate of the air pressure in the first bearing cavity (110) and the air pressure in the second bearing cavity (210), enabling the preset reagent to pass through the carrier (812) multiple times in the first direction, or reducing the passing rate of the preset reagent through the carrier (812).