DNA synthesizer

Abstract

The invention discloses a DNA synthesizer, and relates to the technical field of biology. The DNA synthesizer comprises a shell assembly, a mobile module, a synthesis unit and a separate injection unit, the mobile module is mounted in the shell assembly; the synthesis unit comprises a bearing part and a synthesis plate arranged on the bearing part, the bearing part is arranged on the moving module, a synthesis cavity is defined by the bearing part and the shell assembly, a protective gas inlet and a protective gas outlet are formed in the bearing part, and a sealing structure which is in sliding friction with the inner wall of the shell assembly is arranged on the bearing part; an adjusting mechanism used for driving the sealing structure to be away from or close to the shell assembly is arranged on the bearing part, and the moving module is used for driving the synthesis unit to move in at least one direction; the dispensing unit is arranged on the shell assembly and is used for injecting a reagent into the synthesis plate; the structure of the DNA synthesizer is improved, multiple types of genes can be synthesized, the application is wide, the whole structure is compact, the synthesis cavity is small in size, the loss of synthesis environment protection gas is effectively reduced, and the synthesis cost is remarkably reduced.

Description

Technical Field

[0001] The present invention relates to the field of biotechnology, and in particular to a DNA synthesizer. Background Art

[0002] At present, artificially synthesized DNA is the only known way to modify gene sequences in a targeted manner. It is widely used in many fields such as protein modification and life sciences, such as nucleic acid drugs, enzyme engineering, gene testing, gene therapy, etc.

[0003] The existing gene synthesizer includes a synthesis chamber and a linear motion mechanism arranged in the synthesis chamber, a synthesis plate is installed on the linear motion mechanism, and an injection needle plate is arranged on the top wall of the synthesis chamber. The linear motion mechanism drives the synthesis column of the synthesis plate to move to the target injection steel needle to inject the target reagent.

[0004] Since this synthesis chamber needs to accommodate the entire linear motion mechanism, the volume of the synthesis chamber is restricted by the size of the linear motion mechanism. The volume of the synthesis chamber is generally large. In order to control the humidity of the synthesis environment, a lot of argon needs to be injected as a synthesis environment protection gas. This leads to a large loss of argon, which indirectly leads to high synthesis costs. Summary of the invention

[0005] The main purpose of the present invention is to provide a DNA synthesizer, aiming to reduce the volume of the synthesis chamber and the loss of the synthesis environment protection gas, so as to save the synthesis cost.

[0006] To achieve the above object, the present invention provides a DNA synthesizer, comprising:

[0007] Shell assembly;

[0008] A mobile module is installed in the housing assembly;

[0009] a synthesis unit, the synthesis unit comprising a bearing and a synthesis plate arranged on the bearing, the bearing being arranged on the moving module and surrounding the shell assembly to form a synthesis chamber, the bearing being provided with a protective gas inlet and a protective gas outlet communicating with the synthesis chamber, the bearing being provided with a sealing structure slidingly rubbing against an inner wall of the shell assembly, the bearing being provided with an adjusting mechanism for driving the sealing structure to move away from or close to the shell assembly, and the moving module being used to drive the synthesis unit to move in at least one direction; and

[0010] The injection unit is arranged on the shell assembly and is used for injecting reagents into the synthesis column of the synthesis plate.

[0011] Optionally, the sealing structure includes an elastic member, a sealing gasket and a sealing ring. The edge of the supporting member is provided with an abutment arm, and the abutment arm is concavely provided with a groove. The sealing gasket is elastically arranged in the groove through the elastic member, and the sealing ring is arranged on the sealing gasket. A transparent member is provided on the top of the shell assembly, and the sealing gasket abuts against the transparent member and can slide relative to each other.

[0012] Optionally, the adjustment mechanism is a plurality of adjustment screws, which are respectively arranged at the bottom of the support member and are used to adjust the height position of the support member.

[0013] Optionally, a humidity sensor for detecting the humidity of the protective gas in the synthesis chamber and generating a humidity signal is provided in the synthesis chamber. The DNA synthesizer also includes a gas-liquid pipeline system, and the gas-liquid pipeline system includes a main pipeline suitable for connecting with a gas supply device and a gas-liquid branch and a protective gas branch respectively connected to the main pipeline, the gas-liquid branch is connected to the dispensing unit, the protective gas branch is connected to the protective gas inlet, and a solenoid valve is provided on the protective gas branch. The controller of the solenoid valve is communicatively connected to the humidity sensor and is used to control the on and off of the protective gas branch according to the humidity signal so that the humidity of the protective gas in the synthesis chamber is at a target humidity value.

[0014] Optionally, the target humidity value is 15%RH~25%RH.

[0015] Optionally, a leakage sensor is provided in the synthesis chamber for detecting whether there is liquid in the synthesis chamber and generating a leakage signal. A waste liquid tank is installed in the synthesis chamber. The waste liquid tank is provided with a waste liquid reflux hole and a drainage hole. The drainage hole is connected to a waste liquid collection container through a drainage pipeline. A drainage valve is provided at the drainage hole. The controller of the drainage valve is communicatively connected to the leakage sensor and is used to control the opening and closing of the drainage hole according to the leakage signal.

[0016] Optionally, the shell assembly is provided with a plurality of first reagent bottle positions suitable for loading monomer bottles and a plurality of second reagent bottle positions suitable for loading large reagent bottles, the gas-liquid branch is divided into a first gas-liquid branch and a second gas-liquid branch, a plurality of the first reagent bottle positions are arranged in parallel on the first gas-liquid branch, the first gas-liquid branch is connected to the corresponding liquid outlet steel needle of the dispensing unit, a plurality of the second reagent bottle positions are arranged in parallel on the second gas-liquid branch, the second gas-liquid branch is connected to the corresponding liquid outlet steel needle of the dispensing unit.

[0017] Optionally, at least part of the first reagent bottle positions and / or at least part of the second reagent bottle positions are arranged one-to-one with the liquid outlet steel needle, at least part of the first reagent bottle positions and / or at least part of the second reagent bottle positions are arranged one-to-four with the liquid outlet steel needle, and at least part of the first reagent bottle positions and / or at least part of the second reagent bottle positions are arranged one-to-eight with the liquid outlet steel needle.

[0018] Optionally, the carrier is provided with a receiving port for accommodating the synthetic board, a drainage plate is provided in the receiving port, a sealing rubber pad is provided between the synthetic board and the drainage plate, the synthetic board, the sealing rubber pad and the holes on the drainage plate are connected one-to-one, and the drainage plate is suitable for connecting to a liquid collection container.

[0019] Optionally, a pressing mechanism is provided on the bearing member, and the pressing mechanism is located at the edge of the receiving opening and is used to press the synthetic board onto the sealing pad.

[0020] In the technical scheme of the present invention, the DNA synthesizer includes a housing assembly, a mobile module, a synthesis unit and a dispensing unit; the mobile module is installed in the housing assembly; the synthesis unit includes a bearing and a synthesis board arranged on the bearing, the bearing is arranged on the mobile module and is surrounded by the housing assembly to form a synthesis chamber, the bearing is provided with a protective gas inlet and a protective gas outlet connected to the synthesis chamber, the bearing is provided with a sealing structure that slides and rubs with the inner wall of the housing assembly, the bearing is provided with an adjustment mechanism for driving the sealing structure away from or close to the housing assembly, the mobile module is used to drive the synthesis unit to move in at least one direction; the dispensing unit is arranged on the housing assembly and is used to inject reagents into the synthesis column of the synthesis board. It can be understood that the present invention improves the structure of the DNA synthesizer, the synthesis chamber is formed by the bearing of the synthesis board and part of the top wall or side wall of the housing assembly, and its volume is only determined by the size of the bearing and the synthesis board thereon. Compared with the prior art, the volume of the synthesis chamber of the DNA synthesizer of the present invention can be greatly reduced, effectively reducing the loss of the synthesis environment protection gas, and significantly reducing the synthesis cost. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the structures shown in these drawings without paying creative work.

[0022] Figure 1 It is a structural schematic diagram of an embodiment of a DNA synthesizer of the present invention;

[0023] Figure 2It is a structural schematic diagram of another angle of an embodiment of a DNA synthesizer of the present invention;

[0024] Figure 3 An exploded view of a mobile module, a synthesis unit and a dispensing unit in an embodiment of a DNA synthesizer of the present invention;

[0025] Figure 4 It is a structural schematic diagram of a mobile module and a synthesis unit in an embodiment of a DNA synthesizer of the present invention;

[0026] Figure 5 It is a schematic diagram of the structure of a synthesis unit in one embodiment of a DNA synthesizer of the present invention;

[0027] Figure 6 An exploded view of a synthesis unit in one embodiment of a DNA synthesizer of the present invention;

[0028] Figure 7 It is a structural schematic diagram of the gas path connection block of the carrier in one embodiment of the DNA synthesizer of the present invention;

[0029] Figure 8 Schematic diagram of the gas-liquid pipeline system in one embodiment of the DNA synthesizer of the present invention.

[0030] Description of Figure Numbers:

[0031] 10. Shell assembly; 20. Mobile module; 30. Synthesis unit; 40. Dispensing unit; 31. Carrier; 32. Synthesis plate; 33. Sealing structure; 34. Adjustment mechanism; 30a. Synthesis chamber; 31a. Protective gas inlet; 31b. Protective gas outlet; 311. Gas path connection block; 311a. Conducting groove; 311b. Connector jack; 321. Synthesis column; 331. Elastic member; 332. Steel ring; 333. Sealing pad; 334. Sealing ring; 11. Transparent member; 35. Humidity sensor; 51. Main line; 52. Gas-liquid branch; 53. Protective gas branch; 36. Liquid leakage sensor; 37. Waste liquid tank; 102. Second reagent bottle position; 100. Monomer bottle; 200. Large reagent bottle; 41. Liquid outlet steel needle; 38. Pressing mechanism; 300. Waste liquid collection container.

[0032] The realization of the purpose, functional features and advantages of the present invention will be further explained in conjunction with embodiments and with reference to the accompanying drawings. DETAILED DESCRIPTION

[0033] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0034] It should be noted that all directional indications in the embodiments of the present invention (such as up, down, left, right, front, back, etc.) are only used to explain the relative position relationship, movement status, etc. between the components under a certain specific posture (as shown in the accompanying drawings). If the specific posture changes, the directional indication will also change accordingly.

[0035] In the description of the present invention, it should be noted that, unless otherwise clearly specified and limited, the terms "installed", "connected", and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be indirectly connected through an intermediate medium, or it can be the internal communication of two components. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0036] In addition, the descriptions of "first", "second", etc. in the present invention are only used for descriptive purposes and cannot be understood as indicating or implying their 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 addition, the meaning of "and / or" appearing in the full text is to include three parallel solutions. Taking "A and / or B" as an example, it includes solution A, or solution B, or a solution that satisfies both A and B. In addition, the technical solutions between the various embodiments can be combined with each other, but it must be based on the ability of ordinary technicians in this field to implement. When the combination of technical solutions is contradictory or cannot be implemented, it should be deemed that such a combination of technical solutions does not exist and is not within the scope of protection required by the present invention.

[0037] The invention provides a DNA synthesizer.

[0038] Reference Figures 1 to 5In one embodiment of the present invention, the DNA synthesizer includes a housing assembly 10, a mobile module 20, a synthesis unit 30 and a dispensing unit 40; the mobile module 20 is installed in the housing assembly 10; the synthesis unit 30 includes a carrier 31 and a synthesis plate 32 arranged on the carrier 31, the carrier 31 is arranged on the mobile module 20 and is surrounded by the housing assembly 10 to form a synthesis chamber 30a, the carrier 31 is provided with a protective gas inlet 31a and a protective gas outlet 31b connected to the synthesis chamber 30a, and the carrier 31 is provided with a protective gas outlet 31b and a protective gas outlet 31b connected to the synthesis chamber 30a. A sealing structure 33 is provided for sliding friction with the inner wall of the housing assembly 10, and an adjusting mechanism 34 is provided on the carrier 31 for driving the sealing structure 33 away from or close to the housing assembly 10, so as to ensure that the carrier 31 can slide smoothly and make the synthesis chamber 30a have good airtightness; the moving module 20 is used to drive the synthesis unit 30 to move in at least one direction; the dispensing unit 40 is provided on the housing assembly 10, and is used to inject reagents into the synthesis columns 321 of the synthesis plate 32, and the number of synthesis columns 321 is not limited. It should be noted that the common number of synthesis columns 321 in industrial DNA synthesizers is 96 columns, 192 columns, and 384 columns. Synthesizers with more synthesis columns 321 are relatively rare, and are mainly suitable for large laboratories, public experimental platforms and commercial synthesis institutions.

[0039] In this embodiment, the sealing structure 33 may be a single sealing member such as a sealing rubber ring, or may be a structure composed of multiple components that can achieve sliding sealing, which is not limited here.

[0040] In this embodiment, the carrier 31 may preferably be in the shape of a tray, so as to reduce the number of components of the synthesis unit 30 as much as possible, reduce the complexity of the structure, and ensure the airtightness of the side of the synthesis chamber 30a, thereby preventing water vapor in the environment from entering the synthesis chamber 30a and affecting DNA synthesis. Of course, in some other embodiments, the carrier 31 may also adopt other structures, which are not limited here.

[0041] The moving module 20 may include an X-axis module and / or a Y-axis module and / or a Z-axis module, preferably an X-axis module and a Y-axis module, to improve the synthesis efficiency, which is not limited here.

[0042] It can be understood that the present invention improves the structure of the DNA synthesizer. The synthesis chamber 30a is formed by the supporting member 31 supporting the synthesis plate 32 and a part of the top wall or side wall of the shell assembly 10, and its volume is only determined by the size of the supporting member 31 and the synthesis plate 32 thereon. Compared with the prior art, the volume of the synthesis chamber 30a of the DNA synthesizer of the present invention is greatly reduced, which effectively reduces the loss of the synthesis environment protection gas and significantly reduces the synthesis cost.

[0043] By adopting the above-mentioned synthesis chamber 30a structure, the present invention can reduce the chamber volume to 2.9L or less, making the synthesis environment easier to control, and greatly saving the consumption of protective gases such as argon. Compared with the large chamber volume of 30L of the existing DNA synthesizer, the synthesis chamber 30a volume of the present invention is reduced by nearly 10 times, and the results of cost reduction and efficiency improvement are remarkable.

[0044] Main reference Figure 5 and Figure 6 In one embodiment, the sealing structure 33 may include an elastic member 331, a sealing gasket 333 and a sealing ring 334. A contact arm is provided at the edge of the carrier 31, and a groove is concavely provided on the contact arm. The sealing gasket 333 is elastically arranged in the groove through the elastic member 331. The sealing ring 334 is arranged on the sealing gasket 333. A transparent member 11 is provided on the top of the shell assembly 10, and the sealing gasket 333 contacts the transparent member 11 and can slide relatively.

[0045] In this embodiment, the elastic member 331 may be an elastic silicone ring, or may be a plurality of metal springs arranged in the groove at intervals, such as Figure 6 As shown, this embodiment is preferably a plurality of metal springs, and a steel ring 332 or a ring-shaped component of other materials can be arranged between the plurality of metal springs and the sealing gasket 333, so that the sealing gasket 333 is subjected to a more uniform force, thereby improving the sealing performance of the sealing structure 33. The sealing gasket 333 can be made of materials such as silicone. The sealing ring 334 can be made of materials such as PTFE. The transparent member 11 can be tempered glass for convenient observation of the synthesis situation, etc., which is not limited here.

[0046] The use of PTFE sealing ring 334 and tempered glass for sliding friction is an innovative point of the present invention, and its purpose is that the two can effectively achieve surface-to-surface contact, achieve close fit through spring force, and achieve effective sealing. In addition, there is sliding friction between the bearing member 31 of the synthesis unit 30 and the tempered glass, and the PTFE sealing ring 334 and the tempered glass have better wear resistance when in contact. The smaller friction coefficient between the two, while being able to achieve good sealing, also has better durability.

[0047] In this embodiment, Figure 5 As shown, the adjustment mechanism 34 may use a plurality of adjustment screws, which are respectively arranged at the bottom of the carrier 31 and used to adjust the height position of the carrier 31. To ensure that the carrier 31 can slide smoothly and the synthesis chamber 30a has good airtightness.

[0048] The sealing adjustment principle between the PTFE sealing ring 334 and the tempered glass is as follows: the adjusting screw can adjust the supporting part 31 upward or downward to lift or lower it in the vertical direction; when the adjusting screw adjusts the supporting part 31 upward until the PTFE sealing ring 334 contacts the tempered glass of the upper cover, it continues to adjust upward by a certain amount, at which time the PTFE sealing ring 334 will compress the spring, and the PTFE sealing ring 334 will fit tightly with the tempered glass under the action of the spring force; the silicone pad between the spring and the PTFE can be deformed with compression, and the silicone pad is buckled on the spring steel ring 332 to perfectly isolate and seal the PTFE sealing ring 334 from the spring, thus forming a closed cavity structure.

[0049] During the DNA synthesis process, the humidity in the synthesis chamber 30a (synthesis environment) needs to be strictly controlled. Figure 5 and Figure 6 In one embodiment, a protective gas inlet 31a is provided on one side of the bottom of the synthesis chamber 30a, and a protective gas outlet 31b is provided on the other side for controlling the humidity in the chamber. Protective gases such as argon enter from one side and are discharged from the other side, which neither forms a positive pressure in the chamber nor regulates the humidity in the chamber.

[0050] Further, a humidity sensor 35 for detecting the humidity of the protective gas in the synthesis chamber 30a and generating a humidity signal may be provided in the synthesis chamber 30a. The DNA synthesizer also includes a gas-liquid pipeline system, which includes a main pipeline 51 suitable for communicating with the gas supply device and a gas-liquid branch 52 and a protective gas branch 53 respectively connected to the main pipeline 51. The gas-liquid branch 52 is connected to the injection unit 40, and the protective gas branch 53 is connected to the protective gas inlet 31a. A solenoid valve is provided on the protective gas branch 53. The controller of the solenoid valve is connected to the humidity sensor 35 and is used to control the on-off of the protective gas branch 53 according to the humidity signal, so that the humidity of the protective gas in the synthesis chamber 30a is at the target humidity value. The humidity sensor 35 can be a temperature and humidity detection sensor that detects both temperature and humidity, which is not limited here.

[0051] In this embodiment, the target humidity value is 15%RH to 25%RH, preferably 20%RH.

[0052] Specifically, when the target humidity value is 20% RH, a temperature and humidity detection sensor can be set on the carrier 31 to monitor the temperature and humidity in the reaction chamber in real time. The sensor cooperates with the argon gas intake control solenoid valve: when the humidity detected by the sensor has reached 15% RH, the argon gas intake control solenoid valve closes the intake; when the humidity detected by the sensor rises to 20% RH, the argon gas intake control solenoid valve opens the intake regulation. This mode greatly reduces the argon gas consumption while meeting the synthetic environment.

[0053] In order to make the protective gas introduced into the synthesis chamber 30a be quickly and evenly distributed in the synthesis chamber 30a, and to make the protective gas or air be quickly discharged, mainly refer to Figure 5 and Figure 7 In one embodiment, the protective gas inlet 31a and the protective gas outlet 31b are respectively arranged at the edges of both sides of the carrier 31, and both can include a plurality of air holes evenly spaced along the width direction of the carrier 31. Preferably, the diameter of the air holes is 3.0 mm, the number is 18, and the distance between the air holes can be set to 10.0 mm.

[0054] In addition, if Figure 5 and Figure 7 As shown, a gas circuit connection block 311 can be provided at the bottom surface of the carrier 31 at positions corresponding to the protective gas inlet 31a and the protective gas outlet 31b to install a joint for connecting the protective gas branch 53. In this embodiment, in order to allow the gas to be quickly discharged or discharged and to make the protective gas in the cavity as evenly distributed as possible, the gas circuit connection block 311 can be set in a rectangular parallelepiped shape, and a "V"-shaped conducting groove 311a can be opened on the top of the gas circuit connection block 311. The notch of the conducting groove 311a covers / connects all the air holes, and at least one joint plug hole 311b is provided at the bottom of the groove for plugging the above-mentioned joint, preferably 3 joint plug holes 311b and 3 joints, and the 3 joint plug holes 311b are respectively arranged at the two ends and the middle of the conducting groove 311a. The joint plug hole 311b can include a connecting section connected to the conducting groove 311a and a fixed section for fixing the joint. The diameter of the connecting section can be set to 6.0 mm, and the diameter of the fixed section is designed according to the specific joint model, which is not limited here.

[0055] Main reference Figure 5 In one embodiment, a leakage sensor 36 for detecting whether there is liquid in the synthesis chamber 30a and generating a leakage signal may be provided in the synthesis chamber 30a. A waste liquid tank 37 is installed in the synthesis chamber 30a. The waste liquid tank 37 is provided with a waste liquid reflux hole and a drainage hole. The drainage hole is connected to the waste liquid collection container 300 through a drainage pipeline. A drainage valve is provided at the drainage hole. The controller of the drainage valve is communicated with the leakage sensor 36 and is used to control the opening and closing of the drainage hole according to the leakage signal.

[0056] In this embodiment, the liquid leakage sensor 36 communicates and cooperates with the waste liquid tank 37 drain switch solenoid valve. When a program error or damage occurs in one or some of the liquid pumping solenoid valves, resulting in control failure, the liquid reagent will be discharged into the cavity. When the liquid reagent accumulates to a certain amount and is sensed by the liquid leakage sensor 36, the waste liquid solenoid valve opens, and the leaked liquid is discharged from the waste liquid tank 37. A leakage reflux hole is provided on the bottom side of the waste liquid tank 37. Its purpose is also to enable the liquid reagent to be discharged to the waste liquid tank 37 through this reflux hole when it accidentally leaks into the cavity.

[0057] To ensure the sealing of the bottom of the synthetic board 32 and avoid gas and liquid leakage, refer to Figure 5 and Figure 6 In one embodiment, a receiving port for receiving the synthetic board 32 may be provided on the carrier 31, a drainage plate is provided in the receiving port, a sealing rubber pad is provided between the synthetic board 32 and the drainage plate, the synthetic board 32, the sealing rubber pad and the holes on the drainage plate are connected one to one, and the drainage plate is suitable for connecting to a liquid collection container.

[0058] In this embodiment, a pressing mechanism 38 is provided on the carrier 31, and the pressing mechanism 38 is located at the edge of the receiving opening. The pressing mechanism 38 is used to press the composite board 32 onto the sealing rubber pad. The pressing mechanism 38 may include a pressing member and a pressing knob screwed on the pressing member. Before the synthesis begins, the composite board 32 is first placed into the work station, i.e., the receiving opening, and the pressing member of the composite board 32 is manually pushed inward, and then the pressing knob is rotated to press the pressing member down on the composite board 32, so that the lower surface of the composite board 32 is tightly attached to the sealing rubber pad to form a seal.

[0059] The working process is to first adjust the screw into place, then open the needle plate with the liquid outlet steel needle 41 installed, then put in the synthesis plate 32, and clamp it in place through the clamping mechanism 38, then cover the needle plate, and finally press the start button on the device, then the system software controls the mobile module 20 to drive the synthesis plate 32 to move according to the preset pitch, and the liquid begins to be synthesized.

[0060] Existing gene synthesizers have the problem of small bottle positions and large equipment size. The number of bottle positions determines the number of monomer types that can be added to the equipment. In principle, the more bottle positions there are, the more types that can be synthesized and the wider the application, so the more bottle positions there are, the larger the equipment size will be.

[0061] In this regard, the present invention has made corresponding improvements and innovations, and designed a miniaturized and high-quality DNA synthesizer, which has made certain contributions to reducing the cost and increasing the efficiency of DNA synthesizers:

[0062] Based on the above embodiments, please combine Figure 1 , Figure 2 and Figure 8 The shell assembly 10 of the DNA synthesizer is provided with a plurality of first reagent bottle positions suitable for loading monomer bottles 100 and a plurality of second reagent bottle positions 102 suitable for loading large reagent bottles 200. The gas-liquid branch 52 is divided into a first gas-liquid branch and a second gas-liquid branch. The plurality of first reagent bottle positions are arranged in parallel on the first gas-liquid branch, and the first gas-liquid branch is connected to the liquid outlet steel needle 41 of the corresponding dispensing unit 40. The plurality of second reagent bottle positions 102 are arranged in parallel on the second gas-liquid branch, and the second gas-liquid branch is connected to the liquid outlet steel needle 41 of the corresponding dispensing unit 40.

[0063] Further, at least part of the first reagent bottle position and / or at least part of the second reagent bottle position 102 are arranged one-to-one with the liquid outlet steel needle 41, at least part of the first reagent bottle position and / or at least part of the second reagent bottle position 102 are arranged one-to-four with the liquid outlet steel needle 41, and at least part of the first reagent bottle position and / or at least part of the second reagent bottle position 102 are arranged one-to-eight with the liquid outlet steel needle 41.

[0064] Specifically, the front of the DNA synthesizer can be arranged with 24 100-position interfaces for monomer bottles (compared with 8 100-position interfaces for monomer bottles of the existing DNA synthesizer, the number of bottle positions of the DNA synthesizer of the present invention has increased by 3 times), of which 16 100-position interfaces for 500ml monomer bottles are arranged, 8 100-position interfaces for 30-60ml monomer bottles are arranged, and 9 large reagent bottle 200-position interfaces are arranged on the side of the device. In this embodiment, in order to control the volume of the device, all reagents are designed to correspond to 3 control liquid injection schemes, namely 1 to 1 (1 reagent is controlled by 1 liquid injection control solenoid valve, corresponding to 1 liquid outlet steel needle 41), 1 to 4 (1 reagent is controlled by 4 liquid injection control solenoid valves, corresponding to 4 liquid outlet steel needles 41), and 1 to 8 (1 reagent is controlled by 8 liquid injection control solenoid valves, corresponding to 8 liquid outlet steel needles 41), wherein the 1 to 1 and 1 to 4 liquid injection modes have 8 reagents respectively, and the rest all adopt the 1 to 8 liquid injection mode.

[0065] The distribution principle is that conventional and commonly used reagents are designed as a 1 to 8 liquid discharge mode, and unconventional reagents such as modified monomers are designed as a 1 to 1 or 1 to 4 liquid discharge mode. In this way, while controlling the synthesis time, the length of the equipment is also effectively controlled. When the liquid type in the synthesis program is a conventional reagent, the corresponding liquid discharge mode is 1 to 8 liquid discharge. At this time, the support 31 equipped with the synthesis plate 32 only performs reciprocating motion in the X-axis direction to receive liquid for synthesis; when the liquid type in the synthesis program includes an unconventional monomer reagent, the support 31 equipped with the synthesis plate 32 first drives the synthesis column 321 to move into place along the X-axis direction, and then moves 2 times (1 to 4 liquid discharge) or 8 times (1 to 1 liquid discharge) along the Y-axis direction.

[0066] The present invention can meet the access ports of 100 positions for 24 monomer bottles and 200 positions for 9 large reagent bottles through the design of the above-mentioned structural layout, which can basically meet the bottle position requirements of all artificial gene synthesis on the market. In addition, the present invention designs the cavity structure of the small cavity tray, which greatly reduces the volume of the synthesis cavity 30a, and combines the temperature and humidity sensing system to greatly reduce the argon consumption and save the synthesis cost. The present invention reduces the overall size of the DNA synthesizer to about 1090mm in length, about 713mm in width, and about 918mm in height by adopting the above-mentioned gas-liquid path system and the small cavity tray structure.

[0067] The present invention uses an XY biaxial moving module 20 to drive the synthesis plate 32 to move in both directions, and adopts a liquid arrangement scheme of one reagent corresponding to one liquid injection steel needle and one reagent corresponding to four liquid injection steel needles in combination with some modified monomers. Under the conditions of meeting 100 positions of 24 monomer bottles and a variety of flexible synthetic methods, the volume of the equipment is effectively controlled, and the laboratory space occupied by the equipment is greatly reduced. Compared with the conventional 1 to 8 scheme, the cost of the solenoid valve of the DNA synthesizer of the present invention can save about 60,000.

[0068] The above descriptions are only optional embodiments of the present invention, and are not intended to limit the patent scope of the present invention. All equivalent structural changes made using the contents of the present invention's specification and drawings, or directly / indirectly applied in other related technical fields, are included in the patent protection scope of the present invention.

Claims

1. A DNA synthesizer, characterized in that: include: Housing assembly (10); A movable module (20) is installed in the housing assembly (10); A synthesis unit (30), the synthesis unit (30) comprising a bearing member (31) and a synthesis plate (32) arranged on the bearing member (31), the bearing member (31) being arranged on the movable module (20) and surrounding the shell assembly (10) to form a synthesis chamber (30a), the bearing member (31) being provided with a protective gas inlet (31a) and a protective gas outlet (31b) which are in communication with the synthesis chamber (30a), the bearing member (31) being provided with a sealing structure (33) which slides and rubs against the inner wall of the shell assembly (10), the bearing member (31) being provided with an adjusting mechanism (34) for driving the sealing structure (33) to move away from or close to the shell assembly (10), and the movable module (20) being used to drive the synthesis unit (30) to move in at least one direction; as well as The dispensing unit (40) is arranged on the housing component (10) and is used to inject reagents into the synthesis column (321) of the synthesis plate (32).

2. The DNA synthesizer according to claim 1, characterized in that The sealing structure (33) comprises an elastic member (331), a sealing gasket (333) and a sealing ring (334); an abutting arm is provided at the edge of the carrier (31); a groove is concavely provided on the abutting arm; the sealing gasket (333) is elastically arranged in the groove through the elastic member (331); the sealing ring (334) is arranged on the sealing gasket (333); a transparent member (11) is provided on the top of the housing assembly (10); the sealing gasket (333) abuts against the transparent member (11) and can slide relative to the transparent member (11).

3. The DNA synthesizer according to claim 1, characterized in that The adjustment mechanism (34) is a plurality of adjustment screws, which are respectively arranged at the bottom of the support member (31) and are used to adjust the height position of the support member (31).

4. The DNA synthesizer according to claim 1, characterized in that: The synthesis chamber (30a) is provided with a humidity sensor (35) for detecting the humidity of the protective gas in the synthesis chamber (30a) and generating a humidity signal. The DNA synthesizer also includes a gas-liquid pipeline system, the gas-liquid pipeline system includes a main pipeline (51) suitable for communicating with a gas supply device and a gas-liquid branch pipeline (52) and a protective gas branch pipeline (53) respectively connected to the main pipeline (51). The gas-liquid branch pipeline (52) is connected to the injection unit (40), and the protective gas branch pipeline (53) is connected to the protective gas inlet (31a). The protective gas branch pipeline (53) is provided with a solenoid valve. The controller of the solenoid valve is communicatively connected to the humidity sensor (35) and is used to control the on-off of the protective gas branch pipeline (53) according to the humidity signal, so that the humidity of the protective gas in the synthesis chamber (30a) is at a target humidity value.

5. The DNA synthesizer according to claim 4, characterized in that The target humidity value is 15%RH to 25%RH.

6. The DNA synthesizer according to claim 1, characterized in that: The synthesis chamber (30a) is provided with a leakage sensor (36) for detecting whether there is liquid in the synthesis chamber (30a) and generating a leakage signal. The synthesis chamber (30a) is provided with a waste liquid tank (37). The waste liquid tank (37) is provided with a waste liquid reflux hole and a drainage hole. The drainage hole is connected to a waste liquid collection container (300) through a drainage pipeline. A drainage valve is provided at the drainage hole. The controller of the drainage valve is communicatively connected to the leakage sensor (36) and is used to control the opening and closing of the drainage hole according to the leakage signal.

7. The DNA synthesizer according to claim 4, characterized in that The shell assembly (10) is provided with a plurality of first reagent bottle positions suitable for loading monomer bottles (100) and a plurality of second reagent bottle positions (102) suitable for loading large reagent bottles (200); the gas-liquid branch (52) is divided into a first gas-liquid branch and a second gas-liquid branch; a plurality of the first reagent bottle positions are arranged in parallel on the first gas-liquid branch, and the first gas-liquid branch is connected to the corresponding liquid outlet steel needle (41) of the dispensing unit (40); a plurality of the second reagent bottle positions (102) are arranged in parallel on the second gas-liquid branch, and the second gas-liquid branch is connected to the corresponding liquid outlet steel needle (41) of the dispensing unit (40).

8. The DNA synthesizer according to claim 7, characterized in that At least part of the first reagent bottle position and / or at least part of the second reagent bottle position (102) is arranged one-to-one with the liquid outlet steel needle (41), at least part of the first reagent bottle position and / or at least part of the second reagent bottle position (102) is arranged one-to-four with the liquid outlet steel needle (41), and at least part of the first reagent bottle position and / or at least part of the second reagent bottle position (102) is arranged one-to-eight with the liquid outlet steel needle (41).

9. The DNA synthesizer according to claim 1, characterized in that: The carrier (31) is provided with a receiving opening for receiving the synthetic board (32), a drainage plate is provided in the receiving opening, a sealing rubber pad is provided between the synthetic board (32) and the drainage plate, the synthetic board (32), the sealing rubber pad and the holes on the drainage plate are connected one to one, and the drainage plate is suitable for connecting to a liquid collection container.

10. The DNA synthesizer according to claim 9, characterized in that: The bearing member (31) is provided with a pressing mechanism (38), which is located at the edge of the receiving opening and is used to press the synthetic board (32) onto the sealing rubber pad.

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