DNA inkjet synthesis equipment

Abstract

The present invention discloses a DNA inkjet synthesis device, comprising a main frame, a multi-channel inkjet head module, a syringe pump module, and a controller. The main frame is provided with a power assembly and a workbench. The power assembly includes an X-axis slide module arranged on one side of the workbench, a Y-axis slide module provided on the X-axis slide module, and a Z-axis slide module provided on the Y-axis slide module. The multi-channel inkjet head module includes a base connected to a blowpipe, a pipette, and multiple liquid pipes, the output ends of which are capable of producing microliter-level droplets. The syringe pump module includes a blowpipe, a pipette, multiple liquid storage bottles, and an injection mechanism. The blowpipe is connected to the blowpipe, the pipette is connected to the pipette, the pipette is connected to the pipette, the pipette is connected to the waste liquid bottle, and the injection mechanism is used to extract liquid from the liquid storage bottle and output it to the liquid pipe. The power assembly, syringe pump module, and controller are electrically connected. The device has the advantages of being compact and portable, and each module is easy to assemble and deploy, with low self-assembly cost.

Description

Technical Field

[0001] The present invention relates to the technical field of DNA synthesis equipment, in particular to a DNA inkjet synthesis equipment. Background Art

[0002] With the development of biology, humans have gradually entered an era of actively rewriting biological genetic information according to their own ideas, moving from the era of passively reading biological genetic information to the era of artificially synthesized genes (DNA). Artificially synthesized genes (DNA) are used in scientific research, medical testing, medicine, agriculture, industry and other fields.

[0003] Currently, the primary method for artificially synthesizing DNA is chemically splicing oligonucleotides one by one to create long DNA fragments. Existing DNA inkjet synthesizers are typically desktop devices. Computer software controls the inkjet printheads to sequentially dispense the required base monomer solution, deprotection solution, capping solution, coupling solution, and oxidation solution onto a synthesis substrate to synthesize the desired DNA sequence.

[0004] In related technologies, DNA inkjet synthesizers are relatively bulky and require a high level of professional expertise to operate. Therefore, professional experimenters are required to operate DNA synthesis experiments in the laboratory. Since DNA chemical synthesis requires an anhydrous and oxygen-free environment to achieve a high yield, the overly large desktop DNA inkjet synthesizer cannot be installed in the anhydrous and oxygen-free glove box equipped in general laboratories, affecting the progress of the experiment. Summary of the Invention

[0005] The present invention aims to solve at least one of the technical problems in the related art to a certain extent. To this end, the present invention provides a DNA inkjet synthesis device that adopts a miniaturized modular design, is easy to install and deploy, and is compact and portable.

[0006] According to an embodiment of the present invention, the DNA inkjet synthesis device includes a main frame, a multi-channel inkjet head module, an injection pump module and a controller. The main frame is provided with a power assembly and a workbench, the workbench is used to carry a synthesis substrate, the power assembly includes an X-axis slide module arranged on one side of the workbench, the X-axis slide module is provided with a Y-axis slide module, and the Y-axis slide module is provided with a Z-axis slide module; the multi-channel inkjet head module is connected to the Z-axis slide module, the multi-channel inkjet head module includes a machine base, and the machine base is connected to A liquid blowing tube, a liquid suction tube and multiple liquid tubes, the output end of the liquid tube can produce μL-level small droplets; the injection pump module is connected to the main frame, the injection pump module includes a liquid blowing pump, a liquid suction pump, multiple liquid storage bottles and an injection mechanism, the liquid blowing tube is connected to the liquid blowing pump, the liquid suction tube is connected to the liquid suction pump, the liquid suction pump is connected to a waste liquid bottle, and the injection mechanism is used to extract the liquid in the liquid storage bottle and output it to the liquid tube; the controller is connected to the main frame, and the power assembly, the injection pump module and the controller are electrically connected.

[0007] The DNA inkjet synthesis device according to the embodiment of the present invention has at least the following beneficial effects:

[0008] Based on data provided by the DNA synthesis software, a controller controls the power assembly and syringe pump module, thereby controlling the various droplets produced by the multiple liquid channels of the multi-channel inkjet head module. These droplets, such as the required base monomer solution, deprotection solution, capping solution, coupling solution, and oxidation solution, are then deposited onto the synthesis substrate supported by the workbench in a sequence and at pre-set locations, automatically completing the cyclic synthesis steps of deprotection, nucleotide grafting, end-capping, and oxidation activation. The simplified design of the DNA inkjet synthesis device offers the advantages of compact size and portability. Each module is easy to assemble and deploy, with low self-assembly costs. It is easily assembled and used by non-expert lab technicians, and can be installed in a typical anhydrous and oxygen-free glove box.

[0009] According to some embodiments of the present invention, the injection mechanism includes multiple driving members and multiple injectors, the injectors are provided with a piston chamber, a piston is arranged in the piston chamber, the push rod of the piston is connected to the driving member, the injectors are connected to the liquid circuit tube and the liquid inlet tube, and the liquid inlet tube is connected to the liquid storage bottle.

[0010] According to some embodiments of the present invention, the injection mechanism also includes a two-position three-way solenoid valve, the normally open end of the two-position three-way solenoid valve is connected to the liquid circuit tube, the normally closed end of the two-position three-way solenoid valve is connected to the liquid inlet pipe, and the common end of the two-position three-way solenoid valve is connected to the injector.

[0011] According to some embodiments of the present invention, the injection pump module includes a vertical plate bracket, multiple driving members are fixed on both sides of the vertical plate bracket, multiple injectors are arranged on the outside of the driving member, the liquid storage bottle is arranged above the driving member, and the blowing pump and the suction pump are fixed on both sides of the upper end of the vertical plate bracket.

[0012] According to some embodiments of the present invention, the machine base includes a bottom plate, an intermediate plate and a cover plate, the side of the intermediate plate is provided with a plurality of embedded grooves, the liquid pipe is installed in the embedded grooves, the bottom plate covers the plurality of embedded grooves, the cover plate is provided with two positioning grooves, the blowing pipe and the suction pipe are installed in the positioning grooves, and the middle plate covers the two positioning grooves.

[0013] According to some embodiments of the present invention, the base has two intermediate plates, which are stacked, and each intermediate plate is provided with five embedded grooves.

[0014] According to some embodiments of the present invention, the sides of the two intermediate plates are each provided with a mounting block, the mounting block is fixed to the base plate by bolts, the cover plate is provided with a fixing block, the fixing block is fixed to the base plate by bolts, and the mounting block is staggered with the fixing block.

[0015] According to some embodiments of the present invention, the power assembly has two X-axis slide modules, and the two X-axis slide modules are arranged on both sides of the workbench.

[0016] According to some embodiments of the present invention, the controller is mounted on the bottom surface of the main frame, and the controller includes a plurality of power modules and a plurality of motor controllers.

[0017] According to some embodiments of the present invention, the waste liquid bottle is fixed on the rear side of the main frame, the input end of the waste liquid bottle is connected to the suction tube, the output end of the waste liquid bottle is connected to the suction tube, and the suction tube is connected to the negative pressure end of the suction pump.

[0018] Additional aspects and advantages of the present invention will be set forth in part in the description which follows and, in part, will be obvious from the description which follows, or may be learned by practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the following description of the embodiments with reference to the accompanying drawings, in which:

[0020] Figure 1 is a schematic structural diagram of a DNA inkjet synthesis device according to some embodiments of the present invention;

[0021] Figure 2is a bottom view of a DNA inkjet synthesis device according to some embodiments of the present invention;

[0022] Figure 3 is a schematic structural diagram of a multi-channel inkjet head module in some embodiments of the present invention;

[0023] Figure 4 Schematic diagram of a multi-channel inkjet head module in some embodiments of the present invention Figure 1 ;

[0024] Figure 5 Schematic diagram of a multi-channel inkjet head module in some embodiments of the present invention Figure 2 ;

[0025] Figure 6 Schematic diagram of the structure of the injection pump module in some embodiments of the present invention.

[0026] Figure Number:

[0027] Main frame 100, power assembly 110, X-axis slide module 111, Y-axis slide module 112, Z-axis slide module 113, workbench 120;

[0028] Multi-channel inkjet head module 200, base 210, bottom plate 211, middle plate 212, embedded groove 2121, mounting block 2122, cover plate 213, positioning groove 2131, fixing block 2132, liquid blowing pipe 220, liquid suction pipe 230, air suction pipe 231, liquid channel pipe 240, liquid inlet pipe 241;

[0029] Syringe pump module 300, blowout pump 310, suction pump 320, liquid storage bottle 330, injection mechanism 340, drive member 341, injector 342, push rod 3421, waste liquid bottle 350, two-position three-way solenoid valve 360, vertical plate support 370;

[0030] Controller 400 , power module 410 , motor controller 420 . DETAILED DESCRIPTION

[0031] The following describes embodiments of the present invention in detail. Examples of the embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are intended only to explain the present invention and are not to be construed as limiting the present invention.

[0032] In the description of the present invention, it should be understood that descriptions involving orientations, such as up, down, front, back, left, right, etc., indicating orientations or positional relationships, are based on the orientations or positional relationships shown in the accompanying drawings. They are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation. Therefore, they cannot be understood as limitations on the present invention.

[0033] In the description of the present invention, "several" means one or more, "many" means more than two, "greater than," "less than," and "exceed" are understood to exclude the number itself, while "above," "below," and "within" are understood to include the number itself. The use of "first" and "second" in the description is solely for the purpose of distinguishing technical features and should not be construed as indicating or implying relative importance, implicitly specifying the number of the indicated technical features, or implicitly specifying the order of the indicated technical features.

[0034] In the description of the present invention, unless otherwise clearly defined, terms such as setting, installing, and connecting should be understood in a broad sense, and technicians in the relevant technical field can reasonably determine the specific meanings of the above terms in the present invention based on the specific content of the technical solution.

[0035] Reference Figures 1 to 6 An embodiment of the present invention provides a DNA inkjet synthesis device, including a main frame 100, a multi-channel inkjet head module 200, a syringe pump module 300 and a controller 400. The main frame 100 is the main body of the DNA inkjet synthesis device and is used to install other components. A miniaturized main frame 100 is used, and a power component 110 and a workbench 120 are provided on the main frame 100. The workbench 120 is used to carry a synthesis substrate. The synthesis substrate can be fixed by a clamp or directly loaded. The power assembly 110 includes an X-axis slide module 111, a Y-axis slide module 112 and a Z-axis slide module 113. The X-axis slide module 111 is arranged on one side of the workbench 120, the Y-axis slide module 112 is set on the X-axis slide module 111, and the Z-axis slide module 113 is set on the Y-axis slide module 112. The multi-channel inkjet head module 200 is connected to the Z-axis slide module 113. The multi-channel inkjet head module 200 can be driven by the X-axis slide module 111, the Y-axis slide module 112 and the Z-axis slide module 113 to realize movement in the X, Y and Z directions.

[0036] The multi-channel inkjet head module 200 includes a base 210, which is connected to a blowing tube 220, a suction tube 230 and a plurality of liquid tubes 240. It can be understood that the plurality of liquid tubes 240 can be set according to the number of chemical reagents actually used, or some margins can be reserved. The following is an explanation using 10 liquid tubes 240 as an example. The output end of the liquid tube 240 can produce μL-level small droplets. A nozzle can be set to produce μL-level small droplets, or the end of the liquid tube 240 can be set to a shape that can produce μL-level small droplets.

[0037] The injection pump module 300 is connected to the main frame 100. The injection pump module 300 includes a liquid blowing pump 310, a liquid suction pump 320, multiple liquid storage bottles 330 and an injection mechanism 340. The liquid blowing tube 220 is connected to the liquid blowing pump 310, the liquid suction tube 230 is connected to the liquid suction pump 320, and the liquid suction pump 320 is connected to the waste liquid bottle 350. After the experiment is completed, the waste liquid is sucked away and sent to the waste liquid bottle 350 through the liquid suction tube 230 and the liquid suction pump 320, and then the liquid blowing pump 310 and the liquid blowing tube 220 are used to blow dry the residual reagent on the synthetic substrate. The injection mechanism 340 is used to extract the liquid in the liquid storage bottle 330 and output it to the liquid line pipe 240; the controller 400 is connected to the main frame 100, and the power component 110, the injection pump module 300 and the controller 400 are electrically connected.

[0038] During operation, the DNA inkjet synthesis device, based on data provided by the DNA synthesis software, is controlled by the controller 400, which controls the power assembly 110 and the syringe pump module 300. This controls the various droplets produced by the multiple liquid channels 240 of the multi-channel inkjet head module 200, delivering the required base monomer solution, deprotection solution, capping solution, coupling solution, and oxidation solution, etc., which are then deposited onto the synthesis substrate on the workbench 120 in a sequence and at pre-set positions, automatically completing the cyclic synthesis steps of deprotection, nucleotide grafting, end-capping, and oxidation activation. The simplified design of the DNA inkjet synthesis device offers the advantages of being compact and portable. Each module is easy to assemble and deploy, with low self-assembly costs. It is easy for non-professional laboratory technicians to assemble and use, and can be installed in an anhydrous and oxygen-free glove box equipped in a typical laboratory, facilitating experiments.

[0039] Reference Figure 6In some embodiments, the injection mechanism 340 includes multiple driving members 341 and multiple injectors 342. The injector 342 can be a glass syringe with a piston chamber in which a piston is disposed. The piston push rod 3421 is connected to the driving member 341. The syringe is connected to the liquid tube 240 and the liquid inlet tube 241. The liquid inlet tube 241 is connected to the liquid storage bottle 330. The driving member 341 drives the push rod 3421 to draw chemical reagents from the liquid storage bottle 330 through the liquid inlet tube 241 and then output them through the liquid tube 240. Two one-way valves can be installed on the syringe to ensure that only liquid can be drawn in from the liquid inlet tube 241 and output from the liquid tube 240. The driving member 341 can be a structure such as a stepping motor with a screw-nut pair, a gear rack, or a standard part such as an electric push rod or a cylinder.

[0040] It can be understood that the injection mechanism 340 can adopt a two-position three-way solenoid valve 360, and the sample injector 342 and the two-position three-way solenoid valve 360 ​​correspond one to one, and there are also 10 of them. The normally open end of the two-position three-way solenoid valve 360 ​​is connected to the liquid line tube 240, and the normally closed end of the two-position three-way solenoid valve 360 ​​is connected to the liquid inlet tube 241. The common end of the two-position three-way solenoid valve 360 ​​is connected to the sample injector 342. When the sample injector 342 inhales, the two-position three-way solenoid valve 360 ​​actuates to connect the liquid inlet tube 241; when outputting, the two-position three-way solenoid valve 360 ​​actuates to connect the liquid line tube 240.

[0041] Reference Figure 1 and Figure 6 In some embodiments of the present invention, the injection pump module 300 includes a vertical plate bracket 370, which is installed at the rear end of the main frame 100. The 10 driving members 341 are divided into two groups and fixed on both sides of the vertical plate bracket 370. The 10 injectors 342 are also divided into two groups and arranged on the outside of the driving member 341. The liquid storage bottle 330 is arranged above the driving member 341. The blowing pump 310 and the suction pump 320 are fixed on both sides of the upper end of the vertical plate bracket 370. The arrangement is tight, the structure is compact, and the volume is reduced.

[0042] Reference Figures 3 to 5 In some embodiments of the present invention, the base 210 includes a bottom plate 211, an intermediate plate 212 and a cover plate 213. The side of the intermediate plate 212 is provided with multiple embedded grooves 2121, and each liquid tube 240 is installed in an embedded groove 2121. The bottom plate 211 covers the multiple embedded grooves 2121 to clamp the liquid tube 240. The cover plate 213 is provided with two positioning grooves 2131. The blowing tube 220 and the suction tube 230 are respectively installed in the two positioning grooves 2131. The intermediate plate 212 covers the two positioning grooves 2131 to clamp the blowing tube 220 and the suction tube 230.

[0043] It is understandable that, considering that the number of the liquid pipes 240 is 10, the base 210 may have two intermediate plates 212 , which are stacked, and each intermediate plate 212 is provided with five embedded grooves for easy installation.

[0044] It can be understood that in order to facilitate assembly, the sides of the two intermediate plates 212 are provided with mounting blocks 2122, and the mounting blocks 2122 of the two intermediate plates 212 are staggered, and the mounting blocks 2122 are fixed to the base plate 211 by bolts. The cover plate 213 is provided with a fixing block 2132, and the fixing block 2132 is fixed to the base plate 211 by bolts. The mounting blocks 2122 and the fixing blocks 2132 are also staggered, and the overall structure is easy to disassemble and assemble.

[0045] Reference Figure 1 In some embodiments of the present invention, the power component 110 has two X-axis slide modules 111, the two X-axis slide modules 111 are arranged on both sides of the workbench 120, the two ends of the Y-axis slide module 112 are installed on the two X-axis slide modules 111, and the Z-axis slide module 113 is installed in the center of the Y-axis slide module 112. The X-axis slide module 111, the Y-axis slide module 112 and the Z-axis slide module 113 can all adopt a screw nut pair driven by a stepper motor, which is conducive to precise position control.

[0046] Reference Figure 1 and Figure 2 In some embodiments of the present invention, four legs are provided on the bottom of the main frame 100, and the controller 400 is installed on the bottom of the main frame 100 to make full use of the space. The controller 400 includes multiple power modules 410 and multiple motor controllers 420 to respectively control the X-axis slide module 111, the Y-axis slide module 112, the Z-axis slide module 113, the blowing pump 310, the suction pump 320 and the driving part 341. The controller 400 controls multiple two-position three-way solenoid valves 360.

[0047] Reference Figure 1 In some embodiments of the present invention, the waste liquid bottle 350 is fixed to the rear side of the main frame 100 by a bracket, the input end of the waste liquid bottle 350 is connected to the pipette 230, the output end of the waste liquid bottle 350 is connected to the suction pipe 231, and the suction pipe 231 is connected to the negative pressure end of the suction pump 320. When aspirating liquid, the suction pump 320 sucks away the air in the waste liquid bottle 350, thereby generating suction to suck away the chemical reagent through the pipette 230.

[0048] The embodiments of the present invention are described in detail above with reference to the accompanying drawings. However, the present invention is not limited to the above embodiments. Various changes can be made within the knowledge of ordinary technicians in the relevant technical field without departing from the scope of the present invention.

Claims

1. DNA inkjet synthesis device, characterized in that, include: A main frame, wherein a power assembly and a workbench are provided on the main frame, wherein the workbench is used to carry the synthetic substrate, the power assembly includes an X-axis slide module arranged on one side of the workbench, a Y-axis slide module is provided on the X-axis slide module, and a Z-axis slide module is provided on the Y-axis slide module; A multi-channel inkjet head module is connected to the Z-axis slide module. The multi-channel inkjet head module includes a base, to which a liquid blowing pipe, a liquid suction pipe, and a plurality of liquid pipes are connected. The output end of the liquid pipe can produce μL-level droplets. A syringe pump module is connected to the main frame, comprising a blowout pump, a suction pump, a plurality of liquid storage bottles, and an injection mechanism. The blowout tube is connected to the blowout pump, the suction tube is connected to the suction pump, and the suction pump is connected to a waste liquid bottle. The injection mechanism is used to extract liquid from the liquid storage bottles and output it to the liquid line tube. A controller connected to the main frame, the power assembly, the injection pump module and the controller are electrically connected; The injection mechanism includes multiple driving members and multiple injectors, each of which is provided with a piston cavity in which a piston is arranged, a push rod of the piston is connected to the driving member, and the injector is connected to the liquid line tube and the liquid inlet tube, and the liquid inlet tube is connected to the liquid storage bottle; The injection mechanism further comprises a two-position three-way solenoid valve, wherein the normally open end of the two-position three-way solenoid valve is connected to the liquid pipe, the normally closed end of the two-position three-way solenoid valve is connected to the liquid inlet pipe, and the common end of the two-position three-way solenoid valve is connected to the injector; The waste liquid bottle is fixed on the rear side of the main frame, the input end of the waste liquid bottle is connected to the suction pipe, the output end of the waste liquid bottle is connected to the suction pipe, and the suction pipe is connected to the negative pressure end of the suction pump.

2. The DNA inkjet synthesis device according to claim 1, characterized in that The injection pump module includes a vertical plate bracket, multiple driving members are fixed on both sides of the vertical plate bracket, multiple injectors are arranged on the outside of the driving member, the liquid storage bottle is arranged above the driving member, and the blowing pump and the suction pump are fixed on both sides of the upper end of the vertical plate bracket.

3. The DNA inkjet synthesis device according to claim 1, characterized in that The machine base includes a bottom plate, an intermediate plate and a cover plate. The side of the intermediate plate is provided with multiple embedded grooves, the liquid pipe is installed in the embedded grooves, the bottom plate covers the multiple embedded grooves, the cover plate is provided with two positioning grooves, the blowing pipe and the suction pipe are installed in the positioning grooves, and the middle plate covers the two positioning grooves.

4. The DNA inkjet synthesis device according to claim 3, characterized in that The machine base has two intermediate plates, which are stacked together, and each intermediate plate is provided with five embedded grooves.

5. The DNA inkjet synthesis device according to claim 4, characterized in that The sides of the two intermediate plates are each provided with a mounting block, which is fixed to the bottom plate by bolts. The cover plate is provided with a fixing block, which is fixed to the bottom plate by bolts. The mounting block is staggered with the fixing block.

6. The DNA inkjet synthesis device according to claim 1, characterized in that The power assembly has two X-axis slide modules, and the two X-axis slide modules are arranged on both sides of the workbench.

7. The DNA inkjet synthesis device according to claim 1, characterized in that The controller is installed on the bottom surface of the main frame, and the controller includes multiple power modules and multiple motor controllers.

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