High-throughput DNA synthesis device based on ink-jet printing

Abstract

The invention relates to a high-throughput DNA synthesis device based on ink-jet printing. The high-throughput DNA synthesis device comprises a plurality of ink boxes, a sealing assembly, a lifting assembly, a bearing jig and a moving assembly. Each ink box is arranged at the corresponding ink jet station and is used for temporarily storing the DNA basic group reagent and jetting the DNA basic group reagent through an ink jet port, and the ink jet port can automatically control the volume of liquid drops. The bearing jig is used for bearing the reaction pore plate. And the plurality of sealing assemblies are respectively arranged at the reaction stations and are used for being in sealing fit with the bearing jig to form a closed reaction cavity. The multiple lifting assemblies are arranged on the connection stations below the reaction station and used for driving the bearing jig to rise, and the reaction pore plate is matched with the sealing assembly. The moving assembly is used for driving the bearing jig to move between the ink jet station and the connection station. According to the invention, the parallel operation of reagent ink jet, closed reaction and reaction and sample adding is realized, the liquid drop control precision, the reaction stability and the equipment operation efficiency are improved, and the device is suitable for high-density and high-flux DNA synthesis scenes.

Description

Technical Field

[0001] This invention relates to the field of inkjet printing technology, and in particular to a high-throughput DNA synthesis device based on inkjet printing. Background Technology

[0002] DNA synthesis technology is a crucial foundational support for many cutting-edge fields, including bioengineering, pharmaceutical development, disease diagnosis, and data storage. In recent years, with the expansion of synthesis scale and the increasing demand for personalization, the research and application of high-throughput DNA synthesis equipment have received widespread attention.

[0003] Currently, commonly used high-throughput DNA synthesis methods mainly employ a multi-channel pipette loading method, which involves adding various reaction reagents required for synthesis to the target region in stages using a multi-channel pipette to complete the stepwise synthesis of nucleotides. While this method offers a certain level of automation, it still presents the following technical challenges: First, when switching between different reagents, the pipette tip needs to be changed frequently, which is cumbersome and consumes a lot of consumables, increasing operating costs.

[0004] Second, the traditional tip-head sample addition method requires each reagent to be aspirated and added separately, which is costly and time-consuming, making it difficult to meet the needs of high throughput. Furthermore, since the spacing between tip heads is fixed, it is difficult to adapt to high-density reaction plates, which limits the improvement of throughput.

[0005] Third, the entire synthesis process usually relies on multiple independent devices (such as spotting devices, reaction devices, and cleaning devices) to work together. The system integration is low, the operation process is complex, the space occupied is large, and the overall work efficiency is low, making it difficult to meet the actual application needs of high-density, high-throughput DNA synthesis. Summary of the Invention

[0006] Therefore, the technical problem to be solved by the present invention is to overcome the problems in the prior art and provide a high-throughput DNA synthesis device based on inkjet printing.

[0007] To address the aforementioned technical problems, this invention provides a high-throughput DNA synthesis apparatus based on inkjet printing, comprising: Multiple ink cartridges, each used to temporarily store a selected DNA base reagent, each ink cartridge is set at a corresponding inkjet station, and each ink cartridge is connected to an inkjet nozzle for spraying the reagent to a target area located below it. Multiple support fixtures are used to support reaction plate with multiple reaction holes; Multiple sealing components are used to seal with the support fixture to form a closed reaction chamber for accommodating the reaction plate. Each sealing component is disposed at a corresponding reaction station, and a connection station is provided below each reaction station. A movable component for driving the carrier fixture to reciprocate between the target area below the inkjet station and the connecting station; and, Multiple lifting components are initially positioned below the docking station. They are used to rise and dock with the carrying fixture when the carrying fixture moves to the docking station, and during the continued rising process, they drive the carrying fixture and the reaction orifice plate to rise away from the moving components until they reach the reaction station, thereby enabling the carrying fixture to seal with the corresponding sealing component.

[0008] In one embodiment of the present invention, a working box is also included, wherein the plurality of ink cartridges are arranged at intervals along the X-axis on the top plate of the working box, and the top plate is provided with a clearance hole at the position corresponding to the inkjet nozzle, so that the ejected droplets can pass through the clearance hole and enter the target area below. The multiple sealing components are also arranged at intervals along the X-axis on the top plate of the work box, and are arranged parallel to the multiple ink cartridges; The support fixture, lifting assembly, and moving assembly are arranged inside the working chamber. The lifting assembly can drive the support fixture to move up and down along the Z-axis, and the moving assembly can drive the support fixture to move along the X-axis and Y-axis, so as to realize the transfer between any inkjet station and any connecting station.

[0009] In one embodiment of the present invention, the outer side of the working chamber is provided with an input pipe for introducing protective gas, so that the internal cavity of the working chamber forms a protective atmosphere environment.

[0010] In one embodiment of the present invention, the moving component includes an X-axis motorized slide, a Y-axis motorized slide, and a connecting fork. The Y-axis electric slide is slidably connected to the X-axis electric slide, and the connecting fork is slidably connected to the Y-axis electric slide. The connecting fork is used to carry and transfer the carrying fixture to the connecting position.

[0011] In one embodiment of the present invention, the moving component further includes a slider and a guide rail, the guide rail being arranged parallel to the X-axis electric slide, one end of the Y-axis electric slide being slidably connected to the X-axis electric slide, and the other end cooperating with the guide rail through the slider.

[0012] In one embodiment of the present invention, a first positioning post is provided on the connecting fork, and a first positioning hole is provided at the bottom of the bearing fixture. The first positioning post cooperates with the first positioning hole to achieve bearing positioning.

[0013] In one embodiment of the present invention, the lifting assembly includes a lifting cylinder and a lifting plate connected to the telescopic rod of the lifting cylinder.

[0014] In one embodiment of the present invention, a second positioning post is provided on the lifting plate, and a second positioning hole is provided at the bottom of the bearing fixture, wherein the second positioning post matches the second positioning hole.

[0015] In one embodiment of the present invention, the sealing assembly includes an opening formed on the top surface of the top plate of the work box, and an openable sealing cover disposed at the opening; When the support fixture and the reaction orifice plate are raised to the reaction station, the reaction orifice plate extends into the opening, and the support fixture fits against the bottom surface of the top plate of the work box, thereby forming a closed reaction chamber with the sealing cover.

[0016] In one embodiment of the present invention, the support fixture includes a T-shaped block having a receiving groove for accommodating the reaction plate, wherein the top surface of the reaction plate extends beyond the top surface of the T-shaped block. The bottom surface of the top plate of the work box is provided with a positioning groove, which is connected to the opening. When the supporting fixture is raised to the reaction position, the lateral part of the T-block extends into the positioning groove and is in close contact with the bottom of the groove.

[0017] In one embodiment of the present invention, the supporting fixture further includes a waste liquid cavity located below the receiving tank, the waste liquid cavity being connected to the receiving tank, and a supporting surface for supporting the reaction orifice plate being provided at the connection between the receiving tank and the waste liquid cavity, the waste liquid cavity being used to collect waste liquid falling from all the holes of the reaction orifice plate.

[0018] In one embodiment of the present invention, the bottom of the supporting fixture is provided with a drain port, and the drain port is provided with an openable valve structure for discharging waste liquid in the waste liquid chamber when needed.

[0019] In one embodiment of the present invention, the valve structure includes a female valve head, a male valve head, and a threaded cylinder mounted on the lifting assembly. The female valve head is installed at the drain port, and the screw of the threaded cylinder extends along the lifting direction and is fixedly connected to the male valve head through a connector. When the bearing fixture is in the reaction position, the male valve head can be inserted into the female valve head and open its internal valve core when the screw of the threaded cylinder extends, so that a communication passage is formed between the female valve head, the male valve head and the connector, thereby discharging waste liquid from the connector.

[0020] In one embodiment of the present invention, the sealing cover is provided with a first high-pressure gas pipe and a second high-pressure gas pipe communicating with the sealed reaction chamber. The first high-pressure gas pipe is used to input a first set high-pressure gas required for the reaction into the sealed reaction chamber, and the second high-pressure gas pipe is used to input a second set high-pressure gas to remove waste liquid from the reaction orifice plate into the sealed reaction chamber.

[0021] In one embodiment of the present invention, a pressure detector is provided on the sealing cover for detecting the gas pressure inside the sealed reaction chamber.

[0022] In one embodiment of the present invention, a plurality of ink bottles are further included, each ink bottle being used to store a selected DNA base reagent and being connected to the corresponding ink cartridge.

[0023] In one embodiment of the present invention, a plurality of liquid receiving boxes are further included, which are disposed one-to-one below the plurality of ink cartridges for receiving DNA base reagents splashed from the inkjet nozzle.

[0024] Compared with the prior art, the above-described technical solution of the present invention has the following advantages: The inkjet printing method of this invention is a non-contact operation, avoiding the operational complexity and consumable waste caused by frequent tip head replacements in traditional multi-gun printing. Simultaneously, after inkjet printing, the ink cartridge can promptly collect excess or accidentally sprayed reagent through a corresponding drip tray below, effectively preventing droplet contamination and printhead clogging, thereby reducing reagent waste and enhancing the stability and cleanliness of equipment operation.

[0025] The high-throughput DNA synthesis apparatus based on inkjet printing provided by this invention mainly includes an ink cartridge support fixture, a sealing assembly, a lifting assembly, and a moving assembly. Multiple ink cartridges are used to temporarily store selected DNA base reagents, and each inkjet nozzle preferably uses a piezoelectric inkjet method for reagent dispensing, enabling precise control of the volume of each ejected droplet.

[0026] The support fixture in this invention is used to support a reaction plate with multiple reaction wells, and is driven by a moving component to move between the target area below the inkjet station and the connection station, realizing automatic switching between multiple stations. Compared with the complex process in the prior art where the reaction unit and the sample loading unit belong to different devices and require manual or robotic arm transfer of samples, this invention completes the two key steps of inkjet sample loading and reaction processing in a single device through an integrated structure, which improves system integration, simplifies the process flow, reduces equipment operation and maintenance costs, and improves overall operating efficiency. It is suitable for high-throughput, rapid-reaction DNA synthesis scenarios.

[0027] In this invention, the lifting assembly is initially positioned below the docking station and cooperates with the carrying fixture. When the carrying fixture moves to the docking station, it rises to dock with the fixture, and then continues to rise, propelling it into the reaction station. This allows the reaction plate to tightly engage with the sealing assembly above, forming a sealed reaction chamber. This structure effectively isolates the external environment, preventing impurities or interfering gases from entering the reaction area, while also preventing the volatilization of reaction reagents, ensuring the stability of reaction conditions, and improving the reliability of DNA synthesis.

[0028] In this invention, the carrier fixture can reciprocate between the target area below the inkjet station and the docking station. At the docking station, a lifting component rises from below to connect the carrier fixture, and then continues to rise to push it into the reaction station, causing the reaction plate to fit against the sealing component, completing the sealing reaction operation. Since multiple carrier fixtures can alternately operate between stations, reagent inkjet printing and reaction operations can be performed in parallel without interference. This structural design effectively reduces waiting time between stations, improves overall operational efficiency, and thus better meets the efficiency and cycle time requirements of high-throughput DNA synthesis processes. Attached Figure Description

[0029] To make the content of this invention easier to understand, the invention will be further described in detail below with reference to specific embodiments and accompanying drawings, wherein... Figure 1 This is a schematic diagram of the structure of a DNA synthesis device based on inkjet printing in a preferred embodiment of the present invention; Figure 2 This is a schematic diagram of the main body of the DNA synthesis device based on inkjet printing in a preferred embodiment of the present invention; Figure 3 This is a schematic diagram of the main body of the DNA synthesis device based on inkjet printing in a preferred embodiment of the present invention (with the working chamber removed). Figure 4 This is a side view of a DNA synthesis apparatus based on inkjet printing in a preferred embodiment of the present invention (with the work chamber removed). Figure 5 This is a schematic diagram of the structure of the moving component in a preferred embodiment of the present invention; Figure 6 This is a schematic diagram of the Y-axis electric slide table in a preferred embodiment of the present invention; Figure 7 This is a schematic diagram of the lifting assembly and valve structure in a preferred embodiment of the present invention; Figure 8 This is a schematic diagram of the lifting assembly in a preferred embodiment of the present invention; Figure 9 This is a schematic diagram showing the state of the support fixture supporting the reaction orifice plate in a preferred embodiment of the present invention; Figure 10 This is a schematic diagram of the structure of the support fixture in a preferred embodiment of the present invention; Figure 11 This is a schematic diagram of the bottom structure of the support fixture in a preferred embodiment of the present invention; Figure 12 This is a schematic diagram of the sealing cap in a preferred embodiment of the present invention; Figure 13 This is a schematic diagram of the openings and positioning grooves on the top plate of the work box, cut along the XZ direction in a preferred embodiment of the present invention.

[0030] Explanation of reference numerals in the accompanying drawings: 10, Ink cartridge; 20, Support fixture; 21, Receiving groove; 22, Waste liquid chamber; 23, Supporting surface; 24, First positioning hole; 25, Second positioning hole; 26, Lateral portion of the T-block; 30, Sealing assembly; 31, Sealing cover; 311, Hinge; 312, Handle; 40, Lifting assembly; 41, Lifting cylinder; 42, Lifting plate; 421, Second positioning post; 43, Vertical plate; 44, Mounting plate; 50, Moving assembly; 51. X-axis electric slide; 52. Y-axis electric slide; 53. Slider; 54. Guide rail; 55. Connecting fork; 551. First positioning post; 60. Reaction orifice plate; 70. Working box; 71. Opening; 72. Positioning groove; 80. Pressure detector; 90. Valve structure; 91. Valve female head; 92. Valve male head; 93. Threaded cylinder; 94. Connector; 100. Electrical control box; 110. Operation panel; 120. Input pipe; 130. Liquid receiving box. Detailed Implementation

[0031] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, so that those skilled in the art can better understand and implement the present invention. However, the embodiments described are not intended to limit the present invention.

[0032] See Figures 1 to 4As shown, this embodiment of the invention discloses a high-throughput DNA synthesis apparatus based on inkjet printing, including multiple ink cartridges 10, a support fixture 20, multiple sealing components 30, multiple lifting components 40, and a moving component 50. Furthermore, the high-throughput DNA synthesis apparatus based on inkjet printing also includes an electrical control box 100 and an operation box 110 with an operation screen.

[0033] Multiple ink cartridges 10 are respectively installed at multiple inkjet printing stations. Each ink cartridge 10 temporarily stores a DNA base reagent, such as adenine (A), guanine (G), thymine (T), and cytosine (C), and has an inkjet nozzle communicating with its interior. The inkjet nozzle uses piezoelectric inkjet technology, which can precisely control the volume of the ejected droplets to spray the reagent onto the target area located below it, i.e., the corresponding position of the reaction plate 60. The ink cartridges 10 can be commercially available automatic inkjet cartridges 10. Of course, the inkjet method is not limited to piezoelectric inkjet; it can also be automatic inkjet methods such as pneumatic inkjet and electromagnetic inkjet.

[0034] The support fixture 20 is used to mount and support the reaction plate 60. Each support fixture 20 supports one reaction plate 60, and the reaction plate 60 has multiple reaction wells for DNA synthesis reactions. Preferably, the reaction plate 60 can be a 96-well plate, but is not limited to this structure.

[0035] Multiple sealing components 30 are respectively installed at multiple reaction stations to seal with the corresponding support fixtures 20 to form a closed reaction chamber surrounding the reaction orifice plate 60, ensuring that the reaction process is not disturbed by the external environment.

[0036] Multiple lifting components 40 are installed one-to-one on the connection station below each reaction station to connect the carrying fixture 20 and drive it to rise and fall, so as to realize the lifting and transfer of the fixture from the connection station to the reaction station.

[0037] The moving component 50 is used to drive multiple carrier fixtures 20 to move between the target area below the inkjet station and the docking station, thereby realizing the cyclic switching between inkjet sample dispensing and reaction operations.

[0038] During operation, multiple reaction well plates 60 are first mounted on their corresponding support fixtures 20. The moving component 50 drives the support fixtures 20 to move sequentially to the target areas below the multiple inkjet stations. The ink cartridge 10, based on the required base type, sprays specific DNA base reagents as micro-droplets into the corresponding reaction wells through the inkjet nozzle. If a reaction well plate 60 does not require the reagent from a particular inkjet station, that inkjet step is skipped to avoid accidental spraying. The piezoelectric inkjet structure ensures good repeatability and stability of the spray volume, thereby ensuring consistent sample volume across all reaction wells and improving reaction reliability and experimental reproducibility.

[0039] After inkjet printing is completed, the moving component 50 moves the carrier fixture 20 to the docking station and connects with the lifting component 40. The lifting component 40 rises, bringing the carrier fixture 20 and the reaction orifice plate 60 into the upper reaction station. The reaction orifice plate 60 and the sealing component 30 are sealed together to form a closed reaction chamber for closed environment control of subsequent reaction steps.

[0040] After the reaction is complete, the lifting assembly 40 descends to the receiving station, where the moving assembly 50 receives and carries the fixture 20. The lifting assembly 40 then continues to descend and detaches from the fixture, while the moving assembly 50, carrying the fixture 20, moves to the inkjet station to begin the next inkjet or reaction cycle. While a fixture 20 is moving to the inkjet station and undergoing inkjet processing, the reaction plates 60 at other reaction stations can continue to perform base synthesis reactions. This allows for parallel operation of inkjet sample addition and the reaction process, avoiding waiting at a single station and improving equipment operating efficiency and continuous production cycle time.

[0041] The high-throughput DNA synthesis device based on inkjet printing provided in this invention mainly includes ink cartridges 10, a support fixture 20, a sealing assembly 30, a lifting assembly 40, and a moving assembly 50. Multiple ink cartridges 10 are used to temporarily store selected DNA base reagents. Each inkjet nozzle uses piezoelectric inkjet technology for reagent dispensing, enabling precise control of the volume of each ejected droplet. Compared to the problems of unstable droplet volume and uneven dispensing in existing dot-matrix nozzle dispensing methods, this device, through piezoelectric control, ensures that each reaction well receives the same volume of base reagent, thereby improving the accuracy and consistency of dispensing and enhancing the quality of DNA synthesis.

[0042] In this embodiment of the invention, the support fixture 20 is used to support the reaction plate 60 and is moved between the inkjet station and the docking station by the moving component 50, realizing automatic switching between multiple stations. Compared with the complex process in the prior art where the reaction unit and the sample loading unit belong to different devices and require manual or robotic arm transfer of samples, the present invention completes the two key steps of inkjet sample loading and reaction processing in a single device through an integrated structure, which improves the system integration, simplifies the process flow, reduces equipment operation and maintenance costs, and improves overall operating efficiency. It is suitable for high-throughput, rapid-reaction DNA synthesis scenarios.

[0043] The inkjet printing method of this invention is a non-contact operation, which avoids the operational complexity and waste of consumables caused by the frequent replacement of tip heads in the traditional array gun method.

[0044] The high-throughput DNA synthesis device based on inkjet printing disclosed in this invention is not only suitable for DNA sequence synthesis, but can also be flexibly applied to various biochemical experimental scenarios involving precise distribution of trace liquids and closed reactions, such as RNA synthesis and peptide synthesis.

[0045] See Figures 1 to 4 As shown, specifically, multiple ink cartridges 10 are spaced apart along the X-axis and mounted above the top plate of the work chamber 70. Each ink cartridge 10 has an inkjet nozzle at its bottom, which faces a clearance hole on the top plate, allowing the ejected droplets to accurately pass through the clearance hole and fall into the target area of ​​the reaction plate 60 directly below it. Multiple sealing assemblies 30 are also spaced apart along the X-axis on the top plate of the work chamber 70 and arranged parallel to the multiple ink cartridges 10, so that the sample application area and the reaction area are spatially arranged side by side.

[0046] The support fixture 20, lifting assembly 40, and moving assembly 50 are uniformly arranged within the internal cavity of the work box 70. The lifting assembly 40 is vertically mounted and drives the support fixture 20 up and down along the Z-axis to achieve lifting and lowering of the support fixture 20 between the docking station and the reaction station, thereby completing the docking and disengagement of the reaction orifice plate 60 and the sealing assembly 30. The moving assembly 50 can drive the support fixture 20 to move in both the X and Y axes to achieve efficient transfer between any inkjet station and any docking station.

[0047] In addition, the work box 70 is mounted on the electrical control box 100, and the bottom of the electrical control box 100 is equipped with casters for movement. The electrical control box integrates electrical control components and other parts, and also serves as the supporting base for the entire equipment. The operation box 110 is mounted on the electrical control box 100 by a bracket and has a certain height to facilitate the operator's operation of the control panel.

[0048] By arranging the ink cartridge 10 and sealing assembly 30 in parallel along the X-axis, and by coordinating the movement of the support fixture 20 in the X-axis and Y-axis directions with its vertical lifting action in the Z-axis direction, multiple inkjet stations and reaction stations can be operated alternately and in parallel. This allows for continuous and efficient inkjet sample loading and reaction operations within a limited equipment space, improving the space utilization and operating cycle of the equipment.

[0049] See Figure 1 As shown, in this embodiment of the invention, an input pipe 120 is provided on the outside of the working chamber 70. This input pipe 120 is used to continuously input a protective gas into the internal cavity of the working chamber 70. The protective gas can be an inert gas such as nitrogen or argon. After being introduced through the input pipe 120, it forms a protective atmosphere within the sealed cavity of the working chamber 70, ensuring that the internal environment is isolated from the external air and preventing external moisture, oxygen, or dust from entering the reaction area, thereby reducing interference from the external environment on the synthesis reaction.

[0050] See Figures 3 to 6 ,as well as Figure 10As shown, in this embodiment of the invention, the moving component 50 includes an X-axis electric slide 51, a Y-axis electric slide 52, and a connecting fork 55. The X-axis electric slide 51 is horizontally disposed on the bottom structure inside the work box 70 (e.g., mounted on a base plate), serving as the main load-bearing platform of the moving component 50; the Y-axis electric slide 52 is slidably disposed on the X-axis electric slide 51 and can move along the X-axis direction, forming an orthogonal moving structure; the connecting fork 55 is slidably disposed on the Y-axis electric slide 52 and can achieve linear reciprocating motion along the Y-axis direction, used for transporting and positioning the load-bearing fixture 20.

[0051] The connecting fork 55 is used to support the carrying fixture 20 and move it from the target area below the inkjet station to above the lifting assembly 40 at the connecting station. Through the linkage movement of the XY orthogonal slide table and the connecting fork 55 structure, the carrying fixture 20 can be accurately positioned and smoothly transported in a two-dimensional plane, thereby ensuring that the reaction plate 60 can be accurately aligned below the predetermined position of the inkjet station and the reaction station, and cooperate with the lifting assembly 40 to complete the switching between inkjet sample addition and sealing reaction processes.

[0052] Furthermore, the moving assembly 50 also includes a slider 53 and a guide rail 54, with the guide rail 54 arranged parallel to the moving direction of the X-axis electric slide 51. One end of the Y-axis electric slide 52 is slidably connected to the X-axis electric slide 51 via the slider 53, and the other end is connected to the connecting fork 55, thereby ensuring that the connecting fork 55 runs smoothly during movement.

[0053] Furthermore, the connecting fork 55 is provided with a first positioning post 551, and the bottom of the carrying fixture 20 is provided with a first positioning hole 24 that mates with it. The first positioning post 551 and the first positioning hole 24 are positioned opposite each other and matched in size. When the connecting fork 55 moves to the designated position, the fixture can be automatically limited and aligned to prevent deviation during the transfer process.

[0054] See Figures 7 to 11 As shown, in this embodiment of the invention, the lifting assembly 40 adopts a dual-cylinder lifting structure. Each lifting assembly 40 includes two sets of lifting cylinders 41 arranged side by side. The two cylinders are fixedly installed at the bottom inside the work box 70. The telescopic rod of each lifting cylinder 41 is connected to a horizontally arranged lifting plate 42, and the two lifting plates 42 are flush with each other. The two lifting plates 42 are used to jointly receive and support the bearing fixture 20, thereby driving the vertical lifting of the reaction orifice plate 60.

[0055] Driven synchronously by the two lifting cylinders 41, the lifting plate 42 drives the supporting fixture 20 to rise and fall along the Z-axis, so that the reaction orifice plate 60 is lifted to the corresponding reaction position and seals with the sealing component 30 above, thereby forming a closed reaction chamber.

[0056] To ensure rapid positioning and stable support of the support fixture 20 during lifting, a second positioning post 421 is provided on the upper surface of each lifting plate 42. Specifically, one second positioning post 421 is provided on the upper surface of one lifting plate 42 near its inner edge, and another second positioning post 421 is provided on the upper surface of the other lifting plate 42 near its inner edge, with the two second positioning posts 421 staggered. Two second positioning holes 25 are provided at corresponding positions on the bottom of the support fixture 20, and the second positioning posts 421 match the second positioning holes 25. The second positioning holes 25 are located outside the first positioning holes 24.

[0057] See Figures 12 to 13 As shown, in this embodiment of the invention, the sealing assembly 30 includes an opening 71 on the top surface of the top plate of the working chamber 70, and an openable and closable sealing cover 31 disposed at the opening 71. When the reaction orifice plate 60 is raised to the reaction station by the lifting assembly 40, its upper end engages with the opening of the sealing assembly 30, and the sealing cover 31 is pressed down, forming a closed reaction chamber surrounding the reaction orifice plate 60 with the supporting fixture 20. This structure can effectively isolate external air, prevent gas exchange and reagent evaporation, and ensure the stable progress of the synthesis process. Furthermore, the sealing cover 31 is provided with a first high-pressure gas pipe communicating with the sealed reaction chamber. The first high-pressure gas pipe can input a first set high-pressure gas required for the reaction into the sealed reaction chamber. The pressure of the first set high-pressure gas is 8-15 psi.

[0058] In terms of specific structure, the sealing cover 31 and the opening 71 are connected by a hinge 311, which allows for opening and closing. A handle 312 can also be provided on the sealing cover 31 for easy opening and closing. The sealing parts can be equipped with soft sealing materials such as silicone rings or fluororubber rings, depending on the application requirements, to further improve sealing performance.

[0059] The support fixture 20 includes a block that is T-shaped in overall shape, with a receiving groove 21 on its top for mounting the reaction plate 60. The receiving groove 21 can be a square groove. After the reaction plate 60 is installed, its top slightly extends beyond the top surface of the T-shaped block.

[0060] The bottom surface of the top plate of the work box 70 is provided with a positioning groove 72, which is connected to the opening 71. When the support fixture 20 is raised to the reaction position, the transverse part 26 of the T-block extends into the positioning groove 72 and is pressed against the bottom of the groove, thereby playing the role of positioning and stabilizing the support fixture 20.

[0061] The support fixture 20 also includes a waste liquid chamber 22 located below the receiving tank 21. The waste liquid chamber 22 is connected to the receiving tank 21. The connection between the receiving tank 21 and the waste liquid chamber is provided with a support surface 23 for supporting the reaction orifice plate 60. The waste liquid chamber 22 is used to collect the waste liquid falling from all the holes of the reaction orifice plate 60.

[0062] Furthermore, the sealing cover 31 is provided with a second high-pressure gas pipe communicating with the sealed reaction chamber, for introducing a second set high-pressure gas into the sealed reaction chamber to remove waste liquid from the reaction orifice plate 60. This second set high-pressure gas can be blown in from above the reaction orifice plate 60, so that the residual reaction waste liquid or unreacted liquid in the reaction orifice is carried by the airflow under high pressure and discharged from the small drain hole at the bottom of the reaction orifice, and enters the waste liquid chamber 22 below for collection.

[0063] It should be noted that each reaction well of the reaction plate 60 is used to hold various DNA base reagents required for the reaction. To facilitate waste liquid discharge, each reaction well has a drain hole at its bottom. Due to the small size of this drain hole, the initial high-pressure gas input during the reaction will not cause liquid to flow out of the drain hole, thus ensuring the airtightness and liquid stability of the reaction process. After the reaction is completed, a second high-pressure gas with an even higher pressure is introduced through a second high-pressure gas pipe, causing the waste liquid to be discharged from the drain hole. The pressure of the second high-pressure gas is 30-80 PSI. During this process, the target product generated by the reaction will not be discharged with the gas flow, achieving effective waste liquid removal and reaction product retention, thereby achieving a cleaning effect.

[0064] See Figure 12 As shown, in this embodiment, a pressure detector 80 is integrated on the sealing cover 31, which is connected to the sealed reaction chamber through a preset guide tube or interface for real-time acquisition of gas pressure data within the sealed chamber. The pressure detector 80 can be a resistive pressure sensor, a capacitive sensor, or a MEMS pressure sensing element, offering high detection accuracy, fast response speed, and stable feedback of the current gas state within the reaction chamber.

[0065] During the synthesis reaction stage, reaction gas is introduced into the reaction chamber through the first set high-pressure gas pipeline. The pressure detector 80 monitors the gas pressure value in real time, and the control system can use this to determine whether the airtightness is good, ensuring that the reaction is carried out under the set pressure environment and improving the reliability of the reaction. During the cleaning stage, when the second set high-pressure gas enters the sealed reaction chamber to remove waste liquid residue, the pressure detector 80 can also be used to help determine whether the cleaning process meets the standards, so as to avoid residue affecting the results of the next reaction.

[0066] Furthermore, the pressure detector 80 can also be connected to the main control system to form a closed-loop control mechanism, realizing automatic adjustment or abnormal alarm when the air pressure is too high or too low, thereby ensuring the safety and stability of the system operation.

[0067] To prevent liquid accumulation from affecting subsequent processes, a drain port is designed at the bottom of the support fixture 20, and is connected to a set of control valve structures 90 for discharging waste liquid from the waste liquid chamber 22 when needed. The valve structures 90 are located in the space formed between the two lifting cylinders 41.

[0068] See Figures 7 to 8 As shown, to achieve automatic discharge of waste liquid after the reaction, the valve structure 90 includes a female valve head 91 and a male valve head 92 mounted on the lifting assembly 40. The female valve head 91 is installed at the discharge port. A threaded cylinder 93 is mounted on the lifting assembly 40, with its screw arranged along the lifting direction and fixedly connected to the male valve head 92 via a connector 94, allowing the male valve head 92 to move up and down under the drive of the threaded cylinder 93. A vertical plate 43 is fixedly connected to the inner side of each of the two lifting plates 42, and the two vertical plates 43 are connected by a horizontally arranged mounting plate 44. The vertical plates 43 and the mounting plate 44 form a mounting bracket, and the threaded cylinder 93 is mounted on the mounting plate 44. The entire valve structure 90 can rise together with the lifting plates 42.

[0069] When the support fixture 20 moves to the docking station under the drive of the moving component 50, and is then raised to the reaction station by the lifting component 40, it remains at a set height and stops moving. At this time, if waste liquid needs to be discharged, the threaded cylinder 93 is activated to push the screw out, causing the male valve head 92 to be inserted upward into the corresponding female valve head 91. After the male valve head 92 is inserted into place, its front end's pushing mechanism pushes open the valve core inside the female valve head 91, connecting the female valve head 91 and the male valve head 92, and forming a liquid flow path with the connector 94.

[0070] Through this liquid flow path, the waste liquid that has completed the reaction in the reaction orifice plate 60 flows into the connector 94 through the valve female head 91 and the valve male head 92, and is then discharged to the external waste liquid collection device through the drain pipeline, thereby completing the automatic liquid discharge operation.

[0071] The aforementioned drainage mechanism is integrated into the lifting assembly 40, which not only saves space and simplifies the structure, but also enables automatic drainage within the reaction station. The male valve 92 forms a sealed connection with the female valve upon insertion, ensuring that waste liquid is discharged only through the designated channel and does not leak from the interface, thereby preventing pollution of the surrounding environment or affecting the cleanliness of the reaction area.

[0072] In embodiments of the present invention, the high-throughput DNA synthesis apparatus based on inkjet printing further includes multiple ink bottles (not shown in the figure), each ink bottle for storing a DNA base reagent, such as adenine (A), guanine (G), thymine (T), and cytosine (C). Each ink bottle is in fluid communication with a corresponding ink cartridge 10 via a connecting hose or rigid supply tube, for providing a stable and continuous reagent supply to the ink cartridge 10. The ink bottles are preferably made of corrosion-resistant material with a sealing cap 31, and may have a structure with pressure regulation function, and internally equipped with a reagent level scale or level sensor for easy observation or monitoring of reagent balance. The ink bottles can be placed inside the electrical control box 100 or the operation box 110.

[0073] During use, when the reagent in ink cartridge 10 is about to run out, the liquid reagent in the ink bottle can be automatically replenished into ink cartridge 10 through the connecting pipe, eliminating the need for frequent replacement of ink cartridge 10, thereby extending the continuous operation time of the device, reducing the frequency of manual intervention, and improving the efficiency of synthesis operations.

[0074] See Figure 5 As shown in the embodiments of the present invention, the high-throughput DNA synthesis apparatus based on inkjet printing further includes multiple collection boxes 130, which are respectively disposed below the inkjet nozzles of corresponding ink cartridges 10, and arranged one-to-one with the inkjet station. Each collection box 130 is used to collect DNA base reagents that may drip or splash from the inkjet nozzles when not in inkjet operation, to prevent reagent contamination of the device interior or liquid waste. The collection boxes 130 are preferably made of corrosion-resistant and easy-to-clean materials.

[0075] During inkjet printing, if the carrier fixture 20 has not yet moved into place, or if a certain base reagent is not needed at the moment, the liquid receiving box 130 under the printhead can catch the sprayed reagent, such as the liquid sprayed during printhead cleaning or excess droplets. This can prevent printhead clogging and keep the inside of the equipment clean.

[0076] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A high-throughput DNA synthesis device based on inkjet printing, characterized in that, include: Multiple ink cartridges, each used to temporarily store a selected DNA base reagent, each ink cartridge is set at a corresponding inkjet station, and each ink cartridge is connected to an inkjet nozzle for spraying the reagent to a target area located below it. Multiple support fixtures are used to support reaction plate with multiple reaction holes; Multiple sealing components are used to seal with the support fixture to form a closed reaction chamber for accommodating the reaction plate. Each sealing component is disposed at a corresponding reaction station, and a connection station is provided below each reaction station. A movable component for driving the carrier fixture to reciprocate between the target area below the inkjet station and the connecting station; and, Multiple lifting components are initially positioned below the docking station. They are used to rise and dock with the carrying fixture when the carrying fixture moves to the docking station, and during the continued rising process, they drive the carrying fixture and the reaction orifice plate to rise away from the moving components until they reach the reaction station, thereby enabling the carrying fixture to seal with the corresponding sealing component.

2. The high-throughput DNA synthesis apparatus based on inkjet printing according to claim 1, characterized in that: It also includes a work box, wherein the multiple ink cartridges are arranged at intervals along the X-axis on the top plate of the work box, and the top plate has clearance holes at the positions corresponding to the inkjet nozzles, so that the ejected droplets can pass through the clearance holes and enter the target area below; The multiple sealing components are also arranged at intervals along the X-axis on the top plate of the work box, and are arranged parallel to the multiple ink cartridges; The support fixture, lifting assembly, and moving assembly are arranged inside the working chamber. The lifting assembly can drive the support fixture to move up and down along the Z-axis, and the moving assembly can drive the support fixture to move along the X-axis and Y-axis, so as to realize the transfer between any inkjet station and any connecting station.

3. The high-throughput DNA synthesis apparatus based on inkjet printing according to claim 2, characterized in that: The outer side of the working chamber is provided with an input pipe for introducing protective gas, so that the internal cavity of the working chamber forms a protective atmosphere environment.

4. The high-throughput DNA synthesis apparatus based on inkjet printing according to claim 2, characterized in that: The moving assembly includes an X-axis motorized slide, a Y-axis motorized slide, and a connecting fork. The Y-axis electric slide is slidably connected to the X-axis electric slide, and the connecting fork is slidably connected to the Y-axis electric slide. The connecting fork is used to carry and transfer the carrying fixture to the connecting position.

5. The high-throughput DNA synthesis apparatus based on inkjet printing according to claim 4, characterized in that: The moving component also includes a slider and a guide rail. The guide rail is arranged parallel to the X-axis electric slide. One end of the Y-axis electric slide is slidably connected to the X-axis electric slide, and the other end is engaged with the guide rail through the slider.

6. The high-throughput DNA synthesis apparatus based on inkjet printing according to claim 4, characterized in that: The connecting fork is provided with a first positioning post, and the bottom of the bearing fixture is provided with a first positioning hole. The first positioning post and the first positioning hole cooperate to achieve bearing positioning.

7. The high-throughput DNA synthesis apparatus based on inkjet printing according to claim 1 or 2, characterized in that: The lifting assembly includes a lifting cylinder and a lifting plate connected to the telescopic rod of the lifting cylinder.

8. The high-throughput DNA synthesis apparatus based on inkjet printing according to claim 7, characterized in that: The lifting plate is provided with a second positioning post, and the bottom of the bearing fixture is provided with a second positioning hole, the second positioning post and the second positioning hole being matched.

9. The high-throughput DNA synthesis apparatus based on inkjet printing according to claim 2, characterized in that: The sealing assembly includes an opening on the top surface of the top plate of the work box, and an openable and closable sealing cover disposed at the opening; When the support fixture and the reaction orifice plate are raised to the reaction station, the reaction orifice plate extends into the opening, and the support fixture fits against the bottom surface of the top plate of the work box, thereby forming a closed reaction chamber with the sealing cover.

10. The high-throughput DNA synthesis apparatus based on inkjet printing according to claim 9, characterized in that: The support fixture includes a T-shaped block with a receiving groove for accommodating the reaction plate, the top surface of the reaction plate extending beyond the top surface of the T-shaped block; The bottom surface of the top plate of the work box is provided with a positioning groove, which is connected to the opening. When the supporting fixture is raised to the reaction position, the lateral part of the T-block extends into the positioning groove and is in close contact with the bottom of the groove.

11. The high-throughput DNA synthesis apparatus based on inkjet printing according to claim 10, characterized in that: The support fixture also includes a waste liquid chamber located below the receiving tank. The waste liquid chamber is connected to the receiving tank. The connection between the receiving tank and the waste liquid chamber is provided with a support surface for supporting the reaction orifice plate. The waste liquid chamber is used to collect waste liquid falling from all the holes of the reaction orifice plate.

12. The high-throughput DNA synthesis apparatus based on inkjet printing according to claim 11, characterized in that: The bottom of the support fixture is provided with a drain port, and the drain port is provided with an openable valve structure for discharging waste liquid from the waste liquid chamber when needed.

13. The high-throughput DNA synthesis apparatus based on inkjet printing according to claim 12, characterized in that: The valve structure includes a female valve head, a male valve head, and a threaded cylinder mounted on the lifting assembly. The female valve head is installed at the drain port, and the screw of the threaded cylinder extends along the lifting direction and is fixedly connected to the male valve head through a connector. When the bearing fixture is in the reaction position, the male valve head can be inserted into the female valve head and open its internal valve core when the screw of the threaded cylinder extends, so that a communication passage is formed between the female valve head, the male valve head and the connector, thereby discharging waste liquid from the connector.

14. The high-throughput DNA synthesis apparatus based on inkjet printing according to claim 9, characterized in that: The sealing cover is provided with a first high-pressure gas pipe and a second high-pressure gas pipe that are connected to the sealed reaction chamber. The first high-pressure gas pipe is used to input a first set high-pressure gas required for the reaction into the sealed reaction chamber, and the second high-pressure gas pipe is used to input a second set high-pressure gas to remove waste liquid from the reaction orifice plate into the sealed reaction chamber.

15. The high-throughput DNA synthesis apparatus based on inkjet printing according to claim 14, characterized in that: A pressure detector is installed on the sealing cover to detect the gas pressure inside the sealed reaction chamber.

16. The high-throughput DNA synthesis apparatus based on inkjet printing according to claim 1, characterized in that: It also includes multiple ink bottles, each of which stores a selected DNA base reagent and is connected to the corresponding ink cartridge.

17. The high-throughput DNA synthesis apparatus based on inkjet printing according to claim 1, characterized in that: It also includes multiple liquid receiving boxes, which are arranged one-to-one below the multiple ink cartridges to receive DNA base reagents splashed from the inkjet nozzle.

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