DNA synthesis equipment

Abstract

The utility model provides DNA (deoxyribonucleic acid) synthesis equipment. The DNA synthesis equipment comprises a printing nozzle module and at least two cleaning and air drying modules. The printing nozzle module comprises a printing nozzle. The cleaning and air-drying module comprises a shell part capable of being controlled to be opened and closed, a base material mounting part used for bearing a base material to be printed and a cleaning and air-drying part used for cleaning and air-drying the base material. The printing nozzle and the cleaning and air-drying module are configured to move relatively, so that when the printing nozzle prints on the base material in one cleaning and air-drying module, the shell part of the other cleaning and air-drying module can be closed, and the cleaning and air-drying part can clean and air-dry the base material in the other cleaning and air-drying module.

Description

Technical Field

[0001] This application relates to the field of printing technology, and in particular to DNA synthesis equipment. Background Art

[0002] Currently, the application of enzymatic methods for DNA (deoxyribonucleic acid) synthesis is increasing continuously. This is not only because of the increasing demand for synthetic DNA in many fields such as synthetic biology, life sciences, and high-throughput sequencing, but also because of the limitations of chemical synthesis methods for DNA synthesis, such as the upper limit of product length and the use and disposal of organic solvents. Enzymatic synthesis is attractive due to its specificity, production efficiency, and the use of mild aqueous reaction conditions that eliminate the need for handling hazardous waste, becoming the forefront direction of the development of DNA synthesis technology.

[0003] Among them, DNA arrays are powerful tools for high-throughput identification and quantification of nucleic acids. DNA arrays can be prepared by mechanical spotting of pre-synthesized DNA products or by de novo synthesis of DNA on a solid substrate (usually a treated substrate, such as a silicon wafer). Since the sequences of de novo synthesized arrays are stored electronically, the costs and potential errors in amplification, storage, and retrieval are eliminated.

[0004] In existing DNA synthesis equipment, the steps of printing and cleaning the substrate are separate, and the substrate needs to be transferred from one station to another, resulting in low overall synthesis production efficiency. Summary of the Utility Model

[0005] To solve or alleviate at least one technical problem mentioned in the background art, this application provides DNA synthesis equipment.

[0006] The DNA synthesis equipment provided by the embodiments of this application includes:

[0007] A printing nozzle module, the printing nozzle module includes a printing nozzle;

[0008] At least two cleaning and air-drying modules, the cleaning and air-drying module includes a housing part capable of controlling opening and closing, a substrate mounting part for carrying the substrate to be printed, and a cleaning and air-drying part for cleaning and air-drying the substrate;

[0009] The printing nozzle and the cleaning and air-drying module are configured to be able to move relative to each other, so that when the printing nozzle prints on the substrate in one of the cleaning and air-drying modules, the housing part of the other cleaning and air-drying module can be closed, and the cleaning and air-drying part can clean and air-dry the substrate in the other cleaning and air-drying module.

[0010] In at least one embodiment, the housing portion includes a base and a cover portion. A substrate mounting portion that is relatively fixed in position with respect to the base is provided in the base, and a cleaning air drying portion that can move relative to the base is provided inside the cover portion.

[0011] In at least one embodiment, the cover portion can be rotated to cover the base or rotated away from the base to adjust the opening and closing state of the housing portion.

[0012] In at least one embodiment, a first slide rail and a first moving module are provided inside the cover portion. The first moving module is slidably disposed on the first slide rail, and the cleaning air drying portion is connected to the first moving module.

[0013] In at least one embodiment, the cleaning air drying portion includes a plurality of liquid path fixing blocks. A plurality of liquid path tubes are circumferentially arranged on each liquid path fixing block, and the liquid path nozzles of the liquid path tubes are inclined toward the center of the circumference. When the cover portion covers the base, the liquid path nozzles of the liquid path tubes face the substrate.

[0014] In at least one embodiment, the cleaning air drying portion further includes an air path fixing block. The air path fixing block is relatively fixed to the liquid path fixing block, and a plurality of air blowing ports arranged in a row and inclined toward the liquid path fixing block are provided on the air path fixing block. When the cover portion covers the base, the plurality of air blowing ports face the substrate to synchronously dry the substrate after cleaning.

[0015] In at least one embodiment, the substrate mounting portion includes a substrate mounting groove. An elastic pressing block is provided at a corner of the substrate mounting groove, and the elastic pressing block is used to press the substrate in the horizontal direction into the substrate mounting groove.

[0016] In at least one embodiment, the substrate mounting groove is defined by four supports located at the four corners. The supports have positioning edges for positioning the substrate, and negative pressure suction holes are provided in the supports for negative pressure suction of the substrate.

[0017] In at least one embodiment, the base includes a funnel-shaped solution collection slope, a liquid suction port is provided at the bottom of the solution collection slope, and the substrate mounting portion is located above the solution collection slope.

[0018] In at least one embodiment, a gas suction port is further provided in the enclosed space formed by the base and the cover portion.

[0019] By providing at least two cleaning and drying modules, this application enables one cleaning and drying module to synthesize DNA while the other cleaning and drying module performs the washing and drying operations on the substrate, thereby improving the synthesis production efficiency. The substrate is directly arranged in the cleaning and drying module, enabling in-situ cleaning and printing processes, saving time due to reduced movement, and enhancing the overall production efficiency. Description of the Drawings

[0020] Figure 1 Shows a schematic structural view of a DNA synthesis device according to an embodiment of the present application.

[0021] Figure 2 Shows a schematic structural view of a printing nozzle module of a DNA synthesis device according to an embodiment of the present application.

[0022] Figure 3 Shows a top view of a cleaning and drying module of a DNA synthesis device according to an embodiment of the present application.

[0023] Figure 4 Shows a front view of a cleaning and drying module of a DNA synthesis device according to an embodiment of the present application.

[0024] Figure 5 Shows a schematic structural view of a liquid path fixing block and a gas path fixing block of a DNA synthesis device according to an embodiment of the present application.

[0025] Figure 6 Shows a cross-sectional view of a liquid path fixing block of a DNA synthesis device according to an embodiment of the present application.

[0026] Figure 7 Shows a perspective view of a cleaning and drying module of a DNA synthesis device according to an embodiment of the present application from a top view perspective.

[0027] Figure 8 Shows a rear view of a DNA synthesis device according to an embodiment of the present application.

[0028] Description of Reference Numerals

[0029] 100 Printing nozzle module; 110 Printing nozzle; 120 Nozzle movement module; 130 Nozzle liquid storage bottle group; 140 First observation camera;

[0030] 200 Cleaning and air-drying module; 210 housing part; 211 base part; 2111 solution collection slope; 2112 liquid suction port; 212 cover part; 220 substrate mounting part; 221 substrate mounting groove; 2211 support; 2212 positioning edge; 222 elastic pressing block; 230 cleaning and air-drying part; 231 liquid outlet; 232 air blowing port; 233 liquid path fixing block; 234 liquid path pipe; 2341 liquid path spray head; 235 cavity; 236 air path fixing block; 240 first moving module; 250 hinge; 260 first slide rail;

[0031] 300 Substrate;

[0032] 400 Housing part moving module; 410 second moving module; 420 third moving module; 430 fourth moving module;

[0033] 510 Second observation camera; 520 stroboscopic lamp;

[0034] 600 Cleaning liquid bottle group;

[0035] 700 Button control panel; 710 emergency stop switch;

[0036] 800 Equipment housing; 810 air inlet; 820 air outlet; 830 humidity sensor;

[0037] 900 Electrical cabinet Detailed implementation manners

[0038] The following describes exemplary implementation manners of the present application with reference to the accompanying drawings. It should be understood that these specific descriptions are only used to teach those skilled in the art how to implement the present application, rather than to exhaust all feasible ways of the present application, nor to limit the scope of the present application.

[0039] The implementation manner of the present application provides a DNA synthesis device capable of synthesizing DNA by printing.

[0040] In an implementation manner of the present application, refer to Figure 1 , this DNA synthesis device may include a printing nozzle module 100 and at least two cleaning and air-drying modules 200.

[0041] Refer to Figure 2 , the printing nozzle module 100 may include a printing nozzle 110, and the printing nozzle 110 may print relevant materials on a substrate 300 (introduced later) below the printing nozzle 110.

[0042] Refer to Figure 3 , the cleaning and air-drying module 200 may include a housing part 210, and the housing part 210 may be controlled to open and close (introduced later). Among them, Figure 3The cleaning and drying module 200 on the left is in an open state, and the cleaning and drying module 200 on the right is in a closed state.

[0043] The cleaning and drying module 200 may further include a substrate mounting portion 220 for carrying the substrate 300 to be printed. When the housing portion 210 is opened, the printing head 110 can print materials on the substrate 300 located in the housing portion 210.

[0044] The cleaning and drying module 200 may further include a cleaning and drying portion 230 for cleaning and drying the substrate 300. Exemplarily, the cleaning and drying portion 230 may include a liquid outlet 231 for spraying cleaning liquid and a blowing port 232 for blowing air for drying, so as to be able to clean and dry the substrate 300 when the housing portion 210 is closed.

[0045] See Figure 1 、 Figure 2 、 Figure 3 , the printing head 110 and the cleaning and drying module 200 are configured to be able to move relative to each other. Exemplarily, the cleaning and drying module 200 is arranged to be able to move in the X direction and the Y direction, and the printing head 110 is arranged to be able to move in the Z direction, and the X, Y, and Z directions are perpendicular to each other. When the printing head 110 prints on the substrate 300 in one cleaning and drying module 200, the housing portion 210 of the other cleaning and drying module 200 can be closed, and the cleaning and drying portion 230 can clean and dry the substrate 300 therein.

[0046] The DNA synthesis device provided by the present application can realize two-station switching by setting at least two cleaning and drying modules 200, so that while one cleaning and drying module 200 is synthesizing DNA by printing, the other cleaning and drying module 200 can perform washing and drying operations on the substrate 300, improving production efficiency. The present application also directly arranges the substrate 300 in the cleaning and drying module 200, which can realize in-situ cleaning and printing processes, saving time due to reducing the moving process and improving the overall production efficiency.

[0047] See Figure 2 , the printing head module 100 may include a print head movement module 120 that can be controlled to move in the Z direction. The printing head 110 may be connected to the print head movement module 120 so that the printing head 110 can be controlled to move in the Z direction. Multiple printing heads 110 may be provided, and in one example, 5 printing heads may be provided.

[0048] The printing nozzle module 100 may include a nozzle liquid storage bottle group 130, and each liquid storage bottle in the nozzle liquid storage bottle group 130 is connected to each printing nozzle 110 one by one. A positive pressure air source (introduced later) can press the liquid in the nozzle liquid storage bottle group 130 into the printing nozzle 110 for use in printing.

[0049] The printing nozzle module 100 may include a first observation camera 140. The first observation camera 140 faces the substrate 300 and is used to observe the printing result on the substrate 300.

[0050] The printing nozzle module 100 may include a signal driving module. The signal driving module may include a motion control card and an electric driving controller, which are used to control the use of the printing nozzle 110, such as controlling the start and stop of the printing nozzle 110.

[0051] In an embodiment of the present application, referring to Figure 3 , the housing part 210 may include a base part 211 and a cover part 212. A substrate mounting part 220 that is relatively fixed in position with respect to the base part 211 may be provided in the base part 211. A cleaning air and liquid part 230 that moves relative to the position of the base part 211 is provided on the inner side of the cover part 212, so that the cleaning air and liquid part 230 can move to cover the substrate 300.

[0052] Exemplarily, a first slide rail 260 and a first moving module 240 are provided on the inner side of the cover part 212. The first moving module 240 is slidably disposed on (i.e., can be slidably disposed on) the first slide rail 260, and the cleaning air and liquid part 230 is connected to the first moving module 240. For example, the first moving module 240 can drive the cleaning air and liquid part 230 to move relative to the base part 211 in the Y direction.

[0053] In an embodiment of the present application, referring to Figure 4 、 Figure 5 、 Figure 6 , the cleaning air and liquid part 230 includes a plurality of (for example, three) liquid path fixing blocks 233 to achieve full coverage of the position of the substrate 300 in the X direction.

[0054] Referring to Figure 7 , a plurality of (for example, six) liquid path tubes 234 are arranged in a circumferential array on each liquid path fixing block 233. When the cover part 212 is closed on the base part 211, the liquid path nozzles 2341 of the liquid path tubes 234 face the substrate 300. Referring to Figure 6 , a plurality of liquid path nozzles 2341 are arranged facing the substrate 300 and are inclined towards the center of the circle, so that the cleaning liquid can more densely cover the cleaning area and enhance the cleaning effect. Exemplarily, the axial direction of the liquid path nozzle 2341 may form an angle of 30° with the Z direction.

[0055] It can be understood that the liquid path nozzle 2341 of the liquid path tube 234 here facing the substrate 300 includes that the liquid path nozzle 2341 is generally facing the substrate 300 in the up and down directions. Of course, it also includes that after the first moving module 240 and the cleaning and air drying part 230 thereon slide on the first slide rail 260, the liquid path nozzle 2341 is directly opposite to the substrate 300.

[0056] See Figure 6 , a cavity 235 for accommodating the liquid path tube 234 can be provided in the liquid path fixing block 233, and the cross-section of the cavity 235 can be set to gradually shrink from top to bottom, so as to facilitate the accommodation and restraint of the liquid path tube 234.

[0057] In an embodiment of the present application, see Figure 3 , Figure 4 , Figure 5 , the cleaning and air drying part 230 further includes an air path fixing block 236. The air path fixing block 236 is relatively fixed to the liquid path fixing block 233. A plurality of air blowing ports 232 arranged in a row and inclined towards the liquid path fixing block 233 are provided on the air path fixing block 236. When the cover part 212 is covered on the base part 211, the plurality of air blowing ports 232 face the substrate 300 to synchronously dry the substrate 300 after cleaning. Shorten the interval time between cleaning and air drying, reduce the repeated moving actions, and improve the synthetic production efficiency.

[0058] See Figure 4 , Figure 5 , the air blowing port 232 can be circular, and the included angle between the axial direction of the air blowing port 232 and the Z direction can be set to 45°, so as to be able to blow the liquid on the substrate 300 obliquely. Cooperating with the moving function of the first moving module 240, the residual liquid on the substrate 300 can be quickly blown off the upper surface of the substrate 300 to achieve the function of rapid air drying. The air blowing port 232 can be set as a small port to make the blowing air flow rate faster. The gas blown out from the air blowing port 232 can be set as dry gas to enhance the air drying effect and keep the DNA synthesis environment in the cleaning and air drying module 200 dry and stable.

[0059] In an embodiment of the present application, see Figure 3 , the cover part 212 is configured to be able to be controlled to rotate and cover on the base part 211 or rotate away from the base part 211 to adjust the opening and closing state of the housing part 210. For example Figure 3 the cover part 212 of the cleaning and air drying module 200 on the left rotates away from the base part 211, Figure 3 the cover part 212 of the cleaning and air drying module 200 on the right rotates and covers on the base part 211. The cover part 212 can limit the gas circulation range during the cleaning and air drying processes, prevent liquid splashing, and prevent affecting another air drying and cleaning module that is performing printing work with the cover part 212 opened.

[0060] SeeFigure 4 The cleaning and air-drying module 200 may include a hinge 250, and the cover body portion 212 is rotatably connected (or hinged) to the base portion 211 through the hinge 250. The hinge 250 may be a damping hinge.

[0061] The cover body portion 212 may be configured to be capable of automatic opening and closing, for example, the state switching between opening / closing can be achieved through driving devices such as a manipulator, a hydraulic rod, a motor, etc. Of course, non-limitingly, manual assistance for opening and closing is also possible, which is more convenient for maintenance.

[0062] In an embodiment of the present application, referring to Figure 7 , the substrate mounting portion 220 may include a substrate mounting groove 221, and an elastic pressing block 222 is provided at a corner of the substrate mounting groove 221. The elastic pressing block 222 is used to press the substrate 300 in the horizontal direction into the substrate mounting groove 221. Exemplarily, Figure 7 the direction of the pressing force in [] can be leftward and downward. The substrate 300 is quickly positioned through the substrate mounting groove 221 and accurately mounted to a unified position by the elastic pressing block 222, reducing the positioning error and improving the synthetic production efficiency.

[0063] In an embodiment of the present application, referring to Figure 7 , the substrate mounting groove 221 may be defined by four supports 2211 located at the four corners. The supports 2211 have positioning edges 2212 for positioning the substrate 300, and the substrate 300 is stuck in the groove formed by the positioning edges 2212. The substrate 300 may only contact the four supports 2211. Compared with the substrate being flat against a plane, this design of the supports 2211 reduces the contact area between the bottom surface of the substrate 300 and other structures, facilitating loading and unloading. Negative pressure suction holes may also be provided on the supports 2211 for further fixing the position of the substrate 300 through negative pressure suction.

[0064] Referring to Figure 3 , two or more substrate mounting grooves 221 may be provided in one substrate mounting portion 220, making full use of the internal space, so that more rows of DNA arrays can be printed at one time to increase the printing efficiency.

[0065] Referring to Figure 7 , the base portion 211 may include a solution collection inclined surface 2111 formed in a funnel shape. A liquid suction port 2112 may be provided at the bottom of the solution collection inclined surface 2111, and the liquid suction port 2112 may be connected to a negative pressure air source. The substrate mounting portion 220 is located above the solution collection inclined surface 2111, and the liquid after cleaning the substrate 300 can flow from the solution collection inclined surface 2111 to the bottom and be drawn out from the liquid suction port 2112.

[0066] A gas suction port (not shown in the figure) may also be provided in the housing part 210 (inside the sealed space formed by the cover part 212 and the base part 211) for extracting the gas in the housing part 210.

[0067] In one embodiment of the present application, referring to Figure 3 , the DNA synthesis device may include a housing part moving module 400, and the housing part moving module 400 may include a second moving module 410 and a third moving module 420.

[0068] Each cleaning and air-drying module 200 may be installed on the second moving module 410 to achieve fixed positions relative to each other. The second moving module 410 may be slidably installed on the third moving module 420 to move in the Y direction. The third moving module 420 may be slidably installed on the fourth moving module 430 to move in the X direction, so that the cleaning and air-drying module 200 can move in the X direction and the Y direction. It can be understood that the third moving module 420 may also be a slide rail, such that the second moving module 410 can be slidably connected to the third moving module 420.

[0069] In one embodiment of the present application, referring to Figure 3 , the DNA synthesis device may include a second observation camera 510 and a stroboscopic lamp 520. The second observation camera 510 and the stroboscopic lamp 520 may be arranged on both sides in the Y direction of the cleaning and air-drying module 200 for observing the state of the droplets before printing. Exemplarily, the second observation camera 510 and the stroboscopic lamp 520 may be located at both ends in the Y direction of the cleaning and air-drying module 200 and are relatively fixed in position in the horizontal direction with respect to the printing nozzle 110.

[0070] In one embodiment of the present application, referring to Figure 1 , the DNA synthesis device may include a cleaning liquid bottle group 600, and the cleaning liquid bottle group 600 may contain a cleaning liquid (such as a solvent) for supplying to the liquid outlet 231 of the cleaning and air-drying module 200.

[0071] In one embodiment of the present application, the DNA synthesis device may include a positive pressure air source and a negative pressure air source.

[0072] The positive pressure air source may be connected to the gas path fixing block 236 and the liquid path fixing block 233 through one or more valves such as a pressure reducing valve, a solenoid valve, a filter pressure regulating valve, and a pneumatic pressure regulating valve for providing the gas for air-drying and the pressure for the liquid for rinsing. A filter pressure regulating valve may be provided after the positive pressure air source to increase the filtering and regulating functions.

[0073] The negative pressure air source may be connected to the liquid suction port 2112 and the gas suction port through one or more valves such as a pressure reducing valve, a solenoid valve, a filter pressure regulating valve, and a pneumatic pressure regulating valve for sucking the waste liquid and waste gas in the cleaning and air-drying module 200.

[0074] The positive pressure air source and the negative pressure air source can also be connected to the print head 110. For the print head 110, it requires three kinds of air pressures. For example, only connecting the positive pressure air source or the negative pressure air source can achieve the cleaning of the print head 110. When the print head 110 is connected to both the positive pressure air source and the negative pressure air source, the pressure can be adjusted as needed for printing. Exemplarily, the air source and the print head can be connected through four or more two-position three-way solenoid valves. Four or more two-position three-way valves are used to connect the print head 110, the positive pressure air source and the negative pressure air source to achieve air pressure control functions such as positive pressure, negative pressure, control, and air release.

[0075] The working state switching of the two-position three-way solenoid valve can include making the print head 110 only connected to the positive pressure air source, the print head 110 only connected to the negative pressure air source, the print head connected to the filter pressure regulator to achieve the control of the air pressure magnitude, and the print head 110 not connected to the air source to play a role in pressure relief. It can be understood that since there will be residual air pressure in the pipeline when the print head 110 switches the connected air source, the air release position (the print head is not connected to the air source) in the two-position three-way solenoid valve can play a role in pressure relief.

[0076] In one embodiment of the present application, referring to Figure 1 , the DNA synthesis device may include a button control panel 700, and components such as an emergency stop switch 710 and a pneumatic pressure regulating valve may be integrated on the button control panel 700.

[0077] In one embodiment of the present application, referring to Figure 1 , the DNA synthesis device may include an electrical cabinet 900, and related control components, circuit structures, power supply components, etc. may be placed in the electrical cabinet 900. A relay may be provided in the electrical cabinet 900, and the relay is connected to the switch on the control button panel for controlling each component. Of course, the control of different components can be achieved through software settings to simplify the button control panel 700.

[0078] In one embodiment of the present application, referring to Figure 1 、 Figure 8 , the DNA synthesis device may include a device housing 800, and the above components are carried by the device housing 800. The device housing 800 may include an air inlet 810 and an air outlet 820, and the air inlet 810 may be provided above the air outlet 820. A desiccant bucket may be provided at the air inlet 810, and a humidity sensor 830 may be provided at the air outlet 820.

[0079] Exemplarily, the specific process of DNA synthesis by this device may include:

[0080] 1. Surface treatment preparation of the substrate 300.

[0081] Successful DNA synthesis requires a critical balance of good hydrophobicity and reactivity on the surface of the substrate 300. The substrate 300 provides hydrophobicity and does not participate in base ligation during the synthesis process. Regarding the storage of the processed substrate 300, it is recommended to store it in a sealed vapor barrier bag (such as an anti-static type sealed bag used for transporting electronic components), which contains a desiccant packet with an indicator, and store these in a cool and dry place.

[0082] 2. Preparation of DNA synthesis reagents and activators.

[0083] Regarding the preparation of DNA reagents, it is necessary to keep them in a dry state. Most reagents can be purchased in anhydrous form, so only need to be handled and stored in a way to avoid moisture contamination.

[0084] 3. Preparation of cleaning solution.

[0085] Similar to the preparation of synthesis reagents, the preparation process of the cleaning solution also requires good drying treatment of the solution. Regarding the preparation quantity and storage of the solvent, usually 2 - 4 bottles of solvent solution can be prepared at a time, depending on the workload requirements.

[0086] 4. Install and position the substrate 300.

[0087] Carefully take out the previously prepared substrate 300, noting to only hold the edge of the substrate 300. Install it in the substrate installation groove 221 according to the positioning standard. After all the substrates 300 are installed, the surface of each substrate 300 can be blown clean with a blow gun connected to dry gas.

[0088] 5. Dry the internal environment of the equipment.

[0089] Seal the entire equipment and fill the inside of the equipment with dry gas. The relative humidity inside the equipment is monitored by the control software through the humidity sensor 830. When the humidity inside the equipment is stable and below the set value, the drying is completed. During the drying process, the gas inside the equipment is blown outside the equipment by a fan, and the gas entering the air inlet 810 will first pass through a barrel of desiccant for drying and then enter the equipment interior to participate in the gas drying cycle, and continuously circulate the gas inside the equipment to reach the drying standard.

[0090] 6. Pre - wash the surface of the substrate 300.

[0091] When the inside of the equipment is dry and stable, rinse the surface of the substrate 300 with the cleaning solution several times. This helps to remove any possible particles on the surface of the substrate 300 and ensure that the synthesis surface meets the printing requirements. Apply the cleaning solution at the liquid outlet 231 and simultaneously blow - dry the surface of the substrate 300 at the air - blowing port 232, and observe whether there are residual droplets on the surface of the substrate 300. It is normal to have water droplets on the lower surface of the substrate 300.

[0092] 7. Infuse base reagents, activators, and cleaning solutions.

[0093] Load the prepared base reagents and activators into the corresponding closed nozzle liquid storage bottle group 130 through a dry and airtight treatment method, and perform pre-cleaning on the inkjet droplets and printing nozzles 110. In the default setting, the leftmost vial in the liquid storage bottle group is for the activator, and the remaining four are for base reagents respectively. Of course, this layout is adjustable. Similarly, the cleaning solution is stored in the cleaning solution bottle group 600 according to the same steps.

[0094] 8. Clean and test the printing nozzle 110.

[0095] Before starting to dry the internal environment, it is necessary to ensure that all printing nozzles 110 are clean and can eject liquid normally. The specific steps include: 1) Use the control software to make each printing nozzle 110 eject liquid multiple times (usually 5 - 30 times per second) for cleaning. 2) Start the function of testing the printing nozzle 110 in the software, and use the second observation camera 510 to observe the state of each droplet. The software will report the number and location of corresponding faults (if any) of each printing nozzle 110. 3) If the printing nozzle 110 is blocked, carefully adjust the air pressure regulating valve to apply a slight positive pressure to the liquid storage bottle in the nozzle liquid storage bottle group 130 corresponding to the blocked printing nozzle 110, and infuse a small amount of reagent into the printing nozzle 110. 4) Repeat the test function of the printing nozzle 110 to ensure that all printing nozzles 110 are operating normally.

[0096] 9. Start the DNA synthesis operation.

[0097] When the humidity stabilizes and the previous processes are all ready, the correct DNA synthesis mode and program file can be loaded on the control software to perform DNA synthesis. During the synthesis process, the device housing 800 should be avoided from being opened to prevent the introduction of humid air. After the synthesis starts, the printing process should be monitored to ensure that the printing proceeds as expected. In addition, after each layer is printed, the printing nozzle 110 rises along the Z-axis, and the cleaning and drying unit 230 performs cleaning and drying work. At this time, the printing nozzle 110 prints on the substrate 300 in another cleaning and drying module 200.

[0098] 10. Post-treatment of DNA synthesis.

[0099] After the synthesis program is completely finished, the substrate 300 can be cleaned and processed. First, remove the residual synthesis reagents accumulated at the bottom of the substrate 300, and then the base deprotection of the substrate 300 can be carried out. Perform base deprotection on the substrate 300 to remove the protecting groups and expose the bases, making them available for other treatments. This procedure can be carried out in a chemical fume hood while wearing nitrile gloves, goggles, and a laboratory coat.

[0100] 11. Turn off the synthesis equipment.

[0101] If the device needs to be reloaded with solution and printed again in a short time, there is no need to treat the device. However, if it is not used for a period of time, the base reagent and activator can be removed from the reservoir bottle set and replaced with pure solvent (such as ethanol, etc.) to keep the fluid in the nozzle and the connected infusion tube from clogging.

[0102] The advantages of the DNA synthesis device provided by this application include:

[0103] (1) The implementation method of DNA synthesis is efficient. The DNA synthesis equipment provided in the present application is provided with two cleaning and air-drying modules 200, so that the equipment can be switched to a dual-station state, so that one module can synthesize DNA while the other module switches to the substrate 300 washing and drying operation state, and works alternately and cyclically, thereby improving the synthesis production efficiency. Two substrate 300 installation positions can be set in a cleaning and air-drying module 200 to make full use of the internal space. The positioning and installation method of the substrate 300 is reliable and accurate, which basically eliminates the problem of decreased synthesis efficiency caused by the misalignment of the substrate 300, thereby improving the synthesis efficiency. The substrate 300 in the device can be quickly air-dried after cleaning, and the overall environmental humidity stability control function of the device also greatly reduces printing errors caused by environmental humidity, thereby achieving efficient printing.

[0104] (2) The washing method of the substrate 300 is efficient. Driven by the first moving module 240, the liquid path fixing block 233 moves along the Y axis to cover the entire substrate 300, thereby achieving the washing operation. The liquid path pipes 234 on the liquid path fixing block 233 are arranged in a circular shape, so that the cleaning liquid covers the cleaning area more densely, thereby enhancing the cleaning effect.

[0105] (3) The air drying method of the substrate 300 is efficient. The gas path fixing block 236 and the liquid path fixing block 233 are arranged side by side, and the horizontal movement of the first moving module 240 can be used to quickly air dry the substrate 300 after washing, which is highly efficient. The air blowing port 230 is tilted, and the circular air blowing port and small hole design have a faster flow rate. The blown gas is set to dry gas, which has a better air drying effect.

[0106] (4) The internal environment control function of the device is excellent. In this application, the air inlet 810 is set at the upper part, and the air outlet 820 is set at the lower part. The desiccant barrel and the air inlet 810 are designed at the same position. On the one hand, it is convenient to quickly dry the gas entering the device. On the other hand, it is convenient for the operator to replace consumables such as desiccants, which is convenient for later maintenance. In this application, the humidity sensor 830 is set near the air outlet 820, which can more accurately grasp the average humidity of the air inside the device after drying treatment, and cooperate with the desiccant to better control the humidity of the environment. In addition, if the humidity sensor 830 is installed near the air inlet, it is easily eroded by dust and impurities. In this application, the humidity sensor 830 is installed at the air outlet 820, which can reduce the erosion of the humidity sensor 830, thereby extending its service life.

[0107] (5) The environmental treatment effect is friendly. The housing part 210 of the cleaning and air-drying module 200 restricts the flow range of the cleaning liquid and the gas generated during the cleaning process.

[0108] For liquids, the base 211 is funnel-shaped, and the liquid suction port 2112 is located at the lowest position of the solution collection slope 2111, which is convenient for the cleaning liquid to converge and be collected. The waste liquid is collected into the waste liquid bottle through a negative pressure air source. For gases, a gas suction port is also provided inside the housing part 210, and the exhausted gas after cleaning and air-drying can be suctioned through a negative pressure air source to avoid polluting the working environment.

[0109] (6) The installation and positioning of the substrate 300 are fast and accurate. Through the setting of the four supports 2211 in this application, the contact surface of the substrate 300 is reduced, which is convenient for the loading and unloading of the substrate 300 and avoids liquid residue.

[0110] The above are the preferred implementation manners of this application. It should be noted that for those skilled in the art, without departing from the principle of this application, several improvements and refinements can still be made, and these improvements and refinements should also be regarded as the protection scope of this application.

Claims

1. A DNA synthesis device, characterized in that: include: A print head module, the print head module comprising a print head; At least two cleaning and air-drying modules, each of which comprises a housing portion capable of being controlled to open and close, a substrate mounting portion for carrying the substrate to be printed, and a cleaning and air-drying portion for cleaning and air-drying the substrate. The print head and the cleaning and drying module are configured to be able to move relative to each other, so that when the print head prints on the substrate in one cleaning and drying module, the shell portion of the other cleaning and drying module can be closed, and the cleaning and drying tube portion can clean and dry the substrate in the other cleaning and drying module.

2. The DNA synthesis device according to claim 1, characterized in that: The shell portion includes a base and a cover portion, the base portion is provided with the substrate mounting portion fixed relative to the base portion, and the inner side of the cover portion is provided with the cleaning air pipe portion movable relative to the base portion.

3. The DNA synthesis device according to claim 2, characterized in that: The cover body can be rotated to cover the base or rotated away from the base to adjust the opening and closing state of the shell body.

4. The DNA synthesis device according to claim 2, characterized in that: A first slide rail and a first moving module are arranged on the inner side of the cover body. The first moving module is slidably arranged on the first slide rail, and the cleaning air pipe is connected to the first moving module.

5. The DNA synthesis device according to claim 2, characterized in that: The cleaning air dryer includes a plurality of liquid path fixing blocks, each of which is provided with a plurality of liquid path tubes in a circular array, the liquid path nozzles of the liquid path tubes are inclined toward the center of the circle, and when the cover body is covered on the base, the liquid path nozzles of the liquid path tubes are directed toward the substrate.

6. The DNA synthesis device according to claim 5, characterized in that: The cleaning air dryer also includes an air circuit fixing block, which is relatively fixed to the liquid circuit fixing block. The air circuit fixing block is provided with a plurality of blowing ports arranged in a row and inclined toward the liquid circuit fixing block. When the cover body is covered on the base, the plurality of blowing ports face the substrate to simultaneously blow dry the substrate after cleaning.

7. The DNA synthesis device according to claim 1, characterized in that: The substrate installation portion comprises a substrate installation groove, a corner of which is provided with an elastic pressing block, and the elastic pressing block is used to press the substrate in the substrate installation groove in a horizontal direction.

8. The DNA synthesis device according to claim 7, characterized in that: The substrate installation groove is defined by four supports located at four corners, the supports have positioning ribs for positioning the substrate, and negative pressure adsorption holes are arranged in the supports for negative pressure adsorption of the substrate.

9. The DNA synthesis device according to claim 2, characterized in that: The base comprises a funnel-shaped solution collecting slope, a liquid suction port is arranged at the bottom of the solution collecting slope, and the substrate mounting portion is located above the solution collecting slope.

10. The DNA synthesis device according to claim 2, characterized in that: A gas suction port is also arranged in the closed space surrounded by the base and the cover.

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