High-throughput sorting system and nucleic acid synthesis system for nucleic acid synthesis chips

Abstract

The embodiment of the present application provides a high-throughput sorting system for nucleic acid synthesis chips, including a vibration array device, a batch recognition system, a batch pick-and-place system, and multiple storage silos; the vibration array device includes a vibration array disk and a drive mechanism connected to the vibration array disk, the vibration array disk is provided with multiple grooves arranged in an array, and the drive mechanism drives the vibration array disk to perform reciprocating swings of a preset angle and oscillations of a preset frequency, so that the chips placed on the vibration array disk enter the grooves; the batch recognition system performs group recognition on the arrayed chips on the vibration array disk and obtains the identification information of the chips; the batch pick-and-place system performs batch pick-and-place operations on the chips in the vibration array disk and transfers them to corresponding storage silos. The embodiment of the present application can achieve high-throughput sorting of chips, thereby significantly reducing the proportion of sorting time in the entire process, thereby effectively improving the overall production capacity of the system, and ultimately promoting the acceleration of the industrialization process of nucleic acid synthesis technology.

Description

Technical Field

[0001] The present application relates to the field of chip identification and sorting technology, and in particular to a high-throughput sorting system for a nucleic acid synthesis chip and a nucleic acid synthesis system. Background Art

[0002] Nucleic acid synthesis technology is one of the underlying key technologies of synthetic biology, and is also the core supporting technology for the leapfrog development of emerging strategic fields such as nucleic acid storage and nucleic acid computing.

[0003] The chip sorting parallel synthesis method realizes the parallel synthesis of large quantities of microchips through a cyclic process of "identification-sorting-synthesis-convergence". However, the existing technology adopts a single-chip operation method when sorting nucleic acid synthesis chips, that is, each operation link can only process one chip at a time. The existing industrial-grade automated sorting technology is aimed at large-sized materials and is difficult to be directly applied to the high-throughput sorting of nucleic acid synthesis chips. Therefore, there is currently no batch screening equipment specifically for nucleic acid synthesis chips on the market, resulting in the efficiency of the parallel synthesis system in chip identification, allocation, recovery and recycling. In order to improve the overall performance of the parallel high-throughput nucleic acid synthesis system and optimize the proportion of synthesis time in the entire process, it is urgent to develop a set of efficient identification and sorting devices suitable for nucleic acid synthesis chips to achieve accurate screening and efficient allocation of nucleic acid synthesis chips, thereby further releasing the system's production capacity and accelerating the industrialization process of nucleic acid synthesis technology. Summary of the Invention

[0004] The embodiments of the present application provide a high-throughput sorting system for nucleic acid synthesis chips and a nucleic acid synthesis system, which can achieve high-throughput sorting of chips, thereby significantly reducing the proportion of sorting time in the entire process, thereby effectively improving the overall production capacity of the system, and ultimately promoting the acceleration of the industrialization process of nucleic acid synthesis technology.

[0005] The embodiment of the present application provides a high-throughput sorting system for nucleic acid synthesis chips, including a vibration array device, a batch recognition system, a batch pick-and-place system, and multiple storage silos;

[0006] The vibration array device includes a vibration array disk and a driving mechanism connected to the vibration array disk. The vibration array disk is provided with a plurality of grooves arranged in an array for accommodating chips. The driving mechanism is used to drive the vibration array disk to perform reciprocating swings at a preset angle and oscillations at a preset frequency, so that chips placed on the vibration array disk enter the grooves, and each groove can only accommodate one chip.

[0007] The batch recognition system stores a preset nucleic acid synthesis sequence, and is used to perform group recognition of the chips on the vibration array disk, obtain identification information on each chip, and compare the obtained identification information with the preset nucleic acid synthesis sequence to generate pick-and-place operation sorting information;

[0008] The batch pick-and-place system transfers the chips to corresponding storage silos according to the pick-and-place operation sorting information.

[0009] In the high-throughput sorting system for nucleic acid synthesis chips described in the embodiment of the present application, the batch pick-and-place system includes a pick-and-place actuator and a mobile positioning mechanism connected to the pick-and-place actuator;

[0010] The pick-and-place actuator includes a multi-channel pneumatic adsorption unit, which includes vacuum suction nozzles arranged in an array and a pressure pump connected to the vacuum suction nozzles, wherein the arrangement spacing between the vacuum suction nozzles forms a spatial matching relationship with the array arrangement between the grooves on the vibration array disk.

[0011] In the high-throughput sorting system of the nucleic acid synthesis chip described in the embodiment of the present application, the multi-channel pneumatic adsorption unit further includes a nozzle integrated substrate and a plurality of independent vacuum pipes;

[0012] The vacuum nozzles are fixed on the lower surface of the nozzle integrated substrate in an array arrangement. Each of the vacuum nozzles is connected to one end of the vacuum pipe, and the other end of the vacuum pipe is connected to the pressure pump.

[0013] In the high-throughput sorting system of the nucleic acid synthesis chip described in the embodiment of the present application, the vacuum nozzle is a silicone suction cup, and a compression spring is provided on the rear side of the vacuum nozzle, which generates an elastic buffer space of 2-5 mm when working.

[0014] In the high-throughput sorting system of the nucleic acid synthesis chip described in the embodiment of the present application, the batch recognition system includes an illumination module and a camera;

[0015] The lighting module is used to project illumination light onto the chips arranged in an array on the vibration array disk, and the camera is used to perform optical imaging on the chips arranged in an array on the vibration array disk to obtain identification information on each chip.

[0016] In the high-throughput sorting system of the nucleic acid synthesis chip described in the embodiment of the present application, the field of view of the camera is larger than 125 mm×125 mm, and the exposure time of a single frame is less than 0.02 seconds.

[0017] In the high-throughput sorting system of the nucleic acid synthesis chip described in the embodiment of the present application, the surface of the vibration array disk is made of a flexible material.

[0018] In the high-throughput sorting system of the nucleic acid synthesis chip described in the embodiments of the present application, the shape of the groove includes but is not limited to cylindrical, rectangular, square and hemispherical.

[0019] In the high-throughput sorting system for nucleic acid synthesis chips described in the embodiments of the present application, each of the storage silos has a streamlined funnel structure, and a controllable opening and closing door is provided at the bottom of the storage silo for transferring the chips.

[0020] An embodiment of the present application further provides a nucleic acid synthesis system, comprising a nucleic acid synthesis module and a high-throughput sorting system of the nucleic acid synthesis chip described in any one of the above embodiments.

[0021] The high-throughput sorting system for nucleic acid synthesis chips provided in the embodiments of the present application, by providing a vibration array device, a batch recognition system, a batch pick-and-place system, and multiple storage silos, can accurately screen and efficiently distribute batches of chips at one time, thereby achieving high-throughput sorting of chips, thereby significantly reducing the proportion of sorting time in the entire process, thereby effectively improving the overall production capacity of the system, and ultimately promoting the acceleration of the industrialization process of nucleic acid synthesis technology; secondly, by allowing the vibration array disk to perform reciprocating swings at preset angles and low-frequency oscillations, the chip can enter the groove more smoothly, preventing large friction between chips and between the chip and the disk surface of the vibration array disk, which may cause chip damage. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] To more clearly illustrate the technical solutions in the embodiments of the present application, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present application. Those skilled in the art can also derive other drawings based on these drawings without inventive effort.

[0023] Figure 1 This is a schematic diagram of the structure of the high-throughput sorting system of the nucleic acid synthesis chip provided in the embodiments of the present application.

[0024] Figure 2 A schematic structural diagram of the vibration array device provided in an embodiment of the present application.

[0025] Figure 3 Schematic diagram of chip identification by the batch identification system provided in an embodiment of the present application.

[0026] Figure 4 A schematic diagram of the structure of a batch pick and place system provided in an embodiment of the present application.

[0027] Figure 5 A schematic structural diagram of the storage silo provided in an embodiment of the present application.

[0028] Figure 6 This is a graph showing the HPLC test results of the synthesized T10 provided in the examples of this application.

[0029] Description of Figure Numbers:

[0030] 10-Vibration array device 20-Batch recognition system 30-Batch pick and place system

[0031] 40-Storage silo 101-Vibration array disk 102-Drive mechanism

[0032] 201-Lighting module 202-Camera 301-Pick and place actuator

[0033] 1021-Vibration Motor 1022-Rotating Shaft 1023-Connecting Rod

[0034] 1024-Linear Motor 3011-Vacuum Nozzle 3012-Nozzle Integrated Board

[0035] 3013-Vacuum Pipe DETAILED DESCRIPTION

[0036] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the embodiments described are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without making creative efforts are within the scope of protection of this application.

[0037] In the description of the present application, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", "clockwise", "counterclockwise" and the like indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as limiting the present application. In addition, the terms "first" and "second" are used for descriptive purposes only and cannot be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include one or more of the said features. In the description of the present application, "multiple" means two or more, unless otherwise clearly and specifically defined.

[0038] In the description of this application, it should be noted that, unless otherwise expressly specified or limited, the terms "installed," "connected," and "connected" should be understood in a broad sense. For example, they can refer to fixed connections, detachable connections, or integral connections; they can refer to mechanical connections, electrical connections, or mutual communication; they can refer to direct connections or indirect connections through an intermediate medium; they can refer to internal communication between two components or the interaction between two components. Those skilled in the art will understand the specific meanings of the above terms in this application based on specific circumstances.

[0039] In this application, unless otherwise expressly specified or limited, a first feature being "above" or "below" a second feature may include the first and second features being in direct contact, or may include the first and second features being in contact not directly but through another feature between them. Moreover, a first feature being "above," "above," and "above" a second feature may include the first feature being directly above or obliquely above the second feature, or may simply mean that the first feature is higher in level than the second feature. A first feature being "below," "below," and "below" a second feature may include the first feature being directly below or obliquely below the second feature, or may simply mean that the first feature is lower in level than the second feature.

[0040] The disclosure below provides many different embodiments or examples for realizing different structures of the present application. In order to simplify the disclosure of the present application, the components and settings of specific examples are described below. Of course, they are merely examples and are not intended to limit the present application. In addition, the present application may repeat reference numbers and / or reference letters in different examples, and such repetition is for the purpose of simplicity and clarity, and does not itself indicate the relationship between the various embodiments and / or settings discussed. In addition, the present application provides examples of various specific processes and materials, but those of ordinary skill in the art will appreciate the application of other processes and / or the use of other materials.

[0041] The present invention provides a high-throughput sorting system for nucleic acid synthesis chips, which is used in nucleic acid synthesis systems. Figures 1 to 5 The high-throughput sorting system of the nucleic acid synthesis chip includes a vibration array device 10, a batch recognition system 20, a batch picking and placing system 30 and a plurality of storage bins 40.

[0042] The above-mentioned nucleic acid synthesis can be either DNA synthesis or RNA synthesis. This embodiment takes DNA synthesis as an example for explanation. Accordingly, the "nucleic acid synthesis chip" is replaced by "DNA synthesis chip".

[0043] The vibration array device 10 includes a vibration array disk 101 and a driving mechanism 102 connected to the vibration array disk 101. The vibration array disk 101 is provided with multiple grooves arranged in an array for accommodating chips. The driving mechanism 102 is used to drive the vibration array disk 101 to perform reciprocating swings at a preset angle and oscillations at a preset frequency so that the chips placed on the vibration array disk 101 enter the grooves. Each groove can only accommodate one chip, and the chip size is in the millimeter order.

[0044] In some embodiments, the chip size ranges from 1mm to 5mm. For example, the chip size can be 2mm×2mm, 2mm×3mm, 2mm×4mm, 2mm×5mm, 3mm×3mm, 3mm×4mm, 3mm×5mm, 4mm×4mm, 4mm×5mm, and 5mm×5mm, etc.

[0045] In some embodiments, the number of grooves is at least 100, and specifically can be 200, 300, 400, or 500.

[0046] In some embodiments, the shapes of the grooves include, but are not limited to, cylindrical, rectangular, square, and hemispherical.

[0047] In some embodiments, the groove is slightly larger than the chip to allow the chip to enter the groove more smoothly and ensure that each groove can only accommodate one chip. For example, when the chip size is 2mm×2mm, the groove is hemispherical with a diameter ranging from Φ3mm to Φ4mm.

[0048] It should be noted that those skilled in the art can set the shape of the groove according to actual conditions, and no specific limitation is made here. In addition, those skilled in the art can set the size of the groove (such as diameter and depth) according to actual conditions, and only need to ensure that each groove can accommodate only one chip, which is not listed here. Specifically, the specific information of the vibration array device 10: ① Implementation function: Capture chips in batches into the grooves in the vibration array disk 101 to achieve an array arrangement of disordered chips; ② Implementation method: The driving mechanism 102 drives the vibration array disk 101 to swing back and forth, and at the same time drives the vibration array disk 101 to oscillate.

[0049] In some embodiments, the driving mechanism 102 is used to drive the vibration array disk 101 to perform reciprocating swings at a preset angle relative to the horizontal plane of its mounting base, and to generate oscillations at a preset frequency in the vertical plane. Specifically, the preset swing angle can be 45° and the oscillation frequency can be 5 Hz.

[0050] Among them, when sorting DNA synthesis chips in the existing technology, the sorting equipment used may achieve orderly arrangement of materials through a combination of circular vibration and linear vibration. Specifically, the vibration system uses metal materials for transmission, and high-frequency vibration is used to disperse the disordered stacked synthesis chips under intense vibration. However, most DNA synthesis chips are usually silicon-based materials with strong rigidity. Under strong vibration and high-speed vibration, the chips are exposed to high-frequency mechanical shock for a long time, which will generate significant friction between chips and between chips and metal disks, which can easily cause damage to the chip surface or the formation of microcracks, thereby affecting the quality of DNA synthesis. However, the embodiment of the present application allows the vibration array disk 101 to perform reciprocating swings at a preset angle and oscillate at a low frequency (4Hz-6Hz), which can make the chip enter the groove more smoothly and avoid the problem of chip damage caused by large friction between chips and between chips and the disk surface of the vibration array disk 101.

[0051] In addition, the prior art uses a single-material operation method when sorting DNA synthesis chips. The so-called single-material operation means that the chips are arranged in a single row and move forward in sequence on the conveyor belt. The entire process is carried out serially in the form of an assembly line, and each operation link can only sort one chip at a time. The high-throughput sorting system of the nucleic acid synthesis chip of the embodiment of the present application can process batches of chips at each link, which can achieve high-throughput sorting of chips, thereby significantly reducing the proportion of sorting time in the whole process, thereby effectively improving the overall production capacity of the system, and ultimately promoting the acceleration of the industrialization process of DNA synthesis technology. In addition, in the application scenario of DNA synthesis, the assembly line mode of single-material operation often leads to instability in the recognition and sorting process (for example, if the conveyor belt runs too fast, it will affect the camera's recognition of the chip) due to the small size of the chip. Therefore, this method is not suitable for high-throughput DNA synthesis needs.

[0052] Among them, such as Figure 2 As shown, the driving mechanism 102 includes a vibration motor 1021, a rotating shaft 1022, a connecting rod 1023 and a linear motor 1024, and the connection method thereof is as follows: Figure 2 The linear motor 1024 drives the vibration array disk 101 to perform reciprocating swings at a preset angle through the connecting rod 1023. The vibration motor 1021 drives the vibration array disk 101 to vibrate, so that the disordered stacked chips are captured by the grooves during the movement, and a regular array arrangement is achieved.

[0053] The batch recognition system 20 stores a preset nucleic acid synthesis sequence. The batch recognition system 20 is used to perform group recognition on all chips arrayed on the vibration array disk 101, obtain identification information on each chip, and compare the obtained identification information with the preset nucleic acid synthesis sequence and generate pick-and-place operation sorting information.

[0054] The chip identification information can be a QR code printed on the chip surface. Each chip has a corresponding QR code. This means each chip is individually identified using a QR code. The pre-set DNA synthesis sequence information is then assigned to each chip via the QR code. This process then goes through a cycle of visual recognition, mechanical sorting, centralized synthesis, and re-aggregation to achieve high-throughput DNA synthesis. It should be noted that the chip identification signal, in addition to the QR code image signal, can also be a radio frequency (RFID) signal or an optical signal based on a microsensor.

[0055] Among them, the QR code information on the surface of the chip includes the specific number, location, synthesis sequence information, etc. of the chip.

[0056] Among them, in addition to completing recognition through single imaging, other methods such as multi-frame image stitching and dynamic scanning recognition can also be used.

[0057] Among them, the nucleic acid synthesis sequence is provided by the customer and is usually not changed in a sorting and fusion project.

[0058] In some embodiments, the number of chips group-recognized by the batch recognition system 20 matches the number of grooves, that is, the batch recognition system 20 can at least cover the area where the grooves arranged in an array on the vibration array disk 101 are located in one recognition.

[0059] The batch pick-and-place system 30 transfers the chips to the corresponding storage bin 40 according to the pick-and-place operation sorting information.

[0060] In some embodiments, the storage silos can be divided into three categories, namely, temporary base storage silos for storing chips of bases to be synthesized; final synthesis product storage silos for storing chips that have completed synthesis; and temporary QR code abnormality storage silos for storing chips whose QR codes are invalid or cannot be recognized (for example, there are problems such as QR codes being damaged, incomplete, or blurred). The number of each type of storage silo can be one or more, and this application does not impose any restrictions on this. More specifically, the temporary base storage silos include A base storage silos, T base storage silos, C base storage silos, G base storage silos, and composite base storage silos, which are used to store chips of A bases to be synthesized, T bases, C bases, G bases, and composite bases, respectively.

[0061] The system described in the embodiment of the present application can be used for the identification and sorting of large-scale nucleic acid synthesis chips, and its implementation process is as follows: 1) The disorderly stacked batch chips are arranged in an orderly manner into the grooves on the disk through the swing of the vibration array disk 101 at a preset angle; 2) The batch identification system 20 performs group identification on the chips arranged in the array on the vibration array disk 101, obtains the QR code information on the chip surface in batches, and compares the obtained identification information with the preset nucleic acid synthesis sequence to generate pick-and-place operation sorting information; 3) The batch pick-and-place system 30 performs a batch picking operation on the chips in the vibration array disk 101 according to the pick-and-place operation sorting information, and transfers the chips to the corresponding storage silo 40; 4) The chips are gathered in the storage silo 40 to await subsequent operations, such as being transferred to the synthesis module for the next base synthesis.

[0062] In some embodiments, as Figure 3 As shown, the batch recognition system 20 includes an illumination module 201 and a camera 202; the illumination module 201 is used to project illumination light onto the arrayed chips on the vibration array disk 101, and the camera 202 is used to perform optical imaging on the arrayed chips on the vibration array disk 101 to obtain identification information on each chip.

[0063] Specifically, after the chips are arranged regularly, the lighting module 201 evenly illuminates the array area, the camera lens focuses on the chips in the groove, and the camera 202 realizes group recognition through one-time imaging to obtain characteristic information such as the QR code on the chip surface.

[0064] Specifically, the following is the specific information of the batch recognition system 20: ① Implementation function: Identify and analyze the QR code on the chip to obtain the chip identity information; ② Implementation method: The lighting module 201 projects illumination light onto the vibration array disk 101, and the camera 202 focuses on the chip surface in the groove of the vibration array disk 101, and optically images and compares and analyzes the chips arranged in the array on the vibration array disk 101.

[0065] In some embodiments, the field of view of the camera 202 is larger than 125 mm×125 mm, and the exposure time of a single frame is smaller than 0.02 seconds.

[0066] Furthermore, the camera 202 is configured to have an effective pixel resolution ranging from 5800 to 6400 pixels during a single frame image capture process.

[0067] Among them, setting the field of view area of ​​the camera 202 to be greater than 125 mm×125 mm and the single-frame exposure time to be less than 0.02 seconds can increase the number of group recognitions, thereby contributing to the realization of high-throughput sorting effects.

[0068] In some embodiments, the batch picking and placing system 30 includes a picking and placing actuator 301 and a mobile positioning mechanism (not shown in the figure) connected to the picking and placing actuator 301, the picking and placing actuator 301 includes a multi-channel pneumatic adsorption unit, the multi-channel pneumatic adsorption unit includes arrayed vacuum suction nozzles 3011 and a pressure pump (not shown in the figure) connected to the vacuum suction nozzles 3011, wherein the arrangement spacing between the vacuum suction nozzles 3011 forms a spatial matching relationship with the array arrangement between the grooves on the vibration array disk.

[0069] The mobile positioning mechanism is used to drive the pick-and-place actuator 301 to move and position. The pick-and-place actuator 301 is used to perform batch picking operations on the chips in the vibration array disk 101 according to the pick-and-place operation sorting information and transfer the chips to the corresponding storage bin 40.

[0070] Specifically, the mobile positioning mechanism controls the pick-and-place actuator 301 to pick and place the chips in the vibration array disk 101 in batches based on the QR code information of the chips identified by the batch identification system 20, and transfers the chips to the corresponding storage bin 40 according to the pick-and-place operation sorting information.

[0071] Specifically, the arrangement spacing between the vacuum nozzles 3011 corresponds to the arrangement spacing between the grooves on the vibration array disk 101, so that the vacuum nozzles 3011 can smoothly absorb the chips in the grooves.

[0072] Among them, the pressure pump includes a vacuum pump and an air compressor. The vacuum pump is used to provide negative pressure to the vacuum nozzle 3011 to ensure that the vacuum nozzle 3011 can suck up the chip and prevent it from falling; the air compressor is used to provide positive pressure to the vacuum nozzle 3011 to allow the vacuum nozzle 3011 to release the chip to complete the delivery.

[0073] In some embodiments, each vacuum nozzle 3011 can be individually controlled, that is, the presence or absence of a chip at the target location can be controlled to determine whether the vacuum nozzle 3011 performs a pickup operation. Specifically, a vacuum nozzle 3011 with a chip at the target location is controlled to perform a pickup operation; a vacuum nozzle 3011 without a chip at the target location is not controlled to perform a pickup operation.

[0074] Among them, the working method of the vacuum suction nozzle 3011 is as follows: the mobile positioning mechanism first drives the vacuum suction nozzle 3011 to move horizontally based on the QR code information of the chip recognized by the batch recognition system 20 received. After reaching the preset position, it drives the vacuum suction nozzle 3011 down to a preset height position from the chip in the vibration array disk 101. Then, for the vacuum suction nozzle 3011 with the chip at the target position, the vacuum pump is turned on to provide negative pressure (for example, the pressure value is -0.09 MPa) to control it to absorb the chip. Then, the mobile positioning mechanism drives the vacuum suction nozzle 3011 to move to the preset position above the corresponding storage silo 40, turns off the vacuum pump and turns on the air compressor to provide positive pressure (for example, the pressure value is 0.16 MPa) to control the vacuum suction nozzle 3011 to release the chip to complete the delivery.

[0075] Among them, the method for sucking all chips in the vibration array disk 101 is as follows: control the vibration array disk 101 to move forward and backward and cooperate with the mobile positioning mechanism to drive the vacuum suction nozzle 3011 to move left and right to form a cross, and the suction site covers all grooves in the vibration array disk 101.

[0076] In some embodiments, the distance between the nozzles of two adjacent vacuum nozzles 3011 is 10 mm.

[0077] It should be noted that those skilled in the art can set the distance between the nozzles of two adjacent vacuum nozzles 3011 according to actual conditions, and no specific limitation is made here.

[0078] In some embodiments, the vacuum nozzle 3011 is a retractable structure.

[0079] The vacuum nozzle 3011 is a retractable structure (e.g., a compression spring structure), which provides a buffer space. For example, the compression spring creates a 2-5 mm elastic buffer space during operation, thereby preventing damage to the chip caused by excessive downward impact when the vacuum nozzle 3011 is sucking the chip. More specifically, the buffer space (e.g., the buffer length) can be set to 3 mm. Those skilled in the art can adjust this according to actual circumstances, and this is not a specific limitation here.

[0080] In some embodiments, the vacuum nozzle 3011 is a silicone suction cup, and a compression spring is provided on the rear side of the vacuum nozzle 3011. The compression spring generates an elastic buffer space of 2-5 mm when working.

[0081] In some embodiments, the inner diameter of the silicone suction cup is 0.5 mm and the outer diameter is 1 mm.

[0082] The size of the vacuum nozzle 3011 is selected according to the specifications of the chip, and a higher density array chip picking can be achieved by selecting a small-sized nozzle.

[0083] In some embodiments, the number of vacuum nozzles 3011 is set to be less than the number of grooves, for example, 1 / 4, 1 / 3, or 1 / 2 of the number of grooves, further achieving high-throughput sorting while taking into account accuracy and efficiency.

[0084] In some embodiments, as Figure 4 As shown, the multi-channel pneumatic adsorption unit also includes a nozzle integrated substrate 3012 and a plurality of independent vacuum pipes 3013; the vacuum nozzles 3011 are fixed on the lower surface of the nozzle integrated substrate 3012 in an array arrangement, and each vacuum nozzle 3011 is connected to one end of a vacuum pipe 3013, and the other end of the vacuum pipe 3013 is connected to a pressure pump.

[0085] Specifically, the following is the detailed information of the batch picking and placing system 30: ① Implementation function: Batch absorb the chips in the vibration array disk 101 and place them into the target storage silo; ② Implementation method: Through vacuum negative pressure adsorption, combined with a mechanical module to perform movement, positioning, absorption and placement actions.

[0086] In some embodiments, as Figure 5 As shown, each storage bin 40 is generally in a streamlined funnel structure, and a controllable opening and closing door is provided at the bottom of each storage bin 40 for transferring chips.

[0087] The storage silo 40 features a streamlined funnel design, wide at the top and narrow at the bottom, to collect and concentrate the chips. A motorized door is installed at the bottom of the silo, allowing batches of chips to be drawn into the corresponding storage silo. Once the stored quantity reaches a set value, the door opens and the chips are released. Furthermore, the silo is equipped with a motor to vibrate and prevent chips from getting stuck during the loading and unloading process.

[0088] Among them, in addition to the transfer by opening the bottom door, the storage silo 40 can also use dumping, pipeline transportation, robotic arm pick-up and placement, pneumatic transportation and other methods to transfer chips.

[0089] In some embodiments, the surface of the vibration array disk 101 is made of flexible material.

[0090] For example, the surface of the vibration array disk 101 is made of materials such as POM (polyoxymethylene), Teflon (or aluminum alloy with Teflon sprayed on the surface), and PEEK (polyetheretherketone).

[0091] The disk surface of the vibration array disk 101 is made of flexible material, which can reduce the wear of the chip during the movement process (the process of the chip entering the groove from the disk surface) and prevent damage to the chip.

[0092] In some embodiments, a vacant area is reserved on the vibration array disk 101 for storing redundant chips.

[0093] That is, in addition to the plurality of grooves arranged in an array, the vibration array disk 101 is also provided with a vacant area for storing excess chips that are not captured by the grooves.

[0094] Example 1:

[0095] (1) Reagents and materials

[0096] Reagents: acetonitrile (ACN), acetone, deprotection reagent (3% TCA Deblock), activator (0.25 M), oxidant (0.05 M), capping reagent CAP A, and capping reagent CAP B.

[0097] (2) Vibration array disk

[0098] The vibration array disk has 400 grooves, each with a diameter of approximately Φ3mm-Φ4 mm and a depth of 0.3mm-0.6mm.

[0099] (3) Batch recognition system

[0100] It consists of two parts: lighting module and camera.

[0101] (4) Vacuum nozzle

[0102] 100 vacuum nozzles with an outer diameter of 1 mm are arranged in an array, and the arrangement spacing between the vacuum nozzles forms a spatial matching relationship with the array arrangement between the grooves on the vibration array disk.

[0103] (5) Storage silo

[0104] It is equipped with 6 chip storage silos, of which 4 storage silos are A base storage silo, T base storage silo, C base storage silo and G base storage silo, which are used to store chips of A base, T base, C base and G base to be synthesized respectively; the other 2 storage silos are synthesis final product storage silo and QR code abnormality temporary storage silo. Among them, the synthesis final product storage silo is used to store chips that have completed synthesis, and the QR code abnormality temporary storage silo is used to store chips with invalid QR codes or chips that cannot be identified (for example, there are problems such as QR codes being damaged, incomplete, or blurred).

[0105] Experimental procedures

[0106] 1. Chip Preparation: Chemically modified silicon-based chips are used, each with a specific QR code. The chip surface possesses the chemical activity required for DNA synthesis.

[0107] 2. High-throughput Identification and Sorting: After the chips enter the high-throughput sorting system for nucleic acid synthesis chips, the vibrating array plate reciprocates to regularly arrange the randomly stacked chips into grooves. A camera reads and analyzes the QR code information on the arrayed chips. Based on the recognition results, the system controls the vacuum nozzle to collect the chips in batches and transfer them to the corresponding storage silo.

[0108] 3. DNA synthesis: After sorting, the chips containing the bases to be synthesized are temporarily stored in the storage silo and transferred to the corresponding synthesis reaction vessel. The DNA synthesis steps are carried out in sequence, including deprotection, coupling, capping, oxidation, and washing.

[0109] 4. Step loop: Repeat the above steps according to the preset DNA synthesis sequence to gradually complete the synthesis of the target DNA sequence.

[0110] 5. DNA collection: The chips that have completed synthesis are collected together and subjected to aminolysis treatment to release the target DNA molecules to obtain the final DNA synthesis product.

[0111] The synthetic sequence information of this embodiment 1 is as follows:

[0112] T10: TTTTTTTTTT

[0113] Experimental results:

[0114] Table 1. Performance parameters of the high-throughput sorting system for nucleic acid synthesis chips:

[0115]

[0116] 2. DNA synthesis results

[0117] The purified DNA product was subjected to HPLC purity analysis. The HPLC test results of synthetic T10 were as follows: Figure 6 As shown in Table 2, the peak area of ​​the target product is 86.36%, that is, the purity of the primer synthesized by T10 sorting reaches 86.36%. According to formula (1), the coupling efficiency of T10 is 98.54%, where n=10.

[0118] (1)

[0119] Table 2 HPLC test data of synthetic T10

[0120]

[0121] The above examples and experimental results demonstrate that this application has broad application potential in the field of high-throughput DNA synthesis, particularly in parallel synthesis processes on large-scale chips. This application can effectively improve the efficiency of signal recognition-based sorting and has important application prospects in both standalone DNA synthesis chips and centralized reaction systems.

[0122] From the above, it can be seen that the high-throughput sorting system of the nucleic acid synthesis chip provided by the present application has the following advantages: ① Key steps such as group identification, batch sorting and centralized storage can effectively improve the working efficiency of large-scale chip parallel synthesis of nucleic acids; ② It can realize high-throughput sorting of chips and optimize the identification and sorting stages in the chip parallel synthesis process, thereby significantly reducing the proportion of sorting time in the whole process, thereby effectively improving the overall production capacity of the system, and ultimately promoting the acceleration of the industrialization process of nucleic acid synthesis technology; ③ It is friendly to the screening process of large-scale nucleic acid synthesis chips, and the working process has low intensity and short time on the chip, which can significantly reduce the working loss of the chip; ④ It can effectively reduce the mechanical damage of the system to the chip, and at the same time reduce the mutual wear between chips, thereby improving the stability of nucleic acid synthesis and ensuring better synthesis effect.

[0123] In summary, the high-throughput sorting system for nucleic acid synthesis chips provided in the embodiments of the present application, firstly, by providing a vibration array device 10, a batch identification system 20, a batch pick-and-place system 30, and multiple storage silos, batches of chips can be accurately screened and efficiently distributed at one time, thereby achieving high-throughput sorting of chips, thereby significantly reducing the proportion of sorting time in the entire process, thereby effectively improving the overall production capacity of the system, and ultimately promoting the acceleration of the industrialization process of nucleic acid synthesis technology; secondly, by allowing the vibration array disk 101 to perform reciprocating swings at a preset angle and oscillations at a low frequency (4 Hz to 6 Hz), the process of the chip entering the groove can be made smoother, and the problem of chip damage caused by large friction between chips and between the chip and the disk surface of the vibration array disk 101 can be avoided; finally, the disk surface of the vibration array disk 101 is made of a flexible material, which can reduce the wear of the chip during the movement process (the process of the chip entering the groove from the disk surface) and prevent chip damage.

[0124] An embodiment of the present application further provides a nucleic acid synthesis system, comprising a nucleic acid synthesis module and a high-throughput sorting system of the nucleic acid synthesis chip described in any one of the above embodiments.

[0125] Although the present invention relates to a batch pick and place system, the batch pick and place system does not necessarily have to complete batch operations. The system can also complete single pick and place operations.

[0126] In the above embodiments, the description of each embodiment has its own focus. For parts that are not described in detail in a certain embodiment, reference can be made to the relevant descriptions of other embodiments.

[0127] The above is a detailed introduction to a high-throughput sorting system for a nucleic acid synthesis chip provided in an embodiment of the present application. Specific examples are used herein to illustrate the principles and implementation methods of the present application. The description of the above embodiments is only used to help understand the technical solutions and core ideas of the present application. Those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some of the technical features therein with equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the scope of the technical solutions of the embodiments of the present application.

Claims

1. A high-throughput sorting system for nucleic acid synthesis chip, characterized in that: It includes a vibrating array device, a batch recognition system, a batch pick-and-place system, and multiple storage silos; The vibration array device includes a vibration array disk and a driving mechanism connected to the vibration array disk. The vibration array disk is provided with a plurality of grooves arranged in an array for accommodating chips. The driving mechanism is used to drive the vibration array disk to perform reciprocating swings at a preset angle and oscillations at a preset frequency, so that chips placed on the vibration array disk enter the grooves, and each groove can only accommodate one chip. The number of the grooves is at least 100. The batch recognition system stores a preset nucleic acid synthesis sequence, and is used to perform group recognition of the chips on the vibration array disk, obtain identification information on each chip, and compare the obtained identification information with the preset nucleic acid synthesis sequence to generate pick-and-place operation sorting information; The number of chips that the batch recognition system performs group recognition on matches the number of grooves; The batch pick-and-place system transfers the chips to corresponding storage silos according to the pick-and-place operation sorting information.

2. The high-throughput sorting system for nucleic acid synthesis chip according to claim 1, wherein: The batch pick-and-place system includes a pick-and-place actuator and a mobile positioning mechanism connected to the pick-and-place actuator; The pick-and-place actuator includes a multi-channel pneumatic adsorption unit, which includes vacuum suction nozzles arranged in an array and a pressure pump connected to the vacuum suction nozzles, wherein the arrangement spacing between the vacuum suction nozzles forms a spatial matching relationship with the array arrangement between the grooves on the vibration array disk.

3. The high-throughput sorting system for nucleic acid synthesis chip according to claim 2, wherein: The multi-channel pneumatic adsorption unit also includes a nozzle integrated substrate and a plurality of independent vacuum pipes; The vacuum nozzles are fixed on the lower surface of the nozzle integrated substrate in an array arrangement. Each of the vacuum nozzles is connected to one end of the vacuum pipe, and the other end of the vacuum pipe is connected to the pressure pump.

4. The high-throughput sorting system for nucleic acid synthesis chip according to claim 2 or 3, characterized in that: The vacuum suction nozzle is a silicone suction cup. A compression spring is provided at the rear side of the vacuum suction nozzle. The compression spring generates an elastic buffer space of 2-5 mm during operation.

5. The high-throughput sorting system for nucleic acid synthesis chip according to claim 1, wherein: The batch recognition system includes a lighting module and a camera; The lighting module is used to project illumination light onto the chips arranged in an array on the vibration array disk, and the camera is used to perform optical imaging on the chips arranged in an array on the vibration array disk to obtain identification information on each chip.

6. The high-throughput sorting system for nucleic acid synthesis chip according to claim 5, characterized in that: The field of view of the camera is greater than 125 mm×125 mm, and the exposure time of a single frame is less than 0.02 seconds.

7. The high-throughput sorting system for nucleic acid synthesis chip according to claim 1, wherein: The vibration array disk is made of flexible material.

8. The high-throughput sorting system for nucleic acid synthesis chip according to claim 1, wherein: The shapes of the groove include cylindrical, rectangular, square and hemispherical.

9. The high-throughput sorting system for nucleic acid synthesis chip according to claim 1, wherein: Each of the storage silos has a streamlined funnel structure, and a controllable opening and closing door is provided at the bottom of the storage silo for transferring chips.

10. A nucleic acid synthesis system, characterized in that: A high-throughput sorting system comprising a nucleic acid synthesis module and the nucleic acid synthesis chip according to any one of claims 1 to 9.

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