Automated screening device and automated screening platform

Abstract

The present invention provides an automated screening device and an automated screening platform. The automated screening device comprises a base plate, a fluid plate, a liquid storage mechanism, an injection mechanism, and a switching mechanism; a mounting hole is formed in the base plate; the fluid plate is fixed on the base plate, and the fluid plate is provided with a first fluid structure and a plurality of second fluid structures surrounding the first fluid structure; the liquid storage mechanism is fixed on the fluid plate, and a first cavity, an incubation cavity and a plurality of functional cavities are formed in the liquid storage mechanism; the injection mechanism is arranged in the first cavity; the switching mechanism is arranged in the mounting hole and can rotate in the mounting hole, and the switching mechanism can rotate to a position of being communicated with the first fluid structure and any second fluid structure. The automated screening device of the embodiments does not require manual sample transfer, effectively reducing experimental result errors caused by manual operation; and the cavities in the liquid storage mechanism are closed spaces, reducing the risk of sample contamination.

Description

Automated screening device and automated screening platform

[0001] This application claims priority from the following patent applications:

[0002] Priority to the prior application for “Automated Screening Device and Automated Screening Platform” filed with the State Intellectual Property Office of China on July 20, 2023, with patent application number “202310901891.7”;

[0003] Priority to the prior application for patent application number 202321932973.X, filed with the State Intellectual Property Office of China on July 20, 2023, entitled “Automated Screening Device and Automated Screening Platform”;

[0004] The entire contents of said prior application are incorporated into the present application by reference. Technical Field

[0005] The present invention relates to the field of DNA-encoded compound library screening or drug screening, and in particular to an automated screening device and an automated screening platform. Background Art

[0006] Drug discovery, from target screening to final market approval, involves a lengthy and tedious process. Target screening and identification, as the starting point of drug discovery, are crucial to the entire process. Therefore, methods that enable rapid and efficient target screening and identification are crucial to accelerating and improving drug discovery efficiency.

[0007] DNA-encoded library screening (DEL) is a high-throughput drug discovery technology. Its basic principle is to utilize DNA encoding technology to combine large-scale compound libraries with DNA molecules to form a DNA-encoded compound library. The library then screens the interactions between proteins and the encoded compounds to select compounds with high affinity and selectivity. DEL screening can effectively shorten the drug discovery cycle and reduce R&D costs. It can also rapidly identify compounds with high affinity, providing a new approach for drug development. In drug discovery, DEL technology is widely used to discover new drug targets, new drug molecules, and optimize existing drug molecules. For example, by screening drug libraries, anticancer drug molecules with high affinity can be discovered, or new ideas and methods for the treatment of certain diseases can be provided.

[0008] The characteristic of DNA-encoded compound libraries is that each compound is connected to a specific DNA fragment at the molecular level to label the compound's structural information. Currently, the main method for screening DNA-encoded compound libraries is to incubate the active target protein with the DNA-encoded compound library through manual experiments by experimenters. Compounds with strong affinity bind to the protein and are enriched, while compounds with weak affinity or non-binding are washed away. Since the compounds correspond one-to-one with the DNA-encoded information, the structural information of high-affinity compounds can be obtained through high-throughput sequencing technology. After resynthesizing the compounds without DNA tags, activity verification and structural optimization are carried out to obtain lead compounds, which solves the problem of effectively identifying lead compounds when a large number of molecules are screened against the target at the same time.

[0009] Currently, there are no automated instruments or equipment specifically designed for DEL screening on the market. Screening experiments primarily rely on manual labor or other equipment used for extraction and purification. Manually completing experiments inevitably introduces user processing errors, reduces the reproducibility of results, increases sample processing time, and hinders the standardization of some screening methods. Furthermore, existing equipment is not fully compatible with certain application scenarios. Some screening schemes or screening conditions are complex to implement with existing equipment, resulting in a greater risk of sample cross-contamination when processing large numbers of samples and requiring numerous user processing steps.

[0010] Summary of the Invention

[0011] The purpose of the present invention is to provide an automated screening device based on DEL technology, combined with an adapted automated screening platform to solve the problems raised in the above background technology.

[0012] The present invention aims to solve, at least to a certain extent, one of the technical problems in the field of DEL screening. To this end, the present invention provides an automated screening device comprising:

[0013] A liquid storage mechanism, wherein the liquid storage mechanism is formed with a first cavity, an incubation cavity and a plurality of functional cavities;

[0014] an injection mechanism, the injection mechanism having an injection cavity, one end of the injection cavity being disposed in the first cavity;

[0015] a flow distribution mechanism connected to the lower surface of the liquid storage mechanism and used to connect the injection cavity with the incubation cavity or the functional cavity;

[0016] A switching mechanism is connected to the flow distribution mechanism and cooperates with the flow distribution mechanism to enable the injection cavity to communicate with the incubation cavity or the functional cavity through the flow distribution mechanism.

[0017] The automated screening device of the present invention transfers the sample liquid in each cavity through an injection mechanism. The overall design adopts a compact automation and is compatible with a simple operating system. There is no need for manual sample transfer, which effectively reduces the error in experimental results caused by manual operation and increases repeatability. Moreover, each cavity on the liquid storage mechanism is a closed space, and the experimental samples and reagents are integrated inside a liquid storage mechanism. They do not come into contact with the outside world during operation, reducing the risk of sample contamination.

[0018] According to the automated screening device of the present invention, the flow distribution mechanism includes a base plate and a flow distribution disk, and the flow distribution disk is arranged between the base plate and the liquid storage mechanism; the switching mechanism cooperates with the flow distribution disk to enable the injection chamber to communicate with the incubation chamber or the functional chamber through the flow distribution mechanism.

[0019] According to the automated screening device of the present invention, a mounting hole is provided on the bottom plate; the switching mechanism is arranged in the mounting hole and can rotate in the mounting hole, and the switching mechanism can rotate to connect the injection chamber with the incubation chamber or the functional chamber through the distribution disk.

[0020] According to the automated screening device of the present invention, the distribution disk has a first distribution structure and a plurality of second distribution structures surrounding the first distribution structure; the injection chamber is connected to the first distribution structure, the incubation chamber is connected to one of the second distribution structures, and the remaining second distribution structures are connected to the plurality of functional chambers in a one-to-one correspondence; the switching mechanism is capable of rotating to connect the first distribution structure and any one of the second distribution structures.

[0021] According to the automated screening device of the present invention, a sealing plate is provided between the distribution plate and the bottom plate, the sealing plate having a third distribution structure and a plurality of fourth distribution structures surrounding the third distribution structure; the third distribution structure is in correspondence communication with the first distribution structure, and the plurality of fourth distribution structures are in correspondence communication with the plurality of second distribution structures;

[0022] The switching mechanism connects the first flow distribution structure and any one of the second flow distribution structures by connecting the third flow distribution structure and any one of the fourth flow distribution structures.

[0023] According to the automated screening device of the present invention, the width of the fourth flow distribution structure is less than or equal to the width of the second flow distribution structure, and the length of the fourth flow distribution structure is less than or equal to the length of the second flow distribution structure;

[0024] The end of the second flow distribution structure is in a teardrop shape, a circle or an ellipse shape.

[0025] According to the automated screening device of the present invention, a long groove is provided on the upper end surface of the switching mechanism, the first end of the long groove is always connected to the third flow distribution structure, and the second end of the long groove can be connected to any fourth flow distribution structure.

[0026] According to the automated screening device of the present invention, the lower end surface of the switching mechanism is provided with a snap-in groove for connecting the rotating module;

[0027] The switching mechanism is arranged on a switching mechanism base and can rotate relative to the switching mechanism base; the switching mechanism base is arranged in the mounting hole.

[0028] According to the automated screening device of the present invention, the first flow distribution structure is a flow distribution hole or a flow distribution groove, and the second flow distribution structure is a flow distribution hole or a flow distribution groove.

[0029] According to the automated screening device of the present invention, the third flow distribution structure is a flow distribution hole or a flow distribution groove, and the fourth flow distribution structure is a flow distribution hole or a flow distribution groove.

[0030] According to the automated screening device of the present invention, the incubation chamber is independently provided, and a holding space is provided around the incubation chamber;

[0031] A plurality of the functional chambers and the incubation chambers surround the first chamber;

[0032] At least some of the functional cavities have different sizes and volumes.

[0033] According to the automated screening device of the present invention, the incubation chamber is covered with an incubation chamber rubber pad, and the incubation chamber rubber pad is provided with a first air vent;

[0034] The plurality of functional cavities are covered with a functional cavity rubber pad, and the functional cavity rubber pad is provided with a plurality of second ventilation holes, and the plurality of second ventilation holes correspond to the plurality of functional cavities one by one.

[0035] According to the automated screening device of the present invention, a filter membrane is provided at the bottom of the incubation chamber, and the filter membrane is used for supporting fillers and filtering liquids.

[0036] According to the automated screening device of the present invention, the upper end surface of the switching mechanism is coated with at least one layer of hydrophobic sealing material, and the surface of the distribution plate is coated with at least one layer of hydrophobic sealing material.

[0037] The present invention also provides an automated screening platform, comprising the automated screening device of the present invention, a rotating module, a driving mechanism, a temperature control module and an electric control module.

[0038] The present invention also provides an automated screening platform, comprising:

[0039] Automated screening equipment;

[0040] a rotating module, the rotating module being in transmission connection with the switching mechanism to control the rotation of the switching mechanism;

[0041] a driving mechanism, which can clamp the injection mechanism and drive the injection mechanism to inject or aspirate liquid into the incubation chamber or the functional chamber;

[0042] a temperature control module, the temperature control module being movable relative to the incubation chamber and configured to heat the incubation chamber; and

[0043] An electric control module is electrically connected to the rotation module, the driving mechanism and the temperature control module to control the rotation module, the driving mechanism and the temperature control module to work in coordination.

[0044] Additional aspects and advantages of the present invention will be set forth in part in the description which follows and, in part, will be obvious from the description which follows, or may be learned by practice of the invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the invention and, together with the description, serve to explain the principles of the invention.

[0046] FIG1 is a perspective schematic diagram of an automated screening device according to an embodiment of the present invention;

[0047] FIG2 is an exploded schematic diagram of an automated screening device according to one embodiment of the present invention;

[0048] FIG3 is a perspective schematic diagram of a switching mechanism in one embodiment of the present invention;

[0049] FIG4 is a three-dimensional schematic diagram of an automated screening platform in one embodiment of the present invention.

[0050] Figure markings: 11-first cavity; 12-incubation cavity; 121-filter membrane; 13-functional cavity; 14-switching mechanism; 141-long groove; 142-clamping groove; 143-switching mechanism base; 15-injection mechanism; 16-incubation cavity rubber pad; 17-functional cavity rubber pad; 20-rotation module; 30-driving mechanism; 40-temperature control module; 50-electrical control module; 60-bottom plate; 61-mounting hole; 62-fastening screw; 70-distribution plate; 71-first distribution structure; 72-second distribution structure; 73-sealing plate; 731-third distribution structure; 732-fourth distribution structure; 90-liquid storage mechanism. DETAILED DESCRIPTION

[0051] The technical solutions of the present invention will be described in further detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are encompassed within the scope of protection that the present invention is intended to protect.

[0052] 1 and 2 , this embodiment provides an automated screening device, which mainly includes a flow distribution mechanism, a liquid storage mechanism 90 , an injection mechanism 15 and a switching mechanism 14 .

[0053] Among them, the liquid storage mechanism 90 is formed with a first cavity 11, an incubation cavity 12 and a plurality of functional cavities 13; the injection mechanism 15 is arranged in the first cavity 11, and the first cavity 11 can be used as an installation cavity for the injection mechanism 15. The injection mechanism 15 has an injection cavity for injecting or aspirating liquid, and one end of the injection cavity is arranged in the first cavity 11; the flow distribution mechanism is connected to the lower surface of the liquid storage mechanism 90, and is used to connect the injection cavity with the incubation cavity 12 or the functional cavity 13; so that the injection cavity can be connected with the incubation cavity 12 and can also be connected with each functional cavity 13 through the flow distribution mechanism. The switching mechanism 14 is connected to the flow distribution mechanism and cooperates with the flow distribution mechanism so that the injection cavity can be connected with the incubation cavity 12 or the functional cavity 13 through the flow distribution mechanism. The switching mechanism 14 can change the cavity to which the injection cavity is connected, so that the flow distribution mechanism can distribute the liquid according to the experimental requirements.

[0054] Among them, the forms in which the injection chamber can be connected with the incubation chamber 12 or the functional chamber 13 through the switching mechanism 14 include various situations. Specifically, the injection chamber can be connected with only one chamber at the same time and relatively sealed with other chambers, or it can be connected with more than two chambers at the same time. For example: when the injection chamber is connected with the incubation chamber 12, it is relatively sealed with other functional chambers 13; when the injection chamber is connected with a certain functional chamber 13, it is relatively sealed with other functional chambers 13 and the incubation chamber 12; in other embodiments, the injection chamber can also be set to be connected with more than two functional chambers 13 at the same time.

[0055] The automated screening device of the above embodiment transfers the sample liquid in each cavity through the injection mechanism 15. The overall compact automated design is adapted to a simple operating system and does not require manual sample transfer, effectively reducing the error in experimental results caused by manual operation and increasing repeatability. Moreover, each cavity on the liquid storage mechanism 90 is a closed space, and the experimental samples and reagents are integrated inside a liquid storage mechanism 90. They do not come into contact with the outside world during operation, thereby reducing the risk of sample contamination.

[0056] In some embodiments, the flow distribution mechanism includes a base plate 60 and a flow distribution disk 70, which is disposed between the base plate 60 and the liquid storage mechanism 90. The switching mechanism 14 cooperates with the flow distribution disk 70 to connect the injection chamber to the incubation chamber 12 or the functional chamber 13 through the flow distribution mechanism. The base plate 60 and the flow distribution disk 70 can be an integrated structure or a separate structure.

[0057] The base plate 60 primarily serves as a fixture and installation element. It forms the foundation of the entire device and can be snapped onto the screening device base. The sides and bottom of the screening device base contain slots that help secure the base plate 60 to the appropriate machine, allowing the screening device to be securely clamped within the mounting slots and prevent shaking. The distribution plate 70 primarily distributes liquid flow, connecting the injection chamber to the incubation chamber 12 or functional chamber 13.

[0058] In some embodiments, a mounting hole 61 is provided on the base plate 60; the switching mechanism 14 is disposed in the mounting hole 61 and can rotate within the mounting hole 61. The switching mechanism 14 can rotate to connect the injection chamber with the incubation chamber 12 or the functional chamber 13 through the distribution disk 70.

[0059] 1 and 2 , this embodiment provides an automated screening device, which mainly includes a base plate 60 , a distribution plate 70 , a liquid storage mechanism 90 , an injection mechanism 15 and a switching mechanism 14 .

[0060] The liquid storage mechanism 90 is fixed on the distribution disk 70, and the liquid storage mechanism 90 is formed with a first cavity 11, an incubation cavity 12 and a plurality of functional cavities 13; the injection mechanism 15 is arranged in the first cavity 11, and the injection mechanism 15 has an injection cavity. The distribution disk 70 is mainly used for liquid distribution, and the distribution disk 70 is fixed on the base plate 60. The switching mechanism 14 is arranged in the mounting hole 61 and can rotate in the mounting hole 61. The switching mechanism 14 can rotate so that the injection cavity is connected to the incubation cavity 12 or the plurality of functional cavities 13 through the distribution disk 70. In other words, the switching mechanism 14 has multiple rotation positions. At different positions, the cavity connected to the injection cavity is also different, and by rotating the switching mechanism 14, the injection cavity can be connected to any functional cavity 13, and can also be connected to the incubation cavity 12, thereby realizing the flow of liquid between the two connected cavities. The switching mechanism 14 can also make the injection cavity not connected to any cavity at a certain rotation position.

[0061] The switching mechanism 14 cooperates with the distribution plate 70 to connect the injection chamber with the incubation chamber 12 or the functional chamber 13. There are many possible implementations for connecting the injection chamber with the incubation chamber 12 or the functional chamber 13. Those skilled in the art can design a specific connection structure based on actual design requirements. Some specific implementations of the connection structure will be described below, but they do not represent the only achievable connection structure.

[0062] The automated screening device of the above embodiment transfers the sample liquid in each cavity through the injection mechanism 15. The overall compact automated design is adapted to a simple operating system, and there is no need for manual sample transfer, which effectively reduces the error in experimental results caused by manual operation and increases repeatability. Moreover, each cavity on the liquid storage mechanism 90 is a closed space, and the experimental samples and reagents are integrated inside a liquid storage mechanism 90. During operation, there is no contact with the outside world, which reduces the risk of sample contamination. The screening device can adapt to a variety of application scenarios and can be adjusted accordingly according to different sample processing scenarios. Users can assemble modular operating procedures to meet more flexible and detailed screening methods and customized services.

[0063] 1 and 2 , this embodiment provides an automated screening device, which mainly includes a base plate 60 , a distribution plate 70 , a liquid storage mechanism 90 , an injection mechanism 15 and a switching mechanism 14 .

[0064] The base plate 60 forms the foundation of the entire device and can be snapped onto the screening device base. The sides and bottom of the screening device base contain slots that help secure the base plate 60 to the corresponding machine. This allows the screening device to be securely mounted within the mounting slots, preventing it from shaking. The base plate 60 has a mounting hole 61 and multiple screw holes surrounding it.

[0065] The distribution plate 70 is mainly used for liquid distribution. The distribution plate 70 is fixed on the base plate 60. The distribution plate 70 has a first distribution structure 71 and multiple second distribution structures 72 surrounding the first distribution structure 71; specifically, the first distribution structure 71 and the multiple second distribution structures 72 are through holes.

[0066] The liquid storage mechanism 90 is fixed to the distribution plate 70 and is formed with a first cavity 11, an incubation cavity 12, and multiple functional cavities 13. The injection cavity is connected to the first distribution structure 71. The incubation cavity 12 is connected to one of the second distribution structures 72, specifically to the outer end of the second distribution structure 72 (i.e., the end away from the first distribution structure 71). The remaining second distribution structures 72 are connected to the multiple functional cavities 13 in a one-to-one correspondence, specifically to the outer ends of the second distribution structures 72 (i.e., the ends away from the first distribution structure 71). For example, the bottom centers of the first cavity 11, the incubation cavity 12, and the multiple functional cavities 13 are each provided with a central hole for the flow of liquid in and out.

[0067] The injection mechanism 15 is arranged in the first cavity 11. The injection mechanism 15 has an injection cavity. The injection mechanism 15 may include an injection push rod 151 with a piston. The piston is located in the injection cavity. The injection push rod 151 moves the piston in the injection cavity, thereby sucking the liquid in the incubation cavity 12 or the functional cavity 13 into the injection cavity, or transporting the liquid in the injection cavity to the incubation cavity 12 or the functional cavity 13.

[0068] The switching mechanism 14 is arranged in the mounting hole 61 and can rotate in the mounting hole 61. The switching mechanism 14 can rotate to a position connecting the first distribution structure 71 and any one of the second distribution structures 72, so that the injection chamber is connected to the incubation chamber 12 or to any one of the functional chambers 13. When the injection chamber is connected to the incubation chamber 12, the injection chamber and the incubation chamber 12 are sealed relative to other chambers, and the injection push rod 151 can be used to control the flow of liquid between the injection chamber and the incubation chamber 12; similarly, when the injection chamber is connected to a certain functional chamber 13, the injection chamber and the functional chamber 13 are sealed relative to other chambers, and the injection push rod 151 can be used to control the flow of liquid between the injection chamber and the functional chamber 13.

[0069] By setting a first distribution structure 71 and multiple second distribution structures 72 on the distribution disk 70 and cooperating with the switching mechanism 14, convenient communication between the injection chamber and the incubation chamber 12 or the functional chamber 13 is achieved. The sealing effect of the connection is good and easy to implement.

[0070] In some embodiments, a sealing plate 73 is provided between the distribution disc 70 and the base plate 60. The sealing plate 73 has a third distribution structure 731 and a plurality of fourth distribution structures 732 surrounding the third distribution structure 731. The third distribution structure 731 is connected to the first distribution structure 71, and the plurality of fourth distribution structures 732 are connected to the plurality of second distribution structures 72 in a one-to-one correspondence. The switching mechanism 14 connects the first distribution structure 71 with any one of the second distribution structures 72 by connecting the third distribution structure 731 with any one of the fourth distribution structures 732. The provision of the sealing plate 73 improves the overall sealing of the screening device and prevents leakage of the sample liquid. Taking the injection of liquid into the incubation chamber 12 from the injection chamber as an example, the flow path of the liquid is: from the injection chamber, it flows into the first distribution structure 71, the third distribution structure 731, the fourth distribution structure 732, the second distribution structure 72, and the incubation chamber 12 in sequence.

[0071] Specifically, the width of the fourth distribution structure 732 is less than or equal to the width of the second distribution structure 72, and the length of the fourth distribution structure 732 is less than or equal to the length of the second distribution structure 72; the end of the second distribution structure 72 is teardrop-shaped, circular or elliptical.

[0072] In some embodiments, the first flow distribution structure 71 is a flow distribution hole or a flow distribution groove, the second flow distribution structure 72 is a flow distribution hole or a flow distribution groove; the third flow distribution structure 731 is a flow distribution hole or a flow distribution groove, and the fourth flow distribution structure 732 is a flow distribution hole or a flow distribution groove.

[0073] For example, the first flow distribution structure 71 and the third flow distribution structure 731 are both flow distribution circular holes with the same inner diameter, the second flow distribution structure 72 is a flow distribution elongated hole, and the fourth flow distribution structure 732 is a flow distribution elongated groove.

[0074] In some embodiments, the bottom plate 60, the sealing plate 73, the distribution plate 70 and the liquid storage mechanism 90 are connected and fastened by fastening screws 62 to ensure the sealing after the connection.

[0075] In some embodiments, the injection mechanism 15 may be a component similar to a syringe, which is detachably mounted on the first cavity 11 so that syringes of different specifications can be replaced as needed.

[0076] In some embodiments, referring to FIG3 , the switching mechanism 14 can be specifically a switching valve. An elongated groove 141 is formed on the upper end surface of the switching mechanism 14. The first end of the elongated groove 141 is always connected to the third flow distribution structure 731, and the second end of the elongated groove 141 can be connected to any of the fourth flow distribution structures 732. Taking the example of liquid being injected from the injection chamber into the incubation chamber 12, the liquid flow path is as follows: from the injection chamber, it flows into the first flow distribution structure 71, the third flow distribution structure 731, the elongated groove 141 on the switching mechanism 14, the fourth flow distribution structure 732, the second flow distribution structure 72, and the incubation chamber 12 in sequence.

[0077] Furthermore, a snap-in slot 142 for connecting to the rotating module 20 is formed on the lower end surface of the switching mechanism 14 ; the snap-in slot 142 is adapted to snap-in with the rotating module 20 , so that the switching mechanism 14 can rotate under the drive of the rotating module 20 .

[0078] In order to further avoid leakage or communication between different cavities, a switching mechanism base 143 is provided at the bottom of the switching mechanism 14. The switching mechanism 14 is provided on the switching mechanism base 143 and can rotate relative to the switching mechanism base 143; the switching mechanism base 143 is provided in the mounting hole 61.

[0079] In some embodiments, the incubation chamber 12 is independently arranged, and there is a accommodating space around the incubation chamber 12, so as to facilitate the temperature control module 40 to heat the incubation chamber 12; specifically, two mutually isolated protrusions are formed on the liquid storage mechanism 90, the incubation chamber 12 is formed on one of the small protrusions, and the first chamber 11 and all functional chambers 13 are formed on the other large protrusion.

[0080] Spatially, multiple functional chambers 13 and the incubation chamber 12 surround the first chamber 11. At least some of the functional chambers 13 have different sizes and volumes, meaning the functional chambers 13 can have various specifications to meet different experimental requirements. The multiple functional chambers 13 include at least one air exhaust chamber.

[0081] In some embodiments, the incubation chamber 12 is covered with an incubation chamber rubber pad 16, which has a first air hole; the multiple functional cavities 13 are covered with a functional cavity rubber pad 17, which has a multiple second air hole, and the multiple second air holes correspond one-to-one to the multiple functional cavities 13.

[0082] The incubation chamber rubber pad 16 and the functional chamber rubber pad 17 are used to protect the cavity. At the same time, the air holes on the rubber pads are used to ensure that the cavity can be connected to the atmosphere when the injection mechanism 15 extracts or injects liquid, balancing the cavity and external air pressure to ensure smooth operation of the injection device.

[0083] In some embodiments, a filter membrane 121 is provided at the bottom of the incubation chamber 12 , and the filter membrane 121 is used to support fillers and filter liquids.

[0084] In some embodiments, the upper end surface of the switching mechanism 14 is coated with at least one layer of hydrophobic sealing material for achieving a sealing effect. The surface of the distribution plate 70 is coated with at least one layer of hydrophobic sealing material for achieving a sealing effect.

[0085] Referring to FIG. 4 , this embodiment further provides an automated screening platform, comprising the automated screening device of any of the aforementioned embodiments, and further comprising a rotation module 20, a drive mechanism 30, a temperature control module 40, and an electrical control module 50. Because the automated screening platform includes the automated screening device of any of the aforementioned embodiments, all screening steps are integrated within the liquid storage mechanism, minimizing contact with the outside world and reducing external and component contamination. The switching mechanism 14 automates the cleaning, elution, and collection processes involved in the screening process, resulting in a high degree of automation throughout the entire experimental process, making the experiments more standardized and unified.

[0086] Referring to Figure 4, this embodiment further provides an automated screening platform, including the automated screening device of any of the above embodiments, a rotating module 20, a driving mechanism 30, a temperature control module 40 and an electronic control module 50. The rotating module 20 is connected to the switching mechanism 14 in a transmission manner to control the rotation of the switching mechanism 14; the driving mechanism 30 can clamp the injection push rod 151 of the injection mechanism 15, and drive the injection push rod 151 of the injection mechanism 15 to move with the piston in the injection chamber, thereby injecting liquid or aspirating liquid into the incubation chamber 12 or the functional chamber 13; the temperature control module 40 can move relative to the incubation chamber 12 for heating the incubation chamber 12; the electronic control module 50 is electrically connected to the rotating module 20, the driving mechanism 30 and the temperature control module 40 to control the coordinated operation of the rotating module 20, the driving mechanism 30 and the temperature control module 40.

[0087] The following provides a screening method for an automated screening platform, which specifically includes the following steps:

[0088] 5-40 μg of target protein and 1-1.5 nmol of DNA-encoded compound library required for screening are manually injected into the incubation chamber 12 by a pipette or other equipment to complete the loading, and the automated screening platform is started to complete the subsequent automated screening process.

[0089] Specifically, the incubation chamber 12 is pre-loaded with pre-treated immobilized resin beads. 5 to 40 μg of target protein and 1 to 1.5 nmol of the DNA-encoded compound library are manually injected into the incubation chamber 12 using a pipette, and mixed and incubated in the incubation chamber 12 so that the target is immobilized on the immobilized resin beads in the incubation chamber and the small molecule compounds in the DNA-encoded compound library are combined with the target.

[0090] After the incubation is completed, the incubation effluent is drawn out through the injection mechanism 15 and a sample is kept in a reserved vacant functional cavity 13;

[0091] At the beginning of the cleaning process, cleaning liquid is drawn from the functional chamber 13 and injected into the injection chamber. Then, it is pumped back and forth into the incubation chamber 12. The waste liquid is drawn from the incubation chamber 12 and injected into the injection chamber. Then, it is pumped back and forth into the functional chamber 13 containing the waste liquid for disposal. This completes the cleaning process. After repeated cleaning processes, unbound small molecules are washed away by the cleaning liquid.

[0092] At the beginning of the elution process, eluate is drawn from another functional chamber 13 containing eluate and injected into the injection chamber. This is then injected into the incubation chamber 12. The target protein is denatured by heating for a predetermined time, causing small molecules bound to the target to dissociate and enter the eluate. Subsequently, the eluate is injected into another functional chamber 13 storing the sample through the injection chamber. Finally, the small molecules that have entered the eluate are recovered as the sample obtained after screening, completing one elution process. This elution process can be repeated as needed.

[0093] Furthermore, in the above embodiment, the target and the DNA-encoded compound library were incubated in the incubation chamber 12 at room temperature (25°C) for 30 minutes to 1 hour. The immobilized resin beads were washed at least six times. The small molecules bound to the target were then heated at 95°C for 10 minutes to denature the target. After the screening experiment was completed, the screened samples were recovered and subjected to next-generation sequencing (NGS) to identify the molecular species identified.

[0094] The target protein can be changed according to experimental requirements, including but not limited to protein, ribonucleic acid (RNA), etc.

[0095] Among them, the immobilized resin beads required for immobilizing the target protein can be selected according to needs, and the immobilization methods that can be used include but are not limited to the combination of polyhistidine tag (His tag) and nickel-nitrilotriacetic acid (Ni-NTA), the combination of biotin and avidin, and the combination of glutathione S-transferase (GST) and glutathione (GSH).

[0096] Elution can be performed by heating to denature the target protein, or by competitive elution using molecules with a stronger affinity for the immobilized group. Due to technical characteristics, a large number of small molecules in the DNA-encoded compound library that do not bind to the target protein may cause background noise. Screening experimental condition parameters can usually be verified using positive small molecules known to bind to the target protein.

[0097] Multiple rounds of screening can be performed to enrich for binding molecules and improve the signal-to-noise ratio. In subsequent rounds, new target proteins and molecules eluted from the previous round can be added as input samples, and the above screening steps can be repeated.

[0098] The automated screening platform of the above embodiment integrates each operation step of the screening experiment, and all the screening steps are gathered inside the liquid storage mechanism, rarely coming into contact with the outside world, thereby reducing external contamination and component contamination; the switching mechanism 14 connected to the syringe realizes the automation of the cleaning, elution and collection processes in the screening, and the entire experimental process has a high degree of automation, making the experiment more standardized and unified.

[0099] In the description of the present invention, 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", "axial", "radial", "circumferential" and the like to 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 invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as limiting the present invention.

[0100] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of the technical features being referred to. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one such feature. In the description of the present invention, "plurality" means at least two, such as two, three, etc., unless otherwise specifically defined.

[0101] In the present invention, unless otherwise specified or limited, the terms "installed," "connected," "connect," "fixed," etc. should be understood in a broad sense. For example, they can refer to fixed connection, detachable connection, or integration; mechanical connection, electrical connection, or communication; direct connection or indirect connection through an intermediate medium; internal communication between two elements or interaction between two elements, unless otherwise specified. Those skilled in the art will understand the specific meanings of the above terms in the present invention based on specific circumstances.

[0102] In the present invention, unless otherwise expressly specified or limited, when a first feature is "above" or "below" a second feature, it may mean that the first and second features are in direct contact, or that the first and second features are in indirect contact through an intermediary. Furthermore, when a first feature is "above," "above," or "above" a second feature, it may mean that the first feature is directly above or diagonally above the second feature, or simply means that the first feature is at a higher level than the second feature. When a first feature is "below," "below," or "below" a second feature, it may mean that the first feature is directly below or diagonally below the second feature, or simply means that the first feature is at a lower level than the second feature.

[0103] In the present invention, the terms "one embodiment", "some embodiments", "examples", "specific examples", or "some examples" mean that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic expressions of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art can combine and combine different embodiments or examples described in this specification and the features of different embodiments or examples without contradiction.

[0104] Although the embodiments of the present invention have been shown and described above, it will be understood that the above embodiments are illustrative and are not to be construed as limitations on the present invention. A person skilled in the art may change, modify, replace and modify the above embodiments within the scope of the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included within the scope of protection of the present invention.

Claims

1. An automated screening device, characterized in that: include: A liquid storage mechanism (90), wherein the liquid storage mechanism (90) is formed with a first chamber (11), an incubation chamber (12) and a plurality of functional chambers (13); An injection mechanism (15), the injection mechanism (15) having an injection cavity, one end of the injection cavity being arranged in the first cavity (11); a flow distribution mechanism, the flow distribution mechanism being connected to the lower surface of the liquid storage mechanism (90) and being used to connect the injection chamber with the incubation chamber (12) or the functional chamber (13); and A switching mechanism (14), wherein the switching mechanism (14) is connected to the flow distribution mechanism and cooperates with the flow distribution mechanism so that the injection chamber can be connected to the incubation chamber (12) or the functional chamber (13) through the flow distribution mechanism.

2. The automated screening device according to claim 1, characterized in that: The flow distribution mechanism comprises a base plate (60) and a flow distribution disk (70), wherein the flow distribution disk (70) is arranged between the base plate (60) and the liquid storage mechanism (90); the switching mechanism (14) cooperates with the flow distribution disk (70) to enable the injection chamber to communicate with the incubation chamber (12) or the functional chamber (13) through the flow distribution mechanism.

3. The automated screening device according to claim 2, characterized in that: The bottom plate (60) is provided with a mounting hole (61); the switching mechanism (14) is arranged in the mounting hole (61) and is rotatable in the mounting hole (61); the switching mechanism (14) is rotatable so that the injection chamber is connected with the incubation chamber (12) or the functional chamber (13) through the distribution disk (70).

4. The automated screening device according to claim 3, characterized in that: The distribution plate (70) has a first distribution structure (71) and a plurality of second distribution structures (72) surrounding the first distribution structure (71); The injection chamber is in communication with the first flow distribution structure (71), the incubation chamber (12) is in communication with one of the second flow distribution structures (72), and the remaining second flow distribution structures (72) are in communication with the plurality of functional chambers (13) in a one-to-one correspondence; The switching mechanism (14) is rotatable to connect the first flow distribution structure (71) with any one of the second flow distribution structures (72).

5. The automated screening device according to claim 4, characterized in that: A sealing plate (73) is provided between the distribution plate (70) and the bottom plate (60), and the sealing plate (73) has a third distribution structure (731) and a plurality of fourth distribution structures (732) surrounding the third distribution structure (731); the third distribution structure (731) is correspondingly connected to the first distribution structure (71), and the plurality of fourth distribution structures (732) are connected to the plurality of second distribution structures (72) in a one-to-one correspondence; The switching mechanism (14) connects the first flow distribution structure (71) and any one of the second flow distribution structures (72) by connecting the third flow distribution structure (731) and any one of the fourth flow distribution structures (732).

6. The automated screening device according to claim 5, characterized in that: The first flow distribution structure (71) is a flow distribution hole or a flow distribution groove, and the second flow distribution structure (72) is a flow distribution hole or a flow distribution groove; The third flow distribution structure (731) is a flow distribution hole or a flow distribution groove, and the fourth flow distribution structure (732) is a flow distribution hole or a flow distribution groove.

7. The automated screening device according to claim 5, characterized in that: The width of the fourth flow distribution structure (732) is less than or equal to the width of the second flow distribution structure (72), and the length of the fourth flow distribution structure (732) is less than or equal to the length of the second flow distribution structure (72); The end of the second flow distribution structure (72) is in the shape of a teardrop, a circle or an ellipse.

8. The automated screening device according to any one of claims 5 to 7, characterized in that: The upper end surface of the switching mechanism (14) is provided with a long groove (141), the first end of the long groove (141) is always connected to the third distribution structure (731), and the second end of the long groove (141) can be connected to any fourth distribution structure (732).

9. The automated screening device according to any one of claims 3 to 8, characterized in that: The lower end surface of the switching mechanism (14) is provided with a snap-in groove (142) for connecting to the rotating module (20); The switching mechanism (14) is arranged on a switching mechanism base (143) and is rotatable relative to the switching mechanism base (143); the switching mechanism base (143) is arranged in the mounting hole (61).

10. The automated screening device according to any one of claims 1 to 9, characterized in that: The incubation chamber (12) is independently arranged, and a holding space is provided around the incubation chamber (12); A plurality of the functional chambers (13) and the incubation chambers (12) surround the first chamber (11); At least some of the functional chambers (13) have different sizes and volumes.

11. The automated screening device according to any one of claims 1 to 9, characterized in that: The incubation chamber (12) is covered with an incubation chamber rubber pad (16), and the incubation chamber rubber pad (16) is provided with a first air permeable hole; The plurality of functional cavities (13) are covered with a functional cavity rubber pad (17), and the functional cavity rubber pad (17) is provided with a plurality of second air holes, and the plurality of second air holes correspond one-to-one to the plurality of functional cavities (13).

12. The automated screening device according to any one of claims 1 to 9, characterized in that: A filter membrane (121) is arranged at the bottom of the incubation chamber (12), and the filter membrane (121) is used to support fillers and filter liquid.

13. The automated screening device according to any one of claims 2 to 9, characterized in that: The upper end surface of the switching mechanism (14) is coated with at least one layer of hydrophobic sealing material, and the surface of the distribution plate (70) is coated with at least one layer of hydrophobic sealing material.

14. An automated screening platform, characterized in that: include: The automated screening device according to any one of claims 1 to 13, comprising a rotating module (20), a driving mechanism (30), a temperature control module (40) and an electrical control module (50).

15. An automated screening platform, characterized in that: include: The automated screening device according to any one of claims 1 to 13; A rotating module (20), the rotating module (20) being transmission-connected to the switching mechanism (14) so ​​as to control the rotation of the switching mechanism (14); A driving mechanism (30), wherein the driving mechanism (30) is capable of clamping the injection mechanism (15) and driving the injection mechanism (15) to inject liquid into or draw liquid from the incubation chamber (12) or the functional chamber (13); a temperature control module (40), the temperature control module (40) being movable relative to the incubation chamber (12) and being used for heating the incubation chamber (12); as well as An electric control module (50), the electric control module (50) and the rotating module (20), the driving mechanism (30) and the temperature control module (40) Electrically connected to control the rotating module (20), the driving mechanism (30) and the temperature control module (40) to work in coordination.

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