Automatic screening device and automatic screening platform

Abstract

The invention provides an automatic screening device and an automatic screening platform. The automatic screening device comprises a bottom plate, a valve plate, a liquid storage mechanism, an injection mechanism and a switching mechanism, and a mounting hole is formed in the bottom plate; the valve plate is fixed to the bottom plate and provided with a first flow distribution structure and a plurality of second flow distribution structures surrounding the first flow distribution structure. The liquid storage mechanism is fixed on the valve 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 the position where the first flow distribution structure communicates with any second flow distribution structure. According to the automatic screening device, manual sample transfer is not needed, and experimental result errors caused by manual operation are effectively reduced; and each cavity on the liquid storage mechanism is a closed space, so that the sample pollution risk is reduced.

Description

Technical Field

[0001] 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

[0002] Drug discovery requires a long process and tedious steps from target screening to final marketing approval. Among them, target screening and identification, as the starting point of drug discovery, are particularly important to the entire process. Therefore, methods that can quickly and efficiently screen and identify targets have become the key to accelerating and improving the efficiency of drug discovery.

[0003] DNA-encoded compound library / DEL screening technology (DNA-encoded library screening) is a high-throughput drug discovery technology. Its basic principle is to use DNA encoding technology to combine a large-scale compound library with DNA molecules to form a DNA-encoded compound library, and then select compounds with high affinity and selectivity by screening the interaction between proteins and encoded compounds. DEL screening technology can effectively shorten the drug discovery cycle and reduce R&D costs. At the same time, it can quickly identify compounds with high affinity, providing a new way for drug development. In drug discovery, DEL technology is widely used in discovering new drug targets, new drug molecules and optimizing existing drug molecules. For example, by screening the drug library, anti-cancer drug molecules with high affinity can be discovered, or new ideas and methods can be provided for the treatment of certain diseases.

[0004] The characteristic of DNA-encoded compound libraries is that each compound is connected to a specific DNA fragment at the molecular level to mark the compound structure-related information. At present, the main method for screening DNA-encoded compound libraries is to incubate active target proteins and DNA-encoded compound libraries through manual experiments by experimenters. Compounds with strong affinity bind to proteins and are enriched, while compounds with weak affinity or non-binding are washed away. Since the compounds correspond one-to-one to DNA-encoded information, the structural information of high-affinity compounds can be obtained through high-throughput sequencing technology; after resynthesizing compounds without DNA tags, activity verification and structural optimization are carried out to obtain lead compounds, which solves the problem that it is difficult to effectively identify lead compounds when a large number of molecules are screened with targets at the same time.

[0005] There are no automated instruments and equipment dedicated to DEL screening on the current market, and screening experiments are mainly carried out manually or with other equipment used to complete extraction and purification. Manually completing experiments will inevitably introduce user processing errors, reduce the repeatability of results, increase the time used for sample processing, and is not conducive to the standardized operation of some screening methods. On the other hand, existing equipment is not fully compatible with certain application scenarios, some screening schemes or screening conditions are relatively complex to implement with existing equipment, there is a greater risk of sample cross-contamination when processing a large number of samples, and there are many user processing steps. Summary of the invention

[0006] The object 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-mentioned background technology.

[0007] The present invention aims to solve at least one of the technical problems in the DEL screening related technology to a certain extent. To this end, the present invention provides an automated screening device, comprising:

[0008] A liquid storage mechanism, wherein the liquid storage mechanism is formed with a first cavity, an incubation cavity and a plurality of functional cavities;

[0009] An injection mechanism, the injection mechanism having an injection cavity, one end of the injection cavity being disposed in the first cavity;

[0010] A flow distribution mechanism, the flow distribution mechanism is connected to the lower surface of the liquid storage mechanism and is used to connect the injection cavity with the incubation cavity or the functional cavity;

[0011] A switching mechanism 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 or the functional chamber through the flow distribution mechanism.

[0012] The automated screening device of the present invention transfers the sample liquid in each cavity through an injection mechanism. The overall compact automated design is adapted to a simple operating system and does not require manual sample transfer, thereby effectively reducing the experimental result errors caused by manual operation and increasing 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, thereby reducing the risk of sample contamination.

[0013] According to the automated screening device of the present invention, the flow distribution mechanism comprises 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.

[0014] According to the automated screening device of the present invention, a mounting hole is provided on the bottom plate; the switching mechanism is disposed in the mounting hole and can rotate within 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.

[0015] According to the automated screening device of the present invention, the flow distribution disk has a first flow distribution structure and a plurality of second flow distribution structures surrounding the first flow distribution structure; the injection chamber is connected to the first flow distribution structure, the incubation chamber is connected to one of the second flow distribution structures, and the remaining second flow distribution structures are connected to the plurality of functional chambers in a one-to-one correspondence; the switching mechanism can rotate to connect the first flow distribution structure with any one of the second flow distribution structures.

[0016] According to the automated screening device of the present invention, a sealing plate is provided between the distribution plate and the bottom plate, and the sealing plate has a third distribution structure and a plurality of fourth distribution structures surrounding the third distribution structure; the third distribution structure is correspondingly connected to the first distribution structure, and the plurality of fourth distribution structures are correspondingly connected to the plurality of second distribution structures;

[0017] The switching mechanism connects the first flow distribution structure with any one of the second flow distribution structures by connecting the third flow distribution structure with any one of the fourth flow distribution structures.

[0018] 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;

[0019] The end of the second flow distribution structure is in a teardrop shape, a circle or an ellipse shape.

[0020] According to the automated screening device of the present invention, a long groove is provided on the upper end surface of the switching mechanism, a first end of the long groove is always connected to the third flow distribution structure, and a second end of the long groove can be connected to any fourth flow distribution structure.

[0021] 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;

[0022] 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.

[0023] 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.

[0024] 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.

[0025] According to the automated screening device of the present invention, the incubation chamber is independently provided, and there is a holding space around the incubation chamber;

[0026] A plurality of the functional chambers and the incubation chambers surround the first chamber;

[0027] At least some of the functional cavities are of different sizes and volumes.

[0028] 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 permeable hole;

[0029] 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 air holes, and the plurality of second air holes correspond to the plurality of functional cavities one by one.

[0030] 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.

[0031] 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.

[0032] 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.

[0033] The present invention also provides an automated screening platform, comprising:

[0034] Automated screening device;

[0035] A rotating module, the rotating module is transmission-connected with the switching mechanism to control the rotation of the switching mechanism;

[0036] 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;

[0037] a temperature control module, the temperature control module being movable relative to the incubation chamber and being used for heating the incubation chamber; and

[0038] An electric control module is electrically connected to the rotating module, the driving mechanism and the temperature control module to control the rotating module, the driving mechanism and the temperature control module to work in coordination.

[0039] 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

[0040] 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.

[0041] Figure 1 is a three-dimensional schematic diagram of an automated screening device in one embodiment of the present invention;

[0042] Figure 2 is an exploded schematic diagram of an automated screening device in one embodiment of the present invention;

[0043] Figure 3 is a three-dimensional schematic diagram of a switching mechanism in one embodiment of the present invention;

[0044] Figure 4 It is a three-dimensional schematic diagram of an automated screening platform in one embodiment of the present invention.

[0045] Reference numerals:

[0046] 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;

[0047] 20- Rotation module;

[0048] 30- driving mechanism;

[0049] 40-temperature control module;

[0050] 50-Electronic control module;

[0051] 60-base plate; 61-mounting hole; 62-fastening screw;

[0052] 70-distribution plate; 71-first distribution structure; 72-second distribution structure; 73-sealing plate; 731-third distribution structure; 732-fourth distribution structure;

[0053] 90-Liquid storage mechanism. DETAILED DESCRIPTION

[0054] The technical scheme of the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only exemplary descriptions 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 included in the scope that the present invention is intended to protect.

[0055] See also Figure 1 and Figure 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.

[0056] 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 the installation cavity of 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.

[0057] Among them, the injection chamber can be connected with the incubation chamber 12 or the functional chamber 13 through the switching mechanism 14 in various ways. 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.

[0058] The automated screening device of the above-mentioned 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. They do not come into contact with the outside world during operation, thereby reducing the risk of sample contamination.

[0059] In some embodiments, the flow distribution mechanism includes a bottom plate 60 and a flow distribution disk 70, and the flow distribution disk 70 is disposed between the bottom plate 60 and the liquid storage mechanism 90; the switching mechanism 14 cooperates with the flow distribution disk 70 to connect the injection chamber with the incubation chamber 12 or the functional chamber 13 through the flow distribution mechanism. The bottom plate 60 and the flow distribution disk 70 can be an integrated structure or a split structure.

[0060] The bottom plate 60 mainly plays the role of fixing and installing. The bottom plate 60 is the foundation of the entire device. The bottom plate 60 can be clamped on the base of the screening device. The side and bottom of the screening device base include a slot structure that assists the bottom plate 60 to be fixed to the matching machine, so that the screening device can be clamped in the installation slot and the screening device will not shake. The distribution plate 70 mainly plays the role of liquid distribution. The injection cavity is connected to the incubation cavity 12 or the functional cavity 13 through the distribution plate 70.

[0061] In some embodiments, a mounting hole 61 is opened on the bottom plate 60; the switching mechanism 14 is disposed in the mounting hole 61 and can rotate in the mounting hole 61, and the switching mechanism 14 can rotate to connect the injection chamber with the incubation chamber 12 or the functional chamber 13 through the distribution plate 70.

[0062] See also Figure 1 and Figure 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.

[0063] The liquid storage mechanism 90 is fixed on the distribution plate 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 plate 70 is mainly used for the distribution of liquid, and the distribution plate 70 is fixed on the bottom plate 60. The switching mechanism 14 is arranged in the mounting hole 61, and can rotate in the mounting hole 61, and the switching mechanism 14 can rotate so that the injection cavity is connected with the incubation cavity 12 or a plurality of functional cavities 13 through the distribution plate 70. In other words, the switching mechanism 14 has a plurality of rotation positions, and 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 with any functional cavity 13, and can also be connected with the incubation cavity 12, so as to realize the liquid flow between the two connected cavities. The switching mechanism 14 can also make the injection cavity not connected with any cavity at a certain rotation position.

[0064] 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 implementation schemes for the structure of 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 according to actual design requirements. Some specific connection structures will also be introduced below, but they do not represent the only connection structure that can be realized.

[0065] The automated screening device of the above-mentioned 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 experimental result errors 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 the operation, they do not come into contact with the outside world, reducing 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.

[0066] See also Figure 1 and Figure 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.

[0067] The bottom plate 60 is the foundation of the entire device. The bottom plate 60 can be clamped on the screening device base. The side and bottom of the screening device base include a slot structure that assists the bottom plate 60 to be fixed to the matching machine, so that the screening device can be clamped in the mounting slot and the screening device will not shake. The bottom plate 60 is provided with a mounting hole 61, and the bottom plate 60 is also provided with a plurality of screw holes, and the plurality of screw holes surround the mounting hole 61.

[0068] The distribution plate 70 is mainly used for liquid distribution. The distribution plate 70 is fixed on the base plate 60 and 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.

[0069] The liquid storage mechanism 90 is fixed on the distribution plate 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 cavity is connected to the first distribution structure 71; the incubation cavity 12 is connected to one of the second distribution structures 72, specifically connected 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 plurality of functional cavities 13 in a one-to-one correspondence, specifically connected to the outer end of the second distribution structure 72 (i.e., the end away from the first distribution structure 71). For example, the bottom centers of the first cavity 11, the incubation cavity 12 and the plurality of functional cavities 13 are all provided with a central hole, and the central hole is used for the inflow and outflow of liquid.

[0070] 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.

[0071] 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 with the incubation chamber 12 or with any one of the functional chambers 13. When the injection chamber is connected with 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 with a 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.

[0072] By arranging a first distribution structure 71 and a plurality of second distribution structures 72 on the distribution disk 70 and cooperating with the switching mechanism 14, convenient connection between the injection chamber and the incubation chamber 12 or the functional chamber 13 is achieved, and the sealing effect of the connection is good and easy to achieve.

[0073] In some embodiments, 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 connected to the first distribution structure 71 correspondingly, and the plurality of fourth distribution structures 732 are connected to the plurality of second distribution structures 72 one by one; 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 sealing of the screening device as a whole is improved by providing the sealing plate 73 to avoid 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: flowing from the injection chamber 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.

[0074] 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.

[0075] 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.

[0076] 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 long strip hole, and the fourth flow distribution structure 732 is a flow distribution long strip groove.

[0077] 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.

[0078] In some embodiments, the injection mechanism 15 may be a component similar to a syringe, which is detachably mounted on the first chamber 11 , so that syringes of different specifications may be replaced as needed.

[0079] In some embodiments, see Figure 3 The switching mechanism 14 can be specifically a switching valve. 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 flow distribution structure 731, and the second end of the long groove 141 can be connected to any fourth flow distribution structure 732. 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 to the first flow distribution structure 71, the third flow distribution structure 731, the long 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.

[0080] Furthermore, a snap-in groove 142 for connecting to the rotating module 20 is formed on the lower end surface of the switching mechanism 14 ; the snap-in groove 142 is suitable for snapping with the rotating module 20 , so that the switching mechanism 14 can rotate under the driving of the rotating module 20 .

[0081] In order to further avoid leakage or interconnection 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 .

[0082] 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.

[0083] In terms of space, multiple functional chambers 13 and incubation chamber 12 surround first chamber 11; at least some of the functional chambers 13 have different sizes and volumes, that is, the functional chambers 13 can have multiple specifications to meet different experimental requirements. The multiple functional chambers 13 include at least one exhaust chamber.

[0084] 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 chamber rubber pad 17, which has a multiple second air holes, and the multiple second air holes correspond one-to-one to the multiple functional cavities 13.

[0085] 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, thereby balancing the cavity and external air pressure to achieve smooth operation of the injection device.

[0086] In some embodiments, a filter membrane 121 is disposed at the bottom of the incubation chamber 12, and the filter membrane 121 is used to support fillers and filter liquids.

[0087] In some embodiments, the upper end surface of the switching mechanism 14 is coated with at least one layer of hydrophobic sealing material to achieve a sealing effect. The surface of the distribution plate 70 is coated with at least one layer of hydrophobic sealing material to achieve a sealing effect.

[0088] See also Figure 4 This embodiment further provides an automated screening platform, which includes the automated screening device of any of the above embodiments, and also includes a rotating module 20, a driving mechanism 30, a temperature control module 40 and an electric control module 50. Since the automated screening platform includes the automated screening device of any of the above embodiments, all the screening steps of the automated screening platform are integrated inside the liquid storage mechanism, which rarely contacts the outside world, thereby reducing external contamination and component contamination; the automation of the processes such as washing, elution and collection in the screening is realized by the switching mechanism 14, and the entire experimental process has a high degree of automation, making the experiment more standardized and unified.

[0089] See also Figure 4The present embodiment further provides an automated screening platform, comprising an automated screening device according to any of the above embodiments, a rotating module 20, a driving mechanism 30, a temperature control module 40 and an electrical control module 50, wherein the rotating module 20 is transmission-connected to the switching mechanism 14 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 sucking liquid into the incubation chamber 12 or the functional chamber 13; the temperature control module 40 can move relative to the incubation chamber 12 to heat the incubation chamber 12; the electrical control module 50 is electrically connected to the rotating module 20, the driving mechanism 30 and the temperature control module 40 to control the rotating module 20, the driving mechanism 30 and the temperature control module 40 to work together.

[0090] The following provides a screening method for an automated screening platform, which specifically includes the following steps:

[0091] 5 to 40 ug of target protein and 1 to 1.5 nmol of DNA encoding 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.

[0092] Specifically, the incubation chamber 12 is pre-embedded with pretreated immobilized resin beads, and 5 to 40 ug 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;

[0093] After the incubation is completed, the incubation effluent is drawn out through the injection mechanism 15 and stored in a reserved vacant functional cavity 13;

[0094] At the beginning of the cleaning process, the cleaning liquid is drawn out from the functional chamber 13 containing the cleaning liquid and injected into the injection chamber, and then injected into the incubation chamber 12 and pumped back and forth. The cleaning waste liquid is drawn out from the incubation chamber 12 and injected into the injection chamber, and then injected into the functional chamber 13 containing the waste liquid for disposal, completing a cleaning process. After repeating the cleaning process multiple times, the unbound small molecules will be washed away by the cleaning liquid;

[0095] At the beginning of the elution process, the eluent is drawn out from another functional chamber 13 filled with the eluent and injected into the injection chamber, and then injected into the incubation chamber 12 from the injection chamber, and the target protein is denatured by heating for a predetermined time so that the small molecules bound to the target are dissociated and enter the eluent, and then injected into another functional chamber 13 storing the sample through the injection chamber, and finally the small molecules entering the eluent are recovered as the sample obtained after screening, completing an elution process. The elution process can be repeated as needed.

[0096] Furthermore, in the above embodiment, the target and the DNA-encoded compound library are incubated in the incubation chamber 12 at a room temperature of 25°C for 30 minutes to 1 hour; the immobilized resin beads are washed at least 6 times; the small molecules bound to the target are heated at 95°C for 10 minutes to denature the target. After the screening experiment is completed, the screened samples are recovered and subjected to next generation sequencing (NGS) to determine the types of molecules screened.

[0097] Among them, the target protein can be changed according to the experimental requirements, including but not limited to protein, ribonucleic acid (RNA), etc.

[0098] 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, the combination of glutathione S transferase (GST) and glutathione (GSH), etc.

[0099] Among them, the elution method can be heating to denature the target protein, or competitive elution can be performed using molecules with stronger affinity to the solid support group. Among them, due to the technical characteristics, a large number of small molecule compounds in the DNA-encoded compound library that do not bind to the target protein may cause background noise, and the screening experimental condition parameters can usually be verified by positive small molecules known to bind to the target protein.

[0100] Among them, the screening can be carried out for multiple rounds, so as to enrich the binding molecules for multiple rounds and improve the signal-to-noise ratio. In the next round, new target proteins and the molecules eluted in the previous round can be added as input samples, and then the above screening steps are repeated.

[0101] The automated screening platform of the above-mentioned embodiment integrates each operation step of the screening experiment, and all the screening steps are gathered inside the liquid storage mechanism, which rarely contacts 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.

[0102] In the description of the present invention, it is to 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”, etc., indicating orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the referred device or element must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as limiting the present invention.

[0103] In addition, the terms "first" and "second" are used for descriptive purposes only and should not 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 at least one of the features. In the description of the present invention, the meaning of "plurality" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined.

[0104] In the present invention, unless otherwise clearly specified and limited, the terms "installed", "connected", "connected", "fixed" and the like should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral one; it can be a mechanical connection, an electrical connection, or communication with each other; it can be a direct connection, or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements, unless otherwise clearly defined. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0105] In the present invention, unless otherwise clearly specified and limited, a first feature being "above" or "below" a second feature may mean that the first and second features are in direct contact, or the first and second features are in indirect contact through an intermediate medium. Moreover, a first feature being "above", "above" or "above" a second feature may mean that the first feature is directly above or obliquely above the second feature, or simply means that the first feature is higher in level than the second feature. A first feature being "below", "below" or "below" a second feature may mean that the first feature is directly below or obliquely below the second feature, or simply means that the first feature is lower in level than the second feature.

[0106] In the present invention, the terms "one embodiment", "some embodiments", "examples", "specific examples", or "some examples" etc. 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 representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the described specific features, structures, materials or characteristics may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction.

[0107] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary 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 substitutions, improvements, etc. made within the spirit and principles of the present invention shall be included in 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) is electrically connected to the rotating module (20), the driving mechanism (30) and the temperature control module (40) to control the rotating module (20), the driving mechanism (30) and the temperature control module (40) to work in coordination.

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