Automated screening platform and screening method

Abstract

Provided in the present invention are an automated screening platform and a screening method. The automated screening platform comprises: an automated screening device, a driving mechanism, a temperature control module and an electric control module, wherein the automated screening device is provided with a first cavity, an incubation cavity and a plurality of functional cavities; an injection mechanism is provided in the first cavity, and the injection mechanism comprises an injection push rod provided with a piston; a rotating module is in transmission connection with a switching mechanism, so as to control the switching mechanism to rotate; the driving mechanism can clamp the injection push rod; the temperature control module is configured to heat the incubation cavity; and the electric control module is electrically connected to the rotating module, the driving mechanism and the temperature control module, so as to control the driving mechanism and the temperature control module to work cooperatively. The automated screening platform in the present invention integrates each operation step of a screening experiment, and screening steps are all assembled inside the automated screening device, with little contact with the outside, such that external contamination and component contamination are reduced; and the entire experimental process has a high degree of automation, making experiments more standardized and unified.

Description

Automated screening platform and screening method

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

[0002] Priority to the prior application, patent application number 202310898127.9, filed with the State Intellectual Property Office of China on July 20, 2023, entitled “Automated Screening Platform and Screening Method”;

[0003] Priority to the prior application for patent application number 202321927363.0, entitled “Automated Screening Platform,” filed with the State Intellectual Property Office of China on July 20, 2023;

[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 technical field of DNA-encoded compound library screening or drug screening, and in particular to an automated screening platform and screening method. 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] A hallmark of DNA-encoded compound libraries is that each compound is linked to a specific DNA fragment at the molecular level to label the compound's structural information. Currently, the primary method for screening DNA-encoded compound libraries involves manual incubation of the active target protein with the DNA-encoded compound library. Compounds with strong binding affinity are enriched, while compounds with weak or non-binding affinity are removed. Because the compound types correspond one-to-one with the DNA-encoded information, high-throughput sequencing can be used to obtain structural information for high-affinity compounds. Compounds without DNA tags are then resynthesized for activity verification and structural optimization to yield lead compounds, resolving the challenge of effectively identifying lead compounds when screening a large number of molecules simultaneously against the target. Manual experiments inevitably introduce user processing errors, reduce the reproducibility of results, increase sample processing time, and hinder the standardization of some screening methods.

[0009] Currently, there are no automated instruments specifically designed for DEL screening on the market. Screening experiments primarily rely on manual labor or other equipment used for extraction and purification. Existing equipment is not fully compatible with certain application scenarios, and some screening protocols or conditions are complex to implement with existing equipment. There is a significant risk of cross-contamination when processing large numbers of samples, and the user needs to perform multiple steps.

[0010] Summary of the Invention

[0011] The present invention aims to solve, at least to some extent, one of the technical problems in DEL screening. To this end, the present invention provides an automated screening platform (also referred to as a machine, device, or instrument), comprising:

[0012] An automated screening device comprising a first chamber, an incubation chamber, and a plurality of functional chambers, wherein an injection mechanism is provided in the first chamber, the injection mechanism having an injection chamber, and the injection chamber can be communicated with the incubation chamber or the functional chamber via a switching mechanism;

[0013] a driving mechanism, the driving mechanism being connected to the injection mechanism and driving the injection mechanism to perform an injection or aspiration operation;

[0014] a temperature control module, the temperature control module being movable relative to the incubation chamber and configured to heat the incubation chamber; and

[0015] An electric control module is electrically connected to the driving mechanism and the temperature control module to control the driving mechanism and the temperature control module to work in coordination.

[0016] The automated screening platform of the present invention integrates each operational step of the screening experiment, and all screening steps are gathered inside the automated screening device, rarely coming into contact with the outside world, thereby reducing external contamination and inter-group contamination; the entire experimental process is highly automated, making the experiment more standardized and unified.

[0017] According to the automated screening platform of the present invention, an injection push rod is provided in the injection cavity, and the driving mechanism can clamp the injection push rod and perform injection or suction operations by driving the injection push rod to move back and forth along the length direction of the injection mechanism.

[0018] According to the automated screening platform of the present invention, it also includes a rotating module, which is transmission-connected to the switching mechanism to control the rotation of the switching mechanism. By rotating the switching mechanism, the injection chamber is connected to the incubation chamber or the designated functional chamber; the electrical control module is electrically connected to the rotating module to control the coordinated operation of the rotating module.

[0019] According to the automated screening platform of the present invention, the rotation module includes a first driving component, a first photoelectric sensor and a docking assembly;

[0020] The first driving component is in transmission connection with the docking assembly, the docking assembly is in transmission connection with the switching mechanism, and the first photoelectric sensor is provided on the first driving component for detecting the rotation position of the docking assembly.

[0021] According to the automated screening platform of the present invention, the first driving component includes a stepper motor with a reducer, the docking assembly includes a rotating disc and a clamping plate fixed to the center of the rotating disc, the stepper motor is transmission-connected to the rotating disc, and the clamping plate is transmission-connected to the switching mechanism.

[0022] According to the automated screening platform of the present invention, a mounting block is fixedly provided at the end of the stepper motor, and the mounting block has a central circular hole;

[0023] The lower side of the rotating disc has a cylindrical connecting portion, the connecting portion is rotatably matched with the central circular hole, and the stepping motor is transmission-connected to the rotating disc through the connecting portion;

[0024] The first photoelectric sensor is arranged on the mounting block, and a detection block that rotates synchronously with the rotating disk is arranged on the lower side of the rotating disk. The first photoelectric sensor determines the rotation position of the docking assembly by detecting the detection block.

[0025] According to the automated screening platform of the present invention, the driving mechanism comprises: a second driving component, a transmission assembly, a second photoelectric sensor and a clamping claw;

[0026] The second driving component is in transmission connection with the transmission assembly, the transmission assembly is in transmission connection with the clamping jaw, the second photoelectric sensor is used to detect the starting position and the ending position of the clamping jaw, the clamping jaw can clamp the injection push rod and drive the injection push rod to reciprocate along the length direction of the injection mechanism.

[0027] According to the automated screening platform of the present invention, the second driving component includes a stepping motor with an encoder, and the transmission assembly includes a synchronous belt, a synchronous pulley, a lead screw, a first guide rail and a first slider;

[0028] The synchronous belt connects the stepping motor and the synchronous pulley, the synchronous pulley is fixed to the end of the screw rod, the first slider is slidably engaged with the first guide rail, the screw rod is spirally engaged with the first slider, the screw rod is parallel to the first guide rail, and the clamp is fixed on the first slider.

[0029] According to the automated screening platform of the present invention, the screw is fixed by two fixing assemblies, the first slider is located between the two fixing assemblies, and the fixing assembly includes a bearing that cooperates with the screw;

[0030] The clamping jaws are electric clamping jaws or pneumatic clamping jaws.

[0031] According to the automated screening platform of the present invention, the temperature control module includes: a moving module and a heating module, the heating module is used to heat the incubation chamber, and the moving module is connected to the heating module to drive the heating module to move horizontally and vertically relative to the incubation chamber.

[0032] According to the automated screening platform of the present invention, the mobile module includes a third driving component, a second guide rail, a second slider, a first mounting plate, a second mounting plate, a fourth driving component, a third guide rail and a third slider;

[0033] The third driving component and the second guide rail are both fixed to the first mounting plate, the second slider is slidably engaged with the second guide rail, the third driving component is connected to the second slider and can drive the second slider to slide along the second guide rail, the second mounting plate is fixed to the second slider, the fourth driving component and the third guide rail are both fixed to the second mounting plate, the third slider is slidably engaged with the third guide rail, the fourth driving component is connected to the third slider and can drive the third slider to slide along the third guide rail;

[0034] The heating module is fixed to the third slider.

[0035] According to the automated screening platform of the present invention, a third photoelectric sensor for detecting the moving position of the second slider is provided on the first mounting plate, and a fourth photoelectric sensor for detecting the moving position of the third slider is provided on the second mounting plate;

[0036] The third driving component drives the second slider to move in the vertical direction, and the fourth driving component drives the third slider to move in the horizontal direction;

[0037] The first mounting plate and the second mounting plate are both L-shaped.

[0038] According to the automated screening platform of the present invention, the heating module includes a heating block, a heating plate, a thermocouple and a temperature control protection switch;

[0039] The heating block has a hollow cavity, and the lower side of the hollow cavity has an inlet, so that the incubation chamber can enter the hollow cavity through the inlet for heating;

[0040] The heating plate is located on the top of the heating block, the thermocouple is used to detect the temperature of the heating block and the heating plate, and the temperature control protection switch is used to control the heating state of the heating block and the heating plate.

[0041] According to the automated screening platform of the present invention, the automated screening platform further comprises a shell, and the automated screening device, the rotating module, the driving mechanism, the temperature control module and the electrical control module are all located inside the shell.

[0042] According to the automated screening platform of the present invention, the automated screening platform also includes an ultraviolet disinfection system, which includes an ultraviolet lamp, an air intake fan and an exhaust fan. The ultraviolet lamp is located in the outer shell, the air intake fan is arranged at the air inlet of the outer shell, and the exhaust fan is arranged at the exhaust port of the outer shell; a display operation screen is also provided on the outside of the outer shell.

[0043] The present invention also provides a screening method, which uses the automated screening platform of the present invention.

[0044] The screening method according to the present invention is used to screen compounds or drugs and is an affinity screening experiment.

[0045] According to the screening method of the present invention, the screening method includes an incubation stage, a washing stage and an elution stage.

[0046] The specific steps include:

[0047] The target protein and DNA-encoded compound library required for screening are injected into the incubation chamber to complete the loading;

[0048] The incubation chamber is pre-loaded with pre-treated immobilized resin beads. The target protein and the DNA-encoded compound library are added to the incubation chamber for mixed incubation, 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.

[0049] After the incubation is completed, the incubation effluent is drawn out by the injection mechanism and the sample is stored in the empty functional cavity;

[0050] At the beginning of the cleaning process, cleaning liquid is drawn from the functional chamber and injected into the injection mechanism, which then injects it into the incubation chamber and pumps it back and forth. The waste cleaning liquid is drawn from the incubation chamber and injected into the injection chamber, which then injects it into the functional chamber containing the waste liquid for disposal, completing one cleaning process. After repeated cleaning processes, unbound small molecules are washed away by the cleaning liquid.

[0051] At the beginning of the elution process, eluate is drawn from another functional chamber containing eluate and injected into the injection mechanism. The injection mechanism then injects it into the incubation chamber. The target protein is denatured by heating for a predetermined time, causing small molecules bound to the target to dissociate and enter the eluate. The eluate is then injected into another functional chamber storing samples through the injection mechanism. Finally, the small molecules that have entered the eluate are recovered as the sample obtained after screening, completing the elution process. This elution process can be repeated as needed.

[0052] According to the screening method of the present invention, in the step of loading the target protein and the DNA-encoded compound library, 5-40 ug of target protein and 1-1.5 nmol of the DNA-encoded compound library required for screening are injected into the incubation chamber to complete the loading.

[0053] According to the screening method of the present invention, the target protein and the DNA-encoded compound library are incubated in the incubation chamber (12) at a room temperature of 22°C-30°C for a time of 30 minutes-1 hour;

[0054] Washing the immobilized resin beads at least 6 times;

[0055] The small molecule compounds bound to the target are heated at 90°C-100°C for 5-15 minutes to denature the target protein, and the compounds with strong binding ability to the target are collected.

[0056] The automated screening platform and screening method of the present invention integrate each operation step of the manual affinity screening experiment, and all screening steps are gathered inside the automated screening device, without contact with the external environment of the instrument, reducing the risk of external contamination and inter-group contamination; the entire experimental process has a high degree of automation, making the experiment more standardized and unified. The screening method performed by using the automated screening platform solves the problem that there are currently no automated machines specifically used for DEL screening technology in the market; and the automated screening device can independently divide each group of samples into a semi-enclosed space for carrying out the experiments, reducing contamination; and the automated screening device can complete the modularization of the experimental steps, facilitating customized assembly under different experimental conditions.

[0057] 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

[0058] 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.

[0059] FIG1 is a perspective schematic diagram of an automated screening platform according to an embodiment of the present invention;

[0060] FIG2 is a perspective schematic diagram of an automated screening platform with its housing hidden in accordance with an embodiment of the present invention;

[0061] FIG3 is a perspective schematic diagram of an automated screening device according to an embodiment of the present invention;

[0062] FIG4 is an exploded schematic diagram of an automated screening device according to an embodiment of the present invention;

[0063] FIG5 is a perspective schematic diagram of a rotating module according to an embodiment of the present invention;

[0064] FIG6 is an exploded schematic diagram of a rotating module according to an embodiment of the present invention;

[0065] FIG7 is a perspective schematic diagram of a driving mechanism at a certain viewing angle in one embodiment of the present invention;

[0066] FIG8 is a perspective schematic diagram of a driving mechanism in another perspective according to an embodiment of the present invention;

[0067] FIG9 is a perspective diagram of a temperature control module at a certain viewing angle according to an embodiment of the present invention;

[0068] FIG10 is a perspective schematic diagram of a temperature control module in another perspective according to an embodiment of the present invention.

[0069] Figures: 10-Automated screening device; 11-First chamber; 12-Incubation chamber; 121-Filter membrane; 13-Functional chamber; 14-Switching mechanism; 15-Injection mechanism; 151-Injection push rod; 16-Incubation chamber rubber pad; 17-Function chamber rubber pad; 20-Rotation module; 21-First driving component; 211-Mounting block; 22-First photoelectric sensor; 23-Docking assembly; 231-Rotating disc; 232-Clipping plate; 233-Connecting portion; 234-Detection block; 30-Drive mechanism; 31-Second driving component; 32-Transmission assembly; 321-Synchronous belt; 322-Synchronous pulley; 323-Screw rod; 324-First guide rail; 325-First slider; 326-Fixed assembly; 33-Second photoelectric sensor; 34-Clamping claw; 40-temperature control module; 41-third drive component; 42-second guide rail; 43-second slider; 44-first mounting plate; 45-second mounting plate; 46-fourth drive component; 47-third guide rail; 48-third slider; 401-heating block; 402-heating plate; 403-thermocouple; 404-temperature control protection switch; 50-electronic control module; 60-ultraviolet lamp; 61-intake fan; 62-exhaust fan; 70-display operation screen; 80-housing; 90-liquid storage mechanism, 91-flow distribution mechanism. DETAILED DESCRIPTION

[0070] 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.

[0071] 1 and 2 , this embodiment provides an automated screening platform that can be used for screening DNA-encoded compound libraries.

[0072] In some embodiments, the automated screening platform primarily includes: an automated screening device 10, a drive mechanism 30, a temperature control module 40, and an electronic control module 50. The automated screening device 10, drive mechanism 30, temperature control module 40, and electronic control module 50 may all be disposed within a housing 80, or the housing 80 may not be provided depending on the actual situation.

[0073] Specifically, referring to Figures 3 and 4, the automated screening device 10 has a first cavity 11, an incubation cavity 12 and multiple functional cavities 13. An injection mechanism 15 is provided in the first cavity 11. The injection mechanism 15 has an injection cavity, which can be connected to the incubation cavity 12 or the functional cavity 13 through a switching mechanism 14; the driving mechanism 30 is connected to the injection mechanism 15 and drives the injection mechanism 15 to perform injection or suction operations; the temperature control module 40 can move relative to the incubation cavity 12 and is used to heat the incubation cavity 12; the electronic control module 50 is electrically connected to the driving mechanism 30 and the temperature control module 40 to control the driving mechanism 30 and the temperature control module 40 to work together.

[0074] 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.

[0075] The automated screening platform of the above embodiment can integrate each operation step of the screening experiment, and all the screening steps are gathered inside the automated screening device, rarely coming into contact with the outside world, thereby reducing external contamination and inter-group 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.

[0076] In some embodiments, the automated screening device 10 includes a flow distribution mechanism 91, a liquid storage mechanism 90, an injection mechanism 15, and a switching mechanism 14. The first cavity 11, the incubation cavity 12, and the plurality of functional cavities 13 are all formed in the liquid storage mechanism 90; the injection mechanism 15 is disposed in the first cavity 11, and the first cavity 11 can serve as an installation cavity for the injection mechanism 15. The injection mechanism 15 has an injection cavity for injecting or aspirating liquid; the flow distribution mechanism 91 is disposed in the liquid storage mechanism 90, and is used to connect the injection cavity with the incubation cavity 12 or the functional cavity 13; thereby, the injection cavity can be connected to the incubation cavity 12 and can also be connected to each functional cavity 13 through the flow distribution mechanism 91. The switching mechanism 14 is disposed in the flow distribution mechanism 91, and cooperates with the flow distribution mechanism 91 to connect the injection cavity with the incubation cavity 12 or the functional cavity 13 through the flow distribution mechanism 91. The switching mechanism 14 can change the cavity to which the injection cavity is connected, so that the flow distribution mechanism 91 can distribute the liquid according to the experimental requirements.

[0077] The switching mechanism 14 may be a switching valve. The injection mechanism 15 may be a component similar to a syringe. The first cavity 11 may be located at the center of the automated screening device 10 , and the incubation cavity 12 and the plurality of functional cavities 13 are arranged around the first cavity 11 .

[0078] In some embodiments, an injection push rod 151 is provided in the injection cavity. The driving mechanism 30 can clamp the injection push rod 151 and perform injection or suction operations by driving the injection push rod 151 to move back and forth along the length direction of the injection mechanism 15 .

[0079] In some embodiments, the automated screening platform further includes a rotating module 20, which is connected to the switching mechanism 14 in a transmission manner to control the rotation of the switching mechanism 14, and the injection chamber is connected to the incubation chamber 12 or the designated functional chamber 13 by rotating the switching mechanism 14; the switching mechanism 14 has multiple rotational positions, and at different positions, the chambers connected to the injection chamber are also different, and by rotating the switching mechanism 14, the injection chamber can be connected to any functional chamber 13, and can also be connected to the incubation chamber 12, thereby realizing the flow of liquid between the two connected chambers. The switching mechanism 14 can also prevent the injection chamber from being connected to any chamber at a certain rotational position. The electronic control module 50 is electrically connected to the rotating module 20 to control the coordinated operation of the rotating module 20. In other embodiments, the switching mechanism 14 can also realize the switching of the chambers connected to the injection chamber by other control methods, and those skilled in the art can replace the switching methods other than "rotation" according to actual needs.

[0080] In some embodiments, the automated screening platform mainly includes: an automated screening device 10, a rotation module 20, a drive mechanism 30, a temperature control module 40, an electrical control module 50 and an outer shell 80. The automated screening device 10, the rotation module 20, the drive mechanism 30, the temperature control module 40 and the electrical control module 50 are all located on the inner side of the outer shell 80.

[0081] 3 and 4 , the automated screening device 10 comprises a first chamber 11, an incubation chamber 12, and a plurality of functional chambers 13. An injection mechanism 15 is disposed within the first chamber 11. The injection mechanism 15 comprises an injection chamber, and an injection push rod 151 with a piston is disposed within the injection chamber. The injection chamber can be connected to the incubation chamber 12 and the plurality of functional chambers 13 via a switching mechanism 14, thereby enabling the liquid within the injection mechanism 15 to be transported to the incubation chamber 12 and the plurality of functional chambers 13, and also enabling the liquid within the incubation chamber 12 and the plurality of functional chambers 13 to be transferred to the injection mechanism 15. Cleaning fluid, eluent, blocking fluid, etc. can be placed in the functional chamber 13, and an empty functional chamber 13 can be used for sample collection.

[0082] For example, a filter membrane 121 may be provided in the incubation chamber 12 so that the immobilized resin beads can be smoothly settled and spread on the filter membrane 121 at the bottom of the incubation chamber. When the incubation liquid is collected, the immobilized resin beads are retained in the incubation chamber by the filter membrane 121 .

[0083] The rotating module 20 is connected to the switching mechanism 14 in a transmission manner to control the rotation of the switching mechanism 14, and by rotating the switching mechanism 14, the injection chamber is connected to the incubation chamber 12 or the designated functional chamber 13; the ways in which the injection chamber is connected to the incubation chamber 12 or the designated functional chamber 13 include but are not limited to distribution plate connection, pipeline connection, etc.

[0084] For example, the DNA-encoded compound library is first injected into the incubation chamber 12. After the incubation is completed, the liquid in the incubation chamber 12 can be transferred to the injection chamber of the injection mechanism 15. Then, the switching mechanism 14 is rotated to connect the injection chamber with one of the functional chambers 13. The injection push rod 151 is pushed to transport the DNA-encoded compound incubation effluent to the corresponding functional chamber 13.

[0085] Furthermore, different functional chambers 13 may be provided with different sizes and volumes so as to accommodate different liquids respectively.

[0086] The drive mechanism 30 can clamp the injection push rod 151 and drive it to reciprocate along the length of the injection mechanism, thereby extracting, discharging, or transferring liquid. The temperature control module 40 can move relative to the incubation chamber 12 to heat the incubation chamber 12, thereby incubating the compounds in the incubation chamber 12 at a specified temperature. The electrical control module 50 is electrically connected to the rotation module 20, the drive mechanism 30, and the temperature control module 40 to control the coordinated operation of the rotation module 20, the drive mechanism 30, and the temperature control module 40.

[0087] 5 and 6 , the rotation module 20 includes a first drive component 21, a first photosensor 22, and a docking assembly 23. The first drive component 21 is in transmission connection with the docking assembly 23, which is in transmission connection with the switching mechanism 14. The first photosensor 22 is disposed on the first drive component 21 and is used to detect the rotational position of the docking assembly 23. The provision of the first photosensor 22 allows for accurate control of the rotational angle of the first drive component 21, thereby ensuring accurate communication between the injection chamber and the incubation chamber 12 or the designated functional chamber 13.

[0088] Specifically, the first drive component 21 includes a stepper motor with a speed reducer. The docking assembly 23 includes a rotating disc 231 and a snap-on plate 232 fixed to the center of the rotating disc 231. The stepper motor is in driving connection with the rotating disc 231, and the snap-on plate 232 is in driving connection with the switching mechanism 14. The bottom of the switching mechanism 14 has a notch, and the snap-on plate 232 snaps into the notch, thereby driving the switching mechanism 14 to rotate.

[0089] Furthermore, a mounting block 211 is fixedly mounted on the end of the stepper motor, and the mounting block 211 has a central circular hole. The lower side of the rotating disk 231 has a cylindrical connecting portion 233, which rotates in conjunction with the central circular hole. The stepper motor is connected to the rotating disk 231 through the connecting portion 233. The first photoelectric sensor 22 is mounted on the mounting block 211. In other words, the first photoelectric sensor 22 can be mounted directly on the first drive component 21 or indirectly on the first drive component 21 through the mounting block 211. A detection block 234 is mounted on the lower side of the rotating disk 231, which rotates synchronously with the rotating disk 231. The first photoelectric sensor 22 determines the rotational position of the docking assembly 23 through the detection block 234.

[0090] In some embodiments, multiple functional cavities 13 are covered with a functional cavity rubber pad 17, and the incubation cavity 12 is covered with an incubation cavity rubber pad 16. The functional cavity rubber pad 17 has multiple small holes, each corresponding to a functional cavity, and the incubation cavity rubber pad 16 has a single small hole. The provision of the functional cavity rubber pad 17 and the incubation cavity rubber pad 16 prevents impurities from entering the functional cavities 13 and incubation cavity 12. Furthermore, the small holes ensure fluidity during liquid injection and output.

[0091] In some embodiments, referring to Figures 7 and 8, the driving mechanism 30 includes: a second driving component 31, a transmission assembly 32, a second photoelectric sensor 33 and a clamp 34; the second driving component 31 is transmission-connected to the transmission assembly 32, the transmission assembly 32 is transmission-connected to the clamp 34, the second photoelectric sensor 33 is used to detect the starting position and the ending position of the clamp 34, the clamp 34 can clamp the injection push rod and drive the injection push rod to reciprocate along the length direction of the injection mechanism 15.

[0092] Specifically, the second drive component 31 includes a stepper motor with an encoder, and the transmission assembly 32 includes a synchronous belt 321, a synchronous pulley 322, a screw 323, a first guide rail 324, and a first slider 325. The synchronous belt 321 connects the stepper motor and the synchronous pulley 322, the synchronous pulley 322 is fixed to the end of the screw 323, the first slider 325 slides with the first guide rail 324, the screw 323 is spirally engaged with the first slider 325, the screw 323 is parallel to the first guide rail 324, and the clamp 34 is fixed to the first slider 325. The first guide rail 324 and the second drive component 31 can be installed on different surfaces of the same fixed plate. Two first guide rails 324 can be provided, and both first guide rails 324 slide with the first slider 325 to ensure the stability of the movement of the first slider 325. The screw rod 323 is inserted into the middle of the first slider 325 and is screw-matched with the first slider 325 . As the screw rod 323 rotates, the first slider 325 moves along the length direction of the screw rod 323 .

[0093] In the above embodiment, the first guide rail 324 and the screw rod 323 are parallel to each other.

[0094] Furthermore, the screw rod 323 is fixed by two fixing assemblies 326 , the first slider 325 is located between the two fixing assemblies 326 , and the fixing assembly 326 includes a bearing that cooperates with the screw rod 323 , thereby reducing the rotational resistance of the screw rod 323 .

[0095] In some embodiments, the gripper 34 is an electric gripper or a pneumatic gripper.

[0096] Referring to Figures 9 and 10, the temperature control module 40 includes a mobile module and a heating module. The heating module is used to heat the incubation chamber 12. The mobile module is connected to the heating module and is used to drive the heating module to move horizontally and vertically relative to the incubation chamber 12. The mobile module can be used to control the heating module to move to the position of the heating incubation chamber 12 or to withdraw from the position of the heating incubation chamber 12. The movement direction of the mobile module includes at least horizontal and vertical directions. The mobile module can also be a multi-degree-of-freedom manipulator.

[0097] Specifically, the mobile module includes a third driving component 41, a second guide rail 42, a second slider 43, a first mounting plate 44, a second mounting plate 45, a fourth driving component 46, a third guide rail 47 and a third slider 48; the third driving component 41 and the second guide rail 42 are both fixed on the first mounting plate 44, the second slider 43 slides with the second guide rail 42, the third driving component 41 is connected to the second slider 43, and can drive the second slider 43 to slide along the second guide rail 42, the second mounting plate 45 is fixed on the second slider 43, and moves synchronously with the second slider 43.

[0098] The fourth driving component 46 and the third guide rail 47 are both fixed on the second mounting plate 45, the third slider 48 slides with the third guide rail 47, the fourth driving component 46 is connected to the third slider 48, and can drive the third slider 48 to slide along the third guide rail 47; the heating module is fixed to the third slider 48.

[0099] The third driving component 41 and the fourth driving component 46 can both be synchronous motors with encoders.

[0100] Furthermore, a third photoelectric sensor for detecting the moving position of the second slider 43 is provided on the first mounting plate 44, and a fourth photoelectric sensor for detecting the moving position of the third slider 48 is provided on the second mounting plate 45; the third driving component 41 drives the second slider 43 to move in the vertical direction, and the fourth driving component 46 drives the third slider 48 to move in the horizontal direction; the first mounting plate 44 and the second mounting plate 45 are both L-shaped.

[0101] 9 and 10 , the heating module includes a heating block 401, a heating plate 402, a thermocouple 403 and a temperature control protection switch 404; the heating block 401 has a hollow cavity, and the lower side of the hollow cavity has an inlet so that the incubation chamber 12 can enter the hollow cavity through the inlet for heating; the heating plate 402 is located on the top of the heating block 401, the thermocouple 403 is used to detect the temperature of the heating block 401, and the temperature control protection switch 404 is used to prevent the heating block 401 from overheating.

[0102] In some embodiments, the automated screening platform also includes a UV disinfection system, which includes a UV lamp 60, an intake fan 61, and an exhaust fan 62. The UV lamp 60 is located within the housing 80 and provides global illumination, providing sufficient coverage. The intake fan 61 is located at the air inlet of the housing 80, and the exhaust fan 62 is located at the exhaust outlet of the housing 80. The UV disinfection system significantly improves the environment within the housing 80, preventing bacterial growth. During operation, the intake fan 61 and exhaust fan 62 operate simultaneously, accelerating the circulation of air within the housing 80.

[0103] The outer side of the housing 80 is also provided with a display operation screen 70. The display operation screen 70 mainly provides instrument parameter configuration and working process prompts.

[0104] This embodiment further provides a screening method using an automated screening platform, which is any of the automated screening platforms described above. The screening method is simple to operate, highly automated, and is less likely to contaminate samples during operation.

[0105] Furthermore, the above screening method can be used to screen compounds or drugs.

[0106] In some embodiments, the screening method comprises an incubation phase, a washing phase, and an elution phase.

[0107] Specifically, the screening method comprises the following steps:

[0108] Incubation stage: The target protein and DNA-encoded compound library required for screening are injected into the incubation chamber 12 to complete the sample loading; the incubation chamber 12 is pre-embedded with pre-treated immobilized resin beads, and the target protein and the DNA-encoded compound library are added to the incubation chamber for mixed incubation, so that the target is immobilized on the immobilized resin beads in the incubation chamber, and at the same time, the small molecule compounds in the DNA-encoded compound library are combined with the target; after the incubation is completed, the incubation effluent is extracted by the injection mechanism 15 and the sample is retained in the vacant functional chamber 13.

[0109] Cleaning stage: 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 mechanism 15, and then injected into the incubation chamber 12 by the injection mechanism 15 and pumped back and forth. The cleaning waste liquid is drawn out from the incubation chamber 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 repeated cleaning multiple times, the unbound small molecule compounds will be washed away.

[0110] Elution phase: At the beginning of the elution process, eluent is drawn from another functional chamber 13 containing eluent and injected into the injection mechanism 15. The injection mechanism 15 then injects the eluent into the incubation chamber 12. The target protein is heated for a predetermined time to denature, causing small molecules bound to the target to dissociate and enter the eluent. The eluent is then injected into another functional chamber 13 storing the sample through the injection mechanism 15. Finally, the small molecules that have entered the eluent are recovered as the sample obtained after screening, completing the elution process. This elution process can be repeated as needed.

[0111] In a specific embodiment, the screening method comprises the following steps:

[0112] The 5-40 μg target protein and 1-1.5 nmol of the DNA-encoded compound library required for screening are manually injected into the incubation chamber 12 using a pipette or other device to complete the sample loading, and the automatic screening platform is activated to complete the subsequent automatic screening process. Specifically, the incubation chamber 12 is pre-loaded with pre-treated immobilized resin beads. The target protein and the DNA-encoded compound library are added to the incubation chamber 12 for mixed incubation, so that the target protein is immobilized on the immobilized resin beads in the incubation chamber, and the small molecule compounds in the DNA-encoded compound library bind to the target.

[0113] After the incubation is completed, the incubation effluent is drawn out by the injection mechanism 15 and a sample is retained in an empty functional cavity 13;

[0114] At the beginning of the cleaning process, cleaning liquid is drawn from the functional chamber 13 and injected into the injection mechanism 15. The injection mechanism 15 then injects the liquid into the incubation chamber 12 and pumps it back and forth. The waste liquid is drawn from the incubation chamber and injected into the injection chamber. The waste liquid is then injected into the functional chamber 13 for disposal, completing the cleaning process. After repeated cleaning cycles, unbound small molecules are removed by the cleaning liquid.

[0115] At the beginning of the elution process, eluate is drawn from another functional chamber 13 containing eluate and injected into the injection mechanism 15. The injection mechanism 15 then injects the eluate into the incubation chamber 12. The target protein is heated for a predetermined time to denature, causing small molecules bound to the target to dissociate and enter the eluate. The eluate is then injected into another functional chamber 13 storing the sample through the injection mechanism 15. 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.

[0116] Furthermore, in the above embodiment, the target protein and the DNA-encoded compound library are incubated in the incubation chamber 12 at room temperature of 22°C-30°C, specifically 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 90°C-100°C for 5-15 minutes to denature the target protein, specifically 95°C for 10 minutes to denature the target protein.

[0117] 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.

[0118] The target protein can be changed according to experimental requirements, including but not limited to protein, ribonucleic acid (RNA), etc.

[0119] 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).

[0120] 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.

[0121] 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 the eluted molecules from the previous round are added as input samples, and the screening steps are repeated.

[0122] The optimized incubation time, resin bead dosage, and protein dosage save time and cost; the optimized washing solution dosage and number of times provide stable and accurate screening data.

[0123] Regarding the screening method, this embodiment further provides the following comparative examples and embodiments, which are as follows.

[0124] Comparative example - manual screening experimental group:

[0125] Incubation phase: Add 5 μg of target protein, 120 μl of pre-cleaved immobilized resin beads, and 2E11 molecules of positive compound to the spin column and incubate for 1 hour. For the control group, no protein was added. Collect the supernatant after incubation.

[0126] Washing stage: Add 600 μl of washing solution to the centrifuge tube each time, wash 10 times, and collect each washing solution.

[0127] Elution stage: Add 200 μl of elution buffer to the centrifuge column, place in a thermostatted incubator, heat at 95°C for 10 minutes, and collect the sample. Repeat the elution and collection once.

[0128] Two rounds of screening were performed. Fractions were collected and quantitatively analyzed by qPCR. The molecular weight of the positive markers in each fraction is shown in Appendix 1.1 and 1.2.

[0129] Appendix 1.1 (Routine manual screening of first round data)

[0130] Appendix 1.2 (Second round of routine manual screening data)

[0131] Example - Automatic Screening Experimental Group

[0132] Set up and review automated screening platform processes;

[0133] Incubation phase: Add 5 μg of target protein, 120 μl of pre-cleaned immobilized resin beads, and 2E11 molecules of positive compound to the incubation chamber and incubate for 1 hour. For the control group, no protein was added. Collect the supernatant after incubation into the corresponding chamber.

[0134] Washing stage: Washing step, each wash volume is 1000ul, wash times 6 times. Collect each wash solution.

[0135] Elution: Heat the incubation chamber to 95°C for 10 minutes after adding 200 μl of elution buffer. Collect the elution buffer into the sample collection chamber. Repeat this step once.

[0136] Screening was performed in two rounds.

[0137] Each fraction was collected and quantitatively analyzed by qPCR. The molecular weight of the positive markers in each fraction is shown in Appendix 2.1 and 2.2.

[0138] Appendix 2.1 (First round data of the fully automated screening platform)

[0139] Appendix 2.2 (Second round data of the fully automated screening platform)

[0140] Combining the results of the comparative examples and the examples, it can be seen that the automated screening platform can effectively implement and complete the screening experiment according to the established experimental plan. 1) Both the comparative examples and the examples prove that the target protein can effectively immobilize the positive molecules screened, and the recovery of the eluted molecules in the protein group is much higher than the recovery of the eluted molecules in the control group. 2) Comparing the protein groups of the automated screening experiment and the manual screening experiment, molecules of similar orders of magnitude were obtained; except for the second round of screening, the number of molecules screened in the control group was also similar. The difference in the second round of screening in the control group was due to the fact that the cleaning efficiency would decrease when the liquid concentration was low due to the dead volume limitation of the automated screening device, but it did not affect the determination of the screening result 1). 3) After performing a t-test between the two groups of experiments conducted in the comparative example and the example, it can be seen that there was no statistically significant difference in the number of molecules in the sample processing of each component of the two automated screening platforms, while there was a statistically significant difference in the second elution of the protein group and the first cleaning process of the control group during manual operation, further illustrating that the automated screening platform of the present invention did not bring about differences in the number of molecules during operation, and was more stable and more repeatable than the manual experiment.

[0141] 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 operate in a specific orientation, and therefore should not be understood as limiting the present invention.

[0142] 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.

[0143] 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.

[0144] 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.

[0145] 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.

[0146] 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 platform, characterized in that: include: An automated screening device (10), the automated screening device (10) comprising a first chamber (11), an incubation chamber (12) and a plurality of functional chambers (13), wherein an injection mechanism (15) is arranged in the first chamber (11), the injection mechanism (15) comprising an injection chamber, and the injection chamber can be connected to the incubation chamber (12) or the functional chamber (13) via a switching mechanism (14); a driving mechanism (30), the driving mechanism (30) being connected to the injection mechanism (15) and driving the injection mechanism (15) to perform an injection or suction operation; 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) being electrically connected to the driving mechanism (30) and the temperature control module (40) so as to control the driving mechanism (30) and the temperature control module (40) to work in coordination.

2. The automated screening platform according to claim 1, characterized in that: An injection push rod (151) is arranged in the injection cavity, and the driving mechanism (30) can clamp the injection push rod (151) and drive the injection push rod (151) to reciprocate along the length direction of the injection mechanism (15) to perform injection or suction operations.

3. The automated screening platform according to claim 2, characterized in that: The invention also comprises a rotating module (20), wherein the rotating module (20) is connected to the switching mechanism (14) in a transmission manner so as to control the rotation of the switching mechanism (14). By rotating the switching mechanism (14), the injection chamber is connected to the incubation chamber (12) or the designated functional chamber (13); and the electric control module (50) is electrically connected to the rotating module (20) so as to control the coordinated operation of the rotating module (20).

4. The automated screening platform according to claim 3, characterized in that: The rotating module (20) comprises a first driving component (21), a first photoelectric sensor (22) and a docking assembly (23); The first driving component (21) is in transmission connection with the docking component (23), the docking component (23) is in transmission connection with the switching mechanism (14), and the first photoelectric sensor (22) is arranged on the first driving component (21) for detecting the rotational position of the docking component (23).

5. The automated screening platform according to claim 4, characterized in that: The first driving component (21) comprises a stepping motor with a reducer, the docking assembly (23) comprises a rotating disc (231) and a clamping plate (232) fixed at the center of the rotating disc (231), the stepping motor is transmission-connected to the rotating disc (231), and the clamping plate (232) is transmission-connected to the switching mechanism (14).

6. The automated screening platform according to claim 5, characterized in that: A mounting block (211) is fixedly provided at the end of the stepping motor, and the mounting block (211) has a central circular hole; The lower side of the rotating disc (231) has a cylindrical connecting portion (233), the connecting portion (233) is rotatably matched with the central circular hole, and the stepping motor is transmission-connected to the rotating disc (231) via the connecting portion (233); The first photoelectric sensor (22) is arranged on the mounting block (211), and a photoelectric sensor is arranged on the lower side of the rotating disk (231). The rotating disk (231) rotates synchronously with a detection block (234), and the first photoelectric sensor (22) determines the rotation position of the docking assembly (23) by detecting the detection block (234).

7. The automated screening platform according to any one of claims 2 to 6, characterized in that: The driving mechanism (30) comprises: a second driving component (31), a transmission assembly (32), a second photoelectric sensor (33) and a clamping claw (34); The second driving component (31) is in driving connection with the transmission assembly (32), and the transmission assembly (32) is in driving connection with the clamp (34). The second photoelectric sensor (33) is used to detect the starting position and the ending position of the clamp (34). The clamp (34) is capable of clamping the injection push rod (151) and driving the injection push rod (151) to reciprocate along the length direction of the injection mechanism (15).

8. The automated screening platform according to claim 7, characterized in that: The second driving component (31) comprises a stepping motor with an encoder, and the transmission assembly (32) comprises a synchronous belt (321), a synchronous pulley (322), a screw rod (323), a first guide rail (324) and a first slider (325); The synchronous belt (321) connects the stepping motor and the synchronous pulley (322), the synchronous pulley (322) is fixed to the end of the screw rod (323), the first slider (325) is slidably matched with the first guide rail (324), the screw rod (323) is spirally matched with the first slider (325), the screw rod (323) is parallel to the first guide rail (324), and the clamp (34) is fixed on the first slider (325).

9. The automated screening platform according to claim 8, characterized in that: The screw rod (323) is fixed by two fixing components (326), the first sliding block (325) is located between the two fixing components (326), and the fixing component (326) includes a bearing matched with the screw rod (323); The clamp (34) is an electric clamp or a pneumatic clamp.

10. The automated screening platform according to any one of claims 1 to 9, characterized in that: The temperature control module (40) comprises: a moving module and a heating module, the heating module is used to heat the incubation chamber (12), and the moving module is connected to the heating module and is used to drive the heating module to move horizontally and vertically relative to the incubation chamber (12).

11. The automated screening platform according to claim 10, characterized in that: The moving module comprises a third driving component (41), a second guide rail (42), a second slider (43), a first mounting plate (44), a second mounting plate (45), a fourth driving component (46), a third guide rail (47) and a third slider (48); The third driving component (41) and the second guide rail (42) are both fixed on the first mounting plate (44); the second slider (43) is slidably matched with the second guide rail (42); the third driving component (41) is connected to the second slider (43) and can drive the second slider (43) to slide along the second guide rail (42); the second mounting plate (45) is fixed to the second slider (43); the fourth driving component (46) and the third guide rail (47) are both fixed on the second mounting plate (45); the third slider (48) is slidably matched with the third guide rail (47); the fourth driving component (46) is connected to the third slider (48) and can drive the third slider (48) to slide along the third guide rail (47); The heating module is fixed to the third slider (48).

12. The automated screening platform according to claim 11, characterized in that: The first mounting plate (44) is provided with a third photoelectric sensor for detecting the moving position of the second slider (43), and the second mounting plate (45) is provided with a fourth photoelectric sensor for detecting the moving position of the third slider (48); The third driving component (41) drives the second slider (43) to move in a vertical direction, and the fourth driving component (46) drives the third slider (48) to move in a horizontal direction; The first mounting plate (44) and the second mounting plate (45) are both L-shaped.

13. The automated screening platform according to any one of claims 10 to 12, characterized in that: The heating module comprises a heating block (401), a heating plate (402), a thermocouple (403) and a temperature control protection switch (404); The heating block (401) has a hollow cavity, and the lower side of the hollow cavity has an inlet, so that the incubation cavity (12) can enter the hollow cavity through the inlet for heating; The heating plate (402) is located on the top of the heating block (401), the thermocouple (403) is used to detect the temperature of the heating block (401) and the heating plate (402), and the temperature control protection switch (404) is used to control the heating state of the heating block (401) and the heating plate (402).

14. The automated screening platform according to any one of claims 1 to 13, characterized in that: The automated screening platform further comprises a housing (80), and the automated screening device (10), the rotating module (20), the driving mechanism (30), the temperature control module (40) and the electrical control module (50) are all located inside the housing (80).

15. The automated screening platform according to claim 14, characterized in that: The automated screening platform also includes an ultraviolet disinfection system, which includes an ultraviolet lamp (60), an air intake fan (61) and an exhaust fan (62), wherein the ultraviolet lamp (60) is located in the housing (80), the air intake fan (61) is arranged at the air inlet of the housing (80), and the exhaust fan (62) is arranged at the exhaust port of the housing (80); a display operation screen (70) is arranged on the outside of the housing (80).

16. A screening method, characterized in that: Use the automated screening platform described in any one of claims 1 to 15.

17. The screening method according to claim 16, characterized in that The screening method is used to screen compounds or drugs.

18. The screening method according to claim 16 or 17, characterized in that The screening method includes an incubation phase, a washing phase and an elution phase.

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