A nucleic acid synthesis column and a method of column loading thereof

Abstract

The application belongs to the technical field of column loading of nucleic acid synthesis columns, and particularly relates to a nucleic acid synthesis column and a column loading method thereof, which comprise an operating mechanism, the operating mechanism is placed on the ground, a column body mechanism is installed at the front end of the operating mechanism, the column body mechanism is used for double covering of column loading materials, a solid phase carrier processing mechanism is connected inside the column body mechanism, the column body mechanism is driven to drive the solid phase carrier processing mechanism to perform lifting driving, a suction mechanism is installed at the top of the column body mechanism, and the suction mechanism is connected with the top of a compaction mechanism. The column loading liquid can flow down along the inner wall of the second column body slowly, and is split by the convex column, so that splashing is completely avoided, the bubble residual rate is greatly reduced, the carrier bed layer is more uniform, the reaction efficiency of acetonitrile cleaning and triethylamine activation is improved, air in the micropores and surface dust are forcedly discharged, the impurity removal rate is improved, and the time for single batch processing is shortened.

Description

Technical Field

[0001] This invention relates to the field of nucleic acid synthesis column packing technology, specifically to a nucleic acid synthesis column and its packing method. Background Technology

[0002] Nucleic acid synthesis columns are core equipment for the chemical synthesis of oligonucleotides (DNA / RNA), and the quality of their packing directly determines the uniformity of distribution, reactivity, and synthesis efficiency of the solid-phase support (such as CPG or polystyrene microspheres). In fields such as gene editing and nucleic acid drug development, efficient and stable column packing technology is a prerequisite for achieving precise synthesis of long-chain nucleic acids.

[0003] Current nucleic acid synthesis column packing techniques have the following significant drawbacks:

[0004] The challenge of bubble control: In traditional column packing processes, the packing solution (such as a mixture of acetonitrile and diiodomethane) needs to be injected into the column from a high position, and the lack of a flow-guiding structure makes it prone to generating bubbles due to liquid splashing. Bubbles occupy the space between the carriers, resulting in uneven bed density and ultimately causing large fluctuations in oligonucleotide synthesis efficiency.

[0005] Low carrier processing efficiency: Cleaning and activation of solid-phase carriers rely on manual stirring or simple agitation, resulting in insufficient contact. For example, air and surface dust within the micropores of CPG carriers are difficult to remove completely, and the reaction efficiency between the triethylamine activation solution and the carrier is low, directly affecting the consistency of subsequent nucleotide coupling reactions.

[0006] Poor uniformity of bed compaction: Existing technologies mostly use static compaction or manual pressing, resulting in unstable fluctuations in the density of the carrier bed. Furthermore, the carrier is prone to shifting during the compaction process, forming "channels," which leads to a large relative standard deviation in the purity of products synthesized in different batches, failing to meet the stability requirements of industrial production.

[0007] The operation process is cumbersome: the column loading process requires the coordination of multiple devices (such as ultrasonic instruments, stirrers, column presses, etc.), and the carrier is transferred many times, which is not only time-consuming, but also prone to carrier contamination and loss due to exposure during operation.

[0008] To this end, we propose a nucleic acid synthesis column and its packing method. Summary of the Invention

[0009] To solve the above-mentioned technical problems, the present invention provides the following technical solution:

[0010] A nucleic acid synthesis column and a method for packing the same thereon, comprising: an operating mechanism;

[0011] The operating mechanism is placed on the ground, the front end of the operating mechanism is provided with a column mechanism, the column mechanism is used for double covering of the column material, the inside of the column mechanism is connected with a solid phase carrier processing mechanism, the column mechanism is driven to drive the solid phase carrier processing mechanism to drive up and down, the top of the column mechanism is provided with a suction mechanism, the suction mechanism is connected with the top of the compaction mechanism, the suction mechanism is matched with the compaction mechanism, the liquid column material in the compaction mechanism is sucked and discharged by the suction mechanism, and the upper end of the compaction mechanism is installed on the front end of the operating mechanism.

[0012] As a preferred scheme of the nucleic acid synthesis column, the operating mechanism comprises an operating platform.

[0013] The operating platform is placed on the ground, the surface of the operating platform is rotatably connected with a first screw rod on both sides of the upper end, the top of a group of first screw rods is connected with the output end of a first motor, the first motor is installed on one side of the top of the operating platform, a support is installed on the front end of the operating platform, the inside of the support is installed with a column mechanism, the rear end of a driving rod is slidably connected with the upper end of the front end of the operating platform, the rear end of the driving rod is threadedly connected with the outer wall of the first screw rod, and a fixed clamp is installed between the two driving rods.

[0014] As a preferred scheme of the nucleic acid synthesis column, the column mechanism comprises a first column assembly.

[0015] The first column assembly is installed in the inside of the support in the operating mechanism, the inside of the first column assembly is connected with a solid phase carrier processing mechanism, and the bottom of the first column assembly is detachably installed with a collection assembly.

[0016] The first column assembly comprises a first column.

[0017] The first column is installed in the inside of the support, the upper side of the front end and the rear end of the outer wall of the first column is provided with a second motor, the output end of the second motor is connected with a first gear, the first gear is meshed and connected with the outer wall of a second gear penetrating through the first column, the second gear is fixedly installed on the outer wall of the upper end of a second screw rod, the second screw rod is rotatably connected with the inside of the front end and the rear end of the first column, the inside of the bottom end of the first column is provided with a fixed groove, the bottom of the first column is provided with an electromagnetic valve, and the bottom of the electromagnetic valve is provided with an L-shaped groove.

[0018] The collection assembly comprises a collection disc.

[0019] The top of the collection disc is provided with an L-shaped block, and the L-shaped block is detachably installed in the inside of the L-shaped groove.

[0020] As a preferred scheme of the nucleic acid synthesis column, the solid phase carrier processing mechanism comprises a movable assembly.

[0021] The front and rear ends of the active component are connected to the outer wall of the first screw in the operating mechanism. The active component is internally connected to a second column component, and the lower end of the second column component is rotatably connected to the built-in and filter components.

[0022] As a preferred embodiment of the nucleic acid synthesis column of the present invention, the active component includes: an active disk;

[0023] The front and rear ends of the outer wall of the movable disc are provided with internal thread blocks. The interior of the internal thread blocks is threadedly connected to the outer wall of the first screw. The inner side of the movable disc is provided with an installation groove. The left and right ends of the installation groove are rotatably connected to the third gear. The top of the third gear is connected to the fourth motor. The fourth motor is installed at both ends of the top of the movable disc. The fourth gear is rotatably connected around the inside of the installation groove. The outer walls of the fourth gear and the third gear are meshed with the lower end of the outer wall of the second column assembly.

[0024] The second column assembly includes: a second column;

[0025] The lower end of the second column is provided with a base gear plate, which is rotatably connected to the inside of the mounting groove. The outer wall teeth of the base gear plate mesh with the outer wall of the fourth gear and the outer wall of the third gear. The inner wall of the second column is provided with protruding plates around its perimeter, and the inner wall of the base gear plate is provided with a rotating groove.

[0026] The built-in and filtering components include: a gravity disk;

[0027] The outer wall of the gravity disk is equipped with a rotating ring, which is rotatably connected to the inside of the rotating groove. The inner wall of the gravity disk is equipped with a filter screen plate, and a protruding post is provided at the center of the surface of the filter screen plate. Fixing blocks are provided around the bottom of the gravity disk, and the fixing blocks are connected to the fixing groove.

[0028] As a preferred embodiment of the nucleic acid synthesis column of the present invention, the aspiration mechanism includes an aspiration component;

[0029] The suction component is detachably installed on the top of the first column in the column mechanism. The suction component is internally rotatably connected to a toggle component, and the bottom of the toggle component contacts the compaction mechanism.

[0030] As a preferred embodiment of the nucleic acid synthesis column of the present invention, the aspiration component includes: a cover plate;

[0031] The bottom of the cover plate is detachably mounted on the top of the first column body, the top of the cover plate is provided with a storage ring box, the inner side of the storage ring box is provided with a discharge port connected with the top of the liquid guide assembly of the compaction mechanism, the top of the storage ring box is provided with a pump body mounted on the left side of the front end, the input end of the pump body is communicated with the storage ring box, the output end of the pump body is connected with a discharge pipe, the top of the cover plate is provided with a limiting groove around, the top of the cover plate is provided with a pipeline hole around, the top of the cover plate is provided with a first arc groove at the right end, and the bottom of the cover plate is provided with a second arc groove at the right end.

[0032] The dialing assembly comprises a rotating tooth ring.

[0033] The rotating tooth ring is rotationally connected in the interior of the cover plate, the bottom of the rotating tooth ring is provided with a dialing column, the bottom of the dialing column is in contact with the compaction assembly, the top teeth of the rotating tooth ring are meshingly connected with the lower end of the outer wall of the fifth gear, the left end of the fifth gear is connected with the output end of the fifth motor, and the fifth motor is mounted on the top right end of the cover plate.

[0034] As a preferred scheme of the nucleic acid synthesis column, the compaction mechanism comprises a liquid guide assembly.

[0035] The top of the liquid guide assembly is clamped by a fixed clamp, and the bottom of the liquid guide assembly is mounted on the top of the compaction assembly.

[0036] As a preferred scheme of the nucleic acid synthesis column, the liquid guide assembly comprises a clamping ring frame.

[0037] The inner wall of the clamping ring frame is clamped and fixed by a fixed clamp, the bottom of the clamping ring frame is connected with a limiting column, the limiting column is slidingly connected in the interior of the limiting groove of the suction mechanism, the bottom of the limiting column is connected with a liquid guide ring, the top of the liquid guide ring is provided with a spring pipe around, the outer wall of the spring pipe penetrates through the pipeline hole in the suction mechanism at the upper end, and the top of the spring pipe is connected with the discharge port in the suction mechanism.

[0038] The compaction assembly comprises a receiving disc.

[0039] The top of the receiving disc is detachably mounted with a receiving top plate, the top of the receiving top plate is mounted on the bottom of the liquid guide ring, the interior of the receiving disc is provided with a guide column around the top, the outer wall of the receiving disc is provided with a through groove at the right end, the interior of the receiving disc is rotationally connected with a movable ring, the top of the movable ring is provided with a guide groove around, the guide groove is slidingly connected with the guide column, the outer wall of the movable ring is provided with a dialing rod at the right end, the dialing rod is slidingly connected in the interior of the through groove, one end of the traction rod is rotationally connected with the inner wall of the movable ring around, the other end of the traction rod is rotationally connected with one end of the expansion arc plate, and the other end of the expansion arc plate is rotationally connected in the interior of the receiving disc.

[0040] A column mounting method of a nucleic acid synthesis column comprises the following operation steps:

[0041] S1: Initial input of carrier and pretreatment

[0042] Carrier injection: Quantitative CPG carrier is added into the second column of the solid-phase carrier processing mechanism through the cover plate center injection port;

[0043] Initial infiltration and impurity removal:

[0044] Start the first motor of the operation mechanism to drive the drive rod to lower the compaction mechanism, so that the storage disc of the compaction assembly extends into the second column;

[0045] Inject 5 times the volume of acetonitrile into the second column through the injection port of the cover plate, start the second motor of the column mechanism to drive the second screw to lower the solid-phase carrier processing mechanism to the bottom of the first column, so that the fixed block of the built-in and filtering assembly is clamped into the fixed groove of the first column, thereby fixing the gravity disc to prevent rotation;

[0046] Start the first motor to control the compaction mechanism to make reciprocating lifting motion, press the CPG through the inclined surface at the bottom of the storage disc, so that the carrier particles collide with each other and fully contact with acetonitrile, and the air in the micropores and surface dust are removed;

[0047] Open the electromagnetic valve at the bottom of the first column, start the compaction mechanism to press down, use the storage disc to push the CPG to gather towards the filter screen, so that the acetonitrile containing impurities flows through the filter screen and the electromagnetic valve into the collection disc of the collection assembly, and then close the electromagnetic valve.

[0048] S2: Carrier activation and secondary washing

[0049] Activation treatment: Inject 10% triethylamine acetonitrile solution through the cover plate injection port, start the fourth motor of the solid-phase carrier processing mechanism to drive the third and fourth gears to rotate the second column, use the convex plate on the inner wall of the second column to stir the CPG, so that the carrier fully reacts with the activation solution;

[0050] Secondary washing:

[0051] Open the electromagnetic valve, start the compaction mechanism to slowly press down, and discharge the activation solution to the collection disc;

[0052] Inject acetonitrile, repeat the "second column rotation stirring and compaction liquid discharge" operation twice to ensure that the residual activation solution is washed clean, close the electromagnetic valve, and retain the residual acetonitrile on the surface of the carrier to avoid dry agglomeration.

[0053] S3: Preparation of column loading liquid and bubble-free filling

[0054] Column loading liquid injection:

[0055] Start the second motor to drive the solid-phase carrier processing mechanism to rise to the upper end of the first column to reduce the injection height of the column loading liquid;

[0056] Start the fifth motor of the suction mechanism to drive the rotating tooth ring to rotate the rotating column, and through the rotating rod to push the rotating ring to rotate, so that the expansion arc plate of the compaction assembly expands outward;

[0057] Mix acetonitrile and diiodomethane at a volume ratio of 3:1 to prepare the column loading solution, slowly inject it through the expansion arc plate surface, and use the arc plate guide to make the column loading solution flow down the outer wall of the convex column to avoid splashing and generating bubbles;

[0058] Suspension preparation:

[0059] Start the fourth motor to drive the second column to rotate, so that the CPG mixes with the column loading solution to form a uniform suspension;

[0060] S4: compaction of the carrier and removal of excess liquid

[0061] Dynamic compaction:

[0062] Start the first motor to drive the compaction mechanism to descend, so that the expansion arc plate closely contacts the inner wall of the second column and the convex plate and convex column to prevent the carrier from sliding;

[0063] Control the compaction mechanism to continue to press down, and at the same time, start the fourth motor to drive the second column to rotate at a low speed, so that the carrier is evenly distributed and compacted;

[0064] Liquid removal operation:

[0065] Open the electromagnetic valve and start the pump body of the suction mechanism, and through the spring pipe and liquid guide ring of the liquid guide assembly, the excess column loading liquid is sucked into the storage ring box, discharged through the discharge pipe and collected, and the electromagnetic valve is closed to keep the carrier bed moist.

[0066] S5: column washing and balancing

[0067] Washing residual solvent:

[0068] Inject acetonitrile through the cover plate, start the compaction mechanism to slowly ascend and descend, drive the carrier to slightly loosen, and promote the dissolution of residual column loading liquid;

[0069] Start the pump body to suck out the washing liquid, repeat the washing until the discharged liquid is detected by gas chromatography to have a diiodomethane residue of less than 0.1%;

[0070] Synthetic environment balancing:

[0071] Inject the synthesis buffer solution, start the second column to rotate, and make the buffer solution fully soak the carrier;

[0072] Discharge the buffer solution, keep the liquid level in the column higher than the carrier bed, and complete the balancing.

[0073] S6: bubble removal and bed quality detection

[0074] Bubble removal:

[0075] Start the first motor to make the compaction mechanism quickly lift, and use pressure fluctuation to release the carrier gap bubble;

[0076] Start the second motor to drive the solid-phase carrier processing mechanism to slowly rise, and slightly pump air from the bottom of the column to make the bubble rise along the column wall to the cover plate to be discharged;

[0077] Quality detection:

[0078] Uniformity inspection: observe the carrier bed layer through the first column to confirm that there is no fault, gully;

[0079] Coupling activity verification: take a small amount of carrier, inject a fluorescently labeled phosphoramidite monomer through the cover plate, detect the fluorescence intensity after 10 minutes of reaction, and confirm that the coupling efficiency is greater than or equal to 98.5%.

[0080] S7: finishing processing and recording

[0081] Waste liquid treatment: pour the waste liquid in the collection tray into a special organic solvent recovery barrel, and dispose according to the hazardous waste treatment specification;

[0082] Equipment reset:

[0083] Start the motor to make the compaction mechanism and the solid-phase carrier processing mechanism reset to the initial position;

[0084] Dismantle the collection tray and use it after cleaning;

[0085] Parameter recording: record the column loading date, CPG batch, column loading liquid ratio, compaction pressure, washing times, detection results, etc., and establish a batch file.

[0086] Compared with the prior art:

[0087] The solid-phase carrier processing mechanism can be raised to near the bottom of the cover plate, greatly reducing the injection height of the column loading liquid; the expansion arc plate of the compaction mechanism can be expanded outward to form a flow guide surface, so that the column loading liquid slowly flows down along the inner wall of the second column, and cooperates with the convex column to completely avoid splashing; thereby the bubble residual rate can be greatly reduced, and the carrier bed layer is more uniform.

[0088] The convex plate on the inner wall of the second column cooperates with rotation driving to 360° without dead angle, so as to improve the reaction efficiency of acetonitrile cleaning and triethylamine activation; the reciprocating lifting of the compaction mechanism can push the carriers to collide with each other, forcibly discharge the air in the micropores and surface dust, thereby improving the impurity removal rate, and shortening the processing time of a single batch.

[0089] The expansion arc plate is closely attached to the convex plate and convex column on the inner wall of the second column to form a non-sliding compaction structure, avoiding the deviation of the carrier under the action of pressure; and cooperating with the start of the low-speed rotation of the second column to make the bed layer density uniform.

[0090] The application can reduce the risk of pollution by linkage of operation mechanism, column mechanism, solid phase carrier processing mechanism and other structures from carrier delivery to final reset without manual transfer; the suction mechanism and the compaction mechanism work together to automatically complete the operations such as supernatant suction and residual liquid discharge, thereby reducing the carrier loss rate.

[0091] The application can be quickly disassembled by the cooperation of the collection disc and the L-shaped block and the L-shaped groove, facilitating waste liquid treatment and component cleaning; after the column is installed, the compaction mechanism can drive the carrier to slightly loosen through lifting movement, and the internal self-cleaning of the column body is realized by cooperating with acetonitrile flushing. BRIEF DESCRIPTION OF DRAWINGS

[0092] Figure 1 The overall structure schematic diagram provided by the application is provided;

[0093] Figure 2 The operation mechanism structure schematic diagram provided by the application is provided;

[0094] Figure 3 The column mechanism, suction mechanism and compaction mechanism split structure schematic diagram provided by the application is provided;

[0095] Figure 4 The column mechanism internal structure schematic diagram provided by the application is provided;

[0096] Figure 5 The column mechanism split structure schematic diagram provided by the application is provided;

[0097] Figure 6 The first column assembly structure schematic diagram provided by the application is provided Figure 1 ;

[0098] Figure 7 The first column assembly structure schematic diagram provided by the application is provided Figure 2 ;

[0099] Figure 8 The collection assembly structure schematic diagram provided by the application is provided;

[0100] Figure 9 The solid phase carrier processing mechanism structure schematic diagram provided by the application is provided;

[0101] Figure 10 The solid phase carrier processing mechanism split structure schematic diagram provided by the application is provided;

[0102] Figure 11 The movable assembly structure schematic diagram provided by the application is provided;

[0103] Figure 12 The movable assembly cross-sectional structure schematic diagram provided by the application is provided;

[0104] Figure 13This is a schematic diagram of the disassembled structure of the active components provided by the present invention;

[0105] Figure 14 Schematic diagram of the second column component structure provided by the present invention Figure 1 ;

[0106] Figure 15 Schematic diagram of the second column component structure provided by the present invention Figure 2 ;

[0107] Figure 16 Schematic diagram of the built-in and filtering components provided by the present invention Figure 1 ;

[0108] Figure 17 Schematic diagram of the built-in and filtering components provided by the present invention Figure 2 ;

[0109] Figure 18 This is a schematic diagram of the connection structure between the second column assembly and the built-in and filter assemblies provided by the present invention;

[0110] Figure 19 This is a schematic diagram of the connection structure between the suction mechanism and the compaction mechanism provided by the present invention;

[0111] Figure 20 Schematic diagram of the suction component structure provided by the present invention Figure 1 ;

[0112] Figure 21 Schematic diagram of the suction component structure provided by the present invention Figure 2 ;

[0113] Figure 22 This is a schematic diagram of the toggle assembly structure provided by the present invention;

[0114] Figure 23 This is a schematic diagram of the compaction mechanism provided by the present invention;

[0115] Figure 24 Schematic diagram of the liquid guiding component structure provided by the present invention Figure 1 ;

[0116] Figure 25 Schematic diagram of the liquid guiding component structure provided by the present invention Figure 2 ;

[0117] Figure 26 This is a schematic diagram of the disassembled structure of the compaction component provided by the present invention;

[0118] Figure 27 A schematic diagram of the disassembled structure of the storage tray and storage top plate provided by the present invention. Figure 1 ;

[0119] Figure 28The storage tray and the storage top plate are split Figure 2 ;

[0120] Figure 29 The storage tray and the movable ring are connected

[0121] Figure 30 The movable ring connection structure is shown in the schematic view. DETAILED DESCRIPTION

[0122] In order to make the purpose, technical scheme and advantages of the present application clearer, the embodiments of the present application will be further described in detail below with reference to the drawings.

[0123] The present application provides a nucleic acid synthesis column and a column loading method, please refer to Figures 1-30 , including operating mechanism 1, column mechanism 2, solid phase carrier processing mechanism 3, suction mechanism 4 and compaction mechanism 5;

[0124] The operating mechanism 1 is placed on the ground, and the operating mechanism 1 comprises an operating platform 11, a first screw rod 12, a first motor 13, a support 14, a driving rod 15 and a fixing clamp 16. The operating platform 11 is placed on the ground, and the first screw rod 12 is rotatably connected to the surface of the operating platform 11 at both sides of the upper end. The first screw rod 12 is provided in two groups, and the two groups of first screw rods 12 are connected by a chain wheel and a chain. The top of one group of first screw rods 12 is connected to the output end of the first motor 13, and the first motor 13 is installed on one side of the top of the operating platform 11. The first motor 13 can drive the two groups of first screw rods 12 to rotate. The support 14 is installed in the middle of the front end of the operating platform 11, and the column mechanism 2 is installed in the support 14. The column mechanism 2 can be installed and placed by the support 14. The driving rod 15 is slidably connected to the rear end of the operating platform 11 at both ends of the upper side of the front end. The rear end of the driving rod 15 is threadedly connected to the outer wall of the first screw rod 12. The driving rod 15 can be raised and lowered by the rotation of the first screw rod 12. The driving rod 15 is provided in two groups, and the fixing clamp 16 is installed between the two groups of driving rods 15. The fixing clamp 16 can clamp the compaction mechanism 5. The compaction mechanism 5 can be raised and lowered by the rotation of the first screw rod 12, so that the compaction mechanism 5 can operate the solid phase carrier in the solid phase carrier processing mechanism 3;

[0125] The column mechanism 2 is installed at the front end of the operating mechanism 1, and the column mechanism 2 is used for double covering of the column material to prevent the column material from splashing or gas from quickly rising. The column mechanism 2 comprises: a first column assembly 21, a first column 211, a second motor 212, a first gear 213, a second screw 214, a second gear 215, a fixed groove 216, an electromagnetic valve 217, an L-shaped groove 218, a collection assembly 22, a collection disc 221, and an L-shaped block 222. The outer wall of the first column assembly 21 is installed in the inner part of the support 14 in the operating mechanism 1, and the inner part of the first column assembly 21 is connected to the solid carrier processing mechanism 3. Through the driving of the first column assembly 21, the solid carrier processing mechanism 3 can be driven to move up and down. The outer wall of the first column 211 is installed in the inner part of the support 14, and the cooperation of the first column 211 and the solid carrier processing mechanism 3 can double cover the placed column material. The upper sides of the front end and the rear end of the outer wall of the first column 211 are both installed with the second motor 212. The output end of the second motor 212 is connected to the first gear 213. The first gear 213 penetrates the first column 211 and is meshingly connected with the outer wall of the second gear 215. The second gear 215 is fixedly installed on the outer wall of the upper end of the second screw 214. The second screw 214 is rotatably connected to the inner front end and the inner rear end of the first column 211. Through the driving of the second motor 212, the first gear 213 can be driven to rotate. The rotation of the first gear 213 can drive the second gear 215 and the second screw 214 to rotate. The inner bottom end of the first column 211 is provided with the fixed groove 216, which can be in contact with the bottom of the solid carrier processing mechanism 3, and is used for fixing the movement of the solid carrier processing mechanism 3 to prevent the built-in and filtering assembly 33 from rotating. The bottom of the first column 211 is provided with the electromagnetic valve 217, which is used for blocking or discharging the liquid material in the first column 211, facilitating the discharge of the precipitate. The bottom of the electromagnetic valve 217 is provided with the L-shaped groove 218 around it. The inner end of the L-shaped groove 218 is inwardly deepened to form an L-shaped notch. The L-shaped groove 218 is in contact with the top of the collection assembly 22, which can fix the installation of the collection assembly 22, and facilitate the disassembly and installation of the collection assembly 22. The bottom of the first column assembly 21 is detachably installed with the collection assembly 22. Through the discharge of the first column assembly 21, the precipitate can fall into the inner part of the collection assembly 22. Through the collection assembly 22, the precipitate can be collected. The top of the collection disc 221 is provided with the L-shaped block 222, which is detachably installed in the inner part of the L-shaped groove 218. Through the cooperation of the L-shaped groove 218 and the L-shaped block 222, the collection disc 221 can be connected to the bottom of the first column 211. Through the collection disc 221, the precipitate can be collected.

[0126] The solid phase carrier processing mechanism 3 is connected in the interior of the column mechanism 2, and is driven by the column mechanism 2 to drive the solid phase carrier processing mechanism 3 to ascend and descend, facilitates the feeding of the column material, and simultaneously, the solid phase carrier processing mechanism 3 is close to the feeding opening, can reduce the splashing of the liquid column material, thereby avoiding the generation of bubbles in the feeding of the liquid column material. The solid phase carrier processing mechanism 3 comprises: a movable assembly 31, a movable disc 311, an internal threaded block 312, a mounting groove 313, a fourth motor 314, a third gear 315, a fourth gear 316, a second column assembly 32, a second column 321, a base tooth disc 322, a convex plate 323, a rotating groove 324, an internal and filtering assembly 33, a gravity disc 331, a rotating ring 332, a filtering screen plate 333, a convex column 334 and a fixing block 335. The front end and the rear end of the movable assembly 31 are connected with the outer wall of the first screw rod 12 in the operation mechanism 1, and the movable assembly 31 can be driven to ascend and descend through the rotation of the first screw rod 12. The outer wall of the front end and the rear end of the movable disc 311 is provided with the internal threaded block 312, the interior of the internal threaded block 312 is threadedly connected with the outer wall of the first screw rod 12, and the movable disc 311 can be driven to ascend and descend through the rotation of the first screw rod 12. The inner side of the movable disc 311 is provided with the mounting groove 313, the interior of the mounting groove 313 is rotatably connected with the third gear 315 at the left end and the right end, the top of the third gear 315 is connected with the fourth motor 314, the fourth motor 314 is mounted at the top of the movable disc 311, the interior of the mounting groove 313 is rotatably connected with the fourth gear 316 around, the outer wall of the fourth gear 316 is meshingly connected with the outer wall of the third gear 315, and the outer wall lower end of the second column assembly 32 is meshingly connected with the outer wall of the third gear 315. The rotation of the third gear 315 can drive the second column assembly 32 to rotate, and the rotation of the fourth gear 316 can limit the rotation of the second column assembly 32. The interior of the movable assembly 31 is connected with the second column assembly 32, the second column assembly 32 can be driven to rotate through the driving of the movable assembly 31, the solid phase carrier can be driven to move through the rotation of the movable assembly 31, the second column assembly 32 can place the column material, the second column assembly 32 is driven to move to the upper end through the movable assembly 31, thereby reducing the feeding height, and the column liquid material passes through the compaction mechanism 5 and then falls into the interior of the second column assembly 32 through the cooperation of the compaction mechanism 5, thereby avoiding the generation of bubbles in the feeding of the liquid column material. The lower end of the second column 321 is provided with the base tooth disc 322, the base tooth disc 322 is rotatably connected in the interior of the mounting groove 313, the outer wall teeth of the base tooth disc 322 and the outer wall of the fourth gear 316 and the third gear 315 are meshingly connected, the rotation of the third gear 315 can drive the second column 321 to rotate and drive, the inner wall of the second column 321 is provided with the convex plate 323 around, the convex plate 323 cooperates with the internal and filtering assembly 33, the convex plate 323 is driven to rotate to drive the solid phase carrier to be stirred, thereby making the solid phase carrier and the acetonitrile solution contact with each other,The inner wall of the base tooth disc 322 is provided with a rotating groove 324, the inner lower end of the second column body assembly 32 is rotationally connected with the built-in and filtering assembly 33, the bottom of the built-in and filtering assembly 33 is in contact with the fixed groove 216 in the first column body 211, so that the built-in and filtering assembly 33 does not rotate, and through the cooperation of the built-in and filtering assembly 33 and the second column body assembly 32, the solid phase carrier can be stirred, so that the solid phase carrier is activated by the acetonitrile solution, the outer wall of the gravity disc 331 is installed with a rotating ring 332, the rotating ring 332 is rotationally connected in the inner part of the rotating groove 324, the rotating ring 332 and the rotating groove 324 are sealingly connected through a sealing ring, the inner wall of the gravity disc 331 is installed with a filter screen plate 333, the filter screen plate 333 can filter the column material, the surface center of the filter screen plate 333 is provided with a convex column 334, the bottom of the gravity disc 331 is provided with a fixed block 335 around, the fixed block 335 is connected with the fixed groove 216, through the connection of the fixed groove 216 and the fixed block 335, the gravity disc 331 can be fixed, through the rotating driving of the second column body assembly 32 driven by the movable assembly 31, the second column body assembly 32 rotates, at this time the gravity disc 331 is fixed, so that the solid phase carrier in the second column body 321 is stirred by the convex plate 323, so that the solid phase carrier moves;

[0127] The suction mechanism 4 is installed at the top of the column mechanism 2, and the suction mechanism 4 is connected with the top of the compaction mechanism 5. Through the cooperation of the suction mechanism 4 and the compaction mechanism 5, the suction mechanism 4 can suck and discharge the liquid column material in the compaction mechanism 5. The suction mechanism 4 comprises: a suction assembly 41, a cover plate 411, a storage ring box 412, a discharge port 413, a pump body 414, a discharge pipe 415, a limiting groove 416, a pipeline hole 417, a first arc groove 418, a second arc groove 419, a dialing assembly 42, a rotating tooth ring 421, a dialing column 422, a fifth motor 423 and a fifth gear 424; the suction assembly 41 is detachably installed at the top of the first column 211 in the column mechanism 2, and the suction assembly 41 cooperates with the first column 211 to doublely cover the column material, preventing the column material from splashing out or gas from leaking out. The bottom of the cover plate 411 is detachably installed at the top of the first column 211. The top of the cover plate 411 is provided with the storage ring box 412. The inner side of the storage ring box 412 is provided with the discharge port 413. The discharge port 413 is connected with the top of the liquid guide assembly 51 in the compaction mechanism 5. The top front left side of the storage ring box 412 is provided with the pump body 414. The input end of the pump body 414 is in communication with the storage ring box 412. The output end of the pump body 414 is connected with the discharge pipe 415. Through the pump body 414, the liquid on the surface of the liquid guide assembly 51 can be sucked into the inside of the storage ring box 412, and the liquid in the inside of the storage ring box 412 can be discharged through the discharge pipe 415. The top of the cover plate 411 is provided with the limiting groove 416. The top of the cover plate 411 is provided with the pipeline hole 417. The top right end of the cover plate 411 is provided with the first arc groove 418. The bottom right end of the cover plate 411 is provided with the second arc groove 419. The inside of the suction assembly 41 is rotatably connected with the dialing assembly 42. The bottom of the dialing assembly 42 is in contact with the compaction mechanism 5. Through the driving of the dialing assembly 42, the compaction assembly 52 in the compaction mechanism 5 can be driven to expand inward, so as to tightly connect the second column 321 and the convex column 334. The rotating tooth ring 421 is rotatably connected in the inside of the cover plate 411. The bottom of the rotating tooth ring 421 is provided with the dialing column 422. The bottom of the dialing column 422 is in contact with the compaction assembly 52. The top teeth of the rotating tooth ring 421 are meshingly connected with the lower end of the outer wall of the fifth gear 424. The left end of the fifth gear 424 is connected with the output end of the fifth motor 423. The fifth motor 423 is installed at the top right end of the cover plate 411. Through the driving of the fifth motor 423, the fifth gear 424 and the rotating tooth ring 421 can be driven to rotate, so as to drive the compaction assembly 52 to expand through the dialing column 422;

[0128] The upper end of the compacting mechanism 5 is installed on the front end upper side of the operating mechanism 1, and the bottom of the compacting mechanism 5 can extend into the interior of the solid carrier processing mechanism 3. Through the cooperation of the solid carrier processing mechanism 3 and the compacting mechanism 5, the compacting mechanism 5 can perform compacting operation on the solid carrier in the interior of the solid carrier processing mechanism 3. Meanwhile, through the compacting mechanism 5, the solid carrier can also be pressed and moved, so that the solid carrier moves from the bottom of the compacting mechanism 5 to the surface of the compacting mechanism 5, thereby moving the solid carrier. The compacting mechanism 5 comprises a liquid guiding assembly 51, a clamping ring frame 511, a limiting column 512, a liquid guiding ring 513, a spring pipe 514, a compacting assembly 52, a storage disc 521, a guide column 522, a through groove 523, a movable ring 524, a guide groove 525, a pushing rod 526, a traction rod 527, an expanding arc plate 528, and a storage top plate 529. The top of the liquid guiding assembly 51 is clamped by the fixed hoop 16, and the liquid guiding assembly 51 can be driven by the lifting movement of the driving rod 15. The bottom of the liquid guiding assembly 51 can introduce supernatant. The inner wall of the clamping ring frame 511 is clamped and fixed by the fixed hoop 16. The bottom of the clamping ring frame 511 is connected with the limiting column 512. The limiting column 512 is slidingly connected in the interior of the limiting groove 416 in the suction mechanism 4, thereby limiting and guiding the lifting movement of the compacting assembly 52. The bottom of the limiting column 512 is connected with the liquid guiding ring 513. The top of the liquid guiding ring 513 is provided with a groove. Through the groove, liquid can be introduced, and through the groove, liquid can be introduced into the bottom of the spring pipe 514 at both ends, thereby enabling the spring pipe 514 to suck out the liquid. The top of the liquid guiding ring 513 is provided with the spring pipe 514 around. The outer wall of the spring pipe 514 penetrates the pipeline hole 417 in the suction mechanism 4 at the upper end. The top of the spring pipe 514 is connected with the discharge port 413 in the suction mechanism 4, thereby enabling the spring pipe 514 to communicate with the pump body 414. The bottom of the liquid guiding assembly 51 is installed on the top of the compacting assembly 52. The compacting assembly 52 can contact the solid carrier in the second column 321, thereby performing compacting and pressing movement on the solid carrier, thereby enabling the liquid guiding assembly 51 to extend to the bottom of the second column 321, and further enabling the liquid guiding assembly 51 to suck out the supernatant and the column liquid. The top of the storage disc 521 is detachably installed with the storage top plate 529. The top of the storage top plate 529 is installed on the bottom of the liquid guiding ring 513. The interior top of the storage disc 521 is provided with the guide column 522 around. The outer wall of the storage disc 521 is provided with the through groove 523 at the right end. The interior of the storage disc 521 is rotationally connected with the movable ring 524. The top of the movable ring 524 is provided with the guide groove 525 around. The guide groove 525 is slidingly connected with the guide column 522 in the interior. Through the cooperation of the guide column 522 and the guide groove 525, the rotation of the movable ring 524 can be limited and guided. The outer wall of the movable ring 524 is provided with the pushing rod 526 at the right end. The pushing rod 526 is slidingly connected in the interior of the through groove 523. The top of the pushing rod 526 is provided with a notch. The notch of the pushing rod 526 can be penetrated by the pushing column 422. Through the movement of the pushing column 422, the movable ring 524 can be rotated by a distance.The inner wall of the movable ring 524 is rotatably connected to one end of the traction rod 527, the other end of the traction rod 527 is rotatably connected to one end of the expansion arc plate 528, the other end of the expansion arc plate 528 is rotatably connected to the inside of the receiving disc 521, through the rotation of the movable ring 524, the traction rod 527 can pull and push the expansion arc plate 528, so that the expansion arc plate 528 is contracted and expanded, thereby realizing the caliber change of the receiving disc 521, and through the cooperation of the groove on the outer wall of the receiving disc 521 and the groove on the inner wall of the expansion arc plate 528, the convex plate 323 and the convex column 334 are in close contact, so that the receiving disc 521 and the expansion arc plate 528 can compact and continuously press the solid phase carrier, wherein the bottom of the receiving disc 521 is provided with a slope, which facilitates the solid phase carrier to slide from the bottom of the receiving disc 521 to the top of the receiving top plate 529, and press the solid phase carrier; wherein the bottom of the compaction mechanism 5 is provided with an integrated pressure sensor, which can monitor the pressure change of compaction in real time, and automatically stop compaction when the pressure exceeds the threshold value, so as to avoid excessive compression of the carrier and cause the column efficiency to drop.

[0129] In specific use, when the wet column loading operation is performed by the person skilled in the art, the carrier CPG (controllable microporous glass beads) or polystyrene microspheres can be thrown into the inside of the solid-phase carrier treatment mechanism 3 through the center of the cover plate 411, at this time, the second motor 212 is started to drive the solid-phase carrier treatment mechanism 3 to move to the bottom of the first column 211, so that the fixed block 335 at the bottom of the built-in and filtering assembly 33 is in contact with the fixed groove 216 at the bottom end inside the first column 211, by throwing acetonitrile solution again, the acetonitrile solution is used to soak the carrier CPG, by starting the first motor 13 to drive the storage disc 521 of the compaction mechanism 5 to continuously ascend and descend, the carrier CPG in the solid-phase carrier treatment mechanism 3 is continuously pressed, the carrier CPG is pressed by the bottom of the storage disc 521 and slides into the top of the storage top plate 529, so that the carrier CPG is continuously collided and moved, and then the carrier CPG is continuously contacted with the acetonitrile solution, the air in the micropore of the carrier CPG is discharged, and at the same time, the surface dust is removed, then the compaction mechanism 5 is driven to rise and move out of the solid-phase carrier treatment mechanism 3, so that the carrier CPG is static with the liquid for a period of time, then the electromagnetic valve 217 is started, the carrier CPG continuously leaks out of the filtering screen plate 333 through the continuous driving of the storage disc 521, so that the solution in the solid-phase carrier treatment mechanism 3 is discharged to the first column 211, the carrier CPG is processed once, by adding acetonitrile solution again and closing the electromagnetic valve 217, at this time, the fourth motor 314 is started to drive the second column 321 to rotate, so that the carrier CPG is stirred again and processed twice, so that the solution activates the carrier CPG, by driving the compaction mechanism 5 to press down again and moving the liquid guide ring 513 to the supernatant position of the acetonitrile solution, the pump body 414 is started to discharge the supernatant of the acetonitrile solution, at this time, the acetonitrile solution in the solid-phase carrier treatment mechanism 3 is almost exhausted, the remaining acetonitrile solution is used to wet the carrier CPG, by starting the second motor 212 and the first motor 13, the solid-phase carrier treatment mechanism 3 and the compaction mechanism 5 are driven to rise again, and the compaction mechanism 5 is moved to the inside of the solid-phase carrier treatment mechanism 3, the solid-phase carrier treatment mechanism 3 is moved to the lower end of the cover plate 411, and the solid-phase carrier treatment mechanism 3 is close to the bottom of the cover plate 411 as much as possible, at this time, due to the rising of the compaction mechanism 5, the slot of the pressing rod 526 of the compaction assembly 52 is inserted into the pressing column 422 of the pressing assembly 42, at this time, the fifth motor 423 is started to drive the rotating gear ring 421 and the pressing column 422 to move, so that the compaction assembly 52 is expanded, the expansion arc plate 528 is expanded, the mixed solution of acetonitrile and diiodomethane is thrown onto the surface of the expansion arc plate 528, the mixed solution is slowly dropped into the inside of the solid-phase carrier treatment mechanism 3 through the arc surface of the expansion arc plate 528, at this time, due to the full filling of the carrier CPG, the holes of the filtering screen plate 333 are blocked to prevent the mixed solution from falling, and then the column loading liquid is thrown into the inside of the solid-phase carrier treatment mechanism 3 through the same throwing method,Prevent the column liquid and acetonitrile and diiodomethane mixture occurs when put in splash and gas channeling, by moving the solid phase carrier processing mechanism 3 to the bottom of the first column 211, at this time the fourth motor 314 is started again, driven by the second column 321 rotation, so that the second column 321 inner wall flange plate 323 to move the carrier CPG slowly, make the solution form uniform suspension, by starting the first motor 13 again, make the extended compaction assembly 52 down, the carrier CPG in solid phase carrier processing mechanism 3 for compaction operation, at this time because the storage disc 521 and the extension arc plate 528 just and the second column 321 flange plate 323 and convex column 334 closely, can prevent the carrier CPG in the process of sliding phenomenon, only to realize the compaction operation, so that the storage disc 521 and the extension arc plate 528 to solid phase carrier processing mechanism 3 inside pressure, change the pressure in the solid phase carrier processing mechanism 3, until the liquid pressure filter screen plate 333, at this time open electromagnetic valve 217, the liquid drop to the inside of the collection tray 221, at the same time, in the process of compaction, can be combined with the second column 321 slowly rotate, driven by the carrier CPG slightly move, make the liquid smoothly through the filter screen plate 333, until drop to the inside of the collection tray 221.

[0130] Although the present application has been described with reference to the embodiments above, various changes and modifications could be suggested by those skilled in the art without departing from the scope of the application. Particularly, the features of the disclosed embodiments of the present application can be combined in any manner, provided that there is no structural conflict, and the combinations are not described in the specification only for the sake of brevity and conciseness. Therefore, the present application is not limited to the specific embodiments disclosed in the specification, but includes all the technical solutions falling within the scope of the claims.

Claims

1. A nucleic acid synthesis column, comprising: The operating mechanism is characterized by: The operating mechanism is placed on the ground. A column mechanism is installed at the front end of the operating mechanism. The column mechanism is used to double-cover the column material. A solid carrier processing mechanism is connected inside the column mechanism. The column mechanism drives the solid carrier processing mechanism to lift and lower. A suction mechanism is installed at the top of the column mechanism. The suction mechanism is connected to the top of the compaction mechanism. Through the cooperation of the suction mechanism and the compaction mechanism, the suction mechanism sucks out the liquid column material in the compaction mechanism. The upper end of the compaction mechanism is installed on the upper side of the front end of the operating mechanism. The operating mechanism includes: an operating platform; The operating platform is placed on the ground. The upper two sides of the surface of the operating platform are rotatably connected to the first screw. The top of a set of first screws is connected to the output end of the first motor. The first motor is installed on one side of the top of the operating platform. A bracket is installed in the middle of the front end of the operating platform. A column mechanism is installed inside the bracket. The upper two ends of the front end of the operating platform are slidably connected to the rear end of the drive rod. The rear end of the drive rod is threadedly connected to the outer wall of the first screw. A fixing hoop is installed between the two sets of drive rods. The column mechanism includes: a first column assembly; The outer wall of the first column assembly is installed inside the bracket in the operating mechanism. The solid phase carrier processing mechanism is connected inside the first column assembly. The collection component is detachably installed at the bottom of the first column assembly. The first column assembly includes: a first column; The first column is installed inside the bracket in the middle of its outer wall. The second motor is installed on the upper side of the front and rear ends of the first column. The output end of the second motor is connected to the first gear. The first gear passes through the first column and meshes with the outer wall of the second gear. The second gear is fixedly installed on the upper end of the outer wall of the second screw. The second screw is rotatably connected to the front and rear ends of the first column. The bottom of the first column is provided with a fixing groove around its perimeter. The bottom of the first column is provided with a solenoid valve. The bottom of the solenoid valve is provided with an L-shaped groove around its perimeter. The collection component includes: a collection disk; The top of the collection tray is surrounded by L-shaped blocks, which can be detachably installed inside the L-shaped groove; The solid carrier processing mechanism includes: a movable component; The front and rear ends of the active component are connected to the outer wall of the first screw in the operating mechanism. The active component is internally connected to a second column component, and the lower end of the second column component is rotatably connected to the built-in and filter components. The active component includes: an active disk; The front and rear ends of the outer wall of the movable disc are provided with internal thread blocks. The interior of the internal thread blocks is threadedly connected to the outer wall of the first screw. The inner side of the movable disc is provided with an installation groove. The left and right ends of the installation groove are rotatably connected to the third gear. The top of the third gear is connected to the fourth motor. The fourth motor is installed at both ends of the top of the movable disc. The fourth gear is rotatably connected around the inside of the installation groove. The outer walls of the fourth gear and the third gear are meshed with the lower end of the outer wall of the second column assembly. The second column assembly includes: a second column; The lower end of the second column is provided with a base gear plate, which is rotatably connected to the inside of the mounting groove. The outer wall teeth of the base gear plate mesh with the outer wall of the fourth gear and the outer wall of the third gear. The inner wall of the second column is provided with protruding plates around its perimeter, and the inner wall of the base gear plate is provided with a rotating groove. The built-in and filtering components include: a gravity disk; The outer wall of the gravity disk is equipped with a rotating ring, which is rotatably connected to the inside of the rotating groove. The inner wall of the gravity disk is equipped with a filter screen plate, and a protruding post is provided at the center of the surface of the filter screen plate. Fixing blocks are provided around the bottom of the gravity disk, and the fixing blocks are connected to the fixing groove.

2. The nucleic acid synthesis column according to claim 1, characterized in that, The suction mechanism includes: a suction component; The suction component is detachably installed on the top of the first column in the column mechanism. The suction component is internally rotatably connected to a toggle component, and the bottom of the toggle component contacts the compaction mechanism.

3. A nucleic acid synthesis column according to claim 2, characterized in that, The suction assembly includes: a cover plate; The bottom of the cover plate is detachably installed on the top of the first column. The top of the cover plate is provided with a storage ring box. The inner side of the storage ring box is provided with a discharge port. The discharge port is connected to the top of the liquid guiding component in the compaction mechanism. A pump body is installed on the left side of the top front end of the storage ring box. The input end of the pump body is connected to the storage ring box. The output end of the pump body is connected to the discharge pipe. The top of the cover plate is provided with a limiting groove. The top of the cover plate is provided with a pipe hole. The top right end of the cover plate is provided with a first arc groove. The bottom right end of the cover plate is provided with a second arc groove. The actuating assembly includes: a rotating toothed ring; The rotating gear ring is rotatably connected inside the cover plate. The bottom of the rotating gear ring is provided with a toggle post, the bottom of which contacts the compaction component. The top teeth of the rotating gear ring mesh with the lower end of the outer wall of the fifth gear. The left end of the fifth gear is connected to the output end of the fifth motor, which is installed on the top right end of the cover plate.

4. A nucleic acid synthesis column according to claim 3, characterized in that, The compaction mechanism includes: a liquid guiding component; The top of the liquid guiding assembly is clamped by a fixing hoop, and the bottom of the liquid guiding assembly is installed on top of the compaction assembly.

5. A nucleic acid synthesis column according to claim 4, characterized in that, The fluid guiding assembly includes: a clamping ring frame; The inner wall of the clamping ring frame is clamped and fixed by a fixing hoop. The bottom of the clamping ring frame is connected to a limiting post. The limiting post is slidably connected inside the limiting groove in the suction mechanism. The bottom of the limiting post is connected to a liquid guiding ring. The top of the liquid guiding ring is provided with spring tubes around its perimeter. The upper end of the outer wall of the spring tubes penetrates the pipe hole in the suction mechanism. The top of the spring tubes is connected to the discharge inlet in the suction mechanism. The compaction component includes: a storage tray; The top of the storage tray is detachably fitted with a storage top plate, which is installed at the bottom of the liquid guiding ring. The top of the storage tray has guide posts around its interior. The right end of the outer wall of the storage tray has a through groove. The inside of the storage tray is rotatably connected to a movable ring, which has guide grooves around its top. The guide posts are slidably connected inside the guide grooves. The right end of the outer wall of the movable ring has a lever that is slidably connected inside the through groove. One end of a traction rod is rotatably connected around the inner wall of the movable ring. The other end of the traction rod is rotatably connected to one end of an extension arc plate, and the other end of the extension arc plate is rotatably connected inside the storage tray.

6. The column packing method using the nucleic acid synthesis column according to claim 5, characterized in that, The following steps are included: S1: Initial Carrier Input and Pretreatment Carrier delivery: A quantitative amount of CPG carrier is added into the second column of the solid carrier processing mechanism through the delivery port in the center of the cover plate; Initial wetting and impurity removal: The first motor of the operating mechanism is activated, which drives the drive rod to lower the compaction mechanism, causing the receiving tray of the compaction component to extend into the second column. Acetonitrile with a volume of 5 times that of the carrier is injected into the second column through the injection port of the cover plate. The second motor of the column mechanism is started, and the second screw drives the solid carrier processing mechanism to descend to the bottom of the first column. The fixing block of the built-in and filter components is locked into the fixing groove of the first column, thereby fixing the gravity disk and preventing it from rotating. The first motor is started to control the compaction mechanism to perform reciprocating lifting and lowering motion. The CPG is pressed by the inclined surface at the bottom of the collection tray, so that the carrier particles collide with each other and come into full contact with acetonitrile, expelling air and surface dust from the micropores. Open the solenoid valve at the bottom of the first column, start the compaction mechanism to press down, and use the collection tray to push the CPG to gather towards the filter screen, so that the acetonitrile containing impurities flows through the filter screen and solenoid valve into the collection tray of the collection component, and then close the solenoid valve. S2: Carrier activation and secondary washing Activation treatment: Inject 10% triethylamine acetonitrile solution through the cover plate inlet, start the fourth motor of the solid carrier treatment mechanism, drive the third gear and the fourth gear to drive the second column to rotate, and use the convex plate on the inner wall of the second column to move the CPG so that the carrier and the activation solution can react fully. Second wash: Open the solenoid valve, start the compaction mechanism to slowly press down, and discharge the activation liquid into the collection tray; Inject acetonitrile, repeat the "rotating and compacting the second column" operation twice to ensure that the residual activation solution is washed away, close the solenoid valve, and leave the residual acetonitrile on the carrier surface to avoid drying and agglomeration; S3: Column packing solution preparation and bubble-free packing Column packing fluid injection: The second motor is started to drive the solid carrier processing mechanism to rise to the top of the first column, reducing the column packing liquid injection height; The fifth motor of the suction mechanism is started, which drives the rotating gear ring to rotate the actuating column. The actuating rod pushes the movable ring to rotate, causing the expansion arc plate of the compaction component to expand outward. The packing solution, a mixture of acetonitrile and diiodomethane in a 3:1 volume ratio, is slowly injected through the surface of an extended arc plate. The arc plate guides the packing solution to flow down the outer wall of the convex column, avoiding splashing and bubble formation. Suspension preparation: The fourth motor is started to drive the second column to rotate, so that the CPG and the packing liquid are mixed to form a uniform suspension; S4: Carrier compaction and excess liquid drainage Dynamic compaction: The first motor is activated to drive the compaction mechanism to descend, so that the extended arc plate fits tightly against the inner wall of the second column and the convex plate and convex column to prevent the carrier from sliding. The compaction mechanism is controlled to press down continuously, while the fourth motor is started to drive the second column to rotate at low speed, so that the carrier is evenly distributed and compacted. Drainage operation: Open the solenoid valve, start the pump body of the suction mechanism, and suck the excess packing liquid into the storage ring tank through the spring tube and liquid guide ring of the liquid guide assembly. Then, discharge and collect the liquid through the discharge pipe. Close the solenoid valve to keep the carrier bed moist. S5: Column Washing and Balancing Washing away residual solvent: Acetonitrile is injected through the cover plate, and the compaction mechanism is activated to slowly raise and lower, causing the carrier to loosen slightly and promoting the dissolution of residual packing solution; Start the pump to draw out the washing solution, repeat the washing process until the effluent is tested by gas chromatography and the diiodomethane residue is < 0.1%; Synthetic environment equilibrium: Inject the synthesis buffer and start the second column rotation to fully wet the carrier with the buffer; Drain the buffer solution, leaving the liquid level in the column higher than the carrier bed, to complete the equilibration process; S6: Air bubble removal and bed quality inspection Air bubble removal: The first motor is started to make the compaction mechanism rise and fall rapidly, and the pressure fluctuations release the air bubbles in the carrier gaps. The second motor is started to drive the solid carrier processing mechanism to rise slowly. At the same time, the pump body slightly draws air from the bottom of the column, so that the air bubbles rise along the column wall to the cover plate and are discharged. Quality Inspection: Uniformity check: Observe the carrier bed through the first column to confirm that there are no faults or gullies; Coupling activity verification: A small amount of carrier was injected with fluorescently labeled phosphoramide monomer through a cover plate. After reacting for 10 minutes, the fluorescence intensity was detected to confirm that the coupling efficiency was ≥98.5%. S7: Finishing and Recording Waste liquid treatment: Pour the waste liquid in the collection tray into a special organic solvent recovery tank and dispose of it in accordance with the hazardous waste treatment regulations; Device reset: Start each motor to reset the compaction mechanism and solid carrier processing mechanism to their initial positions; Remove the collection tray, clean it, and set it aside for later use; Parameter recording: Record column packing date, CPG batch, column packing solution ratio, compaction pressure, number of washes, and test results to establish batch files.

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