A device for monitoring the progress of a biochemical reaction synthesis by HPLC on line

Abstract

The application discloses a device for monitoring the progress of biochemical reaction synthesis online by HPLC, which comprises a workbench, a liquid chromatograph installed on the workbench, and a plurality of magnetic heating stirring devices; the magnetic heating stirring device comprises a stirrer, a reaction kettle is fixedly installed on the stirrer, and a kettle cover is detachably installed on the reaction kettle; the device further comprises a cap-screwing sampling mechanism; the device further comprises a sampling test tube assembly line mechanism, the sampling test tube assembly line mechanism comprises a transmission belt which is arranged in a transmission connection mode, a plurality of test tube cladding sleeves are installed on the transmission belt, and test tubes are installed in the test tube cladding sleeves; the device further comprises a rotary mixing assembly, the rotary mixing assembly comprises a support which is arranged in a liftable mode, a pair of rotary and stirring seats which are matched with each other are rotationally connected to the bottom of the support, and the rotary and stirring seats are driven by motors respectively; a fixed stirring structure is fixedly connected to the bottom of the support; the device further comprises a liquid injection mechanism and a test tube discharging mechanism. Through the above structure, sampling detection in an assembly line mode is realized, and completely automatic processing is achieved without manual operation.

Description

Technical Field

[0001] This invention belongs to the field of HPLC online monitoring of reaction processes, and particularly relates to an HPLC online monitoring device for biochemical reaction synthesis processes. Background Technology

[0002] High-performance liquid chromatography (HPLC) is a precision instrument for chemical analysis, capable of quantitative and qualitative analysis of substances. In biological and chemical synthesis processes, HPLC can be used for quantitative analysis to monitor reaction progress, specifically for quantitative analysis of target products to guide the optimization and improvement of reaction conditions.

[0003] Therefore, in the laboratory stage, the screening of chemical reaction processes often involves simultaneously conducting multiple reactions under predetermined temperatures, pressures, and material ratios. During the reactions, samples are taken at specific time intervals and analyzed by HPLC to determine the reaction progress and ultimately screen for the optimal process conditions. Consequently, in actual practice, the sampling and testing volume during process screening is extremely large.

[0004] Existing technologies only allow for initial sampling and testing. After testing, the process conditions are modified based on the detected structure, and the reaction is restarted (with altered reaction conditions) for further testing. The drawback of this method is that the biological / chemical reaction process and HPLC detection are performed separately and cannot be synchronized. Therefore, in practical work, if the HPLC detection of the biological / chemical reaction process could be performed simultaneously, enabling online monitoring by the HPLC system, it would not only allow for rapid detection using the HPLC's fast detection capabilities, but also enable real-time adjustment of reaction parameters, such as changing the reaction pressure and temperature, based on the detected structure.

[0005] Achieving real-time HPLC detection of the reaction process is not only challenging, but also requires solving the following technical problems:

[0006] 1. Process screening reactions often involve several reactions under different process conditions occurring simultaneously. One of the technical challenges is how to quickly sample the materials in each reactor and prepare them into HPLC samples, and then use HPLC for efficient detection to obtain rapid results.

[0007] 2. The traditional method involves manual sampling and sample preparation by laboratory personnel (from sampling to sample dissolution). This process requires opening each reaction vessel for sampling. Furthermore, the sampling for process screening is characterized by sampling once at specific time intervals. Therefore, the entire reaction involves a large number of samples, making the sample preparation task very arduous and labor-intensive, which is the second technical challenge.

[0008] 3. For special reactions, such as those where materials are prone to deterioration after being removed from the reactor, it is necessary to quickly sample each reactor and prepare samples that can be injected. This requires high operating speed and a large number of qualified personnel, which is the third technical challenge.

[0009] Therefore, to address the aforementioned technical challenges, if an automated synthesis, sampling, and detection device capable of real-time monitoring of the reaction process is developed, enabling rapid sampling of each reactor during the reaction process and preparation of samples ready for direct injection, and real-time adjustment of the reaction based on the liquid phase detection structure, it would not only reduce the amount of reaction setup required during process screening and improve process screening efficiency, but also fundamentally reduce the labor intensity of operation. More importantly, it would allow for rapid sampling and sample preparation for the aforementioned specific reactions. Summary of the Invention

[0010] Based on the above background, the purpose of this invention is to provide an HPLC device for online monitoring of biochemical reaction synthesis processes.

[0011] To achieve the above objectives, the present invention adopts the following technical solution:

[0012] An HPLC online monitoring device for biochemical reaction synthesis process includes a workbench, a liquid chromatograph mounted on the workbench, and several magnetic heating and stirring devices.

[0013] The magnetic heating stirring device includes a stirrer, on which a reaction vessel is fixedly mounted, and the reaction vessel is detachably fitted with a vessel lid.

[0014] It also includes a screw-on sampling mechanism, which opens the lid of the vessel and samples the material inside.

[0015] It also includes a sampling test tube production line mechanism that works in conjunction with the capping sampling mechanism. The sampling test tube production line mechanism includes a transmission belt with a transmission connection, and several test tube clips are installed on the transmission belt. Test tubes are installed inside the test tube clips.

[0016] It also includes a swirling mixing assembly located on the side of the transmission belt. The swirling mixing assembly includes a support that can be raised and lowered. A pair of mating swirling seats are rotatably connected to the bottom of the support. The swirling seats are driven by motors mounted on the support.

[0017] The bottom of the support is fixedly connected to a fixed stirring structure that extends into the test tube to assist in stirring;

[0018] It also includes a dispensing mechanism for injecting dissolving reagents into test tubes;

[0019] When the conveyor belt carries several empty test tubes through the liquid injection mechanism, the liquid injection mechanism injects the dissolving reagent. The conveyor belt then moves the test tubes carrying the reagents to the location of the magnetic heating and stirring device. The capping and sampling mechanism opens the lid of the vessel, takes a sample, and injects the sample liquid into the test tube. The conveyor belt continues to move the sample test tubes to the position of the vortex mixing component. The vortex mixing component descends to the vortex friction seat and presses against both sides of the test tube. Driven by the motor, the rotating vortex friction seat drives the test tube to rotate, and the material inside the test tube is stirred by the fixed stirring structure that extends into the test tube.

[0020] It also includes a test tube feeding mechanism installed on the workbench, which removes the sample test tubes, injects them into sample vials, and then loads them into the liquid chromatograph for detection.

[0021] Preferably, the stirrer is a magnetic stirrer, and the vessel body is fixedly connected to the magnetic stirrer;

[0022] The reactor is a small reactor with a volume of 1-2.5L; the reactor lid is threaded onto the neck of the reactor.

[0023] The top of the vessel lid is integrally formed with a straight protrusion that cooperates with the screw-on sampling mechanism.

[0024] Preferably, the capping sampling mechanism includes a movable seat that moves on the worktable, a rotating table that is fixedly installed on the top of the movable seat, a fixed rail that is fixedly connected to the rotating table, and a transverse moving arm structure that is slidably installed on the top of the fixed rail.

[0025] The transverse moving track is slidably connected to a lifting arm structure that can be raised and lowered; the lifting arm structure includes a lifting arm, and a double-claw cylinder that cooperates to unscrew the lid is installed on the inner side of the lifting arm. A rotary motor is fixedly installed on the cylinder of the double-claw cylinder, and the rotary motor is fixedly installed on the lifting arm.

[0026] An electric pipette structure is installed on the outside of the lifting arm.

[0027] Preferably, the transverse moving arm structure includes a transverse sliding tooth portion slidably connected to the top position of the fixed track, and the transverse sliding tooth portion is integrally formed with a vertically arranged hanging bracket portion;

[0028] A first cylinder is installed at the outer end of the fixed track, and the piston rod of the first cylinder is fixedly connected to the vertical bracket.

[0029] The lifting arm structure includes a lifting slide tooth part that is slidably connected to the vertical frame part, and the lifting slide tooth part is integrally formed with a connecting arm part. The rotary motor and electric pipette structure are fixedly installed at the position of the connecting arm part.

[0030] A second cylinder is fixedly installed on the top of the vertical frame, and the piston rod of the second cylinder is fixedly installed on the connecting arm.

[0031] Preferably, the sampling tube assembly line mechanism further includes a driving pulley and a driven pulley installed on both sides of the transmission belt;

[0032] The workbench is equipped with a pulley motor that drives the active pulley; the test tube clamp includes a mounting part installed on the transmission belt, and the mounting part is integrally formed with a tube sleeve part that mates with the test tube.

[0033] Preferably, the vortex mixing assembly further includes a fixed bracket fixedly installed on the workbench, a third cylinder fixedly installed on the top of the fixed bracket, and the piston rod of the third cylinder fixedly installed on the bracket;

[0034] Telescopic guide rails are installed on both sides of the top of the bracket, and the fixed ends of the telescopic guide rails are fixedly installed on the fixed bracket.

[0035] The rotating massage seat is made of elastic rubber, and the outer side wall of the rotating massage seat is integrally formed with several protruding ribs.

[0036] Preferably, the fixed stirring structure includes a fixed rod fixedly connected to the center position of the bottom of the support, and a small stirring head is welded and fixedly connected to the bottom of the fixed rod.

[0037] Preferably, the liquid injection mechanism includes a liquid pump fixedly installed on the workbench, and a liquid injection pipe is installed at the outlet end of the liquid pump;

[0038] The feed end of the liquid pump is connected to the reagent bottle through a feed pipe.

[0039] Preferably, the test tube feeding mechanism includes an electric gripper for holding the test tube, and a swing arm structure is installed at the bottom of the electric gripper. The swing arm structure includes a first swing arm and a second swing arm that is hinged to the first swing arm.

[0040] The second swing arm is fixedly mounted at the bottom of its outer end with a first motor that drives the first swing arm to swing, and also includes a second motor that drives the second swing arm to rotate. A mounting base for mounting the second motor is fixedly mounted on the worktable.

[0041] Preferably, a first test tube support and a second test tube support are respectively provided on both sides of the test tube feeding mechanism. The first test tube support is used to place sample test tubes, and the second test tube support is used to place idle test tubes.

[0042] The present invention has the following beneficial effects:

[0043] 1. This invention solves numerous technical problems in existing technologies during process screening, such as the simultaneous occurrence of several reactions under different process conditions, the need for sampling and testing of materials in each reactor at specific times, resulting in large sampling and testing workloads, and the inability to link testing with the reaction process. This invention utilizes a streamlined production line to achieve a fully automated process from opening multiple reactors, sampling, supplying the necessary test tubes, injecting the sampled material into the test tubes, injecting dissolving reagents into the test tubes, mechanically rotating the test tubes for dissolution, and subsequently removing the test tubes from the conveyor belt and replenishing them with new ones.

[0044] This technology enables rapid sampling and sample preparation, which, combined with efficient HPLC detection, allows for real-time sampling and detection during the reaction process in process screening. It also allows for timely adjustment of process parameters based on the detected structure during the reaction, thereby fundamentally improving process screening efficiency, reducing labor intensity, and increasing overall efficiency.

[0045] 2. In the structural design, the swirling mixing assembly includes a height-adjustable support, a swirling friction seat, and a motor drive, a third cylinder, and a telescopic guide rail mounted on the support. During operation, driven by the third cylinder, the support descends, and a pair of swirling friction seats mounted on the support clamp and squeeze the two side walls of the test tube. Simultaneously, driven by the motor, the swirling friction seats rotate, applying friction to the test tube and causing it to rotate (the test tube is inserted into the sleeve but not completely locked). During rotation, the material inside the test tube is stirred and agitated, promoting dissolution and clearing.

[0046] The above structure cleverly solves the technical problem of automatically stirring and dissolving samples inside test tubes during the transmission of the belt.

[0047] The ingenious structural design allows the material inside the test tube to be stirred by rotating the test tube after sampling, thus aiding in dissolution.

[0048] 3. Taking advantage of the rotation of the test tube and the lifting and lowering of the support, the bottom center of the support is fixedly connected to a fixed stirring structure that extends into the test tube to assist in stirring.

[0049] As the support descends, the fixed stirring structure extends precisely into the test tube and stirs it using the test tube's rotation. Specifically, the fixed stirring structure includes a fixed rod fixedly connected to the center of the bottom of the support, with a small stirring head welded to the bottom of the rod. The small stirring head has multiple protruding plates.

[0050] When the support is pushed down by the cylinder, the small stirring head-fixed rod first gradually penetrates into the test tube, and then the rotary rubbing seat descends and presses onto the test tube (under normal circumstances, the fixed rod-small stirring head is located below the rotary rubbing seat).

[0051] The ingenious structure described above enables the automated dissolution of materials sampled from test tubes.

[0052] 4. This invention realizes a complete automated mechanical structure device from screwing on the cap, taking samples, putting the sampled material into the test tube, injecting the dissolving reagent into the test tube, rotating and stirring the test tube, to the subsequent removal of the sample test tube from the conveyor belt. It fundamentally realizes a highly efficient basis for HPLC sample preparation by adopting a fully automated method. Attached Figure Description

[0053] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the structures shown in these drawings without creative effort.

[0054] Figure 1 This is a schematic diagram of the planar structure of the HPLC online monitoring device for biochemical reaction synthesis process in an embodiment of the present invention;

[0055] Figure 2 This is a schematic diagram of the three-dimensional structure in an embodiment of the present invention;

[0056] Figure 3 This is a schematic diagram of the cap-tightening sampling mechanism in an embodiment of the present invention;

[0057] Figure 4 This is a schematic diagram of the cap-tightening sampling mechanism from another perspective in an embodiment of the present invention;

[0058] Figure 5 This is a schematic diagram of the structure of the swirl mixing component in an embodiment of the present invention;

[0059] Figure 6 This is a schematic diagram of the structure of the rotary friction seat in an embodiment of the present invention;

[0060] Figure 7 This is a schematic diagram of the fixed stirring structure in an embodiment of the present invention;

[0061] Figure 8 This is a schematic diagram of the liquid injection mechanism in an embodiment of the present invention;

[0062] Figure 9 This is a schematic diagram of the test tube feeding mechanism in an embodiment of the present invention;

[0063] Figure 10 This is a schematic diagram of the structure of the double-strand drive belt mounting movable seat and the movable seat sliding on the track in an embodiment of the present invention;

[0064] Figure 11 This is an embodiment of the present invention. Figure 2 A structural diagram from another perspective.

[0065] The realization of the objective, functional features and advantages of the present invention will be further explained in conjunction with the embodiments and with reference to the accompanying drawings. Detailed Implementation

[0066] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0067] It should be noted that all directional indications (such as up, down, left, right, front, back, etc.) in the embodiments of the present invention are only used to explain the relative positional relationship and movement of each component in a certain specific posture (as shown in the figure). If the specific posture changes, the directional indication will also change accordingly.

[0068] Furthermore, in this invention, descriptions involving "first," "second," etc., are for descriptive purposes only and should not be construed as indicating or implying their relative importance or implicitly specifying the number of technical features indicated. Therefore, a feature defined with "first" or "second" may explicitly or implicitly include at least one of that feature. Additionally, the technical solutions of the various embodiments can be combined with each other, but only on the basis of being achievable by those skilled in the art. When the combination of technical solutions is contradictory or impossible to implement, such a combination of technical solutions should be considered non-existent and not within the scope of protection claimed by this invention.

[0069] Example 1

[0070] like Figure 1-11 As shown, an HPLC online monitoring device for biochemical reaction synthesis includes a workbench, a liquid chromatograph 1 mounted on the workbench (located at the top front and left side of the workbench), and several magnetic heating and stirring devices 2 (located to the right of the liquid chromatograph 1, arranged side by side). The reason is that, under process screening conditions, multiple reactions (under different conditions) often proceed simultaneously.

[0071] The magnetic heating and stirring device 2 is a conventional reaction device disclosed in the prior art, and its structure is the same as that of existing magnetic stirring reaction devices. It includes a stirrer 21 (magnetic stirrer 21), and a reaction vessel 22 (a small reaction vessel 22 of 1-1.5L, such as a high-pressure resistant reaction vessel 22) is fixedly mounted on the stirrer 21. Similar to the existing reaction vessel 22, a vessel cover 23 is installed at the neck position of the reaction vessel 22, which can be connected by a threaded connection.

[0072] Similar to the existing structure, temperature, pressure and other sensors are installed inside the reactor 22 (not shown in the figure).

[0073] Therefore, in order to enable unmanned operation of opening the reactor 22 lid and taking samples during the reaction process, the present invention discloses the following technical solution:

[0074] It also includes a screw-on sampling mechanism 5, which opens the lid 23 and samples the material inside the vessel.

[0075] Specifically, the capping sampling mechanism 5 includes a movable seat 581 that moves on the worktable. Specifically, in the conventional manner, a track 5811 (recessed installation) that cooperates with the movable seat 581 is fixedly connected inside the worktable, and the movable seat 581 slides on the track 5811 (e.g., by means of pulleys).

[0076] like Figure 10 As shown, according to existing drive structures, such as belt drive, belt drive pulleys are installed on both sides of the worktable (the worktable has a hollow internal structure), and the pulleys are driven by two drive belts 59 (the track 5811 is located precisely between the drive belts). The bottom of the movable seat 581 is fixed on the drive belts 59, and the movement is achieved through the drive belts 59. Simultaneously, the drive pulley at one end of the drive belt 59 is driven by a motor. Using belt drive to traction the movable seat 581 is a conventional drive method disclosed in the prior art.

[0077] During operation, the moving seat 581 is moved by a motor-driven transmission belt, so that it moves along the track 5811 to the station of each magnetic stirring reaction device and stops, waiting for the cap to be screwed on and the sample taken.

[0078] Example 2

[0079] like Figure 1-11 As shown, in this embodiment, based on the structure of embodiment 1, a rotating platform 58 is fixedly installed on the top of the above-mentioned movable seat 581. The rotating platform 58 is a conventional self-rotating turntable device disclosed in the prior art. Its main structure includes a housing, and a rotary drive motor is installed inside the housing. The output shaft of the rotary drive motor is fixed on the fixed track 5811 described below.

[0080] The output shaft of the rotary table 58 is fixedly connected to a fixed rail 5811, and a transverse moving arm structure is slidably mounted on the top of the fixed rail 5811. The transverse moving arm structure allows the mesh vessel to move closer to or further away from its position.

[0081] Meanwhile, the transverse moving track 5811 is slidably connected to a lifting arm structure that can be raised and lowered; the lifting arm structure includes a lifting arm 55, and a double-claw cylinder 52 (a cylinder with two claws disclosed in the prior art) is installed on the inner side of the lifting arm 55 to cooperate in unscrewing the lid 23. A rotary motor 51 is fixedly installed on the cylinder barrel of the double-claw cylinder 52, and the rotary motor 51 is fixedly installed on the lifting arm 55; an electric pipette structure is installed on the outer side of the lifting arm 55.

[0082] The structure of the electric pipette is the electric pipette 53 disclosed in the prior art. In order to be able to pipette into the vessel, the electric pipette 53 is equipped with a high-temperature resistant metal capillary tube 531 in the existing manner.

[0083] Specifically, the transverse sliding arm structure includes a transverse sliding tooth portion 541 slidably connected to the top position of the fixed track 5811 (specifically, the transverse sliding tooth portion 541 has a number of protruding sliding teeth integrally formed, and correspondingly, the fixed track 5811 has multiple cooperating sliding tooth grooves, so as to improve the sliding accuracy). The transverse sliding tooth portion 541 has a vertically arranged hanging bracket portion 54 integrally formed.

[0084] A first cylinder 59 is installed at the outer end of the fixed track 5811 (the outer end of the fixed track 5811 is integrally formed with a protruding cylinder seat, and the cylinder barrel of the first cylinder 59 is fixed on the cylinder seat), and the piston rod of the first cylinder 59 is fixedly connected to the vertical bracket 54.

[0085] Meanwhile, the lifting arm 55 structure includes a lifting slide tooth part 551 (the structure is the same as the above-mentioned transverse slide tooth part) that is slidably connected to the vertical bracket part 54. The lifting slide tooth part 551 is integrally formed with a connecting arm part, and the rotary motor 51 and the electric pipette 53 are fixedly installed at the position of the connecting arm part.

[0086] The top of the suspension section 54 is fixedly mounted with a second cylinder 56 (similarly, a cylinder seat is welded to the top of the suspension section 54, and the cylinder barrel of the second cylinder 56 is fixed on the cylinder seat), and the piston rod of the second cylinder 56 is fixedly mounted on the connecting arm.

[0087] During operation, when the capping sampling mechanism 5 moves to the position of the first reactor 22 on the right, the transverse moving track 5811 moves under the push of the first cylinder 59 to the position of the double-claw cylinder 52 directly above the reactor 22 (the electric pipette 53 is located in front of the double-claw cylinder 52, at which point the double-claw cylinder 52 is located in front of the entire reactor and offset from the reactor position). Subsequently, driven by the second cylinder 56, the double-claw cylinder 52 follows the lifting arm 55 structure down to the height corresponding to the lid 23. Then, the two claws of the double-claw cylinder 52 clamp the inline protrusion of the lid 23 (the top of the lid 23 is integrally formed with an inline protrusion 231 that cooperates with the capping sampling mechanism 5). Then, driven by the rotary motor 51 and as the second cylinder 56 pulls back the piston rod, the lid 23 is gradually unscrewed.

[0088] After the lid 23 is screwed on, the first cylinder 59 pulls back the horizontal moving arm structure until the electric pipette 53 is directly above the reactor 22. At the same time, the second cylinder 56 drives the lifting arm structure to descend until the high-temperature resistant metal tube 531 connected to the electric pipette 53 extends into the reactor and the reaction material is extracted under the action of the electric pipette 53.

[0089] Then, screw the lid 23 back on in the reverse manner to complete the sampling process.

[0090] Once sampling is complete, the sample is directly sent to the sampling tube production line below, waiting to be transferred to the next station for further processing.

[0091] The above-mentioned structure enables sampling in a fully automated manner. The entire process requires no manual operation and realizes the entire process of opening and sampling multiple reaction vessels 22 involved in the experiment through the above-mentioned device, which is automatically completed by mechanical structure.

[0092] Example 3

[0093] like Figure 1-11 As shown, this embodiment, based on the structure of Embodiment 2, often involves multiple reactors 22 reacting simultaneously during the process screening. Therefore, the sampling workload is large, requiring a significant number of test tubes. After sampling, the material is placed in test tube A, which then needs to be moved to the next station for further processing. Therefore, to fundamentally achieve the goal of placing samples into test tubes (sample tubes) after sampling from multiple reactors, allowing the sample tubes to be moved synchronously to subsequent stations, and ensuring a continuous supply of available test tubes A, this invention innovatively employs the following assembly line structure to facilitate sampling from multiple reactors.

[0094] Specifically, the aforementioned structure also includes a sampling tube assembly line mechanism 3 that works in conjunction with the capping sampling mechanism 5. The sampling tube assembly line mechanism 3 includes a transmission belt 34 with a transmission connection. Specifically, the sampling tube assembly line mechanism 3 also includes a drive pulley 31 and a driven pulley installed on both sides of the transmission belt 34 (according to the existing pulley installation structure, the axles of the drive pulley 31 and the driven pulley are rotatably connected to the worktable), and a pulley motor (concealed installation) driving the drive pulley is installed inside the worktable. Simultaneously, several test tube clips 32 are installed on the transmission belt 34. The test tube clips 32 are made of plastic, and their structural shape is as follows: the test tube clip 32 includes an mounting part (fixed by rivets) installed on the transmission belt 34, and the mounting part has an integrally formed tube sleeve part that mates with the test tube.

[0095] At the same time, each tube sleeve contains a clean test tube.

[0096] During operation, when the aforementioned capping and sampling mechanism 5 is working, a clean test tube (pre-filled with solvent) is carried by a belt driven by a pulley motor and positioned just behind the capping and sampling mechanism 5. After the capping and sampling mechanism 5 completes sampling, the rotating table 58 rotates 180 degrees. At this time, the electric pipette 53 is positioned just above the test tube A. Therefore, when driven by the second cylinder 56, the lifting arm 55 descends again, and the electric pipette 53 places the aspirated reaction material into the test tube A.

[0097] Following the above method, material samples were taken from each reactor 22 and placed into test tube A to complete the sampling.

[0098] The sample is in a test tube. The solvent in test tube A will initially dissolve the sampled material, but it cannot be completely dissolved. In the existing technology, the transmission method relies on manually dripping solvent into the test tube, and the sampled liquid is drawn into the test tube through a pipette and then shaken.

[0099] The cap-tightening sampling mechanism 5 effectively replaces manual opening of the cap, suction of material with a straw, and tightening of the cap. This structure achieves an initial improvement in efficiency.

[0100] The test tubes are carried by the aforementioned transmission belt 34, which enables a fully automated solution to the problems of large test tube consumption and large sample test tube volume that require sampling of each of the multiple reactors 22 at specific intervals during the working process and the screening process.

[0101] Example 4

[0102] like Figure 1-11As shown, this embodiment, based on the structure of embodiment 3, pre-injects solvent into the test tube when it moves to the position corresponding to the reactor 22 and is ready to receive the material taken out by the capping sampling mechanism 5. Therefore, the above structure also includes a liquid injection mechanism for injecting dissolving reagent into test tube A (located at the upstream end of the reactor 22 - with reference to the belt drive direction). In this way, each test tube A carried by the belt is pre-injected with solvent when it is ready to receive the sampled material, which prepares for the subsequent dissolution of the material after sampling and the subsequent mechanical rotation and dissolution of the material by the vortex mixer.

[0103] Specifically, the liquid injection mechanism 4 includes a liquid pump 41 fixedly installed on the workbench (installed on the top right side of the workbench, fixedly installed by a liquid pump 41 bracket), the liquid outlet end of the liquid pump 41 is connected to an injection pipe 43 through a metal pipe 41 (specifically, according to the existing liquid spraying structure, an electromagnetic valve 431 is installed on the injection pipe 43); the feed end of the liquid pump 41 is connected to a reagent bottle 42 through a feed pipe 412 (the reagent bottle 42 contains conventional reagents such as methanol).

[0104] The above structure enables the belt to carry test tube A into the injection mechanism station. After the belt stops, the injection mechanism injects dissolved reagent into test tube A. In this way, each test tube A is injected with reagent after passing through, waiting to dissolve the sample material.

[0105] The above structure enables a streamlined process from injecting solvent into test tube A to subsequent sampling, where the sample material is placed into test tube A and the solvent dissolves in test tube A.

[0106] Example 5

[0107] like Figure 1-11 As shown, in this embodiment, based on the structure of embodiment 4, after the sampling mechanism 5 takes a sample, the sample material is placed in test tube A. The solvent in test tube A dissolves, but test tube A still needs to be shaken to ensure that the material is fully dissolved (incomplete dissolution will affect subsequent chromatographic injection and may easily clog the chromatographic column or pipeline).

[0108] Therefore, based on the characteristics of the conveyor belt carrying test tube A in the assembly line, this invention innovatively adopts the following mechanical structure to achieve the dissolution of materials in test tube A.

[0109] Specifically, the above structure also includes a swirling mixing assembly 33 located on the side of the transmission belt 34 (located on the left side of the injection mechanism, downstream of the belt movement direction). The swirling mixing assembly 33 includes a height-adjustable bracket. The bottom of the bracket 3351 is rotatably connected to a pair of cooperating swirling seats 334 (the swirling seats 334 are made of elastic rubber, and the outer side wall of the swirling seats 334 is integrally formed with several circumferentially distributed convex structures. The swirling seats 334 are cylindrical in shape, and the gap between the pair of swirling seats 334 is slightly smaller than the diameter of the test tube A). The swirling seats 334 are driven by motors 335 mounted on the bracket 3351 (small motors are used, and the motor host is fixed at the bottom of the bracket 3351).

[0110] Meanwhile, the vortex mixing assembly 33 also includes a fixed bracket 331 fixedly installed on the workbench, and a third cylinder 332 (the cylinder barrel is fixed on the fixed bracket 331) is fixedly installed on the top of the fixed bracket 331, and the piston rod of the third cylinder 332 is fixedly installed on the bracket 3351.

[0111] Meanwhile, in order to increase the accuracy of the lifting and lowering of the cylinder-driven bracket 3351-rotating friction seat 334, telescopic guide rails 333 are respectively installed on both sides of the top of the bracket 3351 (the telescopic guide rail 333 is a conventional telescopic guide rail 333 rod disclosed in the prior art, whose main structure includes a telescopic guide rod part and a sleeve part fixedly installed at the top position of the bracket 3351, and the sleeve part is fixed on the fixed bracket 331). The fixed end of the telescopic guide rail 333 is fixedly installed on the fixed bracket 331.

[0112] During operation, driven by the third cylinder 332, the support 3351 descends, and a pair of rotating friction seats 334 mounted on the support 3351 precisely squeeze and clamp the two side walls of test tube A. Driven by the motor, the rotating friction seats 334 on both sides rotate, exerting friction on test tube A and causing it to rotate (test tube A is inserted into the sleeve but not completely locked). During rotation, the material inside test tube A is stirred and rotated, promoting the dissolution and clearing of the material.

[0113] Example 6

[0114] like Figure 1-11 As shown, in this embodiment, based on the structure of embodiment 5, in order to further enhance the stirring and dissolving effect, the bottom center of the support 3351 is fixedly connected to a fixed stirring structure that extends into the test tube A to assist stirring, taking advantage of the rotation of test tube A and the lifting and lowering characteristics of support 3351.

[0115] After the support 3351 descends, the fixed stirring structure extends precisely into test tube A and uses the rotation of test tube A to stir the mixture. Specifically, the fixed stirring structure includes a fixed rod 336 fixedly connected to the center of the bottom of the support 3351, and a small stirring head 3361 is welded and fixedly connected to the bottom of the fixed rod 336. The small stirring head 3361 has multiple protruding convex plates.

[0116] When the support 3351 is pushed down by the cylinder, the small stirring head 3361 and the fixed rod 336 first gradually penetrate into the test tube A, and then the rotary rubbing seat 334 descends and presses onto the test tube A (under normal circumstances, the fixed rod 336 and the small stirring head 3361 are located below the rotary rubbing seat 334).

[0117] The ingenious structure described above enables the automated dissolution of the material sampled from test tube A.

[0118] The dissolved sample in test tube A has been prepared and is ready for manual injection into the sample vial.

[0119] Example 6

[0120] like Figure 1-11 As shown, in this embodiment, based on the structure of embodiment 5, after the material in sample tube A has been fully dissolved following the above method, it is ready to be removed from the conveyor belt 34 for subsequent injection into the sample bottle.

[0121] Furthermore, after removing sample tube A, a new clean sample tube A needs to be added. Therefore, to achieve the above technical solution, the present invention makes the following improvements:

[0122] The above structure includes a test tube A feeding mechanism 8 (located downstream of the vortex mixer 33) installed on the workbench. The test tube A is removed by the test tube A feeding mechanism 8, and then injected into the sample bottle and loaded into the liquid chromatograph 1 for detection.

[0123] Specifically, the test tube A feeding mechanism 8 includes an electric gripper 81 for holding the test tube A (the electric gripper 81 is a conventional double-gripper structure electric gripper 81 disclosed in the prior art). A swing arm structure 82 is installed at the bottom of the electric gripper 81. The swing arm structure 82 is a conventional small swing arm disclosed in the prior art. Its main structure includes a first swing arm 821 and a second swing arm 823 that is hinged to the first swing arm 821.

[0124] Meanwhile, in the existing manner, an electric push rod 811 is installed at the bottom of the outer end of the first swing arm 821 to push the electric gripper 81 to rise and fall.

[0125] Similar to the existing swing arm structure, the bottom outer end of the second swing arm 823 is fixedly equipped with a first motor that drives the first swing arm 821 to swing (the output shaft is fixed to the inner core of the first swing arm 821), and also includes a second motor that drives the second swing arm 823 to rotate. A mounting base 822 for mounting the second motor is fixedly installed on the worktable (the second motor is installed in the mounting slot on the mounting base 822).

[0126] During operation, when test tube A is moved to the position of test tube A unloading mechanism 8 by the transmission belt 34, the first swing arm 821 is driven by the first motor to move towards test tube A. At this time, the two jaws of the electric gripper 81 open, and as the first swing arm 821 continues to move, the two jaws of the electric gripper 81 fully extend into both sides of test tube A, clamping the sample test tube A. Then, the electric push rod 811 lifts the electric gripper 81 to remove the gripped test tube A. After removal, it moves towards the first test tube support 6. At the same time, the second swing arm 823 rotates in coordination, and through the action of the two swing arms, the test tube A is carried to the positive direction of the first test tube support 6 and placed down according to the hole position on the test tube A support.

[0127] The method of replenishing test tube A is basically similar to the action of grabbing test tube A described above.

[0128] Therefore, a first test tube support 6 and a second test tube support 7 are respectively provided on both sides of the above-mentioned test tube A feeding mechanism 8. The first test tube support 6 is used to place the sample test tube A, and the second test tube support 7 is used to place the empty test tube A.

[0129] Example 7

[0130] like Figure 1-11 As shown, this embodiment, based on the above embodiments, should be noted that the above embodiments disclose a complete automated production line mechanical structure device for realizing the entire process from capping, sampling, placing the sampled material into test tube A, injecting dissolving reagent into test tube A, rotating and stirring test tube A, to subsequently removing the sample test tube A from the conveyor belt 34. Similar to existing automated control methods, the above mechanical structure is controlled by a conventional automated control system program disclosed in the prior art, such as a PLC control system. The PLC control system enables the coordinated operation of the cylinder, motor, and electric gripper 81. Using a PLC control system is a common industrial application based on PLC. Those skilled in the art can clearly understand the specific control principle, method, and structure of the PLC control system used in this invention by consulting existing technologies, such as PLC control on production lines.

[0131] Of course, the above description is not intended to limit the present invention, and the present invention is not limited to the examples given above. Any changes, modifications, additions or substitutions made by those skilled in the art within the scope of the present invention should also fall within the protection scope of the present invention.

Claims

1. An HPLC online monitoring device for biochemical reaction synthesis process, characterized in that, Includes a workbench, a liquid chromatograph mounted on the workbench, and several magnetic heating and stirring devices; The magnetic heating stirring device includes a stirrer, on which a reaction vessel is fixedly mounted, and the reaction vessel is detachably fitted with a vessel lid. It also includes a screw-on sampling mechanism, which opens the lid of the vessel and samples the material inside. It also includes a sampling test tube production line mechanism that works in conjunction with the capping sampling mechanism. The sampling test tube production line mechanism includes a transmission belt with a transmission connection, and several test tube clips are installed on the transmission belt. Test tubes are installed inside the test tube clips. It also includes a swirling mixing assembly located on the side of the transmission belt. The swirling mixing assembly includes a support that can be raised and lowered. A pair of mating swirling seats are rotatably connected to the bottom of the support. The swirling seats are driven by motors mounted on the support. The bottom of the support is fixedly connected to a fixed stirring structure that extends into the test tube to assist in stirring; It also includes a dispensing mechanism for injecting dissolving reagents into test tubes; When the conveyor belt carries several empty test tubes through the liquid injection mechanism, the liquid injection mechanism injects the dissolving reagent. The conveyor belt then moves the test tubes carrying the reagents to the location of the magnetic heating and stirring device. The capping and sampling mechanism opens the lid of the vessel, takes a sample, and injects the sample liquid into the test tube. The conveyor belt continues to move the sample test tubes to the position of the vortex mixing component. The vortex mixing component descends to the vortex friction seat and presses against both sides of the test tube. Driven by the motor, the rotating vortex friction seat drives the test tube to rotate, and the material inside the test tube is stirred by the fixed stirring structure that extends into the test tube. It also includes a test tube feeding mechanism installed on the workbench, which removes the sample test tubes, injects them into sample vials, and then loads them into the liquid chromatograph for detection.

2. The apparatus for monitoring the progress of a biochemical reaction by HPLC online according to claim 1, wherein, The stirrer is a magnetic stirrer, and the reactor body is fixedly connected to the magnetic stirrer; The reactor is a small reactor with a volume of 1-2.5L; the reactor lid is threaded onto the neck of the reactor. The top of the vessel lid is integrally formed with a straight protrusion that cooperates with the screw-on sampling mechanism.

3. The apparatus for monitoring the progress of a biochemical reaction by HPLC online according to claim 1, wherein, The capping sampling mechanism includes a movable seat that moves on the worktable, a rotating table that is fixedly installed on the top of the movable seat, a fixed rail that is fixedly connected to the rotating table, and a transverse moving arm structure that is slidably installed on the top of the fixed rail. The transverse moving track is slidably connected to a lifting arm structure that can be raised and lowered; the lifting arm structure includes a lifting arm, and a double-claw cylinder that cooperates to unscrew the lid is installed on the inner side of the lifting arm. A rotary motor is fixedly installed on the cylinder of the double-claw cylinder, and the rotary motor is fixedly installed on the lifting arm. An electric pipette structure is installed on the outside of the lifting arm.

4. The device for monitoring the progress of biochemical reaction synthesis on-line by HPLC according to claim 3, characterized in that, The lateral moving arm structure includes a lateral sliding tooth portion slidably connected to the top position of the fixed track, and the lateral sliding tooth portion is integrally formed with a vertically arranged hanging bracket portion. A first cylinder is installed at the outer end of the fixed track, and the piston rod of the first cylinder is fixedly connected to the vertical bracket. The lifting arm structure includes a lifting slide tooth part that is slidably connected to the vertical frame part, and the lifting slide tooth part is integrally formed with a connecting arm part. A rotary motor and an electric pipette structure are fixedly installed at the position of the connecting arm part. A second cylinder is fixedly installed on the top of the vertical frame, and the piston rod of the second cylinder is fixedly installed on the connecting arm.

5. The apparatus for monitoring the progress of a biochemical reaction by HPLC online according to claim 1, wherein, The sampling tube assembly line mechanism also includes a drive pulley and a driven pulley installed on both sides of the transmission belt; The workbench is equipped with a pulley motor that drives the active pulley; the test tube clamp includes a mounting part installed on the transmission belt, and the mounting part is integrally formed with a tube sleeve part that mates with the test tube.

6. The apparatus for monitoring the progress of a biochemical reaction by HPLC online according to claim 5, wherein, The vortex mixing assembly also includes a fixed bracket fixedly installed on the workbench, a third cylinder fixedly installed on the top of the fixed bracket, and the piston rod of the third cylinder fixedly installed on the bracket. Telescopic guide rails are installed on both sides of the top of the bracket, and the fixed ends of the telescopic guide rails are fixedly installed on the fixed bracket. The rotating massage seat is made of elastic rubber, and the outer side wall of the rotating massage seat is integrally formed with several protruding ribs.

7. The HPLC online monitoring device for biochemical reaction synthesis process according to claim 6, characterized in that, The fixed stirring structure includes a fixed rod fixedly connected to the center of the bottom of the support, and a small stirring head is welded and fixedly connected to the bottom of the fixed rod.

8. The apparatus according to claim 1, wherein the apparatus is characterized by: The liquid injection mechanism includes a liquid pump fixedly installed on the workbench, and a liquid injection pipe is installed at the liquid outlet end of the liquid pump. The feed end of the liquid pump is connected to the reagent bottle through a feed pipe.

9. The apparatus for monitoring the progress of a biochemical reaction by HPLC online according to claim 1, wherein, The test tube feeding mechanism includes an electric gripper for holding test tubes, and a swing arm structure is installed at the bottom of the electric gripper. The swing arm structure includes a first swing arm and a second swing arm that is hinged to the first swing arm. The second swing arm is fixedly mounted at the bottom of its outer end with a first motor that drives the first swing arm to swing, and also includes a second motor that drives the second swing arm to rotate. A mounting base for mounting the second motor is fixedly mounted on the worktable.

10. The apparatus for monitoring the progress of a biochemical reaction by HPLC online according to claim 9, wherein, The test tube feeding mechanism is provided with a first test tube support and a second test tube support on both sides. The first test tube support is used to place sample test tubes, and the second test tube support is used to place empty test tubes.

Images