Polypeptide synthesis reactor
By using a coaxial inverted stirring paddle and liquid level sensor system in the polypeptide synthesis reactor, the problem of poor mixing uniformity is solved, and more uniform mixing and higher reaction efficiency is achieved.
Patent Information
- Application Number
- CN202421508097.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2024-06-28
- Publication Date
- 2025-04-22
- Estimated Expiration
- 2034-06-28
AI Technical Summary
The material mixing uniformity in the polypeptide solid-phase synthesis reactor is poor, especially in large reactors produced in industrial production. It is difficult to achieve uniform mixing of conventional stirring methods and vortexes are easily generated.
The coaxial inverted stirring paddle and liquid level sensor system is adopted. The coaxial inverted stirring paddle reduces the formation of vortex by rotating the impeller in the opposite direction. The liquid level sensor monitors the vortex by detecting the liquid level difference and controls the reverse rotation of the stirring paddle through a three-phase asynchronous motor to block the generation of vortex.
It effectively improves the uniformity of material mixing, reduces the formation of vortex, ensures full mixing of reactants and improves reaction efficiency.
Smart Images

Figure CN222778075U_ABST
Abstract
Description
Technical Field
[0001] The present application relates to the technical field of polypeptide synthesis, and in particular to a polypeptide synthesis reactor. Background Art
[0002] The solid phase synthesis of peptides is a process that uses resin as an insoluble solid phase carrier to sequentially connect different amino acids to the solid phase carrier. The reaction process requires adding different amino acids in batches, and each amino acid needs to be completely mixed and reacted before adding the next amino acid, and repeating the process. Therefore, the solid phase synthesis of peptides has high requirements for the uniformity of material mixing, otherwise the incomplete reaction will cause the obtained product to be different from the target product.
[0003] A solid-liquid mixing reaction occurs in a peptide synthesis reactor. The characteristics of this type of reaction are that solids tend to sink to the bottom and the solid-liquid ratio at the bottom of the reactor is the largest. In order to ensure uniform mixing, it is necessary to prevent solids from sinking to the bottom as much as possible. This is especially true for large-scale reactors for industrial production, where a large amount of material is processed at one time. Conventional stirring methods are difficult to achieve uniform mixing, and existing peptide synthesis reactors are in urgent need of improvement. Utility Model Content
[0004] The main purpose of the present application is to provide a peptide synthesis reactor, aiming to solve the problem of poor mixing uniformity of materials in current peptide solid phase synthesis reactions.
[0005] In order to achieve the above-mentioned object, the present application provides a polypeptide synthesis reactor, comprising a reaction tank body, a coaxial counter-rotating stirring paddle and a processor, wherein the reaction tank body comprises a top cover, and the coaxial counter-rotating stirring paddle is inserted from the top cover into the reaction tank body;
[0006] The top cover is provided with a three-phase asynchronous motor, which is connected to the coaxial counter-rotating stirring paddle and drives the coaxial counter-rotating stirring paddle to rotate;
[0007] A first liquid level sensor and a second liquid level sensor are arranged below the top cover; the first liquid level sensor is close to the side wall of the reaction tank body, and the second liquid level sensor is close to the central axis of the reaction tank body;
[0008] The first liquid level sensor and the second liquid level sensor are electrically connected to the processor, and the processor is electrically connected to the three-phase asynchronous motor.
[0009] Optionally, the first liquid level sensor and the second liquid level sensor are any one or two of a radar liquid level sensor, a laser liquid level sensor and an ultrasonic liquid level sensor.
[0010] Optionally, the coaxial counter-rotating stirring paddle comprises a first stirring shaft located at the top and a second stirring shaft extending to the bottom; the first stirring shaft and the second stirring shaft are coaxial;
[0011] The first stirring shaft is provided with a spiral belt stirring impeller, and the second stirring shaft is provided with a four-blade folding open turbine stirring impeller.
[0012] Optionally, the ratio of the paddle diameter of the four-blade folding open turbine stirring impeller to the diameter of the reaction tank body is (0.35-0.5):1.
[0013] Optionally, the distance between the four-blade folding open turbine stirring impeller and the bottom surface of the reaction tank body is 1 / 5-1 / 4 of the diameter of the reaction tank body.
[0014] Optionally, a three-blade propulsion impeller is further provided on the second stirring shaft, and the three-blade propulsion impeller is arranged above the four-blade folding open turbine stirring impeller.
[0015] Optionally, the three-blade propeller impeller is provided with a turbulence hole.
[0016] Optionally, a shock-absorbing base is provided on the top cover, and the processor is provided on the shock-absorbing base.
[0017] Optionally, the shock-absorbing base includes a mounting groove, four damping rods are arranged at four corners of the mounting groove, and shock-absorbing springs are arranged on the outer sides of the damping rods.
[0018] Optionally, the ratio of the paddle diameter of the screw-ribbon stirring impeller to the diameter of the reaction tank body is (0.5-0.8):1.
[0019] Compared with the prior art, the beneficial effects achieved by this application are:
[0020] The coaxial inverted agitator adopted in the present application is a stirring device that can realize opposite rotation directions on the same axis at the same time. The two impellers rotate in opposite directions to offset each other's torque. At the same time, the opposite rotation directions will effectively weaken the formation of vortex, making the liquid mixing more uniform. In addition, in order to prevent the continuous formation of vortex during the mixing process, the present application provides two liquid level sensors, which monitor the vortex by detecting the liquid level difference near the side wall of the reaction tank and the center of the tank. When the vortex is generated, the coaxial inverted agitator is controlled by a three-phase asynchronous motor to rotate in the opposite direction (in the opposite direction of the original rotation direction), which effectively plays a role in disturbing the flow, blocking the generation of vortex and improving the uniformity of material mixing. BRIEF DESCRIPTION OF THE DRAWINGS
[0021] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on the structures shown in these drawings without paying any creative work.
[0022] Figure 1 This is a schematic diagram of the structure of a polypeptide synthesis reactor in one embodiment of the present application;
[0023] Figure 2 This is a schematic diagram of the structure of a spiral ribbon stirring impeller in one embodiment of the present application;
[0024] Figure 3 This is a schematic diagram of the structure of a shock-absorbing base in an embodiment of the present application.
[0025] Explanation of symbols: 1-reaction tank body, 101-top cover, 2-coaxial counter-rotating stirring paddle, 201-first stirring shaft, 202-second stirring shaft, 3-three-phase asynchronous motor, 4-first liquid level sensor, 5-second liquid level sensor, 6-screw-type stirring impeller, 601-connecting rod, 7-four-leaf folding open turbine stirring impeller, 8-three-leaf propulsion impeller, 9-processor, 10-shock-absorbing base, 11-damping rod, 12-shock-absorbing spring.
[0026] The realization of the purpose, functional features and advantages of this application will be further explained in conjunction with embodiments and with reference to the accompanying drawings. DETAILED DESCRIPTION
[0027] The following will be combined with the drawings in the embodiments of the utility model to clearly and completely describe the technical solutions in the embodiments of the utility model. Obviously, the described embodiments are only part of the embodiments of the utility model, not all of the embodiments. Based on the embodiments of the utility model, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the utility model.
[0028] It should be noted that all directional indications in the embodiments of the present invention (such as up, down, left, right, front, back...) are only used to explain the relative position relationship, movement status, etc. between the components under a certain specific posture (as shown in the accompanying drawings). If the specific posture changes, the directional indication will also change accordingly.
[0029] In the present invention, unless otherwise clearly specified and limited, the terms "connection", "fixation", etc. should be understood in a broad sense. For example, "fixation" can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements, unless otherwise clearly defined. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.
[0030] In addition, if there are descriptions involving "first", "second", etc. in the embodiments of the utility model, the descriptions of "first", "second", etc. are only used for descriptive purposes and cannot be understood as indicating or implying their relative importance or implicitly indicating the number of technical features indicated. Therefore, the features defined as "first" and "second" may explicitly or implicitly include at least one of the features. In addition, the meaning of "and / or" appearing in the full text includes three parallel schemes. Taking "A and / or B" as an example, it includes scheme A, or scheme B, or a scheme that satisfies both A and B. In addition, the technical solutions between the various embodiments can be combined with each other, but it must be based on the ability of ordinary technicians in this field to implement. When the combination of technical solutions is contradictory or cannot be implemented, it should be deemed that such a combination of technical solutions does not exist and is not within the scope of protection required by the utility model.
[0031] The solid phase synthesis of peptides is a process that uses resin as an insoluble solid phase carrier to sequentially connect different amino acids to the solid phase carrier. The reaction process requires adding different amino acids in batches, and each amino acid needs to be completely mixed and reacted before adding the next amino acid, and repeating the process. Therefore, the solid phase synthesis of peptides has high requirements for the uniformity of material mixing, otherwise the incomplete reaction will cause the obtained product to be different from the target product.
[0032] What takes place in the peptide synthesis reactor is a solid-liquid mixing reaction. The characteristics of this type of reaction are that the solids are easy to sink to the bottom and the solid-liquid ratio at the bottom of the reactor is the largest. In order to mix evenly, it is necessary to prevent the solids from sinking to the bottom as much as possible. Especially for large-scale reactors for industrial production, the amount of materials processed at one time is large, and it is difficult to achieve uniform mixing. When stirring with a conventional agitator, vortices often occur, which means that the materials are not mixed evenly. Therefore, the generation of vortices should be avoided as much as possible during the stirring process.
[0033] The present application provides a polypeptide synthesis reactor, comprising a reaction tank body 1, a coaxial counter-rotating stirring paddle 2 and a processor 9, wherein the reaction tank body 1 comprises a top cover 101, and the coaxial counter-rotating stirring paddle 2 is inserted from the top cover 101 into the reaction tank body 1;
[0034] The top cover 101 is provided with a three-phase asynchronous motor 3, which is connected to the coaxial counter-rotating stirring paddle 2 and drives the coaxial counter-rotating stirring paddle 2 to rotate;
[0035] A first liquid level sensor 4 and a second liquid level sensor 5 are disposed below the top cover 101; the first liquid level sensor is close to the side wall of the reaction tank body 1, and the second liquid level sensor is close to the central axis of the reaction tank body 1;
[0036] The first liquid level sensor and the second liquid level sensor are electrically connected to the processor 9 , and the processor 9 is electrically connected to the three-phase asynchronous motor 3 .
[0037] The coaxial counter-rotating stirring paddle 2 is a stirring device that can realize opposite rotation directions on the same axis at the same time. It includes at least two impellers. The two impellers rotate in opposite directions to offset each other's torque. At the same time, the opposite rotation directions can effectively weaken the formation of vortexes, making the liquid mixing more uniform; but in a larger reactor, the material flow rate is large, the flow state is affected by many factors and is difficult to control, so it is difficult to achieve a mixing reaction without vortexes throughout the process.
[0038] In order to prevent the continuous formation of vortices during the mixing process, the present application is equipped with two liquid level sensors, which monitor the vortex by detecting the liquid level difference near the side wall of the reaction tank 1 and the center of the tank. When a vortex is generated, the three-phase asynchronous motor 3 controls the coaxial reverse stirring paddle 2 to rotate in the opposite direction (in the opposite direction of the original rotation direction), which plays a role in flow disturbance, effectively blocks the generation of vortices, and improves the uniformity of material mixing.
[0039] The rotation direction of the three-phase asynchronous motor 3 is consistent with the rotation direction of the rotating magnetic field, and the rotation direction of the rotating magnetic field depends on the phase sequence of the three-phase current. Therefore, the rotation direction of the motor can be changed by changing the phase sequence of the three-phase alternating current. This requirement can be met by using only two AC contactors. When the forward contactor KM1 works, the motor rotates forward; when the reverse contactor KM2 works, the motor reverses because the two power lines are swapped. The on-off control of the contactor can be achieved through an electromagnetic switch, which is controlled by the processor 9. The working procedure of the three-phase asynchronous motor 3 can be designed as follows: when a vortex is detected, the three-phase asynchronous motor 3 reverses for a preset time and then resumes forward rotation; or when the vortex disappears, that is, when the data difference between the two liquid level sensors is less than a preset threshold, the motor resumes forward rotation.
[0040] As an optional embodiment of the present application, since the tank needs to be stirred, the first liquid level sensor 4 and the second liquid level sensor 5 are any one or two of a radar liquid level sensor, a laser liquid level sensor and an ultrasonic liquid level sensor. The above-mentioned liquid level sensors can be installed under the top cover 101 without contacting the reaction material.
[0041] In addition, when selecting a liquid level sensor, the specific size of the reactor and the requirements for installation facilities in the tank must be considered; for example, when ultrasonic pulses are working, there is a certain emission angle. From the lower edge of the ultrasonic liquid level sensor to the surface of the measured medium, there must be no obstacles in the area radiated by the emitted ultrasonic beam. Therefore, when installing, it is necessary to avoid facilities in the tank, such as ladders, stirring shafts, and heating equipment.
[0042] The laser level sensor has no requirement for the radiation range, as long as there are no obstacles in its detection path. The first level sensor 4 and the second level sensor 5 may not be the same sensor, and the processor 9 can calculate the level difference after processing the data collected by the two level sensors.
[0043] The liquid level sensor may specifically be the SIRD-702GWR corrosion-resistant radar liquid level sensor of Sino-Inst Company.
[0044] The processor may specifically include an STM32 main control chip to realize data processing and motor control.
[0045] As an optional embodiment of the present application, the coaxial counter-rotating stirring paddle 2 includes a first stirring shaft located at the top and a second stirring shaft extending to the bottom; the first stirring shaft and the second stirring shaft are coaxial;
[0046] The first stirring shaft is provided with a spiral-belt stirring impeller 6 , and the second stirring shaft is provided with a four-blade folding open turbine stirring impeller 7 .
[0047] For the peptide solid phase synthesis reaction, what occurs in the reactor is the mixing of resin and liquid, i.e., solid-liquid mixing reaction. The characteristics of this type of reaction are that the solid is easy to sink to the bottom and the solid-liquid ratio at the bottom of the reactor is the largest. In order to mix evenly, it is necessary to prevent the solid from sinking to the bottom as much as possible; therefore, a four-blade folding open turbine stirring impeller 7 is used at the bottom of the reactor. This impeller can effectively suspend the settled resin solids and is suitable for the situation where the solid-liquid ratio is relatively large.
[0048] The spiral-ribbon stirring impeller 6 is formed by spirally winding a steel belt with a certain pitch, and is an axial flow paddle, which can effectively promote axial mixing of the liquid, and the outer edge of the steel belt is often designed to be close to the inner wall of the tank body, which can promote the flow of materials at the side wall of the tank body. The steel belt of the spiral-ribbon stirring impeller 6 is supported and connected to the first stirring shaft through a connecting rod 601. In the existing design, the connecting rod 601 and the stirring shaft are perpendicular to each other, but in order to prevent the second liquid level sensor 5 from mismonitoring, the top connecting rod 601 is designed to be inclined, that is, the end connected to the first stirring shaft is lower, and the end connected to the steel belt is higher; when a vortex is formed, the liquid level in the middle will drop, and the lower connecting rod 601 close to the stirring shaft can ensure that the connecting rod 601 there is always below the liquid level to the greatest extent, and the second liquid level sensor 5 can always monitor the height of the liquid level without misidentifying the height of the connecting rod 601.
[0049] As an optional embodiment of the present application, the ratio of the paddle diameter of the screw-ribbon stirring impeller 6 to the diameter of the reaction tank body 1 is (0.5-0.8):1.
[0050] As an optional embodiment of the present application, the ratio of the paddle diameter of the four-blade folding open turbine stirring impeller 7 to the diameter of the reaction tank body 1 is (0.35-0.5):1.
[0051] As an optional embodiment of the present application, the distance between the four-blade folding open turbine stirring impeller 7 and the bottom surface of the reaction tank body 1 is 1 / 5-1 / 4 of the diameter of the reaction tank body 1. If the impeller is too close to the bottom, the accumulation of particles at the bottom of the tank will cause the impeller to start up, and if the impeller is too far from the bottom, the suspension effect on the particles at the bottom of the tank will be weakened, so it needs to be controlled within an appropriate range.
[0052] As an optional embodiment of the present application, a three-blade propulsion impeller 8 is further provided on the second stirring shaft, and the three-blade propulsion impeller 8 is arranged above the four-blade folding open turbine stirring impeller 7. The propulsion impeller is a typical axial flow impeller, that is, it can effectively promote the axial flow of the liquid and promote the mixing between the upper layer liquid and the lower layer liquid. At the same time, the shear force generated by the three-blade propulsion impeller 8 is smaller than that of the turbine stirring impeller, which can reduce the shear force on the material, thereby preventing the material from being damaged.
[0053] As an optional embodiment of the present application, a flow disturbance hole is provided on the three-blade propulsion impeller 8. The flow disturbance hole is provided on the blade and can be a circular hole or a long strip hole. The fluid can achieve a more irregular flow through the flow disturbance hole, thereby increasing the uniformity of mixing.
[0054] The present application uses the above-mentioned different impellers in combination to suspend the resin solid particles in the solution, and effectively promotes the axial flow and mixing of the liquid to improve the reaction efficiency.
[0055] As an optional embodiment of the present application, in order to save space, a shock-absorbing base 10 is provided on the top cover 101, and the processor 9 is provided on the shock-absorbing base 10. The continuous stirring of the reactor during operation will generate certain vibrations, and the processor 9 is prone to malfunction when working in a vibrating environment for a long time, so a shock-absorbing design is required.
[0056] As an optional embodiment of the present application, the shock-absorbing base 10 includes a mounting groove, four damping rods 11 are arranged at the four corners of the mounting groove, and shock-absorbing springs 12 are arranged outside the damping rods 11. The processor 9 is installed in the mounting groove and supported by the four damping rods 11 and the shock-absorbing springs 12. The damping rods 11 and the shock-absorbing springs 12 can absorb the energy generated by the vibration of the reactor, reduce the vibration amplitude of the processor 9, thereby reducing the failure rate and extending its service life.
[0057] Those skilled in the art will appreciate that the embodiments described herein are intended to help readers understand the principles of the present invention, and should be understood that the protection scope of the present invention is not limited to such specific statements and embodiments. Those skilled in the art can make various other specific variations and combinations based on the technical inspirations disclosed in the present invention without departing from the essence of the present invention, and these variations and combinations are still within the protection scope of the present invention.
Claims
1. A polypeptide synthesis reactor, characterized in that: It comprises a reaction tank body, a coaxial counter-rotating stirring paddle and a processor, wherein the reaction tank body comprises a top cover, and the coaxial counter-rotating stirring paddle is inserted into the reaction tank body through the top cover; The top cover is provided with a three-phase asynchronous motor, which is connected to the coaxial counter-rotating stirring paddle and drives the coaxial counter-rotating stirring paddle to rotate; A first liquid level sensor and a second liquid level sensor are arranged below the top cover; the first liquid level sensor is close to the side wall of the reaction tank body, and the second liquid level sensor is close to the central axis of the reaction tank body; The first liquid level sensor and the second liquid level sensor are electrically connected to the processor, and the processor is electrically connected to the three-phase asynchronous motor.
2. A polypeptide synthesis reactor according to claim 1, characterized in that: The first liquid level sensor and the second liquid level sensor are any one or two of a radar liquid level sensor, a laser liquid level sensor and an ultrasonic liquid level sensor.
3. A polypeptide synthesis reactor according to claim 1, characterized in that: The coaxial counter-rotating stirring paddle comprises a first stirring shaft located at the top and a second stirring shaft extending to the bottom; the first stirring shaft and the second stirring shaft are coaxial; The first stirring shaft is provided with a spiral belt stirring impeller, and the second stirring shaft is provided with a four-blade folding open turbine stirring impeller.
4. A polypeptide synthesis reactor according to claim 3, characterized in that: The ratio of the paddle diameter of the four-blade folding open turbine stirring impeller to the diameter of the reaction tank body is (0.35-0.5):
1.
5. A polypeptide synthesis reactor according to claim 3, characterized in that: The distance between the four-blade folding open turbine stirring impeller and the bottom surface of the reaction tank body is 1 / 5-1 / 4 of the diameter of the reaction tank body.
6. A polypeptide synthesis reactor according to claim 3, characterized in that: The second stirring shaft is also provided with a three-blade propulsion impeller, and the three-blade propulsion impeller is arranged above the four-blade folding open turbine stirring impeller.
7. A polypeptide synthesis reactor according to claim 6, characterized in that: The three-blade pusher impeller is provided with a flow disturbance hole.
8. A polypeptide synthesis reactor according to claim 1, characterized in that: The top cover is provided with a shock absorbing base, and the processor is provided on the shock absorbing base.
9. A polypeptide synthesis reactor according to claim 8, characterized in that: The shock-absorbing base comprises a mounting groove, four damping rods are arranged at four corners of the mounting groove, and shock-absorbing springs are arranged outside the damping rods.
10. A polypeptide synthesis reactor according to claim 3, characterized in that: The ratio of the paddle diameter of the screw-ribbon stirring impeller to the diameter of the reaction tank body is (0.5-0.8):1.