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In order to meet the requirements of aseptic and easy cleaning, the application of magnetic stirring devices in the biopharmaceutical industry is becoming more and more extensive. This article starts with the classification, main internal structure and working principle of magnetic stirring devices, and briefly describes the different forms of paddles in magnetic stirring devices. The application, combined with the user’s field use, delineated the operating parameters of different blades.
Part 1 Background
Domestic science and technology and production technology are changing with each passing day, and the biopharmaceutical industry has increasingly stringent requirements for the sealing of mixing devices. The combined use of the reaction tank and the stirring device is an important part of the entire production process, so cGMP (Dynamic Drug Manufacturing Regulations) has particularly strict requirements on the in-line cleaning (CIP) and in-line sterilization (SIP) of reaction equipment.
In this context, the application prospect of magnetic stirring technology is widely favored by technicians in the industry. The magnetic stirring device replaces the mechanical dynamic sealing structure of the mechanical stirring device with a static sealing structure. This structure can transmit kinetic energy without contact, and can completely solve the leakage problem of the mechanical dynamic seal and packing seal, and fully realize the material working chamber and drive. The isolation function of the chamber is one of the hot development directions in the biopharmaceutical reaction system.
Some European and American countries started early in the field of magnetic drive technology research and accumulated rich application experience. In the field of biopharmaceuticals, safety is the primary goal. However, the paddles, bearings and spacers installed and welded in the tank of the magnetic stirring device will all come into contact with the material, which poses a considerable safety hazard. However, with the advancement of new chemical materials technology, the materials on the stirring device have all achieved safety verification, and 316L, ceramic carbide bearings, etc. all meet safety requirements. Enterprises such as ALFA and Nov Aseptic in Sweden, ZETA in Austria, Aerre Inox in Italy and IKA in Germany have made outstanding contributions to the mixing field.
Domestic research on mixing and stirring, especially magnetic stirring, started relatively late, but in recent years, this field has also developed rapidly. In line with the acceleration of domestic technology and production, magnetic stirring devices almost cover research and development, testing, small test, pilot test and large-scale production. In various fields, especially in dealing with high power, high torque and high temperature and high speed, it has occupied a certain market share.
In the past 30 years, the composition and structure of magnetic stirring devices have not changed much, but the paddle form and bearing selection have developed rapidly. For different material conditions, equipment suppliers have realized corresponding solutions in terms of rotation speed, reaction disturbance, propulsion force, and shear sensitivity by changing the form of the blade. The application of ceramic ball bearings and cemented carbide (silicon carbide, silicon nitride, etc.) sliding bearings basically meets the requirements of CIP and SIP in the field of biopharmaceuticals.
Part 2 Structure Of Magnetic Stirring Device
The magnetic stirring device is mainly composed of a driving motor, an inner magnetic sleeve connected to the motor, a spacer sleeve connected to the tank, an outer magnetic sleeve integrated with or connected to the stirring blade, and bearings. The device relies on magnetic transmission, that is, based on the principle of magnetism, using the same-sex repulsion and opposite-sex attraction principle between magnet materials to form an effect, and transmit the torque and speed of the drive motor to the stirring blades in a non-contact manner, thereby driving the reaction tank. The mixing of the internal materials achieves the purpose of full reaction.
According to the structure of the transmission device, the magnetic stirring device can be divided into: cylinder magnetic stirring device and disc magnetic stirring device; according to the application occasion, it can be divided into: experimental type and production type magnetic stirring device; according to the installation method, it can be divided into: top magnetic stirring device Stirring device and bottom magnetic stirring device; according to the driving mode, it can be divided into: internal magnetic drive stirring device and external magnetic drive stirring device.
The cylindrical magnetic stirring device adopts the structure of the outer magnetic ring embedded with the inner magnetic ring, and an isolation sleeve is set between the inner and outer magnetic rings to completely isolate the inner and outer space of the reaction tank. The three are installed concentrically, and the working parting surface is cylindrical. The magnets installed in the inner and outer magnetic sleeves are tile-shaped structures. This structure has the characteristics of large transmission torque, so the main application occasions of this type of stirring device are high viscosity occasions.
The driving magnetic sleeve and the driven magnetic sleeve of the disk magnetic stirring device are installed axially face to face, the working surfaces are mutually parallel planes, and the magnets are mostly fan-shaped structures. Similarly, in order to isolate the space inside and outside the reaction tank, an isolation sealing device is also arranged between the two magnetic sleeves. Although the transmission form of this structure simplifies the form of the magnet, the transmitted torque is smaller than that of the cylindrical magnetic stirring device, so it is mainly used in occasions where the viscosity of the material is relatively small.
The experimental magnetic stirring device is mainly used for mixing materials with low viscosity. At present, the stirring devices used in the laboratory mainly include electric direct drive and magnetic drive. Compared with the two, the magnetic stirring device has more advantages in the following links: good sealing, and the rotor with the paddle wrapping the magnet is installed in the reaction tank. , is completely isolated from the driving magnet, and the electric drive blade is difficult to achieve complete sealing due to the main shaft connection; it is easy to disassemble and assemble, with lower noise and better running stability.
Compared with the experimental magnetic stirring device, the production-type magnetic stirring device needs to have greater torque and stability because of the larger material volume, viscosity and operating radius of gyration. Some devices are also equipped with cleaning interfaces, cooling structures and sterilization process modules. Moreover, compared with the experimental magnetic stirring device, its complexity is correspondingly increased, so higher requirements are placed on the processing technology and assembly technology.
Top magnetic stirring device, this type of stirring device is installed on the top or eccentric area of the top of the reaction tank. Compared with the bottom installation, the advantage of this installation method is that the magnet can be kept away from the material to be stirred, thereby reducing the possibility of corrosion of the driven magnet installed in the tank. However, with the continuous improvement of production technology, the volume of the reaction tank continues to increase, and the magnetic stirring device installed on the top is also constantly developing towards a large-scale trend. The following disadvantages are gradually highlighted: the stirring shaft is lengthened, resulting in long The larger the diameter ratio, the weaker the bending resistance of the shaft, especially when dealing with high-viscosity materials, the stirring shaft is easy to bend or even deflect and break, resulting in production stop or even scrapping of material batches; the size of the stirring device increases and the gravity increases , it is required that the magnetic force on the top can overcome the gravity of the stirring shaft and paddle to be further improved. If a rotating support is added at the bottom to solve the weight, that is, the effect of rotation and bending, it may increase the risk of damage to the support and cause the material to stop production and be scrapped.
Compared with the top magnetic stirring device, the bottom magnetic stirring device has a very short protruding drive shaft, so the length-to-diameter ratio is smaller, and its advantages are more obvious when dealing with materials that are prone to sedimentation. Compared with the top magnetic stirring device, the bottom magnetic stirring device consists of fewer parts, which are mainly composed of paddles, driven magnets (normally integrated with the paddles), isolation sleeves welded in the reaction tank, installation It is composed of the active magnet on the driving device, the driving device, the seal, the ceramic positioning bearing and other components. Its advantages are: the isolation sleeve and the reaction tank are integrally formed to ensure sealing; the equipment omits the long drive shaft, the structure is more compact, and high speed can be achieved; the stirring effect is better when dealing with low liquid level and the reaction of materials that are easy to sink.
Part 3 Key Points Of Structural Design Of Magnetic Stirring Device
3.1 Isolation Sleeve
The spacer of the stirring device is located between the driven magnetic rotor and the active magnetic rotor. During the rotation of the magnetic rotor, the spacer will be in an alternating magnetic field. According to Faraday’s principle, the changing magnetic field will generate an electric field, thereby forming a current, so that the eddy current will Will produce. Compared with the reaction work, the eddy current will weaken the magnetic field, resulting in a decrease in the transmission torque. In addition, the loss will appear in the form of heat energy, and the released heat energy may affect temperature-sensitive materials.
In order to reduce the generation of eddy current, especially to solve the problem of heat generation, we should mainly start from the following aspects: In terms of isolation sleeve materials, 316L, titanium alloy, Hastelloy and other high-resistance materials are used for manufacturing, and the conductive current is reduced and solved from the source of the material. Problem: In terms of the wall thickness of the isolation sleeve, considering the space in the reaction tank and the effective transfer of energy, the wall thickness of the isolation sleeve can be reduced as much as possible while meeting the requirements of energy transfer between the inner and outer rotors. On the premise of meeting a series of installation processes such as welding In this way, the transmission radius can be effectively reduced; a cooling medium is added, and a space for the cooling medium to pass through is added in the isolation sleeve, and the heat exchange structure is used to control the temperature rise and physically reduce the temperature, thereby ensuring the reaction stability of materials with high temperature sensitivity.
3.2 Rolling Bearings
Through magnetic transmission, the dependence on packing seals (currently not applicable in the field of biopharmaceuticals) and mechanical seals in the process of transmission mechanical transmission is directly eliminated at the material level, effectively solving the problems of dynamic seal leakage and incomplete space isolation. However, in order to achieve the concentricity of the driven rotor and the driving rotor, positioning bearings are currently the best choice. In this way, whether it is a top magnetic or a bottom magnetic stirring device, it is difficult to avoid a problem: the contact between the bearing and the reaction material. Especially for the magnetic stirring device at the bottom, it is unavoidable for the bearing to be in contact with the medium for a long time. At the same time, due to the accumulation of precipitated substances, impurities can easily enter between the bearing raceway and the rollers, and there may be a risk of increased wear on the bearing.
For positioning bearings, Bola Precision Machinery mainly uses ceramic bearings with strong corrosion resistance and wear resistance (as shown in Figure 2) to realize the positioning of the master and slave rotors. The rotating flow channel is formed, and the lubricating film is formed between the bearings by the flow of materials to achieve the purpose of lubricating the bearings.
3.3 Stirring Paddles
The core component of the mixer to achieve mixing, mass transfer and heat transfer is the paddle. Its function is to provide a suitable energy flow field for the materials in the reaction tank through rotation to achieve the purpose of mixing and contact. At present, according to the stirring process, the basic form of the paddle can be divided into paddle type, turbine type, propulsion type, anchor type, frame type, ribbon type and rake type.
(1) Paddle Blade
Paddle blades usually have a two-blade structure. In the field of biopharmaceuticals, due to the need for easy cleaning, welding is often used instead of threaded fastening to avoid dead zone problems at the connection. The most common forms are straight or hinged. The straight paddle can make the material move circularly to a greater extent, while the folded paddle can make the material move circularly, and at the same time, because it is inclined to the axis of the rotating shaft, it can also generate a certain driving force in the axial direction. , to make the material move up and down, so that the material can be more fully contacted and reacted. Usually, paddle blades are mainly used in the occasions where the rotational speed is relatively low (100 r/min), and the edge speed is less than 5 m/s.
(2) Turbine Blades
The blades of the turbine blades are straight, beveled and curved, and the number of blades is usually 3, 4 or 6. Compared with the paddle type, the shear force generated during the stirring process is greater, which can make the material disperse more finely. Normally, the speed of the turbine blade can reach 300 r/min, which is suitable for medium and high viscosity occasions.
(3) Pusher Blades
Its name comes from marine propellers. Compared with the folded blades, the difference is that the blade surface is helical, with 2 to 5 blades, and the most widely used is 3 blades. The reaction tank using this kind of blade mainly contains materials that are sensitive to shear, and it needs gentle force while it needs to be fully stirred. Usually, the pusher blade is mainly used in the occasions where the speed is below 500 r/min and the edge speed is less than 15 m/s.
(4) Anchor Type, Frame Type, Ribbon Type Blades
The remarkable common feature of these three is that the edge of the blade is very close to the wall of the reaction tank, and its shape is mainly determined by the actual shape of the reaction tank. Since the ratio of the blade diameter to the reaction tank is closer to 1, the stirring effect on the material in the middle of the reaction tank is poorer than that of the aforementioned type of blades. But for materials with higher concentration and better settling performance, they can realize the up and down disturbance of materials to a greater extent. Therefore, these three structures are mainly used in occasions where the viscosity of the material is high and the requirements for the speed of the equipment are low.
The selection of stirring blades is mainly determined according to the viscosity, concentration, settling performance and shear sensitivity of the material. The combination of two or more blades is also common in the current reaction field, such as turbine and rake The combination of different types can effectively reduce the accumulation of air bubbles due to the dispersion effect produced by the turbine blades. The rake-type sawtooth structure can effectively pierce the air bubbles to control the height of the reaction liquid and avoid blocking the respirator on the upper wall of the tank. .
Part 4 Outlook
The significance of mechanical structure design is to solve the problems encountered in production and use. How to combine the characteristics of the process to combine and re-innovate the classic mechanical structure is the primary problem facing the application-oriented manufacturing enterprises. In order to effectively solve the hygienic problems in the field of biopharmaceuticals, reasonable processing technology changes can be adopted to reduce or eliminate areas where potential materials may exist, and at the same time, design verification, performance verification, operation verification and riboflavin testing are carried out before delivery. For the traceability issue that the biopharmaceutical industry is concerned about, on the one hand, equipment manufacturers need to carry out quality control from the source of materials, paying attention to the combination of documents and material consistency; Fusion, through intelligent penetration measurement, realizes the connection between mixing and material reaction, and further introduces audit trail mode to provide necessary data support for traceability.