The biological reaction apparatus (Bioreactor) designed elementary

【The biological reaction apparatus (Bioreactor) designed elementary 】

Micro-giant BioEngineering 2007.05.10

Southern Taiwan University of Science and Technology Department of Biotechnology speech


Life science brings the hope of the new century, and bioengineering technology gives the possibility to practice this hope. New energy alternatives, functional health food development, special chemical raw material replacement, protein medicine, environmental engineering, bacterial culture method, waste reduction or reuse, the anti-aging of medicine, the replacement of antibiotics, quality agriculture with biologics, enzymes for industrial food and feed...etc. They all use microbial manufacturing processes to try or successfully get results or improve. With the progress and complexity of new biotechnologies, it is more important to investigate the root causes, step-by-step research experiments, and practical operations. Therefore, "bioreactor" is an indispensable core technology for this purpose, which covers machinery, chemical industry, electronics, electrical machinery, automatic control, and microbiology six specialized fields. This chapter will continue the five professional fields mentioned above and focus on microbiology, trying to make a complete discussion based on my two cents and practical experience.

1. Broad definition:

It refers to a device that uses chemical procedures to successfully carry out microbial proliferation, metabolism, or catalytic reactions (cell culture).

2. Description of the device system instrument control flow chart: (See attached figure 1 for details)

3. Device composition:

3.1 Power unit

3.2 Transmission unit (including mechanical seal group)

3.3 Agitation system

3.4 vessel

3.5 Stainless Steel Shell and Tube Condenser

3.6 Sterilization Control Valve

3.7 Steam decompression and filtration system

3.8 Temperature control piping valve

3.9 Sterile ventilation control piping valve

3.10 Exhaust gas tank pressure piping valve

3.11 Dosing and feeding control valve

3.12 Transfer inoculation transmission control valve (including sampling valve)

3.13 Electrode (pH, O2, temperature, AF) and field relative instrument SENSOR (rotation speed, pressure), piping rack

3.14 Instrument control electrical automatic control box

3.15 Other attachments

3.16 Utilities

4. Description of each department:

4.1 Power unit:

Roughly composed by motor + reducer, commonly known as the motor reducer.

Sometimes a cross steering gear is added or a reducer with the output shaft and the input shaft forming 90° is used due to the installation position. In the large (above 100kL) or part of the lower mixing tank with the pulley reduction structure, this model must pay attention to the problem of the slip and the driveshaft needs to be strengthened. The motor reducer can be divided into horizontal, vertical, and upside-down (sometimes used for lower magnetic stirrer without shaft seal) types according to the installation position. The calculation of horsepower and the different types of agitation systems (mainly impellers) and the influence of shear force on microorganisms will be discussed in a follow-up special issue.

◎ Motor:

Generally, it is necessary to consider the operating voltage, frequency (related to the area of use and power consumption), indoor or outdoor type, explosion-proof grade (partial hydrogen production or contents such as alcohol, etc., or use air motor), display transmission position (vertical, horizontal, inverted), rotational speed (number of poles), etc. Certainly, if it is used for pilot plant or Lab., the noise dB value should preferably be less than 70dB within 2 meters (the total noise value has other factors to be considered).


Generally, according to the transmission mode, it can be divided into planetary gear type, cycloidal gear type, and helical gear type.

The selected factor is preferably pointed contact, because the angle of the incident angle of the contact surface does not change much, resulting in lower noise and higher transmission efficiency, especially suitable for fluid changes (turbulent flow, Reynolds number Re> 4,000) agitation use. For "transmission coefficient", please select "variable load".

4.2 Transmission unit (including mechanical seal group):

See attached figure 2 for details. It consists of the motor base, the transmission base, the transmission base board, the transmission shaft, the coupling, the bearing, the oil seal, and the mechanical shaft seal.

Motor base:

It is used to connect the motor reducer and transmission base. The early material was SS400 (black iron), and the surface was painted with sandblasting or paint. However, after two or three years of use in the fermentation factory, if the washing tank is wet or close to the sea breeze, the rustiness will cause rust powder to invade the bearing and even enter the shaft seal, causing abnormal transmission noise, and then damage.

Transmission base:

For placing shaft seals, bearings, and connecting cover plates. The material is the same as the above description. In addition to rigidity, the height of the transmission seat should be carefully paid attention to the problem of "transmission span". "Transmission span" refers to the distance between the upper and lower bearings. Insufficient transmission span will cause the swing angle of the stirring shaft to be too large, which will cause damage to the mechanical shaft seal in advance, resulting in poor airtightness or dead corners and contamination.

the transmission base board:

To undertake the transmission seat (if it is a small vessel, the flat cover is the transmission base board). The material should be the same as that of the inner tank wetted part, generally SUS316 or above 316L. When welding to the vessel, pay attention to the centrality and horizontal correction.

the transmission shaft:

Transfer the power of the power unit to the agitation unit. The general small vessel (below about 50L) is designed to be integrated in consideration of high speed, rigidity, and centrality (this means the transmission shaft = stirring shaft). The disadvantage is that it is difficult to maintain (when disassembling the transmission system). Fortunately, it can be ignored due to the small vessel is lighter. In addition, there are places on the transmission shaft that are in contact with bearings, oil seals, and shaft seals. Therefore, the surface needs to be plated with hard chrome to increase wear resistance, improve the life of the agitation shaft, and avoid biting and scratching the shaft surface to damage the airtightness. Especially because the transmission shaft is made of the same stainless steel as the wetted part, the rigidity and toughness are not as good as S45C (medium carbon steel) or SF (forged steel) steel. To have both corrosion resistance and wear resistance, the surface is electroplated with a layer of chromium (Cr) of about 0.03 ~0.06t mm, and the process of precision grinding cannot be omitted.


As its name implies, for connecting the output shaft of the motor reducer and the transmission shaft. Generally, chain transmission types CR series (small shaft diameter below 30 can use spider type) to transmit power. This type of flexible coupling can absorb 3~5 degree deflection angle, reduce transmission amplitude, and effectively transmit the maximum power. There is also a rigid coupling with flanged linkage (Key). It should be noted that the design concept of this model takes the output shaft of the reducer as the first span point on the upper part of the "transmission span", so do not design more than two span points, and the reducer is better to increase the size of the one.


For the first span point on the upper part, UKF or UCF block bearing can be used. Please note: It is necessary to add an inclined cone sleeve because it helps to automatically correct the assembly center during assembly. For the second span point in the lower part, it is recommended to use a set of self-aligning ball or roller bearings, plus an oil seal ring, to provide a lubricating oil filling port. Please note: Above 1,000rpm, select high-precision bearings with small ball clearance.

(Mechanical) shaft seal:

In the early days (about 20 years ago), a ground-type tightening strip (PTFE material) was used, and a tightening washer was added 3 to 6 times around the shaft to form a sealing material, but it has its shortcomings in use, so it is no longer used. Replaced with Mechanicals Seal. The mechanical shaft seal can be roughly divided into wet type and dry type according to the lubrication method. If the wet type is used, it must be noted that the lubricating fluid must be sterile water, and the sterile water generator must be set up in a single set of devices (One by one), which cannot be shared. To avoid contamination of a single set of sterile water, it will not affect other bioreactors in the plant. If Dry Mechanicals Seal is used, the above problems are exempted. The new mechanical shaft seal is provided with a cassette design, which can greatly reduce the technical requirements for equalizing pressure on the assembly surface, but due to the inner sleeve design, the increase in the shaft diameter leads to an increase in manufacturing costs. The mechanical shaft seal is roughly divided into a rotary ring and a fixed ring. The fixed ring can be made of tungsten carbide or ceramics, and the rotary ring can be made of graphite or carbon. Metal parts can be made of SUS316, SUS316L, or titanium. The shaft seal soft sealing material (ex. O ring or packing ring) is made of Viton or EPDM, and Teflon is not recommended. Because the grinding precision of the folding surface (for the grinding surface) is too high, the mirror adsorption effect will occur during the sterilization stage, and there will be slip when there is no dowel pin, which will destroy the soft sealing material. Mechanical shaft seals are used in the biotechnology industry. In addition to normal considerations, pay attention to the high temperature and cooling water (Drain) discharge problems generated by the moist heat sterilization method during the sterilization stage. Because maintaining 121°C for 20~30min during sterilization will result in residual condensed water. Therefore, the steam enters and exits up and down, so that there will be no dead angle resulting in incomplete sterilization of the shaft seal. In the design or selection of the shaft seal, it is necessary to pay attention to the design of thermal insulation. The fermented heat generated during the incubation period will transfer to the transmission system along the stirring shaft, which will cause the shaft seal or bearing seal to be damaged early.

Ps. Pay attention to the design of the (mechanical) shaft seal, the first channel is the closest to the liquid contact part of the culture container, and other sealing materials ex. oil seals or other bearings cannot be added during this period. There is also no shaft seal design, such as magnetic stirring, but the transmission power leakage is large, and there are doubts about tripping. If it is in the lower part, because it occupies the lowest point, there will be doubts about residual material at the discharge port, and it is not used now.

4.3 Agitation system:

It is composed of agitator shafts, defoaming wings, impellers, baffles, shaft support bases and other parts.

Agitator shaft:

The material should be the same as that of the wetted part (usually SUS316 or SUS316L), and there is a flanged coupling on the upper end of the shaft to connect the drive shaft. At the junction with the impellers, for small (under 200L) pilot plant cultivation device vessels, set screws will be designed on the wheel shell of the stirring wing, but there must be 2 screws at 90° to each other to prevent sliding or shifting, and can easily change the propeller position. As for the medium and large culture, it is necessary to have a key way design. If it is necessary to change the position of the propeller, a long key must be designed for the impellers wheel housing to slide to the desired position and then lock it with set screws. If you are worried about impellers loosening and sliding, you can design a headed key below the long key. For medium and large (above 500L) culture tanks at the lower end of the shaft, a shaft support seat must be designed to reduce the offset of the stirring center.

Defoaming wing:

Also known as foaming wing or defoaming wing, it is a simple Impeller (flat paddle) design and is often used as one of the physical defoaming strategies. However, in practice, it is found that when the foaming overflows, most of them are attached to the bridging phenomenon and stacked along the barrel wall. Therefore, how to destroy the bridging of the barrel wall in the early stage of foam generation is the current physical defoaming strategy. New design. In addition, there is another design with both physical and chemical defoaming strategies, that is, the defoaming agent is passed through the lower edge of the defoaming wing, and then evenly sprinkled after the rotating action, so that the surface of the broth (Broth) is at the same dose. The surface area of the lower contact liquid surface is increased, and the effect of the defoamer is increased.


Generally, when aerobic organisms are cultivated, Turbine type (also known as Rushton type) is often used, which can be divided into six wings, four wings, inclined plates, and curved plates. For this common type, when the air sparger is too close to the stirring wing, bubbles will aggregate or flood, and when it is too far away, it is not easy to be broken and dispersed by the stirring wing. The turbine type is better than the propeller type. However, if it is an anaerobic or anaerobic biological culture, the focus of the blade type should be placed on the viscosity of the material or the form of solid content and the amount, and attention should be paid to precipitation.

Ps. Pay attention to the turbine type airfoil design, the optimal tangential speed of the outer edge of the airfoil diameter is 2~5 M/sec operation.


It is placed on the wall of the container and can be divided into three groups (below 50L) or four groups. Its function is to increase the degree of turbulence during stirring, to achieve uniform temperature, uniform gas and solution transfer, and liquid medicine (acid, alkali, defoaming, etc.) and nutrient sources (nitrogen, carbon, trace elements) to add dispersity. And when the stirring is destroyed, the vortex phenomenon is generated in the center (that is, the eddy current is broken). In large-scale culture devices (above 50kL), due to the insufficient heat transfer area of the interlayer, special direct tube bundle replaces the original baffle position, which can not only increase the heat transfer area but also achieve a turbulent flow state. However, it relatively increases the difficulty of cleaning.

Shaft support bases:

In medium and large-scale (500L or more) culture devices, due to the lengthening of the suspension shaft, a shaft support seat is designed at the end of the stirring shaft to support the stirring shaft, which can absorb the deflection and increase the transmission stability. The lining design can absorb the corresponding force, but is not responsible for axial stress. The material is mainly Teflon (Teflon), and sometimes glass fiber is added to increase the hardness. PEEK is a good choice when considering strong acid or alkali and hardness.

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