K L a is a measure of the oxygen transfer efficiency in a bioreactor.
They can utilize sunlight as a low-cost energy source.
By changing the agitation in rpm.
Single-Use Bioreactor.
Waste water treatment and biofuel production with algae.
A Rushton impeller is commonly used for mixing and aeration in bioreactors, providing high shear and efficient gas dispersion.
Better mixing and oxygen transfer, less 'dead zones', reduced foaming, and better scalability.
Both have low shear forces.
Waste water treatment and biofuel production with algae.
They limit the chance of variation and contaminations (biologically & chemically).
The main components of a bioreactor include the vessel, agitator, aeration system, temperature control system, pH control system, and sampling ports.
Advantages include higher productivity, constant nutrient supply, reduced downtime between batches, and better control over environmental conditions.
The main types of fermentation include alcoholic fermentation, lactic acid fermentation, and acetic acid fermentation.
Large-Scale Perfusion and Concentrated Fed-Batch Operation.
In a perfusion bioreactor, cells remain in the bioreactor while the product is harvested continuously.
A membrane bioreactor is a system where enzymes or cells are trapped within a membrane, rather than being immobilized.
A chemostat is a continuous process used for microbial growth.
Low shear stress, simple setup, and can be integrated with single-use technologies.
They are widely used in biopharmaceutical development and vaccine production.
CHO cells are preferred due to their ability to perform post-translational modifications and their suitability for large-scale culture.
It provides gentle mixing, reduces shear stress on cells, and improves gas exchange.
Orbitally shaken tubes and benchtop bioreactors.
A chemostat is a continuous fermentation system where cells and product are harvested at a constant rate.
A stirred tank bioreactor is a type of bioreactor that uses mechanical agitation to mix the contents, ensuring uniform distribution of cells and nutrients.
The typical volume of mini-bioreactors mentioned is 5 liters.
The KLa value is crucial because it influences the growth rate of aerobic microorganisms by determining the amount of dissolved oxygen available in the culture medium.
Increased agitation typically enhances the KLa value by improving mixing and increasing the surface area for gas exchange.
An airlift reactor is a type of bioreactor that uses air or gas to agitate the culture medium and promote mixing and mass transfer.
Algae cultivation.
The main components of an airlift bioreactor include a riser section, a downcomer section, and a gas sparger.
Flat panel reactors are typically used to cultivate microalgae and other photosynthetic organisms.
Packed bed reactors provide high surface area for reactions, good temperature control, and are suitable for exothermic reactions.
Airlift bioreactors are commonly used in applications such as wastewater treatment, fermentation processes, and the cultivation of microorganisms and plant cells.
Fermentation is significant in food production as it enhances flavors, preserves food, and can improve nutritional value.
A membrane bioreactor is similar to packed-bed and fluidized-bed bioreactors but does not immobilize cells or enzymes.
Cheaper to start up, no cleaning down time, no cleaning validation needed, every run is exactly similar in bag and setting, no steam sterilization/autoclaving needed, and no cross-contamination from previous runs.
Advantages include better control over environmental conditions, scalability, and the ability to handle large volumes of culture.
Continuous fermentation is a process where nutrients are continuously added to the bioreactor while products are continuously removed, maintaining a steady state of microbial growth and product formation.
Scale-up is challenging due to light penetration limitations.
Factors influencing KLa include agitation speed, gas flow rate, temperature, and the properties of the liquid medium.
Aeration provides oxygen to aerobic organisms and helps in the removal of carbon dioxide produced during fermentation.
Advantages include improved nutrient supply, better cell density, and continuous removal of waste products, which can enhance overall productivity.
Lactic acid fermentation is typically performed by bacteria, such as Lactobacillus, and some animal cells.
The main function of a PID controller is to maintain a desired setpoint by adjusting control inputs based on the error between the setpoint and the process variable.
The Proportional component produces an output that is proportional to the current error value.
The Integral component accumulates the error over time and adjusts the output to eliminate residual steady-state error.
Yeast acts as a catalyst in fermentation, converting sugars into alcohol and carbon dioxide through metabolic processes.
They are used for the cultivation of algae for various applications, including biofuels and bioproducts.
Small scale production of therapeutic proteins or other products for the pharmaceutical industry.
Stainless steel bioreactors are commonly used.
The main function of stirring is to enhance mass transfer, improve mixing, and maintain homogeneity of the culture medium.
An important consideration is the discussion about upscaling and downscaling techniques.
A flat panel reactor is a type of photobioreactor designed to cultivate algae using a flat panel configuration, which allows for efficient light exposure and gas exchange.
They offer lower shear forces, better nutrient distribution, and improved cell viability.
Mixing in an airlift bioreactor is achieved through the upward flow of gas bubbles, which creates a circulation pattern that mixes the culture medium.
A higher KLa value indicates a more efficient oxygen transfer process, which is essential for maintaining optimal culture conditions.
Tubular reactor and raceway pond.
By heating or cooling.
Aerobic and anaerobic cultures.
Limitations include lower productivity compared to continuous processes and the need for downtime between batches.
Higher substrate concentrations can lead to increased product formation up to a certain point, after which inhibition may occur.
Tubular reactors are enclosed systems with tubes, while raceway ponds are open systems with a shallow channel.
Very simple and cheap design, low operating costs, suitable for aerobic cultures sensitive to shear stress.
Marine impellers are designed for fluid flow and are often used in applications requiring moderate shear and good mixing capabilities.
The primary function is to provide a gentle and controlled environment for cell culture, mimicking natural conditions.
It enhances mass transfer and oxygenation while reducing shear stress on cells, promoting better growth.
A bioreactor that utilizes a wave rocking motion to provide mixing and aeration for cell cultures.
Single-use bioreactors are disposable bioreactor systems designed for one-time use, eliminating the need for cleaning and sterilization between batches.
An airlift bioreactor is a type of bioreactor that uses air or gas to circulate the culture medium, promoting mixing and mass transfer without mechanical agitation.
Using a cascade system where agitation increases when DO is decreasing.
They are commonly used for the cultivation of sensitive cells, such as stem cells and various mammalian cell lines.
Both are suitable for continuous processes.
A tubular reactor is a type of photobioreactor that uses long, transparent tubes to cultivate algae, allowing for efficient light exposure.
Flat panel photobioreactors are commonly used in applications such as biofuel production, wastewater treatment, and carbon dioxide sequestration.
A raceway pond is an open system for cultivating algae, characterized by a shallow, circular channel that promotes mixing and light exposure.
Raceway ponds are generally more cost-effective and easier to scale up for large-scale algae production.
A higher K L a value indicates a higher Oxygen Transfer Rate (OTR).
Limited scalability, limited oxygen transfer and mixing, not suitable for viscous cultures.
More complex design and slightly higher operating costs.
Mini-bioreactors are commonly made from glass and stainless steel (SS).
KLa represents the volumetric mass transfer coefficient for oxygen, indicating how effectively oxygen is transferred from the gas phase to the liquid phase.
They are commonly used for microbial fermentation, cell culture, and production of biopharmaceuticals.
Critical parameters include temperature, pH, dissolved oxygen levels, and agitation speed.
The main advantage of flat panel reactors is their ability to maximize light exposure while minimizing the volume of culture medium, leading to higher biomass productivity.
In batch fermentation, all nutrients are added at the beginning, while in fed-batch fermentation, nutrients are added incrementally during the process.
A packed bed reactor is a type of reactor where the catalyst is packed into a bed and the reactants flow through the bed, allowing for chemical reactions to occur.
Aeration is crucial for providing oxygen to the cells and removing carbon dioxide produced during metabolism.
Advantages include simplicity of operation, ease of monitoring, and the ability to produce high concentrations of products.
Fluidized bed reactors offer improved mixing, uniform temperature distribution, and higher reaction rates due to better contact between phases.
The Derivative component predicts future error based on its rate of change and helps to dampen the system response.
pH affects microbial growth and product formation, and it is crucial to maintain optimal pH levels throughout the fermentation process.
Membrane bioreactors can be used for processes where immobilizing cells or enzymes is not possible.
A continuous bioreactor with cell retention.
A higher KLa value indicates a higher Oxygen Transfer Rate (OTR).
Limited scalability and low mixing and oxygen transfer capacity.
A stirred tank bioreactor is a vessel used for bioprocessing where agitation is provided to mix the contents and enhance mass transfer.
They can capture CO2 via photosynthesis.
Increased mixing speed creates higher shear forces with greater distances.
Advantages include increased cell density, improved product yield, and better control over metabolic byproducts.
The design, including impeller type and tank geometry, significantly influences mixing efficiency and mass transfer rates.
Mixing in an airlift reactor is achieved by introducing air or gas into the bottom of the reactor, creating bubbles that rise and induce circulation in the liquid.
Suitable for a wide range of cell types, good process control (mixing, oxygen transfer, pH and temperature), scalable from lab to industrial scale.
The main components of an airlift reactor include the riser, downcomer, gas sparger, and the liquid reservoir.
Higher agitation speeds can increase DO levels by enhancing oxygen transfer.
Airlift reactors are commonly used in wastewater treatment, fermentation processes, and the cultivation of sensitive cell types.
By changing the feed rate.
Temperature control is vital as it influences microbial metabolism, growth rates, and the overall yield of the fermentation process.
A Pitched blade impeller is designed to provide a balance between mixing and pumping, suitable for applications where both are necessary.
Expensive per run, one bag needed per run, no flexibility in bag design, possible plastic particle extraction, large waste stream, and lower oxygen transfer rate.
They can suffer from contamination and inconsistent environmental conditions.
They have high energy consumption due to using artificial light.
By adding acid or base.
The advantages include reduced risk of contamination, lower operational costs, and faster turnaround times for production.
Challenges include maintaining stable operating conditions, potential contamination, and the need for precise control of nutrient feed rates.
Bioreactor dimensions, impeller shape, size, position, sparger type, bubble size, and medium components like antifoam and salts.
A fluidized bed reactor is a reactor in which solid particles are suspended in an upward-flowing fluid, allowing for enhanced mass and heat transfer.
The temperature control system maintains the desired temperature for optimal microbial growth and metabolic activity.
They are commonly used in the production of monoclonal antibodies, vaccines, and other therapeutic proteins due to their ability to maintain high cell viability and productivity.
Sampling ports allow for the extraction of samples for analysis without disrupting the bioprocess.
Fluidized-bed bioreactors have higher shear forces but better mixing.
CHO (Chinese Hamster Ovary) cells are commonly used for large-scale antibody production.
A pressure increase is necessary.
A rocking motion that creates waves in the culture medium.
They are primarily used in tissue engineering and regenerative medicine.
A perfusion bioreactor is a type of bioreactor where fresh medium is continuously added and culture fluid is simultaneously removed, allowing for the maintenance of optimal cell growth conditions.
They are commonly used in biopharmaceutical manufacturing, vaccine production, and cell culture processes.
PID stands for Proportional, Integral, and Derivative.
Challenges include the need for precise control of flow rates, potential shear stress on cells, and the complexity of system design and operation.
Common microorganisms include bacteria, yeast, and fungi, depending on the desired product and fermentation conditions.
Airlift reactors typically have lower shear stress on cells, better gas-liquid mass transfer, and reduced energy consumption.
To control foam formation.
The duration can vary widely, typically ranging from a few hours to several days, depending on the organism and product.
Monoclonal antibodies are antibodies that are made by identical immune cells, which are clones of a unique parent cell, and are specific to a particular antigen.
Process control and types of upstream processes
Higher agitation speed, higher air flow, higher O2 content, higher pressure, and higher temperature.
Higher culture growth rate and higher cell density.
Cascade control with agitation, airflow, gas mixture, and pressure.
In packed-bed bioreactors, immobilized enzymes or cells are attached to a layer inside the reactor, while in fluidized-bed bioreactors, they are attached to beads or fibres.
Higher pressure can help increase DO levels in the bioreactor.
Monitoring is crucial for adjusting nutrient feed rates, maintaining optimal growth conditions, and preventing overfeeding or nutrient depletion.
By changing the flow rate in l/min.
Single-use bioreactors can simplify the scalability of bioprocesses by allowing for easy transition from small-scale to larger-scale production without the need for extensive cleaning protocols.
Tuning is important in PID controllers to optimize the response of the system, ensuring stability and minimizing oscillations.
Fed-batch fermentation is a process where substrates are added to the bioreactor during the fermentation process, allowing for better control of nutrient levels and cell growth.
The wave motion creates a dynamic environment that enhances nutrient distribution and oxygen transfer.
Flat panel reactors facilitate gas exchange by having a large surface area that allows for efficient diffusion of gases such as CO2 and O2 into and out of the culture medium.
Common organisms include yeast, bacteria, and some fungal species that require controlled nutrient levels for optimal growth.
Mechanical stirring can cause shear stress, aeration efficiency can be limited in highly viscous cultures.
Advantages of airlift bioreactors include lower shear stress on cells, better oxygen transfer rates, and reduced energy consumption compared to mechanically agitated bioreactors.
The pH control system regulates the acidity or alkalinity of the culture medium, which is crucial for maintaining optimal growth conditions.
Antibiotics, enzymes, proteins or monoclonal antibodies, vaccines, and biofuels.
Tubular reactors allow for better control of light and nutrient conditions, which can enhance algae growth.
The agitator mixes the culture to ensure uniform distribution of nutrients, temperature, and cells, and to enhance mass transfer.
In a perfusion bioreactor, fresh medium is continuously supplied and waste is removed, whereas in a fed-batch bioreactor, nutrients are added in batches without removing culture fluid until the end of the process.
Alcoholic fermentation is a biological process in which sugars are converted into alcohol and carbon dioxide by yeast.
In continuous fermentation, substrates are continuously fed and products are continuously removed, whereas batch fermentation involves a single batch of substrate that is processed until completion before the next batch is started.
Batch fermentation is a process where microorganisms are cultured in a closed system for a specific period, and all the nutrients are added at the beginning.
A key consideration is ensuring that the materials used do not leach harmful substances into the culture medium.
Acetic acid fermentation is the process where ethanol is oxidized to acetic acid by acetic acid bacteria.
The main difference is that in packed bed reactors, the catalyst is stationary, while in fluidized bed reactors, the catalyst is in motion due to the fluid flow.
They are used for immobilized cell culture, enzyme reactions, and continuous processes.
Membrane bioreactors share the same advantages and disadvantages as packed-bed and fluidized-bed bioreactors.
Single-use bioreactors are typically made from plastic materials that are compatible with the bioprocess and can withstand sterilization methods.
The primary product of lactic acid fermentation is lactic acid, which can accumulate in muscles during intense exercise.
They have complex designs and are difficult to scale up.
Packed-bed bioreactors have lower shear forces but poor mixing.
Yield and cell density.
