Glossary

3.4 Biochemical Reactor Engineering

4 min read•july 22, 2024

and are key to understanding bioprocesses. These concepts help predict how microorganisms grow, use substrates, and produce desired products in various bioreactor setups.

Mathematical models and equations like Monod's describe microbial growth in different reactor types. Factors like temperature, pH, and oxygen levels greatly impact bioprocess efficiency. Choosing the right bioreactor design is crucial for optimizing production and product quality.

Microbial Growth and Enzyme Kinetics

Principles of microbial growth kinetics

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  • describes relationship between and
    • μ\mu represents specific growth rate how quickly biomass increases per unit of existing biomass
    • μmax\mu_{max} achieved when substrate is not limiting
    • SS substrate concentration (glucose, lactose) available for microbial growth
    • KsK_s substrate concentration at which specific growth rate is half of μmax\mu_{max}
  • YX/SY_{X/S} ratio of biomass produced to substrate consumed
    • ΔX\Delta X change in biomass concentration (cell dry weight)
    • ΔS\Delta S change in substrate concentration consumed by microorganisms
  • Microbial growth kinetics crucial for predicting biomass production and substrate utilization in bioreactors

Mathematical models for bioreactors

  • closed system with no inflow or outflow of materials
    • describe changes in biomass, substrate, and product concentrations over time
      • dXdt=μX\frac{dX}{dt} = \mu X biomass growth proportional to existing biomass and specific growth rate
      • dSdt=−1YX/SμX\frac{dS}{dt} = -\frac{1}{Y_{X/S}}\mu X substrate consumption related to biomass growth and yield coefficient
      • dPdt=YP/XμX\frac{dP}{dt} = Y_{P/X}\mu X product formation linked to biomass growth and product yield coefficient YP/XY_{P/X}
    • Integrate equations numerically or analytically to predict concentration profiles throughout the batch process
  • initially operates as a batch system with controlled addition of substrate
    • Mass balance equations modified to include substrate feed term
      • dSdt=−1YX/SμX+FV(Sf−S)\frac{dS}{dt} = -\frac{1}{Y_{X/S}}\mu X + \frac{F}{V}(S_f - S) substrate balance includes consumption and feed terms
      • dVdt=F\frac{dV}{dt} = F volume changes due to substrate feed rate FF
    • Optimize feed rate to maintain desired substrate concentration and prevent substrate inhibition or limitation
  • () operates with continuous inflow of fresh medium and outflow of culture broth
    • Mass balance equations include dilution terms for inflow and outflow
      • dXdt=μX−DX\frac{dX}{dt} = \mu X - DX biomass balance includes growth and outflow terms
      • dSdt=−1YX/SμX+D(Sf−S)\frac{dS}{dt} = -\frac{1}{Y_{X/S}}\mu X + D(S_f - S) substrate balance includes consumption, inflow, and outflow terms
      • dPdt=YP/XμX−DP\frac{dP}{dt} = Y_{P/X}\mu X - DP product balance includes formation and outflow terms
    • determines operating conditions for constant biomass, substrate, and product concentrations

Effects of operating conditions

  • Temperature affects reaction rates and enzyme stability
    • relates kk to temperature TT and EaE_a
      • k=Ae−EaRTk = A e^{-\frac{E_a}{RT}} higher temperatures increase reaction rates but may denature enzymes
    • Optimize temperature to balance growth rate and enzyme stability (mesophiles 20-45°C, thermophiles 45-80°C)
  • pH influences enzyme activity and microbial growth
    • Maintain pH within optimal range for the specific bioprocess (lactic acid bacteria pH 5.5-6.5, E. coli pH 6.5-7.5)
    • Use buffers (phosphate, Tris) or pH control systems (acid/base addition) to maintain desired pH
  • critical for aerobic bioprocesses
    • Maintain dissolved oxygen above critical level to avoid oxygen limitation (typically >20% saturation)
    • Aeration and agitation increase (OTR) from gas to liquid phase
      • OTR=kLa(C∗−CL)OTR = k_La(C^* - C_L) OTR proportional to volumetric mass transfer coefficient kLak_La and concentration driving force
    • Monitor dissolved oxygen using sensors (polarographic, optical) and control using feedback loops (adjust agitation, aeration, or oxygen enrichment)

Design of bioreactor configurations

  • versatile and widely used configuration
    • Advantages good mixing, heat transfer, and oxygen transfer
    • affects fluid flow patterns and shear stress
      • generates radial flow and high shear suitable for microbial fermentations
      • creates axial flow and lower shear ideal for shear-sensitive mammalian cells
    • prevent vortex formation and improve mixing by promoting turbulence and radial flow
    • distributes air or oxygen-enriched gas for aeration and oxygen transfer
  • suitable for shear-sensitive cells and low-viscosity broths
    • Advantages low shear, simple design, and efficient oxygen transfer
    • Riser and downcomer sections create liquid circulation loop
      • Riser contains gas-liquid mixture with lower density and upward flow
      • Downcomer contains liquid only with higher density and downward flow
    • Liquid circulation driven by density difference between riser and downcomer eliminates need for mechanical agitation
    • Sparger at the bottom of the riser distributes gas for aeration and creates gas-liquid mixture
  • enables continuous operation and easy product separation
    • Advantages high enzyme stability, easy product separation, and continuous operation
      • Adsorption enzymes attached to solid support (cellulose, silica) by physical forces (van der Waals, hydrogen bonding)
      • Covalent bonding enzymes chemically bound to solid support (agarose, polyacrylamide) by stable covalent bonds
      • Entrapment enzymes trapped within a porous matrix (alginate, chitosan) by gelation or cross-linking
      • Encapsulation enzymes enclosed within a permeable membrane (liposomes, microcapsules) by emulsification or interfacial polymerization
    • Reactor configurations
      • immobilized enzymes packed into a column with substrate flowing through the bed
      • immobilized enzymes suspended by upward flow of substrate minimizing mass transfer limitations
      • enzymes confined by a selective membrane allowing continuous substrate and product flow
  • Optimizing bioreactor configuration based on bioprocess requirements
    • Consider shear sensitivity, oxygen demand, mixing requirements, and downstream processing
    • Conduct experiments and simulations to compare different configurations and operating conditions
      • Maintain similar hydrodynamic conditions (power input per volume, mixing time) at larger scales
      • Ensure adequate mixing and oxygen transfer by adjusting impeller design, aeration rate, and reactor geometry
      • Address heat transfer limitations by implementing cooling systems (jacket, coils, external heat exchangers)

Key Terms to Review (32)

Activation Energy: Activation energy is the minimum amount of energy required for a chemical reaction to occur. It plays a crucial role in determining the rate of reactions, as higher activation energies typically mean slower reactions, while lower activation energies facilitate faster reactions. This concept is essential for understanding how catalysts work, how biological systems function, and how separations can be optimized in reactive processes.
Airlift bioreactor: An airlift bioreactor is a type of bioreactor that uses air or gas to mix and circulate the liquid medium, enhancing mass transfer and providing a controlled environment for biological reactions. This design typically consists of a riser section where air is injected, causing the liquid to rise, and a downcomer section where the liquid flows back down, promoting effective mixing and nutrient distribution. Its unique design makes it suitable for cultivating microorganisms and cells in various bioprocesses.
Arrhenius Equation: The Arrhenius Equation is a mathematical expression that relates the rate constant of a chemical reaction to the temperature and activation energy required for the reaction to occur. It emphasizes how temperature affects reaction rates, showing that as temperature increases, the reaction rate generally increases due to more molecules having sufficient energy to overcome the activation barrier. This concept is crucial in understanding catalytic processes, biochemical reactions, and advanced reaction kinetics.
Baffles: Baffles are structures used in reactors to control fluid flow, improve mixing, and enhance heat and mass transfer during biochemical reactions. By disrupting the flow pattern of fluids, baffles help prevent vortex formation and dead zones, leading to more efficient reactions and improved yield. Their design and placement are crucial for optimizing reactor performance in various biochemical processes.
Batch bioreactor: A batch bioreactor is a type of vessel used for cultivating microorganisms or cells in a closed system where all ingredients are added at the beginning and the product is harvested at the end of the fermentation process. This setup allows for precise control over conditions like temperature, pH, and nutrient levels, making it ideal for producing specific products, such as pharmaceuticals or enzymes, during a set period. The operation is characterized by its simplicity and ability to produce high yields of desired products without continuous monitoring.
Chemostat: A chemostat is a type of bioreactor that maintains a continuous culture of microorganisms or cells by constantly supplying fresh nutrient media while removing an equal volume of spent media. This system allows for the regulation of growth conditions, such as nutrient concentration and dilution rate, enabling precise control over the microbial population and metabolic activity. Chemostats are crucial for studying microbial physiology, kinetics, and production processes in biochemical reactor engineering.
Continuous Bioreactor: A continuous bioreactor is a type of bioreactor where the input of nutrients and the removal of products occur continuously, allowing for a steady-state operation of microbial or cell cultures. This design maximizes production efficiency by maintaining optimal growth conditions for microorganisms, which leads to higher yields of desired products over time. Unlike batch reactors, which operate in discrete cycles, continuous bioreactors support ongoing biological processes and can be tailored to various biochemical reactions.
Dissolved Oxygen: Dissolved oxygen refers to the amount of oxygen that is present in water, which is crucial for the survival of aquatic organisms. This parameter is essential in biochemical processes, as it supports aerobic respiration in microorganisms, which are often involved in biochemical reactions within various reactor systems. The concentration of dissolved oxygen affects microbial activity, substrate utilization, and overall efficiency in biochemical reactor operations.
Enzyme immobilization methods: Enzyme immobilization methods refer to the various techniques used to confine enzymes to a certain location, typically within a solid support, to enhance their stability, reusability, and overall effectiveness in biochemical processes. By fixing enzymes in place, these methods facilitate easier separation from reaction mixtures, allow for continuous operation in reactors, and help control enzyme activity under varying operational conditions. This has significant implications for biochemical reactor design and operation.
Enzyme reactions: Enzyme reactions are biochemical processes in which enzymes act as catalysts to accelerate chemical reactions, typically involving substrates that are transformed into products. These reactions are crucial in various biological functions, including metabolism and cellular processes, as they lower the activation energy required for reactions to proceed, thereby increasing reaction rates.
Fed-batch bioreactor: A fed-batch bioreactor is a type of bioreactor system where substrates are added to the culture during the fermentation process without removing any of the culture fluid. This method allows for better control over growth conditions and nutrient levels, leading to improved product yields and higher cell densities. The fed-batch approach strikes a balance between batch and continuous systems, allowing for optimal nutrient utilization while minimizing waste production.
Fluidized Bed Reactor: A fluidized bed reactor is a type of chemical reactor that facilitates the interaction between gas and solid particles by suspending the solid material in an upward flow of gas, creating a fluid-like behavior. This design allows for efficient mixing, increased surface area for reactions, and improved heat and mass transfer, making it suitable for a variety of applications including catalysis, biochemical processes, and advanced mass transfer operations.
Half-Saturation Constant: The half-saturation constant, often represented as $$K_s$$, is a key parameter in biochemical reactor engineering that indicates the substrate concentration at which the growth rate of microorganisms is half of its maximum value. This constant is crucial for understanding how microorganisms interact with substrates, as it provides insights into the efficiency of substrate utilization and helps optimize conditions in bioreactors for various biochemical processes.
Immobilized Enzyme Reactor: An immobilized enzyme reactor is a bioreactor that uses enzymes that are fixed or attached to a solid support to catalyze chemical reactions. This setup allows for the continuous use of enzymes, enhancing reaction efficiency and stability while simplifying product recovery and enzyme reuse. The immobilization technique often improves the operational characteristics of the reactor, allowing for better control over reaction conditions and higher enzyme activity.
Impeller Design: Impeller design refers to the engineering process of creating the rotating component within a pump or mixer that imparts energy to the fluid, facilitating its movement and mixing. A well-designed impeller is crucial in biochemical reactor engineering, as it directly influences the efficiency of mass transfer, mixing, and shear forces within the reactor, impacting biological reactions and overall process performance.
Mass Balance Equations: Mass balance equations are fundamental mathematical representations used to account for the mass entering, leaving, and accumulating within a system. They are essential in the analysis of biochemical reactors, where they help ensure that all inputs, outputs, and transformations of materials are accurately accounted for during processes such as fermentation or enzymatic reactions. By applying these equations, engineers can optimize reactor designs, enhance efficiency, and predict the behavior of biological systems under various conditions.
Maximum Specific Growth Rate: The maximum specific growth rate refers to the highest rate at which a microbial population can increase in biomass per unit of biomass under optimal conditions. This concept is crucial in understanding the dynamics of microbial growth in various environments, particularly within biochemical reactors where conditions can be fine-tuned for efficiency and productivity.
Membrane Reactor: A membrane reactor is a type of chemical reactor that integrates a membrane separation process with a chemical reaction, allowing for selective removal of products or reactants during the reaction. This design enhances reaction rates and yields by shifting equilibrium positions and minimizing product inhibition. Membrane reactors are particularly valuable in biochemical processes, where they can improve efficiency and selectivity by controlling the environment within the reactor.
Microbial growth kinetics: Microbial growth kinetics refers to the study of the rates of microbial population growth and the factors that influence these rates over time. This concept is essential for understanding how microorganisms proliferate in various environments, as well as their behavior in biochemical reactors, where controlling these rates is critical for optimizing production processes. Various models and equations, like the Monod equation, are employed to describe and predict microbial growth under different conditions, making it a foundational concept in biochemical engineering.
Monod Equation: The Monod Equation is a mathematical model that describes the growth rate of microorganisms as a function of substrate concentration. It is similar to the Michaelis-Menten equation used in enzyme kinetics, providing insights into how microorganisms utilize substrates for growth in biochemical processes. This equation is fundamental in understanding microbial kinetics and optimizing bioprocesses in biochemical reactor engineering.
Oxygen Transfer Rate: Oxygen transfer rate refers to the speed at which oxygen is transferred from a gas phase to a liquid phase, particularly in biological processes where microorganisms utilize oxygen for respiration. This rate is crucial in biochemical reactor engineering as it directly influences the efficiency of microbial growth, substrate utilization, and product formation. A higher oxygen transfer rate typically leads to improved reaction rates and overall productivity in bioprocesses.
Packed Bed Reactor: A packed bed reactor is a type of chemical reactor that contains a fixed bed of solid catalyst particles through which reactants flow. This design is essential for various reactions, especially in biochemical processes and advanced mass transfer applications, as it provides a large surface area for reactions while allowing for effective heat and mass transfer. The configuration of these reactors can significantly influence reaction kinetics and overall reactor performance.
Pitched blade turbine: A pitched blade turbine is a type of mixing device commonly used in various types of reactors, particularly in biochemical processes, to enhance fluid mixing and improve mass transfer. This turbine features blades that are angled or pitched, allowing for better fluid dynamics and promoting effective mixing, which is crucial for reactions involving microorganisms or biochemical substances. The design of the blades helps to create flow patterns that are beneficial for the homogeneous distribution of reactants and the removal of products.
Reaction rate constant: The reaction rate constant, often represented as 'k', is a proportionality factor in the rate law that relates the rate of a chemical reaction to the concentration of the reactants. It provides insight into how quickly a reaction occurs under specific conditions, such as temperature and pressure, and is essential for understanding reaction kinetics in various chemical processes.
Rushton Turbine: A Rushton turbine is a type of impeller commonly used in biochemical reactors to promote mixing and facilitate gas-liquid interactions. It is characterized by its flat-blade design, which enhances liquid circulation and improves the transfer of oxygen to microorganisms in fermentation processes. The efficiency of the Rushton turbine makes it essential in applications such as bioprocessing and wastewater treatment.
Scale-up Considerations: Scale-up considerations refer to the factors and strategies involved in transitioning a biochemical process from a laboratory or pilot scale to full-scale production. This involves not only increasing the volume of reactants and products but also addressing challenges related to mixing, heat transfer, mass transfer, and the impact of changes in reaction kinetics at larger scales. Understanding these aspects is crucial for ensuring that the process remains efficient, cost-effective, and sustainable when scaled up.
Sparger: A sparger is a device used to introduce gas into a liquid, usually in the form of small bubbles. This process is crucial in various applications, particularly in biochemical reactor engineering, where it enhances gas-liquid mass transfer and promotes efficient mixing for microbial growth or biochemical reactions. By increasing the surface area for gas exchange, spargers play a vital role in optimizing the conditions for processes such as fermentation and aerobic respiration.
Specific Growth Rate: The specific growth rate is a measure of the increase in biomass or cell concentration of a microorganism per unit time, usually expressed as a rate constant. It is a crucial parameter in biochemical reactor engineering, as it helps in predicting how fast microorganisms will reproduce under specific conditions, which can affect the efficiency and productivity of bioprocesses.
Steady-State Analysis: Steady-state analysis is the examination of a system when its variables are constant over time, meaning that the input and output rates are equal, resulting in no accumulation within the system. This concept is crucial in understanding how biochemical reactors operate, as it allows for simplified modeling and control of reaction kinetics and mass transfer processes. By assuming steady conditions, engineers can predict performance and optimize reactor design without the complexities introduced by transient states.
Stirred Tank Bioreactor: A stirred tank bioreactor is a type of vessel used for the cultivation of microorganisms, cells, or enzymes, where mixing is achieved through mechanical agitation. This design promotes uniform distribution of nutrients and gases, which is essential for optimal growth and production in biochemical processes. The ability to control environmental conditions such as temperature, pH, and dissolved oxygen levels makes stirred tank bioreactors a widely used choice in both research and industrial applications for bioprocessing.
Substrate concentration: Substrate concentration refers to the amount of substrate present in a biochemical reaction, typically measured in moles per liter (M). It plays a critical role in determining the rate of enzymatic reactions and affects how efficiently microorganisms or enzymes convert substrates into products. Understanding substrate concentration is essential for optimizing conditions in biochemical reactors, as it directly influences reaction kinetics and yields.
Yield Coefficient: The yield coefficient is a critical parameter in biochemical reactor engineering that quantifies the efficiency of a microbial culture in converting substrates into biomass or products. This coefficient expresses the amount of biomass produced per unit of substrate consumed, providing insight into the metabolic performance of microorganisms during fermentation processes. Understanding this term is essential for optimizing bioprocesses and improving overall productivity in various applications, such as biofuel production and waste treatment.
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