2 Biochemical ReactorA device in which living cells or enzyme systems are used to promote biochemical transformation of matterUses:pharmaceutical industriesChemical industryWaste treatmentBiomedical applications
3 2 types:Microbial fermenter- cell growth is used to produce metabolites, biomass, transformed substrates, or purified solventsEnzyme reactors (cell free)- immobilized enzymes often used for fluid-fluid and solid-fluid contractors
4 Designing a bioreactor: The coupled set of mass balance equations which describe the conversion of reactants to productsEx: Substrate S is converted to cells (X) and Product (P).Growth of cells… (dX/dT)V = (rx) ( V)Consumption of substrate… (dS/dT)V = (rs)(V)Product formation… (dP/dT)V = (rp)(V)
5 Constitutive Rate Expressions for Biological Processes Model of Microbial GrowthSegregated- cells are different from one anotherNon-segregated models lump the population into one biophase interacting with external environment and is one species in solution; they are mathematically simpleExternal environment influences cell response and can confer new growth characteristics on the cell
6 Unstructured Growth Models Simple relationships that describe exponential growthKinetics of cell growth are described using cell and nutrient concentration profilesMalthus’s simple model: rx = µX where rx is the increase in dry cell weight and µ(hr-1) is a constant.dX/dt = kX(1-βX) was proposed as a cell concentration-dependent inhibition term by Verhulst, Pearl, and Reed.
7 Monod ModelDeveloped by Jaques Monod, exemplifies the effect of nutrient concentration based on E. coli growth are various sucrose concentrations and assumes only the limiting substrate is important in determining the rate of cell proliferation
8 For the Monod Model Cell growth might follow the form rx = µX = µmaxSX/Ks + Sand batch growth at constant volumedX/dt = µmaxSX/Ks + Sµmax is max specific growth rate of cellsKs is value of the limiting nutrient concentrationTwo limiting forms:At high substrate concentrations S>>Ks, µ= µmaxAt low substrate concentrations S<<Ks, µ= µmax/KsS
9 Models of Growth and Non-growth Associated Product Formation Primary metabolites- growth associated; rate of production parallels growth of cell population; Ex: gluconic acidSecondary metabolites- non-growth associated; kinetics do not depend on culture growth rate; Ex: antibiotics, vitaminsIntermediate products- partially growth associated; Ex: amino acids, lactic acid
10 Mass transfer in Bioreactors Possible resistances:In a gas filmAt the gas-liquid interfaceIn a liquid at the gas-liquid interfaceIn the bulk liquidIn a liquid film surrounding the solidAt the liquid-solid interfaceIn the solid phase containing the cellsAt the sites of biochemical reactions
11 Definition of Mass Transfer Coefficient Relates transfer rates to concentration terms and is defined as a mass balance for a certain reactant or product species in the reactor…Na = kLa(Ci x g – CL)Na= Oxygen transfer rate (through the air bubbles)CL = local dissolved oxygen concentration in bulk liquid at any timeCg= oxygen concentration in the liquid at the gas- liquid interface at infinite timea= interfacial areakL= local liquid phase mass transfer coefficient
12 Bioreactor types and modes Bubble ColumnsSystems with Stationary InternalsThe above take on this correlation:KLa = constant Vnswhere n is in the range in the bubble flow regimeStirred-Tank Reactorsuses this correlation: KLa = (Pg/V)n (VSr)
13 Power Requirements Air-lift Systems Agitated Un-gassed Systems The power input through a reactor can be high in larger reactorsThe power input is estimated as: Pg = GRT ln (P1/P0)Agitated Un-gassed SystemsIn the turbulent flow regime, P ~ ρn3D5In the laminar flow regime, P ~ 1/Re P ~ µN2D3where P is proportional to viscosity but independent of densityGassed SystemsPower required is less than un-gassed with reduction Pg/P given as PgP = f(NA)
14 Scale-Up Scale-up methods based on… Fixed power input Fixed mixing timeFixed oxygen transfer coefficientFixed environmentFixed impeller tip speed
15 Scale-up at fixed KLaIt may be impossible to maintain equal volumetric gas flow rates since the linear velocity through the vessel will increase differently with the scaleIt may be possible to decrease the volume of gas per volume of liquid per minute on scale-up while increasing power input by changing reactor geometry and power input per unit volume
16 Scale-up on Flow Basis which becomes: N2 = N1 = (V2/V1)1/3(D1/D2)5/3 Design based on constant input of agitator power per unit reactor volume : P1/V1 = P2/V2For constant power input in vessels that are geometrically similarρN31D51/V1 = ρN32D52/V2which becomes: N2 = N1 = (V2/V1)1/3(D1/D2)5/3
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