INTRODUCTION

Kinetics: - The study of “REACTION RATE”

Model:– Represents Empirical* Objects,

Phenomena, and Physical Processes in
a Logical and Objective Way to
Construct A Formal System for which
Reality is the only Interpretation

Modelling:- The method of choice for obtaining

precise prediction
*based on observation or experience rather than theory or pure logic
▪ Bioprocess engineers frequently relied on modelling
to aid their understanding of the evolution in
biological systems during fermentation process.
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▪ Often, a biological theory will lead to mathematical

formulation, and the validity of this theory is tested
by comparing predicted responses with data from
actual experiments.
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▪ Accurate quantitative models, even for complex

biological systems will lead to rational design,
control, optimization and simulation* of the process.
▪ *imitation of a situation or process.
▪ The function of biological model is to describe
the metabolic reaction rates and their
stoichiometry on the basis of present and past
fermenter conditions

▪ The main difficulties for modelling are:

➢ To identify the most important factors that

influence the growth process,
➢ And finding a suitable model structure for
intracellular processes.
TWO TYPES OF KINETIC MODEL
STRUCTURED Takes into account the aspects of cell components such as
concentrations of metabolites, enzymes, lipids, and RNA.
Ideally, model should be able to imitate the cell physiology,
metabolism and cell generation.
The model is said to behave analogously to a cell changing its
composition when responding to perturbations in the
extracellular environment.

UNSTRUCTURED Simplistic takes on cell as a uniform quantity, without internal

dynamics (It considers no form of “structure” in the
protoplasmic mass) whose reaction rate depends ONLY upon
the conditions in the liquid phase of the reactor

Only Contain Kinetics of GROWTH, SUBSTRATE UPTAKE and

PRODUCT FORMATION
Adequate for Many Technological Purposes and are Sufficient
in Understanding Fermentation Processes.
MODEL VARIABLES
▪ Central to the development of any model, is the
definition of the components within biological
systems in terms of MACROSCOPIC VARIABLES, e.g.,

➢ Concentrations of chemical substances

➢ Amount of energy
➢ Temperature
MODEL VARIABLES
What is the
difference
between
intermediate
variables and
kinetic
parameters?

Kinetics
parameters
refer to
specific growth
rate, max spec
growth rate,
doubling time,
yield
coefficient etc.
MODEL VARIABLES
VARIABLES
State Variables:
Define the state of the process and there
is one for each extensive property, for
example
Operating Variables:
These are variables the values of which
can be set by the operator of the process,
for example
Intermediate Variables:
These are all the volumetric rates which
can all be expressed in terms of the state
variables listed above.
EXAMPLES
xv - Viable cell concentration;
xd - Non-viable cell
concentration;
S - Limiting substrate
concentration;
P - Product concentration.
D - dilution rate
F - volumetric feed flow rate
These are all the volumetric rates
rx, rd, rSx, rSm, rSp and rP, which can
all be expressed in terms of the
state variables listed above.
BALANCE EQUATION
▪ The basis of macroscopic description is the
balance equation.
▪ For each of ‘extensive quantity’, i.e. a quantity
which is additive with respect to parts of the
whole system, a balance equation (whether it is
mass or energy) can be derived, and its general
structure always takes on the form of:

Accumulation = Transport + Conversion

BALANCE EQUATION
▪ Here two types of mechanisms are distinguished by which
the total amount of an extensive quantity in the system can
vary;
➢ Transport towards the system
➢ Conversion as in transformation processes occurring in the
system.
▪ The balance equations result in the so-called state equations
of the model, which describes the TIME DEPENDENCE of the
state variables of the system.
GENERAL BALANCE EQUATION
For a well-mixed
fermenter,
Fi, Xi, Si, Pi
Xo = X
So = S
Po = P
F = bulk liquid flow (g/L.h)
V, X,
X = cell concentration (g/L) S, P
S = limiting substrate conc. (g/L)
Fo, Xo, So, Po
P = product conc. (g/L)
V = volume of liquid medium (L)
R ate of accumulation = R ate of input - R ate of output

1. Biomass balance: rx = rate of cell growth

(g/L.h)
d(VX)/dt) = FiXi + rXV – FoX – Vrd (1) rs = rate of limiting
substrate consumption
2. Substrate balance: (g/L.h)
rp = rate of product formation
d(VS)/dt = Fi Si – VrS –FoS (2) (g/L.h)
rd = Rate of death or
3. Product balance: deactivation of cells
(g/L.h)
d(VP)/dt = Fi Pi +Vrp –FoP (3)
i and o = inlet and outlet
4. Overall balance for volume change: conditions

dV/dt = Fi –Fo (4)

With the mass balance equations, different
kind of processes can be described:

a) Batch:
Fi = Fo = 0, V = constant
b) Fed-batch:
Fi 0, Fo = 0, V constant
c) Continuous:
D.V= Fi =F o 0, V = constant
(D = dilution rate, h-1)
KINETIC MODELS
▪ In terms microbial culture inside a fermenter,
complementing the balance models are related
kinetic equations for:
➢ Rates of cell growth or death,
➢ Substrate consumption
➢ Product formation
➢ Equations representing rates of heat and mass transfer
➢ Equations representing system property changes
➢ Equilibrium relationships
➢ and also process control
MODELLING PROCEDURES
▪ Combination of these relationships provides a basis
for the quantitative description of the process and
made up of basic mathematical model (can be only
few equations to very complex)
▪ Modelling Procedures (Fig 1):
❖ Properly define of the bioprocess
❖ Available theory must then be expressed in mathematical
terms
❖ Having develop a model, the equations are to be solved
❖ The computer prediction must be checked and if necessary
the model is to be revised
 ▪ Once working model is established, it
can be used with reasonable
confidence to characterize
performance of fermentation under
different conditions, by assigning
numerical values to important process
parameters.
▪ Model can be resolved using
appropriate numerical computation
method
▪ Predictions are again compared with
the actual practical results. This
procedure is known as SIMULATION
▪ Simulation may be used to confirm that
appropriate parameter values are
“correct”.
▪ Simulation can also be used to test
probable behavior through variation of
process conditions.
▪ This will lead to model being used for
process optimization, and in advanced
control strategies.
What is the difference between physical and
mathematical model?
 MODEL COMPUTATION
▪ Many software available to tackle parametric estimation problems that are
commonly encountered in fermentation processes.

▪ Unknown values of process variables are usually resolved through regression

analysis (i.e., a statistical process for estimating the relationships among
variables).

▪ Regression analysis is considered a classic subject in applied math where 3

formal problems or analyses; parametric estimation, regression, and
correlation are interrelated.

▪ Regression is usually curve-fitting procedure consists of selecting a

mathematical model, in this case the working process model, and then
applying parametric estimation to determine the unknown coefficients.

▪ Prior to performing a straightforward curve-fitting, users must first need to

reduce the kinetic equations of the biological process (usually as differential
equation) to linear algebraic model. It is normal both algebraic regression and
(ordinary or partial) differential regression models exist in problems
pertaining to bioprocess technology.
MODEL COMPUTATION
▪ Widely available solver for simple models = MS EXCEL
▪ Professional Graphing Software with Customized
Regression Wizard, e.g.
❖ Graph Pad Prism
❖ SigmaPlot with Enzyme Kinetic Module (Systat)
❖ Curve Expert

▪ MATLAB or FREEMAT (free of charge)

▪ Dynamic Modeler –
❖ Berkeley Madonna
❖ European Simulation Language (ESL)