Advanced Principles of Chemical Engineering

CE30240
Prof Mirella Di Lorenzo – M.Di.Lorenzo@bath.ac.uk

A recap on cellular reactions and Bioreactor Modelling

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 Discussion Points

• What is a Bioprocess?
• Upstream Bioprocessing
• Downstream Bioprocessing

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 Aims of this part of the course:
• To provide an understanding of the various biological
reactor and separation process strategies that can be
employed to produce biochemicals in a controllable
and predictable process through the exploitation of
bacteria, yeast and higher organisms.
• To introduce the main unit operations used in the
separation of materials of biological origin.
• To provide an understanding of the role of each
operation within a multi-unit process and how this is
influenced by the properties of the process stream.

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 Introduction – Why bioprocesses?
• In a bioprocess, living organisms (or part of them, e,g,
enzymes) are used to produce commercial products
• Cells can perform certain types of chemistry better
than anything else.
• They can conduct multistep syntheses and conversions
with very high selectivity
• They can synthesise complex organic chemicals, e.g. L-
amino acids, antibiotics.
• They are the premier synthesis machines for proteins.

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The diverse biochemical process industry
PRODUCTS BELONG TO MULTIPLE CLASSES
• Small Molecules
• Proteins
• Nucleic Acids
• Carbohydrates
• Catabolites & Anabolites
• Cells and Viruses
PRODUCTS & PROCESSES REGULATED
• FDA (Food & Drug Administration), EMEA (European
Medicines Agency)
• EPA (Environmental Protection Act)
• OSHA (Occupational Safety & Health Administration)

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 Fermentation products
Small molecules Macromolecules
▪ organic acids (citric, lactic) ▪ peptides (insulin)
▪ amino acids (lysine, ▪ enzymes (amylases,
proteases)
phenylalanine)
▪ polysaccharides (dextran,
▪ antibiotics (pencillins, xanthan)
cephalosporin) ▪ therapeutic proteins (inteferons)
▪ organic non-acids (ethanol, ▪ vaccines (foot and mouth,
butanol) hepatitis)
▪ vitamins
Complex products
Cellular material ▪ alcoholic beverages
▪ yeast (baking, brewing) ▪ fermented foods
▪ Mammalian cells (tissue engineering)

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 Worldwide industrial biotech market

J.A. Kent et al. (eds.), Handbook of Industrial Chemistry and

Biotechnology, DOI 10.1007/978-3-319-52287-6_27

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Chemical and Biochemical engineers
are powerful!
• We can manipulate life at its most basic level: the genetic!
• We now have a tool to probe the mysteries of life in a way
unimaginable 30 years ago.
• New visions and new hopes emerge: personalised therapies;
synthetic organs; nutritious food; superorganisms to degrade
pollutants; a wide range of consumer products and industrial
processes.
• Engineers play a key role in converting these visions into reality:
biological systems are very complex but they obey the rules of
chemistry and physics and they are susceptible to engineering
analysis

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 Discussion Points

Whole cell systems

• What is the goal of upstream

bioprocessing?
• What do we need to consider to model a
bioreactor

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 Going up in scale… Production of α-1-antitrypsin
From bench or lab scale to pilot scale. for treatment of cystic fibrosis

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 Larger scale production fermenter
train – these examples from China.

Production bioreactors for making

glutamic acid – the precursor for
mono-sodium glutamate (MSG).
Each bioreactor has a working
volume of 250,000 litres. They are
about 30 metres tall. You can find
bioreactors up to 500,000 litres.
Bioreactors for industrial bioethanol
production are of similar scale.
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 Bristol Waste Water Treatment Works - Avonmouth, UK
Handing waste from about 1 million people.
Photo courtesy of Wessex Water.

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 Cellular reactions
• For microbes growth is a result of physicochemical
processes.
• Bacterial growth is a complex process involving
numerous anabolic (synthesis of cell constituents and
metabolite) and catabolic (breakdown of cell
constituents and metabolites) reactions
• Microorganisms can grow under a variety of physical,
chemical and nutritional conditions.
• Organisms extract nutrients partly for energy
production and partly for biosynthesis and product
formation

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 Cellular reactions
Cells are considered as large source of
enzymes: there is analogy in both these
catalysts

X+S nX + mP
cell + reactant More cell + product (including energy)

The rate of growth is directly related to cell

concentration and cellular production is an
outcome of this reaction

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 Cellular reactions
Cellular reactions are considered in a similar fashion
like enzymatic reactions by Monod’s equation
 max S
=
(K S + S ) (1)

Where:
1 𝑑𝑋
µ= specific growth rate (time-1) 𝜇= (2)
𝑋 𝑑𝑡
µmax= maximum specific growth rate (time-1)
Ks= Monod’s constant (wt/vol)
S= reactant/substrate concentration (wt/vol)

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 Effect of substrate concentration
on growth: Monod’s model

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 Double reciprocal plot

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 Cell Yield
• The Monod equation can also be expressed as a function of substrate
utilisation given that growth is related to substrate utilisation by a
constant called the cell yield:

𝑑𝑺 𝟏 𝑑𝑿 (3)
=
𝑑𝒕 𝒀 𝑑𝒕
• Where: Y is the cell yield (mass/mass), defined as the unit amount of
cell mass produced per unit amount of substrate consumed.
• The more efficiently a substrate is degraded the higher the value of Y
• Y depends on both the structure of the substrate being utilised and
the intrinsic physiological properties of the degrading microorganism.
• By combining equations 1 and 3, we can express microbial growth in
terms of substrate disappearance:

𝑑𝑺 𝟏 𝜇𝑚𝑎𝑥 𝑆𝑿
=−
𝑑𝒕 𝒀 𝑲𝒔 + 𝑆 (4)
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 Typical growth curve for a batch
system
𝑑𝑋
=0
𝑑𝑡

𝑑𝑋
= 𝜇𝑋
𝑑𝑡

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Generalised bioreactor mass balancing:
Gi Go Co

Fi Si C Fo So Xo Po

V X
S P

X = biomass concentration (g L-1) V = volume (L)

S = substrate concentration (g L-1) F = liquid flow (L h-1)
P = product concentration (g L-1) G = gas flow (L h-1)
C = CO2 concentration (g L-1) Subscripts: i = in, o = out

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 Kinetics and yields:
There are other forms of
 max S
Kinetics: = kinetic model, including cell
(K S + S ) death rates, and also
substrate or product
Biomass formation: rX =  X inhibition.
X Y(X/S) = biomass produced /
Substrate consumption: rS =
Y( X / S ) substrate consumed
 X Y( P / S ) Y(P/S) = product produced /
Product formation: rP =
Y( X / S ) substrate consumed

 X Y( C / S ) Y(C/S) = CO2 produced /

CO2 formation: rC =
Y( X / S ) substrate consumed

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 Reading
• There is no single text book for this course,
reading will be suggested as appropriate.
• Key references:
– P M Doran, Bioprocess Engineering Principles,
Academic Press, 1995
– Shuler & Kargi, Bioprocess Engineering – Basic
Concepts, 2nd Edition, Prentice Hall, 2002
– Blanch & Clark, Biochemical Engineering, CRC Taylor
& Francis, 1997
• Check also suggested reading by MDL on
Moodle

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