BPE-12806 Bioprocess Engineering Basics
All relevant information for every lecture are given online on blackboard. The last lecture is
not included, because the theory of the book and the lecture did not match. This is a
summary of the given information on blackboard per lecture. The chapters are from the
book Bioprocess Engineering Principles, by Pauline M. Doran, second edition.
Contents
Lecture 1 ..................................................................................................................................... 1
Chapter 3 Presentation and Analysis of Data ....................................................................... 1
Chapter 11 Unit Operations ................................................................................................ 1
Lecture 2 ..................................................................................................................................... 6
Chapter 4 Material balances ................................................................................................. 6
Lecture 3 ..................................................................................................................................... 9
Chapter 2 Introduction to Engineering Calculations............................................................. 9
Chapter 3 Presentation and Analysis of Data ..................................................................... 10
Lecture 4 ................................................................................................................................... 11
Chapter 5 Energy Balances.................................................................................................. 11
Lecture 5 ................................................................................................................................... 15
Chapter 12 Homogeneous Reactions ................................................................................ 15
Chapter 14 Reactor Engineering ....................................................................................... 20
Lecture 6 ................................................................................................................................... 21
Chapter 9 Heat transfer ...................................................................................................... 21
Lecture 1
Chapter 3 Presentation and Analysis of Data
Flow diagrams or flow sheets are simplified pictorial representations of processes used to
present relevant process information and data.
When flow diagrams are applied in calculations, the operating conditions, masses, and
concentrations of material handled by the process are also specified.
Detailed engineering flow sheets are useful for plant construction work and troubleshooting
because they show all piping, valves, drains, pumps, and safety equipment. Standard
symbols are adopted to convey the information as concisely as possible.
Chapter 11 Unit Operations
In a typical fermentation process, raw materials are altered most significantly by the
reactions occurring in the fermenter. However, physical changes before and after
fermentation are also important to prepare the substrates for reaction and to extract and
purify the desired product from the culture broth.
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,In fermentation broths, the desired product is present within a complex mixture of many
components. Any treatment of the culture broth after fermentation to concentrate and
purify the product is known as downstream processing. In most cases, downstream
processing only requires physical modification of the broth material.
Although each recovery scheme will be different, the sequence of steps in downstream
processing can be generalised:
1. Cell removal: the removal of cells from the fermentation liquor. Filtration,
microfiltration, and centrifugation are typical unit operations for cell removal.
2. Cell disruption and cell debris removal: these downstream processing steps are
required when the product is located inside the cells. Unit operations are used to
break open the cells and release their contents for subsequent purification.
3. Primary isolation: a wide variety of techniques is available for primary isolation. The
aim of primary isolation is to remove components with properties that are
substantially different from those of the product. Typically, processes for primary
isolation are relatively nonselective, however significant increases in product quality
and concentration can be accomplished.
Solvent extraction, aqueous two-phase liquid extraction, adsorption, precipitation,
and ultrafiltration are used for primary isolation.
Large volumes of culture liquid must be treated at this stage. As intermediate storage
of this liquid is impractical and disposal expensive, the processes and equipment
used for primary isolation must be robust and reliable. A desirable feature of primary
isolation processes is that a significant reduction in liquid volume is achieved. This
reduces the equipment size and operating costs.
4. Product enrichment: these processes are highly selective and are designed to
separate the product from impurities with properties close to those of the product.
Chromatography is a typical unit operation at this stage.
5. Final isolation: at this stage, the product reaches its final purity. Typical operations
for liquid products is ultrafiltration, and for solid products crystallisation followed by
centrifugation or filtration and drying.
The performance of downstream processing operations can be characterised quantitatively
using 2 parameters: the concentration factor and the separation factor .
[𝑝𝑟𝑜𝑑𝑢𝑐𝑡]𝑎𝑓𝑡𝑒𝑟 𝑡𝑟𝑒𝑎𝑡𝑚𝑒𝑛𝑡
𝛿=
[𝑝𝑟𝑜𝑑𝑢𝑐𝑡]𝑏𝑒𝑓𝑜𝑟𝑒 𝑡𝑟𝑒𝑎𝑡𝑚𝑒𝑛𝑡
[𝑝𝑟𝑜𝑑𝑢𝑐𝑡]
( ) 𝑎𝑓𝑡𝑒𝑟 𝑡𝑟𝑒𝑎𝑡𝑚𝑒𝑛𝑡
[𝑐𝑜𝑛𝑡𝑎𝑚𝑖𝑛𝑎𝑛𝑡]
𝛼=
[𝑝𝑟𝑜𝑑𝑢𝑐𝑡]
( ) 𝑏𝑒𝑓𝑜𝑟𝑒 𝑡𝑟𝑒𝑎𝑡𝑚𝑒𝑛𝑡
[𝑐𝑜𝑛𝑡𝑎𝑚𝑖𝑛𝑎𝑛𝑡]
A concentration factor of > 1 indicates that the product is enriched during the treatment
process. The separation factor represents the change in product concentration relative to
that of some key contaminating compound.
Individual downstream processing operations may achieve high concentration factors even
though separation remains relatively poor, and vice versa.
Some downstream processing operations cost more than others. More expensive operations
lead to more expensive product. Generally, the higher the starting concentration, the
cheaper is the final material.
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, One of the first steps in downstream processing is the removal of cells from the culture
liquid. The major process options for cell removal are filtration, microfiltration, and
centrifugation. Filtration and microfiltration are based on particle size, centrifugation relies
on particle density.
Cell removal from microbial fermentation can be very challenging. Prior to filtration or
centrifugation, it may be necessary to pretreat or precondition the fermentation broth to
improve the efficiency of cell separation. Heating is used to denature proteins and enhance
the filterability of mycelial broths. Pretreatments that reduce the viscosity of the broth are
beneficial for both filtration and centrifugation. Filter aids, which are solid particles used to
increase the speed of filtration, are often applied to fermentation broths prior to filtering.
The general features of unit operations used for cell removal are described here:
• Filtration: cell solids are retained on a filter cloth to form a porous cake while liquid
filtrate passes through the cloth. However, the liquid filtrate usually contains a small
proportion of solids that escape through the filter cloth. This is reflected in the
filtrate clarity. On a large scale, filtration isn’t the best option because more of the
cells will escape through the filter cloth.
• Microfiltration: microfiltration uses microporous membranes and cross-flow filtration
methods to recover the cells as a fluid concentrate. Microfiltration is an attractive
option for harvesting cells containing intracellular products or cells as product. Cell
recovery using microfiltration is typically close to 100%. In many cases, microfiltration
is less expensive than filtration or centrifugation.
• Centrifugation: this can be an effective strategy for cell recovery when the cells are
too small and difficult to filter using conventional filtration. Centrifugation is suitable
for recovery of cells as product and for preprocessing of both intracellular and extra-
cellular components. Centrifugation of fermentation broths produces a thick,
concentrated cell sludge or cream that contains mare extracellular liquid than is
produced in conventional filtration.
• Other operations: there are also other methods available:
o Gravity settling or sedimentation is suitable for cells that form aggregates or
flocs of sufficient size and density to settle quickly under gravity.
o Foam flotation relies on the selective adsorption or attachment of cells to gas
bubbles rising through liquid. The cells are recovered by skimming foam layers
that collect on top of the liquid.
Decisions about which type of cell removal operation to use for a particular application are
usually made after a considerable amount of experimental testing.
Filtration: solid particles are separated from a fluid-solid mixture by forcing the fluid through
a filter medium or filter cloth that retains the particles. Filtration can be performed using
either vacuum or positive-pressure equipment. The pressure difference exerted across the
filter to separate fluid from the solids is called the filtration pressure drop.
Most microbial filter cakes are compressible: the porosity of the cake declines as the
pressure drop across the filter increases. This can cause reduced filtration rates and product
loss.
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