Bioprocess basic principles ppt.ppt

BIOPROCESS
PRINCIPLES
Unit Operations in
Upstream& DownstreamProcessing

August 29, 2022 Unit Operation in a Bioprocess
(Upstream & Downstream)
Definition
These “fundamental” operations are what are
called “unit operations”.
Chemical and Bioprocess Industries
consist of widely varying sequences of
steps that have different combinations
for different manufacturing cycles.
What is a Unit operation?
However these widely varying steps can be reduced or broken down
to simple operations which are identical in fundamentals regardless
of the material being processed.

Historical Definition
 This definition was used by A.D Little in 1915 to
describe Unit Operations.
 “Unit operations deal mainly with the transfer of
energy and the transfer and change of materials
primarily by physical means”.
 What is a Unit Process?

Different Unit Operations
 Drying
 Distillation
 Adsorption
 Membrane separation
 Leaching
 Sedimentation
 Mixing
 Liquid Liquid Extraction
 Absorption
TRANSPORT PHENOMENA
 Momentum Transfer
 Fluid Flow
 Sedimenation
 Mixing
 Heat Transfer
 Drying
 Evaporaytion (SHMT)
 Distillation
 Mass Tranfer
 Absorption
 Adsorptin
 Distillation

Stages of a Bioprocess
 A biotechnical process to produce a product can be
subdivided into five successive major segments, with
some overlap:
• upstream processing
• fermentation
• downstream processing
• product finishing
• treatment of waste if any

Stages of a Traditional
Bioprocess

Stages of a Bioprocess (Details)
 Preparation of sterile medium.
 Addition (inoculation) of microbe ( pure culture) into this
medium
 Cultivation (incubation) under controlled conditions
 Sterilising fermentation apparatus and preparing and
sterilising feed streams to the fermentor
FERMENTATION
 Isolation and purification of the product from the fermented
medium
 Packaging of the product
 Treatment of the waste products if any

Unit Operations in a Bioprocess

Upstream Processing
“Pure Upstream processing” has essentially
three functions:
 Growth of a pure culture of microorganisms in one
or more steps its scale up and strain development.
 Sterilization of the apparatus and piping.
 Mixing and sterilizing the necessary raw materials
and fermentation media to be supplied to the
fermentation unit.

Fermentation Stage
 Sometimes considered as an Upstream process while some
bioprocess engineers consider it as a separate Stage in itself.
Never considered as a downstream processing stage
 Actual fermentation is commonly a batch or fed batch
process in a stirred tank fermentor.
 It lasts from a few hours to several days.
 The optimal conditions for growth of the organisms and
production of the product are established. Those include
temperature, pH, sterile aeration and, in fed-batch processes,
continuous addition of substrate at its optimal composition.

SCALE UP (DEFINITION)
 Shake flash Experiments
 Lab scale fermentor (5-10 L)
 Pilot scale fermentor (300-3000 L)
 Commercial fermentor (10,000-500,000 L)
•Scale up: The transfer of a process from small-scale
laboratory equipment to large-scale commercial
equipment

lab flask
(100 mL)
lab-scale
fermentor
(1–10 L)
pilot plant
scale
(300-3000 L)
commercial scale
(10,000-500,000 L)
Scale up

Industrial Scale up

Industrial Fermentation Setting

Fermentor sizes for various purposes

Some problems in Scale up
 Oxygen transfer is much more difficult to obtain in
large-scale
 Mixing and aeration more easily accomplished in
small volumes
 Methods of temperature control must change with
scale-up
 Sterilization protocols must change with scale-up
 Bioprocess Engineers required with Chemical
Engineering skills: adept in gas and mass transfer,
fluid dynamics, mixing, thermodynamics

Downstream processing
 Downstream processing (DSP) encompasses all processes
following the fermentation.
 In “downstream processing”, the fermentor is emptied after
the fermentation is complete. The microorganisms are killed
and, if necessary, removed by ultrafiltration. The liquor may
be concentrated by evaporation. If necessary, the active
ingredient may be isolated by a suitable separation process
such as crystallization, ion-exchanging or chromatography.
The subsequent product finishing is intended to transform
the product into the desired marketable form, e. g., into a dry
pourable granulation. That is accomplished by classical
drying and granulation processes.

Unit Operations in
Down Stream Processing
Pre- treatment
Solid /liquid
Separation
Concentration
Purification
Formulation
Cell disruption
Stabilization
Sterilization
Pasteurization
Flocculation
Filtration
Sedimentaion
Centrifugation
Membranes
Precipitation
Evaporation
Extraction
Freeze Concentration
Precipitation
Extraction
Diafilteration
Adsorption
Chromatography
Drying
Prilling
Extrusion
Granulation
Tabletting

Relationship (between cost and
and fermentation concentration)

Separation Range of
Downstream Unit Operations

Product Quality Profile
(during Downstream Processing Stages)

Differences
Upstream Processing Downstream processing
Live Organisms No organisms
Large Volume Progressively Less Volume
Many Components Progressively less
components
Heterogeneous mixture Homogenous Mixture
Fewer Operations Many Operations
Lower Cost materials Higher Cost materials

Downstream Processing
 Downstream Processing begins upstream…why?
 A “holistic” approach to DSP is required and the
entire process as a whole should be considered. The
economic use of cheap industrial fermentation
sources could cause interactions that could increase
downstream processing difficulty and cost.. Hence a
balance should be sought in the whole process
which should be done by the Bioprocess Engineer.

Research Areas in Upstream
processing
 Research areas in upstream processing being carried out today
 Testing, modeling, optimization, control of novel or
improved recombinant and non-recombinant cell cultures
 New biochemical reactors, and new biological processes to
produce useful and high value products.
 Basic genome and proteome based biomolecular engineering
studies that lead to improved design and performance of
fermentation and cell culture processes.
 By using on-line and real time sensing and monitoring
techniques and high throughput analytical techniques
 Quantitative assessment of biomolecular rate processes
inside a cell toward increasing aeration and transfer rates

Research Areas in
Downstream processing
 The capability to purify bioproducts in a cost-effective
manner on a commercial scale and to meet the required high
purity specification for the medical grade bioproducts is an
important technical goal of R & D.
 Research in areas as posttranslational protein processing,
protein refolding, protein purification techniques, membrane
technology,
 Various types of chromatography including bioaffinity
systems, separation techniques using combined force fields,
and filtration methods.

Bioprocess basic principles ppt.ppt

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Bioprocess basic principles ppt.ppt