𝑑𝑋
=µ∙𝑋
𝑑𝑡
𝑙𝑛 2
µ
𝑞𝑆
𝑐𝑠
𝑛
𝑐𝑠 + 𝑘𝑠
𝑞𝑃
𝐴 = 𝑙 ∙ ෍ 𝜀𝑖 ∙ 𝑐𝑖
max 𝑓 𝑥
𝑖=1 𝑦 = 𝑚 ∙ 𝑥 + 𝑛
∆𝑡
𝑐𝑃
𝑘𝐿 𝑎
Dr. Donya Kamravamanesh. MSc.
€
𝐷=µ
Bioprocess Technology II -CHEM-E3140
𝑞𝑠 = 𝑞𝑠,𝑚𝑎𝑥 ∙
𝑡𝑑 =
µ
𝑢(𝑡)
Introduction to the Course
Bioprocess Technology II-CHE-E3140
𝑛
About me: Donya Kamravamanesh
•
Born in 1985
•
Studied Biochemistry and Biotechnology and Bioprocess technology
❖ Diploma thesis: “Production of recombinant protein disulfide isomerase in E.coli”
•
Researcher and Project assistant at the Technical University of Vienna
❖ Bioprocess development for biological industrial wastewater treatment
❖ Bioprocess analytics for improving production of penicillin
•
PhD studies at the Technical University of Vienna
❖ PhD thesis: ”A quantitative, time-resolved approach to bioprocess understanding for economic production of
biopolymer polyhydroxyalkanoates.”
•
Postdoctoral research fellow at Tampere University
• University Lecturer at Aalto
Tehran (1985-2003)
Pune (2003-2012)
Vienna (2013-2019)
Tampere (2019-2022)
Bioprocess Technology II-Donya Kamravamanesh
Aalto (2023-?)
2
Introduce yourself
Bioprocess Technology II-Donya Kamravamanesh
3
Prerequisites and study material
❖ Bioprocess technology I (CHEM-C2310)
❖ Advanced mathematics knowledge
❖ Enzymatic reactions
❖ Principle of aerobic and anaerobic metabolism
❖ Microbiology (CHEM-E3120)
❖ Thermodynamics
❖ Biochemistry knowledge (CHEM-E1300)
Shuler et al. Bioprocess Engineering Basic Concepts
- Part 3 (page 61-103)- Enzymes, Part 5 (page 145-165)- Major metabolic pathways
- Part 6 (page 113-139)- Cell growth, Part 7 (page 227-242)- Microbial stoichiometry
Doran 2nd Edition, Bioprocess Engineering principles
• Study the following chapters: 8 (pages 255-311), 9 (pages 333-353), 10 (pages 393-427),
11 (parts 11.3, 11.4, 11.5, 11.10, 11.11, 11.12), 12 (pages 632-659), and 14 (pages 790-810)
Bioprocess Technology II-Donya Kamravamanesh
4
Intended Learning Outcome
After the completion of this course, the students can
❖ …explain the principles of bioreactor set-up in batch, fed-batch, and chemostat modes
❖ …solve the bioprocess engineering problems both on the laboratory scale as well as on
the industrial scale
❖ …design and set up bioprocesses in batch, fed-batch, and chemostat modes
❖ …apply the engineering principles to design sustainable bioprocesses for a circular
bioeconomy
❖ …modify existing bioprocesses to improve productivity and sustainability
❖ …identify and evaluate various downstream processing techniques and scale up such a
process for commercial applications
Bioprocess Technology II-Donya Kamravamanesh
5
Material and sources
❑ Doran, Bioprocess Engineering Principles, 2nd Edition, Academic
Press
❑ Stanbury et al., Principles of Fermentation Technology, 3rd
Edition, Butterworth-Heinemann
❑ Shuler et al., Bioprocess Engineering Basic Concepts, 2nd/3rd
Edition, Prentice Hall PTR
❑ Bailey et al., Bioprocess Engineering Fundamentals, 2nd Edition,
McGraw-Hill Chemical Engineering Series
❑ Illanes et al., Problem Solving in Enzyme Biocatalysis, John Wiley
& Sons Ltd
Bioprocess Technology II-Donya Kamravamanesh
6
Course Content
•
•
•
•
•
•
•
•
Bioprocess engineering objectives for design
Bioreactor configuration
Model industrial-scale bioprocesses
Sustainable bioprocessing
Microbial growth and production kinetics in batch, fed-batch, and chemostat
Bioprocess scale-up and considerations
Design and control of bioprocesses
Downstream processing and scale-up of unit operations
Bioprocess Technology II-Donya Kamravamanesh
7
Workload and Evaluation
•
•
•
•
•
5 Cr = 135 h workload (1 Cr ~ 27h)
Lectures ~16h
Calculation exercises sessions ~12h
Individual calculation exercise activities and quizzes ~ 40h
Independent study → The rest is independent studies, learning diaries, etc.
Final grade (100%)
Learning diary and
viva voce (30%)
Quizzes (15%)
Calculation
Exercises (25%)
Bioprocess Technology II-Donya Kamravamanesh
Written exam
(30%)
8
Calculation exercises and quizzes
•
•
•
•
•
After each lecture, a calculation exercise and a quiz will be open on MyCourses.
Check the deadlines in the timetable
The quizzes are 15% of the final grade
Calculation exercises are 25% of the final grade
Shortly after the deadline a recorded session on calculation exercises problem solving and
answers will be available in MyCourses.
• Check the recorded video if everything is clear then you don’t need to attend the
Calculation exercise sessions, if you have any doubts then we can meet in the calculation
exercise sessions to answer your questions, etc.
• Evaluation criteria- Students' approach toward problem-solving will be evaluated. You
can decide on any technique to address the problem, however, a logical justification
should be provided.
Bioprocess Technology II-Donya Kamravamanesh
9
Learning diary and Viva voce
• Learning diaries are your take on different topics taught during the course, they are not
your lecture notes but a summary of what you learned during a session. (Not more than
one page per session)
• The viva voce is an oral examination of your learning diary and might include plotting
and simple calculations
• We will discuss your learning diary in the form of question and answer during an oral
examination.
• Book a time for your Viva voce in advance, the time sloths will be available on the
MyCourses page.
Bioprocess Technology II-Donya Kamravamanesh
10
Written examination
• Choose 3 from 5 questions
• Questions are based on the content taught during calculation exercise sessions
and lectures.
Evaluation criteria- Students' approach toward problem-solving will be
evaluated. You can decide on any technique to address the problem, however, a
logical justification should be provided. The same applies to problem-solving in
calculation exercises.
Bioprocess Technology II-Donya Kamravamanesh
11
Timetable for Bioprocess Technology-II (CHEM-E3140)
Lecture and date
Outline
Deadline for
calculation
exercises and
respective quiz
Calculation exercise
session
Pre-exercise
(recorded lecture)
Material balancing, kinetics of
growth and stoichiometry
23.10.2023
26.10.2023
(10:15-12:00)
Lecture 1- 24.10.2023
(08:15-10:00)
Mixing in bioreactors
31.10.2023
02.11.2023
(10:15-12:00)
Lecture 2- 27.10.2023
(12:15-14:00)
Scale-up of bioprocesses
07.11.2023
09.11.2023
(10:15-12:00)
Lecture 3- 02.11.2023
(08:15-10:00)
Batch, fed-batch and chemostat
operation
12.11.2023
14.11.2023
(15:15-17:00)
Lecture 4- 09.11.2023
(08:15-10:00)
Downstream processing scaleup I
17.11.2023
23.11.2023
(08:15-10:00)
Lecture 5- 13.11.2023
(08:15-10:00)
Downstream processing scaleup II
22.11.2023
28.11.2023
(14:15-16:00)
Lecture 6- 20.11.2023
Lecture 7- 21.11.2023
(08:15-10:00)
Industrial applications of
bioprocessing (2 lectures)
28.11.2023
30.11.2023
(10:15-12:00)
Lecture 8- 30.11.2023
(08:15-10:00)
From single cell to a process
----
----
Exam 7.12.2023 (09:00-13:00)
•
•
The location for the lectures is Ke3 - A302 – Chemical Engineering
Calculation Exercises are either in Ke3 or Ke4– Chemical Engineering
Bioprocess Technology II-Donya Kamravamanesh
12
𝑑𝑋
=µ∙𝑋
𝑑𝑡
𝑙𝑛 2
µ
𝑞𝑆
𝑐𝑠
𝑛
𝑐𝑠 + 𝑘𝑠
𝑞𝑃
𝐴 = 𝑙 ∙ ෍ 𝜀𝑖 ∙ 𝑐𝑖
max 𝑓 𝑥
𝑖=1 𝑦 = 𝑚 ∙ 𝑥 + 𝑛
∆𝑡
𝑐𝑃
𝑘𝐿 𝑎
Dr. Donya Kamravamanesh. MSc.
€
𝐷=µ
Bioprocess Technology II -CHEM-E3140
𝑞𝑠 = 𝑞𝑠,𝑚𝑎𝑥 ∙
𝑡𝑑 =
µ
𝑢(𝑡)
Lecture I
Introduction to Bioprocessing and
mixing in bioreactors
𝑛
Intended Learning Outcomes
After this lecture, students
❑ … Know the goal and principles in bioprocess engineering
❑ … can distinguish various reactor configuration
❑ … can determine mixing in various reactor types
Bioprocess Technology II-Donya Kamravamanesh
14
Portfolio of workhorses and products
•
Mammalian cell lines:
-
•
Escherichia coli:
-
•
Power to gas: methane from gaseous substrates
Extremophiles
-
•
Analysis and control of morphology (Penicillin)
Methanogenic archaea:
-
•
Novel physiological processes and cell factories
Glycoengineering
Filamentous fungi:
-
•
Chemicals, fusion proteins and antibody fragments
Ghosts and integrated bioprocess development
Tunable promoter technologies
Pichia pastoris:
-
•
Monoclonal antibodies and vaccines
Waste streams to value-added material
Microalgae and cyanobacteria
-
Biomaterial, bioplastics, drug discovery and biofuel production using photosynthesis
Bioprocess Technology II-Donya Kamravamanesh
15
Bioreactor Types
• Type 1. continuously stirred tank reactor (CSTR)
• Adv: efficient gas transfer, commercial availability and flexible operating conditions
• Type 2. Bubble column bioreactors
• The flow rate of the air/gas influences the performance factors —O2 transfer, and
mixing.
• Type 3. Airlift bioreactors
• Internal loop and external loop airlift bioreactors
• Type 4. The fluidized bed reactors
• Can be used for fluid-suspended biocatalysts such as immobilized enzymes,
immobilized cells, and microbial flocs
• Type 5. Packed bed bioreactors (Trickle bed reactors)
• Catalysts are mainly immobilized
• Type 6. Photobioreactors
• Instead of mass transfer the focus is light penetration to facilitate photosynthesis
Bioprocess Technology II-Donya Kamravamanesh
16
Basic Considerations in Bioreactor Design
Performance-based on reactor design and operation
❑ Reactor configuration
❑ Reactor size
❑ Mode of operation
❑ Cultivation parameters
❑ Monitored parameters and analytics needed
❑ Downstream processing
Bioprocess Technology II-Donya Kamravamanesh
17
Basic Considerations in Bioreactor Design
Bioprocess Technology II-Donya Kamravamanesh
Proteins from cell
culture
Vitamin B12
Penicillin
Baker's yeast
Value range of fermentation products
Single cell protein
Wastewater treatment
Biofuels and
Biopolymers
What is the product?
How much does the product cost?
What is the production cost?
Bioreactor design is based on scientific and economical feasibility and sustainability
18
Bioprocess design
Factors contributing to the production costs
❑ Research and product development
❑ Reactor building
❑ Raw materials and media
❑ Upstream operation (labor, energy, water, waste disposal, depreciation insurance)
❑ Downstream processing (material, labor, energy, water, waste treatment, depreciation
insurance)
❑ Filling and packaging
❑ Logistics (transportation and storage)
❑ Administration and marketing
Bioprocess Technology II-Donya Kamravamanesh
19
Cost determining factors in bioprocess design
• Research and development (R & D)
(maximizing the scale-up speed, minimizing batch-to-batch variation, maximizing
product quality and purity, minimizing the contamination risk, optimizing
cultivation conditions, media optimization, strain improvement)
• Raw materials
(minimizing the substrate cost, maximizing conversion efficiency and product
yield)
• Upstream processing
(maximizing volumetric and specific rate in minimum reactor size)
• Downstream processing
(maximizing product concentration ad minimizing contaminations and impurities)
Bioprocess Technology II-Donya Kamravamanesh
20
Reactor configuration
Aerated Stirred tank reactor
• Aspect ratio (height : diameter
ratio typically is 3:1 for
increased OTR)
• Liquid volume/working volume
is 70-80% of total volume
leaving 20-30% headspace
• High stirrer power
• Sparger
• Foam control
Bioprocess Technology II-Donya Kamravamanesh
21
Mixing in bioreactors
Mixing is used in bioprocesses to …
-
Blend soluble components of the media such as sugars, nutrients, trace elements, etc.
-
Disperse gases in the form of tiny bubbles.
-
Maintain suspension of cells and cell aggregates
-
Where necessary, disperse immiscible liquid to form an emulsion or suspension of fine
droplets.
-
Facilitate heat transfer to and from the liquid
Bioprocess Technology II-Donya Kamravamanesh
22
Mixing in CSTRs
𝐶𝐵𝐹
1
=
𝐷𝑇
12
𝐻𝐿
1
=
𝐷𝐿 1.25
𝐶𝑖
1
=
𝐷𝑇 2/6
𝐿𝐵 1
=
𝐷𝑖 4
𝐷𝑖
1
=
𝐷𝑇 3/4
Pauline M. Doran, in Bioprocess Engineering
Principles (Second Edition), 2013
𝑊𝐵
1
=
𝐷𝑇 10/12
Bioprocess Technology II-Donya Kamravamanesh
23
Rushton radial flow impeller and baffled tank
Bioengineering AG China
Bioprocess Technology II-Donya Kamravamanesh
24
Mixing in CSTRs- baffles
• Assist mixing and create turbulence in the fluid by
breaking up the circular flow generated by rotation of the
impeller
• Welded brackets inside vertical walls of the tank
• Four equally spaced baffles are usually sufficient to
prevent liquid swirling, vortex formation, stagnant zones
and cell sedimentation.
• The optimum baffle width WBF depends on the impeller
design and fluid viscosity but is of the order
𝑊𝐵
1
=
𝐷𝑇
10/12
𝐶𝐵𝐹
1
=
𝐷𝑇
50
Figure - Baffle arrangements: (a) baffles attached to the wall for low-viscosity liquids;
(b) baffles set away from the wall for moderate-viscosity liquids;
(c) baffles set away from the wall and at an angle for high-viscosity liquids.
Bioprocess Technology II-Donya Kamravamanesh
25
Spargers
• Wide variety of designs
• Simple open pipes, perforated tubes, porous diffusers, and complex two-phase
injector devices
• Can release gas bubbles at a single or multiple locations
• As the bubbles rise from the sparger into the impeller zone, they are subjected to
very high shear forces from operation of the stirrer that cause bubble break-up
• The diameter of large ring spargers (Ds) and the separation between the sparger
and impeller (Ss) can have an important influence on the efficiency of gas
dispersion. Porous Gas Sparger - YouTube
Stainless steel sintered porous sprayer/manufactured by SAIFILTER
Bioprocess Technology II-Donya Kamravamanesh
26
Flow patterns in stirred tank reactors
• Depending on impeller design, size and geometry of
vessel and fluid properties
• Rotational – around stirrer shaft (for bulk mixing),
baffles should be installed to create turbulence and
prevent vortexing
• Radial- central axis to tank sides and back again (for
bulk mixing), blades aligned parallel to the stirred
shaft, two liquid patterns, circular flow reduced by
baffles
• Axial flow- up and down the height of vessel,
inclined/ pitched blade with angel less than 90˚ with
plane of rotation. Fluid goes downward first and then
upwards with a deflection from floor. Baffles required
for enhanced turbulence
Pauline M. Doran, in Bioprocess Engineering Principles (Second Edition), 2013
Bioprocess Technology II-Donya Kamravamanesh
27
Different impellers
Liquid flow in the bioreactors
A- Rushton radial flow impeller
B- axial flow hydrofoil impeller
Pauline M. Doran, in Bioprocess Engineering Principles (Second Edition), 2013
Bioprocess Technology II-Donya Kamravamanesh
28
Impellers in CSTRs
High efficiency
turbulent flow
Ragless impeller
Gas dispersion
Concave disc
High efficiency
deep tank
Rushton
Axial flow
Maxflow
Pauline M. Doran, in Bioprocess Engineering Principles (Second Edition), chapter 8-mixing, 2013
Chemineer Impellers | NOV
Bioprocess Technology II-Donya Kamravamanesh
29
Gas flow patterns in stirred tanks
Two-phase flow pattern
Impeller flooding• The gas handling capacity of impeller is exceeded when gas surrounds impeller due to
high gassing rate or low stirrer rate
• No contact with liquid, poor mixing and gas dispersion
Impeller loading• Increased stirrer speed/reduced gas flow- blades disperse gas and liquid towards wallcomplete gas dispersion-desirable
• Gas recirculation in the tank occurs due to high stirrer speed- high residence time
Flooding tendency of impeller
𝑝𝑟𝑜𝑗𝑒𝑐𝑡𝑒𝑑 𝑏𝑙𝑎𝑑𝑒 𝑎𝑟𝑒𝑎
• 𝑠𝑜𝑙𝑖𝑑𝑖𝑡𝑦 𝑟𝑎𝑡𝑖𝑜 = 𝑎𝑟𝑒𝑎 𝑜𝑓 𝑐𝑖𝑟𝑐𝑙𝑒 𝑠𝑤𝑒𝑝𝑡 𝑜𝑢𝑡 𝑏𝑦 𝑖𝑚𝑝𝑒𝑙𝑙𝑒𝑟 𝑟𝑜𝑡𝑎𝑡𝑖𝑜𝑛
• Impeller with low solidity ratio is flooded at low gas velocity
• Impeller with high solidity ratio (>90) = improved gas handling
Pauline M. Doran, in Bioprocess Engineering Principles (Second Edition), 2013
Bioprocess Technology II-Donya Kamravamanesh
30
Impeller tip speed
• Since maximum shear is experienced at the highest velocities, and the highest velocities
are associated with those at the tip of the impeller, the impeller tip speed (ND) is
assumed proportional to the shear stress exerted on the cells.
𝐼𝑚𝑝𝑒𝑙𝑙𝑒𝑟 𝑡𝑖𝑝 𝑠𝑝𝑒𝑒𝑑(𝑚𝑠 −1 ) = 𝜋𝑁𝑖 𝐷𝑖
• Typically, mixing in fermenters is carried out using turbines or propellers.
• Turbines and propellers are remote-clearance impellers; this means they have diameters
of 1/4 to 2/3 the DT, thus allowing considerable clearance between the rotating impeller
and the vessel walls. They are operated at relatively high speeds to generate impeller tip
velocities of the order of 3 m s-1.
• Turbines and propellers are recommended for mixing liquids with viscosities between 1
and about 104 centipoise (1 centipoise = 0.001 kg m-1 s-1), which includes most
fermentation broths
Bioprocess Technology II-Donya Kamravamanesh
31
Stirrer power requirements
• Average power consumption per unit volume for industrial bioreactors is
10 kW m-3 for small vessels (~0.1 m3) to 1-2 kW m-3 for large vessels (~100 m3)
𝑠𝑡𝑖𝑟𝑟𝑒𝑟 𝑝𝑜𝑤𝑒𝑟 𝑖𝑛𝑝𝑢𝑡 𝑃 = 2𝜋 𝑁𝑖 𝑀
M: induced torque, Ni= stirrer speed
*Torque is the tendency of a force to cause an object to rotate.
•
For Ungassed Newtonian fluids power requirement depends on stirrer
speed, impeller shape and diameter, tank geometry, and density and viscosity
of fluid
𝑁𝑖 𝐷𝑖2 𝜌
𝑖𝑚𝑝𝑒𝑙𝑙𝑒𝑟 𝑅𝑒𝑦𝑛𝑜𝑙𝑑𝑠 𝑛𝑢𝑚𝑏𝑒𝑟 𝑅𝑒𝑖 =
𝜇
𝑃𝑜𝑤𝑒𝑟 𝑛𝑢𝑚𝑏𝑒𝑟 𝑁𝑝 =
𝑃
𝜌𝑁𝑖3 𝐷𝑖5
Di: impeller diameter, ρ: fluid density, µ: fluid viscosity, P: power
•
Once power number (Np) is known the power can be calculated as
𝑃 = 𝑁𝑝 𝜌𝑁𝑖3 𝐷𝑖5 (unit is kg 𝑚2 𝑠 −3 𝑜𝑟 𝑊)
Bioprocess Technology II-Donya Kamravamanesh
32
Relationship between Reynolds number and power number depends on flow regime
1
In laminar region 𝑁𝑝 ∝ 𝑅𝑒 or 𝑃 = 𝑘1 𝜇 𝑁𝑖2 𝐷𝑖3 , K1 is proportionality constant
𝑖
In turbulent region 𝑃 = 𝑁′𝑝 𝜌 𝑁𝑖3 𝐷𝑖5
Bioprocess Technology II-Donya Kamravamanesh
33
Proportionality constant for different impellers
Proportionality constant (k1) and constant power number (N’P) in the turbulent regime for
defined geometries of the previous slide
Pauline M. Doran, in Bioprocess Engineering Principles (Second Edition), chapter 8-mixing, 2013
• The power required for turbulent flow is independent of the viscosity of the
fluid but proportional to the density. The turbulent regime is fully developed at
Rei ˃104 for most small impellers in baffled vessels. Without baffles, turbulence
may not be fully developed until Rei ˃105; the value of N’P is also reduced to as
little as 10 to 50% of that with baffles
Bioprocess Technology II-Donya Kamravamanesh
34
Gassed liquids
• Liquids into which gas is sparged have reduced power requirements for stirring.
• Gas bubbles decrease the density of the fluid
• Gas bubbles have a profound impact on the hydrodynamic behavior of fluid around the
impeller.
• Potential for energy and cost savings during operation of the impeller
• The stirrer motor must be large enough to provide sufficient power during any abrupt
change from gassed to ungassed conditions. Therefore, the decrease in impeller power
consumption with gassing represents an under-utilization of the capacity of the stirrer
motor.
• Power input by gassing can be calculated using the equation:
𝑃𝑉 = 𝐹𝑔 𝜌 𝑔 𝐻𝐿
where 𝐹𝑔 is the volumetric flow rate of gas at the temperature and average pressure of the
liquid in the tank, 𝜌 is the liquid density, g is gravitational acceleration, and 𝐻𝐿 is the
liquid height.
Dr.Techn. Donya Kamravamanesh
35
Assessing efficiency of Mixing
Mechanism of mixing
• Distribution (macromixing)
• Dispersion (either micro- or macromixing depending on the scale of fluid motion)
• Diffusion (micromixing)
Assessing the efficiency of mixing
Efficacy of mixing in a CSTR can be expressed as mixing time tm, which is defined as the
time required to achieve less than 10% concentration difference after injection of a tracer
tm: mixing time
tc: circulation time
td: dead time before the
addition is first detected
AGITATION DEVICES (thermopedia.com)
Bioprocess Technology II-Donya Kamravamanesh
36
Mixing Time
Continuously stirred tank reactors (CSTRs)
The mixing time tm, is dependent on
- Stirrer speed
- Reactor geometry
- Liquid viscosity
Which are used to form the Reynold’s number (Rei)
𝑅𝑒𝑖 =
𝑁𝑖 𝐷𝑖2 𝜌
𝜇
Ni: stirrer speed
Di: impeller diameter
ρ: fluid density
µ: fluid viscosity
➢ Conceptually, Ni tm represents the number of stirrer rotations required to
homogenize the liquid after the addition of a small pulse of tracer.
Bioprocess Technology II-Donya Kamravamanesh
37
Mixing Time
Continuously stirred tank reactors (CSTRs)
• For turbulent conditions (Rei > 5 * 103), Nitm remains rather constant and
the following equation for mixing time tm has been developed empirically
for baffled vessels stirred with a single impeller regardless of impeller type
used and liquid height equal to tank diameter
𝑡𝑚 =
2/3
5.9𝐷𝑇
𝜌𝑉𝐿 1/3 𝐷𝑇 1/3
(
) ( )
𝑃
𝐷𝑖
❖ Can be applied to gassed vessels if the impeller is not flooded
DT: tank diameter
Di: impeller diameter
VL: liquid volume
ρ: fluid density
P: power input
➢ P is the power input; stirrer speed is directly related to the power input. The higher the
stirrer speed the higher the power input
Bioprocess Technology II-Donya Kamravamanesh
38
Scale-up
𝑃
• Scale-up is carried out at constant power per unit volume 𝑉 if vessels are geometrically
similar so the
𝐷𝑇
𝐷𝑖
𝐿
remains constant, density remains same in both vessels
• The ratio of mixing time in two reactors can be presented as
𝑡𝑚2
𝐷𝑇2
=
𝑡𝑚1
𝐷𝑇1
2/3
Scale-up of mixing time and power input
𝑉𝐿2
𝑃2 =
𝑉𝐿1
5/3
𝑃1
Bioprocess Technology II-Donya Kamravamanesh
39
Mixing time
• The volume of a cylindrical tank can be determined using the equation
𝐷𝑇 2
𝑉𝐿 = 𝜋
𝐻𝐿
2
• For a cylindrical tank with a liquid height equal to the tank diameter, the geometric
formula to determine the volume of a cylinder is
𝜋 3
𝑉𝐿 = 𝐷𝑇
4
• The equation for mixing time could also be applied under turbulent conditions and we can
express P as N’P and we can have
5.4 1
𝑡𝑚 =
𝑁𝑖 𝑁′𝑃
1/3
𝐷𝑇
𝐷𝑖
2
The equation above indicates that mixing time reduces with increase in stirrer
speed
Bioprocess Technology II-Donya Kamravamanesh
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Improving the mixing
• Baffles are necessary for CSTRs as they produce greater turbulence
• For efficient mixing, the impeller should be mounted below the geometric center of the
vessel.
• Complete gas dispersion and solid suspension are influenced by various aspects of tank
geometry including the impeller off-bottom clearance, type of sparger, clearance between
the sparger and the impeller, and base profile of the tank.
• The power required increases substantially when extra impellers are fitted on the same
stirrer shaft. Furthermore, depending on the impeller design and the separation allowed
between the impellers, mixing efficiency can be lower with multiple impellers than in
single-impeller systems.
• The location of the feed point (or feed points) is also important. Mixing can be improved
substantially by feeding directly into the impeller zone.
Bioprocess Technology II-Donya Kamravamanesh
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Reactor configuration
CSTRs vs air-driven reactors
For low viscosity fluids
• Adequate mixing and mass transfer possible for CSTRs, bubble columns and
airlift reactors <50 m3
• For large-scale reactors (50-500 m3) air driven reactors are more economically
feasible (cheap to build, install and operate)
• For very large reactors (>500 m3) CSTRs due to high power input requirement
are not feasible.
For highly viscose fluids
• Adequate mixing only possible in CSTRs, as great power input is obtained via
mechanical agitation
• Air driven reactors are the design of choice as the heat input in CSTRs by
frictional heat is high
Bioprocess Technology II-Donya Kamravamanesh
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Reactor configuration
Bubble column reactors
• No mechanical agitation
• Aeration and mixing are achieved by gassing
• Requires less energy than mechanical stirring
• No stirrer sealing is required
• Low capital cost and low maintenance cost
• Requires a sparger
• Hydrodynamics and mass transfer are fully
dependent on the behavior of bubbles released
from spargers
• Applied industrially for production of bakers’
yeast also in photo bioreactors
• Common aspect ratios are 3:1 and 6:1
Bubble column reactor - Wikipedia
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Reactor configuration
Bubble column reactors
[PDF] Bubble column reactors | Semantic Scholar
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44
Bubble column reactors
• The liquid mixing time depends solely on the flow regime
• For the linear liquid velocity 𝑢𝐿
𝑢𝐿 = 0.9(𝑔𝐷𝑢𝐺 )0.33
With, 𝑢𝐺 =
𝑣𝑜𝑙𝑢𝑚𝑒𝑡𝑟𝑖𝑐 𝑔𝑎𝑠 𝑓𝑙𝑜𝑤 𝑟𝑎𝑡𝑒 𝑎𝑡 1 𝑎𝑡𝑚
𝑟𝑒𝑎𝑐𝑡𝑜𝑟 𝑐𝑟𝑜𝑠𝑠 𝑠𝑒𝑐𝑡𝑖𝑜𝑛𝑎𝑙 𝑎𝑟𝑒𝑎
𝑢𝐿 : linear liquid velocity
𝑢𝐺 : gas superficial velocity
g: gravitational acceleration
D: column diameter
𝑡𝑚 : mixing time
H: column height
The mixing time then can be described as
𝐻
𝑡𝑚 = 11 𝐷 (𝑔 𝑢𝐺 𝐷 −2 )−0.33
Determination of mass transfer coefficient depends mainly on diameter of bubbles and gas
hold-up
- however, in bubble columns determination of these parameters is impossible to determine
- For non-viscous media in heterogenous flow the 𝐾𝐿 𝑎 is proposed as:
𝑘𝐿 𝑎 ≈ 0.32 𝑢𝐺0.7
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Reactor Configuration
Airlift reactors
• Mixing is done through gassing
• A more defined pattern of liquid flow
compared to bubble column reactors
• A higher degree of stability allowing
higher gas flow rates
• Both upward and downflowing streams
are possible
• Upcoming= riser
• Down coming=downcomer
More stable than the bubble column reactor
They can be built in capacities ˃˃1000 m3
A 1500 m3 with 100m height air-lift has
been built in microbial cell growth for
production of single cell proteins (SCP)
Pauline M. Doran, in Bioprocess Engineering Principles (Second
Edition), 2013
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Packed/ trickle bed reactor
➢ Three-phase reactor system (Solid
support, liquid media, and gas)
➢ Cells/ enzymes are immobilized on
porous solid support e.g. carrier material
➢ Medium is circulating through the bed
using pumps
➢ Used in processes where the growth of
the microorganisms or enzymatic reaction
is rather slow
➢ Not suitable for fast-growing cultures as
they can block the passage of gas and
liquid through the reactor
➢ Used in gaseous processes e.g. biological
hydrogen methanation
➢Important factor in scale-up is the H:D
ratio and the carrier material
Pauline M. Doran, in Bioprocess Engineering Principles
(Second Edition), 2013
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