Brock University - Department of Chemistry



 Bioreactor Processes (Biotech 3P09)
J. Atkinson
Text:  Bioprocess Enginneering Principles (BEP), by Pauline Doran

 
1. Introduction (BEP p. 1-8)
- requirements for a biotech process
•  marketable product
•  suitable organism or enzyme for large scale production work
•  available cheap raw materials
•  proper reactor design and construction consistent with the growth form of the organism or kinetics of the biocatalyst
•  understanding of the kinetics of organism's growth and nutrient requirements, variables that effect product yield
•  efficient and cost effective means of purification of the product

2.  Fermentation  (BEP p. 282-295, 355-376)
(a)  growth kinetics for microorganisms, plant and animal cells
•  single limiting substrate (Monod equation)
•  specific growth rates, yield co-efficients, productivity
•  growth in batch, fed-batch, continuous well-mixed and plug-flow reactors
•  immobilized systems (BEP p.297-327)
•  innoculation
(b)  physics of liquid culture (BEP p. 129-163, 333-344)
•  Newtonian and non-Newtonian liquids
•  shear stress and shear rate
•  KLa and Reynold's number
•  impeller design in well-mixed reactors
•  power demands for mixing
(c)  media preparation
•  economics and availability
•  suitability
•  sterilzation: thermal batch and continuous (BEP p. 377-386)
•  filtration: depth and absolute
•  supplimentation
(d)  transport phenomena and scale-up (BEP  p. 190-217)
•  O2 supply and sterilization
•  O2 transport through liquid interfaces
•  airlift reactors and bubble columns
•  foaming control
•  heat transfer and cooling requirements (BEP p. 164-170)
(e)  process monitoring (BEP p. 348-352)
•  online: pH, temperature, CO2, O2
•  specific sensors:  biosensors for starting materials, product, metabolites, toxins,
•  cell number / biomass

3.  Product recovery
•  small organics:  dialysis, extraction, precipitation
•  secreted versus non secreted proteins (and solublevs  insoluble)
•  macromolecules:  precipitation with organic solvents, salts, *T, *pH, membrane filtration
•  centrifugation
•  chromatography:  ion exchange, size exclusion (gel permeation), affinity gels / membranes
•  new rigid chromatography media
•  industrial low pressure radial colums
 

Textbook The main text for this course is Bioprocess Engineering Principles by Pauline M. Doran
 Several other texts on reactor and process technology are held in our library including the following:
 (1) Biotechnology. A textbook of Industrial Microbiology, by W.Crueger and A.Crueger,1989
 (2) Biotechnology: Principles and Applications, by I.J.Higgins, D.J.Best and J.Jones, 1985.
 (3) Biochemical Engineering Fundamentals , by  J.E.Bailey and D.F.Ollis, 1986
 Bailey and Ollis is a rather advanced text but comprehensive in its scope and may be of help for mre detailed questions that you have either about course material or in researching for a seminar.
 
Labs  The laboratory portion of this course will be split into two sections.  The first eight weeks of the term will be devoted to wet labs.
  Sept 21 - Sept 28:   Determination of specific growth rates
  Oct 5 - Oct 12:  Beer Making
  Oct 19 - Oct 26:  Bioreactor production of a-galactosidase
  Nov 2    Ion-exchange Chromatography

 Failure to complete less than four of the labs constitutes an incomplete course and the receipt of a failing grade.

  The remainder of the laboratory sessions will be devoted to computer modeling of reactor phenomena.  We will be using a software package called BioPro Designer.  It is a sophisticated industrial process simulator, from raw material mixing and sterilization to product fermentation and purification.  It even simulates the expenses for your process so that you can see whether you make any money given your choice of selling price per kilogram.   This software is available to those of you who have a computer at home.  In order for you to receive it you must have 5 virus free, IBM-formatted, diskettes.  The instructor will make five copies available to selected members of the class who will each be responsible for copying four or so more copies for distribution.  The PC Labs are scheduled on the same time as the normal laboratory sessions.  Feel free to explore the program at you own speed prior to this portion of the course.
   Portions of the assignments may use a PC compatible program called Basic Biochemical Engineering.  This package is freely distributable and infact can be ftp'd anonymously from the author's site at ftp.rpi.edu in the directory pub/faculty/bungay.  If you have access to the World Wide Web the same software can be obtained at:
 http://www.eng.rpi.edu:80/dept/chem-eng/WWW/faculty/bungay/bunedpro.html
    I can also make the software available to you if you provide me with a formatted diskette.  If you have an IBM-PC at home I strongly suggest taking this disk home and doing a tour of the tutorials and simulations that are provided.  Your computer needs the BASIC or GWBASIC subprogram, usually in you DOS folder, for this to run.  More specific directions will be provided with the assignments which will be handed out in approximately every two weeks beginning in the last week of September.
Mini-projects:  Each student will write a brief description (approximately five pages of text, not including pictures and diagrams) of some aspect of biotechnology that emphasizes the use of bioreactors or process  tecnology.  These will be due by Friday, November 13).  A list of potential topics will be made available early in the term.  You may choose another topic, but clear it with me first. These should be referenced to the relevant journals and books.  Keep in mind that you may have to make a trip to the McMaster library to obtain some materials so,  plan ahead!
Midterm A 1.5 hr  midterm examination will be held in class on Tuesday, October 20, 1998.
Marking     Mini-project    10%
    Midterm exam    10
    Assignments (3)   20
    Labs (5)    25
    Final exam    35

It is the policy of the Department of Chemistry, that to acheive a passing grade in this course, a minimum of thirty percent (30%) must be acheived on the final examination. Material handed in late will be penalized 10% per day late. At least four (4) of the five lab sessions must be attended and submitted for marking to constitute completion of this course.  Completion of fewer than four labs will result in a failing grade for the course.

For access to software for completion of assignemnt 1


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Revised: Septemeber 14, 1998
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