The University of Western Ontario Faculty of Engineering DEPARTMENT OF CHEMICAL AND BIOCHEMICAL ENGINEERING

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1 The University of Western Ontario Faculty of Engineering DEPARTMENT OF CHEMICAL AND BIOCHEMICAL ENGINEERING CBE 4403B - BIOCHEMICAL SEPARATION PROCESSES COURSE OUTLINE Description The main objective of this course is to introduce the student to the basic fundamentals of downstream separation and purification processes such as membrane separation processes, protein separation and purification and other separation processes of economic importance to the fermentation industry. Prerequisites CBE 2290A/B or Biology 1222 or Biology Unless you have either the requisites for this course or written special permission from your Dean to enroll in it, you may be removed from this course and it will be deleted from your record. This decision may not be appealed. You will receive no adjustment to your fees in the event that you are dropped from a course for failing to have the necessary prerequisites. Corequisites Antirequisites Contact Hours 3 lecture hours 1 tutorial hour Instructor Dr. Wankei Wan (TEB 433) Telephone: ext: wkwan@uwo.ca Undergraduate Assistant Lisa Drysdale (TEB 477) Telephone: edrysda4@uwo.ca Required Text J. Krijgsman, Product Recovery in Bioprocess Technology, Butterworth-Heinemann, Will be

2 CBE 4403B Course Outline 2 available at the University Bookstore ( M# 4933). Reference Text M.L. Schuler, F. Kargi, Bioprocess Engineering: Basic Concepts, Prentice Hall, Course Notes Course notes will be available for download from OWL. Laboratory Notes Laboratory Units SI units will be used. General Learning Objectives Knowledge Base x Individual Work x Ethics and Equity Problem Analysis x Team Work Economics and Project Management x Investigation Communication Life-Long Learning x Design x Professionalism x Engineering Tools x Impact on Society x General Learning Objectives This course deals with downstream separation and purification unit operations of a bioprocess, and complements the other three Biochemical Engineering courses: CBE 2290a - Fundamentals of Biochemcial and Environmental Engineering, CBE 3301a - Biochemical Reaction Engineering, and CBE 3320b - Bioprocess Engineering. Completion of all four Biochemical Engineering courses will provide information and background which will be useful in the design of a typical bioprocess. In many commercial bioprocesses, separation and purification of the final product represent the major component of the total production cost. The objectives of this course are to enable the student to identify appropriate combinations of separation and purification technologies for various types of bioproducts and to apply fundamental principels to the design of these unit operations. Specific Learning Objectives: Introduction Distinguish bioproduct market sectors. Describe general stages in bioproduct recovery processes. Calculate yield, and purification and separation factors.

3 CBE 4403B Course Outline 3 Select prospective unit operations based on bioproduct size and recovery stage. Ask critical questions relevant to recovery process design. Release of Intracellular Components Compare morphology and cell wall structure of cell types representative of fermentation broths. Describe operations used to prepare cells for disruption. Identify various non-mechanical methods of cell disruption. Describe the principles of operation for bead mills and high-pressure homogenizers. Describe how various factors influence performance of bead mills and homogenizers. Calculate parameters describing bioproduct release kinetics. Quantitatively analyze various processing modes (multi-pass, batch recycle and continuous recycle) for cell disruption. Solid-liquid Separation Describe common broth pre-treatment methods employed prior to solid-liquid separation. Determine specific cake resistance and medium resistance for constant-pressure filtration. Calculate parameters describing compressible filter cakes, given V vs. t data. Describe the principles of operation of common types of process filters. Calculate required filter area for given processing rate using rotary vacuum filtration. Calculate centrifugal acceleration, G-factor and drift velocity. Describe the principles of operation of common types of process centrifuges. Use sigma concept to scale up tubular and disc-stack centrifuges. Describe laboratory and pilot scale testing methods for centrifugal separations. Concentration of Bioproducts - I (Membrane Separation) Distinguish micro-, ultra- and hyper-filtration according to particle size and pressure difference. Compare and contrast cross-flow vs. dead-end filtration. Describe the principles of operation of common types of cross-flow filtration modules. Define rejection co-efficient, concentration factor, permeate yield and non-permeate yield for batch and continuous modes of operation. Calculate mass-transfer coefficient and permeate flux from both experimental data and dimensionless correlations. Determine final concentration and required membrane area for various operating modes (batch recycle, and single and multi-stage feed-and-bleed). Quantitatively describe continuous- and discrete-batch diafiltration processes. Concentration of Bioproducts - II Describe the principles of operation of aqueous two-phase extraction.

4 CBE 4403B Course Outline 4 Describe how the electric double layer surrounding a protein molecule influences precipitation. Describe the principles of operation of common precipitation methods (salting-out, isoelectric ph, organic solvents, non-ionic polymers, polyelectrolytes, and affinity interactions). Specify the operating limits of a precipitate aging process. Sorption Processes Fit adsorption data to Langmuir, Freundlich or linear isotherms. Calculate bioproduct recovery in batch adsorption process, given operating and equilibrium data. Explain how various factors could influence the design of a continuous stirred-tank adsorption process. Predict the behavior of breakthrough curves for various types of adsorption isotherms. Calculate breakthrough time and fraction of bed used from supplied data. Use the concept of transfer units or theoretical plates to determine the rate-controlling step from column adsorption experiments. Calculate peak resolution and selectivity, and column efficiency, from given chromatographic results. Size chromatographic separation process via productivity analysis of given operating parameters. Identify important engineering properties of chromatographic media. Describe the principles of operation of ion exchange and common types of affinity chromatography. Calculate chromatographic distribution coefficient from equilibrium data, and use it to estimate elution volume from column void volume. Describe the principles of operation of size exclusion chromatography, and use the concept of available distribution coefficient (K av) to select appropriate media and predict elution volume. Apply resolution-related criteria to scale up of chromatographic processes. Contrast important requirements of pilot- vs. production-scale chromatographic systems. Describe fundamental equipment requirements and basic configuration and operation of chromatographic systems. Polishing and Formulation Apply mass and enthalpy balances to calculate bioproduct yield and cooling load of crystallization processes. Describe common methods of creating supersaturated solutions. Identify principle design considerations in batch crystallization. Describe, using suitable examples, the various objectives commonly encountered in bioproduct formulation. Describe the formulation stages in the production of various types of bioproduct.

5 CBE 4403B Course Outline 5 Evaluation The final course mark will be determined as follows: Assignments 15 % Mid-term Examination 35 % Final Examination 50 % The mid-term and final examinations will be open-book examinations. Note (1) Students must pass the final examination to pass this course. Students who failed the final exam will be assigned 48% if the aggregate mark is more than 50%, or the aggregate mark. (2) Assignments are to be handed in the CBE 4403A locker (#TBA) in TEB on the specified due date provided by the Instructor. Repeating All Components of the Course In accordance with Senate and Faculty Policy, students who failed the final exam will be assigned 48% if the aggregate mark is more than 50%, or the aggregate mark. No special permissions will be granted enabling a student to retain laboratory, assignment or test marks from previous years. Previously completed assignments and laboratories cannot be resubmitted for grading by the student in subsequent years. Use of English In accordance with Senate and Faculty Policy, students may be penalized up to 10% of the marks on all assignments, tests, and examinations for the improper use of English. Additionally, poorly written work with the exception of the final examination may be returned without grading. If resubmission of the work is permitted, it may be graded with marks deducted for poor English and/or late submission. Attendance Attendance to all lectures, tutorials and laboratories is mandatory. Any student who, in the opinion of the instructor, is absent too frequently from class or laboratory periods in any course, will be reported to the Dean (after due warning has been given). On the recommendation of the Department concerned, and with the permission of the Dean, the student will be debarred from taking the regular examination in the course. Cheating University policy states that cheating is a scholastic offense. The commission of a scholastic offense is attended by academic penalties, which might include expulsion from the program. If you are caught cheating, there will be no second warning (see Scholastic Offence Policy in the Western Academic Calendar). Plagiarism Students must write their essays and assignments in their own words. Whenever students take an idea or a passage of text from another author, they must acknowledge their debt both by using

6 CBE 4403B Course Outline 6 quotation marks where appropriate and by proper referencing such as footnotes or citations. Plagiarism is a major academic offence (see Scholastic Offence Policy in the Western Academic Calendar). The University of Western Ontario has software for plagiarism checking. Students may be required to submit their work in electronic form for plagiarism checking. Conduct Students are expected to arrive at lectures on time, and to conduct themselves during class in a professional and respectful manner that is not disruptive to others. Sickness and Other Problems Students should immediately consult with the instructor or Department Chair if they have any problems that could affect their performance in the course. Where appropriate, the problems should be documented. The student should seek advice from the Instructor or Department Chair regarding how best to deal with the problem. Failure to notify the Instructor or Department Chair immediately (or as soon as possible thereafter) will have a negative effect on any appeal. Please contact the course instructor if you require material in an alternate format or if any other arrangements can make this course more accessible to you. You may also wish to contact Services for Students with Disabilities (SSD) at x for any specific question regarding an accommodation. Notice Students are responsible for regularly checking their Western and notices posted on Instructors' doors. Consultation Students are encouraged to discuss problems with their teaching assistant and/or instructor in tutorial sessions. Office hours will be arranged for the students to see the instructor and teaching assistants. Other individual consultation can be arranged by appointment with the appropriate instructor. Accreditation (AU) Breakdown Engineering Science = 100% January 09, 2018/wkw