78657 - Downstream Processing of Biological Molecules

Course Unit Page

Academic Year 2018/2019

Learning outcomes

At the end of the course the student has knowledge of downstream and purification processes used for the industrial production of biological molecules.

Course contents

REQUIREMENTS

A prior knowledge and understanding of basic chemical engineering principles and, in particular, unit operations, thermodynamics and transport phenomena are required.

Fluent spoken and written English.

COURSE CONTENTS

BIOREACTORS AND DOWNSTREAM PROCESSES MODULE I (3 CFU)

  • Elements of reaction kinetics: reaction rate, order of reaction, catalysis, enzymes, kinetics of biological interest: Monod kinetic model, structured and segregated models.
  • Mass and energy balances for ideal reactors: batch, CSTR and PFR.
  • System of expression: bacterial cells, yeast and mammalian cells.
  • Operating modes and performance analysis of bioreactor: continuous systems, batch and semi-continuous (fed-batch). Conduction of bioreactors and problems of conversion.
  • Air-lift bioreactors and agitated bioreactors with immobilized biomass: configurations, features and operating modes.
  • Biological waste water treatment: activated sludge and supported biomass systems (biological filters, RBC), membrane bioreactors (MBR).

BIOREACTORS AND DOWNSTREAM PROCESSES MODULE II (6 CFU)
DOWNSTREAM PROCESSES of BIOLOGICAL MOLECULES (6 CFU)

  • Principles of separation processes, choice of the appropriate unit operation for a given separation.
  • Cell lysis: osmotic, chemical and mechanical methods.
  • Sedimentation: equation of motion, equilibrium sedimentation. Centrifugation: description and use of different centrifuges. Sigma analysis.
  • Filtration: conventional and cross flow filtration. Filter media and equipment.
  • Flocculation: theory of electrical double layer, DLVO theory, flocculant agents.
  • Protein precipitation: protein solubility (salting in and salting out), precipitate formation phenomena, design of precipitation systems.
  • Membrane separation processes: classification based on the driving force, description and use of different membrane processes in biotechnology. Membrane modules: plate and frame, hollow fiber, tubular. Concentration polarization: film theory model. Microfiltration, ultrafiltration and diafiltration. Membrane fouling. Sterile filtration and filtration for virus removal.
  • Liquid/liquid extraction: extraction with solvent, extraction in aqueous phase. Stage calculation. Scale-up and design of extractors.
  • Adsorption: fundamental principles, equilibrium isotherms.
  • Chromatography: process description, chromatographic techniques. Chromatography column dynamics: plate theory, column efficiency, Van Deemter equation, theory of adsorption chromatography.
  • Crystallization: crystal formation and their characteristics. Phase diagrams- Protein crystallization. Crystallizers.
  • Monoclonal antibody production: process analysis and economic evaluation. Polishing steps: AEX, CEX, HIC and mixed mode chromatography.
  • Examples of other biotechnological processes: recombinant insulin production, citric acid.
Use of process simulators to size apparatuses and bioprocess design.

Readings/Bibliography

P.M. Doran, Bioprocess Engineering Principles, 2nd Ed., Elsevier, 2013.

Froment G.F., Bischoff K.B., Chemical reactor analysis and design, John Wiley, 1990.

R.G. Harrison, P. Todd, S. Rudge and D. Petrides, Bioseparations Science and Engineering, 2nd Ed. Oxford U. Press, NY, 2015.

Process scale bioseparations for the biopharmaceutical industry, A.A. Shukla, M.R. Etzel. S. Gadam Editors, CRC, Taylor & Francis, 2007.

M. L. Shuler and F. Kargi, Bioprocess Engineering, 2nd Ed., Prentice Hall, 2002.

Teaching methods

Class lectures and term paper.

Assessment methods

Achievements will be assessed with the term paper project and the final exam. The final exam consists of a written test that comprises:

  • a preliminary part to verify the prior knowledge (basic elements of chemical engineering necessary to fully understand the course content)
  • open questions about the course content.

This is based on analytical assessment of the "expected learning outcomes" as described above, and in particular, at the end of the course the student should be able to:

  • Knowledge of the main unit operations of a biotech process.
  • Master the fundamentals of bioreactors.
  • Understand the principles behind a given separation process and size the apparatus.
  • Design a bioprocess as a sequence of unit operations.

Higher grades will be awarded to students who demonstrate a deep understanding of bioprocessing and a clear and concise presentation of the course contents, together with the capability to carry on a technical conversation.

To obtain a passing grade, students are required to demonstrate a knowledge ot the basic principles of the main unit operations of a bioprocess and a comprehensible use of technical language.

A failing grade will be awarded if the student shows knowledge gaps on the key concepts of the course, on basic chemical engineering principles and inappropriate use of technical language.

The grade breakdown is 70% for the final exam and 30% for the term paper project.

Teaching tools

A combination of blackboard and slide projector according to the lecture topic.

Power point presentations that will be made available on http://campus.unibo.it/ with access to University of Bologna students.

Reading material that will be made available during the course as well as guided suggestions for individual literature search.

Office hours

See the website of Cristiana Boi