Short Programs

Bioreactors and Bioprocessing

This course is in development for 2013 or beyond. The below description should be taken as an example of content and is subject to change. If you are interested in this course, please
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Overview  |  Learning Objectives  |  Outline  |  Participants' Comments  |  Lecturers  |  Location  |  Updates

Overview

Especially designed for professionals new to the field of bioreactors and bioprocessing, this course will provide hands-on experience in upstream processing, including cell culture and fermentation. The focus will be on the selection, preparation, and operation of bioreactors (in the batch, fed-batch, and perfusion modes) and related instrumentation (including optical sensors). Traditional and disposable (plastic) single-use bioreactors (SUB) suitable for microbial and mammalian cells (suspension or adherent) will be utilized during the course. Tutorials will be included on how to interpret the data commonly collected from bioreactor instrumentation.

For the novice in bioengineering and biology, who would like a good overview of the field before attending the course, the instructor recommends the following text:

Bioprocess Engineering: Basic Concepts (2nd Edition) (Hardcover) by Michael L. Shuler, Fikret Kargi (Prentice Hall)

Learning Objectives

1. Evaluate the results of hands-on upstream processing experiments.
2. Describe the selection, preparation, and operation of bioreactors and instrumentation.
3. Analyze how to interpret the data collected from bioreactor instrumentation.
4. Examine cell culture and fermentation technology through applied biochemical engineering.
5. Assess the results of laboratory experiments with either microbial or animal cell systems, using suspension cells or attached cells.
6. Compare the results of experiments with traditional bioreactors and with novel bioreactors.

Outline

The course will provide participants with an introduction to cell culture and fermentation technology through applied biochemical engineering. Participants will work in teams on experiments with either microbial (e.g. recombinant E. coli, Pichia pastoris) or animal cell systems (e.g. CHO, hybridoma cells, cancer cells) and will use suspension systems. Students will conduct experiments with traditional bioreactors (e.g. stirred-tank reactor, STR, spinner flasks) and with novel bioreactors (e.g. rock-bed single-use bioreactor, rotary cell culture system, air-lift single-use reactor, fluidized-bed reactor). The general outline of the course will be:

1 Cell Culture/Fermentation (CCF) Introduction

1.1 What types of industries are using CCF technology?
1.2 What is the current direction of the CCF market?
1.3 Who's Who in CCF technology: bioreactors, sensors, instrumentation and media?
1.4 Laboratory design and biosafety considerations

2 Upstream Process and Bioreactor Selection

2.1 Description of technologies: traditional vs. novel bioreactors
2.2 Hands-on Experiments

a. Preparation of bioreactor

b. Inoculum development and sterile techniques

c. Preparation of bioreactor instrumentation devices including:

• Temperature probes
• pH and dissolved gas probes

d. Inoculation

e. Operation, sampling and analysis

• Manual and automated cell counting methods
• Off-line measurements: glucose, lactate, L-glutamine, L-glutamate, ammonia (enzyme-based analyzers) and apoptosis assays (flow cytometry)
• On-line measurements (e.g. CO2 and O2)
• Product measurement: HPLC
• How to measure and calculate cellular consumption rates
• How to use consumption rates to determine feeding strategies, medium supplements, and process control

f. Medium design and selection

3 Mass Transfer and Bioreactor Design

3.1 What is kLa and fundamentals of mass transfer?
3.2 Absorption and desorption volumetric mass transfer coefficients
3.3 Oxygen sensors (polarographic and optical)
3.4 Off-gas analyzers
3.5 How can I determine the kLa of my bioreactor (hands-on)?

a. Dynamic method

b. Oxygen-balance method

c. Mass transfer correlations

3.6 How to use dissolved oxygen measurements to design, control and scale up my process

a. Head space sparging

b. Bubble sparging

c. Impeller selection/rotation

4 Process Goals and Bioreactor Mode of Operation

4.1 What are the different modes of operation?

a. Batch

b. Fed-batch

c. Repeated fed batch

d. Continuous

e. Perfusion

f. Integrated bioreactor-purification unit

4.2 Hands-on Experiments (a combination of those listed below)

a. Batch and repeated batch

• STR
• Rock-bed bioreactor (e.g., Wave® reactor)

b. Perfusion

• Spin Filter with STR
• Hollow fiber (traditional TFF and novel alternating TFF) with STR
• Rock-bed bioreactor
• Fluidized-bed reactor

c. Fed-Batch

• Glucose feeding strategy
• Oxygen uptake rate feeding strategy

d. Continuous culture

• Substrate-feeding strategy
• Process-controlled stirred vessel bioreactor system

The outline above intends to highlight the topics and experiments that will be discussed and performed, respectively. The students will gain hands-on experience in a cutting edge biotechnology facility using the latest equipment, relevant to today's industry.

Participants are requested to wear proper clothing for lab work (shorts and sandals should be avoided). Cloth lab coats, safety glasses, and nitrile gloves will be provided. Furthermore, access to computers and to internet/email will be provided in the laboratory.

Participants' Comments

Senior Supervisor - Manufacturing, BioMarin Pharmaceutical Inc.
"I liked how the course was broken up into classroom (theory) and lab work. It was nice to see different technologies in the lab and get some hands-on experience with it."

Senior Project Manager, Genentech
"Excellent experience. Professor Jean-Francois Hamel and his team did a terrific job keeping the program interesting. Provides background information on the theory and practice of using bioreactors. This is a new subject area for me and it will allow me to do a better job managing projects in this area at my company. In addition, I noticed that while several members of my MIT class had more advanced knowledge of bioreactors the course was still beneficial to them."

Engineer, Genentech
"It's a good refreshing course for person who has been out from the lab for a while. It's also a good introductory course for people who have no cell culture and fermentation experiences."

Lecturers

The program is under the direction of Jean-Francois Hamel, a Research Engineer in the MIT Department of Chemical Engineering.

Location

This course takes place on the MIT campus in Cambridge, Massachusetts. We can also offer this course for groups of employees at your location. Please contact the Short Programs office for further details.

Updates

There are no updates at this time.