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Overview Learning Objectives Outline Lecturers Apply

Bioreactors and Bioprocessing [20.14s]

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Date: TBD, 2010 | Tuition: $4,000 (tentative) | Continuing Education Units (CEUs): 2.8 (tentative)

This class is tentatively planned for 2010.

Overview

This course will provide hands-on experience in upstream processing and will focus on the selection, preparation, and operation of bioreactors and instrumentation. Both the traditional bioreactor technology (stirred-tank reactor, STR) and the single-use bioreactor technology (SUB) will be employed in the course. Included will be tutorials on how to interpret the data commonly collected from bioreactor instrumentation. This course is especially well suited for newcomers to the field of bioreactors and bioprocessing.

The course is intended for engineers, chemists, biologists, biochemists, biotechnologists and also professionals from other disciplines who are interested in biochemical engineering, cell culture, fermentation technology or downstream processing. Each concept and topic covered (including cell and product kinetics, bioreactor design, oxygen mass transfer and scale-up) will be explained for the beginner - without assuming detailed prior knowledge.

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)

To review evaluations and photos from this course in 2008, please visit http://stellar.mit.edu/S/course/20/su08/20.14S/.

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 k_La 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 k_La 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.

Lecturers

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