Short Programs

Team Projects in Bioprocess and Biological Engineering [20.15s]

Date: TBD, 2011 | Tuition: $4,000 (tentative) | Continuing Education Units (CEUs): 2.8 (tentative)

Course Summary  |  Learning Objectives  |  Who Should Attend  |  Program Outline  | 
On-Site Courses  |  About the Lecturers  |  Updates

Course Summary

This course provides experience with state-of-the-art bioprocessing equipment and techniques. Participants will execute two focused experiments (covering different topics), learn how to interpret the data they collect, and report results in writing. The experiments address common real-life industrial/commercial challenges, and are designed to teach participants how to tackle them with rigorous engineering approaches. Because participants choose their two experiments (from seven options), this course is especially suited for those who would want both 1) exposure to industry-standard bioprocessing methods and 2) a more in-depth understanding of particular bioprocessing topics.

Learning Objectives

1. Prepare and operate a bioreactor and associated instrumentation.
2. Understand cell culture and fermentation technology through applied biochemical engineering.
3. Learn to interpret data collected from bioreactor instrumentation.
4. Assess results of laboratory experiments with either microbial or animal cell systems.
5. Two of the following (choose two topics):
   
   a. Compare traditional bioreactors to novel single-use bioreactors.
   b. Compare traditional agitated bioreactors to airlift bioreactors.
   c. Evaluate instrumentation for determining total cell concentration.
   d. Evaluate instrumentation for determining dissolved oxygen.
   e. Evaluate the perfusion system.
   f. Compare fed-batch system to batch system to spinner flask system.
   g. Evaluate the effect of shear on cell viability.

Who Should Attend

The course is intended for engineers, chemists, biologists, biochemists, biotechnologists and also professionals from other disciplines who are interested in biochemical engineering, cell culture, and fermentation technology. Each concept and topic covered 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)

Program 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.) Students will conduct experiments with traditional bioreactors (e.g. stirred-tank reactor [STR], spinner flasks) and with novel bioreactors (e.g. Wave bioreactors, air-lift reactors), and with a variety of bioprocessing instrumentation. The general outline of the course will depend on the two topics chosen:

1. Single-use rock-bed bioreactors (SUB) vs. traditional STR [Cell Culture Project]

1.1 What are the uses of a single-use bioreactor? When is it appropriate to use an SUB instead of an STR?

1.2 Can the Wave, a novel single-use bioreactor, be used with microbial systems?

1.3 Experience using both reactors:

• Preparation of bioreactors
• Calibration of bioreactor instrumentation, including temperature, pH, and dO₂ probes
• Inoculation and sterile techniques
• Operation, sampling, optical density readings, and analysis

1.4 Calculations: growth rate

2. Single-use airlift bioreactor (SUB) vs. traditional STR [Microbial Fermentation Project]

2.1 Description of the challenge of providing enough oxygen without too much shear

2.2 Comparison of the airlift bioreactor and the STR

2.3 Experience using both reactors:

• Preparation of bioreactors
• Calibration of bioreactor instrumentation, including temperature, pH, and dO₂ probes
• Inoculation and sterile techniques
• Operation, sampling, optical density readings, and analysis

2.4 Calculations: growth rate

3. Comparing probes for determining total cell concentration [Microbial Fermentation Project]

3.1 Description of why total cell concentration (TCC) one of the most critical fermentation parameters

3.2 Comparison of equipment used to determine TCC

3.3 Experience using both reactors:

• Bug Eye
• Optek probe
• Finesse TruCell Probe

3.4 Calculations: growth rate, TCC to dry cell weight (DCW), optical density, and cell enumeration conversions

4. Measuring dissolved oxygen: liquid electrolyte vs. optical sensors [Cell Culture and Microbial Fermentation Projects]

4.1 Explanation of why oxygen is usually the limiting nutrient, and why monitoring dissolved oxygen is critical. (Also, what is kLa and why is it useful?)

4.2 Comparison of liquid electrolyte sensor to optical sensor

4.3 Experience using STR reactor:

• Preparation of bioreactor
• Calibration of bioreactor instrumentation, including temperature, pH, and dO₂ probes
• Inoculation and sterile techniques
• Operation, sampling, optical density readings, and analysis

4.4 Calculations: Oxygen uptake rate (OUR), overall mass transfer coefficient (kLa)

5. Perfusion project [Cell Culture Project]

5.1 Explanation of the difficulty achieving high viable cell concentrations, and an introduction to the possible systems: batch, fed-batch, repeated fed-batch, continuous, perfusion, integrated bioreactor-perfusion unit

5.2 Experience with the perfusion system

• Setting up and running the perfusion system/STR reactor
• Analysis of spent medium
  • HPLC product measurement (e.g. monoclonal antibody)
  • Off-line measurements: glucose, lactate, L-glutamine, L-glutamate, ammonia (enzyme-based analyzers) and apoptosis assays (flow cytometry)
  • Automated cell counting

5.3 Calculations: substrate consumption rate, product formation rate, viable and total cell concentrations, specific and volumetric productivities, yield coefficients related to medium utilization, waste products formation

6. Fed Batch system [Cell Culture and Microbial Fermentation Projects]

6.1 Explanation of the difficulty achieving high viable cell concentrations, and an introduction to the possible systems: batch, fed-batch, repeated fed-batch, continuous, perfusion, integrated bioreactor-perfusion unit

6.2 Comparison of fed-batch to batch to spin flask system

6.3 Experience with the fed batch system:

• Preparation of two bioreactors and fed batch system
• Calibration of bioreactor instrumentation, including temperature, pH, and dO₂ probes
• Inoculation and sterile techniques
• Operation, sampling, optical density readings, and analysis

6.4 Calculations: substrate consumption rate, product formation rate, viable and total cell concentrations, specific and volumetric productivities, yield coefficients related to medium utilization, waste products formation

7. Shear Sensitivity and Animal Cell Culture

7.1 Description of the challenge of providing enough oxygen without too much shear

7.2 Comparison of single-use bioreactors set at different rocking speeds

7.3 Comparison of spinner flasks set at different agitation speeds

7.4 Experience with Wave bioreactor

• Preparation of bioreactor
• Inoculation and sterile techniques
• Operation, sampling, optical density readings, and analysis

7.4 Calculations: impeller tip speed, growth rate, death rate

Note: The outline above intends to highlight the topics and experiments that will be available. 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). Lab coats and safety glasses will be provided. Furthermore, access to computers and to internet/email will be provided in the laboratory.

On-site Courses

We can also offer this course for groups of employees at your location. Please contact the Short Programs office for further details.

About The Lecturers

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

Updates

This class is tentatively planned for 2011, depending on the level of interest. Email the Short Programs office to express your interest in taking this course. Please include your industry and learning goals.