Bioreactors and Bioprocessing
This course is currently in development and will not be offered in 2016
*This course has limited enrollment. Apply early to guarantee your spot.
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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)
Fundamentals: Core concepts, understandings and tools (40%)
Latest Developments: Recent advances and future trends (30%)
Industry Applications: Linking theory and real-world (30%)
Lecture: Delivery of material in a lecture format (20%)
Discussion or Groupwork: Participatory learning (20%)
Labs: Demonstrations, experiments, simulations (60%)
Introductory: Appropriate for a general audience (80%)
Specialized: Assumes experience in practice area or field (10%)
Advanced: In-depth explorations at the graduate level (10%)
Who Should Attend
This course is designed for people in roles such as: process associate, process engineer, technician, validation engineer, research associate, plant engineer, manufacturing specialist, chemist, and quality control analytical chemist.
Industries and companies that would benefit from this course include manufacturing, research and development, government, consulting, legal, academia, biopharma, petrochemical and bioenergy, industrial engineering (e.g., automation and control), analytical instrumentation, software, as well as start-ups in those areas.
- Applications of engineering principles and concepts to bioprocess systems.
- Gain a practical understanding of the bioprocess platforms and PAT tools that are available for cultivating and monitoring microbial and mammalian cells.
- Learn how to collect data, evaluate data to determine suitability for further analysis, and use experimentally-obtained data to characterize key features of bioprocesses.
- Develop an appreciation for balancing theory with empiricism, through the use of correlations, approximations and engineering judgment.
- Gain experience with industry-standard software tools, for visualizing the process and interpreting data in real time
- Acquire an enhanced ability to design bioprocesses, using experimental and computational tools.
- Increased appreciation for the role of bioprocess research and engineering in various fields, such as Biopharma and Energy
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. suspension CHO, adherent Monkey cells) and will use both suspension and microcarrier systems. Students will conduct experiments with an advanced 24-minibioreactor system, traditional bioreactors (e.g. stirred-tank reactor, STR, spinner flasks) and with single-use bioreactors (e.g. rocking bag bioreactor, air-lift reactor, and rectangular Pad reactor). They will learn and practice the concepts of batch, fed-batch and continuous bioprocessing. 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: minireactor platform and process scale, traditional vs. single-use 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 and Lab-on-a-chip® analyzer)
- On-line measurements (e.g. CO2 and O2)
- Product measurement: HPLC and Lab-on-a-chip®
- 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)?
- Dynamic method
- 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-PAT tools
4.2 Hands-on Experiments
- a. Batch and repeated batch
- Wave® bioreactor
- b. Perfusion
- Microfluidics-cell separator with STR
- Ceramic membrane with STR
- c. Fed-Batch
- Glucose feeding strategy
- Oxygen uptake rate feeding strategy
- d. Continuous culture
- Substrate-feeding strategy
- Process-controlled stirred vessel bioreactor system
5. Process Analytical Technologies (PAT) and Operating in an online environment
Participants will be introduced to PAT tools such as for measuring cell concentration, cell viability, glucose substrate, and metabolic O2 and CO2 in real time, and learn how those data can be managed in an online environment. They will practice with innovative hardware PAT tools and the powerful PI system, used toward the management of real-time data and events, on site or remotely. This on-line capability can be used for process monitoring, trending, and troubleshooting key process parameters. Students can track whether their process is operating efficiently and even make changes directly, in some cases.
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 will be provided. Furthermore, access to computers and to internet/email will be provided in the laboratory.
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."
"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."
The program is under the direction of Jean-Francois Hamel, a Research Engineer in the MIT Department of Chemical Engineering.
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 complete the Custom Programs request form for further details.