10.26
Project Descriptions
Spring, 2002
Faculty
No. Title Advisor
1 Scaling Up Monoclonal Antibody in Novel and Traditional Bioreactors JFH
2 A Novel Fluidized-Bed Perfusion Bioreactor for Antibody Production JFH
3 Integration of Bioreactor with Novel Centrifuge for Improving Process JFH
Performance
4 Development of Process Control Loops for Operation of a Mammalian Cell JFH
Bioreactor for Protein Production
5 Performance Testing of a Proton-Exchange Membrane (PEM) Fuel Cell JM
6 Characterization of a Palladium-based Membrane Purifier for Production JM
of Fuel-Cell-Quality Hydrogen
7 Characterization of a H2-Selective Membrane System for Production of JM
Fuel-Cell-Quality Hydrogen
8 Mass Transport of Bioactive Molecules from Arterial Stents BSJ
9 Evaluation of New Instrument to Measure Swelling in Polymers BSJ
10 Reduction of Purge Time for an Airlock WHD
11 Heat and Mass Transfer during Cooking of Mashed Potatoes WHD/CKC
12 Enhancement of Dialysis with Ultrasonic Energy WHD/CKC
13 Hydrogen Storage on Carbon Nanostructures JBH
14 Separation of Fullerenes by Fractional Crystallization JBH
15 Modelling of Drag Reduction by Polymers in Crude Oil Pipelines: PSV
1. Effect of Injection and Mixing of the Polymeric Additive
16 Modelling of Drag Reduction by Polymers in Crude Oil Pipelines: PSV
2. Effect of Polymer Degradation on Drag Reduction
Massachusetts Institute of Technology
Department of Chemical
Engineering
Chemical Engineering Laboratory, Course 10.26
Spring 2002
Project
title: Scaling up Monoclonal Antibody in Novel
and Traditional Bioreactors
Project
location: Lab 13-3095
Sponsored
by: DasGip mbH (http://www.dasgip.de/),
Division of Bioengineering (BEH) and Biotechnology Process Engineering Center
(BPEC)
Consultants: Jose Manny Otero Mansour Sindi
Lab 16-436, ext. 3-2765 Lab 16-436, ext. 3-2765
E-mail: manny1@mit.edu E-mail: msindi@mediaone.net
Faculty
advisor: Jean-François Hamel
Office
56-483, ext. 8-6665
E-mail: jhamel@mit.edu
Objective
To
demonstrate: 1) the equivalency of CellFerm-Pro®
with traditional stirred-tank reactors for cell culture process development
and, 2) the scale-up ability of over two orders of magnitude.
In this project, students will:
·
Learn general techniques and processes relevant to a
career in the biotechnology and pharmaceutical industries.
·
Learn analytical techniques, such as cell counting and
lab-on-a chip technology.
·
Use aseptic techniques for maintaining a pure culture
in a bioreactor for several days.
·
Learn the operation of state-of-the-art
process-controlled bioreactors. Dr. Rix from DasGip will come from Gerrmany,
especially to give a lecture on the CellFerm-Pro®
to the students.
Desired
Student Team Background
1. Microbiology,
fermentation engineering or cell culture techniques; course 7.02 or equivalent.
3. Analytical techniques
in protein and antibody analysis (e.g. gel electrophoresis).
Project
Background
At
the industrial scale, hybridoma cells have become
standard cell lines for production of monoclonal antibodies. Bioprocess
development of hybridoma cell culture is dependent on
the ability to optimize a culture system at relatively small volumes, in a
short period, and cost-effectively. Traditional small-volume vessels may
include T-flasks, spinner flasks, roller bottles, shaker flasks, or other
conventional bioreactors that are simple to operate. However, these bioreactors
do not lend themselves to optimization of pH, dissolved oxygen levels,
temperature levels, or agitation.
Typically, optimization studies conducted as part of a process
development and scale up are done in liter-size fermentors.
Their operation is time consuming and costly in terms of cell culture medium.
New technologies, such as offered by the CellFerm-Pro®,
offer the potential to carry out optimization studies more efficiently in a
multi-vessel system using 10 times less cell culture medium per vessel (as low
as 50 mL). As a result, if equivalency of data
generated by the CellFerm-Pro® and
traditional STRs can be shown, the CellFerm-Pro® could quickly become the workhorse
standard for conducting optimization of cell culture processes, and as a result
could serve as the starting point for scaling up industrial processes.
Massachusetts Institute of Technology
Department of Chemical
Engineering
Chemical Engineering Laboratory, Course 10.26
Spring 2002
Project
title: A Novel Fluidized-Bed Perfusion
Bioreactor for Antibody Production
Project
location: Lab 56-454
Sponsored
by: Amersham Biosciences (http://bioprocess.apbiotech.com/),
and Biotechnology Process Engineering Center (BPEC)
Consultant: Rudolph Czirbik
Ph:
800-526-3593
Fax:
(732) 457-8301
E-mail: mailto:rudolf.czirbik@am.amershambiosciences.com
Faculty
advisor: Jean-François Hamel
Office
56-483, ext. 8-6665
E-mail: jhamel@mit.edu
Objective
This
project will study the antibody (Ab) production of hybridoma cells in a novel CytopilotÒ fluidized-bed bioreactor.
The study will be conducted through the analysis of key parameters including
glucose levels, medium composition, waste product concentration and antibody
titer.
In this project, students will:
·
Learn general techniques and processes relevant to a
career in the biotechnology and pharmaceutical industries.
·
Learn analytical techniques, such as cell counting and
lab-on-a chip technology.
·
Use aseptic techniques for maintaining a pure culture
in a bioreactor for several days.
·
Learn the operation of state-of-the-art
process-controlled bioreactors.
Desired Student Team Background
1. Microbiology, fermentation
engineering or cell culture techniques.
2. Course 7.02 or equivalent.
3. Analytical techniques
in protein and antibody analysis (e.g. gel electrophoresis).
Project
Background
Hybridoma cells are the product of fusing myeloma cells and B-lymphocytes, the latter being isolated from a host organism. The exposure of the host to the target antigen results in the B-lymphocytes raising Ab against the antigen. Myeloma cells are cancer cells, hence they reproduce indefinitely. Thus hybridoma cells produce the desired antibodies and grow indefinitely.
The
CytopilotÒ is a
laboratory scale fluidized-bed reactor for cell culture,designed
for continuous operation as a perfusion system, i.e. fresh medium is added at
the same rate as the spent medium is removed. In the CytopilotÒ, hybridoma cells
attach to and grow in the core of the microcarriers.
The microcarriers protect cells from shear forces in
the fluidized bed, while allowing nutrients to reach the cells through the
pores. The fluidized bed allows circulation of O2 and nutrients
throughout the column. Hybridoma cells produce and
release the antibodies into the supernatant.
Massachusetts Institute of Technology
Department of Chemical Engineering
Chemical Engineering Laboratory, Course 10.26
Spring 2002
Project title: Integration of
Bioreactor with Novel Centrifuge for improving Process Performance
Project location: Lab 16-436
Sponsored by: Kendro Lab Products and
Consultant: Rick Bradley
Ph: (800) 522-7746
E-mail:
bradlerd@kendro.com
Faculty advisor: Jean-François Hamel
Office 56-483, ext. 8-6665
E-mail: jhamel@mit.edu
Objective
This
project will aim to: 1) study the effect of integrating a novel centrifuge with
a stirred-tank bioreactor on process performance, and 2) assess the potential
of the centrifuge to separate dead and live cells and to recycle the live cells
back to the bioreactor. This work will be conducted through the analysis of key
parameters including glucose levels, medium composition, cell concentration,
cell viability, waste product concentration and antibody titer.
In this project, students will:
·
Learn general techniques and processes relevant to a
career in the biotechnology and pharmaceutical industries.
·
Learn analytical techniques, such as cell counting and
lab-on-a chip technology.
·
Use aseptic techniques for maintaining a pure culture
in a bioreactor for several days.
·
Learn the operation of state-of-the-art
process-controlled bioreactor and centrifuge.
Desired Student Team Background
1. Microbiology,
fermentation engineering or cell culture techniques.
2. Course 7.02 or equivalent.
3. Analytical techniques
in protein and antibody analysis (e.g. gel electrophoresis).
Background
A
major component of the process for making monoclonal antibodies by cell culture
is the ability to produce gram quantities of product using a robust and simple
process. The commercial importance of monoclonal antibodies for diagnostic or
therapeutic applications has fueled the demand for their efficient production.
The Kendro Company has recently introduced the Centritech centrifuge which can be coupled with a
bioreactor for continuous operation of a bioreactor in the perfusion mode, in
which fresh medium is fed to the bioreactor at the same rate as spent medium is
removed. This study will produce data to determine the performance and the
economy of the perfusion system and assess the feasibility of removing dead
cells from the bioreactor selectively.
Massachusetts Institute of Technology
Department of Chemical Engineering
Chemical Engineering
Laboratory, Course 10.26
Spring 2002
Project
Title: Development of
Process Control Loops for Operation of a Mammalian Cell Bioreactor for Protein
Production
Project Location: Undergraduate
Chemical Engineering Lab
Biotechnology
Section
Sponsored
By:
Consultant: Jose M. Otero
(Manny)
Lab 16-436,
ext. 3-2165
E-mail: manny1@mit.edu
Faculty Advisor: Jean-François
Hamel
Office 56-483,
ext. 8-6665
E-mail: jhamel@mit.edu
Objective
To
develop a process control strategy for fed-batch culture of animal cells.
In this project, students will:
·
Learn how to design and implement a process control
scheme for maintaining parameters (e.g. glucose concentration) in a bioreactor.
·
Learn techniques relevant to a career in the
biotechnology and pharmaceutical industries.
·
Learn the operation of a state-of-the-art
process-controlled bioreactor.
Desired
Student Team Background and Support
·
Prior knowledge of process
control would be helpful. Expert consultants from PID Control Systems and
Honeywell will be available and provide necessary background.
·
No prior knowledge of cell
culture is needed.
Project
Background
Bioreactors have long been used to develop
and produce therapeutic and diagnostic agents serving many purposes, from
combating infectious disease to facilitating analytical chemistry
techniques. Critical to operation of
modern day bioreactors, which may vary in scale from 1 L to 10,000 L, is the ability
to provide automated control for process variables including temperature,
dissolved oxygen, pH, foam level control, and glucose/lactate
concentrations. For example, glucose is
often used as the control parameter in fed-batch techniques for achieving
high-cell density cultures while minimizing toxic lactate production. Control
modules such as the proportional-integral-derivative (PID) control can be very
effective in maintaining glucose to a low level (<1 g/L) through the feeding
of a concentrated solution of glucose.
The
elements of PID control may be better understood by evaluating each component
individually. The control unit provided
by Honeywell for this project has been interfaced to a computer and can easily
be programmed. The bioreactor available for the project is a state-of-the-art
stirred-tank reactor.
Project 5
10.26
Chemical Engineering Project Laboratory
Spring
2002
Performance Testing of a Proton-Exchange Membrane (PEM) Fuel Cell
Faculty Advisor: Industrial
Consultant
Dr. Jerry Meldon K.M. Abraham
Room 66-260 Chief Technology Officer
Tel: 617 452-3460 E-KEM Sciences
Jerry.Meldon@tufts.edu
Tel: 781-444-8453
Fax 781 455-6899
Ekemtec@aol.com
Goal
Determination of performance characteristics of a PEM fuel cell.
Background
Fuel cells generate electric power with higher thermodynamic efficiency and less environmental impact than conventional fossil-fuel-fired power plants. It is anticipated that the first fuel cell modules to capture a significant shares of the markets for stationary (home, industry, etc.) and/or mobile (vehicular) power sources will be low-temperature (<100oC) systems based on polymeric cation-exchange membranes (generally referred to as Proton-Exchange or PolyElectrolyte Membranes, PEMs). Such membranes consist of an organic polymer matrix with negatively charged sulfonate side groups, which is sandwiched between porous electrodes. The immobilized negative charge makes the membranes almost exclusively permeable to neutral molecules like water and cations like hydrogen ions. The cathode is exposed to humidified gas containing hydrogen, the anode to humidified oxygen or air. The overall chemical reaction is simply H2 + ½ O2 = H2O.
Our goal in this project is to characterize the performance of a PEM fuel cell.
Approach
· The open literature contains extensive information on fuel cell technology. The recent monograph, Fuel Cells Explained, by J. Larminie and A. Dicks, provides an excellent, lucid introduction to the field A website which provides useful links is: http://chemengineer.about.com/cs/fuelcells1/index.htm
Search the literature for basic information on fuel cells and specifics on the design and operation of PEM fuel cells.
· Develop a preliminary design of a small bench-scale system, based on your own simplified theoretical model and mathematical analysis, keeping in mind the data you will be obtaining (see below) and the availability of advice from the industrial consultant. The apparatus will be centered on a fuel cell along the lines shown in the figure. Determine whether an inexpensive system, or at least parts of one, is commercially available. If not, determine the cost of assembling your own. Verify that necessary ancillary equipment such as a multimeter is available for use.
· After deciding upon and securing the necessary parts, assemble the system and perform preliminary shakedown tests.
· Design and execute an experimental program to characterize the performance of the fuel cell in terms of current and power densities, efficiency and constancy of performance (in the short term) as functions of gas flowrates, use of pure oxygen vs. air and , if feasible, temperature and pressures.
Project xx
10.26
Chemical Engineering Project Laboratory
Spring
2002
Design and Characterization of a Reactor that Produces Hydrogen for Fuel Cells
Faculty Advisor: Industrial
Consultant
Dr. Jerry Meldon Dr. Charles Kruger
Room 66-260 WJA Inc.
Voice Mailbox
Tel:
617 627-2338
Goal
Identification of optimal conditions for operating a catalytic reactor to produce hydrogen for fuel cells via steam reforming of methanol, ethanol or both.
Background
Fuel cells generate electric power with considerably higher thermodynamic efficiency and less environmental impact than conventional fossil-fuel-fired power plants. It is anticipated that the fuel cell design which will be the first to capture a significant share of the markets for stationary (home, industry, etc.) and/or mobile (vehicular) power sources are “low-temperature” (<100oC) systems based on polymeric cation-exchange membranes. The latter membranes, which are permeable to hydrogen ions (protons) but impermeable to anions, are sandwiched between porous electrodes. The cathode is exposed to hydrogen, the anode to oxygen. See Projects xxx and xxxx for further details.
The primary obstacle to large-scale commercialization of fuel cells is cost. Size is also a major concern, particularly in vehicular applications. A third issue is the source of hydrogen. Not only is there currently no nationwide hydrogen distribution network, there is public resistance to the idea of handling and/or storage of pressurized hydrogen. The most attractive alternative is to generate hydrogen on demand from sources the public will accept..
The most promising such sources, for which there is extensive technical know-how, are mixtures of steam plus a hydrocarbon(s) [e.g, coal, and components of natural gas (methane) and oil]. When any of these mixtures are fed to a suitably designed catalytic reactor, hydrogen is formed via steam reforming of the hydrocarbon.
This project focuses on hydrogen production from mixtures of steam plus methanol and/or ethanol, for which the reforming reactions are:
CH3OH
+ H2O = CO2 + 3H2
C2H5OH
+ 3H2O = 2CO2 + 6H2
There is at least one side reaction, the (reverse) water-gas-shift (WGS):
CO2
+ H2 = CO + H2O
There is substantial interest in using either alcohol as a hydrogen source because of the relative safety, comparatively low reforming temperature, and potential use of biomass (e.g., agricultural and forestry waste products) as a feedstock for fermentation-based alcohol production. Note that the use of biomass minimizes the buildup of atmospheric CO2.
Our goal in this project is to use a bench-scale reactor to carry out an experimental investigation of catalytic steam reforming of one or both these alcohols, and thereby provide reliable data to engineers engaged in large-scale hydrogen production for fuel cells.
Approach
1) The open literature contains extensive data on the performance of various catalysts in steam reforming of each alcohol, as well as data on the WGS reaction and the potential for catalyst coking and/or poisoning. Search the recent literature (1980-present), summarize your findings, determine the availability of desired catalyts, and make recommendations regarding choice of alcohol(s), catalyst(s) and ranges of operating conditions (type of reactor, temperature, pressure, space velocity, etc.) to investigate experimentally
2) Design and construct a reactor to produce sufficient hydrogen to operate a low wattage fuel cell (the industrial consultant will provide guidance with respect to wattage and reactor design and construction).
3) Design and execute an experimental program to obtain data that will make possible the rational choice of operating conditions for a pilot-plant-scale reactor.
Project 7
10.26
Chemical Engineering Project Laboratory
Spring
2002
Characterization of a H2-Selective Membrane System for Production of Fuel-Cell-Quality Hydrogen
Faculty Advisor: Industrial
Consultant
Dr. Jerry Meldon Dr. Walter Juda
Room 66-260 WJA Inc.
Tel:
Jerry.Meldon@tufts.edu
Tel: 617 627-2786