Microbioreactors for bioprocess development

This thesis presents the design, fabrication, and characterization of a microbioreactor integrated with automated sensors and actuators as a step towards high-throughput bioprocess development. In particular, this thesis demonstrates the feasibility of culturing microbial cells in microliter-volume reactors in batch, continuous, fed-batch operations. The microbioreactor is fabricated out of poly(methylmethacrylate) and poly(dimethylsiloxane). Active mixing is made possible by a miniature magnetic stir bar. Online optical measurements for optical density, pH, and dissolved oxygen are integrated. Oxygenation in the microbioreactor is characterized and reproducible batch fermentation of Escherichia coli and Saccharomyces cerevisiae are demonstrated and benchmarked with benchscale bioreactors. Global gene expression analysis of S. cerevisiae exhibits physiological and molecular characteristics which parallel those of large-scales. A microchemostat, continuous culture of microbial cells, is realized in the microbioreactor. E. coli cells are fed by pressure-driven single phase flow of fresh medium through a microchannel. Chemotaxis, the back growth of bacterial cells into the medium feed channel, is prevented by local heating.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Chemical Engineering

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2006

Author dc:creator

• Zhang, Zhiyu (Scientist in chemical engineering) Massachusetts Institute of Technology

Advisor dc:contributor.advisor

• Klavs F. Jensen.

• Chemical Engineering.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/39638

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/39638