title: Microbioreactor arrays with parametric control for high-throughput experimentation.
abstract: A scalable array technology for parametric control of high-throughput cell cultivations is demonstrated. The technology makes use of commercial printed circuit board (PCB) technology, integrated circuit sensors, and an electrochemical gas generation system. We present results for an array of eight 250 microl microbioreactors. Each bioreactor contains an independently addressable suite that provides closed-loop temperature control, generates feed gas electrochemically, and continuously monitors optical density. The PCB technology allows for the assembly of additional off-the-shelf components into the microbioreactor array; we demonstrate the use of a commercial ISFET chip to continuously monitor culture pH. The electrochemical dosing system provides a powerful paradigm for reproducible gas delivery to high-density arrays of microreactors. Growth data are presented for Escherichia coli cultured in the array with varying microaerobic conditions using electrochemically generated oxygen. Additionally, we present data on carbon dioxide generation for pH dosing.
authors.affiliation: Berkeley Sensor & Actuator Center (BSAC), Dept. of Electrical Engineering and Computer Science, 497 Cory Hall, University of California at Berkeley, Berkeley, California 94720, USA.
authors.forename: Michel M
authors.initials: MM
authors.lastname: Maharbiz
authors.forename: William J
authors.initials: WJ
authors.lastname: Holtz
authors.forename: Roger T
authors.initials: RT
authors.lastname: Howe
authors.forename: Jay D
authors.initials: JD
authors.lastname: Keasling
mesh_terms: D019149:Bioreactors / Q000382:microbiology*; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods; D004563:Electrochemistry / Q000295:instrumentation* / Q000379:methods; D004566:Electrodes; D004867:Equipment Design; D019544:Equipment Failure Analysis; D004926:Escherichia coli / Q000254:growth & development* / Q000378:metabolism*; D005246:Feedback / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008904:Miniaturization / Q000379:methods; D010100:Oxygen / Q000378:metabolism*; D013696:Temperature
chemical_list: D010100:Oxygen