title: A platform for high-throughput bioenergy production phenotype characterization in single cells.
abstract: Driven by an increasing number of studies demonstrating its relevance to a broad variety of disease states, the bioenergy production phenotype has been widely characterized at the bulk sample level. Its cell-to-cell variability, a key player associated with cancer cell survival and recurrence, however, remains poorly understood due to ensemble averaging of the current approaches. We present a technology platform for performing oxygen consumption and extracellular acidification measurements of several hundreds to 1,000 individual cells per assay, while offering simultaneous analysis of cellular communication effects on the energy production phenotype. The platform comprises two major components: a tandem optical sensor for combined oxygen and pH detection, and a microwell device for isolation and analysis of single and few cells in hermetically sealed sub-nanoliter chambers. Our approach revealed subpopulations of cells with aberrant energy production profiles and enables determination of cellular response variability to electron transfer chain inhibitors and ion uncouplers.
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, 1001S. McAllister Ave., Tempe, AZ 85287, USA.
authors.forename: Laimonas
authors.initials: L
authors.lastname: Kelbauskas
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, 1001S. McAllister Ave., Tempe, AZ 85287, USA.
authors.forename: Honor
authors.initials: H
authors.lastname: Glenn
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, 1001S. McAllister Ave., Tempe, AZ 85287, USA.
authors.forename: Clifford
authors.initials: C
authors.lastname: Anderson
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, 1001S. McAllister Ave., Tempe, AZ 85287, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Messner
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, 1001S. McAllister Ave., Tempe, AZ 85287, USA.
authors.forename: Kristen B
authors.initials: KB
authors.lastname: Lee
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, 1001S. McAllister Ave., Tempe, AZ 85287, USA.
authors.forename: Ganquan
authors.initials: G
authors.lastname: Song
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, 1001S. McAllister Ave., Tempe, AZ 85287, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Houkal
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, 1001S. McAllister Ave., Tempe, AZ 85287, USA.
authors.forename: Fengyu
authors.initials: F
authors.lastname: Su
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, 1001S. McAllister Ave., Tempe, AZ 85287, USA.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, 1001S. McAllister Ave., Tempe, AZ 85287, USA.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, 1001S. McAllister Ave., Tempe, AZ 85287, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, 1001S. McAllister Ave., Tempe, AZ 85287, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Bussey
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, 1001S. McAllister Ave., Tempe, AZ 85287, USA.
authors.forename: Roger H
authors.initials: RH
authors.lastname: Johnson
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute, Arizona State University, 1001S. McAllister Ave., Tempe, AZ 85287, USA.
authors.forename: Deirdre R
authors.initials: DR
authors.lastname: Meldrum
mesh_terms: D019149:Bioreactors; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology*
chemical_list: D010100:Oxygen