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J Biomed Opt. 2012 Mar;17(3):037008. doi: 10.1117/1.JBO.17.3.037008.

Method for physiologic phenotype characterization at the single-cell level in non-interacting and interacting cells.

Author information

1
Arizona State University, Biodesign Institute, Tempe, Arizona, USA. lkelbaus@asu.edu

Abstract

Intercellular heterogeneity is a key factor in a variety of core cellular processes including proliferation, stimulus response, carcinogenesis, and drug resistance. However, cell-to-cell variability studies at the single-cell level have been hampered by the lack of enabling experimental techniques. We present a measurement platform that features the capability to quantify oxygen consumption rates of individual, non-interacting and interacting cells under normoxic and hypoxic conditions. It is based on real-time concentration measurements of metabolites of interest by means of extracellular optical sensors in cell-isolating microwells of subnanoliter volume. We present the results of a series of measurements of oxygen consumption rates (OCRs) of individual non-interacting and interacting human epithelial cells. We measured the effects of cell-to-cell interactions by using the system's capability to isolate two and three cells in a single well. The major advantages of the approach are: 1. ratiometric, intensity-based characterization of the metabolic phenotype at the single-cell level, 2. minimal invasiveness due to the distant positioning of sensors, and 3. ability to study the effects of cell-cell interactions on cellular respiration rates.

PMID:
22502580
PMCID:
PMC3602818
DOI:
10.1117/1.JBO.17.3.037008
[Indexed for MEDLINE]
Free PMC Article
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