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

Laimonas Kelbauskas, Shashanka P. Ashili, Jeff Houkal, Dean Smith, Aida Mohammadreza, Kristen B. Lee, Jessica Forrester, Ashok Kumar, Yasser H. Anis, Thomas G. Paulson, Cody A. Youngbull, Yanqing Tian, Mark R. Holl, Roger H. Johnson, Deirdre Meldrum

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17 Scopus citations

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 trie 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.

Original languageEnglish (US)
Article number037008
JournalJournal of biomedical optics
Volume17
Issue number3
DOIs
StatePublished - Mar 1 2012

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Keywords

  • Cell-cell interactions
  • Heterogeneity
  • Microfabrication
  • Microfluidics
  • Optical sensing
  • Respiration
  • Single-cell

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Biomaterials
  • Atomic and Molecular Physics, and Optics
  • Biomedical Engineering

Cite this

Kelbauskas, L., Ashili, S. P., Houkal, J., Smith, D., Mohammadreza, A., Lee, K. B., Forrester, J., Kumar, A., Anis, Y. H., Paulson, T. G., Youngbull, C. A., Tian, Y., Holl, M. R., Johnson, R. H., & Meldrum, D. (2012). Method for physiologic phenotype characterization at the single-cell level in non-interacting and interacting cells. Journal of biomedical optics, 17(3), [037008]. https://doi.org/10.1117/1.JBO.17.3.037008