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Proceedings Article

A novel method for multiparameter physiological phenotype characterization at the single-cell level

[+] Author Affiliations
Laimonas Kelbauskas, Shashanka Ashili, Jeff Houkal, Dean Smith, Aida Mohammadreza, Kristen Lee, Ashok Kumar, Cody Youngbull, Yanqing Tian, Roger Johnson, Mark Holl, Deirdre Meldrum

Arizona State Univ. (USA)

Yasser Anis

Cairo Univ. (Egypt)

Tom Paulson

Fred Hutchinson Cancer Research Ctr. (USA)

Proc. SPIE 7902, Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues IX, 79021Q (February 10, 2011); doi:10.1117/12.875483
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From Conference Volume 7902

  • Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues IX
  • Daniel L. Farkas; Dan V. Nicolau; Robert C. Leif
  • San Francisco, California, USA | January 22, 2011

abstract

Non-genetic intercellular heterogeneity has been increasingly recognized as one of the key factors in a variety of core cellular processes including proliferation, stimulus response, carcinogenesis and drug resistance. Many diseases, including cancer, originate in a single or a few cells. Early detection and characterization of these abnormal cells can provide new insights into the pathogenesis and serve as a tool for better disease diagnosis and treatment. We report on a novel technology for multiparameter physiological phenotype characterization at the single-cell level. It is based on real-time measurements of concentrations of several metabolites by means of extracellular optical sensors in microchambers of sub-nL volume containing single cells. In its current configuration, the measurement platform features the capability to detect oxygen consumption rate and pH changes under normoxic and hypoxic conditions at the single-cell level. We have conceived, designed and developed a semi-automated method for single-cell manipulation and loading into microwells utilizing custom, high-precision fluid handling at the nanoliter scale. We present the results of a series of measurements of oxygen consumption rates (OCRs) of single human metaplastic esophageal epithelial cells. In addition, to assess the effects of cell-to-cell interactions, we have measured OCRs of two and three cells placed in a single well. The major advantages of the approach are a) multiplexed characterization of cell phenotype at the single-cell level, b) minimal invasiveness due to the distant positioning of sensors, and c) flexibility in terms of accommodating measurements of other metabolites or biomolecules of interest.

© (2011) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.
Citation

Laimonas Kelbauskas ; Shashanka Ashili ; Jeff Houkal ; Dean Smith ; Aida Mohammadreza, et al.
"A novel method for multiparameter physiological phenotype characterization at the single-cell level", Proc. SPIE 7902, Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues IX, 79021Q (February 10, 2011); doi:10.1117/12.875483; http://dx.doi.org/10.1117/12.875483


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