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

Laimonas Kelbauskas, Shashanka Ashili, Jeff Houkal, Dean Smith, Aida Mohammadreza, Kristen Lee, Ashok Kumar, Yasser Anis, Tom Paulson, Cody Youngbull, Yanqing Tian, Roger Johnson, Mark Holl, Deirdre Meldrum

Research output: Chapter in Book/Report/Conference proceedingConference contribution

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.

Original languageEnglish (US)
Title of host publicationImaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues IX
DOIs
StatePublished - Apr 20 2011
EventImaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues IX - San Francisco, CA, United States
Duration: Jan 22 2011Jan 25 2011

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume7902
ISSN (Print)1605-7422

Other

OtherImaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues IX
CountryUnited States
CitySan Francisco, CA
Period1/22/111/25/11

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ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Atomic and Molecular Physics, and Optics
  • Biomaterials
  • Radiology Nuclear Medicine and imaging

Cite this

Kelbauskas, L., Ashili, S., Houkal, J., Smith, D., Mohammadreza, A., Lee, K., Kumar, A., Anis, Y., Paulson, T., Youngbull, C., Tian, Y., Johnson, R., Holl, M., & Meldrum, D. (2011). A novel method for multiparameter physiological phenotype characterization at the single-cell level. In Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues IX [79021Q] (Progress in Biomedical Optics and Imaging - Proceedings of SPIE; Vol. 7902). https://doi.org/10.1117/12.875483