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 publicationProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume7902
DOIs
StatePublished - 2011
EventImaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues IX - San Francisco, CA, United States
Duration: Jan 22 2011Jan 25 2011

Other

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

Fingerprint

phenotype
Oxygen
Metabolites
Phenotype
cells
Optical sensors
oxygen consumption
Biomolecules
Time measurement
Oxygen Consumption
metabolites
Fluids
Sensors
Pharmaceutical Preparations
pathogenesis
Drug Resistance
Cell Communication
optical measuring instruments
Carcinogenesis
stimuli

ASJC Scopus subject areas

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

Cite this

Kelbauskas, L., Ashili, S., Houkal, J., Smith, D., Mohammadreza, A., Lee, K., ... Meldrum, D. (2011). A novel method for multiparameter physiological phenotype characterization at the single-cell level. In Progress in Biomedical Optics and Imaging - Proceedings of SPIE (Vol. 7902). [79021Q] https://doi.org/10.1117/12.875483

A novel method for multiparameter physiological phenotype characterization at the single-cell level. / Kelbauskas, Laimonas; Ashili, Shashanka; Houkal, Jeff; Smith, Dean; Mohammadreza, Aida; Lee, Kristen; Kumar, Ashok; Anis, Yasser; Paulson, Tom; Youngbull, Cody; Tian, Yanqing; Johnson, Roger; Holl, Mark; Meldrum, Deirdre.

Progress in Biomedical Optics and Imaging - Proceedings of SPIE. Vol. 7902 2011. 79021Q.

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

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 Progress in Biomedical Optics and Imaging - Proceedings of SPIE. vol. 7902, 79021Q, Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues IX, San Francisco, CA, United States, 1/22/11. https://doi.org/10.1117/12.875483
Kelbauskas L, Ashili S, Houkal J, Smith D, Mohammadreza A, Lee K et al. A novel method for multiparameter physiological phenotype characterization at the single-cell level. In Progress in Biomedical Optics and Imaging - Proceedings of SPIE. Vol. 7902. 2011. 79021Q https://doi.org/10.1117/12.875483
Kelbauskas, Laimonas ; Ashili, Shashanka ; Houkal, Jeff ; Smith, Dean ; Mohammadreza, Aida ; Lee, Kristen ; Kumar, Ashok ; Anis, Yasser ; Paulson, Tom ; Youngbull, Cody ; Tian, Yanqing ; Johnson, Roger ; Holl, Mark ; Meldrum, Deirdre. / A novel method for multiparameter physiological phenotype characterization at the single-cell level. Progress in Biomedical Optics and Imaging - Proceedings of SPIE. Vol. 7902 2011.
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