4.8 Article

Digital microfluidic isolation of single cells for -Omics

Journal

NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41467-020-19394-5

Keywords

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Funding

  1. Genome Canada
  2. Connaught Innovation Award
  3. Canadian Foundation for Innovation (CFI)
  4. Ontario Research Fund (ORF)
  5. Natural Sciences and Engineering Research Council (NSERC)
  6. University of Toronto's Medicine by Design initiative - Canada First Research Excellence Fund (CFREF)
  7. Canadian Institutes for Health Research (CIHR)
  8. Medicine by Design
  9. University of Toronto Faculty of Arts and Science
  10. Precision Medicine initiative (PRiME)
  11. Canada Research Chair (CRC) program

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We introduce Digital microfluidic Isolation of Single Cells for -Omics (DISCO), a platform that allows users to select particular cells of interest from a limited initial sample size and connects single-cell sequencing data to their immunofluorescence-based phenotypes. Specifically, DISCO combines digital microfluidics, laser cell lysis, and artificial intelligence-driven image processing to collect the contents of single cells from heterogeneous populations, followed by analysis of single-cell genomes and transcriptomes by next-generation sequencing, and proteomes by nanoflow liquid chromatography and tandem mass spectrometry. The results described herein confirm the utility of DISCO for sequencing at levels that are equivalent to or enhanced relative to the state of the art, capable of identifying features at the level of single nucleotide variations. The unique levels of selectivity, context, and accountability of DISCO suggest potential utility for deep analysis of any rare cell population with contextual dependencies. Multi-Omic approaches are a powerful way for obtaining in-depth understanding of a cell's state. Here the authors present DISCO, combining digital microfluidics, laser cell lysis, and artificial intelligence-driven image processing to analyze single-cell genomes, transcriptomes and proteomes in a mixed population.

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