Microfluidic-assisted analysis of replicating DNA molecules

Nat Protoc. 2009;4(6):849-61. doi: 10.1038/nprot.2009.54. Epub 2009 May 14.

Abstract

Single molecule-based protocols have been gaining popularity as a way to visualize DNA replication at the global genomic- and locus-specific levels. These protocols take advantage of the ability of many organisms to incorporate nucleoside analogs during DNA replication, together with a method to display stretched DNA on glass for immunostaining and microscopy. We describe here a microfluidic platform that can be used to stretch and to capture labeled DNA molecules for replication analyses. This platform consists of parallel arrays of three-sided, 3- or 4-microm high, variable-width capillary channels fabricated from polydimethylsiloxane by conventional soft lithography, and of silane-modified glass coverslips to reversibly seal the open side of the channels. Capillary tension in these microchannels facilitates DNA loading, stretching and glass coverslip deposition from microliter-scale DNA samples. The simplicity and extensibility of this platform should facilitate DNA replication analyses using small samples from a variety of biological and clinical sources.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Chromosome Mapping / methods
  • DNA / analysis
  • DNA / chemistry*
  • DNA / genetics*
  • DNA Replication*
  • Genes
  • Genomics / methods
  • Glass
  • Indicators and Reagents
  • Microfluidic Analytical Techniques / methods*
  • Miniaturization / methods
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Silicon

Substances

  • Indicators and Reagents
  • DNA
  • Silicon