Continuous analysis of dye-loaded, single cells on a microfluidic chip

Lab Chip. 2011 Apr 7;11(7):1333-41. doi: 10.1039/c0lc00370k. Epub 2011 Feb 16.

Abstract

Continuous analysis of two dyes loaded into single mammalian cells using laser-based lysis combined with electrophoretic separation was developed and characterized on microfluidic chips. The devices employed hydrodynamic flow to transport cells to a junction where they were mechanically lysed by a laser-generated cavitation bubble. An electric field then attracted the analyte into a separation channel while the membranous remnants passed through the intersection towards a waste reservoir. Phosphatidylcholine (PC)-supported bilayer membrane coatings (SBMs) provided a weakly negatively charged surface and prevented cell fouling from interfering with device performance. Cell lysis using a picosecond-pulsed laser on-chip did not interfere with concurrent electrophoretic separations. The effect of device parameters on performance was evaluated. A ratio of 2 : 1 was found to be optimal for the focusing-channel : flow-channel width and 3 : 1 for the flow-channel : separation-channel width. Migration times decreased with increased electric field strengths up to 333 V cm(-1), at which point the field strength was sufficient to move unlysed cells and cellular debris into the electrophoretic channel. The migration time and full width half-maximum (FWHM) of the peaks were independent of cell velocity for velocities between 0.03 and 0.3 mm s(-1). Separation performance was independent of the exact lysis location when lysis was performed near the outlet of the focusing channel. The migration time for cell-derived fluorescein and fluorescein carboxylate was reproducible with <10% RSD. Automated cell detection and lysis were required to reduce peak FWHM variability to 30% RSD. A maximum throughput of 30 cells min(-1) was achieved. Device stability was demonstrated by analyzing 600 single cells over a 2 h time span.

Publication types

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

MeSH terms

  • Animals
  • Cell Extracts
  • Cell Line, Tumor
  • Cell Separation
  • Dimethylpolysiloxanes / chemistry
  • Electricity
  • Electrophoresis
  • Equipment Design
  • Fluorescent Dyes / metabolism*
  • Glass / chemistry
  • Hydrodynamics
  • Lasers
  • Mice
  • Microfluidic Analytical Techniques / instrumentation
  • Microfluidic Analytical Techniques / methods*
  • Oligopeptides / chemistry
  • Oligopeptides / isolation & purification
  • Single-Cell Analysis / instrumentation
  • Single-Cell Analysis / methods*

Substances

  • Cell Extracts
  • Dimethylpolysiloxanes
  • Fluorescent Dyes
  • Oligopeptides
  • baysilon