Evaluation of digital PCR for absolute DNA quantification

Anal Chem. 2011 Sep 1;83(17):6474-84. doi: 10.1021/ac103230c. Epub 2011 Aug 1.

Abstract

The emerging technique of microfluidic digital PCR (dPCR) offers a unique approach to real-time quantitative PCR for measuring nucleic acids that may be particularly suited for low-level detection. In this study, we evaluated the quantitative capabilities of dPCR when measuring small amounts (<200 copies) of DNA and investigated parameters influencing technical performance. We used various DNA templates, matrixes, and assays to evaluate the precision, sensitivity and reproducibility of dPCR, and demonstrate that this technique can be highly reproducible when performed at different times and when different primer sets are targeting the same molecule. dPCR exhibited good analytical sensitivity and was reproducible outside the range recommended by the instrument manufacturer; detecting 16 estimated targets with high precision. The inclusion of carrier had no effect on this estimated quantity, but did improve measurement precision. We report disagreement when using dPCR to measure different template types and when comparing the estimated quantities by dPCR and UV spectrophotometry. Finally, we also demonstrate that preamplification can impose a significant measurement bias. These findings provide an independent assessment of low copy molecular measurement using dPCR and underline important factors for consideration in dPCR experimental design.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Dehydrogenase / genetics
  • Alcohol Dehydrogenase / metabolism
  • Arabidopsis Proteins / genetics
  • Arabidopsis Proteins / metabolism
  • DNA / analysis*
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / metabolism
  • Microfluidic Analytical Techniques / instrumentation
  • Microfluidic Analytical Techniques / methods
  • Microfluidic Analytical Techniques / standards*
  • Real-Time Polymerase Chain Reaction / standards*
  • Spectrophotometry, Ultraviolet

Substances

  • Arabidopsis Proteins
  • DNA
  • Alcohol Dehydrogenase
  • Fusion Proteins, bcr-abl