Coulomb blockage of hybridization in two-dimensional DNA arrays

Arnold Vainrub, Bernard Pettitt

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Experiments on DNA microarrays have revealed substantial differences in hybridization thermodynamics between DNA free in solution and surface tethered DNA. Here we develop a mean field model of the Coulomb effects in two-dimensional DNA arrays to understand the binding isotherms and thermal denaturation of the double helix. We find that the electrostatic repulsion of the assayed nucleic acid from the array of DNA probes dominates the binding thermodynamics, and thus causes the Coulomb blockage of the hybridization. The results explain, observed in DNA microarrays, the dramatic decrease of the hybridization efficiency and the thermal denaturation curve broadening as the probe surface density grows. We demonstrate application of the theory for evaluation and optimization of the sensitivity, specificity, and the dynamic range of DNA array devices.

Original languageEnglish (US)
Number of pages1
JournalPhysical Review E - Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics
Volume66
Issue number4
DOIs
StatePublished - Oct 17 2002
Externally publishedYes

Fingerprint

DNA Microarray
deoxyribonucleic acid
Thermodynamics
Probe
Mean-field Model
Dynamic Range
Helix
biopolymer denaturation
Electrostatics
Specificity
Decrease
Curve
Optimization
Evaluation
thermodynamics
probes
nucleic acids
Demonstrate
Experiment
helices

ASJC Scopus subject areas

  • Statistical and Nonlinear Physics
  • Statistics and Probability
  • Condensed Matter Physics

Cite this

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AB - Experiments on DNA microarrays have revealed substantial differences in hybridization thermodynamics between DNA free in solution and surface tethered DNA. Here we develop a mean field model of the Coulomb effects in two-dimensional DNA arrays to understand the binding isotherms and thermal denaturation of the double helix. We find that the electrostatic repulsion of the assayed nucleic acid from the array of DNA probes dominates the binding thermodynamics, and thus causes the Coulomb blockage of the hybridization. The results explain, observed in DNA microarrays, the dramatic decrease of the hybridization efficiency and the thermal denaturation curve broadening as the probe surface density grows. We demonstrate application of the theory for evaluation and optimization of the sensitivity, specificity, and the dynamic range of DNA array devices.

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