Letter abstract

Nature Biotechnology 26, 825 - 830 (2008)
Published online: 29 June 2008 | doi:10.1038/nbt1416

Electrostatic readout of DNA microarrays with charged microspheres

Nathan G Clack1,3, Khalid Salaita2,3 & Jay T Groves1,2


DNA microarrays are used for gene-expression profiling, single-nucleotide polymorphism detection and disease diagnosis1, 2, 3. A persistent challenge in this area is the lack of microarray screening technology suitable for integration into routine clinical care4, 5. Here, we describe a method for sensitive and label-free electrostatic readout of DNA or RNA hybridization on microarrays. The electrostatic properties of the microarray are measured from the position and motion of charged microspheres randomly dispersed over the surface. We demonstrate nondestructive electrostatic imaging with 10-mum lateral resolution over centimeter-length scales, which is four-orders of magnitude larger than that achievable with conventional scanning electrostatic force microscopy. Changes in surface charge density as a result of specific hybridization can be detected and quantified with 50-pM sensitivity, single base-pair mismatch selectivity and in the presence of complex background. Because the naked eye is sufficient to read out hybridization, this approach may facilitate broad application of multiplexed assays.

  1. Biophysics Graduate Group, University of California, Berkeley, California 94720-3220, USA.
  2. Department of Chemistry, University of California, Berkeley, California 94720-3220, USA.
  3. These authors contributed equally to this work.

Correspondence to: Jay T Groves1,2 e-mail: jtgroves@lbl.gov


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