Publication I October 30, 2008

Switchable DNA interfaces for the highly sensitive
detection of label-free DNA targets

We report a method to detect label-free oligonucleotide targets. The
conformation of surface-tethered probe nucleic acids is modulated by
alternating electric fields, which cause the molecules to extend away
from or fold onto the biased surface. Binding (hybridization) of
targets to the single-stranded probes results in a pronounced enhancement of the layer-height modulation amplitude, monitored
optically in real time. The method features an exceptional detection
limit of <3  108 bound targets per cm2 sensor area. Single base-pair
mismatches in the sequences of DNA complements may readily be
identified; moreover, binding kinetics and binding affinities can be
determined with high accuracy. When driving the DNA to oscillate at
frequencies in the kHz regime, distinct switching kinetics are revealed
for single- and double-stranded DNA. Molecular dynamics are used to
identify the binding state of molecules according to their characteristic kinetic fingerprints by using a chip-compatible detection format.