Label-free detection of DNA using field-effect transistors

Electronic DNA sensors based on field-effect transistor arrays operating in liquid environment, offer an alternative method for the detection of biomolecular binding events, without the requirement to label the target molecules. These semiconductor devices are sensitive to electrical charge variations that occur at the surface/electrolyte interface. Using such devices, the hybridization reaction of oligonucleotides with complementary single-stranded oligonucleotides, which are immobilized on the oxide surface of the transistor gate, can be detected. The detection principle is based on the intrinsic: charge of the nucleic acid molecules in liquid environment. In this article we present a summary of the 'DNA BioFET' project, which has been conducted in our group in recent years. We compare an electrostatic and a covalent immobilization protocol for the probe DNA. Most important for reliable signal readout is the use of a differential approach, for which a DNA microarray represents an ideal bioassay. With our FET setup we can either use a chip-to-chip reference with two electrically identical chips, which are coated with different probe sequences. A more sophisticated method, which makes use of the DNA microarray technology, was established with an aligned microspotting system enabling the coating of different channels out of the microarray with different probe sequences. So far our current chip design uses 16 channels enabling first proof-of-principle experiments. The detection method itself, however, offers the possibility to be up scaled to many thousands of sensor spots like currently used in fluorescence based DNA microarray chips. (c) 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.