Label-free and high-resolution protein/DNA nanoarray analysis using Kelvin probe force microscopy.

Using the scanning probe technique known as Kelvin probe force microscopy it is possible to successfully devise a sensor for charged biomolecules. The Kelvin probe force microscope is a tool for measuring local variations in surface potential across a substrate of interest. Because many biological molecules have a native state that includes the presence of charge centres (such as the negatively charged backbone of DNA), the formation of highly specific complexes between biomolecules will often be accompanied by local changes in charge density. By spatially resolving this variation in surface potential it is possible to measure the presence of a specific bound target biomolecule on a surface without the aid of special chemistries or any form of labelling. The Kelvin probe force microscope presented here is based on an atomic force microscopy nanoprobe offering high resolution (<10 nm), sensitivity (<50 nM) and speed (>1,100 microm s(-1)), and the ability to resolve as few as three nucleotide mismatches.