Sequence Genomes by Pulling on DNA Molecules

Miniaturization has driven down the cost of tools used in bioanalysis and diagnostics, with single molecules becoming the ultimate detection limit. I will describe how one can exploit mechanical properties of individual biomolecules to determine changes in their state or structure. Our aim is to build a force-spectroscopy-on-a-chip device that can detect and manipulate many (millions) single molecules in parallel. A critical element of this approach is the design of materials properties of molecular handles or probes. By tuning interactions of these probes with magnetic or electric fields, we are able to apply piconewton forces to individual DNA molecules and record their response with a single base sensitivity. The technique is attractive for following the process of DNA polymerization or hybridization, because the method is label free and can be implemented with natural enzymes and substrates. I will discuss potential applications of this approach to high throughput analyses such as genome sequencing.