A high-throughput platform for analysis of single-molecule protein-DNA interactions
One of the least appreciated aspects of TIRFM-based biochemistry is the difficulty of obtaining statistically relevant information from experiments designed to monitor the progress of individual biochemical reactions. This is especially difficult when using relatively complex, long DNA molecules such as those needed to study complex aspects of DNA repair. To overcome this problem we are developing new technologies that use fluid lipid bilayers to render surfaces inert to biological molecules and combine this with micro- and nano-scale materials engineering, which will enable us to construct parallel arrays containing hundreds of individual DNA molecules with user-defined positions, orientations, tensions, and topologies. These DNA arrays will allow parallel processing of hundreds, or possibly thousands, of individual protein-nucleic acid interactions in a single TIRFM experiment and will serve as an incredibly powerful tool for single-molecule research.