Single molecule methods have proven to be powerful tools that can yield complementary information to standard, ensemble averaged techniques. Single molecule methods typically involve either passive observation of single molecules (often through fluorescence) or direct manipulation of single molecules with tools such as optical tweezers or atomic force microscopes. In this talk, I will present work that I've done to help make advances in both passive observation (single molecule tracking) and active manipulation of single molecules. Importantly, the applications of this work involve not only biophysics, but also surface/interfacial phenomena.
In previous work at the University of Colorado at Boulder, we developed high throughput methods to track 10^4-10^6 single molecules, orders of magnitude more than typically reported. We also developed novel statistical methods to investigate these large statistical ensembles and identify important rare events and populations. Using these methods, we investigated mechanisms of interfacial protein aggregation, made the first single molecule observations of desorption-mediated surface diffusion and developed a super-resolution method of mapping non-covalent surface chemistry.
In my current work at JILA, I am helping to develop state-of-the-art methods for manipulation and control of single molecules. We have developed an ultrastable measurement platform for use in single molecule experiments. The long term stability of this platform (sub-nm lateral drift over 4 hours, sub-nm vertical drift over 1 hour) will not only provide reliable short term sub 0.1 nm precision, but also provide new opportunities for long-time-scale measurements on a single molecule. Importantly, this technology is compatible with optical tweezers, AFM and optical microscopes. In a complementary effort, we are developing new surface protocols to improve reliability of single molecule manipulation and force measurements. By making improvements in both instrumentation and sample preparation, we are advancing the state of the art in precision control of a single molecule.