Physical Chemistry Seminar: Professor Randall Goldsmith, University of Wisconsin–Madison
About the Seminar
"Label-free Detection and Hydrodynamic Profiling of Single Solution-Phase Molecules using Optical Microcavities"
The vast majority of chemistry and biology occurs in solution, and new label-free analytical techniques that can help resolve solution-phase complexity at the single-molecule level can provide new microscopic perspectives of unprecedented detail. Here, we use the increased light-molecule interactions in high-finesse fiber Fabry-Pérot microcavities to detect individual biomolecules as small as 1.2 kDa (10 amino acids) with signal-to-noise ratios >100, even as the molecules are freely diffusing in solution. Our method delivers 2D intensity and temporal profiles, enabling the distinction of sub-populations in mixed samples. Strikingly, we observe a linear relationship between passage time and molecular radius, unlocking the potential to gather crucial information about diffusion and solution-phase conformation. Furthermore, mixtures of biomolecule isomers of the same molecular weight can also be resolved. Detection is based on a novel molecular velocity filtering and dynamic thermal priming mechanism leveraging both photo-thermal bistability and Pound-Drever-Hall cavity locking. This technology holds broad potential for applications in life and chemical sciences and represents a major advancement in label-free in vitro single-molecule techniques.
About the Speaker
Randall Goldsmith is the Helfaer Professor of Chemistry and an affiliate of the Department of Electrical and Computer Engineering. He completed undergraduate degrees in chemistry and biology (2002) at Cornell University. He received his Ph.D at Northwestern University (2008) studying photoinduced electron transfer under the direction of Professors Michael Wasielewski and Mark Ratner, and performed postdoctoral work at Stanford University with Professor W.E. Moerner, where he became profoundly convinced that molecules deserve to be looked at one at a time. He has been a faculty member in the Department of Chemistry at the University of Wisconsin Madison since 2011 where his research interests span single-molecule spectroscopy, micro and nanophotonics, chemical catalysis, photochemistry, and biophysics. His work has been recognized with a DARPA young faculty award, NSF CAREER award, Alzheimer’s Association Young Faculty Award, Dreyfus Teacher-Scholar Award, and Journal of Physical Chemistry Lectureship Award. He was recently designated a Schmidt Futures Polymath.