Madison Reporter

Scientists at the University of Wisconsin–Madison have developed the most sensitive method yet for detecting and profiling a single molecule, potentially advancing drug discovery and the development of advanced materials. The new technique, detailed in the journal Nature, marks a significant advancement in observing individual molecules without fluorescent labels.

“We’re very excited about this,” said Randall Goldsmith, a UW–Madison professor of chemistry who led the work. “Capturing behaviors at the level of single molecules is an amazingly informative way of understanding complex systems, and if you can build new tools that grant better access to that perspective, those tools can be really powerful.”

The method relies on an optical microresonator or microcavity. This device traps light in an extremely tiny space where it can interact with a molecule. Microcavities are more commonly found in physics or electrical engineering labs but have now been applied to chemistry through Goldsmith’s interdisciplinary approach.

Goldsmith has pursued single-molecule studies since his postdoctoral research at Stanford University under chemist W.E. Moerner, who received the Nobel Prize in Chemistry in 2014 for developing methods to observe single molecules using light.

The newly developed microcavity technique allows researchers to detect a molecule's presence and gather information such as its movement speed through water. This data helps determine the molecule’s shape or conformation.

“Conformation at the molecular level is incredibly important, particularly for thinking about how biomolecules interact with each other,” explained Goldsmith. He added that this could be crucial for assessing whether small-molecule drugs interact significantly with proteins by inducing conformational changes.

The team has filed a patent for their device and plans to refine it over the next few years while exploring various applications in spectroscopy.

This research was funded primarily by the National Institutes of Health (R01GM136981), with resonator construction supported by Q-NEXT Quantum Center under award number DE-FOA-0002253 from the U.S. Department of Energy's Office of Science.