Researchers Develop The World's Most Sensitive Method For Observing Single Molecules

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Credit: Carlos Saavedra/UW–Madison

University of Wisconsin–Madison researchers have developed a novel method for detecting and profiling single molecules. The method is the most sensitive to date and provides an effective tool to better understand how molecules interact with each other. 

The method, published in Nature, provides an observational method to image individual molecules without the aid of fluorescent labels. Label-free methods are gaining popularity among researchers worldwide as while they are useful for many applications, they can alter and obscure how molecules naturally interact with each other. 

"We're very excited about this," said Randall Goldsmith, a UW–Madison professor of chemistry. "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 the use of an optical microresonator, or microcavity, that contains small mirrors to bounce fiber optic light throughout the cavity. This reflected light can be used to detect the presence of a molecule and glean insight into key characteristics such as its shape or conformation. 

 "Conformation at the molecular level is incredibly important, particularly for thinking about how biomolecules interact with each other," says Goldsmith. "Let's say you have a protein and you have some small-molecule drug. You want to see if the protein's druggable, which is to say, 'Does the drug have some kind of major interaction with the protein?' One way you might be able to see that is if it introduces a conformational change."

The team has patented the technology and plans to refine and optimize it over the coming years. "We're excited about many other applications in spectroscopy," added Goldsmith. "We hope we can use this as a stepping stone to other ways to learn about molecules."


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