As researchers tease apart the intricate biochemical operations within a cell, they need an entirely new class of tools to take some fundamental measurements. But at scales of only a few nanometres, measuring even elementary properties like temperature can become dauntingly difficult.

This challenge is now being met by a novel molecular switch architecture developed at the Université de Montréal. Chemistry professor Alexis Vallée-Belisle and his coworkers have been manipulating strands of DNA that respond directly to changes in temperature, so that they change shape and generate a fluorescent resonance energy transfer that is detectable as a light signal. Since this response is limited to the size of the molecular structure itself, the arrangement essentially functions as a thermometer operating in a region that might be as little as five nanometres across. 

The university team’s work was recently published in Nano Letters, where they confirmed that these tiny thermo-switches can be calibrated to measure temperatures over a range from 25 C to 90 C, to an accuracy of plus or minus 0.05 C.  

Even in its earliest incarnations, the technique is leading to interesting results, such as real-time monitoring of enzyme activity. For example, the team found that the temperature at the point of reaction was notably higher than the average temperature of the solution containing the enzyme. When Vallée-Belisle offered this information up at a recent conference, the experimental evidence was met with skepticism by several of his colleagues, who are more familiar with the notion that temperature at this scale is expected to diffuse fast enough to not create a local increase at the nanoscale. Vallée-Belisle begged to differ and continues to refine the design of these sensors, which he regards as crucial to answering important questions in biochemistry.

“My feeling is that it will open a lot of doors,” he says. “When you don’t have the tool to answer a question, often you don’t ask the question. For the field of nanothermometry, there are a lot of questions that people are going to start asking and we’ll have the tools to start showing evidence to validate one hypothesis or another.”