Researchers at UCSB have recently developed biosensors that can better detect concentration levels of certain molecular markers.

Chemistry professor Kevin Plaxco and lead author of the study Alexis Vallée-Bélisle have made significant improvements in biosensors. The improvements allow for more accurate diagnostic tests when monitoring patient health and will help guide physicians toward more appropriate disease treatment.

Current biosensors are not able to measure very large or very small variations in target molecular marker concentrations. By developing sensors that have such capabilities, Plaxco, Vallée-Bélisle and their team hope to increase the sensitivity of medical testing.

“One of the limitations of current biosensors is their precision, which is confined to a fixed, well-defined ‘dynamic range’ of target concentrations,” Vallée-Bélisle said in an email. “Specifically, the useful dynamic range of typical biomolecule binding events spans an 81-fold range of target concentrations. Our improved sensors can now detect variation of target concentration by up to 1,000,000-fold or be much more precise and detect very small changes in target concentration.”

A key breakthrough for the researchers was the result of observing nature. The researchers observed that organisms are better able monitor their surroundings by using multiple receptors with different affinities for the same target molecule. Upon witnessing this natural phenomenon, the team proceeded to mimic this method in the lab.

“Nature combines in a very elegant way multiple receptors, each displaying a different affinity for their common target,” Vallée-Bélisle said in a press release. “So that is what we did.”

The researchers mimicked nature by combining sets of molecular beacons — types of biosensors used to detect DNA mutations — that all bind to the same target molecule with differing affinities, enabling the creation of sensors with specific dynamic ranges. Additionally, the research team built sensors with ‘custom’ dynamic ranges, in which sensors are insensitive to a certain range of concentrations but highly sensitive in detecting concentrations above or below the selected concentration range.

“That the dynamic range of biosensor is no longer limited to an 81-fold dynamic range,” Vallée-Bélisle said. “We can engineer any optimized dynamic range that we want.”

Despite the breakthroughs already achieved, the researchers hope to improve upon their own findings in the future. By observing the way that nature already senses the concentration of various molecules, the team hopes to continue finding new ways of increasing the sensitivity of biosensors.

“We are now working on designing even more precise biosensors by mimicking allosteric mechanisms, another strategy used by nature,” Vallée-Bélisle said.

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