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Fields & Applications Clinical, Genomics & DNA Analysis

Single-Molecule Diagnosis?

new nanopore-based sensor improves the sensitivity of single-molecule detection, providing insights into ionic dynamics and molecular translocation – opening the door to more precise molecular identification in diagnostics. 

The core of the sensor is a nanoscale pore through which individual molecules, such as DNA or proteins, pass – temporarily blocking ionic currents. These changes are measured with voltage-clamp recordings, a technique used to track the reduction in ionic flow caused by molecular translocation. The researchers, from UC Riverside, also employed finite element modeling (FEM) to simulate ionic transport and charge distribution within the nanopore, uncovering phenomena, such as concentration polarization and negative capacitance.

To demonstrate the system’s capabilities, the researchers conducted DNA translocation experiments using λ-DNA and 10-kbp DNA. These tests revealed distinct differences in ionic current signatures based on molecular structure, such as DNA folding states, underscoring the sensor’s ability to identify subtle molecular variations. Simulations using COMSOL Multiphysics further supported these findings.

By capturing signals at the single-molecule level, the sensor allows researchers to study ionic and molecular dynamics in real time, potentially providing clearer insights into processes such as protein folding and DNA sequencing. But the improved signal preservation also offers potential for more precise molecular identification in diagnostics. And that’s why the tool is being investigated for use in portable diagnostic devices, with applications in early detection of diseases.

“Nanopores offer a way to catch infections sooner – before symptoms appear and before the disease spreads,” said Kevin Freedman, assistant professor of bioengineering and lead author of the study, in a press release. “This kind of tool could make early diagnosis much more practical for both viral infections and chronic conditions.”

The study’s insights into nanopore behavior also suggest applications in developing molecular memory devices and other nanoscale technologies.

“I’m confident that nanopores will become part of everyday life,” Freedman said. “This discovery could change how we’ll use them moving forward.”

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