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A new nanopore-based diagnostic tool developed by scientists at the University of California, Riverside, could revolutionize the speed and precision of illness detection. Unlike current tests that often require large quantities of biological material, this device captures signals from individual molecules—ushering in a new era of diagnostic sensitivity.
Kevin Freedman, assistant professor of bioengineering at UC Riverside, explained the breakthrough: “Right now, you need millions of molecules to detect diseases. We’re showing that it’s possible to get useful data from just a single molecule. This level of sensitivity could make a real difference in disease diagnostics.”
A New Circuit Model for Single-Molecule Detection
At the core of this advancement is a nanopore—a microscopic opening through which molecules such as DNA and proteins pass one at a time. As these molecules traverse the nanopore, they temporarily block the passage of ions in a solution, generating a measurable change in ionic flow. “Our detector measures the reduction in flow caused by a protein or bit of DNA passing through and blocking the passage of ions,” Freedman said.
Unlike traditional sensors that rely on external filters to reduce noise, this nanopore system acts as its own filter, eliminating interference from background molecules. This not only preserves critical molecular signals but also increases the accuracy of diagnostic results.
The research team developed a new circuit model to address the challenge of detecting extremely small signals generated by individual molecules. The model ensures reliable data collection even when certain molecules go undetected by accounting for subtle changes in the nanopore's behavior.
Diagnostic Applications and Beyond
Freedman envisions the nanopore technology enabling portable diagnostic kits that could detect infections within 24 to 48 hours of exposure. This represents a significant improvement over current tests, which may take days to yield results.
“Nanopores offer a way to catch infections sooner—before symptoms appear and before the disease spreads,” Freedman said. Such a capability could transform early diagnosis of fast-spreading diseases, allowing for timely interventions.
Another exciting frontier for this technology lies in single-molecule protein sequencing. Unlike DNA sequencing, which decodes genetic instructions, protein sequencing reveals how these instructions are expressed and modified in real time. Achieving single-molecule protein sequencing could illuminate previously inaccessible aspects of disease biology and therapeutic design.
“There’s a lot of momentum toward developing protein sequencing because it will give us insights we can’t get from DNA alone,” Freedman said. “Nanopores allow us to study proteins in ways that weren’t possible before.”
A Tool for the Future
This nanopore technology is part of a broader effort funded by the National Human Genome Research Institute, where Freedman’s team is exploring applications for sequencing single proteins. The research builds on his prior work with nanopores in detecting nanoscale entities such as viruses and small molecules.
Freedman expressed optimism about the broader implications of nanopore technology: “There’s still a lot to learn about the molecules driving health and disease. This tool moves us one step closer to personalized medicine.” As the technology becomes more affordable and accessible, it may find applications in routine healthcare and at-home diagnostics, signaling a shift in how molecular diagnostics are integrated into daily life. “I’m confident that nanopores will become part of everyday life,” Freedman said. “This discovery could change how we’ll use them moving forward.”
Publication Details
Farajpour, N., Bandara, Y.M.N.D.Y., Lastra, L. et al. Negative memory capacitance and ionic filtering effects in asymmetric nanopores. Nat. Nanotechnol. (2025). https://doi.org/10.1038/s41565-024-01829-5
Kevin Freedman, assistant professor of bioengineering at UC Riverside, explained the breakthrough: “Right now, you need millions of molecules to detect diseases. We’re showing that it’s possible to get useful data from just a single molecule. This level of sensitivity could make a real difference in disease diagnostics.”
A New Circuit Model for Single-Molecule Detection
At the core of this advancement is a nanopore—a microscopic opening through which molecules such as DNA and proteins pass one at a time. As these molecules traverse the nanopore, they temporarily block the passage of ions in a solution, generating a measurable change in ionic flow. “Our detector measures the reduction in flow caused by a protein or bit of DNA passing through and blocking the passage of ions,” Freedman said.
Unlike traditional sensors that rely on external filters to reduce noise, this nanopore system acts as its own filter, eliminating interference from background molecules. This not only preserves critical molecular signals but also increases the accuracy of diagnostic results.
The research team developed a new circuit model to address the challenge of detecting extremely small signals generated by individual molecules. The model ensures reliable data collection even when certain molecules go undetected by accounting for subtle changes in the nanopore's behavior.
Diagnostic Applications and Beyond
Freedman envisions the nanopore technology enabling portable diagnostic kits that could detect infections within 24 to 48 hours of exposure. This represents a significant improvement over current tests, which may take days to yield results.
“Nanopores offer a way to catch infections sooner—before symptoms appear and before the disease spreads,” Freedman said. Such a capability could transform early diagnosis of fast-spreading diseases, allowing for timely interventions.
Another exciting frontier for this technology lies in single-molecule protein sequencing. Unlike DNA sequencing, which decodes genetic instructions, protein sequencing reveals how these instructions are expressed and modified in real time. Achieving single-molecule protein sequencing could illuminate previously inaccessible aspects of disease biology and therapeutic design.
“There’s a lot of momentum toward developing protein sequencing because it will give us insights we can’t get from DNA alone,” Freedman said. “Nanopores allow us to study proteins in ways that weren’t possible before.”
A Tool for the Future
This nanopore technology is part of a broader effort funded by the National Human Genome Research Institute, where Freedman’s team is exploring applications for sequencing single proteins. The research builds on his prior work with nanopores in detecting nanoscale entities such as viruses and small molecules.
Freedman expressed optimism about the broader implications of nanopore technology: “There’s still a lot to learn about the molecules driving health and disease. This tool moves us one step closer to personalized medicine.” As the technology becomes more affordable and accessible, it may find applications in routine healthcare and at-home diagnostics, signaling a shift in how molecular diagnostics are integrated into daily life. “I’m confident that nanopores will become part of everyday life,” Freedman said. “This discovery could change how we’ll use them moving forward.”
Publication Details
Farajpour, N., Bandara, Y.M.N.D.Y., Lastra, L. et al. Negative memory capacitance and ionic filtering effects in asymmetric nanopores. Nat. Nanotechnol. (2025). https://doi.org/10.1038/s41565-024-01829-5
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