Nanopore-Based Tool Detects Disease with Single Molecule

Detecting diseases typically requires identifying millions of molecules. The molecules targeted for detection—such as specific DNA or protein molecules—are extremely small, about one-billionth of a meter in size. As a result, the electrical signals they generate are tiny and require specialized equipment for accurate detection. Scientists have now developed a nanopore-based technology that could revolutionize disease diagnosis by capturing signals from individual molecules, enabling faster and more precise testing than current methods.

Researchers at UC Riverside (Riverside, CA, USA) are working on creating electronic sensors that mimic the behavior of neurons in the brain, capable of "remembering" molecules that have previously passed through the sensor. To achieve this, the team designed a new circuit model that detects small changes in the sensor's behavior. Central to their circuit is a nanopore, an extremely small opening that allows molecules to pass through one at a time. Biological samples are introduced into the system along with salts that break down into ions. When DNA or protein molecules from the sample pass through the nanopore, they cause a reduction in the flow of ions. To process the resulting electrical signals, the system must account for the possibility that some molecules might not be detected as they move through the nanopore.

What sets this discovery apart is that the nanopore not only functions as a sensor but also acts as a filter, minimizing background noise from other molecules that could interfere with detecting critical signals. Traditional sensors require external filters to eliminate unwanted signals, but these filters can unintentionally remove valuable information. The new technology ensures that every molecule's signal is retained, thereby enhancing the accuracy of diagnostic applications. The team at UCR envisions the technology being used to create a compact, portable diagnostic device—roughly the size of a USB drive—that could detect infections at their earliest stages. Unlike current tests, which may take days to detect infections, nanopore sensors could identify them within 24 to 48 hours, offering a significant advantage in diagnosing fast-spreading diseases and enabling earlier treatment.

Apart from diagnostics, this device also holds promise for advancing protein research. Proteins play critical roles in cell function, and even small structural changes can impact health. Current diagnostic tools struggle to differentiate between healthy proteins and disease-causing ones due to their similar structures. However, the nanopore technology can detect subtle differences between individual proteins, which could help physicians create more personalized treatments. Additionally, this research brings scientists closer to achieving single-molecule protein sequencing, a long-sought biological goal. While DNA sequencing reveals genetic information, protein sequencing provides insight into how that genetic information is expressed and modified in real time. This deeper understanding could lead to earlier disease detection and more targeted, personalized therapies.

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

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