Detecting disease with only a single molecule

Because the molecules scientists want to detect (usually some DNA or protein molecules) are about a billionth of a meter wide, the electrical signals they produce are very small and require specialized detection equipment.

“Now, you need millions of molecules to detect disease. We showed that it’s possible to get useful data from just a single molecule. Paper About this tool Nature Nanotechnology. “This level of sensitivity could have a real impact on disease diagnosis.”

Friedman’s lab aims to build electronic detectors that behave like neurons in the brain and can retain memory: specifically, the memory of molecules that have previously passed through the sensor. To this end, scientists at the University of California, Riverside, have developed a new circuit model that can account for small changes in sensor behavior.

At the heart of their circuit is a nanopore—a tiny opening through which molecules pass one at a time. Biological samples are loaded into the circuit along with salts, which dissociate into ions.

If protein or DNA molecules in the sample pass through the pore, this reduces the flow of ions that can pass through. “Our detector measures the reduction in flow caused by the passage of proteins or DNA fragments and blocks the passage of ions,” Freedman said.

Friedman suggested that in order to analyze the electrical signals produced by the ions, the system needs to account for the possibility that some molecules may not be detected as they pass through the nanopores.

What’s unique about this discovery is that the nanopore is not just a sensor, it also acts as a filter, reducing background noise from other molecules in the sample that can mask critical signals.

Traditional sensors require external filters to remove unwanted signals, and these filters can inadvertently remove valuable information from the sample. Friedman’s method ensures that the signal of each molecule is preserved, thereby improving the accuracy of diagnostic applications.

Freedman envisions the device being used to develop a small, portable diagnostic kit (no larger than a USB drive) that can detect infections at their earliest stages. While today’s tests may not record infection for several days after exposure, nanopore sensors can detect infection within 24 to 48 hours. This capability would provide significant advantages for rapidly spreading diseases, enabling early intervention and treatment.

“Nanopores provide a faster way to detect infections before symptoms appear and before the disease spreads,” Friedman said. “This tool could make early diagnosis of viral infections and chronic diseases more practical.”

In addition to diagnostics, the device is expected to advance protein research. Proteins play important roles in cells, and even small changes in their structure can affect health. Because of the similarities between healthy and disease-causing proteins, current diagnostic tools have difficulty distinguishing between them. However, nanopore devices can measure subtle differences between individual proteins, which could help doctors design more personalized treatments.

The research also brings scientists closer to achieving single-molecule protein sequencing, a long-sought goal in biology. DNA sequencing reveals genetic instructions, while protein sequencing provides insights into how these instructions are expressed and modified on the fly. This deeper understanding could lead to earlier detection of disease and more precise treatments tailored to each patient.

“There is a huge incentive to develop protein sequencing because it will provide us with insights that we cannot get from DNA alone,” Freedman said. “Nanopores allow us to study proteins in ways that were previously impossible.”

Nanopores are the focus of a research grant Friedman received from the National Human Genome Research Institute, where his team will attempt to sequence a single protein. This work builds on Friedman’s previous research on improving nanopores for sensing molecules, viruses and other nanoscale entities. He sees these advances as signs of a possible future shift in molecular diagnostics and biological research.

“There is still much to learn about the molecules that drive health and disease,” Friedman said. “This tool brings us one step closer to personalized medicine.”

Friedman predicts nanopore technology will soon become a standard feature in research and healthcare tools. As these devices become cheaper and more readily available, they could find a place in routine diagnostic kits used at home or in the clinic.

“I believe nanopores will become part of everyday life,” Friedman said. “This discovery could change the way we use them in the future.”