UC Riverside scientists have developed a nanopore-based tool that could help diagnose diseases much more quickly and with greater accuracy than current tests allow, by capturing signals from individual molecules.
Because the molecules scientists want to detect – usually certain DNA or protein molecules – are about a billionth of a meter wide, the electrical signals they produce are very weak and require specialized detection instruments.
“Currently, millions of molecules are needed to detect diseases. We show that it is possible to obtain useful data from a single molecule,” said Kevin Freedman, assistant professor of bioengineering at UCR and lead author of a paper on the tool. In Natural nanotechnology. “This level of sensitivity could make a real difference in the diagnosis of diseases. »
Freedman’s lab aims to build electronic detectors that behave like neurons in the brain and can retain memories: in particular, memories of molecules previously passed through the sensor. To do this, UCR scientists developed a new circuit model that takes into account small changes in the sensor’s behavior.
At the heart of their circuit is a nanopore, a small opening through which molecules pass one at a time. Biological samples are loaded into the circuit with salts which dissociate into ions.
If protein or DNA molecules from the sample pass through the pore, this reduces the flow of ions that can pass through. “Our detector measures the reduction in flux caused by a protein or piece of DNA passing through and blocking the passage of ions,” Freedman said.
To analyze the electrical signals generated by the ions, Freedman suggests, the system must account for the likelihood that some molecules will go undetected as they pass through the nanopore.
What sets this finding apart is that the nanopore is not just a sensor but acts as a filter itself, reducing background noise from other molecules in a sample that might obscure critical signals.
Traditional sensors require external filters to remove unwanted signals, and these filters can accidentally remove valuable information from samples. Freedman’s approach ensures that the signal from each molecule is preserved, improving the accuracy of diagnostic applications.
Freedman envisions the device being used to develop a small, portable diagnostic kit, no larger than a USB stick, that could detect infections in the early stages. Although current tests cannot record infections several days after exposure, nanopore sensors can detect infections within 24 to 48 hours. This capability would provide a significant advantage for rapidly spreading diseases, enabling earlier intervention and treatment.
Nanopores offer a way to detect infections earlier, before symptoms appear and before the disease spreads. This type of tool could make early diagnosis much more practical for viral infections and chronic diseases. »
Kevin Freedman, assistant professor of bioengineering at UCR
In addition to diagnostics, the device shows promise for advancing protein research. Proteins play an essential role in cells and even slight changes in their structure can affect health. Current diagnostic tools struggle to differentiate between healthy and disease-causing proteins due to their similarities. The nanopore device, however, can measure subtle differences between individual proteins, which could help doctors design more personalized treatments.
The research also brings scientists closer to single-molecule protein sequencing, a long-sought goal in biology. While DNA sequencing reveals genetic instructions, protein sequencing provides insight into how these instructions are expressed and modified in real time. This deeper understanding could lead to earlier disease detection and more precise therapies tailored to each patient.
“There is a lot of momentum toward developing protein sequencing because it will give us information that we can’t get from DNA alone,” Freedman said. “Nanopores allow us to study proteins in a way that was not possible before. »
The nanopores are the subject of a Freedman-funded research grant from the National Human Genome Research Institute, in which his team will attempt to sequence unique proteins. This work builds on Freedman’s previous research aimed at refining the use of nanopores to detect molecules, viruses and other entities at the nanoscale. He sees these advances as a sign of how molecular diagnostics and biological research may evolve in the future.
“There is still much to learn about the molecules that drive health and disease,” Freedman said. “This tool brings us even closer to personalized medicine. »
Freedman expects nanopore technology to soon become a standard feature in research and healthcare tools. As these devices become more affordable and accessible, they could find their way into everyday diagnostic kits used at home or in clinics.
“I am convinced that nanopores will become part of everyday life,” Freedman said. “This discovery could change how we use them in the future.” »
