By Nathan Boyd

How could you go about finding one particular bee in a hive bustling with activity? Extending this analogy to early cancer and pathogen detection gives the sense of what is required when cell biologists search for one type of biomolecule in a crowded and constantly-changing environment.

In his laboratory at the University of California, Santa Cruz, biomolecular engineer Nader Pourmand and his group have pioneered the development of biosensors–tools that can detect and quantify specific molecules hiding among an array of biological minutiae.

Biosensors capitalize on paired interactions that exist in nature to first detect specific substrates; the base-pairing interactions of DNA, the exact match between an antibody and antigen, and the chemical preferences that bond one molecule to the next are general examples of this natural Velcro. Conveniently, when a partner of a natural duet is also in contact with an electrode, the physical interaction that occurs when a partner finds its mate can be converted into an electrical signal.

The biosensors developed in the Pourmand laboratory to bind DNA and proteins use a mechanism they call STING, for Signal Transduction by Ion NanoGating. They fabricate the STING biosensors using quartz precursors known as nanopipettes that have openings roughly 50 nanometers in diameter. By mounting antibodies or chemical functional groups to the tip of the quartz opening, the nanopipette can be used as a probe to interrogate a desired system. When electrolytes flow through the nanopipette, they create a tiny electrical current that can be measured. As targets bind at the tip of the nanopipette, the current is altered, either because the opening is obstructed or because of the electrical makeup of the bound molecules. The net result is a unique electrical signature of the target molecule.

The story of the nanopipette as a biosensor goes back nearly a decade to Stanford University’s Genome Technology center, where Pourmand and colleagues were inspired by the concept of single-molecule DNA sequencing using nanopores. The expense and complexity of nanopore technology soon led researchers to develop a simpler alternative: researchers using STING can easily customize nanopipettes to detect biomolecules in only a few hours.

Now Paolo Actis, a postdoctoral scholar in Pourmand’s group with a background in electrochemistry, leads the charge to revolutionize STING’s capability. “It’s amazingly cheap and easy to fabricate,” he says. “Instead of fishing for substrates with other technologies, you can actually target a specific molecule or cell.”

Actis suggests that the emerging field of biosensor technology is poised to experience revolutionary advances in coming years. Because the field is highly interdisciplinary, Actis believes physicists, biologists, and analytical chemists will all contribute to develop STING to its full potential.

Actis and the Pourmand group have recently collaborated with NASA on a landmark project that applies STING technology to detecting trace amounts of toxic molecules in solution. “These toxins are very dangerous in closed environments, and very potent,” says Actis.

His assay is based on an immunoassay where the STING sensor contains antibodies used to detect HT2 toxin, a mycotoxin that NASA has identified as a potential hazard in future space missions. “The goal was to do better at detecting mycotoxin than methods currently available,” Actis said.

Indeed, tests on this method show that STING detects a much broader range of toxin concentration, and it is 1000 times more sensitive than today’s gold standard of immunodetection, enzyme-linked immunosorbent assay (ELISA).

With demonstrated analyte detection in hand, STING is scheduled to be applied in vivo. Pourmand’s latest project probes the immediate environment of a single cell for antigens connected to human papillomavirus (HPV).

Once STING is shown to work in vivo, Actis plans to go beyond the cellular environment to detect substrates on the surface of, and even within, a single cell. Someday, early pathogen and cancer detection could feel the STING of revolutionary developments in biosensor technology.