Single-molecule tracking promises discoveries, cures

New ways of imaging individual proteins and lipids will ultimately change science and medicine. Already, scientists who develop techniques for single-molecule detection envision broader applications. For example, Frank Vollmer, principal investigator at the Laboratory of Nanophotonics and Biosensing at the Max Planck Institute for the Science of Light (Erlangen, Germany), sees many other uses of his photonic microsystem. Although Vollmer started by detecting single molecules of DNA, he says, "A single-molecule biosensor can resolve the fleeting interactions between a molecule and any kind of receptor, with immediate applications in clinical diagnostics."

To reach those applications, Vollmer needs to move from a prototype to a commercial device. So far, he says, "We're at a stage where we're ready to build a sensor that can be used in academia as a simple tool to study biomolecules." He adds, "We're also getting ready to try this in a hospital, where we can implement these sensors for real detection problems."

Some of the greatest future advances in science and medicine could arise from exploring other nucleic acids. "About 75 percent of the human genome codes for RNA, compared to just under two percent for protein, and we are only beginning to understand what all of that RNA is doing," says Nils G. Walter, director of the Single Molecule Analysis in Real-Time (SMART) Center at the University of Michigan at Ann Arbor.

As part of Walter’s research, he explores RNA at the single-molecule level, and he takes a variety of approaches. "We can count the number of RNA molecules in a spot with super-resolution microscopy," he says. "From this, you can learn about functional RNA assemblies inside the cell."

He also built a prism-based TIRF microscope—modeled after one made by Steven Chu, now in the department of physics at Stanford University in California—to immobilize RNA to a surface. "Then," says Walter, "we can change the buffer conditions or measure rate constants of RNA undergoing conformational changes over time."

These single-molecule manipulations will change how scientists study biological mechanisms and learn to modify them.