Credit: © 2009 Wiley

Stimulated by how the mammalian nose works, scientists have recently begun to develop sensors based on arrays of supramolecular receptors that generate a measurable signature output to identify molecules. Measuring proteins in such a way could provide an accurate method for diagnosing diseases that are characterized by protein imbalance.

Now David Margulies and Andrew Hamilton from Yale University have developed1 a recognition system based on DNA that can identify proteins in samples as small as a single microlitre drop. The sensors are based on G-quadruplexes — structures made up of four strands of guanine-rich DNA that self-assemble into a square arrangement. Each of the four strands can be functionalized with a fluorophore. If two different fluorophores are used then the four strands can assemble into six different possible structures, creating an ensemble of different G-quadruplexes with a distinct fluorescence emission.

Non-specific interactions between a protein and the various G-quadruplex structures of an ensemble result in measurable changes to its fluorescence signature. Using an ensemble of G-quadruplexes functionalized with three fluorophores — pyrene, tamra and fluoroscein — Margulies and Hamilton showed that five proteins, including the related avidin and streptavidin, could be detected and distinguished by monitoring changes in fluorescence.