By controlling the exact position and location of the chemical bases within a synthetic replica of DNA, Yan programmed a single stranded genomic DNA, M13, into nanotiles to contain the probes for specific gene expression targets. On the surface of each DNA probe tile is a dangling single stranded piece of DNA that can bind to the RNA target of interest. Each probe actually contains two half probes, so when the target RNA comes in, it will hybridize to the half probes and turn the single stranded dangling probes into a stiff structure.
The group uses a powerful instrument, atomic force microscopy (AFM), which allows the researchers to image the tiles at the single molecule level.
After binding to the DNA probe, the DNA-RNA hybridization becomes stiffened, it can be sensed by the atomic force microscope cantilever (blue arm), shown by bright line on the DNA tile, which is due to a height increase. The result is a mechanical, label-free detection of RNA.