Direct Optical Detection of Aptamer Conformational Changes Induced by Target Molecules

Aptamers are single-stranded DNA/RNA oligomers that fold into three-dimensional conformations in the presence of specific molecular targets. Surface-enhanced Raman spectroscopy (SERS) of thiol-bound DNA aptamer self-assembled monolayers on Au nanoshell surfaces provides a direct, label-free detection method for the interaction of DNA aptamers with target molecules. A spectral cross-correlation function, Gamma, is shown to be a useful metric to quantify complex changes in the SERS spectra resulting from conformational changes in the aptamer induced by target analytes. While the pristine, unexposed anti-PDGF (PDGF = platelet-derived growth factor) aptamer yields highly reproducible spectra with Gamma = 0.91 +/- 0.01, following incubation with PDGF, the reproducibility of the SERS spectra is dramatically reduced, yielding Gamma = 0.67 +/- 0.02. This approach also allows us to discriminate the response of a cocaine aptamer to its target from its weaker response to nonspecific analyte molecules.