A chip-based "bipolar" DNA switch modulated by intermolecular interactions

Herein, we report a unique “bipolar” DNA switch that integrates an anti-adenosine aptamer (a 12-base mismatch loop) in the middle of a complementary DNA double helix. The electrochemical signal change of methylene blue attached to the distal end of the DNA switch upon ligand binding is dependent on the DNA surface density. At high surface density, it switches on by increasing the peak current; at low surface density, it switches on by decreasing the peak current. No significant change of either the integrated charge (peak area) or the electron transfer rate is observed; only the shape of the reduction peak changes. Rather than by removal of perturbations or by change of surface accessibility, the switching is caused by a change of intermolecular interactions. The high specificity, reusability and stability of the DNA switch suggest the possibility of designing a new class of biosensors in which analyte binding produces large changes in intermolecular interactions.