Real-time single-molecule dynamics observed with a nanoscale transistor

Direct observation of single molecular reactions and motions are impossible by optical techniques due to diffraction limits. However, ensemble measurements of binding dynamics in biological systems offer limited understanding of individual actors in metabolic and reproductive pathways. Questions of protein folding and mis-folding are one area where a more complete view is needed, as over 50% of human cancers and many other diseases are linked to subtle changes in protein conformation that lead to alterations of their function. Here we report the direct observation of molecular reactions and dynamics at sub-millisecond timescales by coupling the reaction state of antibodies and other proteins to the conductivity of a nanscale single electron transistor (SET). By preparing quantum-dot SETS that are the same size (7nm) as the biomolecules under study, the sensitivity of the devices can be utilized to measure the subtle fluctuations in molecular charge associated with single binding events. This "molecular gating" effect is capable of sensing the small electric dipole fluctuations associated with protein folding even in the absence of charge creation/annihilation.