Entropic Trapping of a Singly Charged Molecule in Solution.

We demonstrate the ability to confine a single molecule in solution by spatial modulation of its local configurational entropy. Previously we established electrostatic trapping of a charged macromolecule by geometric tailoring of a repulsive electrical interaction potential in a parallel plate system. However, since the lifetime of the trapped state depends exponentially on the electrical charge of the molecule, the electrostatic interaction alone is often insufficient in magnitude to stably confine molecules carrying a net charge of magnitude ≤5 e. Here we show that the configurational entropy of a thermally fluctuating molecule in a geometrically modulated system can be exploited to spatially confine weakly charged molecules in solution. Measurement of the configurational entropy contribution reveals good agreement with theoretical expectations. This additional translational contribution to the total free energy facilitates direct optical imaging and measurement of the effective charge of molecules on the size scale of ∼1 nm and a charge as low as 1 e, physical properties comparable with those of a monovalent ion in solution.