Molecular electrometry

Matter in solution is in constant motion. Microscopic particles are constantly bombarded by the surrounding water molecules causing them to randomly walk through their environment. This motion occurs in the context of interactions with surrounding matter: short-range dispersion forces and long-range electrostatic forces to name a few. The main goal of this sphere of activity is to quantify the long-range electrostatic force simply by observing motion of molecules in an electrostatic free energy landscape. Such a landscape may be viewed as a two-dimensional manifold of uniform spatial free energy that is peppered with well-defined potential wells. As molecules diffuse through the landscape molecules they randomly fall into these energy minima and can then take a while to escape. We measure the confinement time of a molecule inside a “trap”, and use this measurement to determine the effective charge of the molecule which turns out to be a direct measure of the molecule’s interaction strength with an electrical potential. Because we measure the time for a molecule to escape a potential well and because of the exponential nature of Boltzmann statistics, we are able to measure the effective charge of a molecule with very high precision. We termed this technique escape-time electrometry (ETe).

The effective charge of a molecule in solution can provide us with a host of structural, chemical and conformational information. Measurement of the geometrical dimensions of nucleic acid helices, identification of protein post translational modifications (PTMs) and detection of molecular binding events are all ongoing experiments in the lab. The single molecule precision of ETe also lends itself to generating charge spectra, where we aim to measure precisely the charge of each single molecule in a mixture with a view to quantifying molecular-state homogeneity inherent to heterogeneous biological samples at the ultimate (single molecule) sensitivity limit.

More fundamentally, ETe allows us to probe the nature of electrostatic interactions, and has been instrumental in revealing regimes where the standing theories of electrostatics are no longer valid, spurring new research into and enhancing our understanding of intermolecular and interparticle interactions in fluids.