  Electronic biosensors are a natural fit for field-deployable diagnostic
devices, because they can be miniaturized, mass produced, and integrated with
circuitry. Unfortunately, progress in the development of such platforms has
been hindered by the fact that mobile ions present in biological samples screen
charges from the target molecule, greatly reducing sensor sensitivity. Under
physiological conditions, the thickness of the resulting electric double layer
is less than 1 nm, and it has generally been assumed that electronic detection
beyond this distance is virtually impossible. However, a few recently-described
sensor design strategies seem to defy this conventional wisdom, exploiting the
physics of electrical double layers in ways that traditional models do not
capture. In the first strategy, charge screening is decreased by constraining
the space in which double layers can form. The second strategy uses external
stimuli to prevent double layers from reaching equilibrium, thereby effectively
reducing charge screening. The goal of this article is to describe these
relatively new concepts, and to offer theoretical insights into mechanisms that
may enable electronic biosensing beyond the double-layer. If these concepts can
be further developed and translated into practical electronic biosensors, we
foresee exciting opportunities for the next generation of diagnostic
technologies.
