The present invention generally relates, in some aspects, to nanoscale wire devices and methods for use in determining analytes suspected to be present in a sample. Certain embodiments of the invention provide a nanoscale wire that has improved sensitivity, as the carrier concentration in the wire is controlled by an external gate voltage, such that the nanoscale wire has a Debye screening length that is greater than the average cross-sectional dimension of the nanoscale wire when the nanoscale wire is exposed to a solution suspected of containing an analyte. This Debye screening length (lambda) associated with the carrier concentration (p) inside nanoscale wire is adjusted, in some cases, by adjusting the gate voltage applied to an FET structure, such that the carriers in the nanoscale wire are depleted.