Amplifying the Electrochemical Footprint of < 1000 Molecules in a Dissolving Microdroplet

Abstract

The ability to detect and positively identify molecules under extremely dilute conditions is important for the health of both humankind and the environment. At present, few measurement science techniques can robustly approach the measurement of just a few thousand molecules. Here, we present an electrochemical platform for the detection and positive identification of fewer than 1,000 molecules of decamethylferrocene ((Cp*)2FeII). We achieve this remarkable detection threshold by trapping (Cp*)2FeII in a 1,2-dichloroethane microdroplet, which is allowed to dissolve into an aqueous continuous phase while on a gold microelectrode (radius~6.25 m). Because electrochemistry is not sensitive enough to observe the charge of less than 1,000 molecules, we dissolved M amounts hexacyanoferrate (III) in the aqueous continuous phase. The biphasic reaction between hexacyanoferrate (III) and Cp2*(Fe)II allows for a feedback loop when the microelectrode is biased sufficiently negative to reduce Cp2*(Fe)III. This feedback loop, a typical EC’ catalytic mechanism, amplifies the electrochemical signal of Cp2*(Fe)II when the droplet is of small enough dimensions for feedback to occur. Our results demonstrate that clever biphasic reactions can be coupled with dissolving droplets to access extremely low limits of quantitation in electroanalysis.