Dissolving microdroplet electroanalysis enables attomolar-level detection.

Trace detection is critical for identifying chemicals that would otherwise remain undetectable. While analytical techniques, such as spectroscopy, spectrometry, and electrochemical sensors, are effective at detecting low concentrations, achieving attomolar sensitivity remains a significant challenge. Here, we present an electroanalytical approach that leverages partitioning kinetics to detect attomolar concentrations of redox-active analytes. Using (Cp*)Fe as a model system, we demonstrate trace-level detection by facilitating the transfer of (Cp*)Fe from the bulk aqueous phase into 1,2-dichloroethane (DCE) microdroplets positioned atop a gold microelectrode (radius ∼6.25 μm). This partitioning arises from the greater solubility of (Cp*)Fe in DCE relative to its limited solubility in water, enriching the analyte concentration near the electrode as the microdroplets slowly dissolve into the aqueous phase. Additionally, we explored the role of oxygen in enhancing the electrochemical response: oxygen removal hindered detection at 1 aM, while oxygen saturation significantly amplified the redox peak signal. These findings underscore oxygen's role, which is likely a bimolecular reaction between oxygen and (Cp*)Fe in signal amplification. An EC' catalytic mechanism likely amplifies the electrochemical signal of (Cp*)Fe when the droplet is sufficiently small for feedback to occur, enabling attomolar detection of (Cp*)Fe. This study introduces a partitioning-based electroanalytical strategy taking advantage of an an EC' catalytic mechanism for ultra-low detection limits, offering promising applications in trace chemical analysis and advanced sensor technologies.