Dissolving Microdroplet Electroanalysis Enables Attomolar-Level Detection

Abstract

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 a novel electroanalytical approach leveraging partitioning kinetics to detect attomolar concentrations of redox-active analytes. Using (Cp*)₂FeII as a model system, we demonstrate trace-level detection by facilitating the transfer of (Cp*)₂FeII 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 higher solubility of (Cp*)₂FeII in DCE compared to its limited solubility in water, enriching the analyte concentration near the electrode as the microdroplets 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*)₂FeII in signal amplification. An EC’ catalytic mechanism amplifies the electrochemical signal of Cp2*(Fe)II when the droplet is of small enough dimensions for feedback to occur, enabling attomolar detection of (Cp*)₂FeII. This study introduces a partitioning-based electroanalytical with an EC’ catalytic mechanism strategy with ultra-low detection limits, offering promising applications in trace chemical analysis and advanced sensor technologies.