Abstract

Scanning Electrochemical Microscopy (SECM) provides a highly precise, non-invasive bioanalytical platform for the high-resolution spatiotemporal tracking of cell surface morphology and localized biochemical activity. To isolate specific pathological targets from complex biological samples, this methodology is coupled with a customized microfluidic chip engineered to selectively capture and control the release of GD2-positive cells. After targeted microfluidic enrichment, the isolated cells undergo SECM using specialized nanodisk electrodes operating in negative-feedback mode. By evaluating continuous feedback currents and the hindered diffusion of biocompatible redox mediators, the system accurately maps 3D topographical features while completely bypassing the mechanical deformation risks associated with contact-based scanning. Critical operational parameters required for rigorous single-cell analysis—such as precise Z-approach curves, sub-micron piezo-driven hopping-mode intervals, and nanodisk signal attenuation modeling—have been optimized to ensure viability in native physiological buffers. Beyond label-free structural imaging, this integrated SECM configuration enables the simultaneous mapping of specific antigen distributions across the membranes of the captured GD2-positive cells. Analyzing these localized electrochemical signals yields rich datasets reflecting mechanotransduction, receptor clustering, and real-time cellular responses. Built to address the complex requirements of next-generation intelligent medical sensing and diagnostics, this technique integrates robustly into clinical multi-omics and single-cell drug efficacy workflows. By combining specific microfluidic cell isolation with advanced nanoscale topographical tracking, this platform offers a highly versatile, label-free analytical tool for researchers and clinical laboratories investigating soft biological interfaces.