A Tunable Micro-/Nanogap-Based Resistive Pulse Sensing Platform for Particle and Biomaterial Detection

Abstract Materials at micro-/nanoscales possess strong correlations between their structural and functional properties, making precise structural characterization essential for understanding their physicochemical properties. Resistive pulse sensing (RPS), a Coulter principle-based approach, offers real-time and label-free detection of single micro-/nanoparticles through transient ionic resistance changes within a fluidic channel. Despite its promise, most RPS devices rely on costly, low-yield nanofabrication techniques, limiting device flexibility and scalability. In this study, we present a facile and structurally tunable RPS device fabricated using only conventional photolithography and soft lithography. We formed various micro-/nanogaps by trapping a polystyrene (PS) microparticle within a tapered microchannel via evaporation-driven transport, allowing precise control of the gap size by adjusting the microchannel dimension and the particle diameter. The particle-assisted micro-nanogap-based RPS device detected and characterized target analytes across a broad range of sizes, demonstrating both fabrication simplicity and practical versatility. Furthermore, we characterized cell-derived particulate materials obtained from three cell lines and compared their size distributions with those obtained using conventional sizing methods, thereby demonstrating the practical applicability of the device for population-level analysis of heterogeneous particulate samples. Overall, the proposed RPS device provides a cost-effective and accessible approach for high-sensitivity, real-time structural characterization of diverse micro- and nanomaterials, and could serve as a useful tool for future biological and diagnostic applications.