Amino Functionalization Significantly Boosts Nanopipette Sensitivity to Viscosity

Cytoplasmic viscosity dynamically varies when cells respond to physiological, pathological, or external stimuli. Precise analysis of these minimal fluctuations requires high sensitivity for real-time, high-fidelity monitoring. Herein, we developed an amino-functionalized nanopipette as a highly sensitive nanosensor for real-time dynamic monitoring of cytoplasmic viscosity in DU-145 human prostate cancer cells under both hypertonic and hypotonic conditions. Amino functionalization significantly enhanced the nanopipette's sensitivity to viscosity. Within a scanning window of -1.0 V to +1.0 V, it yielded a 189.56-fold increase at +1.0 V and up to a 17.96-fold improvement at their respective optimal applied potentials. This enhancement is primarily attributed to the increased interfacial charge density introduced by amino groups, which strengthens both the electrical double-layer effect and electroosmotic flow. Notably, the nanosensor exhibits high sensitivity, excellent selectivity, and good reversibility in both voltammetry and chronoamperometry, while maintaining its viscosity-response performance across a wide range of electrolyte concentrations and pH levels. This work not only provides a powerful tool for dynamic monitoring of cytoplasmic viscosity but also presents a strategy to enhance viscosity sensitivity through inner-wall chemical modification, which regulates nanoscale mass transport.