Tunable resistive pulse sensing (TRPS) is an experimental technique that has been used to study and characterise colloidal particles ranging from approximately 50 nm in diameter up to the size of cells. The primary aim of this Review is to provide a guide to the characteristics and roles of TRPS in recent applied research. Relevant studies reflect both the maturation of the technique and the growing importance of submicron colloids in fields such as nanomedicine and biotechnology. TRPS analysis of extracellular vesicles is expanding particularly swiftly, while TRPS studies also extend to on-bead assays using DNA and aptamers, drug delivery particles, viruses and bacteria, food and beverages, and superparamagnetic beads. General protocols for TRPS measurement of particle size, concentration and charge have been developed, and a summary of TRPS technology and associated analysis techniques is included in this Review.

This experimental study concerns the occurrence of biphasic pulses generated during tunable resistive pulse sensing (TRPS) of 200 nm carboxylate polystyrene spheres. In TRPS, a short-lived pulse in ionic current is observed when an individual colloid passes through a pore which separates two fluid reservoirs. The pulse is conventionally resistive, but conductive pulses are observed under certain experimental conditions, as well as biphasic pulses which include both resistive and conductive components. The experimental variables investigated here include the concentration of the phosphate-buffered saline electrolyte, particle charge, pore size, applied voltage, and the direction of particle motion. The onset upper electrolyte concentration for biphasic pulses in TRPS is ∼50 mM, and the ordering of biphasic pulse components can be interpreted using ionic concentration polarization if the conductive component is generated when the particle is in the ion depletion region. Besides providing fundamental understanding, the results are important for the TRPS technique, which is becoming widely used for particle-by-particle measurements of submicron colloids.