The use of a "size-tunable" polyurethane resistive pulse sensor for quantitative sizing of nano- and microparticles is presented. A linear relationship, as first suggested by Maxwell, between particle volume and change in electric resistance across the pore was observed. Particle sizes were quantified for a given size-tunable membrane, by first creating a linear calibration curve to a series of monodisperse carboxylated polystyrene particles of various diameters and then applying this curve to calculate the size of "unknown" nanoparticles. The diameters of a selection of synthetic and biological particles, being PMMA and nonfunctionalized polystyrene particles, along with biological nanoparticles (adenovirus) were calculated using this methodology. Calculated particle diameters and coefficients of variation were shown to be in good agreement with both transmission electron microscopy and dynamic light scattering results.

The prospect of characterizing individual nanoparticles, molecules, or DNA base pairs has generated considerable interest in resistive pulse sensing. In addition to size and concentration analysis, this technique also has the capacity to measure the charge density of objects in situations where electrophoretic forces dominate their motion. Here we present a methodology to simultaneously extract, via appropriate theoretical models, the size and ζ-potential of objects from the resistive pulse signal they generate. The methodology was demonstrated using a size-tunable elastic pore sensor to measure a complex "bimodal" suspension composed of two particle sets with different size and charge. Elastically tuning the size of the pore sensor, by stretching the elastic pore membrane, enables a larger sample size range to be analyzed, improves measurement sensitivity, and fine-tunes the forces acting on objects. This methodology represents a new approach for investigating and understanding the fundamental behavior of nanoscale dispersions.

Since the first reported use of a biological ion channel to detect differences in single stranded genomic base pairs in 1996, a renaissance in nanoscale resistive pulse sensors has ensued. This resurgence of a technique originally outlined and commercialized over fifty years ago has largely been driven by advances in nanoscaled fabrication, and ultimately, the prospect of a rapid and inexpensive means for genomic sequencing as well as other macromolecular characterization. In this pursuit, the potential application of these devices to characterize additional properties such as the size, shape, charge, and concentration of nanoscaled materials (10 – 900 nm) has been largely overlooked. Advances in nanotechnology and biotechnology are driving the need for simple yet sensitive individual object readout devices such as resistive pulse sensors. This review will examine the recent progress in pore-based sensing in the nanoscale range. A detailed analysis of three new types of pore sensors – in-series, parallel, and size-tunable pores – has been included. These pores offer improved measurement sensitivity over a wider particle size range. The fundamental physical chemistry of these techniques, which is still evolving, will be reviewed.

Tunable nanopores fabricated in elastomeric membranes have been used to study the dependence of ionic current blockade rate on the concentration and electrophoretic mobility of particles in aqueous suspensions. A range of nanoparticle sizes, materials and surface functionalities has been tested. Using pressure-driven flow through a pore, the blockade rate for 100 nm carboxylated polystyrene particles was found to be linearly proportional to both transmembrane pressure (between 0 and 1.8 kPa) and particle concentration (between 7 × 10(8) and 4.5 × 10(10) ml( - 1)). This result can be accurately modelled using Nernst-Planck transport theory, enabling measurement of particle concentrations. Using only an applied potential across a pore, the blockade rates for carboxylic acid and amine coated 500 and 200 nm silica particles were found to correspond to changes in their mobility as a function of the solution pH. Scanning electron microscopy and confocal microscopy have been used to visualize changes in the tunable nanopore geometry in three dimensions as a function of applied mechanical strain. The pores were conical in shape, and changes in pore size were consistent with ionic current measurements. A zone of inelastic deformation adjacent to the pore has been identified as important in the tuning process.

A novel method using resistive pulse sensors for electrokinetic surface charge measurements of nanoparticles is presented. This method involves recording the particle blockade rate while the pressure applied across a pore sensor is varied. This applied pressure acts in a direction which opposes transport due to the combination of electro-osmosis, electrophoresis, and inherent pressure. The blockade rate reaches a minimum when the velocity of nanoparticles in the vicinity of the pore approaches zero, and the forces on typical nanoparticles are in equilibrium. The pressure applied at this minimum rate can be used to calculate the zeta potential of the nanoparticles. The efficacy of this variable pressure method was demonstrated for a range of carboxylated 200 nm polystyrene nanoparticles with different surface charge densities. Results were of the same order as phase analysis light scattering (PALS) measurements. Unlike PALS results, the sequence of increasing zeta potential for different particle types agreed with conductometric titration.