Tunable resistive pulse sensing (TRPS) is a method used in single particle analysis. It provides quantitative size measurements that can be used for a range of applications. It is a fast and accurate alternative to previous sizing methods including electron microscopy, ultracentrifugation, chromatography, and gel electrophoresis.
Resistive pulse sensors move particles through a pore, one at a time. The particle is detected as a transient blockade of current, and the magnitude of the blockade can be measured. The magnitude of the blockade is proportional to the size of the particle.
Some types of materials used to make pore-based sensors include:
Polyethylene terephthalate (PET)
A fixed pore size sensor is limited in the range of sizes of particles that it can measure. Size-tunable pores overcome that limitation by matching pore size closely to particle size.
In one study, a resizable elastomeric thermoplastic polyurethane nanopore as shown to improve detection and discrimination between particle size populations in a polydisperse suspension. The ability to change the pore size also allowed detection of nanoparticles with and without a DNA surface coating.
Combining resizable nanopores with resistive pulse-sensing provides a sensitive and flexible method for analyzing single molecules.
The particle surface charge, or zeta potential, can also be measured with tunable resistive pulse sensing. This was demonstrated using conical thermoplastic polyrurethane pores. The zeta potential measurement is based on the duration of the resistive pulse signal.
Another approach used solid state pyramidal nanopores to measure zeta potential of citrated gold and some types of viruses. Translocation duration of the nanoparticles was measured as a function of voltage. In addition to zeta potential, the inverse translocation time versus voltage dependency electrophoretic mobility was also calculated.
Creating a nanopore
There are many methods for creating nanopores used in resistive pulse sensing. Those include the use of inorganic nanotubes, track-etched polymer films, nanopipettes drawn from thin-walled quartz capillaries, and carbon nanotubes. However, a tunable nanopore requires the ability to dynamically tailor the size of the aperture.
One study presents the metered penetration of a polyurethane membrane with a sharpened probe as a method for creating a self-sealing nanometer-scale aperture. The pore can then be adjusted across a spectrum of aperture geometries for detecting and controlled gating of DNA molecules.
The membranes are created first by injection molding of thermoplastic polyurethane into a cruciform shape. The polyurethane is then penetrated by a probe with voltage applied across the membrane. The size of the pore is adjusted by stretching and relaxing the arms of the cruciform.
The utility of the resizable aperture was demonstrated by adding DNA to the electrolyte reservoir and allowing it to diffuse through the pore. The scientists found that DNA translocated through the pore, and that reducing the size of the aperture created a barrier to DNA. The resizable apertures were found to have utility as Coulter-type stochastic particle sensors, and it was demonstrated that controlled gating of DNA can be used to trap single particles.
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