Abstract:
Accurate characterisation of micro- and nanoparticles is of key importance in a variety of scientific fields from colloidal chemistry to medicine. Tuneable resistive pulse sensing (TRPS) has been shown to be effective in determining the size and concentration of nanoparticles in solution. Detection is achieved using the Coulter principle, in which each particle passing through a pore in an insulating membrane generates a resistive pulse in the ionic current passing through the pore. The distinctive feature of TRPS relative to other RPS systems is that the membrane material is thermoplastic polyurethane, which can be actuated on macroscopic scales in order to tune the pore geometry.
In this thesis we attempt to extend existing TRPS techniques to enable the characterisation of nanoparticle charge and shape. For the prediction of resistive pulses produced in a conical pore we characterise the electrolyte solutions, pore geometry and pore zeta-potential and use known volume calibration particles. The first major investigation used TRPS to quantitatively measure the zeta-potential of carboxylate polystyrene particles in solution. We find that zeta-potential measurements made using pulse full width half maximum data are more reproducible than those from pulse rate data. We show that particle zeta-potentials produced using TRPS are consistent with literature and those measured using dynamic light scattering techniques.
The next major task was investigating the relationship between pulse shape and particle shape. TRPS was used to compare PEGylated gold nanorods with spherical carboxylate polystyrene particles. We determine common levels of variation across the metrics of pulse magnitude, duration and pulse asymmetry. The rise and fall gradients of resistive pulses may enable differentiation of spherical and non-spherical particles.
Finally, using the metrics and techniques developed during charge and shape investigations, TRPS was applied to Rattus rattus red blood cells, Shewanella marintestina bacteria and bacterially-produced polyhydroxyalkanoate particles. We find that TRPS is capable of producing accurate size distributions of all these particle sets, even though they represent nonspherical or highly disperse particle sets. TRPS produces particle volume measurements that are consistent with either literature values or electron microscopy measurements of the dominant species of these particle sets. We also find some evidence that TRPS is able to differentiate between spherical and non-spherical particles using pulse rise and fall gradients in Shewanella and Rattus rattus red blood cells. We expect TRPS to continue to find application in quantitative measurements across a variety of particles and applications in the future.
