Temperature-programmed electrospray-differential mobility analysis for characterization of ligated nanoparticles in complex media.

An electrospray-differential mobility analyzer (ES-DMA) was operated with an aerosol flow-mode, temperature-programmed approach to enhance its ability to characterize the particle size distributions (PSDs) of nanoscale particles (NPs) in the presence of adsorbed and free ligands. Titanium dioxide NPs (TiO2-NPs) stabilized by citric acid (CA) or bovine serum albumin (BSA) were utilized as representative systems. Transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry were used to provide visual information and elemental-based PSDs, respectively. Results show that the interference resulting from electrospray-dried nonvolatile salt residual nanoscale particles (S-NPs) could be effectively reduced using the thermal treatment process: PSDs were accurately measured at temperatures above 200 °C for CA-stabilized TiO2-NPs and above 400 °C for BSA-stabilized TiO2-NPs. Moreover, TEM confirmed the volumetric shrinkage of S-NPs due to thermal treatment and also showed that the primary structure of TiO2-NPs was relatively stable over the temperature range studied (i.e., below 700 °C). Conversely, the shape factor for TiO2-NPs decreased after treatment above 500 °C, possibly due to a change in the secondary (aggregate) structure. S-NPs from BSA-stabilized TiO2-NPs exhibited higher global activation energies toward induced volumetric shrinkage than those of CA-stabilized TiO2-NPs, suggesting that activation energy is dependent on ligand size. This prototype study demonstrates the efficacy of using ES-DMA coupled with thermal treatment for characterizing the physical state of NPs, even in a complex medium (e.g., containing plasma proteins) and in the presence of particle agglomerates induced by interaction with binding ligands.