The development of nanotechnology necessitates appropriate tools for nanoparticle characterization to assure product quality, evaluate safety and facilitate manufacturing. The properties of interest particularly relevant to nanomedicine and environmental ecotoxicology include size, shape, aggregation, concentration, dissolution, surface chemistry, and composition etc. Engineered nanoparticles in a complex matrix, at realistic concentration are two of the major challenges for analytical scientist. Potential transformation of pristine engineered nanomaterials when put in contact with either biological or environmental media further complicate the analytical task.

In this dissertation, I aim to optimize and extend the application of novel hyphenated instruments consisting of differential mobility analysis (DMA) and inductively coupled plasma-mass spectrometry (ICP-MS) for real time size classification and elemental detection in biomedical and environmental fields. I have applied DMA-ICP-MS in quantitatively characterizing anti-tumor drug delivery platform to assist design and performance evaluation. Optimal balance among drug loading, stability and release performance was achieved and evaluated by DMA-ICP-MS.

I have further developed a novel analytical methodology including DMA and ICP-MS operating in single particle mode (i.e. spICP-MS). I successfully demonstrated and validated the method for accurate and simultaneous size, mass and concentration measurement by NIST reference materials. DMA-spICP-MS was shown with the capability to characterize nanoparticle aggregation state and surface coating. In addition, this technique was shown to be useful for real-world samples with high ionic background due to its ability to remove dissolved ions yielding a cleaner background.

Given this validated DMA-spICP-MS method, I applied it to quantifying the geometries of seven gold nanorod samples with different geometries. It was demonstrated that DMA-spICP-MS can achieve fast quantification of both length and diameter with accuracy comparable with TEM analysis. This method provided the capability to separate nanorods from spheres quantifying the geometry for each population.

Finally, an interesting open and high-order rosette protein structure was investigated by electrospray-DMA. The staining procedure was optimized and effect of electrospray process on protein particle structure was evaluated. Protein particle after electrospray was largely maintained. Mobility simulation by MOBCAL showed close matches with experimental data and enabled peak assignment to various particle assembly structures.