Kate L. Klein, Ian M. Anderson


Surface and Microanalysis Science Division,

Material Measurement Laboratory, NIST



With the growing applications of nanoparticles, especially in health-related fields, there is rising concern over the toxicity and fate of engineered nanoparticles upon their release into our bodies and our surroundings.  Toxicology studies in the literature consist of highly conflicting, difficult-to-compare results, due in part to uncertainties and lack of uniformity in critical material properties such as hydrodynamic size distribution, aggregation behavior, and reactivity in solution.  There is an urgent need for a characterization technique that combines the ability to image functional nanostructures in their relevant aqueous (“in vitro”) environment with the high spatial resolution necessary to probe the features of individual nanostructures. 

This research addresses the above challenge using a newly developed transmission electron microscopy (TEM) liquid flow cell specimen holder.  The rapid image acquisition of the TEM coupled with the capacity to flow liquid through the probed region also enables dynamic experiments, currently inaccessible by other techniques such as cryo TEM, thus providing a unique in situ approach to study particle behavior in a prescribed chemical environment.

Data were acquired from a microfluidic cell comprised of two silicon microchips with electron-transparent silicon nitride windows.  The microfluidic cell interfaces with a specialized holder that provides fluid circulation through the sample area from the outside of the electron microscope.  We report on the imaging and energy-loss characteristics of the microfluidic flow cell system using 300 kV conventional TEM, specifically relating the effect of multiple inelastic scattering in the fluid to spatial resolution.  Furthermore, we demonstrate the utility of this technique for in vitro imaging of functional nanoparticles through preliminary studies of citrate-stabilized metal nanoparticles.  The ability to observe directly nanoparticle attributes and behavior in relevant media will provide crucial information for related in vivo studies.