Exploration of Organic Nanomaterials with Liquid-Phase Transmission Electron Microscopy

Conspectus Organic,soft materials withsolution-phase nanoscale structures,such as emulsions, hydrogels, and thermally responsive materials,are inherently difficult to directly image via dry state and cryogenic-transmissionelectron microscopy (TEM). Therefore, we lack a routine microscopymethod with sufficient resolution that can, in tandem with scatteringtechniques, probe the morphology and dynamics of these and many relatedsystems. These challenges motivate liquid cell (LC) TEM method development,aimed at making the technique generally available and routine. Todate, the field has been and continues to be dominantly focused onanalyzing solution-phase inorganic materials. These mostly metallicnanoparticles have been studied at electron fluxes that can allowfor high-resolution imaging, in the range of hundreds to thousandsof e(-) & ANGS;(-2) s(-1). Despite excellent contrast, in these cases, one often contendswith knock-on damage, direct radiolysis, and sensitization of thesolvent by virtue of enhanced secondary electron production by theimpinging electron beam. With an interest in soft materials, we faceboth related and distinct challenges, especially in achieving a high-enoughcontrast within solvated liquid cells. Additionally, we must be awareof artifacts associated with high-flux imaging conditions in termsof direct radiolysis of the solvent and the sensitive materials themselves.Regardless, with care, it has become possible to gain real insightinto both static and dynamic organic nanomaterials in solution. Thisis due, in large part, to key advances that have been made, includingimproved sample preparation protocols, image capture technologies,and image analysis, which have allowed LCTEM to have utility. To enablesolvated soft matter characterization by LCTEM, a generalizable multimodalworkflow was developed by leveraging both experimental and theoreticalprecedents from across the LCTEM field and adjacent works concernedwith solution radiolysis and nanoparticle tracking analyses. Thisworkflow consists of (1) modeling electron beam-solvent interactions,(2) studying electron beam-sample interactions via LCTEM coupled withpost-mortem analysis, (3) the construction of "damage plots"displaying sample integrity under varied imaging and sample conditions,(4) optimized LCTEM imaging, (5) image processing, and (6) correlativeanalysis via X-ray or light scattering. In this Account, we presentthis outlook and the challenges we continue to overcome in the directimaging of dynamic solvated nanoscale soft materials.