Exploration of Organic Nanomaterials with Liquid-Phase Transmission Electron Microscopy

ConspectusOrganic, soft materials with solution-phase nanoscale structures, such as emulsions, hydrogels, and thermally responsive materials, are inherently difficult to directly image via dry state and cryogenic-transmission electron microscopy (TEM). Therefore, we lack a routine microscopy method with sufficient resolution that can, in tandem with scattering techniques, probe the morphology and dynamics of these and many related systems. These challenges motivate liquid cell (LC) TEM method development, aimed at making the technique generally available and routine. To date, the field has been and continues to be dominantly focused on analyzing solution-phase inorganic materials. These mostly metallic nanoparticles have been studied at electron fluxes that can allow for high-resolution imaging, in the range of hundreds to thousands of e^- Å^-2 s^-1. Despite excellent contrast, in these cases, one often contends with knock-on damage, direct radiolysis, and sensitization of the solvent by virtue of enhanced secondary electron production by the impinging electron beam. With an interest in soft materials, we face both related and distinct challenges, especially in achieving a high-enough contrast within solvated liquid cells. Additionally, we must be aware of artifacts associated with high-flux imaging conditions in terms of direct radiolysis of the solvent and the sensitive materials themselves. Regardless, with care, it has become possible to gain real insight into both static and dynamic organic nanomaterials in solution. This is due, in large part, to key advances that have been made, including improved sample preparation protocols, image capture technologies, and image analysis, which have allowed LCTEM to have utility. To enable solvated soft matter characterization by LCTEM, a generalizable multimodal workflow was developed by leveraging both experimental and theoretical precedents from across the LCTEM field and adjacent works concerned with solution radiolysis and nanoparticle tracking analyses. This workflow consists of (1) modeling electron beam-solvent interactions, (2) studying electron beam-sample interactions via LCTEM coupled with post-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) correlative analysis via X-ray or light scattering. In this Account, we present this outlook and the challenges we continue to overcome in the direct imaging of dynamic solvated nanoscale soft materials.