Liquid-Phase Transmission Electron Microscopy (LP-TEM) offers the opportunity to study nanoscale dynamics of phenomena related to materials and life science in a native liquid environment and in real time. Until now, the opportunity to control/induce such dynamics by changing the chemical environment in the liquid flow cell (LFC) has rarely been exploited due to an incomplete understanding of hydrodynamic properties of LP-TEM flow systems. This manuscript introduces a method for hydrodynamic characterization of LP-TEM flow systems based on monitoring transmitted intensity while flowing a strongly electron scattering contrast agent solution. Key characteristic temporal indicators of solution replacement for various channel geometries were experimentally measured. A numerical physical model of solute transport based on realistic flow channel geometries was successfully implemented and validated against experiments. The model confirmed the impact of flow channel geometry on the importance of convective and diffusive solute transport, deduced by experiment, and could further extend understanding of hydrodynamics in LP-TEM flow systems. We emphasize that our approach can be applied to hydrodynamic characterization of any customized LP-TEM flow system. We foresee the implemented predictive model driving the future design of application-specific LP-TEM flow systems and, when combined with existing chemical reaction models, to a flourishing of the planning and interpretation of experimental observations.

Applying a continuous flow to rinse radiolytic species from the irradiated volume is a widely proposed strategy to reduce beam-related artefacts in Liquid-Phase Transmission Electron Microscopy (LP-TEM). However, this has not been verified either experimentally or theoretically to date. Here we explore an extended numerical model implementing radiolytic chemistry, diffusion and liquid convection to study the peculiarities of beam-induced chemistry in the presence of a flowing liquid within a heterogenously irradiated nanoconfined channel corresponding to a LP-TEM flow cell. Intruigingly, the concentration of some principal chemical species, predominantly hydrogen radicals and hydrated electrons, is found to grow significantly rather than to decrease in respect to zero-flow when moderate flow conditions are applied. This counterintuitive behaviour is discussed in terms of reactants’ lifetimes, spatial separation of the reaction network and self-scavenging by secondary radiolytic species. In the presence of a flow the consumption of highly reactive species is suppressed due to removal of the self-scavengers, and as a result their concentration in the irradiated area increases. A proof of concept for the supply of scavengers by the flow is demonstrated. Unravelling the effect of flow on radiolysis spawns direct implications for LP-TEM flow experiments providing yet one more control parameter for adjusting the chemistry in the irradiated/imaging area, in particular for mitigation strategies by continuous supply of scavengers.

Liquid-phase transmission electron microscopy is a burgeoning experimental technique for monitoring nanoscale dynamics in a liquid environment, increasingly employing microfluidic reactors to control the composition of the sample solution. Current challenges comprise fast mass transport dynamics inside the central nanochannel of the liquid cell, typically flow cells, and reliable fixation of the specimen in the limited imaging area. In this work, we present a liquid cell concept – the diffusion cell – that satisfies these seemingly contradictory requirements by providing additional on-chip bypasses to allow high convective transport around the nanochannel in which diffusive transport predominates. Diffusion cell prototypes are developed using numerical mass transport models and fabricated on the basis of existing two-chip setups. Important hydrodynamic parameters, i.e., the total flow resistance, the flow velocity in the imaging area, and the time constants of mixing, are improved by 2-3 orders of magnitude compared to existing setups. The solution replacement dynamics achieved within seconds already match the mixing timescales of many ex-situ scenarios, and further improvements are possible. Diffusion cells can be easily integrated into existing liquid-phase transmission electron microscopy workflows, provide correlation of results with ex-situ experiments, and can create additional research directions addressing fast nanoscale processes.