Abstract
In situ imaging for direct visualization is important for physical and biological sciences. Research endeavors into elucidating dynamic biological and nanoscale phenomena frequently necessitate in situ and time-resolved imaging. In situ liquid cell electron microscopy (LC-EM) can overcome certain limitations of conventional electron microscopies and offer great promise. This review aims to examine the status-quo and practical challenges of in situ LC-EM and its applications, and to offer insights into a novel correlative technique termed microfluidic liquid cell electron microscopy. We conclude by suggesting a few research ideas adopting microfluidic LC-EM for in situ imaging of biological and nanoscale systems.
Highlights
Central to nanoscale characterization of materials, especially those in biological milieu, is direct visualization
We conclude with an outlook in terms of the future applications of microfluidic liquid cell electron microscopy (LC-EM) for imaging complex biological and nanoscale systems
For LC-EM, chip-based microfluidics would be of practical interest to most bioimaging applications
Summary
Central to nanoscale characterization of materials, especially those in biological milieu, is direct visualization. Strategies to improve spatial resolutions for LC-EMs include appropriate materials selection for the liquid cell membrane, chromatic aberration correction, and energy filtering Such strategies must be weighed against electron dosage which should remain sufficiently low as not to damage biological samples. While it is typically advised to maintain a low imaging time for biological samples, graphene sheets ensure prolonged in situ imaging times of up to tens of minutes (Yuk et al, 2012; Park et al, 2015; Keskin and de Jonge, 2018; Narayanan et al, 2020) The use of both graphene sheets as liquid cell membranes and free radical scavengers (Schneider et al, 2014) can partially remediate one major damaging mechanism to the liquid layer. It is best that we relate additional in vivo characterization techniques with in situ imaging
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