Liquid Cell Electron Microscopy for Nanoparticle Characterization

Liquid cell electron microscopy (LC-EM) has emerged as a transformative tool for observing nanoparticles in their native, fluid environment with nanometre spatial resolution and millisecond temporal resolution. By enclosing a thin layer of liquid between electron-transparent windows—typically silicon nitride or graphene—researchers can directly visualise dynamic processes such as nucleation, growth, self-assembly and chemical transformations. This approach bridges the gap between ex situ structural analysis and the true, operando behaviour of colloidal particles. Key advantages include real-time tracking of particle trajectories, measurement of interparticle forces and identification of transient states that are inaccessible to conventional dry-state imaging. Advances in cell design, beam-dose management and image processing have progressively mitigated radiolytic artefacts, enabling more quantitative insights into reaction pathways and the influence of ligands, solvents or applied potentials. LC-EM thus provides unparalleled mechanistic understanding across disciplines from materials synthesis to catalysis and energy storage, facilitating the rational design of next-generation nanomaterials.

Research from Nature Portfolio

Seminal in situ studies have revealed the atomic-scale details of crystal growth by oriented attachment. High-resolution imaging of citrate-stabilised gold nanoparticles demonstrated how ligand overlap directs rotational alignment and facet-specific coalescence, elucidating the energetic favourability of {111} interfaces in real time. Complementary work on zinc oxide employed tailored fluid cells and advanced simulations to quantify interparticle torques and potential wells, showing that electrostatic ion–solvent correlations drive pre-alignment well before van der Waals attractions dominate. In another foundational contribution, liquid-cell observations of branched nanocrystal self-assembly uncovered the balance of dipolar and entropic forces governing chain-length distributions, with combined statistical-mechanical modelling providing direct access to the underlying interaction potentials.

Liquid Cell Electron Microscopy for Nanoparticle Characterization publication trend

The graph below shows the total number of articles in liquid cell electron microscopy for nanoparticle characterization across all publications each year (not limited to Nature Index journals).

Technical terms

Liquid Cell Transmission Electron Microscopy (LC-TEM): A technique in which a liquid sample is confined between electron-transparent windows to allow high-resolution imaging of dynamic processes in situ.

Radiolysis: The decomposition of solvent molecules by the electron beam, generating reactive species that can alter sample chemistry and dynamics.

Oriented Attachment: A non-classical crystal growth mechanism in which particles rotate and align along specific crystallographic facets before coalescing into larger crystals.

Energy Dispersive X-ray Spectroscopy (EDXS): An analytical method for determining elemental composition by detecting X-rays emitted under electron-beam excitation.

Microfabricated Liquid Cell: A miniature chamber formed on silicon or boron nitride chips with thin, transparent windows to enclose liquids for electron-microscopy studies.

References

1. Liquid cell transmission electron microscopy and its applications. Royal Society Open Science (2020).
2. In-situ liquid cell transmission electron microscopy investigation on oriented attachment of gold nanoparticles. Nature Communications (2018).
3. Direction-specific interaction forces underlying zinc oxide crystal growth by oriented attachment. Nature Communications (2017).
4. In situ microscopy of the self-assembly of branched nanocrystals in solution. Nature Communications (2016).
5. Insights into Electrocatalyst Transformations Studied in Real Time with Electrochemical Liquid-Phase Transmission Electron Microscopy. Accounts of Chemical Research (2023).
6. Nanometer Resolution Elemental Mapping in Graphene-Based TEM Liquid Cells. Nano Letters (2018).