Liquid Electrochemical TEM (ec-TEM)

• Liquid ec-TEM is an advanced microscopy technique that employs sealed liquid cells to directly image nanoscale electrochemical processes.
• It integrates innovative cell designs such as nanoaquarium and graphene-based cells to achieve high spatial resolution, even at atomic scales.
• Combining high-resolution imaging and spectroscopy, ec-TEM facilitates quantitative mapping of dynamic reactions in energy, catalysis, and material science.

Liquid Electrochemical Transmission Electron Microscopy (ec-TEM) is an advanced analytical technique that facilitates the real-time visualization and analysis of nanoscale electrochemical processes in liquids. By combining sealed or environmental liquid cells with transmission electron microscopy (TEM), ec-TEM enables direct observation of phenomena such as colloidal assembly, nanoparticle nucleation, electrochemical deposition, and interfacial reactions under controlled potential, with spatial resolution down to atomic scales. Recent innovations integrate spectroscopy, tomography, and correlative analysis, greatly expanding the capabilities of ec-TEM for material science, energy research, and catalysis.

1. Principles of Liquid Cell Design and Electrochemical Integration

The core challenge for liquid TEM is the incompatibility between liquid specimens and the high-vacuum environment required for electron microscopy. Sample thickness and evaporation limit both imaging and analytical fidelity. To overcome these constraints, cell architectures such as the nanoaquarium—a nano-Hele-Shaw device with a hermetically sealed 100 nm chamber sandwiched between two 50 nm silicon nitride membranes—allow stable liquid imaging (Grogan et al., 2010). These Si₃N₄ windows are robust, electron transparent, and compatible with microfabrication. Importantly, embedded electrodes for actuation and sensing transform the liquid cell into an electrochemical microreactor, enabling controlled potential application and in situ studies of deposition, redox reactions, and interfacial phenomena.

Graphene-based liquid cells, incorporating patterned hBN spacers and stacked graphene windows, further reduce background and scattering thanks to graphene’s ultralow scattering cross-section and superb mechanical/chemical stability (Kelly et al., 2017). This design supports sub-30 nm liquid layers, greatly enhancing spatial and analytical resolution, with robust sealing that tolerates repeated vacuum cycling and thermal expansion.

2. Imaging Modalities and Spectroscopic Capabilities

Liquid ec-TEM supports high-resolution imaging modes (TEM, STEM-HAADF) and advanced spectroscopy, notably electron energy-loss spectroscopy (EELS). Conventional X-ray analysis is ineffective due to detector shadowing by the cell holder, while core-loss EELS suffers from multiple inelastic scattering in thick liquid layers (above ~3 mean free paths). Valence EELS, probing low-loss excitations (plasmons, interband transitions, optical gaps), remains effective in thicker layers (up to 6–7 mean free paths), facilitating chemical identification and local electronic property determination—even in zeptoliter volumes (Holtz et al., 2012).

Valence EELS enables quantitative analysis using Beer’s law for thickness ($I = I_0 \exp(-t/\lambda)$), the free-electron model for plasmon energy ($E_p = \hbar \sqrt{\frac{n e^2}{\epsilon_0 m_e}}$), and Poisson statistics for single scattering ($P = (t/\lambda) \exp(-t/\lambda)$). These measurements provide direct insight into electron density and dielectric structure, discrimination between phases (metallic and liquid), and dynamic evolution during reactions such as copper deposition in CuSO₄ electrolyte.

Energy dispersive X-ray spectroscopy (EDXS) in engineered graphene liquid cells achieves elemental mapping at ~1 nm resolution for particles in solution. For example, dynamic tracking of Au–Fe core-shell nanoparticle formation during reduction of Fe ions reveals compositional gradients at nanometer resolution (Kelly et al., 2017).

3. In Situ Observation of Dynamic Electrochemical/Colloidal Processes

The integration of embedded electrodes enables real-time actuation and monitoring of processes such as diffusion-limited aggregation, homogeneous nucleation, and electrochemical deposition. In the nanoaquarium, imaging at 20–30 kV revealed the aggregation dynamics of 5 nm and 50 nm gold particles, forming fractal structures with dimensions consistent with light scattering theory—indicating minimal beam-induced artefacts (Grogan et al., 2010).

Advanced platforms can resolve single atom dynamics in realistic environments. Double graphene liquid cells (DGLCs) allow direct imaging of individual Pt atoms on monolayer MoS₂, revealing dramatic changes in resting site preference and atomic mobility under liquid vs. vacuum conditions due to solvent-mediated surface defect substitution and enhanced diffusivity ($D > 0.25$ nm²/s in liquid vs. $<0.2$ nm²/s in vacuum) (Clark et al., 2022). These findings confirm that coordination and reactivity at catalytic interfaces depend critically on local solvation and environmental composition.

Fast electron tomography in liquid cells, utilizing compressed sensing and advanced registration algorithms, reconstructs full 3D morphologies of colloidal assemblies while preserving native structure. In contrast to dried samples, liquid-phase reconstructions reveal increased interparticle distances and distorted, less compact configurations, quantitatively capturing ligand layer thicknesses and the authentic packing architecture of polystyrene-capped Au nanoparticles and Au nanorods (Esteban et al., 2023).

4. Correlative Approaches and Multimodal Analysis

Correlating ec-TEM imaging with ex situ compositional and spectroscopic techniques is essential to deconvolve reaction mechanisms and degradation pathways in energy materials. For Na-ion and Li-ion battery studies, in situ microbattery cells with controlled electrolyte flow and cycling regimes enable the visualization of solid electrolyte interphase (SEI/CEI) formation, dissolution, and plating phenomena. For instance, coupled ec-TEM and GC/MS resolved the appearance of foam-like Na structures—associated with gas release and capacity degradation—as well as the formation of specific organic degradation products traced to electrolyte reactions (Moncayo et al., 2023, Gallegos-Moncayo et al., 14 Oct 2025).

Such correlative strategies extend to cryogenic workflows marrying TEM with atom probe tomography (APT). After operando imaging, MEMS nanochips containing liquid–solid interfaces are rapidly frozen, transferred via inert gas modules to a cryogenic plasma-focused ion beam for milling and subsequent APT. This unlocks near-atomic 3D compositional mapping of electrode–electrolyte interfaces, overcoming limitations of beam scattering and allowing direct correlation between in situ morphological dynamics and chemical state (Mulcahy et al., 26 Apr 2025).

5. Radiation Chemistry and Experimental Control

Electron-induced radiolysis is an inherent aspect of liquid cell TEM, resulting in the generation of reactive species (OH·, $e^-_{aq}$, H·, H₂O₂) by energy deposition in water or electrolytes. The kinetics of radiolytic species formation and decay are described by reaction–diffusion equations:

$$\frac{\partial C_i}{\partial t} = G_i \, \dot{D} - \sum_j k_{ij} C_i C_j + D_i \nabla^2 C_i$$

where $G_i$ is the G-value, $\dot{D}$ the dose rate, $k_{ij}$ reaction constants, and $D_i$ diffusivities (Koo et al., 27 Feb 2024). Radiolytic species can artificially accelerate or skew observed electrochemical reactions (e.g., oxide shell growth, altered redox equilibria). Mitigation guidelines include minimizing dose rate via scanning modalities, optimizing electrolyte flow for efficient washout, incorporating radical scavengers, and fine-tuning cell geometry to control species accumulation. Adhering to these protocols ensures experimental fidelity and that the observed nanoscale processes are representative of intrinsic electrochemical phenomena, not artifacts of radiolysis.

6. Technical Challenges, Solutions, and Future Prospects

Persistent technical challenges include electron beam scattering in thick cells, limited tilt range for 3D studies due to cell geometry, low signal-to-noise ratio for spectroscopy/tomography, and managing beam-induced sample modification. Solutions center on nanofabrication of ultrathin cell windows (graphene, Si₃N₄, hBN), precise control of liquid layer thickness/volume, robust environmental sealing, and integration of advanced analytical methodologies (EELS, EDXS, tomography, correlative workflows).

Open-cell environmental TEM techniques enable in situ hydration for imaging on standard grids, using salt particles for droplet nucleation and precise temperature/vapor control. While this approach is less common and technically demanding, it offers greater flexibility in sample geometry and future integration with external stimuli such as in situ illumination for photocatalysis studies (Levin et al., 2023).

Future directions in ec-TEM include expanding cell architectures for more complex chemical environments, refining multimodal correlative analysis, improving cryogenic protocols, and integrating real‐time spectroscopy/tomography at atomic resolution. Methodological advances will increasingly emphasize the minimization of radiolytic and imaging artefacts and the faithful preservation of native electrochemical states at interfaces. These capabilities are central to the design and optimization of next-generation batteries, catalysts, and functional materials operating in liquid environments.