Scanning Transmission Electron Microscopy

Atomic-scale phase imaging is central to resolving defects, interfaces, and weakly scattering atoms that govern the behavior of nanoscale materials. Electron ptychography delivers sub-ångström phase sensitivity but remains an offline technique, because its iterative reconstruction is computationally expensive and sensitive to experimental calibration, preventing live use during data acquisition. Here, a ptychography-supervised local inference framework is presented that converts four-dimensional scanning transmission electron microscopy (4D-STEM) into an acquisition-compatible phase-imaging workflow. Physics-constrained reference phase maps reconstructed from a single experimental AuPd dataset serve as teacher labels for a compact model that predicts local phase patches directly from diffraction measurements, without explicit probe input or online iterative optimization. Full-field images are assembled by deterministic overlap stitching. The workflow reaches an online latency of about 0.27 ms per probe position and a throughput of about 20,000 positions per second, an approximately 1,000-fold speed-up over GPU-accelerated ePIE, while preserving atomic-scale lattice contrast and reciprocal-space fidelity. Without fine-tuning, the same model transfers across materials (WS2), defocus conditions (high-entropy alloy nanoparticles), and instruments (hBN at 300 kV). The approach amortizes ptychographic redundancy into a fast, generalizable workflow that enables real-time atomic-scale phase imaging for materials microscopy.

Four-dimensional scanning transmission electron microscopy (4D-STEM) records a two-dimensional diffraction pattern at each electron-probe position, yielding spatially resolved reciprocal-space information but large, heterogeneous data volumes. Here we describe 4D-ImageNet, a collection of 174,000 diffraction patterns comprising 145,000 experimental patterns selected from 29 acquisitions and 29,000 multislice simulations. The experimental data cover acquisition-level labels for Ag, Au, mixed Au-Ag, CoO, Pd and ZnO specimens across multiple fields of view, scan dimensions, camera lengths and exposure times. Each acquisition contributes 5,000 quality-ranked patterns with source scan coordinates and acquisition metadata. A set-prediction detector provides model-derived pseudo-labels for the direct-beam position and Bragg-disk centres, with a confidence score for each disk. The simulation data cover 13 crystal structures and include Euler rotations, reciprocal-space sampling and approximate low-index beam directions. A grouped mixed-domain masked-reconstruction benchmark is provided to assess leakage-resistant loading and evaluation across experimental and simulated data. The dataset is intended for representation learning, disk detection, diffraction-pattern retrieval, orientation analysis and simulation-to-experiment studies.

Mapping crystalline phases at heterogeneous interfaces is essential for understanding material performance and degradation. However, structural heterogeneity, phase overlap, and local disorder complicate diffraction interpretation, while growing data volumes make manual analysis increasingly impractical. We introduce 4DMulti, a physics-guided learning framework for automated multicomponent identification from large-scale four-dimensional scanning transmission electron microscopy (4D-STEM) data. The supporting diffraction data resource comprises over 6 million high-quality experimental patterns and labeled patterns generated by Sim2real. A retrieval-conditioned latent diffusion transformer (Sim2real) translates simulated patterns into experimental-style examples under constraints designed to preserve Bragg geometry, while a rotation-invariant coordinate convolutional network identifies phases across in-plane rotations. 4DMulti achieves 98.82% classification accuracy on a five-phase experimental nanoparticle benchmark, with ablation studies supporting the complementary benefits of domain adaptation and rotation-invariant classification. We define diffraction-inferred structural complexity (DISC), a normalized predictive entropy score that quantifies phase-assignment ambiguity within a specified candidate phase library. We apply 4DMulti to generate structural maps of superconducting heterostructures, corroded alloy surfaces, and degraded solid-state battery interfaces down to single-nanometer spatial resolution. 4DMulti connects simulation-derived crystallographic knowledge to automated experimental interpretation, establishing a foundation for scalable analysis of complex interfaces and data-driven discovery of interfacial design principles.

Ptychographic phase reconstruction is commonly formulated as an iterative inverse problem, requiring repeated object-probe updates and resulting in substantial computational cost for large-scale 4D-STEM data. We present a direct local-to-global learning framework that reconstructs full-field phase maps from diffraction measurements without iterative refinement during inference. The proposed network predicts local wrapped-phase patches from individual diffraction patterns using a sine-cosine representation, and the predictions are assembled into a full-field reconstruction using calibrated scan positions and Gaussian-weighted stitching. To evaluate generalization beyond the training domain, the model is trained on one material and directly applied to another in a zero-shot setting without target-domain fine-tuning. Experiments on AuPd and MoS$_2$ demonstrate consistent cross-material transfer in both directions, with the proposed method achieving the best full-field MSE, PSNR, and MS-SSIM among the evaluated learning-based methods. Compared with the iterative ePIE approach, the proposed direct local-to-global pipeline reduces end-to-end reconstruction time by approximately 10x, demonstrating its potential for efficient and transferable ptychographic reconstruction.

This study systematically benchmarks different data augmentation setups across the baseline YOLO26 model size variants to determine the most effective setup for adenovirus detection in TEM images. The benchmarked setups include NAS, GAS, GMAS, and DAS, all evaluated under identical training conditions. A modified YOLO26 model leveraging P2, expanded STAL, increased topk, and MuSGD was also tested across the same benchmarked setups. The adenovirus dataset, selected from the published TEM virus dataset, was re-annotated by leveraging adenovirus particle positions to generate YOLO-compatible bounding box annotations. The modifications produced their largest performance gains under GAS and GMAS, with modified YOLO26x trained using GAS achieving a mAP@50 of 0.80, Precision of 0.81 and a Recall of 0.80

Super-resolution can make inspection images appear sharper without preserving the evidence needed to detect a defect. We study this failure mode with a benchmark that separates reconstruction from detection and evaluates both at a predeclared low false-positive rate. Ten end-to-end repetitions combine independently generated line/space and contact-hole images with model training, calibration, clean controls, weak defects, and a held-out defect morphology. Every reconstruction is scored by the same local residual detector, while direct and jointly trained detectors form a separate comparison track. Reconstruction fidelity and inspection utility diverge: the two learned reconstruction models attain the highest structural similarity yet detect fewer defect pixels than bicubic interpolation in every paired repetition. A direct DeepLabV3 detector reaches $0.1984\pm0.0385$ recall at $0.000174\pm0.000084$ false-positive rate and satisfies the held-out feasibility criterion in all ten repetitions. An illustrative joint model, DPU-WaferSR, passes independent clean calibration but exceeds the held-out limit in all ten repetitions, demonstrating that calibration success does not guarantee transfer. Weak-defect recall remains near zero for every feasible method. Applying the unchanged policies to 4,591 public Carinthia-S masks further reveals large method-dependent shifts on real SEM texture. These results support a simple conclusion: super-resolution for inspection should be judged by preserved task evidence and operating-point transfer, not reconstruction quality alone.

Organic mixed ionic electronic conductors (OMIECs) are a promising class of polymer materials for applications spanning neuromorphic computation to energy efficient electronics and bioelectronics. Despite being highly tunable, the relationship between structural features and key performance properties such as charge carrier mobility is poorly understood. Scanning nanodiffraction in the transmission electron microscope (TEM) is a powerful probe for elucidating this structure-property relationship, but produces large, noisy datasets that are difficult to interpret because polymer reflections exhibit several distinct morphologies. To address the complexity, we trained a machine learning (ML) model to detect these polymer diffraction peaks and their intensities from synthetic data. Compared to correlative peak detection algorithms, the conventional method for analyzing nanobeam 4D scanning transmission electron microscopy (4DSTEM) data, we show that the ML model is significantly faster and outperforms correlative algorithms in almost all cases, opening up the possibility of near-live visualization of 4DSTEM experiments.

A central premise of autonomous scientific imaging is that smarter navigation, whether Bayesian, RL-based, or otherwise adaptive, is the principal lever for sample-efficient acquisition. We present evidence to the contrary in scanning transmission electron microscopy (STEM), an atomic-resolution imaging modality whose every measurement deposits damaging electron dose. We introduce STEMGym, an open-source Gymnasium benchmark of 15 physics-simulated STEM worlds spanning five materials, three difficulty levels, and four characterisation tasks, scored by the Dose-Efficiency Curve area (DEC-AUC), a single scalar capturing the information-vs-dose Pareto frontier. Across 33 agent configurations under realistic dose budgets, the dominant determinant of dose efficiency is the analyst (perception) pipeline, not the navigator: pairing a trained CNN analyst with naïve raster scanning raises DEC-AUC by 5.5x over a CNN-free raster baseline (0.287 vs.\ 0.052), while substituting Bayesian or adaptive finite-state-machine navigation for raster yields no statistically significant further gain. Production-tier vision-language models further underperform task-specific CNNs by {\sim}13x on crystallographic defect analysis. By decoupling perception, navigation, and planning under a unified dose budget, STEMGym reframes where ML effort should be invested in autonomous electron microscopy and provides the measurement infrastructure to test it.

Energy Dispersive X-ray (EDX) tomography in Scanning Transmission Electron Microscopy (STEM) enables 3D compositional and elemental mapping at the nanoscale, but its use is limited by restricted tilt ranges and low-dose conditions required to avoid beam damage. Limited-angle acquisition introduces missing-wedge artefacts such as elongation and anisotropic resolution, while noisy low-dose data further degrade reconstruction quality and quantitative reliability. Here, we introduce an unsupervised deep learning framework based on Deep Image Prior with total variation regularization (DIP-TV) for limited-angle STEM-EDX tomography. We extend it to a multi-channel formulation (DIPm-TV) that jointly reconstructs multiple elemental maps by exploiting spatial correlations. Using a synthetic 3-channel phantom, we show that the method compensates for severe missing-wedge artefacts corresponding to approximately $100^\circ$ of missing angular range under moderate noise, outperforming simultaneous iterative reconstruction technique and compressed sensing approaches. We apply the method to 3D chemical analysis of Ge-Sb-Te (GST) memory devices in virgin (as-fabricated) and SET (crystalline) operational states. Samples were prepared as cross-sectional focused ion beam lamellae and acquired under a limited-angle tilt range from $-40^\circ$ to $+40^\circ$ with $5^\circ$ steps and a dose of $2.0\times10^5$ $e^-/Ang^2$. The multi-channel approach enables voxel-by-voxel elemental reconstruction using only EDX signals without external structural priors such as high-angle annular dark-field imaging. The reconstructed volumes show near-isotropic spatial resolution and reveal compositional heterogeneities associated with device operation. This approach enables 3D chemical characterization in experimentally accessible sample geometries where conventional methods fail due to severe angular limitations.

Artificial intelligence is rapidly advancing materials characterization, yet most applications in electron microscopy rely solely on image contrast, overlooking the chemical and experimental context that shapes image formation. This limitation makes defect classification inherently ambiguous, as similar contrasts can arise from different materials or imaging conditions. Here we develop a context-aware learning framework that integrates image-derived contrast with metadata describing composition, beam energy, and detector geometry. Using a systematically constructed dataset of ~55 million simulated patches spanning 576 cases across 96 doped monolayer transition-metal dichalcogenides, we show that conditioning on contextual variables transforms defect classification from an ill-posed image-only task into a well-posed, physically grounded problem. The framework achieves over 98% accuracy on simulations and near-human agreement on experimental data, with a 94% reduction in posterior entropy. By emphasizing contextual grounding over architectural complexity, this approach links experimental image contrast to the underlying chemical and imaging conditions, supporting physically grounded defect assignments and a general pathway toward multimodal AI models for autonomous materials characterization.

Analyzing microstructural defects in transmission electron microscopy (TEM) images, particularly in irradiated metal alloys, is often limited by the availability of high-quality, labeled data. To address this, we introduce a generative data augmentation approach using a mask-conditioned latent diffusion model (LDM) for synthesizing realistic TEM images with controllable, automatically labeled multi-class defect masks. Without requiring manual annotations for generation, our method enables the creation of synthetic image-mask pairs by sampling distributions learned from experimental masks. These generated data were used to augment small experimental datasets of varying sizes (10, 50, and 100 labeled experimental images) to train a Mask Regional Convolutional Neural Network (R-CNN) model for defect detection and classification. Our results show that generative augmentation yields small overall model performance improvements, with up to a 0.02 gain in the harmonic mean of detection and classification F1 scores. However, we also find that the relative contributions to detection and classification improvement depend on the specific train/test data split. These findings highlight the potential of targeted generative models to enhance deep learning performance in data-scarce microscopy-based image quantification tasks.

Reliable identification of fracture origins in alumina matrix composite hip and knee implants is critical for quality assurance and patient safety, yet current fractographic workflows are time-consuming, partly subjective, and reliant on high-magnification scanning electron microscopy (SEM). We present an interpretable vision-transformer (ViT) workflow for automated classification of fracture causes in an alumina matrix composite (BIOLOX delta, CeramTec GmbH) widely used in total joint replacements. A dataset of 8,493 SEM images (50x-10,000x) was curated from five years of in-production burst and proof tests and annotated into three defect categories defined along the manufacturing chain: green body, hard machining, and material defects. Under severe class imbalance, the fine-tuned ViT reached an accuracy of 0.907 and a macro-F1 of 0.888 in stratified five-fold cross-validation, with a two-stage perceptual-hash/SSIM leakage audit confirming negligible specimen overlap. Notably, performance at low magnification (50x) was comparable to that at high magnification (1k-10kx), indicating that macro-scale features - mirror geometry and hackle line fields - already encode sufficient diagnostic signal. Grad-CAM attributions consistently localised on canonical fractographic cues (mirrors, hackles, pores, machining marks), aligning with established fractographic criteria. Together, these results position interpretable ViTs as a complementary tool for ceramic-implant quality assurance, enabling low-magnification pre-screening and reducing reliance on time-intensive high-magnification inspection.

The transmission electron microscope facilitates the highest-resolution imaging of any instrument ever created, and its limiting factor is no longer spatial resolution but dose efficiency. Low electron doses avoid sample damage but produce noisy images for which, unlike in classical computer vision, there is no ground truth. Autonomous materials experimentation poses a related problem, since closed-loop instruments need representations grounded in the microscope state at acquisition. Both demand representations grounded in how an image was acquired. We release 7,330 paired high-angle annular dark-field scanning-TEM (HAADF-STEM) images and their seven-dimensional acquisition metadata, and propose Contrastive Image-Metadata Pre-training (CIMP), a CLIP-style encoder that aligns the two modalities and reaches 84.4% Top-1 cross-modal retrieval on a held-out split. All seven parameters are individually recoverable from the frozen visual embedding through a linear probe, and we use the embedding to condition a metadata-conditioned style-transfer model that re-renders experimental images under different acquisition parameters. Virtually scaling dwell time and beam current of low-dose images turns this model into a physics-informed denoiser; in a blind user study, experimental microscopists prefer it over the current state-of-the-art denoiser for STEM imagery on 70.2% of trials.

Analytical Dark Field Scanning Transmission Electron Microscopy (ADF-STEM) tomography reconstructs nanoscale materials in 3D by integrating multi-view tilt-series images, enabling precise analysis of their structural and compositional features. Although integrating more tilt views improves 3D reconstruction, it requires extended electron exposure that risks damaging dose-sensitive materials and introduces drift and misalignment, making it difficult to balance reconstruction fidelity with sample preservation. In practice, sparse-view acquisition is frequently required, yet conventional ADF-STEM methods degrade under limited views, exhibiting artifacts and reduced structural fidelity. To resolve these issues, in this paper, we adapt 3D GS to this domain with three key components. We first model the local scattering strength as a learnable scalar field, denza, to address the mismatch between 3DGS and ADF-STEM imaging physics. Then we introduce a coefficient $γ$ to stabilize scattering across tilt angles, ensuring consistent denza via scattering view normalization. Finally, We incorporate a loss function that includes a 2D Fourier amplitude term to suppress missing wedge artifacts in sparse-view reconstruction. Experiments on 45-view and 15-view tilt series show that DenZa-Gaussian produces high-fidelity reconstructions and 2D projections that align more closely with original tilts, demonstrating superior robustness under sparse-view conditions.

Scanning transmission electron microscopy (STEM) has become a cornerstone instrument for semiconductor materials metrology, enabling nanoscale analysis of complex multilayer structures that define device performance. Developing effective metrology workflows for such systems requires balancing automation with flexibility; rigid pipelines are brittle to sample variability, while purely manual approaches are slow and subjective. Here, we present a tunable human-AI-assisted workflow framework that enables modular and adaptive analysis of STEM images for device characterization. As an illustrative example, we demonstrate a workflow for automated layer thickness and interface roughness quantification in multilayer thin films. The system integrates gradient-based peak detection with interactive correction modules, allowing human input at the design stage while maintaining fully automated execution across samples. Implemented as a web-based interface, it processes TEM/EMD files directly, applies noise reduction and interface tracking algorithms, and outputs statistical roughness and thickness metrics with nanometer precision. This architecture exemplifies a general approach toward adaptive, reusable metrology workflows - bridging human insight and machine precision for scalable, standardized analysis in semiconductor manufacturing. The code is made available at https://github.com/utkarshp1161/thickness-mapping-webapp

High-Resolution Transmission Electron Microscopy (HRTEM) enables atomic-scale observation of nucleation dynamics, which boosts the studies of advanced solid materials. Nonetheless, due to the millisecond-scale rapid change of nucleation, it requires short-exposure rapid imaging, leading to severe noise that obscures atomic positions. In this work, we propose a statistical characteristic-guided denoising network, which utilizes statistical characteristics to guide the denoising process in both spatial and frequency domains. In the spatial domain, we present spatial deviation-guided weighting to select appropriate convolution operations for each spatial position based on deviation characteristic. In the frequency domain, we present frequency band-guided weighting to enhance signals and suppress noise based on band characteristics. We also develop an HRTEM-specific noise calibration method and generate a dataset with disordered structures and realistic HRTEM image noises. It can ensure the denoising performance of models on real images for nucleation observation. Experiments on synthetic and real data show our method outperforms the state-of-the-art methods in HRTEM image denoising, with effectiveness in the localization downstream task. Code will be available at https://github.com/HeasonLee/SCGN.

Modern automated microscopy faces a fundamental discovery challenge: in many systems, the most important scientific information does not reside in the immediately visible image features, but in the target space of sequentially acquired spectra or functional responses, making it essential to develop strategies that can actively search for new behaviors rather than simply optimize known objectives. Here, we developed a deep-kernel-learning BEACON framework that is explicitly designed to guide discovery in the target space by learning structure-property relationships during the experiment and using that evolving model to seek diverse response regimes. We first established the method through demonstration workflows built on pre-acquired ground-truth datasets, which enabled direct benchmarking against classical acquisition strategies and allowed us to define a set of monitoring functions for comparing exploration quality, target-space coverage, and surrogate-model behavior in a transparent and reproducible manner. This benchmarking framework provides a practical basis for evaluating discovery-driven algorithms, not just optimization performance. We then operationalized and deployed the workflow on STEM, showing that the approach can transition from offline validation to real experimental implementation. To support adoption and extension by the broader community, the associated notebooks are available, allowing users to reproduce the workflows, test the benchmarks, and adapt the method to their own instruments and datasets.

Electron microscopy has enabled many scientific breakthroughs across multiple fields. A key challenge is the tuning of microscope parameters based on images to overcome optical aberrations that deteriorate image quality. This calibration problem is challenging due to the high-dimensional and noisy nature of the diagnostic images, and the fact that optimal parameters cannot be identified from a single image. We tackle the calibration problem for Scanning Transmission Electron Microscopes (STEM) by employing variational autoencoders (VAEs), trained on simulated data, to learn low-dimensional representations of images, whereas most existing methods extract only scalar values. We then simultaneously estimate the model that maps calibration parameters to encoded representations and the optimal calibration parameters using an expectation maximization (EM) approach. This joint estimation explicitly addresses the simulation-to-reality gap inherent in data-driven methods that train on simulated data from a digital twin. We leverage the known symmetry property of the optical system to establish global identifiability of the joint estimation problem, ensuring that a unique optimum exists. We demonstrate that our approach is substantially faster and more consistent than existing methods on a real STEM, achieving a 2x reduction in estimation error while requiring fewer observations. This represents a notable advance in automated STEM calibration and demonstrates the potential of VAEs for information compression in images. Beyond microscopy, the VAE-EM framework applies to inverse problems where simulated training data introduces a reality gap and where non-injective mappings would otherwise prevent unique solutions.