arXiv subjects

Christian Eggeling

Publications and source records attributed to Christian Eggeling.

10 recordsLinked to original sources

arXiv2026

Physics-Informed Deep Learning Model for Cross-Modality Super-Resolution in Fluorescence Microscopy

Cross-modality image translation offers a route to super-resolution fluorescence microscopy from low-resolution images while reducing phototoxicity and instrumentation demands. However, purely data-driven models can produce visually plausible outputs that are inconsistent with optical image formation. Here, we propose a physics-informed generative adversarial network for confocal-to-STED image translation that incorporates microscope-specific point spread function information into the training objective. Simulated and experimentally measured PSFs were evaluated using a limited paired confocal-STED dataset of TOM20-labeled mitochondria in human primary M2 macrophages acquired across different experimental days. Performance was assessed using reference-based and non-reference-based image-quality metrics, together with complementary frequency- and distribution-sensitive analyses. The no-reference metrics probed physics-relevant image properties, including spatial-frequency content, contrast, and signal-to-noise behavior. PSF-guided models improved structural fidelity, reduced local deviations, and achieved closer agreement with STED references than non-PSF baselines, particularly in frequency-domain analyses. These results demonstrate that optical priors can improve the structural fidelity and physical plausibility of generative microscopy models for cross-modality super-resolution imaging.

cs.CV↗

arXiv2025

Lightweight CycleGAN Models for Cross-Modality Image Transformation and Experimental Quality Assessment in Fluorescence Microscopy

Lightweight deep learning models offer substantial reductions in computational cost and environmental impact, making them crucial for scientific applications. We present a lightweight CycleGAN for modality transfer in fluorescence microscopy (confocal to super-resolution STED/deconvolved STED), addressing the common challenge of unpaired datasets. By replacing the traditional channel-doubling strategy in the U-Net-based generator with a fixed channel approach, we drastically reduce trainable parameters from 41.8 million to approximately nine thousand, achieving superior performance with faster training and lower memory usage. We also introduce the GAN as a diagnostic tool for experimental and labeling quality. When trained on high-quality images, the GAN learns the characteristics of optimal imaging; deviations between its generated outputs and new experimental images can reveal issues such as photobleaching, artifacts, or inaccurate labeling. This establishes the model as a practical tool for validating experimental accuracy and image fidelity in microscopy workflows.

cs.CV↗

arXiv2025

Quantitative EUV ptychography reveals nanoscale morphological responses of bacteria under physiological and antibiotic stress

Table-top extreme ultraviolet (EUV) ptychography enables nanoscale, label-free, and quantitative imaging with intrinsic elemental sensitivity, offering a unique modality for subcellular profiling of bacterial morphology and composition. In this work, we apply a state-of-the-art EUV ptychographic microscope to systematically investigate the structural and compositional features of two model prokaryotic bacteria, Escherichia coli and Bacillus subtilis. With quantitative amplitude and phase reconstructions at 44 nm resolution on a tabletop, we visualize subtle phenomena during bacterial sporulation based on distinct morphological signatures. Notably, we examine the single-cell response of B. subtilis to the antibiotic monazomycin, uncovering ultrastructural disruption and compositional alterations. To further characterize the phenotypic variations, we perform multivariate statistical analysis on extracted morphological features, revealing diversity and clustering patterns associated with defined biological states. This work establishes EUV ptychography as a powerful, element-sensitive imaging platform for label-free bacterial imaging, showcasing its promise for biomedical and antimicrobial research.

physics.bio-ph↗

arXiv2025

Benchmarking of Fluorescence Lifetime Measurements using Time-Frequency Correlated Photons

The investigation of fluorescence lifetime became an important tool in biology and medical science. So far, established methods of fluorescence lifetime measurements require the illumination of the investigated probes with pulsed or amplitude-modulated light. In this paper, we examine the limitations of an innovative method of fluorescence lifetime using the strong time-frequency correlation of entangled photons generated by a continuous-wave source. For this purpose, we investigate the lifetime of IR-140 to demonstrate the functional principle and its dependencies on different experimental parameters. We also compare this technique with state-of-the-art FLIM and observed an improved figure-of-merit. Finally, we discuss the potential of a quantum advantage.

quant-ph↗

arXiv2025

Funnelling super-resolution STED microscopy through multimode fibres

Holographic multimode fibre endoscopes have recently shown their ability to unveil and monitor deep brain structures with sub-micrometre resolution, establishing themselves as a minimally-invasive technology with promising applications in neurobiology. In this approach, holographic control of the input light field entering the multimode fibres is achieved by means of wavefront shaping, usually treating the fibre as a complex medium. In contrast to other unpredictable and highly scattering complex media, multimode fibres feature symmetries and strong correlations between their input and output fields. Both step-index and graded-index multimode fibres offer a specific set of such correlations which, when appropriately leveraged, enable generating high-quality focused pulses with minimal intermodal dispersion. With this, we funnelled pulsed super-resolution STED microscopy with time-gated detection through a custom multimode fibre probe, combining the correlations of both multimode fibre types. We demonstrate resolution improvements over 3-times beyond the diffraction limit and showcase its applicability in bioimaging. This work provides not only a solution for delivering short pulses through step-index multimode fibre segments but also marks a step towards bringing advanced super-resolution imaging techniques with virtually no depth limitations.

physics.optics↗

arXiv2025

Enhancing entangled two-photon absorption of Nile Red via temperature-controlled SPDC

Entangled two-photon absorption can enable a linear scaling of fluorescence emission with the excitation power. In comparison to classical two-photon absorption with a quadratic scaling, this can allow fluorescence imaging or photolithography with high axial resolution at minimal exposure intensities. However, most experimental studies on two-photon absorption were not able to show an unambiguous proof of fluorescence emission driven by entangled photon pairs. On the other hand, existing theoretical models struggle to accurately predict the entangled two-photon absorption behavior of chemically complex dyes. In this paper, we introduce an approach to simulate entangled two-photon absorption in common fluorescence dyes considering their chemical properties. Our theoretical model allows a deeper understanding of experimental results and thus the occurrence of entangled two-photon absorption. In particular, we found a remarkable dependency of the absorption probability on the phase-matching temperature of the nonlinear material. Further, we compared results of our theoretical approach to experimental data for Nile Red.

quant-ph↗

arXiv2023

Laboratory-Based Correlative Soft X-ray and Fluorescence Microscopy in an Integrated Setup

Correlative microscopy is a powerful technique that combines the advantages of multiple imaging modalities to achieve a comprehensive understanding of investigated samples. For example, fluorescence microscopy provides unique functional contrast by imaging only specifically labeled components, especially in biological samples. However, the achievable structural information on the sample in its full complexity is limited. Here, the intrinsic label-free carbon contrast of water window soft X-ray microscopy can complement fluorescence images in a correlative approach ultimately combining nanoscale structural resolution with functional contrast. However, soft X-ray microscopes are complex and elaborate, and typically require a large-scale synchrotron radiation source due to the demanding photon flux requirements. Yet, with modern high-power lasers it has become possible to generate sufficient photon flux from laser-produced plasmas, thus enabling laboratory-based setups. Here, we present a compact table-top soft X-ray microscope with an integrated epifluorescence modality for 'in-situ' correlative imaging. Samples remain in place when switching between modalities, ensuring identical measurement conditions and avoiding sample alteration or destruction. We demonstrate our new method by multimodal images of several exemplary samples ranging from nanoparticles to various multicolor labeled cell types. A structural resolution of down to 50 nm was reached.

physics.ins-det↗

arXiv2021

Protein induced lipid demixing in homogeneous membranes

Specific lipid environments are necessary for the establishment of protein signalling platforms in membranes, yet their origin has been highly debated. We present a continuum, exactly solvable model of protein induced local demixing of lipid membranes. The coupling between a local composition and a local thickness of the membrane induces lipid domains around inclusions with hydrophobic mismatch, even for temperatures above the miscibility critical point of the membrane. The model qualitatively explains the experimentally observed formation of lipid domains induced by anchoring of reconstituted actin in flat supported lipid bilayers.

physics.bio-ph↗

arXiv2017

The 2015 super-resolution microscopy roadmap

Far-field optical microscopy using focused light is an important tool in a number of scientific disciplines including chemical, (bio)physical and biomedical research, particularly with respect to the study of living cells and organisms. Unfortunately, the applicability of the optical microscope is limited, since the diffraction of light imposes limitations on the spatial resolution of the image. Consequently the details of, for example, cellular protein distributions, can be visualized only to a certain extent. Fortunately, recent years have witnessed the development of 'super-resolution' far-field optical microscopy (nanoscopy) techniques such as stimulated emission depletion (STED), ground state depletion (GSD), reversible saturated optical (fluorescence) transitions (RESOLFT), photoactivation localization microscopy (PALM), stochastic optical reconstruction microscopy (STORM), structured illumination microscopy (SIM) or saturated structured illumination microscopy (SSIM), all in one way or another addressing the problem of the limited spatial resolution of far-field optical microscopy. While SIM achieves a two-fold improvement in spatial resolution compared to conventional optical microscopy, STED, RESOLFT, PALM/STORM, or SSIM have all gone beyond, pushing the limits of optical image resolution to the nanometer scale. Consequently, all super-resolution techniques open new avenues of biomedical research. Because the field is so young, the potential capabilities of different super-resolution microscopy approaches have yet to be fully explored, and uncertainties remain when considering the best choice of methodology. Thus, even for experts, the road to the future is sometimes shrouded in mist. The super-resolution optical microscopy roadmap of Journal of Physics D: Applied Physics addresses this need for clarity. It provides guidance to the outstanding questions through a collection of short review articles from experts in the field, giving a thorough discussion on the concepts underlying super-resolution optical microscopy, the potential of different approaches, the importance of label optimization (such as reversible photoswitchable proteins) and applications in which these methods will have a significant impact.

physics.bio-ph↗

arXiv2014

A lipid bound actin meshwork organizes liquid phase separation in model membranes

The eukaryotic cell membrane is connected to a dense actin rich cortex. We present FCS and STED experiments showing that dense membrane bound actin networks have severe influence on lipid phase separation. A minimal actin cortex was bound to a supported lipid bilayer via biotinylated lipid streptavidin complexes (pinning sites). In general, actin binding to ternary membranes prevented macroscopic liquid-ordered and liquid-disordered domain formation, even at low temperature. Instead, depending on the type of pinning lipid, an actin correlated multi-domain pattern was observed. FCS measurements revealed hindered diffusion of lipids in the presence of an actin network. To explain our experimental findings, a new simulation model is proposed, in which the membrane composition, the membrane curvature, and the actin pinning sites are all coupled. Our results reveal a mechanism how cells may prevent macroscopic demixing of their membrane components, while at the same time regulate the local membrane composition.

cond-mat.soft↗