Biology subjects

Herrmann, I. K.

Publications and source records attributed to Herrmann, I. K..

10 recordsLinked to original sources

bioRxiv2026

3D Reconstruction of Nanoparticle Distribution in Tumor Spheroids with Volume Electron Microscopy

AO_SCPLOWBSTRACTC_SCPLOWSpatially resolved characterization of nanomaterial (NM) distribution within cellular ultrastructure is essential for understanding NM fate and activity in biological systems. Volume electron microscopy (vEM) is uniquely positioned to address this challenge, yet fully documented quantitative pipelines that simultaneously segment NMs and cellular structures remain scarce. Here, an end-to-end analytical pipeline is presented based on the example of serial block-face scanning electron microscopy (SBF-SEM) data of tumor spheroids containing nanoparticles (NPs). A hybrid segmentation strategy is adopted: a fine-tuned Cellpose-SAM model for cells and nuclei, and an empirical Bayes approach for AuNPs. The fine-tuned model outperforms both the pre-trained baseline and benchmark experiments in Amira, and shows good generalization to 2D EM datasets of varying sample types, suggesting potential as a general-purpose segmentation model for electron microscopy. Full 3D reconstruction of NP distributions reveals preferential clustering in the perinuclear region, with a median nucleus-to-NP distance of 2.57 {micro}m and NM uptake spanning several orders of magnitude across cells. Furthermore, morphological analysis of segmented cells and nuclei using 3D shape descriptors and local curvature metrics provides quantitative access to features inaccessible from single sections. Together, these results establish a reproducible, open framework for the joint quantitative analysis of NM distribution and cellular morphology in vEM data.

bioinformatics↗

bioRxiv2025

Nanoparticle Metal Mass Uptake Governs Radiosensitizing Efficacy Across 2D, 3D, and In Vivo Models

Despite extensive efforts to develop nanoparticle-based radioenhancers, clinical translation remains limited, partly due to the lack of physiologically relevant in vitro models. To address this gap, we developed a 3D spheroid model of head and neck cancer using FaDu cells and compared it directly to a corresponding in vivo model in a radiotherapy setting. The spheroids exhibited key tumor-like features, including the formation of a hypoxic core and growth kinetics comparable to in vivo tumors. Importantly, the model allowed for long-term monitoring of tumor growth and radiation response. Upon X-ray irradiation, dose-response behavior in spheroids mirrored that observed in vivo. Furthermore, TiO2, HfO2, and Au nanoparticles demonstrated consistent radiosensitization effects in both systems when matched for uptake mass. In contrast, conventional 2D clonogenic assays failed to predict in vivo performance, likely due to their lower radioresistance and unrealistic nanoparticle exposure conditions. This study introduces a robust, scalable, and clinically compatible 3D in vitro platform for preclinical screening of nanoparticle radioenhancers. The system may offer streamlining of development pipelines and support the 3R principles of reduction, replacement, and refinement in radiation oncology research.

cancer biology↗

bioRxiv2024

An Augmented Reality Visor for Intraoperative Visualization, Guidance and Temperature Monitoring using Fluorescence

Fluorescence-guided surgical techniques, including tumor resection and tissue soldering, are advancing the frontiers of surgical precision by offering enhanced control that minimizes tissue damage and improves recovery as well as outcomes. However, integrating the visualization of the fluorescent signal and temperature monitoring seamlessly into surgical workflows has not been fully realized and remains a challenge, thus limiting their effectiveness and wide-spread clinical adoption. To address this issue, we introduce an augmented reality (AR) visor designed to unite nanomaterial excitation along with fluorescence detection, and temperature monitoring during surgical procedures. The AR visor was evaluated using advanced fluorescent nanoparticles, such as indocyanine green-doped particles and singlewalled carbon nanotubes. By consolidating fluorescence visualization, excitation monitoring, and precise temperature control into a single AR platform, we equip surgeons with a comprehensive view of both the surgical field and sub-surface conditions invisible to the naked eye. This integration notably improves the safety and efficacy of fluorescence-guided surgeries, as well as emerging technologies including laser tissue soldering, by ensuring the soldering temperature stays within therapeutic thresholds and the laser is accurately guided by real-time fluorescence signals. The presented technology not only enhances existing surgical techniques but also supports the development of new strategies and sensing technologies in areas where traditional methods fall short, marking significant progress in precision surgery, which could ultimately improve patient care.

bioengineering↗

bioRxiv2024

Cathodoluminescent and Characteristic X-ray-emissive Rare-Earth-doped Core/Shell Immunolabels for Spectromicroscopic Analysis of Cell Surface Receptors

Understanding the localization and the interactions of biomolecules at the nanoscale and in the cellular context remains challenging. Electron microscopy (EM) as a non-Abbe limited technique gives access to the cellular ultra-structure yet results in grey-scale images and averts unambiguous (co-)localization of biomolecules. Multimodal nanoparticle-based immunolabels for correlative cathodoluminescence electron microscopy (CCLEM) and energy-dispersive X-ray spectromicroscopy (EDX-SM) are presented. The single-particle STEM-cathodoluminescence (CL) and characteristic X-ray emissivity of sub-20 nm lanthanide-doped nanoparticles were exploited as unique spectral fingerprints for precise localization and label identification. To maximize the nanoparticle brightness, lanthanides were incorporated in a low-phonon host lattice and separated from the environment using a passivating shell. The core/shell nanoparticles were then functionalized with either folic (terbium-doped) or caffeic acid (europium-doped). Their potential for immunolabeling was successfully demonstrated using HeLa cells expressing different surface receptors that bind to folic or caffeic acid, respectively. Both particle populations showed single-particle CL emission along with a distinctive energy-dispersive X-ray signal, with the latter enabling colour-based localization of receptors within swift imaging times well below 2 mins per {micro}m2 while offering high resolution with a pixel size of 2.78 nm. Taken together, these results open a route to color immunolabelling based on electron spectromicroscopy. Table of Contents O_FIG O_LINKSMALLFIG WIDTH=184 HEIGHT=200 SRC="FIGDIR/small/585848v1_ufig1.gif" ALT="Figure 1"> View larger version (74K): org.highwire.dtl.DTLVardef@1f7c2d3org.highwire.dtl.DTLVardef@117be1eorg.highwire.dtl.DTLVardef@1c2bab2org.highwire.dtl.DTLVardef@16f3677_HPS_FORMAT_FIGEXP M_FIG Small (sub-20 nm) lanthanide-doped nanoparticles were successfully utilized in electron microscopy to label biological structures and contextualize them in the cells ultrastructure. Leveraging unique energy-dispersive X-ray signatures, the nanoparticles location and doping-identity was easily and fast retrieved, demonstrating the methods potential to (co)-localize labels while supplying a holistic impression of the underlying processes, as entire cells could be mapped. C_FIG

bioengineering↗

bioRxiv2024

Robotic Laser Tissue Soldering for Damage-free Soft Tissue Fusion Guided by Fluorescent Nanothermometry

Minimally invasive surgical techniques, including endoscopic and robotic procedures, continue to revolutionize patient care, for their ability to minimize surgical trauma, thus promoting faster recovery and reduced hospital stays. Yet, the suturing of soft tissues ensuring damage-free tissue bonding during these procedures remains challenging due to missing haptics and the fulcrum effect. Laser tissue soldering has potential in overcoming these issues, offering damage-free seamless tissue fusion. To ensure the precision and safety of laser tissue soldering, we introduce feedback controlled fluorescent nanothermometry-guided laser tissue soldering using nanoparticle-protein solders within endoscopic and robotic contexts. Temperature-sensitive fluorescent nanoparticles embedded in the solder provide surgeons with immediate feedback on tissue temperatures during laser application, all while within the confines of minimally invasive (robotic) surgical setups. By integrating fluorescent nanothermometry-guided laser tissue surgery into endoscopic and robotic surgery, we pave the way for a new approach for safe and atraumatic soft tissue joining, especially in regions where traditional suturing is unfeasible.

bioengineering↗

bioRxiv2023

Nanothermometry-enabled intelligent laser tissue soldering

While often life-saving, surgical resectioning of diseased tissues puts patients at risk for post-operative complications. Sutures and staples are well-accepted and routinely used to reconnect tissues, however, their mechanical mismatch with biological soft tissue and invasiveness contribute to wound healing complications, infections, and post-operative fluid leakage. In principle, laser tissue soldering offers an attractive, minimally-invasive alternative for seamless soft tissue fusion. However, despite encouraging experimental observations, including accelerated healing and lowered infection risk, critical issues related to temperature monitoring and control during soldering and associated complications have prevented their clinical exploitation to date. Here, we introduce intelligent laser tissue soldering (iSoldering) with integrated nanothermometry as a promising yet unexplored approach to overcoming the critical shortcomings of laser tissue soldering. We demonstrate that adding thermoplasmonic and nanothermometry nanoparticles to proteinaceous solders enables heat confinement and non-invasive temperature monitoring and control, offering a route to high-performance, leak-tight tissue sealing even at deep tissue sites. The resulting tissue seals exhibit excellent mechanical properties and resistance to chemically-aggressive digestive fluids, including gastrointestinal juice. The iSolder can be readily cut and shaped by surgeons to optimally fit the tissue defect and can even be applied using infrared light from a medically approved light source, hence fulfilling key prerequisites for application in the operating theatre. Overall, iSoldering enables reproducible and well-controlled high-performance tissue sealing, offering new prospects for its clinical exploitation in diverse fields ranging from cardiovascular to visceral and plastic surgery. TeaserIntelligent solders containing nanothermometers and thermoplasmonics offer new route to high-performance tissue sealing.

bioengineering↗

bioRxiv2023

Multiscale Multimodal Characterization and Simulation of Structural Alterations in Failed Bioprosthetic Heart Valves

Calcific degeneration is the most frequent type of heart valve failure, with rising incidence due to the ageing population. The gold standard treatment to date is valve replacement. Unfortunately, calcification oftentimes re-occurs in bioprosthetic substitutes, with the governing processes remaining poorly understood. Here, we present a multiscale, multimodal analysis of disturbances and extensive mineralisation of the collagen network in failed bioprosthetic bovine pericardium valve explants with full histoanatomical context. In addition to highly abundant mineralized collagen fibres and fibrils, calcified micron-sized particles previously discovered in native valves were also prevalent on the aortic as well as the ventricular surface of bioprosthetic valves. The two mineral types (fibers and particles) were detectable even in early-stage mineralisation, prior to any macroscopic calcification. Based on multiscale multimodal characterisation and high-fidelity simulations, we demonstrate that mineral occurrence coincides with regions exposed to high haemodynamic and biomechanical indicators. These insights obtained by multiscale analysis of failed bioprosthetic valves may serve as groundwork for the evidence-based development of more durable alternatives. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=176 SRC="FIGDIR/small/529530v1_ufig1.gif" ALT="Figure 1"> View larger version (57K): org.highwire.dtl.DTLVardef@c7e0b5org.highwire.dtl.DTLVardef@71bdbdorg.highwire.dtl.DTLVardef@15fdc23org.highwire.dtl.DTLVardef@6dbd1c_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2022

Smart sealants for prevention and monitoring of gastrointestinal anastomotic leaks using portable smartphone-controlled ultrasound transducers

Millions of patients every year undergo gastrointestinal surgery. While often lifesaving, sutured and stapled reconnections leak in around 10% of the cases. Penetration of digestive fluids into the peritoneal cavity may lead to dreadful complications, including sepsis and premature death. Modern suture supports and tissue adhesives only insufficiently address the issue. Due to the scarcity of alternatives, surgeons rely on monitoring surrogate markers and clinical symptoms, which oftentimes lack sensitivity and specificity, hence only offering late-stage detection of already fully developed leaks. Here, a first-of-its-kind, modular, intelligent suture support patch capable of sealing and monitoring leaks under harsh gastrointestinal conditions is presented. The smart adhesive layered hydrogel patch provides, in addition to unprecedented tissue sealing under most demanding conditions, unique leak-detection capabilities based on pH and/or enzyme-responsive sensing elements, which can be read out by non-invasive point-of-need ultrasound imaging. Reliable detection of the breaching of sutures in as little as 3 hours in intestinal leak and 15 minutes in gastric leak conditions, and before an actual leak develops, is demonstrated. This technology paves the way for next-generation suture support materials that offer disambiguation in cases of anastomotic leaks based on point-of-need monitoring, without reliance on complex electronics or bulky (bio)electronic implantables. SummaryElectronic-free smart surgical hydrogel sealants leveraging tissue-penetrating polymer networks and trigger-responsive echogenic entities to enable point-of-need monitoring and early anastomotic leak detection using a hand-held ultrasound transducer and a smartphone.

bioengineering↗

bioRxiv2020

Invasive breast tumors are characterized by the presence of crystalline nanoparticles

The presence of calcifications on mammograms is a widely used diagnostic marker for breast cancer. While the clinicopathological analysis of breast tissue is well-developed, an in-depth characterisation of the properties of calcifications at the micro and nano scale remained elusive. In this work, we use nano-analytical methods to investigate the calcification present in healthy breast tissue, as well as in benign and malignant breast tumour tissue biopsies. While polycrystalline apatite with lower crystallinity can be found in all breast tissue samples, we show that magnesium-containing nano and micro spherical particles are found only in malignant invasive breast cancers. These particles concentration increases with cancer progression. The discovery of these spherical particles provides new insights into the characteristics of breast calcification associated with malignant tumours and opens new research pathways to a better understanding of breast tumours and their microenvironment in general.

cancer biology↗

bioRxiv2019

Electron microscopy characterization of minerals formed in vitro by human bone cells and vascular smooth muscle cells

Soft tissue mineralization has been found to be a major component of diseases such as aortic valve stenosis and rheumatic heart disease. Cardiovascular mineralization has been suggested to follow mechanisms similar to those of bone formation with several cell culture models been developed over the years to provide mechanistic insights. These cell models have been characterized by a wide range of biochemical and molecular methods, which identified the presence of osteogenic markers and bone-like cells. However, there is a surprisingly small number of studies where the mineral formed in these cell culture models has been characterized by physico-chemical methods, and even fewer studies have compared this mineral to the one produced by bone cells in cultures. Here we investigated the morphology and composition of the minerals formed in cell cultures of vascular smooth muscle cells and bone cells. Electron microscopy and traditional cell mineralization assays were applied, revealing that vascular cells are indeed able to form calcified nodules of elemental composition similar to bone, however with different morphology. Comparison of morphologies of the two minerals to that found in cardiovascular tissue shows that some of tissue calcification resembles the calcified fibers produced by bone cells in vitro. These results suggest that the characterization of the mineral is of utmost importance and its morphology and chemical properties can contribute an important piece of information in the comprehensive analysis of soft tissue mineralization mechanisms, both in in vitro cell culture as well as in clinical samples.

pathology↗