Small Methods

Journal: Small Methods

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Wiley-VCH

ISSN

2366-9608

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Publications 1 - 10 of 15

Scalable Copper Sulfide Formulations for Super-Resolution Optoacoustic Brain Imaging in the Second Near-Infrared Window
Tang, Lin; Nozdriukhin, Daniil; Kumar Kalva, Sandeep; et al. (2025)
Small Methods
Optoacoustic imaging offers label-free multi-parametric characterization of cerebrovascular morphology and hemodynamics at depths and spatiotemporal resolution unattainable with optical microscopy. Effective imaging depth can greatly be enhanced by employing photons in the second near-infrared (NIR-II) window. However, diminished absorption by hemoglobin along with a lack of suitable contrast agents hinder an efficient application of the technique in this spectral range. Herein, copper sulfide (CuS) micro- and nano-formulations for multi-scale optoacoustic imaging in the NIR-II window are introduced. Dynamic contrast enhancement induced by intravenously administered CuS nanoparticles facilitated visualization of blood perfusion in murine cerebrovascular networks. The individual calcium carbonate microparticles carrying CuS are further shown to generate sufficient responses to enable super-resolution microvascular imaging and blood flow velocity mapping with localization optoacoustic tomography.
Direct In- and Out-of-Plane Writing of Metals on Insulators by Electron-Beam-Enabled, Confined Electrodeposition with Submicrometer Feature Size
Nydegger, Mirco; Wang, Zhu-Jun; Willinger, Marc Georg; et al. (2024)
Small Methods
Additive microfabrication processes based on localized electroplating enable the one-step deposition of micro-scale metal structures with outstanding performance, e.g., high electrical conductivity and mechanical strength. They are therefore evaluated as an exciting and enabling addition to the existing repertoire of microfabrication technologies. Yet, electrochemical processes are generally restricted to conductive or semiconductive substrates, precluding their application in the manufacturing of functional electric devices where direct deposition onto insulators is often required. Here, the direct, localized electrodeposition of copper on a variety of insulating substrates, namely Al2O3, glass and flexible polyethylene, is demonstrated, enabled by electron-beam-induced reduction in a highly confined liquid electrolyte reservoir. The nanometer-size of the electrolyte reservoir, fed by electrohydrodynamic ejection, enables a minimal feature size on the order of 200 nm. The fact that the transient reservoir is established and stabilized by electrohydrodynamic ejection rather than specialized liquid cells can offer greater flexibility toward deposition on arbitrary substrate geometries and materials. Installed in a low-vacuum scanning electron microscope, the setup further allows for operando, nanoscale observation and analysis of the manufacturing process.
Photoswitchable Gold Nanoparticles for Super‐Resolution Radial Fluctuation Imaging in Nanostructured Materials
Probst, Julie; Mathur, Prerit; Gai, Meiyu; et al. (2025)
Small Methods
Camera-based super-resolution approaches surpass the diffraction limit of conventional optical microscopy by relying on the stochastic activation and precise localization of fluorescent molecules. However, traditional probes such as organic dyes and quantum dots present challenges such as photobleaching and blinking variability, which limit their application in super-resolution imaging, particularly in non-liquid environments. Herein, the study demonstrates the potential of gold nanoparticles as a promising alternative for localization-based super-resolution imaging. The study specifically investigates how different surface functionalizations and states (aggregated vs isolated) of gold nanoparticles impact their photoluminescence properties, including fluorescence intensity, lifetime, and blinking behavior. By leveraging the intrinsic photoluminescence of gold nanoparticles, their capability is demonstrated as probes to achieve super-resolution imaging of nano-sized structures, at a resolution down to 100 nm, without the need for conventional imaging buffers. These proof-of-concept applications, which include imaging of silica nanosized wrinkles and logos, reveal that gold nanoparticles exhibit superior photophysical properties compared to common organic fluorophores, offering a promising alternative for super-resolution imaging. This work paves the way for the application of super-resolution fluorescence microscopy in materials science where non-liquid environments often restrict the use of traditional probes.
Multiscale Multimodal Investigation of the Intratissural Biodistribution of Iron Nanotherapeutics with Single Cell Resolution Reveals Co-Localization with Endogenous Iron in Splenic Macrophages
Balfourier, Alice; Tsolaki, Elena; Heeb, Laura; et al. (2023)
Small Methods
Imaging of iron-based nanoparticles (NPs) remains challenging because of the presence of endogenous iron in tissues that is difficult to distinguish from exogenous iron originating from the NPs. Here, an analytical cascade for characterizing the biodistribution of biomedically relevant iron-based NPs from the organ scale to the cellular and subcellular scales is introduced. The biodistribution on an organ level is assessed by elemental analysis and quantification of magnetic iron by electron paramagnetic resonance, which allowed differentiation of exogenous and endogenous iron. Complementary to these bulk analysis techniques, correlative whole-slide optical and electron microscopy provided spatially resolved insight into the biodistribution of endo- and exogenous iron accumulation in macrophages, with single-cell and single-particle resolution, revealing coaccumulation of iron NPs with endogenous iron in splenic macrophages. Subsequent transmission electron microscopy revealed two types of morphologically distinct iron-containing structures (exogenous nanoparticles and endogenous ferritin) within membrane-bound vesicles in the cytoplasm, hinting at an attempt of splenic macrophages to extract and recycle iron from exogenous nanoparticles. Overall, this strategy enables the distinction of endo- and exogenous iron across scales (from cm to nm, based on the analysis of thousands of cells) and illustrates distribution on organ, cell, and organelle levels.
Biomimetic Approach of Brain Vasculature Rapidly Characterizes Inter- and Intra-Patient Migratory Diversity of Glioblastoma
Crestani, Michele; Kakogiannos, Nikolaos; Iori, Simone; et al. (2024)
Small Methods
Glioblastomas exhibit remarkable heterogeneity at various levels, including motility modes and mechanoproperties that contribute to tumor resistance and recurrence. In a recent study using gridded micropatterns mimicking the brain vasculature, glioblastoma cell motility modes, mechanical properties, formin content, and substrate chemistry are linked. Now is presented, SP2G (SPheroid SPreading on Grids), an analytic platform designed to identify the migratory modes of patient-derived glioblastoma cells and rapidly pinpoint the most invasive sub-populations. Tumorspheres are imaged as they spread on gridded micropatterns and analyzed by this semi-automated, open-source, Fiji macro suite that characterizes migration modes accurately. SP2G can reveal intra-patient motility heterogeneity with molecular correlations to specific integrins and EMT markers. This system presents a versatile and potentially pan-cancer workflow to detect diverse invasive tumor sub-populations in patient-derived specimens and offers a valuable tool for therapeutic evaluations at the individual patient level.
Nanothermometry-Enabled Intelligent Laser Tissue Soldering
Cipolato, Oscar; Dosnon, Lucas; Rosendorf, Jachym; et al. (2023)
Small Methods
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, intelligent laser tissue soldering (iSoldering) with integrated nanothermometry is introduced as a promising yet unexplored approach to overcome the critical shortcomings of laser tissue soldering. It demonstrates 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.
Fast Small-Angle X-Ray Scattering Tensor Tomography: An Outlook into Future Applications in Life Sciences
Appel, Christian; Schmeltz, Margaux; Rodriguez-Fernandez, Irene; et al. (2025)
Small Methods
Small Angle-X-ray Scattering Tensor Tomography (SAS-TT) is a relatively new but powerful technique for studying the multiscale architecture of hierarchical structures particularly relevant to life science applications. Currently, the technique is very demanding on synchrotron beamtime, which limits its applications, especially for cases requiring a statistically relevant number of samples. This study reports the first SAS-TT measurement at a macromolecular X-ray crystallography beamline, PX-I at the Swiss Light Source (SLS), with an improvement in acquisition time from 96 h/Mvoxel in the pilot experiments to 6 h/Mvoxel with comparable sampling, defining a new standard for fast SAS-TT with a micrometer beam size and allowing to record a full tomogram in 1.2 h. Measurements are performed on the long and lenticular process of the incus bone, one of the three human auditory ossicles. The main orientation and degree of alignment of the mineralised collagen fibrils are characterised, as well as the size and shape of the mineral particles which show relevant variations in different tissue locations. The study reveals three distinct regions of high fibril alignment, most likely important pathways of sound throughout the ossicular chain, and highlights the technique's potential to aid in future developments in middle ear reconstructive surgery.
Combinatorial Investigation of the Ni-Ta System via Correlated High-Speed Nanoindentation and EDX Mapping
Wheeler, Jeffrey Martin; Gan, Bin; Spolenak, Ralph (2022)
Small Methods
Correlated high-speed nanoindentation and energy-dispersive spectroscopy are applied in a combinatorial investigation of the Ni-Ta system. All seven phases in the system are clearly resolved in the resulting maps, and the mechanical properties and composition ranges for each phase are determined. Good agreement with ab initio calculations is generally observed with some exceptions, most notably NiTa2. This is achieved using a simple correlation method utilizing directly overlaid data matrices to allow compositional labeling of mechanical data. This allows easy data segmentation without requiring complicated statistical deconvolution methods. Without this correlative method, phase deconvolution of the Ni-Ta system would be challenging due to several phases possessing adjacent compositions and mechanical properties. This demonstrates the potential of this new correlative approach for future investigations, particularly those involving complex microstructures and/or compositional variation.
Online 3D Characterization of Micrometer-Sized Cuboidal Particles in Suspension
Binel, Pietro; Jain, Ankit; Jaeggi, Anna; et al. (2023)
Small Methods
Characterization of particle size and shape is central to the study of particulate matter in its broadest sense. Whilst 1D characterization defines the state of the art, the development of 2D and 3D characterization methods has attracted increasing attention, due to a common need to measure particle shape alongside size. Herein, ensembles of micrometer-sized cuboidal particles are studied, for which reliable sizing techniques are currently missing. Such particles must be characterized using three orthogonal dimensions to completely describe their size and shape. To this end, the utility of an online and in-flow multiprojection imaging tool coupled with machine learning is experimentally assessed. Central to this activity, a methodology is outlined to produce micrometer-sized, non-spherical analytical standards. Such analytical standards are fabricated using photolithography, and consist of monodisperse micro-cuboidal particles of user-defined size and shape. The aforementioned activities are addressed through an experimental framework that fabricates analytical standards and subsequently uses them to validate the performance of our multiprojection imaging tool. Significantly, it is shown that the same set of data collected for particle sizing can also be used to estimate particle orientation in flow, thus defining a rapid and robust protocol to investigate the behavior of dilute particle-laden flows.
Shedding new light on nanostructured catalysts with positron annihilation spectroscopy
Mitchell, Sharon; Gerchow, Lars; Warringham, Robbie; et al. (2018)
Small Methods

Publications 1 - 10 of 15

Journal: Small Methods

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