Small Methods

Journal: Small Methods

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Wiley-VCH

ISSN

2366-9608

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Publications 1 - 10 of 17

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.
Two-Layer Droplet Arrays Enable Dynamic Manipulation of Cell Microenvironment During High-Throughput Bacterial Cultivation
Xiong, Bijing; Breitfeld, Maximilian; Dittrich, Petra S. (2025)
Small Methods
Arrays of pico-to-microliter droplets, organized on a surface, enable chemical and biological workflows at high throughput. Here, a platform employing two-layer droplets is presented to enable flexible manipulation of the droplets’ microenvironment for dynamic biological cultivation. Arrays of 6784 agarose droplets (≈2.0 nL per droplet) encapsulating and immobilizing bacterial cells are generated. After that, aqueous droplets (≈3.7 nL) with a defined composition are deposited atop to form a thin liquid layer surrounding the agarose droplets. Chemical exchange between the two layers is extremely fast (equilibrium within 15 s for fluorescein). Moreover, the aqueous layer can be removed, opening the possibility to extract substances from the agarose droplets. Indeed, repeated addition and aspiration of a buffer successfully remove dyes or drugs previously added to the agarose droplets. Therefore, antibiotic drug testing can be performed under both static and transient exposure profiles. The latter reveals that bacterial responses such as bacterial killing and resuscitation are both heterogeneous at the single-cell level. Last, it is exemplified how such droplet manipulation strategy can also be use in long-term experimentation, where medium replenishment, performed at 12-h intervals during a 72-h experiment, enables the cultivation of a slow-growing microorganism in nanoliter droplets.
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.
Human Dermal Microvascular Arterial and Venous Blood Endothelial Cells and Their Use in Bioengineered Dermo-Epidermal Skin Substitutes
Rütsche, Dominic; Nanni, Monica; Cheng, Phil; et al. (2025)
Small Methods
The bioengineering of vascular networks is pivotal to create complex tissues and organs for regenerative medicine applications. However, bioengineered tissues comprising an arterial and venous plexus alongside a lymphatic capillary network have not been explored yet. Here, scRNA-seq is first employed to investigate the arterio-venous endothelial cell marker patterning in human fetal and juvenile skin. Transcriptomic analysis reveals that arterial and venous endothelial cell markers NRP1 (neuropilin 1) and NR2F2 (nuclear receptor subfamily 2 group F member 2) are broadly expressed in fetal and juvenile skin. In contrast, expression of NRP1 and NR2F2 on the protein level is cell-type specific and is retained in 2D (2-dimensional) cultures in vitro. Finally, distinct arterial and venous capillaries are bioengineered in 3D (3-dimensional) hydrogels and rapid anastomosis is demonstrated with the host vasculature in vivo. In summary, the bioengineering of human arterial, venous, and lymphatic capillaries is established, hence paving the way for these cells to be used in regenerative medicine and future clinical applications
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.
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.
Droplet-Based EPR Spectroscopy for Real-Time Monitoring of Liquid-Phase Catalytic Reactions
Moragues, Thomas; Agrachev, Mikhail; Mitchell, Sharon; et al. (2025)
Small Methods
In situ monitoring is essential for catalytic process design, offering real-time insights into active structures and reactive intermediates. Electron paramagnetic resonance (EPR) spectroscopy excels at probing geometric and electronic properties of paramagnetic species during reactions. Yet, state-of-the-art liquid-phase EPR methods, like flat cells, require custom resonators, consume large amounts of reagents, and are unsuited for tracking initial kinetics or use with solid catalysts. To overcome these limitations, a droplet-based microfluidics platform is introduced for real-time EPR monitoring of liquid-phase catalytic reactions. By encapsulating solid and dissolved species within nanoliter droplets, this approach enables precise control over mass transport, reduces reagent consumption, and maintains uniform residence times irrespective of acquisition duration, permitting precise analysis of each spectral component under identical conditions. The platform's compatibility with standard resonators facilitates straightforward integration into any EPR spectrometer. Its versatility is demonstrated by monitoring dynamic ligand exchange processes, key for activating homogeneous catalysts, and tracking redox and radical kinetics in ascorbic acid oxidation by Cu(II) catalysts. Importantly, this method captures both supported and dissolved transition metal species, offering comprehensive insights into catalyst deactivation via metal leaching. This microfluidic approach sets a new standard for liquid-phase in situ EPR measurements, advancing studies of homogeneous and heterogeneous catalytic systems.
Superferromagnetic Disk Particles for Magnetic Particle Imaging
Mayr, Erik M.; Ackers, Justin; Gogos, Alexander; et al. (2025)
Small Methods
Magnetic particle imaging (MPI) offers rapid, highly sensitive tracer-based imaging without ionizing radiation, but its clinical translation remains challenged by the limited performance of existing superparamagnetic (SP) tracers. In this work, precisely engineered disk-shaped nanoparticles fabricated from superferromagnetic (SF) discontinuous metal–insulator multilayers (DMIMs) consisting of SP nanoscale metal islands embedded in a nonmagnetic oxidic matrix are introduced. By leveraging inter-island exchange interactions, robust SF behavior is achieved in extended DMIMs, exhibiting exceptionally high susceptibilities and a sharp magnetization switching at fields below 1 mT. When evaluated in MPI experiments, magnetic disk particles (MDP) with a diameter of 1800 nm patterned from the SF DMIMs demonstrate up to a 1.6-fold improvement in spatial resolution and a 2.4-fold increase in sensitivity compared to Perimag tracers, the current gold standard in MPI. System matrix measurements and hybrid MPI reconstructions further highlight the superior imaging characteristics of MDP tracers in complex, clinically relevant geometries. These findings establish SF DMIM disks as a promising next-generation tracer platform for MPI, with the potential to simplify scanner designs and to pave the way for a clinical translation of MPI.
Charge Detection of Perovskite Nanowires Filled Single-Walled Carbon Nanotubes for CMOS ICs
Yin, Huimin; Zhang, Lingyu; Cao, Jiang; et al. (2025)
Small Methods
Inner doping of semiconducting single-walled carbon nanotubes (s-SWCNTs) with 1D CsPbBr3 nanowires enables powerful electronic modulation while preserving lattice integrity, crucial for nanoelectronics. However, characterizing these heterostructures-identifying CNT type, fill status, doping position, and charge effects at the individual level non-destructively remains challenging. Here, Kelvin Probe Force Microscopy (KPFM), Raman spectroscopy, and scanning electron microscopy (SEM) is employed, to positioning CsPbBr3@CNT heterostructures. Doping induced potential change across the CNT and the polarity of charge transfer can be directly resolved by this method at individual CNT level and a positioning precision of 89 nm, reveals a CNT diameter-dependent doping effect, with surface potential difference peaking at approximate to 130 mV for CNTs of 1.3-1.6 nm diameter, linked to confinement-induced CsPbBr3 phase transitions. This study further fabricates p/n-type field-effect transistors (FETs) on single CNTs with both doped and undoped regions, via a self-aligned top-gate process with low-work-function titanium (Ti) as the contact electrode. These devices demonstrate symmetric performance (on/off ratio > 10(3)) and enabling the realization of inverter with near-ideal voltage transition at half the supply voltage. The maintained device performance after 1 month storage confirms doping stability. These findings can advance the controlled synthesis and application of inner doped CNTs for high-performance nanoelectronics.
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.

Publications 1 - 10 of 17

Journal: Small Methods

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