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Lab-on-a-chip (LOC) applications have emerged as invaluable physical and life sciences tools. The advantages stem from advanced system miniaturization, thus, requiring far less sample volume while allowing for complex functionality, increased reproducibility, and high throughput. However, LOC applications necessitate extensive sensor miniaturization to leverage these inherent advantages fully. Atom-sized quantum sensors are highly promising to bridge this gap and have enabled measurements of temperature, electric and magnetic fields on the nano- to microscale. Nevertheless, the technical complexity of both disciplines has so far impeded an uncompromising combination of LOC systems and quantum sensors. Here, we present a fully integrated microfluidic platform for solid-state spin quantum sensors, like the nitrogen-vacancy (NV) center in diamond. Our platform fulfills all technical requirements, such as fast spin manipulation, enabling full quantum sensing capabilities, biocompatibility, and easy adaptability to arbitrary channel and chip geometries. To illustrate the vast potential of quantum sensors in LOC systems, we demonstrate various NV center-based sensing modalities for chemical analysis in our microfluidic platform, ranging from paramagnetic ion detection to high-resolution microscale NV-NMR. Consequently, our work opens the door for novel chemical analysis capabilities within LOC devices with applications in electrochemistry, high-throughput reaction screening, bioanalytics, organ-on-a-chip, or single-cell studies.

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The characterization of nanoparticles and the correlation of physical properties such as size and shape to their (electro)chemical properties is an emerging field, which may facilitate future optimization and tuning of devices involving nanoparticles. This requires the investigation of individual particles rather than obtaining averaged information on large ensembles. Here, we present atomic force - scanning electrochemical microscopy (AFM-SECM) measurements of soft conductive PDMS substrates modified with gold nanostars (i.e., multibranched Au nanoparticles) in peak force tapping mode, which next to the electrochemical characterization provides information on the adhesion, deformation properties, and Young's modulus of the sample. AFM-SECM probes with integrated nanodisc electrodes (radii < 50 nm) have been used for these measurements. Most studies attempting to map individual nanoparticles have to date been performed at spherical nanoparticles, rather than highly active asymmetric gold nanoparticles. Consequently, this study discusses challenges during the nanocharacterization of individual anisotropic gold nanostars.

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Conductive colloidal probe Atomic Force-Scanning Electrochemical Microscopy (AFM-SECM) is a new approach, which employs electrically insulated AFM probes except for a gold-coated colloid located at the end of the cantilever. Hence, force measurements can be performed while biasing the conductive colloid under physiological conditions. Moreover, such colloids can be modified by electrochemical polymerization resulting, e.g. in conductive polymer-coated spheres, which in addition may be loaded with specific dopants. In contrast to other AFM-based single cell force spectroscopy measurements, these probes allow adhesion measurements at the cell-biomaterial interface on multiple cells in a rapid manner while the properties of the polymer can be changed by applying a bias. In addition, spatially resolved electrochemical information e.g., oxygen reduction can be obtained simultaneously. Conductive colloid AFM-SECM probes modified with poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate ( PEDOT: PSS) are used for single cell force measurements in mouse fibroblasts and single cell interactions are investigated as a function of the applied potential.

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Conductive polymers, and in particular polypyrrole, are frequently used as biomimetic interfaces facilitating growth and/or differentiation of cells and tissues. Hence, studying forces and local interactions between such polymer interfaces and cells at the nanoscale is of particular interest. Frequently, such force interactions are not directly accessible with high spatial resolution. Consequently, we have developed nanoscopic polypyrrole electrodes, which are integrated in AFM-SECM probes. Bifunctional AFM-SECM probes were modified via ion beam-induced deposition resulting in pyramidal conductive Pt-C composite electrodes. These nanoscopic electrodes then enabled localized polypyrrole deposition, thus resulting in polymer-modified AFM probes with a well-defined geometry. Furthermore, such probes may be reversibly switched from an insulating to a conductive state. In addition, the hydrophilicity of such polymer tips is dependent on the dopant, and hence, on the oxidation state. Force studies applying different tip potentials were performed at plasma-treated glass surfaces providing localized information on the associated force interactions, which are dependent on the applied potential and the dopant.

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Mechanical forces affect biological systems in their natural environment in a widespread manner. Mechanical stress may either stimulate cells or even induce pathological processes. Cells sensing mechanical stress usually respond to such stressors with proliferation or differentiation. Hence, for in vitro studies, the ability to impose a controlled mechanical stress on cells combined with appropriate analytical tools providing an immediate answer is essential to understand such fundamental processes. Here, we present a novel uniaxial motorized cell stretching device that has been integrated into a combined fluorescence microscope (FM)-atomic force microscope (AFM) system, thereby enabling high-resolution topographic and fluorescent live cell imaging. This unique tool allows the investigation of mechanotransduction processes, as the cells may be exposed to deliberately controlled mechanical stress while simultaneously facilitating fluorescence imaging and AFM studies. The developed stretching device allows applying reproducible uniaxial strain from physiologically relevant to hyperphysiological levels to cultured cells grown on elastic polydimethylsiloxane (PDMS) membranes. Exemplarily, stretching experiments are shown for transfected squamous cell carcinoma cells (SCC-25) expressing fluorescent labeled cytokeratin, whereby fluorescence imaging and simultaneously performed AFM measurements reveal the cytokeratin (CSK) network. Topographical changes and mechanical characteristics such as elasticity changes were determined via AFM while the cells were exposed to mechanical stress. By applying a cell deformation of approx. 20%, changes in the Young's modulus of the cytoskeletal network due to stretching of the cells were observed. Consequently, integrating a stretching device into the combined atomic force-fluorescence microscope provides a unique tool for dynamically analyzing structural remodeling and mechanical properties in mechanically stressed cells.

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The purpose of this prospective study was to determine the accuracy of ultrasonography in detecting radiolucent foreign bodies and to compare the performance of three newly trained emergency physicians with two experienced ultrasound technologists and one radiologist. One hundred-four chicken thighs were penetrated with a needle-driver, half of them embedded with a 1.5 cm toothpick. An 8.0 MHZ linear array ultrasound probe was used to detect the presence or absence of the foreign body. The overall accuracy (95% confidence interval [CI]) was 82% (79, 85); sensitivity 79% (74, 83), specificity 86% (82, 90), positive predicative value (PPV) 85% (81, 89), and negative predicative value (NPV) 80% (76, 84). The accuracy (95% CI) of the radiologist was 83% (75, 90); of the ultrasound technologists was 85% (80, 90); and of the emergency physicians was 0% (76, 85). The difference in accuracy among the three types of personnel was not statistically significant. Ultrasonography is an accurate modality in detecting radiolucent foreign bodies. Emergency physicians can be trained to provide a degree of accuracy comparable with more experienced ultrasonographers.

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