Thermomechanical Nanostraining of Two-Dimensional Materials.

Local bandgap tuning in two-dimensional (2D) materials is of significant importance for electronic and optoelectronic devices but achieving controllable and reproducible strain engineering at the nanoscale remains a challenge. Here, we report on thermomechanical nanoindentation with a scanning probe to create strain nanopatterns in 2D transition metal dichalcogenides and graphene, enabling arbitrary patterns with a modulated bandgap at a spatial resolution down to 20 nm. The 2D material is in contact via van der Waals interactions with a thin polymer layer underneath that deforms due to the heat and indentation force from the heated probe. Specifically, we demonstrate that the local bandgap of molybdenum disulfide (MoS2) is spatially modulated up to 10% and is tunable up to 180 meV in magnitude at a linear rate of about -70 meV per percent of strain. The technique provides a versatile tool for investigating the localized strain engineering of 2D materials with nanometer-scale resolution.

Growth of Large-Area 2D MoS2 Arrays at Pre-Defined Locations Using Stencil Mask Lithography.

The growth of MoS2 layers of desired dimensions at predefined locations is essential for fabricating opto-electronic devices based solely on MoS2 or on hetero-structures based on MoS2. Here we present a new route for patterned growth of MoS2 by combining radio frequency (RF) magnetron sputtering, stencil mask lithography and vapour phase sulfurization. The present method does not involve chemical etchants and organic photoresist and hence provides a simplified process of achieving MoS2 patterns. Here, the control over the number of layers (mono, few and bulk) of MoS2 is achieved by varying the thickness of Mo films. The statistical variation in thickness i.e., number of MoS2 layers within the individual patterns is investigated from Raman mappings which revealed the uniform growth of 3-4 MoS2 layers. From Kelvin probe force microscopy, the surface potential values of MoS2 patterns lie in the range -350 to -370 mV, which is consistent with 2D MoS2 layer with thickness of 3-4 layers. The surface potential analysis across individual patterns indicates weakly n-type doping of few layers MoS2 with Fermi level located ~0.83-0.85 eV below the conduction band edge.

Planar Optical Nanoantennas Resolve Cholesterol-Dependent Nanoscale Heterogeneities in the Plasma Membrane of Living Cells.

Optical nanoantennas can efficiently confine light into nanoscopic hotspots, enabling single-molecule detection sensitivity at biological relevant conditions. This innovative approach to breach the diffraction limit offers a versatile platform to investigate the dynamics of individual biomolecules in living cell membranes and their partitioning into cholesterol-dependent lipid nanodomains. Here, we present optical nanoantenna arrays with accessible surface hotspots to study the characteristic diffusion dynamics of phosphoethanolamine (PE) and sphingomyelin (SM) in the plasma membrane of living cells at the nanoscale. Fluorescence burst analysis and fluorescence correlation spectroscopy performed on nanoantennas of different gap sizes show that, unlike PE, SM is transiently trapped in cholesterol-enriched nanodomains of 10 nm diameter with short characteristic times around 100 µs. The removal of cholesterol led to the free diffusion of SM, consistent with the dispersion of nanodomains. Our results are consistent with the existence of highly transient and fluctuating nanoscale assemblies enriched by cholesterol and sphingolipids in living cell membranes, also known as lipid rafts. Quantitative data on sphingolipids partitioning into lipid rafts is crucial to understand the spatiotemporal heterogeneous organization of transient molecular complexes on the membrane of living cells at the nanoscale. The proposed technique is fully biocompatible and thus provides various opportunities for biophysics and live cell research to reveal details that remain hidden in confocal diffraction-limited measurements.

In-Plane Plasmonic Antenna Arrays with Surface Nanogaps for Giant Fluorescence Enhancement.

Optical nanoantennas have a great potential for enhancing light-matter interactions at the nanometer scale, yet fabrication accuracy and lack of scalability currently limit ultimate antenna performance and applications. In most designs, the region of maximum field localization and enhancement (i.e., hotspot) is not readily accessible to the sample because it is buried into the nanostructure. Moreover, current large-scale fabrication techniques lack reproducible geometrical control below 20 nm. Here, we describe a new nanofabrication technique that applies planarization, etch back, and template stripping to expose the excitation hotspot at the surface, providing a major improvement over conventional electron beam lithography methods. We present large flat surface arrays of in-plane nanoantennas, featuring gaps as small as 10 nm with sharp edges, excellent reproducibility and full surface accessibility of the hotspot confined region. The novel fabrication approach drastically improves the optical performance of plasmonic nanoantennas to yield giant fluorescence enhancement factors up to 104-105 times, together with nanoscale detection volumes in the 20 zL range. The method is fully scalable and adaptable to a wide range of antenna designs. We foresee broad applications by the use of these in-plane antenna geometries ranging from large-scale ultrasensitive sensor chips to microfluidics and live cell membrane investigations.

Large-Scale Arrays of Bowtie Nanoaperture Antennas for Nanoscale Dynamics in Living Cell Membranes.

We present a novel blurring-free stencil lithography patterning technique for high-throughput fabrication of large-scale arrays of nanoaperture optical antennas. The approach relies on dry etching through nanostencils to achieve reproducible and uniform control of nanoantenna geometries at the nanoscale, over millimeter-sizes in a thin aluminum film. We demonstrate the fabrication of over 400 000 bowtie nanoaperture (BNA) antennas on biocompatible substrates, having gap sizes ranging from (80 ± 5) nm down to (20 ± 10) nm. To validate their applicability on live cell research, we used the antenna substrates as hotspots of localized illumination to excite fluorescently labeled lipids on living cell membranes. The high signal-to-background afforded by the BNA arrays allowed the recording of single fluorescent bursts corresponding to the passage of freely diffusing individual lipids through hotspot excitation regions as small as 20 nm. Statistical analysis of burst length and intensity together with simulations demonstrate that the measured signals arise from the ultraconfined excitation region of the antennas. Because these inexpensive antenna arrays are fully biocompatible and amenable to their integration in most fluorescence microscopes, we foresee a large number of applications including the investigation of the plasma membrane of living cells with nanoscale resolution at endogenous expression levels.

Organic-inorganic-hybrid-polymer microlens arrays with tailored optical characteristics and multi-focal properties.

Plano-convex microlens arrays of organic-inorganic polymers with tailored optical properties are presented. The fine-tuning of each microlens within an array is achieved by confining inkjet printed drops of the polymeric ink onto pre-patterned substrates. The lens optical properties are thus freely specified, and high numerical apertures from 0.45 to 0.9 and focal lengths between 10 µm and 100 µm are demonstrated, confirming theoretical predictions. Combining nanoimprint lithography approaches and inkjet printing enables using the same material for the microlenses and their substrates, improving the optical performances. Microlens arrays with desired specifications are printed reaching yields up to 100% and high lens reproducibility with standard deviations of the apparent contact angle under 1° and of the numerical apertures and focal lengths under 6%. Microlens arrays involving lenses with different characteristics, e.g. multi focal length, and thus focal planes separated by only few microns are printed with the same reproducibility.

Cell shape-dependent early responses of fibroblasts to cyclic strain.

Randomly spread fibroblasts on fibronectin-coated elastomeric membranes respond to cyclic strain by a varying degree of focal adhesion assembly and actin reorganization. We speculated that the individual shape of the cells, which is linked to cytoskeletal structure and pre-stress, might tune these integrin-dependent mechanotransduction events. To this aim, fibronectin circles, squares and rectangles of identical surface area (2000µm(2)) were micro-contact printed onto elastomeric substrates. Fibroblasts plated on these patterns occupied the corresponding shapes. Cyclic 10% equibiaxial strain was applied to patterned cells for 30min, and changes in cytoskeleton and cell-matrix adhesions were quantified after fluorescence staining. After strain, megakaryocytic leukemia-1 protein translocated to the nucleus in most cells, indicating efficient RhoA activation independently of cell shape. However, circular and square cells (with radial symmetry) showed a significantly greater increase in the number of actin stress fibers and vinculin-positive focal adhesions after cyclic strain than rectangular (bipolar) cells of identical size. Conversely, cyclic strain induced larger changes in pY397-FAK positive focal complexes and zyxin relocation from focal adhesions to stress fibers in bipolar compared to symmetric cells. Thus, radially symmetric cells responded to cyclic strain with a larger increase in assembly, whereas bipolar cells reacted with more pronounced reorganization of actin stress fibers and matrix contacts. We conclude that integrin-mediated responses to external mechanical strain are differentially modulated in cells that have the same spreading area but different geometries, and do not only depend on mere cell size.

Reliability of continuous vital sign monitoring in post-operative patients employing consumer-grade fitness trackers: A randomised pilot trial.

Introduction: Fitness trackers can provide continuous monitoring of vital signs and thus have the potential to become a complementary, mobile and effective tool for early detection of patient deterioration and post-operative complications. Methods: To evaluate potential implementations in acute care setting, we included 36 patients after moderate to major surgery in a recent randomised pilot trial to compare the performance of vital sign monitoring by three different fitness trackers (Apple Watch 7, Garmin Fenix 6pro and Withings ScanWatch) with established standard clinical monitors in post-anaesthesia care units and monitoring wards. Results: During a cumulative period of 56 days, a total of 53,197 heart rate (HR) measurements, as well as 12,219 measurements of the peripheral blood oxygen saturation (SpO2) and 28,954 respiratory rate (RR) measurements were collected by fitness trackers. Under real-world conditions, HR monitoring was accurate and reliable across all benchmarked devices (r = [0.95;0.98], p < 0.001; Bias = [-0.74 bpm;-0.01 bpm]; MAPE∼2%). However, the performance of SpO2 (r = [0.21;0.68]; p < 0.001; Bias = [-0.46%;-2.29%]; root-mean-square error = [2.82%;4.1%]) monitoring was substantially inferior. RR measurements could not be obtained for two of the devices, therefore exclusively the accuracy of the Garmin tracker could be evaluated (r = 0.28, p < 0.001; Bias = -1.46/min). Moreover, the time resolution of the vital sign measurements highly depends on the tracking device, ranging from 0.7 to 117.94 data points per hour. Conclusion: According to the results of the present study, tracker devices are generally reliable and accurate for HR monitoring, whereas SpO2 and RR measurements should be interpreted carefully, considering the clinical context of the respective patients.

Edge-Contact MoS2 Transistors Fabricated Using Thermal Scanning Probe Lithography.

The science and engineering of two-dimensional materials (2DMs), in particular, of 2D semiconductors, is advancing at a thriving pace. It is well known that these delicate few-atoms thick materials can be damaged during the processing toward their integration into final devices. Thermal scanning probe lithography (t-SPL) is a gentle alternative to the typically used electron beam lithography to fabricate these devices avoiding the use of electrons, which are well known to deteriorate the 2DMs' properties. Here, t-SPL is used for the fabrication of MoS2-based field effect transistors (FETs). In particular, the use of t-SPL is demonstrated for the first time for the fabrication of edge-contact MoS2 FETs, combining the hot-tip patterning and Ar+ milling to etch the 2DM. To avoid contamination of the contact interface by atmospheric gas molecules, etching and metal deposition are performed without breaking the vacuum conditions in between. With this process, edge-contact MoS2 FETs are successfully fabricated and characterized. On/off ratios up to 108 and 109 are obtained at room temperature in air and vacuum, respectively, i.e., comparable with the best values reported in the literature.

NMR spectroscopy of a single mammalian early stage embryo.

The resolving power, chemical sensitivity and non-invasive nature of NMR have made it an established technique for in vivo studies of large organisms both for research and clinical applications. NMR would clearly be beneficial for analysis of entities at the microscopic scale of about 1 nL (the nanoliter scale), typical of early development of mammalian embryos, microtissues and organoids: the scale where the building blocks of complex organisms could be observed. However, the handling of such small samples (about 100 µm) and sensitivity issues have prevented a widespread adoption of NMR. In this article we show how these limitations can be overcome to obtain NMR spectra of a mammalian embryo in its early stage. To achieve this we employ ultra-compact micro-chip technologies in combination with 3D-printed micro-structures. Such device is packaged for use as plug & play sensor and it shows sufficient sensitivity to resolve NMR signals from individual bovine pre-implantation embryos. The embryos in this study are obtained through In Vitro Fertilization (IVF) techniques, transported cryopreserved to the NMR laboratory, and measured shortly after thawing. In less than 1 h these spherical samples of just 130-190 µm produce distinct spectral peaks, largely originating from lipids contained inside them. We further observe how the spectra vary from one sample to another despite their optical and morphological similarities, suggesting that the method can further develop into a non-invasive embryo assay for selection prior to embryo transfer.

Link between alginate reaction front propagation and general reaction diffusion theory.

We provide a common theoretical framework reuniting specific models for the Ca(2+)-alginate system and general reaction diffusion theory along with experimental validation on a microfluidic chip. As a starting point, we use a set of nonlinear, partial differential equations that are traditionally solved numerically: the Mikkelsen-Elgsaeter model. Applying the traveling-wave hypothesis as a major simplification, we obtain an analytical solution. The solution indicates that the fundamental properties of the alginate reaction front are governed by a single dimensionless parameter λ. For small λ values, a large depletion zone accompanies the reaction front. For large λ values, the alginate reacts before having the time to diffuse significantly. We show that the λ parameter is of general importance beyond the alginate model system, as it can be used to classify known solutions for second-order reaction diffusion schemes, along with the novel solution presented here. For experimental validation, we develop a microchip model system, in which the alginate gel formation can be carried out in a highly controlled, essentially 1D environment. The use of a filter barrier enables us to rapidly renew the CaCl(2) solution, while maintaining flow speeds lower than 1 µm/s for the alginate compartment. This allows one to impose an exactly known bulk CaCl(2) concentration and diffusion resistance. This experimental model system, taken together with the theoretical development, enables the determination of the entire set of physicochemical parameters governing the alginate reaction front in a single experiment.

Stretchable Conductors Fabricated by Stencil Lithography and Centrifugal Force-Assisted Patterning of Liquid Metal.

Embedding liquid metals (LMs) into an elastomer is emerging as a promising strategy for stretchable conductors. Existing manufacturing techniques are struggling between spatial resolution and process complexity and are limited to chemically resistant substrates. Here, we report on a hybrid process combining stencil lithography and centrifugal force-assisted patterning of liquid metal for the development of LM-based stretchable conductors. The selective wetting behavior of oxide-removed eutectic gallium-indium (EGaIn) on metal patterns defined by stencil lithography enables micrometer scale LM patterns on an elastomeric substrate. Stencil lithography allows for defining metal regions without harsh chemical treatments, making it suitable for a wide range of substrates. Microscale LM patterns are achieved by efficiently removing the excess material by the centrifugal forces experienced from spinning the substrate. The proposed approach allows for the creation of LM patterns with a line width as small as 2 µm on a stretchable poly(dimethylsiloxane) (PDMS) substrate. The electrical measurement results show that the fabricated EGaIn devices can endure 40% mechanical strain over several thousands of cycles. Furthermore, a stencil design using microbridges is proposed to address the mechanical stability issue in stencil lithography. An EGaIn conductor with a serpentine structure and an interdigitated capacitor are fabricated and characterized. The results demonstrate that the patterned serpentine conductors retain their functionality with applied mechanical strain up to 80%. The performance of the interdigitated capacitors upon applied strain is in good agreement with the theoretical estimation. Finally, we demonstrate our approach also on poly(octamethylene maleate (anhydride) citrate) (POMaC) substrates to broaden the use of the proposed method to not only flexible and stretchable but also biodegradable substrates, opening a way for in vivo transient microsystem engineering. The work presented here provides a versatile and reliable approach for manufacturing stretchable conductors.

Comparison of hydroxyethylstarch (HES 130/0.4) and 5% human albumin for volume substitution in pediatric neurosurgery: A retrospective, single center study.

OBJECTIVE: Colloid solutions are commonly used to maintain perioperative fluid homeostasis. In regard to perioperative infant-centered care, data about the impact of colloids are rare. New data suggest a possible positive effect of hydroxyethyl starch (HES) concerning blood brain barrier. Therefore we conduct a retrospective single center study of children scheduled for neurosurgery, age < five with a blood loss > 10% of body blood volume, receiving either 6% HES 130/0.4 or 5% human albumin (HA). RESULTS: Out of 913 patients, 86 were included (HES = 30; HA = 56). Compared to HES [16.4 ± 9.2 ml/kg body weight (mean ± SD)] HA group received more colloid volume (25.7 ± 11.3), which had more blood loss [HA 54.8 ± 45.0; HES 30.5 ± 30.0 (%) estimated blood volume] and higher fluid balances. Fibrinogen was decreased and activated partial thromboplastin time was elevated in HA group. Urinary output, creatinine and urea levels did not differ between the two groups. Serum calcium, total protein levels were lower in HES group. HA treated infants tended to have shorter ICU and hospital stays. We conclude that none of the investigated colloid solutions were without leverage to infants. Consequently randomized controlled trials about perioperative goal-directed fluid replacement of children undergoing (neuro)-surgery with major blood loss are needed.

Carbon monoxide has antioxidative properties in the liver involving p38 MAP kinase pathway in a murine model of systemic inflammation.

OBJECTIVE: Reactive oxygen species (ROS) are important in the hepatocellular injury process during a systemic inflammation. We examined the role of carbon monoxide (CO) on the hepatic generation of ROS with in-vivo and in-vitro models of systemic inflammation. METHODS: Using a murine model of bilateral hindlimb ischemia-reperfusion (I/R) we examined the effect of CO treatment on hepatic ROS formation, oxidative status, and cell injury. Cultured HUVEC were used to investigate intracellular pathways. RESULTS: CO treatment reduced hepatic lipid peroxidation, re-established total hepatic glutathione and glutathione disulfide (GSH/GSSG) levels and reduced hepatocellular injury. Inhibition of heme oxygenase (HO) during treatment with CO during hindlimb I/R failed to alter the antioxidant qualities provided by CO. The production of ROS after tumor necrosis factor-α (TNF-α) stimulation in HUVEC was diminished after exposure to CO. Treatment with CO during HO inhibition reduced both ROS formation and cell injury. Inhibiting the p38 MAPK (mitogen-activated protein kinase) pathway with pyridinyl imidazol (SB203580) revealed that the antioxidant potential of CO involved the activation of p38 MAPK. CONCLUSIONS: CO has direct antioxidant potential independently of any HO activity during systemic inflammation. The antioxidant effects afforded by CO involve the activation of the p38 MAPK pathway.

Inexpensive and fast wafer-scale fabrication of nanohole arrays in thin gold films for plasmonics.

In this paper, a fast and inexpensive wafer-scale process for the fabrication of arrays of nanoscale holes in thin gold films for plasmonics is shown. The process combines nanosphere lithography using spin-coated polystyrene beads with a sputter-etching process. This allows the batch fabrication of several 1000 microm(2) large hole arrays in 200 nm thick gold films without the use of an adhesion layer for the gold film. The hole size and lattice period can be tuned independently with this method. This allows tuning of the optical properties of the hole arrays for the desired application. An example application, refractive index sensing, is demonstrated.

NMR microsystem for label-free characterization of 3D nanoliter microtissues.

Performing chemical analysis at the nanoliter (nL) scale is of paramount importance for medicine, drug development, toxicology, and research. Despite the numerous methodologies available, a tool for obtaining chemical information non-invasively is still missing at this scale. Observer effects, sample destruction and complex preparatory procedures remain a necessary compromise. Among non-invasive spectroscopic techniques, one able to provide holistic and highly resolved chemical information in-vivo is nuclear magnetic resonance (NMR). For its renowned informative power and ability to foster discoveries and life-saving applications, efficient NMR at microscopic scales is highly sought after, but so far technical limitations could not match the stringent necessities of microbiology, such as biocompatible handling, ease of use, and high throughput. Here we introduce a novel microsystem, which combines CMOS technology with 3D microfabrication, enabling nL NMR as a platform tool for non-invasive spectroscopy of organoids, 3D cell cultures, and early stage embryos. In this study we show its application to microlivers models simulating non-alcoholic fatty liver disease, demonstrating detection of lipid metabolism dynamics in a time frame of 14 days based on 117 measurements of single 3D human liver microtissues.

Inkjet-printed multicolor arrays of highly luminescent nanocrystal-based nanocomposites.

Inkjet technology is a compelling method for the flexible and cost-effective printing of functional inks. We show that nanocomposite solutions based on polystyrene and differently sized core/shell-type nanocrystals (NCs) formed by a CdSe core coated with a shell of ZnS (CdSe@ZnS) in a single solvent, chloroform, can be reliably dispensed into luminescent, multicolor pixel arrays. This study demonstrates the relevance of parameters like polymer concentration and nozzle diameter, highlighting how the optimal conditions to print NCs embedded in 5 wt% polystyrene nanocomposite are given by a 70-microm-diameter nozzle. The obtained structures show that the bright size-dependent emission of the NCs in the nanocomposite is retained in the printed pixels.

Conduction in rectangular quasi-one-dimensional and two-dimensional random resistor networks away from the percolation threshold.

In this study we investigate electrical conduction in finite rectangular random resistor networks in quasione and two dimensions far away from the percolation threshold p(c) by the use of a bond percolation model. Various topologies such as parallel linear chains in one dimension, as well as square and triangular lattices in two dimensions, are compared as a function of the geometrical aspect ratio. In particular we propose a linear approximation for conduction in two-dimensional systems far from p(c), which is useful for engineering purposes. We find that the same scaling function, which can be used for finite-size scaling of percolation thresholds, also applies to describe conduction away from p(c). This is in contrast to the quasi-one-dimensional case, which is highly nonlinear. The qualitative analysis of the range within which the linear approximation is legitimate is given. A brief link to real applications is made by taking into account a statistical distribution of the resistors in the network. Our results are of potential interest in fields such as nanostructured or composite materials and sensing applications.

Optical Antenna-Based Fluorescence Correlation Spectroscopy to Probe the Nanoscale Dynamics of Biological Membranes.

The plasma membrane of living cells is compartmentalized at multiple spatial scales ranging from the nano- to the mesoscale. This nonrandom organization is crucial for a large number of cellular functions. At the nanoscale, cell membranes organize into dynamic nanoassemblies enriched by cholesterol, sphingolipids, and certain types of proteins. Investigating these nanoassemblies known as lipid rafts is of paramount interest in fundamental cell biology. However, this goal requires simultaneous nanometer spatial precision and microsecond temporal resolution, which is beyond the reach of common microscopes. Optical antennas based on metallic nanostructures efficiently enhance and confine light into nanometer dimensions, breaching the diffraction limit of light. In this Perspective, we discuss recent progress combining optical antennas with fluorescence correlation spectroscopy (FCS) to monitor microsecond dynamics at nanoscale spatial dimensions. These new developments offer numerous opportunities to investigate lipid and protein dynamics in both mimetic and native biological membranes.