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.

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.

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.

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.

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.

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.

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.

Nanopatterning of a Stimuli-Responsive Fluorescent Supramolecular Polymer by Thermal Scanning Probe Lithography.

The miniaturization of nanometer-sized multicolor fluorescent features is of continuous significance for counterfeit security features, data storage, and sensors. Recent advances in engineering of stimuli-responsive supramolecular polymeric materials that respond upon exposure to heat or mechanical force by changing their fluorescence characteristics open new opportunities as functional lithographic resists. Here, we demonstrate the patterning of a thermochromic supramolecular material by thermal scanning probe lithography (t-SPL), an emerging nanofabrication technique, which allows for ultrafast indentation with a heated probe, resulting in both fluorescent and topographic nanofeatures. t-SPL indentation reveals a linear relationship between the temperature at which material softening occurs and the indentation force in the range from 200 to 500 nN. The softening temperature decreases as the heating time increases from 4 µs to 1 ms, following time-temperature superposition behavior. Our results herein confirm that the fluorescence contrast, perceivable as a shift from red to green, was obtained by kinetic trapping of the dissociated state due to ultrarapid cooling when the probe is removed. We use t-SPL to create highly customized fluorescence patterns up to 40 × 40 µm2 in size with a spatial resolution of 86 nm and change the pitch size to modify the fluorescence intensity when observed by fluorescence microscopy. As an application, multifaceted security features with nanometer resolution are explored.

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.

Shape Memory Micro- and Nanowire Libraries for the High-Throughput Investigation of Scaling Effects.

The scaling behavior of Ti-Ni-Cu shape memory thin-film micro- and nanowires of different geometry is investigated with respect to its influence on the martensitic transformation properties. Two processes for the high-throughput fabrication of Ti-Ni-Cu micro- to nanoscale thin film wire libraries and the subsequent investigation of the transformation properties are reported. The libraries are fabricated with compositional and geometrical (wire width) variations to investigate the influence of these parameters on the transformation properties. Interesting behaviors were observed: Phase transformation temperatures change in the range from 1 to 72 °C (austenite finish, (Af), 13 to 66 °C (martensite start, Ms) and the thermal hysteresis from -3.5 to 20 K. It is shown that a vanishing hysteresis can be achieved for special combinations of sample geometry and composition.

Transient Nanoscopic Phase Separation in Biological Lipid Membranes Resolved by Planar Plasmonic Antennas.

Nanoscale membrane assemblies of sphingolipids, cholesterol, and certain proteins, also known as lipid rafts, play a crucial role in facilitating a broad range of important cell functions. Whereas on living cell membranes lipid rafts have been postulated to have nanoscopic dimensions and to be highly transient, the existence of a similar type of dynamic nanodomains in multicomponent lipid bilayers has been questioned. Here, we perform fluorescence correlation spectroscopy on planar plasmonic antenna arrays with different nanogap sizes to assess the dynamic nanoscale organization of mimetic biological membranes. Our approach takes advantage of the highly enhanced and confined excitation light provided by the nanoantennas together with their outstanding planarity to investigate membrane regions as small as 10 nm in size with microsecond time resolution. Our diffusion data are consistent with the coexistence of transient nanoscopic domains in both the liquid-ordered and the liquid-disordered microscopic phases of multicomponent lipid bilayers. These nanodomains have characteristic residence times between 30 and 150 µs and sizes around 10 nm, as inferred from the diffusion data. Thus, although microscale phase separation occurs on mimetic membranes, nanoscopic domains also coexist, suggesting that these transient assemblies might be similar to those occurring in living cells, which in the absence of raft-stabilizing proteins are poised to be short-lived. Importantly, our work underscores the high potential of photonic nanoantennas to interrogate the nanoscale heterogeneity of native biological membranes with ultrahigh spatiotemporal resolution.

Growth Of Organic Semiconductor Thin Films with Multi-Micron Domain Size and Fabrication of Organic Transistors Using a Stencil Nanosieve.

To grow small molecule semiconductor thin films with domain size larger than modern-day device sizes, we evaporate the material through a dense array of small apertures, called a stencil nanosieve. The aperture size of 0.5 µm results in low nucleation density, whereas the aperture-to-aperture distance of 0.5 µm provides sufficient crosstalk between neighboring apertures through the diffusion of adsorbed molecules. By integrating the nanosieve in the channel area of a thin-film transistor mask, we show a route for patterning both the organic semiconductor and the metal contacts of thin-film transistors using one mask only and without mask realignment.

High sensitivity field asymmetric ion mobility spectrometer.

A high sensitivity field asymmetric ion mobility spectrometer (FAIMS) was designed, fabricated, and tested. The main components of the system are a 10.6 eV UV photoionization source, an ion filter driven by a high voltage/high frequency n-MOS inverter circuit, and a low noise ion detector. The ion filter electronics are capable to generate square waveforms with peak-to-peak voltages up to 1000 V at frequencies up to 1 MHz with adjustable duty cycles. The ion detector current amplifier has a gain up to 1012 V/A with an effective equivalent input noise level down to about 1 fA/Hz1/2 during operation with the ion filter at the maximum voltage and frequency. The FAIMS system was characterized by detecting different standard chemical compounds. Additionally, we investigated the use of a synchronous modulation/demodulation technique to improve the signal-to-noise ratio in FAIMS measurements. In particular, we implemented the modulation of the compensation voltage with the synchronous demodulation of the ion current. The analysis of the measurements at low concentration levels led to an extrapolated limit of detection for acetone of 10 ppt with an averaging time of 1 s.

Single-chip electron spin resonance detectors operating at 50GHz, 92GHz, and 146GHz.

We report on the design and characterization of single-chip electron spin resonance (ESR) detectors operating at 50GHz, 92GHz, and 146GHz. The core of the single-chip ESR detectors is an integrated LC-oscillator, formed by a single turn aluminum planar coil, a metal-oxide-metal capacitor, and two metal-oxide semiconductor field effect transistors used as negative resistance network. On the same chip, a second, nominally identical, LC-oscillator together with a mixer and an output buffer are also integrated. Thanks to the slightly asymmetric capacitance of the mixer inputs, a signal at a few hundreds of MHz is obtained at the output of the mixer. The mixer is used for frequency down-conversion, with the aim to obtain an output signal at a frequency easily manageable off-chip. The coil diameters are 120µm, 70µm, and 45µm for the U-band, W-band, and the D-band oscillators, respectively. The experimental frequency noises at 100kHz offset from the carrier are 90Hz/Hz1/2, 300Hz/Hz1/2, and 700Hz/Hz1/2 at 300K, respectively. The ESR spectra are obtained by measuring the frequency variations of the single-chip oscillators as a function of the applied magnetic field. The experimental spin sensitivities, as measured with a sample of α,γ-bisdiphenylene-ß-phenylallyl (BDPA)/benzene complex, are 1×108spins/Hz1/2, 4×107spins/Hz1/2, 2×107spins/Hz1/2 at 300K, respectively. We also show the possibility to perform experiments up to 360GHz by means of the higher harmonics in the microwave field produced by the integrated single-chip LC-oscillators.

Mode Coupling in Plasmonic Heterodimers Probed with Electron Energy Loss Spectroscopy.

While plasmonic antennas composed of building blocks made of the same material have been thoroughly studied, recent investigations have highlighted the unique opportunities enabled by making compositionally asymmetric plasmonic systems. So far, mainly heterostructures composed of nanospheres and nanodiscs have been investigated, revealing opportunities for the design of Fano resonant nanostructures, directional scattering, sensing and catalytic applications. In this article, an improved fabrication method is reported that enables precise tuning of the heterodimer geometry, with interparticle distances made down to a few nanometers between Au-Ag and Au-Al nanoparticles. A wide range of mode energy detuning and coupling conditions are observed by near field hyperspectral imaging performed with electron energy loss spectroscopy, supported by full wave analysis numerical simulations. These results provide direct insights into the mode hybridization of plasmonic heterodimers, pointing out the influence of each dimer constituent in the overall electromagnetic response. By relating the coupling of nondipolar modes and plasmon-interband interaction with the dimer geometry, this work facilitates the development of plasmonic heterostructures with tailored responses, beyond the possibilities offered by homodimers.

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.

Rapid carbon nanotubes suspension in organic solvents using organosilicon polymers.

A strategy for a simple dispersion of commercial multi-walled carbon nanotubes (MWCNTs) using two organosilicones, polycarbosilane SMP10 and polysilazane Ceraset PSZ20, in organic solvents such as cyclohexane, tetrahydrofuran (THF), m-xylene and chloroform is presented. In just a few minutes the combined action of sonication and the presence of Pt(0) catalyst is sufficient to obtain a homogeneous suspension, thanks to the rapid hydrosilylation reaction between SiH groups of the polymer and the CNT sidewall. The as-produced suspensions have a particle size distribution <1µm and remain unchanged after several months. A maximum of 0.47 and 0.50mg/ml was achieved, respectively, for Ceraset in THF and SMP10 in chloroform. Possible applications as polymeric and ceramic thin films or aerogels are presented.