The ability to sense biological inputs using self-contained devices unreliant on external reagents or reporters would open countless opportunities to collect information about our health and environment. Currently, a very limited set of molecular inputs can be detected using this type of sensor format. The development of versatile reagentless sensors that could track molecular analytes in biological fluids remains an unmet need. Here, we describe a new universal sensing mechanism that is compatible with the analysis of proteins that are important physiological markers of stress, allergy, cardiovascular health, inflammation and cancer. The sensing mechanism we developed is based on the measurement of field-induced directional diffusion of a nanoscale molecular pendulum tethered to an electrode surface and the sensitivity of electrontransfer reaction kinetics to molecular size. Using time-resolved electrochemical measurements of diffusional motion, the presence of an analyte bound to a sensor complex can be continuously tracked in real time. We show that this sensing approach is compatible with making measurements in blood, saliva, urine, tears and sweat and that the sensors can collect data in situ in living animals. The sensor platform described enables a broad range of applications in personalized health monitoring.
We report on the achievement of planar memristive devices on monocrystalline ZnO substrates using Ti/Al and Pt/Au contacts with dimensions of 100 x 100 microm(2) and spacings of approximately 60 microm. Effects of both thermal and electro-forming processes on the switching characteristics are investigated. It is observed that the thermally formed devices exhibit an extremely large R(OFF)/R(ON) value of approximately 20 000. The electrically formed devices, on the other hand, demonstrate an exceptional switching stability, with R(OFF)/R(ON) variations of < 2% for durations of over 10(5) s and more than 1800 switching cycles. The dependence of the switching characteristics on the formation processes, as well as the metal electrodes, could be explained by an oxygen vacancy formation/annihilation and migration model.
The analysis of heterogeneous subpopulations of circulating tumor cells (CTCs) is critical to enhance our understanding of cancer metastasis and enable non-invasive cancer diagnosis and monitoring. The phenotypic variability and plasticity of these cells – properties closely linked to their clinical behavior – demand techniques that isolate viable, discrete fractions of tumor cells for functional assays of their behavior and detailed analysis of biochemical properties. Here, we introduce the Prism Chip, a high-resolution immunomagnetic profiling and separation chip which harnesses a cobalt-based alloy to separate a flowing stream of nanoparticle-bound tumor cells with differential magnetic loading into ten discrete streams. Using this approach, we achieve exceptional purity (5.7 log white blood cell depletion) of isolated cells. We test the differential profiling function of the integrated device using prostate cancer blood samples from a mouse xenograft model. Using integrated graphene Hall sensors, we demonstrate concurrent automated profiling of single cells and CTC clusters that belong to distinct subpopulations based on protein surface expression.
Electrodes exhibiting controlled nanoscale separations are required in devices for light detection, semiconductor electronics and medical diagnostics. Here we use low-cost lithography to define micron-separated electrodes, which we downscale to create three-dimensional electrodes separated by nanoscale gaps. Only by devising a new strategy, which we term electrochemical self-inhibited reagent depletion, were we able to produce a robust self-limiting nanogap manufacturing technology. We investigate the method using experiment and simulation and find that, when electrodeposition is carried out using micron-spaced electrodes simultaneously poised at the same potential, these exhibit self-inhibited reagent depletion, leading to defined and robust nanogaps. Particularly remarkable is the formation of fractal electrodes that exhibit interpenetrating jagged elements that consistently avoid electrical contact. We showcase the new technology by fabricating photodetectors with responsivities (A/W) that are one hundred times higher than previously reported photodetectors operating at the same low (1–3 V) voltages. The new strategy adds to the nanofabrication toolkit method that unites top–down template definition with bottom–up three-dimensional nanoscale features.
SUMMARYA new variable-order singular boundary element for two-dimensional stress analysis is developed. This element is an extension of the basic three-node quadratic boundary element with the shape functions enriched with variable-order singular displacement and traction ÿelds which are obtained from an asymptotic singularity analysis. Both the variable order of the singularity and the polar proÿle of the singular ÿelds are incorporated into the singular element to enhance its accuracy. The enriched shape functions are also formulated such that the stress intensity factors appear as nodal unknowns at the singular node thereby enabling direct calculation instead of through indirect extrapolation or contour-integral methods. Numerical examples involving crack, notch and corner problems in homogeneous materials and bimaterial systems show the singular element's great versatility and accuracy in solving a wide range of problems with various orders of singularities. The stress intensity factors which are obtained agree very well with those reported in the literature.
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