Rapid and accurate measurement of biomarkers in tissue and fluid samples is a major challenge in medicine. Here we report the development of a new, miniaturized diagnostic magnetic resonance (DMR) system for multiplexed, quantitative and rapid analysis. By using magnetic particles as a proximity sensor to amplify molecular interactions, the handheld DMR system can perform measurements on unprocessed biological samples. We show the capability of the DMR system by using it to detect bacteria with high sensitivity, identify small numbers of cells and analyze them on a molecular level in real time, and measure a series of protein biomarkers in parallel. The DMR technology shows promise as a robust and portable diagnostic device.A number of new diagnostic platforms have been developed to measure biomolecule abundance with high sensitivity 1 , enable early disease detection 2 and gain valuable insights into biology at the systems level 3 . Some examples include nuclear magnetic resonance (NMR) with hyperpolarized gas 4 , nanowire 5 and nanoparticle 6 sensors, surface plasmon resonance devices 7 and mass spectrometry 8 . Many of these devices and techniques, however, requiring time-consuming purification of samples typically followed by a set of amplification strategies 6 , may lack the ability for the multiplexed measurements that are desirable in identifying complex diseases 1,9 or may not be amenable for easy point-of-care translation.Here we report a chip-based DMR system for rapid, quantitative and multichanneled detection of biological targets. Using readily available magnetic nano-and microparticles as a proximity sensor to amplify molecular interactions 10 , the DMR system can perform highly sensitive (up to 1 × 10 −12 M) and selective measurements on small volumes of unprocessed biological samples. As proof of concept, we show sensitive detection of bacteria, profiling of circulating cells and multiplexed identification of different cancer biomarkers. If implemented with standard microfabrication technology, the DMR system will be a high-throughput, low-cost and portable platform for large-scale sensing.The DMR sensor strategy is based on a self-amplifying proximity assay using magnetic nanoparticles 10 . When a few magnetic nanoparticles bind their intended molecular target Correspondence should be addressed to R.W. (rweissleder@mgh.harvard.edu). Note: Supplementary information is available on the Nature Medicine website.Author Contributions: H.L. designed the device, built the DMR prototype, obtained measurements, analyzed data and wrote the manuscript. E.S. performed all chemical modifications of magnetic nanoparticles and assisted in measurements and data analysis. D.H. collaborated in the development of the NMR electronics of discrete components. R.W. conceived the project, provided overall guidance, designed experiments and targeted nanoparticles, analyzed the data and wrote the manuscript with contributions from all authors.Competing Interests Statement: The authors declare competing financial i...

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Atomically thin two-dimensional (2D) materialssuch as transition metal dichalcogenide (TMD) monolayers and hexagonal boron nitride (hBN)and their van der Waals layered preparations have been actively researched to build electronic devices such as field-effect transistors, junction diodes, tunneling devices, and, more recently, memristors. Twodimensional material memristors built in lateral form, with horizontal placement of electrodes and the 2D material layers, have provided an intriguing window into the motions of ions along the atomically thin layers. On the other hand, 2D material memristors built in vertical form with top and bottom electrodes sandwiching 2D material layers may provide opportunities to explore the extreme of the memristive performance with the atomic-scale interelectrode distance. In particular, they may help push the switching voltages to a lower limit, which is an important pursuit in memristor research in general, given their roles in neuromorphic computing. In fact, recently Akinwande et al. performed a pioneering work to demonstrate a vertical memristor that sandwiches a single MoS 2 monolayer between two inert Au electrodes, but it could neither attain switching voltages below 1 V nor control the switching polarity, obtaining both unipolar and bipolar switching devices. Here, we report a vertical memristor that sandwiches two MoS 2 monolayers between an active Cu top electrode and an inert Au bottom electrode. Cu ions diffuse through the MoS 2 double layers to form atomic-scale filaments. The atomic-scale thickness, combined with the electrochemical metallization, lowers switching voltages down to 0.1−0.2 V, on par with the state of the art. Furthermore, our memristor achieves consistent bipolar and analogue switching, and thus exhibits the synapse-like learning behavior such as the spike-timing dependent plasticity (STDP), the very first STDP demonstration among all 2D-material-based vertical memristors. The demonstrated STDP with low switching voltages is promising not only for low-power neuromorphic computing, but also from the point of view that the voltage range approaches the biological action potentials, opening up a possibility for direct interfacing with mammalian neuronal networks.

Developing a new tool capable of high-precision electrophysiological recording of a large network of electrogenic cells has long been an outstanding challenge in neurobiology and cardiology. Here, we combine nanoscale intracellular electrodes with complementary metal-oxide-semiconductor (CMOS) integrated circuits to realize a high-fidelity all-electrical electrophysiological imager for parallel intracellular recording at the network level. Our CMOS nanoelectrode array has 1,024 recording/stimulation 'pixels' equipped with vertical nanoelectrodes, and can simultaneously record intracellular membrane potentials from hundreds of connected in vitro neonatal rat ventricular cardiomyocytes. We demonstrate that this network-level intracellular recording capability can be used to examine the effect of pharmaceuticals on the delicate dynamics of a cardiomyocyte network, thus opening up new opportunities in tissue-based pharmacological screening for cardiac and neuronal diseases as well as fundamental studies of electrogenic cells and their networks.

Macroelectronic circuits made on substrates of glass or plastic could one day make computing devices ubiquitous owing to their light weight, flexibility and low cost. But these substrates deform at high temperatures so, until now, only semiconductors such as organics and amorphous silicon could be used, leading to poor performance. Here we present the use of low-temperature processes to integrate high-performance multi-nanowire transistors into logical inverters and fast ring oscillators on glass substrates. As well as potentially enabling powerful electronics to permeate all aspects of modern life, this advance could find application in devices such as low-cost radio-frequency tags and fully integrated high-refresh-rate displays.

Current electrophysiological or optical techniques cannot reliably perform simultaneous intracellular recordings from more than a few tens of neurons. Here, we report a nanoelectrode array that can simultaneously obtain intracellular recordings from thousands of connected mammalian neurons in vitro. The array consists of 4,096 platinum-black electrodes with nanoscale roughness fabricated on top of a silicon chip that monolithically integrates 4,096 microscale amplifiers, configurable into pseudo-current-clamp mode (for concurrent current injection and voltage recording) or into pseudo-voltage-clamp mode (for concurrent voltage application and current recording). We used the array in pseudo-voltage-clamp mode to measure the effects of drugs on ion-channel currents. In pseudo-current-clamp mode, the array recorded intracellular action potentials and post-synaptic potentials from over thousands of neurons. In addition, we mapped over 300 excitatory and inhibitory synaptic connections from over 1,700 neurons that were recorded for 19 mins. This high-throughput intracellular-recording technology could benefit functional connectome mapping, electrophysiological screening, and other functional interrogations of neuronal networks. The patch clamp electrode is celebrated for its high-sensitivity intracellular recording that can measure not only action potential (AP) propagation in neurons but also subthreshold events such as postsynaptic potentials (PSPs). Dense, parallel execution of such high-Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Field-effect transistor biomolecular sensors based on low-dimensional nanomaterials boast sensitivity, label-free operation and chip-scale construction. Chemical vapour deposition graphene is especially well suited for multiplexed electronic DNA array applications, since its large two-dimensional morphology readily lends itself to top-down fabrication of transistor arrays. Nonetheless, graphene field-effect transistor DNA sensors have been studied mainly at single-device level. Here we create, from chemical vapour deposition graphene, field-effect transistor arrays with two features representing steps towards multiplexed DNA arrays. First, a robust array yield-seven out of eight transistors-is achieved with a 100-fM sensitivity, on par with optical DNA microarrays and at least 10 times higher than prior chemical vapour deposition graphene transistor DNA sensors. Second, each graphene acts as an electrophoretic electrode for site-specific probe DNA immobilization, and performs subsequent site-specific detection of target DNA as a field-effect transistor. The use of graphene as both electrode and transistor suggests a path towards all-electrical multiplexed graphene DNA arrays.