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Neuromorphic Nanowire Networks (NWNs) are a novel class of information processing hardware devices, combining the advantage of memristive cross-point junctions and neural-like complex network topology. In addition to their low operating power, NWNs are also easy to fabricate with bottom-up self-assembly. Here, we implement the MNIST handwritten digit classification task on simulated NWNs to demonstrate their ability to perform complex learning tasks. Using a CNN-inspired kernel method and a reservoir computing framework, our simulation results attain an accuracy of nearly 98%. Moreover, this is achieved using only a fraction of the total MNIST training data and without requiring hardware accelerators. We also investigate the information theoretic metrics of mutual information (MI), transfer entropy (TE) and active information storage (AIS) to analyze the MNIST learning dynamics of NWNs. We find that MI with respect to classes is maximized after network feature extraction and that TE is largest when MNIST digit boundaries are processed, while AIS is strongest when areas with lower pixel values are presented. Overall, these results suggest the information processing capabilities of neuromorphic NWNs make them promising candidates for complex learning applications.

Disruptive technology in computational devices is required as the universal computing machines approach quantum mechanical limits. Integration of state-of-the-art memristive devices provides optimal scaling of current technologies beyond this limit through the adoption of neuromorphic models. Universal computing machines pioneered by Alan Turing are strictly based on top-down intelligent design. Neuromorphic models instead engage in bottom-up programmability by emulating mammalian brain design and characteristics. Here we show the design, characterization, and implementation of a massively parallel memristor neuromorphic network based on metal chalcogenide atomic switch network (ASN) systems with key characteristics such as short- and long-term potentiation, power-law dynamics, and scale-free topology.

Artificial realizations of the mammalian brain alongside their integration into electronic components are explored through neuromorphic architectures, neuroarchitectectonics, on CMOS compatible platforms. Exploration of neuromorphic technologies continue to develop as an alternative computational paradigm as both capacity and capability reach their fundamental limits with the end of the transistor-driven industrial phenomenon of Moore’s law. Here, we consider the electronic landscape within neuromorphic technologies and the role of the atomic switch as a model device. We report the fabrication of an atomic switch network (ASN) showing critical dynamics and harness criticality to perform benchmark signal classification and Boolean logic tasks. Observed evidence of biomimetic behavior such as synaptic plasticity and fading memory enable the ASN to attain a cognitive capability within the context of artificial neural networks.

The atomic switch technology can be used to emulate the synaptic plasticity underlying short-term and long-term memory functions in the human brain. These functions are realized by transport of metal ions or oxygen ions in sulfide or oxide matrices. The change in conductance of these devices is considered analogous to the change in strength of biological synapses that varies depending on the strength, frequency, and number of stimulating input pulses. The devices also exhibit sensitivity to the moisture in and temperature of the ambient environment, and configurable multifunction including rectification and synaptic plasticity under different electroforming conditions. These observations indicate that the atomic switch technology has great potential for use as an essential building block for neural computing systems.

BackgroundEpidemiological and experimental evidences have shown cancer as a leading cause of death worldwide. Although the folklore use of plants as a reliable source of health-restoring principles is well-documented, the search for more of such plants that are active against diseases, such as cancer, continues. We report here a laboratory-based evidence of the relevance of an ethanol leaf extract of Anogeissus leiocarpus (A2L) in comparison with resveratrol, a natural polyphenol, in cancer therapy.MethodsThe quantitative assessment of flavonoid and phenolic contents involved quercetin and gallic acid as standards, respectively were determined using spectrophotometry. Cytotoxicity was determined fluorometrically using propidium-iodide-staining method. Antioxidant status, adenosine triphosphate (ATP) levels, caspase activities and mitochondrial integrity were assessed using fluorometry/luminometry.ResultsThe antioxidant assay demonstrated that A2L possesses a strong antioxidant capacity as compared with the reference compounds, ascorbic acid and butylated hydroxytoluene. This is further buttressed by the significantly high level of phenolics obtained in the quantitative assessment of the extract. A 72-h post-treatment examination indicated that both A2L and resveratrol modulate the proliferation of HepG2 liver carcinoma cells in a time- and concentration-dependent manner. Determination of the total nuclei area, propidium-iodide negative and positive nuclei areas all further buttress the modulation of cell proliferation by A2L and resveratrol with the indication that the observed cell death is due to apoptosis and necrosis at lower and higher concentrations of treatments respectively. At lower concentrations (0.39-3.13μg/mL), resveratrol possesses higher tendencies to activate caspases 3 and 7. Bioenergetically, both resveratrol and A2L do not adversely affect the cells at lower concentrations (0.39-6.25μg/mL for resveratrol and 12.5-100.0μg/mL for A2L) except at higher concentrations (12.5-25.0μg/mL for resveratrol and 200-800μg/mL for A2L) which are more pronounced in A2L-treated cells. Furthermore, the antioxidant status of HepG2 cells is not perturbed by resveratrol as compared with A2L. Assessment of 24-h post-treatment mitochondrial function shows that resveratrol is not mitotoxic as compared with A2L which exhibits mitotoxicity at its highest concentration.ConclusionsTaken together, findings from this study showed that A2L possesses strong antiproliferative activity and its prospect in the management of hepatocellular carcinoma deserves further investigation.

Neuromorphic networks are formed by random self-assembly of silver nanowires. Silver nanowires are coated with a polymer layer after synthesis in which junctions between two nanowires act as resistive switches, often compared with neurosynapses. We analyze the role of single junction switching in the dynamical properties of the neuromorphic network. Network transitions to a high-conductance state under the application of a voltage bias higher than a threshold value. The stability and permanence of this state is studied by shifting the voltage bias in order to activate or deactivate the network. A model of the electrical network with atomic switches reproduces the relation between individual nanowire junctions switching events with current pathway formation or destruction. This relation is further manifested in changes in 1/f power-law scaling of the spectral distribution of current. The current fluctuations involved in this scaling shift are considered to arise from an essential equilibrium between formation, stochastic-mediated breakdown of individual nanowire-nanowire junctions and the onset of different current pathways that optimize power dissipation. This emergent dynamics shown by polymer-coated Ag nanowire networks places this system in the class of optimal transport networks, from which new fundamental parallels with neural dynamics and natural computing problem-solving can be drawn.

Palpable thyroid lesions are common, and although mostly benign, lethal malignant nodules do occur and may be difficult to differentiate. Here, we introduce the use of a piezoelectric system called Smart-touch fine needle (or STFN) mounted directly onto conventional biopsy needles, to evaluate abnormal tissues, through quantitative real-time measurements of variations in tissue stiffness as the needle penetrates tissue. Using well-characterized biomaterials of known stiffness and explanted animal tissue models, we first established experimental protocols for STFN measures on biological tissues, as well as optimized device design for high signal-to-noise ratio. Freshly excised patient thyroids with varying fibrotic and malignant potential revealed discrete variations in STFN based tissue stiffness/stiffness heterogeneity and correlated well with final histopathology. Our piezoelectric needle sensor reveals mechanical heterogeneity in thyroid tissue lesions and provides a foundation for the design of hand-held tools for the rapid, mechano-profiling of malignant lesions in vivo while performing fine needle aspiration (FNA).

Efforts to achieve a low-power, dynamically complex system become crucial as CMOS fabrication limits are realized. Atomic Switch Networks (ASNs) provide fabrication advantages over traditional CMOS through the combination of top-down and bottom-up techniques, leading to densely inter-connected networks of atomic switches. ASNs show emergent behaviors through the interaction of individual non-linear elements. These properties make ASNs suitable for alternative computational paradigms, such as neuromorphic or reservoir computing. This work examined ASNs' ability to perform Boolean logic operations using non-temporal inputs based on randomized Boolean input streams. Zero and one bits were converted to negative and positive DC voltage pulses, respectfully. Next, a linear readout layer was applied to an array of voltage outputs from the device to reconstruct target output signals for the given task. ASNs produced nearly perfect results at low voltages for AND, OR, and NAND with more than 95% confidence. XOR, which requires non-linearity to solve, was able to be partially solved at high voltages with more than 95% confidence. As opposed to previous works which have investigated temporal computation in ASNs, this work was the first to demonstrate semi-predictable, non-temporal, non-linear behavior within the device. Results demonstrated that the device connectivity is complete enough to perform complex computations.

There are many examples of problems in pattern analysis for which it is often possible to obtain systematic characterizations, if in addition a small number of useful features or parameters of the image are known a priori or can be estimated reasonably well. Often, the relevant features of a particular pattern analysis problem are easy to enumerate, as when statistical structures of the patterns are well understood from the knowledge of the domain. We study a problem from molecular image analysis, where such a domain-dependent understanding may be lacking to some degree and the features must be inferred via machine-learning techniques. In this paper, we propose a rigorous, fully automated technique for this problem. We are motivated by an application of atomic force microscopy (AFM) image processing needed to solve a central problem in molecular biology, aimed at obtaining the complete transcription profile of a single cell, a snapshot that shows which genes are being expressed and to what degree. Reed et al. (“Single molecule transcription profiling with AFM,” Nanotechnology, vol. 18, no. 4, 2007) showed that the transcription profiling problem reduces to making high-precision measurements of biomolecule backbone lengths, correct to within 20–25 bp (6–7.5 nm). Here, we present an image processing and length estimation pipeline using AFM that comes close to achieving these measurement tolerances. In particular, we develop a biased length estimator on trained coefficients of a simple linear regression model, biweighted by a Beaton–Tukey function, whose feature universe is constrained by James–Stein shrinkage to avoid overfitting. In terms of extensibility and addressing the model selection problem, this formulation subsumes the models we studied.

A potential route to extend Moore's law beyond the physical limits of existing materials and device architectures is to achieve nanotechnology breakthroughs in materials and device concepts. Here, we discuss an on-demand WO(3-x)-based nanoionic device where electrical and neuromorphic multifunctions are realized through externally induced local migration of oxygen ions. The device is found to possess a wide range of time scales of memorization, resistance switching, and rectification varying from volatile to permanent in a single device, and these can furthermore be realizable in both two- or three-terminal systems. The gradually changing volatile and nonvolatile resistance states are experimentally demonstrated to mimic the human brain's forgetting process for short-term memory and long-term memory.We propose this nanoionic device with its on-demand electrical and neuromorphic multifunction has a unique paradigm shifting potential for the fabrication of configurable circuits, analog memories, digital-neural fused networks, and more in one device architecture.

We demonstrate memristive operations using gap-type Ag2S atomic switches, in which the growth and shrinkage of an Ag protrusion are controlled by using solid-electrochemical reactions. In addition to conventional memristive operations such as those proposed and demonstrated by resistive random-access memories (ReRAMs) using metal oxide compounds, gap-type Ag2S atomic switches also show new types of memristive operations by storing information from input signals without changing their output until a sufficient number of signals are inputted. The new types of memristive operations resemble the learning process seen in neuroplasticity, where changes occur in the organization of the human brain as a result of experience.

A new sensing method employing a computer-designed broadband voltage pulse sent to an electromechanical resonator is suggested and demonstrated. The pulse spans a user-defined bandwidth around a user-selected center frequency so as to include at least one mechanical resonance. The transient voltage pulse excites mechanical resonance through the piezoelectric effect. The current response signal from the device is recorded and subjected to FFT. Components of the response due to electrical impedance and mechanical resonance are separated and tracked with time upon exposure to solvent vapors, helium, or CO2. Data are shown for both polymer coated quartz tuning forks and piezoelectric microcantilevers with sub-ppm sensitivity for some analytes.

Objectives Streptococcus mutans is considered a major causative of tooth decay due to its ability to rapidly metabolize carbohydrates such as sucrose. One prominent excreted end product of sucrose metabolism is lactic acid. Lactic acid causes a decrease in the pH of the oral environment with subsequent demineralization of the tooth enamel. Biologically relevant bacteria-induced enamel demineralization was studied. Methods Optical profiling was used to measure tooth enamel decay with vertical resolution under one nanometer and lateral features with optical resolution as a result of S. mutans biofilm exposure. Comparison measurements were made using AFM. Results After 72 h of biofilm exposure the enamel displayed an 8-fold increase in the observed roughness average ( R a ), as calculated over the entire measured array. Similarly, the average root mean square (RMS) roughness, R RMS , of the enamel before and after biofilm exposure for 3 days displayed a 7-fold increase. Further, the direct effect of chemically induced enamel demineralization using biologically relevant organic acids was shown. Optical profiles of the enamel surface after addition of a 30% lactic acid solution showed a significant alteration in the surface topography with a corresponding increase in respective surface roughness statistics. Similar measurements with 10% citric acid over seconds and minutes give insight into the demineralization process by providing quantitative measures for erosion rates: comparing surface height and roughness as metrics. Significance The strengths of optical profilometry as an analytical tool for understanding and analyzing biologically relevant processes such as biofilm induced tooth enamel demineralization were demonstrated.

We present an interferometric imaging technique that permits local measurement of mechanical properties and nanomechancial motion in small living animals. Measurements of nanomechanical properties and spatially resolved pulsations of

Silicon micro cantilevers are used as highly sensitive transducers for a wide range of physical, chemical and biochemical stimuli. Vibrating the cantilevers at higher-order resonant modes can achieve extra sensitivity, but the difficulty lies in determining exactly which modes are excited in the cantilever. This problem is exacerbated for cantilever sensors operating in liquid where the computational analysis of the resonance modes is very challenging. Using strobed interferometric microscopy, we are able to image the dynamic behavior of individual (100×500×1 μm 3 ) cantilevers in an eight cantilever array over frequencies from 0–1 MHz. We show how some modifications to the interferometric microscope allow for the spatial visualization of 16 longitudinal modes of cantilevers working in liquid with nanometer-scale amplitudes. We also compare the shift in frequency response and reduction in quality factor for cantilevers resonating in liquid versus in air and simulations in vacuum. Because the resonant frequency spectrum is fairly complex and does not follow simple intuition, our work maps the actual behavior of cantilevers without having any specific knowledge of the sample and environment parameters and without the necessity of involved simulations and calculations.

Change in cell stiffness is a new characteristic of cancer cells that affects the way they spread1,2. Despite several studies on architectural changes in cultured cell lines1,3, no ex vivo mechanical analyses of cancer cells obtained from patients have been reported. Using atomic force microscopy, we report the stiffness of live metastatic cancer cells taken from the body (pleural) fluids of patients with suspected lung, breast and pancreas cancer. Within the same sample, we find that the cell stiffness of metastatic cancer cells is more than 70% softer, with a standard deviation over five times narrower, than the benign cells that line the body cavity. Different cancer types were found to display a common stiffness. Our work shows that mechanical analysis can distinguish cancerous cells from normal ones even when they show similar shapes. These results show that nanomechanical analysis correlates well with immunohistochemical testing currently used for detecting cancer.

We discuss the utility of ASNs as a uniquely scalable physical platform capable of hybrid-CMOS architectures and novel computation. Through a combination of controlled design with spontaneous self-organization, an atomic switch network (ASN) has been produce as a purpose-built complex system. A highly interconnected system of Ag2S resistive switches, the ASN has been shown to produce fault-tolerant switching and a set of complex dynamics similar to biological neural networks.

Silicon micro cantilevers are used as transducers for a wide range of physical, chemical and biochemical stimuli, where they exhibit exquisite sensitivity (10?18?g, 10?15?J, 10?9?M, etc) over a wide range of temperatures (100?mK?1300?K). This is accomplished by inducing static bending in the cantilever structure or by changing the cantilever's resonant behaviour, both easily measurable responses. There is increasing interest in using higher-order resonant modes to achieve extra sensitivity; however, this raises the question of exactly which modes are excited in the cantilever. Using strobed interferometric microscopy we are able to probe the dynamic behaviour of individual (100 ? 500 ? 1??m3) cantilevers in an eight cantilever array over frequencies from 0 to 1?MHz. We present data that enable spatial visualization of 16 cantilever modes with nanometre-scale amplitudes; combined with finite element analysis calculations we directly assign mode indices. We discuss the reversal of specific modes between experiment and theory, the uniformity of individual cantilevers in the array and the clear relationship between boundary conditions and resonant behaviour. Our conclusion is that the assignment of a resonant frequency spectrum is fairly complex and does not necessarily follow simple intuition.

In both the philosophical and visual sense, ‘seeing is believing’ does not apply to nanotechnology, for there is nothing even remotely visible to create proof of existence. On the atomic and molecular scale, data is recorded by sensing and probing in a very abstract manner, which requires complex and approximate interpretations. More than in any other science, visualization and creation of a narrative becomes necessary to describe what is sensed, not seen. Nevertheless, many of the images generated in science and popular culture are not related to data at all, but come from visualizations and animations frequently inspired or created directly from science fiction. Likewise, much of this imagery is based on industrial models and is very mechanistic in nature, even though nanotechnology research is at a scale where cogs, gears, cables, levers and assembly lines as functional components appear to be highly unlikely. However, images of mechanistic nanobots proliferate in venture capital circles, popular culture, and even in the scientific arena, and tend to dominate discourse around the possibilities of nanotechnology. The authors put forward that this new science is ultimately about a shift in our perception of reality from a purely visual culture to one based on sensing and connectivity. Micromegas, a far better observer than his dwarf, could clearly see that the atoms were talking to one another; he drew the attention of his companion, who, ashamed at being mistaken in the matter of procreation, was now very reluctant to credit such a species with the power to communicate. (Voltaire, 1729 pg. 24) Introduction Nanotechnology is more a new science than technology, and the industry being constructed around it, predictably uses old ideas and imagery. During its current rise to prominence, a strange propagandist “nanometer” has emerged in our midst without being clearly realized by any of the participants. It is layered with often highly unlikely ideas of nanotech products that range from molecular sensors in underwear, smart washing machines that know how dirty the clothes are, to artificial red blood cells and nanobots that repair our bodies, all the way up to evil swarms of planet-devouring molecular machines. Sensation-based media happily propagates this powerful and misleading cocktail combining scientific data, graphically intense visualizations together with science fiction artwork. In the past few years, mixed up nanomemes have emerged, where the differences between science fiction novels, front cover stories and images of reputable journals such as Science or Nature are becoming differentiated by the proportion of fiction to fact rather than straight factual content. Venture capitalists, the military, governments around the world as well as educational institutions seduced by this syndrome are portraying nanotech as the savior of our rapidly declining economies and outdated military systems. Dovetailing on the recent frenzied exponential rise and fall of information technologies, and also to a degree by biotechnology, the need for a new cure-all has been identified. Two terms often used interdependently are nanoscience and nanotechnology. Surprisingly, the term nanotechnology predates nanoscience. This is because the dreams of a new technology were proposed before the actual scientific research specifically aimed at producing the technology existed. The term nanotechnology, in its short lifetime, has attracted a variety of interpretation, and there is little agreement, even among those who are engaged in it

Diseased tissues exhibit changes in mechanical properties and thus possess clinical diagnostic significance. We report the design and development of a Fine Needle Elastography (FNE) prototype device integrated with Fine Needle Aspiration Cytology (FNAC) needle that allows for quantitative and sensitive assessment of tissues and materials based on local variations in elastic, friction, and cutting forces on needle insertion. A piezoelectric force-sensor at the base of FNA needle measures the forces opposing needle penetration with micrometer scale resolution. Measurement precision (±5 μm) and axial resolution (~20 μm) of FNE device was tested using control mm size gelatin matrices and unripe pear in assessing needle penetration resistance, force heterogeneity and optimization of needle penetration velocity. Further, we demonstrated the usefulness of FNE in quantitative, biomechanical differentiation of simulated thyroid tumor nodules in an ultrasound neck phantom. Fluid or solid nodules were probed in the phantom study coupled with ultrasound guidance. Our data shows significantly higher force variations (1-D force heterogeneity; HF,a=6.5 mN, HF,q=8.25 mN and stiffness heterogeneity; HS,a=0.0274 kN/m, HS,q=0.0395 kN/m) in solid nodules compared either to fluid nodules or to regions corresponding to healthy thyroid tissue within the ultrasound phantom. The results suggest future applications of in vivo FNE biopsies based on force heterogeneity to diagnose thyroid tumors in areas where ultrasound instrumentation or access to a qualified pathologist for FNAC are unavailable, as well as an ancillary diagnostic tool in thyroid cancer management.

We present a chemical sensor based on a microfabricated array of eight silicon cantilevers actuated at their resonance-frequency and functionalized by polymer coatings. The operating principle relies on transduction of chemical or physical processes into a mechanical response. After exposure to analyte vapor, analyte molecules diffuse into the cantilever coating, which begins to swell. Jointly with the mass increase, a change of interfacial stress between coating and cantilever occurs, resulting in a bending of the cantilevers. Our setup allows the simultaneous detection of cantilever oscillation and bending of eight cantilevers by time-multiplexed optical beam deflection readout. The ac component of the cantilever response is demodulated, and the cantilever resonance-frequency is tracked by a custom-built phase-locked loop. By filtering out the ac component (oscillation), the dc signal (bending) is extracted, yielding information on mass as well as surface stress changes simultaneously. Detection results of water, primary alcohols, alkanes and perfumes are presented.

The semiconductor industry has seen a remarkable miniaturization trend, driven by many scientific and technological innovations. But if this trend is to continue, and provide ever faster and cheaper computers, the size of microelectronic circuit components will soon need to reach the scale of atoms or molecules--a goal that will require conceptually new device structures. The idea that a few molecules, or even a single molecule, could be embedded between electrodes and perform the basic functions of digital electronics--rectification, amplification and storage--was first put forward in the mid-1970s. The concept is now realized for individual components, but the economic fabrication of complete circuits at the molecular level remains challenging because of the difficulty of connecting molecules to one another. A possible solution to this problem is 'mono-molecular' electronics, in which a single molecule will integrate the elementary functions and interconnections required for computation.

A novel chemical sensor based on a micromechanical array of silicon cantilevers is presented. Chemical reactions are transduced by sensitization of cantilevers with coatings such as metals, self-assembled monolayers, or polymers into a mechanical response. This is read out using an optical beam-deflection technique by a sequential readout scheme. Reference cantilever sensors permit subtraction of background signals (differential measurement). Coating of each cantilever sensor with a different sensitive layer allows operation of the array-device as a new form of chemical nose. Detection of hydrogen, primary alcohols, natural flavors, and water vapor is demonstrated. We show that the magnitude of sensor response is proportional to the amount of analyte present.

The C60 electromechanical amplifier is a working 3-terminal device based on the modulation of the tunnel-transport regime through a C60 molecule by a reversible deformation of its cage. We present the advantages of the planarization of this triode such as a surface extension lower than 0.05μm2 on the wafer and a large gain (Gd > 40). High-speed operation (bandwidth greater than 1 GHz) and low energy dissipation in the attojoules range are discussed together with the technological difficulties to fabricate such a planar molecular triode.

We have built and operated a novel setup for the characterization and identification of gases or vapors based on sequential position readout via a beam-deflection technique from a microfabricated array of eight cantilever-type sensors. Each of the cantilevers can be coated on one side with a dif- ferent sensor material to detect specific chemical interactions. We demonstrate that disturbances from vibrations and turbu- lent gas flow can be effectively removed in array sensors by taking difference signals with reference cantilevers. For ex- ample, H2 can be detected by its adsorption on a Pt-coated sensor because a change in surface stress causes a static bending of the sensor. The diffusion of various alcohols into polymethylmethacrylate induces resonance frequency shifts in a dynamic measuring mode and bending in the static mode, which allows one to distinguish between the various alcohols. Sensor devices for detection of gases and vapors via spe- cific coatings are gradually gaining importance in chemistry, materials science, and biochemistry owing to the increas- ing demand for detection of analytes at monolayer coverage. A field of increasing interest is the construction of so-called "electronic noses" capable of discerning different odors via a typical response pattern of the receptor layers to an analyte. Most devices currently applied involve square centimeter- sized detection areas and comparatively large gas volumes (typically 50- 1000 cm 3 ) resulting in relatively long response

Our ability to manipulate atoms and molecules on an individual basis has opened a new experimental frontier that makes feasible the quest for single molecular-scale devices as successors to the transistor. Here, we discuss our realization of the first amplifier using a single fullerene molecule less than 1 nm in diameter as the active element. This C/sub 60/ molecular device works by electromechanical modulation of virtual resonance quantum mechanical tunneling. The equivalent of the grid is achieved by the purely mechanical action of compressing the C/sub 60/ cage voltage. This action reversibly changes the internal electronic structure of the molecule, increasing its conductance in a continuous manner. The first embodiment provides experimental verification with a measured voltage gain of five. The implications of these results indicate a new approach to electronics on the nanoscale, working in a new transport regime for the three-terminal devices. Going beyond these experiments, we discuss possible approaches of creating single-molecule devices and the advantages they promise.

We describe the first single-molecule electromechanical amplifier, the active element of which is one fullerene molecule (C60) with a junction length and width of ∼ 1 nm. Forces in the nano-Newton range are generated by a metallic tip pressing on the molecule in its adsorbed state. This working nanodevice is based on the modulation of virtual resonance tunneling through the molecule by electromechanical deformation of the C60 cage.

Developments in computing hardware are constrained by the operating principles of complementary metal oxide semiconductor (CMOS) technology, fabrication limits of nanometer scaled features, and difficulties in effective utilization of high density interconnects. This set of obstacles has promulgated a search for alternative, energy efficient approaches to computing inspired by natural systems including the mammalian brain. Atomic switch network (ASN) devices are a unique platform specifically developed to overcome these current barriers to realize adaptive neuromorphic technology. ASNs are composed of a massively interconnected network of atomic switches with a density of ∼109 units/cm2 and are structurally reminiscent of the neocortex of the brain. ASNs possess both the intrinsic capabilities of individual memristive switches, such as memory capacity and multi-state switching, and the characteristics of large-scale complex systems, such as power-law dynamics and non-linear transformations of input signals. Here we describe the successful nanoarchitectonic fabrication of next-generation ASN devices using combined top-down and bottom-up processing and experimentally demonstrate their utility as reservoir computing hardware. Leveraging their intrinsic dynamics and transformative input/output (I/O) behavior enabled waveform regression of periodic signals in the absence of embedded algorithms, further supporting the potential utility of ASN technology as a platform for unconventional approaches to computing.

We demonstrate experimentally with an STM operating in ultra-high vacuum and with model calculations that the current-voltage characteristics of a single C60 molecule are linear at low voltage. This is shown to prevail for tip-surface separations larger than the electrical contact point down to when the molecule is physically compressed by the tip. This linear I(V) relationship of a single molecule holds in general as long as its HOMO-LUMO gap in the junction exceeds the voltage used to define the junction electrical resistance and if the molecule is enough coupled to the electrodes.

We describe a highly sensitive new type of calorimeter based on the deflection of a ‘‘bimetallic’’ micromechanical sensor as a function of temperature. The temperature changes can be due to ambient changes, giving a temperature sensor or, more importantly, due to the heat absorbed by a coating on the sensor, giving a heat sensor. As an example we show the results of using the sensor as a photothermal spectrometer. The small dimensions and low thermal mass of the sensor make it highly sensitive and we demonstrate a sensitivity of roughly 100 pW. By applying a simple model of the system the ultimate sensitivity is expected to be of the order of 10 pW. The thermal response time of the cantilever can also be determined, giving an estimate of the minimum detectable energy of the sensor. This we find to be 150 fJ and again from our model, expect a minimum value of the order of 20 fJ.

The characterization of the first in-plane mode of AlN-actuated piezoelectric microcantilevers was done using different techniques. The top electrode of the cantilever was designed to allow for an efficient electrical actuation of these in-plane modes. The detection of the electrically induced in-plane movement was performed optically with the help of a stroboscopic microscope and electrically by means of an impedance analyzer. The quality factor and the resonant frequencies of the in-plane modes were estimated from the above techniques. Our results show quality factor values as high as 3000 for the first in-plane mode in air.

We describe photon-emission scanning-tunneling-microscopy experiments on polycrystalline silver surfaces. By performing a method of simultaneous photon emission and tunneling spectroscopy measurements, we are able to show that the photon emission process and, in particular, the intergranular contrast in the photon maps depend upon interactions between individual grains in the silver film. Factors known to affect photon emission, such as grain shape and surface morphology, are shown to be inconsistent with the detailed structure of the photon maps. We observe that certain grains behave as isolated entities while others radiate in a more collective manner. This is indicative that for these materials the photon emission behavior is strongly affected by grain-boundary effects and we discuss a recent model which takes these into account.

We present the first observations of nanometer resolution mapping of visible-light emission from 85% porous silicon. Using an STM tip as a local source of electrons to excite cathodoluminescence, simultaneous topographic and light intensity profiles are reported. The photon maps reveal contrast in emission intensity on a scale relevant to the proposed dimensions of the luminescence process (~ 4 nm). We suggest that excitation of individual quantum confinement structures has been observed. The technique overcomes the wide disparity in length scales of the photons ((600 ÷ 900) nm) and the characteristic size of the origins of the luminescence ((1 ÷ 5) nm) which have precluded previous experimental correlations of structural and luminescent behaviour.

The pronounced variation of the intensity of photons emitted from the tunneling gap of an STM with respect to the applied bias voltage V t is studied experimentally using simultaneous measurements of tunneling characteristics and photon emission. We show that the structure in isochromat photon spectra are determined by the following: bias-dependent changes in tunneling characteristics, density of initial and final states, and modifications of tip-induced plasmon modes. It is demonstrated that isochromat spectra provide a conclusive test for the inelastic tunneling mechanism. Coupling between tunneling electrons and tip-induced plasmon modes which gives rise to the intense photon emission observed is discussed within this model

About 80% of US adults have some form of dental disease. There are a variety of new dental products available, ranging from implants to oral hygiene products that rely on nanoscale properties. Here, the application of AFM (Atomic Force Microscopy) and optical interferometry to a range of dentistry issues, including characterization of dental enamel, oral bacteria, biofilms and the role of surface proteins in biochemical and nanomechanical properties of bacterial adhesins, is reviewed. We also include studies of new products blocking dentine tubules to alleviate hypersensitivity; antimicrobial effects of mouthwash and characterizing nanoparticle coated dental implants. An outlook on future "nanodentistry" developments such as saliva exosomes based diagnostics, designing biocompatible, antimicrobial dental implants and personalized dental healthcare is presented.

Light emission observed from noble-metal surfaces in an STM has been interpreted as arising from inelastic tunneling excitation of radiative tip-induced plasmon modes. We discuss recent extensions of this work to clean and oxygen-covered transition metal surfaces. Photon intensities observed in the tunnel mode permit mapping and spectroscopic investigation of sub-nanometer areas of the surfaces of Cu, Fe, and Ti. Our results corroborate the theory developed for noble metals. Contrasts in photon maps on an atomic scale caused by adsorbates are discussed.

We report photoelectron emission characteristics from cesiated gold (110) surfaces illuminated by photons using the tip of a scanning tunneling microscope as a local probe. An analysis of tip current as a function of applied bias permits determination of the maximum kinetic energy of impinging photoelectrons whose value is in good agreement with an independent analysis based on macroscopic measurements of the surface workfunction. Based on our preliminary results, possible schemes for the fabrication of local probe photoelectron analysers for use with synchrotron or laser illumination are developed. Additional physical considerations suggest that liquid environments should in particular introduce a useful exponential dependence of the elastic photoemission signal intensity on tip-surface separation.

We have used a scanning-tunneling-microscope tip as a source of both electrons and holes to study injection luminescence from CdS(112\ifmmode\bar\else\textasciimacron\fi{}0) surfaces cleaved in UHV. Band-gap radiation and emission from radiative deep levels are resolved in optical spectra. Isochromat photon-intensity spectra exhibit, as a function of negative tip voltage, discrete steps which are discussed in terms of pair-creation thresholds. For positive tip polarity, hole creation in the valence band results in a continuous increase in the luminescence. Spatial maps of the resulting integrated light intensity acquired simultaneously with the conventional topographs reveal subnanometer-scale image contrasts which are attributed to defects, such as dislocations or radiative deep levels.

Light emission characteristics from the tunnel gap of a scanning tunneling microscope are used to elucidate the interaction of tunneling electrons with tip-induced plasmon modes on Ag, Au, and Cu surfaces. Enhanced redshifted spectra are observed in the tunneling regime. Model calculations of optical spectra in this range agree well with the experimental data. Isochromat spectra are used to demonstrate that the principal excitation process occurs via inelastic tunneling.

We describe a resistless proximal probe-based lithography technique, which enables the direct patterning of complex and submicron-sized structures of various materials. The method is based on a combination of scanning probe microscopy and the shadow masking technique, whereby structures are locally deposited through pinhole-like apertures situated in the proximity of a cantilever tip. Predefined excursions of the sample lead to the direct fabrication of arbitrary structures on the surface. Complex patterns such as rings and intersecting lines with linewidths well below 0.1 μm are presented.

We demonstrate the mechanical probing of tens of cells simultaneously while an interferometric optical profiler measures both the force of the probes and the response of the cells with nanometer accuracy over a wide field.

Mechanisms for controlled approach of a probe tip toward the sample surface are essential in high resolution imaging by scanning probe microscopy (SPM). This work describes the development and performance of an inertial sliding drive capable of translating a relatively large mass (25 g) at up to 1 mms over 1 cm with step sizes of 10-250 nm in ambient conditions using various wave forms as measured by fiber optic interferometry. The drive functions independent of orientation with a threshold voltage of less than 15 V using a single drive signal. Use of piezotube actuators in a radially symmetric arrangement provides guided motion and minimizes differential thermal expansion between critical components. Controlled translation of the entire scanning component in both ambient and electrochemical scanning tunneling microscopy has been routinely achieved with no evidence of tip crash. This device has been specifically designed for use in in situ SPM applications where stability of the sample and that of the liquid environment are paramount.

Self-organized complex systems are ubiquitous in nature, and the structural complexity of these natural systems can be used as a model to design new classes of functional nanotechnology based on highly interconnected networks of interacting units. Conventional fabrication methods for electronic computing devices are subject to known scaling limits, confining the diversity of possible architectures. This work explores methods of fabricating a self-organized complex device known as an atomic switch network and discusses its potential utility in computing. Through a merger of top-down and bottom-up techniques guided by mathematical and nanoarchitectonic design principles, we have produced functional devices comprising nanoscale elements whose intrinsic nonlinear dynamics and memorization capabilities produce robust patterns of distributed activity and a capacity for nonlinear transformation of input signals when configured in the appropriate network architecture. Their operational characteristics represent a unique potential for hardware implementation of natural computation, specifically in the area of reservoir computing-a burgeoning field that investigates the computational aptitude of complex biologically inspired systems.

Here we report application of imaging interferometry to the study of nanomechanical motion in biosensors and living biological systems. Using strobed interferometric microscopy we are able to probe the dynamic behavior of individual (100 x 500 x 1 micron) cantilevers in an eight cantilever array over frequencies from 0 – 1 MHz. In a related approach, we have developed an interferometric method to measure cell-specific mechanical signals in real time. This yields real-time diagnostic information about cell structure, metabolism and movement, along with response to chemical and physical stimuli. Our new approach makes use of “nanomirrors” fixed to the cell membrane. These mirrors act as nanoscopic displacement probes and can be interrogated, rapidly, by optical profiling metrology. Keywords: Optical profiler, microcantilever, live cell imaging 1. MICRO CANTILEVER DYNAMICS Silicon micro cantilevers are used as transducers for a wide range of physical, chemical and biochemical stimuli, where the exhibit exquisite sensitivity (10

WHEN a material absorbs a photon, a fraction of the energy may be transformed into heat. A measurement of photothermal heating as a function of wavelength can provide an absorption spectrum of the material. We have recently1,2 developed a micromechanical sensor capable of detecting heat changes of the order of picojoules (10-12 J). The instrument incorporates a bilayer cantilever of micrometre dimensions which bends in response to heating. Here we show that this device can be used for photothermal spectroscopy with a power sensitivity of 100 pW—two orders of magnitude better than the sensitivity of conventional photothermal deflection spectroscopy3. The small size of the sensor allows picogram quanti-ties of material to be studied, opening up the possibility of spectro-scopic studies on individual cells and bacteria. Being based on silicon technology, the sensor should be compatible with micro-electronic circuitry.

The tip-surface region of a scanning tunneling microscope (STM) emits light when the energy of the tunneling electrons is sufficient to excite luminescent processes. These processes provide access to dynamic aspects of the local electronic structure that are not directly amenable to conventional STM experiments. From monolayer films of carbon-60 fullerenes on gold(110) surfaces, intense emission is observed when the STM tip is placed above an individual molecule. The diameter of this emission spot associated with carbon-60 is approximately 4 angstroms. These results demonstrate the highest spatial resolution of light emission to date with a scanning probe technique.

The most effective therapy for lung cancer is surgical resection, but it recurs in approximately 50% of patients with early stage disease, with recurrence most commonly presenting as metastatic disease. This suggests that micrometastatic disease is often already present at the time of surgery, but below the level of detection of our current imaging studies. This is consistent with the reports of circulating tumor cells in patients with stage-I non-small cell lung cancer (NSCLC). Although metastatic behavior is often considered a late stage event, these clinical findings suggest that the metastatic process is also operative early in the pathogenesis of the disease. These clinical observations are also consistent with recent laboratory-based investigations indicating that dissemination may occur during early tumor development, particularly in the context of the genetic program associated with epithelial-mesenchymal transition (EMT). Our preliminary studies indicate that a key regulator of the EMT program, Snail, is responsible for both transformation and enhanced motility of human bronchial epithelial cells (HBECs). Cells that over-express Snail (HBEC-Snail) show structural features indicative of enhanced motility, including filopodia, lamellipodia, membrane ruffling, and front-rear polarity. HBEC-Snail cells move with up to 50% greater velocity than vector control cells. We find that HBECs expressing genes associated with EMT or bearing common NSCLC driver mutations (p53/KRAS), show marked heterogeneity in their capacity for cell motility. Greater than an order of magnitude difference between the fastest and slowest moving cells was consistently observed in these cells. We hypothesize that enhanced epithelial cell motility is operative during premalignancy and is a driver of early metastatic dissemination. The overarching objective of this research is to elucidate the fundamental mechanisms involved in epithelial cell motility and their potential impact on disease onset and progression by coupling novel in vitro and in vivo models of human lung carcinogenesis and an innovative motility-based cell isolation technique. As a result of isolating these fast moving cells, we have shown that the selected cells move through transwell membranes at a 45- to 120-fold increased frequency compared to their unselected counterparts. We have also found that cellular deformability relates to a motile phenotype. By using atomic force microscopy (AFM) and deformability cytometry (DC), we have determined that highly migratory HBEC-Snail cells are more deformable than unselected cells. In the future, we intend to implant selected cells into mice to determine if there is a physiologically-relevant transformation- or cancer-associated phenotype, such as decreased time to metastasis or increased final metastatic burden. These are the first investigations to tie the physical traits of cell motility and deformability to lung carcinogenesis and early metastatic behavior. We anticipate that further investigation, including transcriptome analysis of selected cells by RNAseq, will yield a more complete understanding of the molecular determinants of lung cancer pathogenesis, which will stimulate development of more effective chemoprevention and early detection, benefiting those at risk for lung cancer and those with early stage disease. These studies were supported by funding from the following: NIH/NCI #T32-CA009120-36 (SMD, PCP, SJP), NCI #U01CA152751 (SMD, TCW), NCI #U01CA152751-S1 (SMD, TCW, SJP), NCI #U01CA152751-AS (SMD, KK), NIH/NHLBI #T32HL072752 (SMD, EL), Department of Veteran Affairs #5I01BX000359 (SMD), University of California Tobacco-Related Disease Research Program (TRDRP) #22DT-0005 (PCP), TRDRP #18FT-0060 (TCW), and TRDRP #20KT-0055 (TCW), Lung Cancer SPORE #P50CA70907 (JDM, JEL), Packard Foundation Fellowship (DDC). Citation Format: Paul C. Pagano, Shivani Sharma, Sean O'Byrne, Henry T. Tse, Stacy J. Park, Elvira L. Liclican, Kostyantyn Krysan, Tonya C. Walser, Jill E. Larsen, John D. Minna, James K. Gimzewski, Dino Di Carlo, Steven M. Dubinett. Cell motility and deformability in the pathogenesis of lung cancer. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr B15.