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The surfaces of the amorphous metal-metalloid alloy Fe80B20, prepared by melt-spinning and by picosecond pulsed laser annealing, respectively, have been investigated by STM, XPS and AES. The results show that the as-quenched (by melt-spinning) surfaces consist of a non-periodic surface structure comprised of basic structural units ≈ 5 nm in size; these features are absent after laser annealing. The native oxide layers on both surfaces were found to be fully dense with a thickness of ≈ 1 nm. The effect of laser annealing was to producea large enhancement of the boron concentration in the first 0.5–1 nm of the surface and to promote the surface oxidation of boron and iron. The results have been interpreted in the context of the known effects of pulsed laser annealing on the thermal stability of this alloy.

This paper describes how multiple interferometric techniques, implemented on a single system, can be combined to provide viable measurements of both biosensors and cells, enabling collection of data in environments and with timescales not previously achievable.

Low temperature scanning tunneling microscopy studies revealed both monomer and dimer forms of decacyclene (DC) on atomically clean Cu(100) and Cu(111). The observed image contrast in DC is strongly bias dependent and also influenced by tip modifications. Alternatively, dimers appear solely as protrusions and are nearly bias independent. We provide evidence of both dimer formation and dissociation and suggest that two DC molecules stack by aligning their molecular planes in a parallel fashion with respect to the surface. Dimers and their surface-dependent properties demonstrate the interplay between surface-molecule and molecule-molecule interactions.

Airborne chem/bio sensors increase in importance every day for applications in homeland security for the detection of bio-hazardous materials and improvised explosive devices (IED); in the spoilage of food; in the health care industry for detecting cancer, diabetes, and other conditions; and in many other industries. A number of ultrasonic sensors have been developed and used in the chem/bio sensing arena: quartz crystal micro balance (QCM), surface acoustic wave (SAW) resonators, and more recently resonant and simply deflected cantilevers. The capacitive micromachined ultrasonic transducer (CMUT) is a "platform" device that has been investigated in many airborne and immersion ultrasound applications. In this work, we explore the use of the CMUT as a Chem/bio sensor. Because the membrane of a CMUT can be a fraction of a micron thick, and the frequency of operation in the MHz range, it is possible to obtain sensitivity in the order of 1 femto-gram mass loading per cell with proper design. Another important attribute of the CMUT as a chem/bio sensor is that many cells are used to make a sensor which helps improve its false alarm rate over existing sensors where only one resonant element is used. Finally, a high mechanical quality factors (Q) realized in CMUTs which results in very low noise floor, which is necessary to make a very sensitive sensor. An array of CMUTs was made resonant in air at 6 MHz with a Q of 160 and a noise floor of 0.4 Hz in a 1 Hz bandwidth, and where each element consisted of 750 cells. Each cell had a diameter of 30 microns and a silicon nitride thickness of 0.85 microns. Six elements of the array were functionalized with different polymers (PAAM, PEG, PSS, PVA) and the sensitivity of the sensors was measured by flowing different analytes (water, ethanol, isopropyl alcohol, toluene) at different concentrations over the sensors. The frequency shift of each resonator was measured using a frequency counter. The sensor had a volume detection sensitivity of 20 ppb, and a calculated mass loading sensitivity of 1 femto-gram. We will also present results from a new generation of sensors operating in the 25 MHz frequency range and with an expected sensitivity improvement of one to two orders of magnitude over the earlier design.

The design of a monomolecular engine such as a rotating motor first requires the preparation of a semi-classical rotating motion of the rotor part of the engine. We show that this can be achieved either by a careful quantum control of the time evolution of an initially prepared rotating quantum wave packet or by controlling the interaction of the rotor (or stator) with a reservoir. This second alternative is illustrated experimentally through the realization of the rotary motion of a hexa-tert-butyl-decacyclene molecule self-assembled in an homomolecular cavity on an ultraclean Cu(100) surface. The conditions to transform such a molecular rotor into a motor with a given motive power are also discussed.

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.

Microtubules (MTs) are linked to cell mechanobiology. "Stable" and "dynamically unstable" microtubule (MT) subtypes are differentially sensitive to growth and distribution in serum starved (SS) versus full serum (FS) conditions. Atomic Force and Immunofluorescence microscopies were used to study the nanomechanical properties of the cell membrane in response to serum conditions and nocodazole. Nanomechanical properties of the cell membrane remain unchanged under SS/FS conditions even though there are drastic MT changes. The cell membrane is shown to depend on unstable MTs and the intermediate filament (IF) networks to maintain local stiffness. Measurements of local membrane nanomechanics in response to nocodazole display characteristic serum dependent decays. The responses suggest that the cell exists in a mechanical transition state. Stiffness is shown to depend on the interplay between dynamically unstable MTs, stable MTs and IFs which all act to impart a distinct cellular type of transient "metastability".

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

Miniaturized molecular grippers for supramolecular construction are described by Francois Diederich and co-workers on p. 147. These grippers are based on resorcin[4]arene cavitands with four quinoxaline bridges; these macrocycles can be switched between a closed (left) and open (right) configuration via temperature changes, pH changes, or stoichiometric metal-ion complexation. The background is a scanning tunneling microscopy image of a self-assembled monolayer of the closed cavitands. Individual gripper “fingers” are seen as lighter spots, four per gripper, which in turn pack into a well-ordered array. Resorcin[4]arene cavitands with four quinoxaline bridges are a family of macrocycles that adopt, at elevated temperature, a contracted, vase-type conformation, capable of guest inclusion, whereas at low temperature they switch to an expanded, kite-type conformation with a large flat surface. The present investigations lay the foundation for the use of such dynamic cavitands as miniaturized mechanical grippers for supramolecular construction at the single-molecule level. New vase–kite switching modes, stimulated by pH changes or stoichiometric metal-ion complexation, have been discovered and monitored by 1H NMR and optical absorption spectroscopy. The solid-state geometries of the two states have been revealed by X-ray crystallography, and the kinetics and thermodynamics of the switching processes in solution as well as their solvent dependency has been investigated in great detail. Monolayers of the cavitand in the vase form have been studied by scanning tunneling microscopy at molecular resolution; conformational switching is also observed in Langmuir monolayers at the air/water interface. Synthetic protocols have been developed for preparation of partially and asymmetrically bridged resorcin[4]arene cavitands, which are also shown to undergo conformational switching. These synthetic advances pave the way to new, dynamic molecular receptors for steroids, tetrathiofulvalene-bridged grippers with the potential to undergo electrochemically induced conformational switching, and systems with greatly extended, rigid cavity walls functionalized at the termini by dipyrrometheneboron difluoride dyes. The latter cavitands are shown by fluorescence resonance energy transfer to undergo geometrically precisely defined motions between a contracted (≈ 7 A linear extension) and a strongly expanded (≈ 7 nm linear extension) state.

The structure and conformation of a molecule determine its chemical and physical properties. Molecular conformation at interfaces is of particular importance in organic thin films1: in organic optoelectronic devices2,3, for example, charge carrier injection is influenced by interfacial properties4. Here we present a real-space conformational analysis of individual porphyrin molecules using scanning tunnelling microscopy5,6. Porphyrins have been used as model systems to study charge transfer7 and in vivo photoactivation of drug precursors8, and have also been used in organic light-emitting diodes9. We find that changes in the porphyrins' conformation occur predominantly by rotations around the bonds to four tertiary butyl appendages, which differ on different metal substrates. On corrugated gold (110) surfaces, we identify two different conformations as the precursory (metastable) and final states of adsorption. This kind of conformational adaptation to a surface may be general for adsorbed organic molecules, and might have important consequences for the technological applications of organic thin films.

Many methods of reproducing nuclear fusion — the process that powers the Sun — at the table-top scale have been tried, but failed to convince. Remember ‘cold fusion’? More recently, fusion linked to sonoluminescence is still controversial. Now comes a claim from the labs of the University of California at Los Angeles of unequivocal evidence of nuclear fusion in a simple room-temperature experiment. They report that gently heating a pyroelectric crystal — material that becomes charged when heated — causes ionization of a surrounding deuterium gas. The ions bombard a deuterated solid target with such energy that a large neutron signal is detected, a hallmark of deuterium fusion. Though not a viable power source, ‘crystal fusion’ may find application as a generator of neutrons for imaging technology. While progress in fusion research continues with magnetic1 and inertial2 confinement, alternative approaches—such as Coulomb explosions of deuterium clusters3 and ultrafast laser–plasma interactions4—also provide insight into basic processes and technological applications. However, attempts to produce fusion in a room temperature solid-state setting, including ‘cold’ fusion5 and ‘bubble’ fusion6, have met with deep scepticism7. Here we report that gently heating a pyroelectric crystal in a deuterated atmosphere can generate fusion under desktop conditions. The electrostatic field of the crystal is used to generate and accelerate a deuteron beam (> 100 keV and >4 nA), which, upon striking a deuterated target, produces a neutron flux over 400 times the background level. The presence of neutrons from the reaction D + D → 3He (820 keV) + n (2.45 MeV) within the target is confirmed by pulse shape analysis and proton recoil spectroscopy. As further evidence for this fusion reaction, we use a novel time-of-flight technique to demonstrate the delayed coincidence between the outgoing α-particle and the neutron. Although the reported fusion is not useful in the power-producing sense, we anticipate that the system will find application as a simple palm-sized neutron generator.

C60 molecules absorbed on a monoatomic Cu step have been reversibly repositioned at room temperature with the tip of a scanning tunneling microscope by performing controlled displacements along the step direction. We demonstrate the feasibility of building an abacus on the nanometer scale using single molecules as ‘‘counters,’’ Cu monoatomic steps as ‘‘rods’’ that constrain the molecular motion to one dimension, and the scanning tunneling microscope as an ‘‘actuator’’ for counting operations.

A fast and extremely sensitive method for reversible thermal analysis of picoliter volumes of solid samples is presented. Using a micromechanical calorimeter based on the deflection of a bimetallic cantilever, enthalpy changes at phase transitions in n‐alkanes (paraffins) are determined. The key role of volume changes associated with phase transitions is discussed together with a method to separate thermal and volume‐induced stresses associated with these phase transitions.

Encapsulation of hemoglobin (Hb) within red blood cells (RBCs) preserves nitric oxide (NO) bioactivity. With encapsulation, millimolar concentrations of Hb quench only a fraction of NO bioactivity, whereas mere micromolar concentrations of cell-free Hb completely quench NO bioactivity. A submembrane cytoskeletal barrier has been hypothesized to account for the lowered quenching of NO bioactivity. In order to substantiate this hypothesis, here, the underlying submembrane cytoskeletal barrier was physically reduced and the rate of NO entry into the modified RBC measured. The submembrane cytoskeletal barrier of normal and depleted RBCs was characterized using atomic force microscopy and the lipid to protein ratio measured. The reduction in the submembrane cytoskeletal barrier resulted in an increase in the rate of NO entry. We suggest that the underlying submembrane cytoskeleton may be a key component of RBC mediated regulation of NO bioavailability.

Using a noncontact atomic-force and scanning-tunneling microscope in ultrahigh vacuum, we have measured the switching energy of a single molecule switch based on the rotation of a di-butyl-phenyl leg in a Cu-tetra-3,5 di-tertiary-butyl-phenyl porphyrin. The mechanics and intramolecular conformation of the switched leg is controlled by the tip apex of the noncontact atomic-force microscope. The comparison between experimental and calculated force curves shows that the rotation of the leg requires an energy less than 100 x 10(-21) J, which is 4 orders of magnitude lower than state-of-the-art transistors.

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.

Nanoparticles have recently gained increased attention as drug delivery systems for the treatment of cancer due to their minute size and unique chemical properties. However, very few studies have tested the biophysical changes associated with nanoparticles on metastatic cancer cells at the cellular and sub-cellular scales. Here, we investigated the mechanical and morphological properties of cancer cells by measuring the changes in cell Young's Modulus using AFM, filopodial retraction (FR) by time lapse optical light microscopy imaging and filopodial disorganization by high resolution AFM imaging of cells upon treatment with nanoparticles. In the current study, nanomechanical changes in live murine metastatic breast cancer cells (4T1) post exposure to a nanodiamond/nanoplatinum mixture dispersed in aqueous solution (DPV576), were monitored. Results showed a decrease in Young's modulus at two hours post treatment with DPV576 in a dose dependent manner. Partial FR at 20 min and complete FR at 40 min were observed. Moreover, analysis of the retraction distance (in microns) measured over time (minutes), showed that a DPV576 concentration of 15%v/v yielded the highest FR rate. In addition, DPV576 treated cells showed early signs of filopodial disorganization and disintegration. This study demonstrates the changes in cell stiffness and tracks early structural alterations of metastatic breast cancer cells post treatment with DPV576, which may have important implications in the role of nanodiamond/nanoplatinum based cancer cell therapy and sensitization to chemotherapy drugs.

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.

We report the self-assembly of single crystals of single-walled carbon nanotubes (SWCNTs) using thermolysis of nano-patterned precursors. The synthesis of these perfectly ordered, single crystals of SWCNTs results in extended structures with dimension on the micrometer scale. Each crystal is composed of an ordered array of tubes with identical diameters and chirality, although these properties vary between crystals. The results show that SWCNTs can be produced as a perfect bulk material on the micrometer scale and point toward the synthesis of bulk macroscopic crystalline material.

We report the specific transduction, via surface stress changes, of DNA hybridization and receptor-ligand binding into a direct nanomechanical response of microfabricated cantilevers. Cantilevers in an array were functionalized with a selection of biomolecules. The differential deflection of the cantilevers was found to provide a true molecular recognition signal despite large nonspecific responses of individual cantilevers. Hybridization of complementary oligonucleotides shows that a single base mismatch between two 12-mer oligonucleotides is clearly detectable. Similar experiments on protein A–immunoglobulin interactions demonstrate the wide-ranging applicability of nanomechanical transduction to detect biomolecular recognition.

We present quantitative and qualitative detection of analyte vapors using a microfabricated silicon cantilever array. To observe transduction of physical and chemical processes into nanomechanical motion of the cantilever, swelling of a polymer layer on the cantilever is monitored during exposure to the analyte. This motion is tracked by a beam-deflection technique using a time multiplexing scheme. The response pattern of eight cantilevers is analyzed via principal component analysis (PCA) and artificial neural network (ANN) techniques, which facilitates the application of the device as an artificial chemical nose. Analytes tested comprise chemical solvents, a homologous series of primary alcohols, and natural flavors. First differential measurements of surface stress change due to protein adsorption on a cantilever array are shown using a liquid cell.

The recent resurgence of activity in molecular electronics, outlined in this review, has evolved through a number of scientific and economic drivers. This can be partially ascribed to developments in nanoscale science and technology such as new fabrication methods and probes that enable individual molecules or small numbers to be connected into actual test devices. The driving force behind this research is clearly the need for suitable alternative technologies to Si-based CMOS, which is expected to reach its limitations in 10-20 years. Our understanding and concepts of what molecular electronics might look like in the future have changed significantly as a result of all of these factors. (2 pages)

In less than ten years, scanning tunnelling microscopy (STM) has developed into a technique of unsurpassed surface sensitivity allowing vacuum–solid, gas–solid and liquid–solid interfaces to be probed on an atom-by-atom basis. On the other hand, solid–solid interfaces buried in the bulk cannot be directly studied with the STM since the tunnel current that flows between tip and sample – the basis of the technique – is governed by the vacuum gap conductivity of the tunnel barrier. This conductivity is determined by the overlap of the wave-functions between the tip and sample which is a surface effect.

We present a novel chemical sensor based on a microfabricated array of silicon cantilevers. Individual cantilevers are sensitized for the detection of analytes using metal coatings. Analyte molecules chemisorbing or physisorbing on the cantilever coating and chemical reactions produce a change in interfacial stress between analyte molecules and cantilever. This leads to a nanomechanical response of the cantilever, i.e. bending. The bending is read out using a time-multiplexed optical beam-deflection technique. From magnitude and temporal evolution of the bending, quantitative information on analyte species and concentration is derived. Here, we demonstrate the detection of ethene and water vapor with such a nanomechanical nose.

Experimental visualization and verification of a single-molecule rotor operating within a supramolecular bearing is reported. Using a scanning tunneling microscope, single molecules were observed to exist in one of two spatially defined states laterally separated by 0.26 nanometers. One was identified as a rotating state and the other as an immobilized state. Calculations of the energy barrier for rotation of these two states show that it is below the thermal energy at room temperature for the rotating state and above it for the immobilized state.

We present a novel chemical sensor based on a micromechanical array of silicon cantilevers sensitized for the detection of analytes using cantilever coatings such as metals, self-assembled monolayers, or polymers. Chemical reactions are transduced into a mechanical response and read out using an optical beam-deflection technique. Detection of primary alcohols, natural flavors, and water vapor is demonstrated.

Ultraprecise measurement tools are indispensable components for most scientific engineering enterprises and for manufacturing process controls. For such applications, micromechanical devices are potentially very promising because a variety of chemical and physical effects can be transduced into a mechanical response on the nanometer scale. Here we discuss micromechanical cantilever-based devices designed and operated to attain ultimate limits in sensitivity and speed, which is achieved by minimizing the sensor size. Such sensors have been used to analyze an entire range of transduction mechanisms down to the nanogram, picoliter, femtojoule, and attomole level. In particular, we use microengineering technologies to design and fabricate a ?anotechnology olfactory sensor (NOSE) device with a volume of only ≈1 mm3. A new sequential readout technique, the fabrication process of cantilever sensor arrays, and the data acquisition electronics components used for sensor experiments are described in detail.

Thermal analytical techniques are routinely used to study mass variation during desorption, adsorption, or decomposition of materials. We have developed a new micromechanical thermogravimetric technique to investigate femtogram mass changes in nanogram sample quantities upon thermal cycling. This method is based on a cantilevertype microbalance, which is simultaneously used to heat the sample and weigh its mass. New measurements of individual zeolite (ZSM-5) microcrystals having a mass of ≈150 ng as well as corresponding finite-element simulations of the miniaturized chemical analytical system are presented.

Chemical information has been essential to our understanding of all processes and mechanisms in science, engineering, and technology. The increasing importance of laterally confined nanometer-sized structures and objects on surfaces and at interfaces demands both high spatial resolution and nondestructive analytical techniques. This chapter gives an account of the various approaches that have evolved from Scanning Probe Microscopies (SPM), which provide chemical information. In particular, we will discuss what types of chemical information can be acquired using various SPM imaging and experimentation techniques. Specifically we address elemental and molecular composition, reactivity, bonding, adsorption and desorption, and site specificity. It is notable that the combination of different techniques provides reliable information with spatial resolution on the nanometer scale. Finally, we exemplify these cooperative approaches to surface analytical problems, and outline the potential for future developments.

We discuss the controlled translation of individual molecules across a surface in two dimensions under ultrahigh vacuum conditions using scanning tunneling microscopy (STM). Based on STM observations and STM elastic scattering quantum chemical (ESQC) plus molecular mechanic calculations, a number of key features for translation are elucidated including the role of molecular flexure. In particular we suggest that single molecule motion via slip-stick, rolling, sliding, and jumping actions can be produced and visualized at the single molecule limit. Additionally we observe “wear” at the single molecule level where a ligand is removed through the action of pushing the molecule over a step. These unique insights provide the framework for a bottom-up approach to friction accessible to theoretical modeling.

The spontaneous emergence of complex behavior in dynamical systems occurs through the collective interaction of nonlinear elements toward a highly correlated, non-equilibrium critical state. Criticality has been proposed as a model for understanding complexity in systems whose behavior can be approximated as a state lying somewhere between order and chaos. Here we present unique, purpose-built devices, known as atomic switch networks (ASN), specifically designed to generate the class of emergent properties which underlie critical dynamics in complex systems. The network is an open, dissipative system comprised of highly interconnected (∼109/cm2) atomic switch interfaces wired through the spontaneous electroless deposition of metallic silver fractal architectures. The functional topology of ASN architectures self-organizes to produce persistent critical dynamics without fine-tuning, indicating a capacity for memory and learning via persistent critical states toward potential utility in real-time, neuromorphic computation.

Introduction: Cell stiffness (Young's E modulus), as measured via Atomic Force Microscopy (AFM) is a newly recognized characteristic of cancer cells. We previously demonstrated that cisplatin-resistant ovarian cancer cells have a stiffer cell membrane as compared to their syngeneic cisplatin-sensitive counterpart, and that cisplatin increases cell stiffness in cisplatin-sensitive cells. Here we examine the role of Rho GTPase in cell stiffness and cisplatin resistance. Experimental Procedures: Prior to AFM analysis, cells were stained with Annexin V-FLUOS and only non-apoptotic cells were chosen for measurements. Cell stiffness was measured via AFM on live cells in physiological buffer. The actin cytoskeleton was visualized using phalliodin-ATTO 647N. Cells were imaged with a Leica TCS SP5 STED confocal system or a Nikon Eclispe 90i. Cisplatin sensitivity was determined via the XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt] cell viability assay. A nonlinear regression curve fit (one phase exponential decay) was used to analyze cisplatin dose response experiments and determine the IC50 (GraphPad Prism). Rho inhibition and activation were accomplished using Rho Inhibitor I and Rho Activator II, respectively (Cytoskeleton, Inc.). Results: The cisplatin IC50 of cisplatin-sensitive (A2780, OVCAR5, SKOV3) and cisplatin-resistant (CP70, OVCAR5-CisR, SKOV3-CisR, RMG-1) cells correlated with Young's E modulus, with increasing IC50 corresponding to a stiffer cell phenotype. Cells that are resistant to cisplatin displayed an actin cytoskeleton that consisted of long stress fibers that spanned the width of the cell. Rho inhibition in CP70 and OVCAR5-CisR cells abolished this network of actin stress fibers, decreased cell stiffness, and increased cisplatin sensitivity. In contrast, Rho activation in A2780 and OVCAR5 cells induced the reorganization of the actin cytoskeleton into long stress fibers, increased cell stiffness, and decreased cisplatin sensitivity. We demonstrated previously that cisplatin increases cell stiffness in cisplatin-sensitive OVCAR5 cells, and here we show that cisplatin induces actin stress fiber formation in these cells. Conclusions: Rho-mediated actin stress fiber formation increases cell stiffness and mediates cisplatin resistance in ovarian cancer cells. Citation Format: Chintda Santiskulvong, Shivani Sharma, Laurent Bentolila, Jian Y. Rao, James Gimzewski, Oliver Dorigo. The role of Rho GTPase in cell stiffness and cisplatin resistance in ovarian cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2122. doi:10.1158/1538-7445.AM2013-2122

Actin remodeling is an area of interest in biology in which correlative microscopy can bring a new way to analyze protein complexes at the nanoscale. Advances in EM, X-ray diffraction, fluorescence, and single molecule techniques have provided a wealth of information about the modulation of the F-actin structure and its regulation by actin binding proteins (ABPs). Yet, there are technological limitations of these approaches to achieving quantitative molecular level information on the structural and biophysical changes resulting from ABPs interaction with F-actin. Fundamental questions about the actin structure and dynamics and how these determine the function of ABPs remain unanswered. Specifically, how local and long-range structural and conformational changes result in ABPs induced remodeling of F-actin needs to be addressed at the single filament level. Advanced, sensitive and accurate experimental tools for detailed understanding of ABP-actin interactions are much needed. This article discusses the current understanding of nanoscale structural and mechanical modulation of F-actin by ABPs at the single filament level using several correlative microscopic techniques, focusing mainly on results obtained by Atomic Force Microscopy (AFM) analysis of ABP-actin complexes.

Two-dimensional positioning of intact individual molecules was achieved at room temperature by a controlled lateral “pushing” action of the tip of a scanning tunneling microscope. To facilitate this process, four bulky hydrocarbon groups were attached to a rigid molecule. These groups maintained sufficiently strong interactions with the surface to prevent thermally activated diffusional motion, but nevertheless allowed controllable translation. Simulations demonstrated the crucial role of flexure during the positioning process. These results outline the key role of molecular mechanics in the engineering of predefined properties on a molecular scale.

We describe a highly sensitive heat detector fabricated using micromechanics and thin film technology based on the principle of the ‘bimetallic strip’. Bending of the structure induced by local heat pulses is detected by using either a optical position sensitive detection scheme or by the piezoresistive effect as employed in conventional Force Microscopy. We demonstrate that this new device can attain a sensitivity to heat fluxes in the picojoule range. An example is given of the device operating as a highly sensitive calorimeter for observation of the catalytic conversion of hydrogen and oxygen to form water over a platinum surface.

An STM tip tunneling on a metal surface at the appropriate bias voltage is a light source. The mechanism for this effect is inelastic tunneling, whereby a tunneling electron gives a portion of its energy to spontaneously radiative electromagnetic modes. As such, photon emission provides us with a tool to look into inelastic tunneling. Here I review some of the interesting physics underlying this fascinating effect and show how the inelastic tunneling probability is governed by the dielectric and geometric properties of both tip and sample on several length scales. I discuss the experiments with respect to spatial confinement of tip-induced plasmon (TIP) modes, and show how tip-sample distance influences the strength of the electromagnetic modes and inelastic tunneling. Finally I present evidence that suggests the inelastic events occur towards the end of tunneling through the barrier elastically.

The performance of a micromechanical calorimeter is described. Small heat pulses or heat fluxes are detected with a micromachined cantilever. The heat is transported on the cantilever towards the heat sink, causing an inhomogeneous temperature distribution which is determined by the geometry and heat conductivity of the cantilever. Those tiny temperature variations (≈10−5 K) cause deflections according to the principles of bimetallic strips. Different deflection sensors, being all based on force microscopy techniques, are implemented and allow the measurement of distances as small as 0.01A. Calibration procedures, such as heating with laser light and internal ohmic resistors, are applied and compared to a model based on classical mechanics and thermodynamics. By optimizing the geometrical dimensions and material properties, such as heat conductivity and thermal expansion coefficients, the ultimate limits of such a device are estimated on the basis of the model.

STM has been used to examine the morphology of a highly anisotropic substrate, TiO2(100)1×3, including the interaction of steps in the two principal azimuths. The ability of this substrate to align adsorbates so as to produce low-dimensional structures has been investigated. One dimensional arrays of segregated impurities are formed in deep troughs produced by a down step immediately followed by an up step. C60 molecules preferentially occupy sites at the top of the microfacet morphology, which contains Ti3+ species. At higher coverage, the corresponding valleys are populated, forming an epitaxial double layer of fcc C60(110).

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A general method based on the combination of electrostatic force microscopy with thermal cycling of the substrate holder is presented for direct, nanoscale characterization of the pyroelectric effect in a range of materials and sample configurations using commercial atomic force microscope systems. To provide an example of its broad applicability, the technique was applied to the examination of natural tourmaline gemstones. The method was validated using thermal cycles similar to those experienced in ambient conditions, where the induced pyroelectric response produced localized electrostatic surface charges whose magnitude demonstrated a correlation with the iron content and heat dissipation of each gemstone variety. In addition, the surface charge was shown to persist even at thermal equilibrium. This behavior is attributed to constant, stochastic cooling of the gemstone surface through turbulent contact with the surrounding air and indicates a potential utility for energy harvesting in applications including environmental sensors and personal electronics. In contrast to previously reported methods, ours has a capacity to carry out such precise nanoscale measurements with little or no restriction on the sample of interest, and represents a powerful new tool for the characterization of pyroelectric materials and devices.

A procedure for depositing thin films of carbon nanostructures is described that overcomes the limitations typically associated with solution based methods. Transparent and conductively continuous carbon coatings can be grown on virtually any type of substrate within seconds. Interfacial surface tension gradients result in directional fluid flow and film spreading at the water/oil interface. Transparent films of carbon nanostructures are produced including aligned ropes of single-walled carbon nanotubes and assemblies of single sheets of chemically converted graphene and graphite oxide. Process scale-up, layer-by-layer deposition, and a simple method for coating non-activated hydrophobic surfaces are demonstrated.