Metal doped polyaniline as neuromorphic circuit elements for in-materia computing.

Polyaniline-based atomic switches are material building blocks whose nanoscale structure and resultant neuromorphic character provide a new physical substrate for the development next-generation, nanoarchitectonic-enabled computing systems. Metal ion-doped devices consisting of a Ag/metal ion doped polyaniline/Pt sandwich structure were fabricated using an in situ wet process. The devices exhibited repeatable resistive switching between high (ON) and low (OFF) conductance states in both Ag+ and Cu2+ ion-doped devices. The threshold voltage for switching was>0.8 V and average ON/OFF conductance ratios (30 cycles for 3 samples) were 13 and 16 for Ag+ and Cu2+ devices, respectively. The ON state duration was determined by the decay to an OFF state after pulsed voltages of differing amplitude and frequency. The switching behaviour is analagous to short-term (STM) and long-term (LTM) memories of biological synapses. Memristive behaviour and evidence of quantized conductance were also observed and interpreted in terms of metal filament formation bridging the metal doped polymer layer. The successful realization of these properties within physical material systems indicate polyaniline frameworks as suitable neuromorphic substrates for in materia computing.

Ascent of atomic force microscopy as a nanoanalytical tool for exosomes and other extracellular vesicles.

Over the last 30 years, atomic force microscopy (AFM) has made several significant contributions to the field of biology and medicine. In this review, we draw our attention to the recent applications and promise of AFM as a high-resolution imaging and force sensing technology for probing subcellular vesicles: exosomes and other extracellular vesicles. Exosomes are naturally occurring nanoparticles found in several body fluids such as blood, saliva, cerebrospinal fluid, amniotic fluid and urine. Exosomes mediate cell-cell communication, transport proteins and genetic content between distant cells, and are now known to play important roles in progression of diseases such as cancers, neurodegenerative disorders and infectious diseases. Because exosomes are smaller than 100 nm (about 30-120 nm), the structural and molecular characterization of these vesicles at the individual level has been challenging. AFM has revealed a new degree of complexity in these nanosized vesicles and generated growing interest as a nanoscale tool for characterizing the abundance, morphology, biomechanics, and biomolecular make-up of exosomes. With the recent interest in exosomes for diagnostic and therapeutic applications, AFM-based characterization promises to contribute towards improved understanding of these particles at the single vesicle and sub-vesicular levels. When coupled with complementary methods like optical super resolution STED and Raman, AFM could further unlock the potential of exosomes as disease biomarkers and as therapeutic agents.

Atomic switch networks-nanoarchitectonic design of a complex system for natural computing.

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.

Phenotypic characterization of the foldase homologue PrsA in Streptococcus mutans.

Streptococcus mutans is generally considered to be the principal etiological agent for dental caries. Many of the proteins necessary for its colonization of the oral cavity and pathogenesis are exported to the cell surface or the extracellular matrix, a process that requires the assistance of the export machineries. Bioinformatic analysis revealed that the S. mutans genome contains a prsA gene, whose counterparts in other gram-positive bacteria, including Bacillus and Lactococcus, encode functions involved in protein post-export. In this study, we constructed a PrsA-deficient derivative of S. mutans and demonstrated that the prsA mutant displayed an altered cell wall/membrane protein profile as well as cell-surface-related phenotypes, including auto-aggregation, increased surface hydrophobicity and abnormal biofilm formation. Further analysis revealed that the disruption of the prsA gene resulted in reduced insoluble glucan production by cell surface localized glucosyltransferases, and mutacin as well as cell surface-display of a heterologous expressed GFP fusion to the cell surface protein SpaP. Our study suggested that PrsA in S. mutans encodes functions similar to those identified in Bacillus, and so is likely to be involved in protein post-export.

Identifying individual DNA species in a complex mixture by precisely measuring the spacing between nicking restriction enzymes with atomic force microscope.

We discuss a novel atomic force microscope-based method for identifying individual short DNA molecules (<5000 bp) within a complex mixture by measuring the intra-molecular spacing of a few sequence-specific topographical labels in each molecule. Using this method, we accurately determined the relative abundance of individual DNA species in a 15-species mixture, with fewer than 100 copies per species sampled. To assess the scalability of our approach, we conducted a computer simulation, with realistic parameters, of the hypothetical problem of detecting abundance changes in individual gene transcripts between two single-cell human messenger RNA samples, each containing roughly 9000 species. We found that this approach can distinguish transcript species abundance changes accurately in most cases, including transcript isoforms which would be challenging to quantitate with traditional methods. Given its sensitivity and procedural simplicity, our approach could be used to identify transcript-derived complementary DNAs, where it would have substantial technical and practical advantages versus established techniques in situations where sample material is scarce.

A flexible, highly stable electrochemical scanning probe microscope for nanoscale studies at the solid-liquid interface.

This work describes the design, fabrication, and application of an ultrastable scanning probe microscope for nanoscale studies at the solid-liquid interface, specifically in electrolyte environments. Quantification of system noise limits in the tunneling mode, mechanical drift rates, and lowest mechanical resonance provided values of < or = 10 pA/Hz(1/2), 2 nm/min (XY) and 0.15 nm/min (Z), and 7.9 kHz, respectively. Measurement of the closed-loop transfer function in the tunneling condition demonstrated linear feedback responses up to 4.2 and 2.5 kHz in ambient and electrochemical conditions. Atomic and molecular resolution imagings have been achieved in ambient, in situ, and electrochemical imaging environments at scan rates up to 80 lines/s. A modular design approach has produced a highly flexible microscope capable of imaging and spectroscopy in tunneling, tapping force [amplitude modulation atomic force microscopy (AFM)], and noncontact force (frequency modulation-AFM) modes.

Vertical inertial sliding drive for coarse and fine approaches in scanning probe microscopy.

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.

Observation of nuclear fusion driven by a pyroelectric crystal.

While progress in fusion research continues with magnetic and inertial confinement, alternative approaches--such as Coulomb explosions of deuterium clusters and ultrafast laser-plasma interactions--also provide insight into basic processes and technological applications. However, attempts to produce fusion in a room temperature solid-state setting, including 'cold' fusion and 'bubble' fusion, have met with deep scepticism. 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 alpha-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.

Direct determination of the energy required to operate a single molecule switch.

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.

Single crystals of single-walled carbon nanotubes formed by self-assembly.

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.

Electronics using hybrid-molecular and mono-molecular devices.

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.

Translating biomolecular recognition into nanomechanics.

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.

Photon emission at molecular resolution induced by a scanning tunneling microscope.

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.