James K. Gimzewski

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.

Nanomechanical analysis of cells from cancer patients

Change in cell stiffness is a new characteristic of cancer cells that affects the way they spread. Despite several studies on architectural changes in cultured cell lines, 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.

Short-term plasticity and long-term potentiation mimicked in single inorganic synapses

Memory is believed to occur in the human brain as a result of two types of synaptic plasticity: short-term plasticity (STP) and long-term potentiation (LTP; refs 1-4). In neuromorphic engineering, emulation of known neural behaviour has proven to be difficult to implement in software because of the highly complex interconnected nature of thought processes. Here we report the discovery of a Ag(2)S inorganic synapse, which emulates the synaptic functions of both STP and LTP characteristics through the use of input pulse repetition time. The structure known as an atomic switch, operating at critical voltages, stores information as STP with a spontaneous decay of conductance level in response to intermittent input stimuli, whereas frequent stimulation results in a transition to LTP. The Ag(2)S inorganic synapse has interesting characteristics with analogies to an individual biological synapse, and achieves dynamic memorization in a single device without the need of external preprogramming. A psychological model related to the process of memorizing and forgetting is also demonstrated using the inorganic synapses. Our Ag(2)S element indicates a breakthrough in mimicking synaptic behaviour essential for the further creation of artificial neural systems that emulate characteristics of human memory.

Observation of a chemical reaction using a micromechanical sensor

We describe a new form of calorimeter designed for use in gaseous and vacuum environments which can sense chemical reactions with an estimated sensitivity limit of approximate to 1 pJ. The device is based on a micromechanical Si lever coated with a thick layer of Al upon which a sample in the form of a thin layer is fixed or deposited. Heat fluxes are detected by measuring the cantilever deflection induced by the differential thermal expansion of the lever (bimetallic effect) using the optical position sensor from a force microscope. The limit of sensitivity to local temperature changes is approximate to 10(-5) K at 300 K. Using this technique the catalytic conversion of H-2 + O-2 to form H2O over a thin Pt overcoated layer is observed to exhibit self-sustained oscillations in the reaction rate on the macroscopic scale.

A femtojoule calorimeter using micromechanical sensors

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.

Learning abilities achieved by a single solid-state atomic switch.

[*] Dr. T. Hasegawa, Dr. T. Ohno, Dr. K. Terabe, Dr. T. Tsuruoka, Dr. T. Nakayama, Prof. M. Aono WPI Center for Materials Nanoarchitectonics (MANA) National Institute for Materials Science (NIMS) 1-1 Namiki, Tsukuba, 305-0044 (Japan) E-mail: hasegawa.tsuyoshi@nims.go.jp Prof. J. K. Gimzewski Department of Chemistry and Biochemistry University of California, Los Angeles 607 Charles E. Young Drive East Los Angeles, CA 90095-1569 (USA)

Nanostructural and Transcriptomic Analyses of Human Saliva Derived Exosomes

Background Exosomes, derived from endocytic membrane vesicles are thought to participate in cell-cell communication and protein and RNA delivery. They are ubiquitous in most body fluids (breast milk, saliva, blood, urine, malignant ascites, amniotic, bronchoalveolar lavage, and synovial fluids). In particular, exosomes secreted in human saliva contain proteins and nucleic acids that could be exploited for diagnostic purposes. To investigate this potential use, we isolated exosomes from human saliva and characterized their structural and transcriptome contents. Methodology Exosomes were purified by differential ultracentrifugation and identified by immunoelectron microscopy (EM), flow cytometry, and Western blot with CD63 and Alix antibodies. We then described the morphology, shape, size distribution, and density using atomic force microscopy (AFM). Microarray analysis revealed that 509 mRNA core transcripts are relatively stable and present in the exosomes. Exosomal mRNA stability was determined by detergent lysis with RNase A treatment. In vitro, fluorescently labeled saliva exosomes could communicate with human keratinocytes, transferring their genetic information to human oral keratinocytes to alter gene expression at a new location. Conclusion Our findings are consistent with the hypothesis that exosomes shuttle RNA between cells and that the RNAs present in the exosomes may be a possible resource for disease diagnostics.

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.

Photon emission with the scanning tunneling microscope

By placing a photon detector near the tip-sample region of a scanning tunneling microscope, we have measured isochromat photon-emission spectra of polycrystalline tantalum and Si(111)7×7 at photon energies of 9.5 eV. Such spectra contain electronic-structure information comparable to inverse photoemission spectroscopy, but with high lateral/spatial resolution. The implications of this new observation are discussed.

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 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.