Richard J. Colton

A BIOSENSOR BASED ON MAGNETORESISTANCE TECHNOLOGY

We are developing a biosensor that will measure, at the level of single molecules, the forces that bind DNA-DNA, antibody-antigen, or ligand-receptor pairs together. The Bead Array Counter (BARC) will use these interaction forces to hold magnetic microbeads to a solid substrate. Microfabricated magnetoresistive transducers on the substrate will indicate whether or not the beads are removed when pulled by magnetic forces. By adapting magnetoresistive computer memory technology, it may be possible to fabricate millions of transducers on a chip and detect or screen thousands of analytes. The multi-analyte capability of this portable sensor would be ideal for on-site testing, while the potential to directly gauge intermolecular interaction strengths suggests drug discovery applications.

Atomistic Mechanisms and Dynamics of Adhesion, Nanoindentation, and Fracture

Molecular dynamics simulations and atomic force microscopy are used to investigate the atomistic mechanisms of adhesion, contact formation, nanoindentation, separation, and fracture that occur when a nickel tip interacts with a gold surface. The theoretically predicted and experimentally measured hysteresis in the force versus tip-to-sample distance relationship, found upon approach and subsequent separation of the tip from the sample, is related to inelastic deformation of the sample surface characterized by adhesion of gold atoms to the nickel tip and formation of a connective neck of atoms. At small tipsample distances, mechanical instability causes the tip and surface to jump-to-contact, which in turn leads to adhesion-induced wetting of the nickel tip by gold atoms. Subsequent indentation of the substrate results in the onset of plastic deformation of the gold surface. The atomic-scale mechanisms underlying the formation and elongation of a connective neck, which forms upon separation, consist of structural transformations involving elastic and yielding stages.

Measuring the nanomechanical properties and surface forces of materials using an atomic force microscope

An atomic force microscope (AFM) has been configured so that it measures the force between a tip mounted on a cantilever beam and a sample surface as a function of the tip–surface separation. This allows the AFM to study both the nanomechanical properties of the sample and the forces associated with the tip–surface interaction. More specifically, the AFM can measure the elastic and plastic behavior and hardness via nanoindentation, van der Waals forces, and the adhesion of thin‐film and bulk materials with unprecedented force and spatial resolution. The force resolution is currently 1 nanonewton, and the depth resolution is 0.02 nm. Additionally, the instrument itself is compact and relatively inexpensive.

The BARC biosensor applied to the detection of biological warfare agents.

The Bead ARray Counter (BARC) is a multi-analyte biosensor that uses DNA hybridization, magnetic microbeads, and giant magnetoresistive (GMR) sensors to detect and identify biological warfare agents. The current prototype is a table-top instrument consisting of a microfabricated chip (solid substrate) with an array of GMR sensors, a chip carrier board with electronics for lock-in detection, a fluidics cell and cartridge, and an electromagnet. DNA probes are patterned onto the solid substrate chip directly above the GMR sensors, and sample analyte containing complementary DNA hybridizes with the probes on the surface. Labeled, micron-sized magnetic beads are then injected that specifically bind to the sample DNA. A magnetic field is applied, removing any beads that are not specifically bound to the surface. The beads remaining on the surface are detected by the GMR sensors, and the intensity and location of the signal indicate the concentration and identity of pathogens present in the sample. The current BARC chip contains a 64-element sensor array, however, with recent advances in magnetoresistive technology, chips with millions of these GMR sensors will soon be commercially available, allowing simultaneous detection of thousands of analytes. Because each GMR sensor is capable of detecting a single magnetic bead, in theory, the BARC biosensor should be able to detect the presence of a single analyte molecule.

On the electrochemical etching of tips for scanning tunneling microscopy

The sharpness of tips used in scanning tunneling microscopy (STM) is one factor which affects the resolution of the STM image. In this paper, we report on a direct‐current (dc) drop‐off electrochemical etching procedure used to sharpen tips for STM. The shape of the tip is dependent on the meniscus which surrounds the wire at the air–electrolyte interface. The sharpness of the tip is related to the tensile strength of the wire and how quickly the electrochemical reaction can be stopped once the wire breaks. We have found that the cutoff time of the etch circuit has a significant effect on the radius of curvature and cone angle of the etched tip; i.e., the faster the cutoff time, the sharper the tip. We have constructed an etching circuit with a minimum cut‐off time of 500 ns which uses two fast metal–oxide semiconductor field effect transistors (MOSFET) and a high‐speed comparator. The radius of curvature of the tips can be varied from approximately 20 to greater than 300 nm by increasing the cutoff time ...

Nanoindentation and contact stiffness measurement using force modulation with a capacitive load-displacement transducer.

We have implemented a force modulation technique for nanoindentation using a three-plate capacitive load-displacement transducer. The stiffness sensitivity of the instrument is ∼0.1 N/m. We show that the sensitivity of this instrument is sufficient to detect long-range surface forces and to locate the surface of a specimen. The low spring mass (236 mg), spring constant (116 N/m), and damping coefficient (0.008 Ns/m) of the transducer allows measurement of the damping losses for nanoscale contacts. We present the experimental technique, important specimen mounting information, and system calibration for nanomechanical property measurement.

A DNA array sensor utilizing magnetic microbeads and magnetoelectronic detection

We describe a multi-analyte biosensor that uses magnetic microbeads as labels to detect DNA hybridization on a micro-fabricated chip. The beads are detected by giant magnetoresistance (GMR) magnetoelectronic sensors embedded in the chip. The prototype device is a tabletop unit containing electronics, a chip carrier with a microfluidic flow cell, and a compact electromagnet and is capable of simultaneous detection of eight different analytes.

Quantitative imaging of nanoscale mechanical properties using hybrid nanoindentation and force modulation

In this article, we present a quantitative stiffness imaging technique and demonstrate its use to directly map the dynamic mechanical properties of materials with nanometer-scale lateral resolution. For the experiments, we use a “hybrid” nanoindenter, coupling depth-sensing nanoindentation with scanning probe imaging capabilities. Force modulation electronics have been added, enhancing instrument sensitivity and enabling measurements of time dependent materials properties (e.g., loss modulus and damping coefficient) not readily obtained with quasi-static indentation techniques. Tip–sample interaction stiffness images are acquired by superimposing a sinusoidal force (∼1 μN) onto the quasi-static imaging force (1.5–2 μN), and recording the displacement amplitude and phase as the surface is scanned. Combining a dynamic model of the indenter (having known mass, damping coefficient, spring stiffness, resonance frequency, and modulation frequency) with the response of the tip–surface interaction, creates maps o...

Nucleation, growth, and structure of fullerene films on Au(111)

Abstract The growth of fullerene films by vapor deposition on Au(111) was studied using UHV-STM, LEED, AES, and TOF-SIMS. The fullerenes were found to grow in a layer-by-layer manner. The molecules initially adsorb at intersections of multiple steps and edges of monatomic steps on narrow terraces. As the coverage is increased, periodic arrays of short chains form at steps separating wider terraces with the periodicity determined by the (23 × √3)− Au (111) reconstruction. At higher coverages, hexagonal layers with a lattice constant of 1.0 nm grow out from the steps on both the upper and lower terraces. The adsorption of the fullerenes lifts the reconstruction indicating a strong interaction between the fullerenes and Au(111). STM indicates that two ordered commensurate structures predominate on the Au(111) surface: (1) a layer with a periodicity of approximately 38 Au spacings; and (2) a layer with a (2√3 × 2√3)R30° unit cell. Second layer molecules were found to display no affinity for step edges. On Au(111), the second layer desorbs at 300°C, while the first layer is strongly bound and does not begin to desorb until 500°C. After annealing to 500°C the remaining C 60 is largely disordered. Intramolecular structure was observed within molecules at the step edges and in the hexagonal arrays.

Biosensor based on force microscope technology

We are developing a sensor capable of detecting biological species such as cells, proteins, toxins, and DNA at concentrations as low as 10−18 M. The force amplified biological sensor will take advantage of the high sensitivity of force microscope cantilevers to detect the presence of as little as one superparamagnetic particle bound to a cantilever by a sandwich immunoassay technique. The device, which will ultimately be small enough for hand‐held use, will perform an assay in about 10 min. Lock‐in detection and use of a reference cantilever will provide a high degree of vibration immunity. An array of ten or more cantilevers will provide greater sensitivity and the capability to detect multiple species simultaneously. The force amplified biological sensor also offers the potential of distinguishing and studying chemical species via its ability to measure binding forces.