Harold G. Craighead

Impermeable Atomic Membranes from Graphene Sheets

We demonstrate that a monolayer graphene membrane is impermeable to standard gases including helium. By applying a pressure difference across the membrane, we measure both the elastic constants and the mass of a single layer of graphene. This pressurized graphene membrane is the worlds thinnest balloon and provides a unique separation barrier between 2 distinct regions that is only one atom thick.

Brain responses to micro-machined silicon devices

Micro-machined neural prosthetic devices can be designed and fabricated to permit recording and stimulation of specific sites in the nervous system. Unfortunately, the long-term use of these devices is compromised by cellular encapsulation. The goals of this study were to determine if device size, surface characteristics, or insertion method affected this response. Devices with two general designs were used. One group had chisel-shaped tips, sharp angular corners, and surface irregularities on the micrometer size scale. The second group had rounded corners, and smooth surfaces. Devices of the first group were inserted using a microprocessor-controlled inserter. Devices of the second group were inserted by hand. Comparisons were made of responses to the larger devices in the first group with devices from the second group. Responses were assessed 1 day and 1, 2, 4, 6, and 12 weeks after insertions. Tissues were immunochemically labeled for glial fibrillary acidic protein (GFAP) or vimentin to identify astrocytes, or for ED1 to identify microglia. For the second comparison devices from the first group with different cross-sectional areas were analyzed. Similar reactive responses were observed following insertion of all devices; however, the volume of tissue involved at early times, <1 week, was proportional to the cross-sectional area of the devices. Responses observed after 4 weeks were similar for all devices. Thus, the continued presence of devices promotes formation of a sheath composed partly of reactive astrocytes and microglia. Both GFAP-positive and -negative cells were adherent to all devices. These data indicate that device insertion promotes two responses-an early response that is proportional to device size and a sustained response that is independent of device size, geometry, and surface roughness. The early response may be associated with the amount of damage generated during insertion. The sustained response is more likely due to tissue-device interactions.

Future lab-on-a-chip technologies for interrogating individual molecules

Advances in technology have allowed chemical sampling with high spatial resolution and the manipulation and measurement of individual molecules. Adaptation of these approaches to lab-on-a-chip formats is providing a new class of research tools for the investigation of biochemistry and life processes.

Cerebral Astrocyte Response to Micromachined Silicon Implants

The treatment of neurologic disorders and the restoration of lost function due to trauma by neuroprosthetic devices has been pursued for over 20 years. The methodology for fabricating miniature devices with sophisticated electronic functions to interface with nervous system tissue is available, having been well established by the integrated circuit industry. Unfortunately, the effectiveness of these devices is severely limited by the tissue reaction to the insertion and continuous presence of the implant, a foreign object. This study was designed to document the response of reactive astrocytes in the hope that this information will be useful in specifying new fabrication technologies and devices capable of prolonged functioning in the brain. Model probes fabricated from single crystal silicon wafers were implanted into the cerebral cortices of rats. The probes had a 1 x 1-mm tab, for handling, and a 2-mm-long shaft with a trapezoidal cross-section (200-microm base, 60microm width at the top, and 130 microm height). The tissue response was studied by light and scanning electron microscopy at postinsertion times ranging from 2 to 12 weeks. A continuous sheath of cells was found to surround the insertion site in all tissue studied and was well developed but loosely organized at 2 weeks. By 6 and 12 weeks, the sheath was highly compacted and continuous, isolating the probe from the brain. At 2 and 4 weeks, the sheath was disrupted when the probe was removed from the fixed tissue, indicating that cells attached more strongly to the surface of the probe than to the nearby tissue. The later times showed much less disruption. Scanning electron microscopy of the probes showed adherent cells or cell fragments at all time points. Thus, as the sheath became compact, the cells on the probe and the cells in the sheath had decreased adhesion to each other. Immunocytochemistry demonstrated that the sheath was labeled with antibodies to glial fibrillary acidic protein (GFAP), an indicator for reactive gliosis. The tissue surrounding the insertion site showed an increased number of GFAP-positive cells which tended to return to control levels as a function of time after probe insertion. It was concluded that reactive gliosis is an important part of the process forming the cellular sheath. Further, the continuous presence of the probe appears to result in a sustained response that produces and maintains a compact sheath, at least partially composed of reactive glia, which isolates the probe from the brain.

Single cell detection with micromechanical oscillators

The ability to detect small amounts of materials, especially pathogenic bacteria, is important for medical diagnostics and for monitoring the food supply. Engineered micro- and nanomechanical systems can serve as multifunctional, highly sensitive, immunospecific biological detectors. We present a resonant frequency-based mass sensor, comprised of low-stress silicon nitride cantilever beams for the detection of Escherichia coli (E. coli)-cell-antibody binding events with detection sensitivity down to a single cell. The binding events involved the interaction between anti-E. coli O157:H7 antibodies immobilized on a cantilever beam and the O157 antigen present on the surface of pathogenic E. coli O157:H7. Additional mass loading from the specific binding of the E. coli cells was detected by measuring a resonant frequency shift of the micromechanical oscillator. In air, where considerable damping occurs, our device mass sensitivities for a 15 μm and 25 μm long beam were 1.1 Hz/fg and 7.1 Hz/fg, respectively. ...

Mechanical resonant immunospecific biological detector

We have demonstrated high-sensitivity detection of bacteria using an array of bulk micromachined resonant cantilevers. The biological sensor is a micromechanical oscillator that consists of an array of silicon-nitride cantilevers with an immobilized antibody layer on the surface of the resonator. Measured resonant frequency shift as a function of the additional cell loading was observed and correlated to the mass of the specifically bound Escherichia coli O157:H7 cells. Deposition and subsequent detection of E. coli cells was achieved under ambient conditions.

Virus detection using nanoelectromechanical devices

We have used a resonating mechanical cantilever to detect immunospecific binding of viruses, captured from liquid. As a model virus, we used a nonpathogenic insect baculovirus to test the ability to specifically bind and detect small numbers of virus particles. Arrays of surface micromachined, antibody-coated polycrystalline silicon nanomechanical cantilever beams were used to detect binding from various concentrations of baculoviruses in a buffer solution. Because of their small mass, the 0.5μm×6μm cantilevers have mass sensitivities on the order of 10−19g∕Hz, enabling the detection of an immobilized AcV1 antibody monolayer corresponding to a mass of about 3×10−15g. With these devices, we can detect the mass of single-virus particles bound to the cantilever. Resonant frequency shift resulting from the adsorbed mass of the virus particles distinguished solutions of virus concentrations varying between 105 and 107pfu∕ml. Control experiments using buffer solutions without baculovirus showed small amounts (<...

Measurement of mechanical resonance and losses in nanometer scale silicon wires

We present data on nanofabricated suspended silicon wires driven at resonance. The wires are electrostatically driven and detected optically. We have observed wires with widths as small as 45 nm and resonant frequencies as high as 380 MHz. We see a strong dependence of the resonant quality factor on the surface to volume ratio.

Large-Scale Arrays of Single-Layer Graphene Resonators

We fabricated large arrays of suspended, single-layer graphene membrane resonators using chemical vapor deposition (CVD) growth followed by patterning and transfer. We measure the resonators using both optical and electrical actuation and detection techniques. We find that the resonators can be modeled as flat membranes under tension, and that clamping the membranes on all sides improves agreement with our model and reduces the variation in frequency between identical resonators. The resonance frequency is tunable with both electrostatic gate voltage and temperature, and quality factors improve dramatically with cooling, reaching values up to 9000 at 10 K. These measurements show that it is possible to produce large arrays of CVD-grown graphene resonators with reproducible properties and the same excellent electrical and mechanical properties previously reported for exfoliated graphene.

High quality factor resonance at room temperature with nanostrings under high tensile stress

Quality factors as high as 207 000 are demonstrated at room temperature for radio-frequency silicon nitride string resonators with cross sectional dimensions on the scale of 100nm, made with a nonlithographic technique. A product of quality factor and surface to volume ratio greater than 6000nm−1 is presented, the highest yet reported. Doubly clamped nanostring resonators are fabricated in high tensile-stress silicon nitride using a nonlithographic electrospinning process. We fabricate devices with an electron beam process, and demonstrate frequency and quality factor results identical to those obtained with the nonlithographic technique. We also compare high tensile-stress doubly clamped beams with doubly clamped and cantilever resonators made of a lower stress material, as well as cantilever beams made of the high stress material. In all cases, the doubly clamped high stress beams have the highest quality factors. We therefore attribute the high quality factors to high tensile stress. Potential dominant...