An Integrated On-Chip System for Nanoliter Molecular Separation and NMR Detection
The goal of this project is the integration of sample injection, capillary electrophoresis, and NMR (nuclear magnetic resonance) detection on a single silicon substrate using MEMS (micro-electro-mechanical systems) fabrication techniques. The integration and microscale dimensions of the system will provide increased separation efficiency, decreased sample volumes (nanoliters), and increased NMR detection coil sensitivity. Most importantly, the precise geometrical control and material choices afforded by using MEMS fabrication techniques will allow optimization of running time, limit of detection, and NMR spectral linewidth.
The goals of this project are twofold. The first is the design, development, and testing of a force-sensitive skin. The finished skin will be capable of conforming to any shape surface and provide touch-sensing capabilities. The second is the use of the skin to study the role of compressive and shear forces distributed against the palmar surface of the hand during grasping activities and to study the role of shear forces in the formation of pressure sores (decubitus ulcers) and surface abrasions in wheelchair-bound subjects.
The goal of this project is to develop new technologies to enable the unique labeling and subsequent automatic sorting of individual embryos. This research will investigate several approaches to the labeling problem including embryo branding and the implantation of a microsized tag on the embryo. Due to the value of bovine embryos and the advantages of group culturing, the prospect of individually labeled embryos is of great interest to breeding services.
The goal of this project is development of novel tactile interface schemes for use by army personnel. One effort will be aimed at demonstrating tactile communication concepts via existing technology, while the second effort (basic research) will focus on an investigation of the mouth as a possible tactile communication site and the potential for the application of micro-electro-mechanical systems technologies to the development of tactile interfaces for the mouth.
RF resonators, also known as RF coils, RF antennas, and electromagnetic probes, are crucial devices for obtaining high-quality magnetic resonance images for clinical diagnosis. In this project, we develop numerical methods for analysis and design of such resonators for MRI applications. Specific mathematical models will be developed for low- and high-field MRI systems, which may include high-frequency phase variation and bioeffect dosimetry for RF fields.
The mathematical basis of tomographic imaging is conventionally rooted in the well-established Fourier or radon transform theories, so that image quality is mainly dependent on how the data space is sampled. In practice, physical and temporal constraints often prevent a sufficient coverage of the data space, resulting in various image artifacts, such as Gibbs ringing, resolution degradation, and various motion effects. This project is aimed at overcoming these problems by developing new model-based imaging techniques that can effectively incorporate a priori information into the imaging process. Application of these techniques to cardiac imaging and functional brain mapping is also addressed.
Magnetic resonance spectroscopic imaging promises to provide an entirely new way to examine the dynamics of human biochemical processes
in vivo
noninvasively. However, its practical applications have been thus far rather limited because of low sensitivity and long imaging time. The primary objective of this research is to develop mathematical methods to effectively utilize the readily available anatomical information to constrain the spectral distribution so that we can reduce imaging time without compromising spatial resolution.
The primary goal of this project is to develop new neural network architectures and learning algorithms useful for multisensory data fusion, recognition of time-varying patterns, and automatic image segmentation. To achieve this goal, work is being carried out to develop a new neuronal model with both regular and modulatory inputs, a new wavelet-based multichannel network architecture, and a dynamical system-based learning rule. Practical issues of hybrid processing with both neural network models and statistical models such as the hidden Markov model are also being investigated in this project.
After two decades of active research, automatic image segmentation remains one of the most challenging problems in image processing and computer vision. This project is aimed at developing a prototype pattern recognition system for automatic segmentation of brain images. This system contains components for multiscale processing, pattern generation, and learning using neural networks. We expect that the computational principles used in building this system will be useful for solving other practical pattern recognition problems.
Magnetic resonance imaging (MRI) systems are one of the most complicated engineering systems ever invented. The primary goal of this project is to develop a virtual laboratory for teaching and learning MRI principles. This lab is based on the World Wide Web so that students can access it from anywhere at any time. It has two major components: a virtual MRI system for students to carry out simulated MRI experiments and a conferencing system for students, teaching assistants, and instructors to interact asynchronously. We expect this lab to provide an effective learning environment for students to conduct virtual MRI experiments and to have asynchronous group discussion.
The primary objective of this project is to develop new signal-processing algorithms for detecting brain activities from functional MRI data. We are investigating a wavelet-transform-based filtering and
t
-test method for signal detection and a multiscale method for image registration and motion correction.
Functional magnetic resonance (MR) techniques provide physiological and biochemical information in a noninvasive fashion. Unlike proton relaxational agents, which act by altering tissue relaxation times (T;i1 and T;i2), functional agents encode physiological information directly in the chemical shift of the NMR active nuclei. We are investigating new functional MR agents to map the partial pressure of oxygen, temperature, or pH in tissues to MR images. The goal is to obtain accurate, localized information
in vivo
within reasonable imaging times. This technology is relevant to radiation therapy and hyperthermia treatment of tumors, where knowledge of local oxygen pressure, temperature, and pH can provide valuable information for optimizing treatment protocols.
The objective of this research is to improve the performance of nuclear magnetic resonance (NMR) microscopy systems by fabricating the radio-frequency (RF) detection coil and preamplifier on a single monolithic GaAs substrate. The RF microcoil will be formed from 4 to 7 turns of a gold conductor in a planar geometry. A simple tuning and impedance matching network will link the RF coil to a single stage, common source configuration, GaAs metal semiconductor field effect transistor (MESFET). The amplifier will be designed for high gain and low noise over the relatively narrow bandwidth needed for NMR signal detection. Gallium arsenide MESFET amplifiers are ideal for this purpose.
The goal of this project is to develop a unique nuclear magnetic resonance imaging microscope (NMRIM) designed to probe the magnetic microstructure of condensed matter and biological systems. The innovative and critical feature of this instrument is the use of planar microcoils fabricated from high-temperature superconductor thin films. This approach links two recently implemented schemes that have successfully enhanced the signal-to-noise ratio in NMR microscopy and microspectroscopy applications: the reduction of detection coil size for enhanced signal sensitivity and the implementation of high-temperature superconductor materials for decreased noise.
The overall goal of this research and development effort is to develop a family of specialized microscopic probes for NMR spectroscopy. The study includes the modeling, design, and construction, followed by experimental testing of, microcoil-based probes with volumes ranging from 5 nL to 1000 nL, each with picomol sensitivity. The major aim is to achieve the spectral resolution necessary for implementation of high-resolution NMR techniques, while maintaining high filling factor for optimal sensitivity.
Liquid chromatography and capillary electrophoresis are powerful and widely used methods of separating complex chemical mixtures into individual components, and NMR spectroscopy is an information-rich chemical detection scheme. However, the relatively poor sensitivity of NMR spectroscopy has limited its application as a detector for microseparations. In this study we propose to develop a new generation of low-volume (5 nL-1 ;gmL) NMR detection cells that employ specially designed RF microcoils to obtain a two order of magnitude improvement in sensitivity.
This project involves the design and fabrication on gallium arsenide substrates of a family of highly sensitive, multiturn planar microcoils for nuclear magnetic resonance (NMR) detection. The microcoils proposed have 1-5 turns, feature sizes of 5 ;gmm to 25 ;gmm, inner diameters from 25 ;gmm to 250 ;gmm, and aspect ratios to greater than 1:1. These microcoils represent the important first stage in the development of an NMR microscope. Using these probes, researchers may for the first time be able to examine cellular-level processes, e.g., drug uptake or metabolic activity, in real time, as it occurs in single cells.
Fast T;i1 mapping techniques can be used to assess the temperature profiles within agricultural products during heating. This can be used as a noninvasive method for assessing efficacy in bacterial kill-rate in foods.
Conventional MRI provides anatomical and spatial information in both medical and nonmedical scanning regimes. Using newly developed agents, we are able to determine noninvasively such measurements as temperature, oxygen levels, and pH. Areas of investigation are chemical synthesis and theoretical modeling of new compounds, optimization of RF coil geometries, and development of post-processing algorithms to increase sensitivity.
The overall aim of this research area is to increase the mass sensitivity of nuclear magnetic resonance by two to three orders of magnitude using extreme miniaturization of the radio-frequency coil used as the detector. Susceptibility matching schemes are being developed to ensure that high-resolution spectra are acquired.
Fluorine- and proton-based phase-transition agents are being synthesized for
in vivo
temperature mapping using magnetic resonance imaging. Applications to hyperthermia treatment of cancer are being investigated.
Combinatorial chemistry is the most recently developed synthetic pathway whereby up to a million new therapeutic drugs can be produced simultaneously. The very small quantities of material (less than 100 pmoles) precludes structural identification by traditional high-resolution NMR. Our efforts are concentrated on designing RF microcoils for operation at high magnetic fields (;mt 11T) for efficient detection of these chemical products.
The aim is to develop microscopic hardware so that single-cell imaging and spectroscopy experiments can be run using the model system
Aplysia californica.
Using techniques such as diffusion-ordered spectroscopy, the physical environment of neuropeptides within vesicles can be determined, giving valuable information on the mode of action of these metabolites.
Using microscopic NMR coils and small magnetic field gradients, the resolution of NMR microscopic imaging can theoretically be improved to 1 to 2 cubic microns. We are investigating the mechanisms which limit resolution and devising new methods to overcome these limitations.