Massood Tabib-Azar - US grants

The Electrical, Mechanical and Chemical Engineering Departments and the Materials Science and Physics Departments will participate in this research activity to gain a fundamental understanding of the properties of microelectromechanical devices and systems so as to be able to carry out experimental research. In addition, this group will conduct research to develop improved process technology for fabrication of three dimensional microcomponents and the design of a demonstrative micro-control system. This research program is organized into three components: o mechanical characterization of micro-components made of semiconductors, metal and ceramics, including static, dynamic fatigue, and tribological properties; o development of improved dry etching and multiple layer fabrication processes and studies of assembly techniques of microsystems and; o study and design of a one dimensional displacement control system for biomedical and applications to probe neural activities or as a tool for microsurgery in the brain.

0116345
Eppell
This is a proposal to: (1) build a near-field scanning optical microscope (NSOM) capable of phase, fluorescence, polarization and second harmonic generation modes, and (2) build a modified NSOM that will use a solid metallic tip, rather than a fiberoptic tip, as an aperatureless near field optical probe. The proposed NSOM, having all of the features desired, cannot be purchased commercially. The investigators will purchase all of the major components, and then modify and assemble them to yield the desired instrument. This equipment will be used in a number of biomedical engineering research projects which include studies on: (1) the mineralization of artificial bone, (2) synapse function in neurons, (3) self-assembled fluorosomes for cancer-targeted gene delivery, (4) liquid crystal alignment on solid substrates, and (5) labeled proteins in the membranes of T cells.

PROPOSAL NO: 0403218
INSTITUTION: Case Western Reserve
PRINCIPAL INVESTIGATOR: Tabib-Azar , Massood
TITLE: NER: Solid Electrolytic Flash Memory Devices


Abstract:

The main objective of this exploratory study is to develop a new class of non-volatile ?memory devices based on solid-electrolytes such as CuxS and AgS
These devices are based on nanometer scale metallic wires grown by passing electric currents through electrodes on thin solid-electrolyte films. Very much like mechanical switches the "1" and "0" states of the memory is given by the presence (i.e., high conductance) state or lack (i.e., low conductance) state of a metallic wire between the electrodes. The proposed devices have a simple "cross-bar" geometry that makes them ideal for very large scale integration with high yield. Non-volatile memories are an integral part of "embedded systems" with growing importance in emerging systems where operating systems are stored in non-volatile memories for easy updating.

There are many other applications of the proposed studies in self-organized and forced assembly of nano-objects self-healing and programmable interconnects and break junctions and in weakly-coupled quantum particles for sensing and information processing. The proposed devices can be used to study and demonstrate real-time growth of wires with fractal geometry in optically transparent solid electrolyte films with interesting and important quantized electrical properties.

0652043
Tabib-Azar
The main objective of this research is to design and implement an array of sensing and stimulating electrodes with integrated low-power electronics and telemetry to study dynamics of the nervous system in intact and behaving animals. A minimally intrusive implantable electrode array capable of recording and stimulating at multiple sites in the nervous system will be used. An experimental preparation in which the dynamics of the nervous system (i.e., the activity in single nerve cells) can be readily related to its overall behavior will be used. The novelty of the proposed system is that it will make it possible to record and control neural activity simultaneously through a remote computer interface. In turn, this will allow novel studies of neurodynamics, since it will be possible to examine the response of the nervous system to specific stimuli. For this reason, the electrode array system will be developed for a biological organism whose neural control and biomechanics have been very well characterized, the marine mollusk Aplysia californica. Results of this research will ultimately have broader applications in human neural prostheses.

The design and fabrication of an 8x8 stimulation and sensing electrode array with different electrode geometries and coating materials to optimize recording and stimulation of many Aplysia neurons simultaneously is proposed. In parallel, design and implementation of a low-power data acquisition and telemetry electronics will take place. These devices will be tested separately and together, forming the sense/stimulate telemetry system in vitro and in vivo in isolated ganglia, semi-intact preparations and in intact and behaving animals.

Genetically-encoded reporters of neural activity are a transformative tool for understanding brain function because they allow for the simultaneous measurement of activity across many neurons defined by genetic and anatomical criteria. The current generation of such reporters use light to signal activity, which limits their ability to be used deep in brain tissue and across the full range of neuronal activity. The goals of the project are to overcome these limitations by developing reporter proteins that can be engineered to emit unique electrical or magnetic signals in response to neural activity. The project will also develop sensors that are optimized for detecting these signals from individual neurons in intact brain tissue in the freely-behaving animal. The proposed 'electrogenetic' toolbox will allow neural activity to be recorded with high fidelity from defined cell types across the entire physiological range of neuronal firing rates, from any location in the mammalian brain, and in the freely-behaving animal. This strategy leverages existing and widely available technology for recording electromagnetic signals in the brain, and thus has the potential to be rapidly adopted for a wide range of neuroscience applications.

This project will develop a new strategy for measuring neural activity from genetically-targeted neurons in the intact brain. An interdisciplinary team of investigators will first use gene therapy techniques to express candidate proteins in particular neurons, then will screen for electrical or magnetic signals using conventional electrodes or nanoscale magnetometer probes. Understanding how neurons of a particular type are activated in the behaving animal is crucial for understanding the neural basis of sensation, cognition and behavior. Indeed, the lack of tools for interrogating identified neurons while they are in action is a major impediment to understanding functional neural circuits in the brain. In addition to breaking this impasse in basic science, a potential broader impact of this project is that the tools to be developed in this proposal may provide information leading to improved diagnosis and treatment of nervous system disorders including mental illness, autism, addiction and epilepsy.

Proposal Title: EAGER: Magnetometer Arrays to Map Brain Circuitry
Institution: University of Utah
Abstract Date:04/09/2014

The proposed room temperature magnetometer arrays will enable innumerable applications in discoveries of new brain circuits and understanding brain ailments. The ability to image brain activities in behaving humans currently is carried out by functional magnetic resonance imaging or electro-encephalography or magnet-encephalography in very constrained environments. It will also advance the frontiers of biosensing to a much higher sensitivity levels only accessible by superconducting quantum interference devices (SQUID) and atomic vapor magnetometers. Magnetometer arrays with a fewer devices can be used to detect the onset of epilepsy and will find numerous applications in wireless health monitoring devices. The magnetometer array will have enormous impact in relating brain circuitry and activity to behavior; it will enable imaging the brain under stressfull conditions similar to the stress test for the cardiovascular system. The research will be carried out by two graduate students (one of the students is from an underrepresented group) and the results will be widely disseminated and used demonstrating the principles of bio-magnetism, bio-sensing and bio feedback.

A novel imaging method capable of whole brain imaging at 100 micron resolution and 1 ms temporal resolution that is fully portable and wireless will be developed. Arrays of small (200 micron), low power (<10 nW/device) room temperature micro-electromechanical multiferroic magnetometers with 10^-18 Tesla/Hz0.5 sensitivity will be designed and fabricated. These arrays will be shielded and embedded in a cap and will enable imaging brain activity in behaving humans in our natural environment. Prototypes have already been constructed that perform at better than 10^-15 Tesla/Hz0.5 sensitivity and this project will improve sensitivity by reducing sensor noise with passive and active (feedback) shielding, construct rectilinear arrays of 10,000 magnetometers that can be combined for full brain coverage, and construct telemetry system for wireless communication with the array. Arrays will be validated by unprecedented spatiotemporal resolution of visual cortex allowing high-speed imaging of orientation and ocular dominance columns.

The investigator will develop field-deployable, inexpensive sensors to detect deadly and pathogenic viruses, in general, and Zika virus as a specific example to demonstrate feasibility. The proposed sensors will change their color when they detect specific viruses without any need for recurring DNA sequencing and amplification that requires time and are expensive for global deployment. Zika virus is expected to re-emerge this summer in Latin America and affect our cities such as Miami. The system can be adopted to detection of many other viruses such as Ebola, Crimean Congo hemorrhage fever, and Lassa fever.


Polymerase chain reaction kits are currently available to detect the ZIKV virus but are time consuming and cannot be deployed in rural areas. The investigator is proposing to developing an aptamer hydrogel with embedded complementary strands that attach to the surface proteins of the ZIKV and absorbs them through its porous cavities causing the hydrogel to undergo (100%) volume and (~30%) color change caused by its embedded 50 nm diameter gold nano-particles.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

Because of the current COVID-19 pandemic, there is severe urgency for accurate point-of-care detection of COVID-19. The investigator will develop colorimetric aptamer-based COVID-19 virus sensors that will change their color or visually indicate the presence of COVID-19 on their sensitive surfaces. COVID-19 aptamers will be synthesized and when bonded with COVID-19 will cause a visible change in the sensor that can be viewed with the naked eye. They will also develop COVID-19 sensors that turn ?red? when COVID-19 is present. The sensor surface is functionalized with the COVID-19 aptamers that is in contact with a buffer solution containing fluorescent microbeads. They are also functionalized with COVID-19 aptamers. The beads do not attach to the sensor surface unless COVID-19 is present to bridge them together. In the presence of COVID-19 the bright red microbeads attach to the sensor surface completely changing its color.


Based on extensive experience with similar sensors designed to detect Zika viruses, biofluids such as stimulant urine does not affect sensor?s performance. Heat inactivated COVID-19 will be used in preliminary experiments. They will be obtained from Zeptometrix corporation and they do not require Bio Safety Level 2 (BSL-2) laboratories for handling. Sensors capable of detecting a single COVID-19 virus will also be developed in this study. Tunneling current sensors (TCS), field-effect transistors using COVID-19 conducting channels, terahertz and UV-VIS spectroscopy, DC conductivity sensors, quartz crystal micro balance and micro-electro-mechanical microbalance will also be developed. Terahertz sensors along with their shorter wavelength optical counterparts have the potential to remotely sense COVID-19 without requiring aptamers. The goal is to have a working COVID-19 handheld sensor in 2 months.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.