Sakhrat Khizroev - US grants

The North American Perpendicular Magnetic Recording Conference (NAPMRC) is designed as a highly interactive focused meeting with the purpose to promote accelerated implementation of perpendicular recording. Following the highly successful 1st NAPMRC convened on January 1-9, 2002 in Miami, FL, the 2nd NAPMRC will be held in Monterey, California on January 6-8, 2003.

This proposal will subsidize the registration fee for students from U.S. institutions. Support from NSF will ensure that the program is open to the widest range of interested applicants from the U.S. universities.

Intellectual Merit
In this proposal, investigators seek funding to purchase a Spinstand System an indispensable tool to test and develop next generation magnetic and alternative recording systems. The spinstand system consists of three parts: 1) Spinstand V2002 the latest model by the leader in the field Guzik Corporation unlike the previous models, it uses a piezoactuator, besides linear motors, to position a head with 1-nm accuracy along a specified track; 2) Read-Write Analyzer RWA2004 also the latest model by Guzik Corporation is capable of the maximum data rate of 4 Gigabit/sec (This is the record-high number among the commercial available products.); and 3) Radio-Frequency (RF) Shielded Enclosure by Raymond EMC necessary to protect the measurements from the stray electromagnetic fields. The total cost for the instrumentations is $315,565. With a rapid progress in information technologies today, it is expected that next generation data storage systems (within the next decade) should be capable of storing, recording and retrieving data with an effective areal density of beyond 10 Terabit/in2 and with a data rate of more than 1 Gbit/sec. At such high data density, the entire library of the U.S. Congress can be recorded in a device the size of a regular music CD. The requirements to the mechanical and electrical parts of a system to test next generation recording systems are unconventionally tight. Also, it is imperative to have the maximum possible data rate when dealing with such massive amounts of information. The unique Spinstand system the PIs seek to purchase is capable of testing recording systems with such high data density. In addition, the system offers the best data rate available in the industry today. The PIs plan to purchase the Spinstand system with the purpose to develop next generation data storage technologies including:

1) Magnetic longitudinal and perpendicular recording for areal densities beyond 1
Terabit/in2;
2) Heat-assisted magnetic recording (HAMR) for areal densities beyond 10 Terabit/in2;
3) Patterned media for areal density beyond 10 Terabit/in2;
4) Unconventional Protein-based storage for areal density beyond 10 Terabit/in2;

In the list above, the last three (especially, the protein-based storage) applications are often labeled as high-risk by companies because of their quite unconventional nature. For economical reasons, if possible, companies prefer to concentrate their research and development on truly incremental improvement of the existing technologies.

Broader Impact
The research around the instrumentation is directed to develop next generation data storage systems including both magnetic and unconventional technologies such as protein-based storage. With the purchase of the Spinstand system, the PIs plan to integrate the open academic environment with their experience and strong ties to the industry to develop some of the most high-risk and innovative data storage technologies. In this process, the PIs have a plan to integrate the Spinstand in the state-of-the-art infrastructure they have recently built in their institutions, Florida International University (FIU) and the University of Houston (UH). For example, it should be mentioned that one of the main reasons to purchase the state-of-the-art Spinstand system at FIU is to close the experimentation loop built recently at FIU for the advanced prototyping of Nanoscale magnetic devices. Finally, this research effort goes along with the FIU's recent strategic decision to expand its research activities in the cutting edge areas of science and technology. In addition, the involvement of two universities in this research automatically broadens the field of interest in the results coming from this proposal.

PROJECT SUMMARY
A very broad range of applications of the proposed research topics brings together researchers from different disciplines of science, Electrical Engineering, Mechanical Engineering and Materials Science, Bioengineering, Physics, and Signal Processing. It is believed that this interdisciplinary interaction will result in synergetic activities with the ground-breaking scientific results.

The objective of this Nanoscale exploratory research is to design a deconvolution-optimized probe tip (DOPT) whose nano-dimension resolving abilities drastically exceed that of current probe tips. The efforts of this design will enable measurement, analysis and understanding at levels capable of markedly improving the current state of realizable nanoscale processes and structures. In the probe tip design, we focus on the scanning probe microscopy (SPM) mode of magnetic force microscopy (MFM) because of (1) the inherently poor spatial resolution afforded by MFM (currently 20 nm) relative to other SPM modes and (2) the immediate implications to manufacturing the next generation of magnetic recording media at densities at 1 TeraBit/in2 and beyond (currently at 100 GigaBit/in2 commercially). The interdisciplinary effort required to achieve this resolution-increase necessitates the marriage of nanoscale magnetic physics and digital signal processing since the only way to overcome the physically imposed and resolution-limiting long range magnetostatic interactions between the magnetic media and the probe tip is through deconvolution processing. Tips will be manufactured for both perpendicular and longitudinal magnetic recording media. This effort will be supported by a close collaboration with Seagate Technology.

The research consists of designing and manufacturing a probe tip whose sensitivity response is optimally designed for magnetostatic interaction removal by digital deconvolution processing. The design process will iterate between (1) designing a digital filter from which a sensitivity response can be extracted that meets manufacturing constraints and (2) establishing tip geometries that exhibit the desired sensitivity responses. Of all the manufacturable tips, the best ones will satisfy the favorable design and digital deconvolution processing filter properties of invertibility, compact support size, separability and symmetry. The designs will have accounted for the physical manufacturing restrictions of minimum tolerable sensitivity main lobe width, maximum tolerable sensitivity response extent and sampling period allowable by the MFM machine. The manufacturing consists of focused ion beam (FIB) trimming of conventional MFM tips along with additional treating so that the tip's response is most sensitive to the longitudinal or perpendicular media under study. To assess the resolution increase achieved, atomic force microscopy measurements (known to achieve Angstrom level resolution) and others will serve as the comparative basis. Preliminary results by the PIs in tip fabrication and deconvolution processing are indicative of the resolution promise that the proposed tip design methodology holds.

The integrated research and education effort will allow a host of undergraduate and graduate students alike to contribute to the design process since much of the underlying concepts in the design are obtained in senior undergraduate or first semester graduate courses. Three existing courses in our curriculum will serve as the avenue for presenting and reinforcing research-based concepts through carefully planned class projects that benefit different phases of the research. Project and research results will also be incorporated into a web-based applet for DOPT design enabling other students and researchers to experiment with various configurations and trade-offs. Because FIU has one of the largest minority student (B.S. and M.S.) engineering concentrations on the U.S. mainland, and responding to the minority PI's leadership in this work, minority students will be positively impacted.

The intellectual merit lies in the proposed research being a substantial, unique and innovative departure from the current process of designing nanoscale probe tips. The most fundamental and important accomplishment of this work will be to demonstrate that sensors that are inhererently physically limited by convolutionally-based phenomena can be designed in conjuction with deconvolution processing such that these believed "limitations" are significantly overcome. The 10-fold resolution-increase expected to be achieved results from signal processing corrections to the physically imposed sensor degradations. Because of this, the proposed deconvolution-optimized probe tip promises to allow for rapid technological developments in nanoscale magnetic devices due to the Angstrom level resolution it is expected to achieve.

The broader impacts resulting from this research are that (1) it is believed that this marriage of tip manufacturing and deconvolution processing can be extended to other types of nonmagnetic interactions, such as Van-der-Waals, with analogous benefits and (2) it will act as a catalyst for the commercial magnetic hard disk storage industry to reach the 1 TeraBit/in2 frontier sooner than what might be considered achievable. The broad societal benefits to increasing bit densities to the levels listed are in the production of smaller, lighter weight hard disks and other magnetic memory devices of improved information capacity that would prove useful in portable devices, such as laptop and tablet computers and personal digital assistants (PDAs), and further fuel the push towards ubiquitous use of wireless devices and wireless infrastructure development.

This NER proposal addresses two of the high-risk/high-reward research and education themes that have been identified by NSF: Manufacturing Processes at the Nanoscale and Multi-scale, Multi-phenomena Theory, Modeling and Simulation at the Nanoscale.

The primary goal of the Conference on Nanoscale Devices and System Integration (NDSI) is a highly focused review of the latest progress in the development of nanoscale devices and component integration of nanoscale systems as well as to single out promising trends in the field as a whole. The conference has a single session format with the invited papers forming the body of the conference. The major topics related to nanotechnology including nanoelectronics, nanophotonics, spintronics, nanomagnetics, nanorobotics, nano/bio inspired systems, fabrication at nanoscale, advance lithography, and nanomaterials are showcased at the conference. The conference provides numerous opportunities for networking among the conference participant, thus promoting the generation of new ideas, striking new collaborations, and advancing the nanoscale science and technology as a whole.

Broader Impact: The specific goal of this funding request is to facilitate student attendance of the Conference. The rationale for the funding request is a strong impact that the participation in such conferences makes on student education. The all-invited-speaker format of the meeting allows students to gain an insight into the technology trends as well as to rapidly educate themselves in a broad array of nanotechnology topics. A three-day conference will include approximately 45 invited talks (mornings and early afternoons) and 60 selected contributed poster presentations (evenings). Regular breaks between the sessions, the well received tradition of the past IEEE conferences led by the PI's, enable the students to have fruitful discussions and to network with the leaders in the field.

A panel discussion "Nanotechnology: present and future challenges" will be held on the second day of the conference, April 5, 2005. The panelists from major funding agencies and leading nanotechnology groups will present their views and answer the questions about the trends in nanoscale science and engineering. We believe that participation in such activities is beneficial to the education and future careers of the student attendees.

Intellectual Merit The objective of this proposal is to explore 3-D magnetic recording in order to produce future high-performance memory devices. There is increasing demand for data and this demand will continue to exponentially grow. However, this year for the first time, researchers witnessed that the recorded data in conventional longitudinal magnetic media becomes highly unstable as the areal density increases beyond approximately 100 Gbit/in2. Most of these known alternative technologies are of 2-D nature and promise to defer the superparamagnetic limit beyond one terabit/in2. However, to defer the superparamagnetic limit substantially beyond the one terabit/in2 mark, it will be necessary to stack recording layers in the third (vertical) dimension. The vertical stacking underlies the concept of 3-D magnetic memory - the primary subject of this proposal. Several implementations of a 3-D memory device are proposed. The physics underlying the alternative implementations will be comparatively studied from both theoretical and experimental perspectives. Through these experiments, it is proposed to use focused ion beam (FIB) to fabricate test structures with sub-100-nm dimensions. The focus will be on the study of three components: 1) medium, 2) write and 3) read processes. One of the proposed mechanisms to access data takes advantage of an earlier developed (for perpendicular recording) method to control strong magnetic fields using a "soft" magnetic underlayer (SUL) under the 3-D recording medium. During the write process, the use of the SUL allows to considerably increase the recording field across the entire thickness of the 3-D medium. During the readback process, the "softness" of the SUL strongly influences the sensitivity field (for the Reciprocity Principle) and thus will be used as a mechanism to identify a uni-field plane (2-D layer). To minimize the inter-symbol interference and improve stability, it is proposed to pattern the recording medium in all three dimensions. The physics of 3-D magnetic recording will be also investigated theoretically with Landau-Lifshits-Gilbert-based micromagnetic modeling and Monte-Carlo-based temperature simulations. Magnetic force microscopy (MFM) and optical Kerr Microscopy will be used to study the intergranular interactions in the recording medium. Finally, to learn how to efficiently analyze and read back information from the bulk of the 3-D medium, it is proposed to take advantage of a signal processing technique such as "constrained deconvolution". Basic Co/Pt-based 3-D medium thin-films necessary for this study will be fabricated inhouse using co-sputter deposition. With optical lithography and following FIB trimming, nanoscale bit cells will be tested. To conduct a comparative study of 3-D magnetic recording, Seagate Technology commits to provide additional recording transducers (for further FIB trimming at FIU) and various forms of recording media (patterned via E-beam-based lithography), and help with additional characterization methods. In addition, to support this work, Seagate has offered to donate a 13-chamber sputtering system by Balzers Corporation. The ultimate goal of this project is to develop guidelines to design an adequate 3-D medium and understand the physics of write and read processes.

Broader Impacts This project is interdisciplinary in nature. Its success depends on the adequate integration of the engineering experience in data storage with the understanding of the basic physics of magnetic recording devices and knowledge of advanced data recognition methods. Based at one of the largest minority-serving and one of the youngest research institutions (FIU), this joint project with strong industrial ties promises to boost the research initiatives at FIU and strongly promote the involvement of underrepresented groups in advanced research. Throughout these research efforts, PIs have established a tradition of inviting leading researchers to offer colloquia at FIU. The interest in research on Nanoscale information systems at FIU has significantly grown due current joint efforts. In one year alone, the number of students (mostly minority) involved in the study of nanoscale magnetic devices has grown from one to twelve. As for the technological impact, due to the nature of this project, it will contribute to the advancement of the multi-billion-dollar data storage industry. From a short-term perspective, similar to popular flash memory today, 3-D magnetic memory could be used as a USB-compatible device with significantly higher data capacity. In the long-term perspective, 3-D magnetic memory may replace conventional magnetic hard-drives and other memory technologies, and under the right circumstances may even transform into single-chip computing. Finally, 3-D memory goes well along the expected general future trend of vertical integration.

GOALI: Dynamics and Manipulation of Logic States in Coupled Nanomagnetic Arrays
Dmitri Litvinov
The objective in this research is to study the dynamic properties of the logic gates and data channels based on networks of interacting nanomagnetic cells. Among the projected properties of magnetic cellular logic are high integration density, high speed, room temperature operation, low power consumption, and, significantly, the resistance to ionizing radiation and electromagnetic shock waves.

Intellectual Merit:
The proposed research will constitute the first dynamics study of logic state propagation in magnetic cellular networks. It will contribute to the understanding of signal propagation in coupled nanomagnetic arrays and the interplay between energy dissipation and statistical variations in geometry and materials properties. Utilizing crystalline magnetic anisotropy of advanced materials instead of shape anisotropy to define the states of the cells will open a route to efficient device scalability down to a superparamagnetic limit near 2-3 nm. Furthermore, moving from the sub-micron regime, the proposed research will be the first to enable cells of a size that could be inserted near the end of the semiconductor technology roadmap.

Broader Impacts:
The impact of this research is to contribute to the understanding of the dynamics phenomena in magnetostatically coupled arrays that are of direct relevance to magnetic data storage and magnetic random access memory. The long-term potential of this work, the development of integrated magnetic computing systems, could foster significant advances in information processing rivaling, if not surpassing, the integrated circuit revolution of the past half-century. The students involved in the program will be at the forefront of a fascinating scientific field with broad industrial potential.

The objective of this research is to study the disruptive technology of protein-based disk recording through recording/storing/retrieving information on the surface of a photosensitive protein using near-field optical transducers (nanolasers) and demonstrate the potential for areal densities beyond 10 Terabit/in2. The approach is to integrate unique and unmatched optical properties of photochromic proteins with the state-of-the-art in the emerging field of heat-assisted magnetic recording. These properties include thermal and structural stability of 2-nm molecules with a photocycle with a characteristic transition time of the order of a few picoseconds.

Intellectual Merit:
The emphasis of this multidisciplinary project will be on the device integration rather than the biophysics of proteins. An "apertureless"
near-field optical system will be utilized to focus light into a spot size of less than 30 nm in diameter. To manufacture unique ultra-high throughput nanolasers, as necessary for adequate signal to noise ratio, focused ion beam will be used to define nanoscale apertures on a metal-coated emitting edge of a semiconducting diode.

Broader Impacts
UCR is one of America's most ethnically diverse research institutions. The investigators commit to make every effort to assure diversity among the students involved in this project and especially with the goal to attract more young people in the region of Inland Empire to enroll in Ph.D.
programs. This effort also calls for outreach to K-12 schools. Finally, it is anticipated that the study of the "high-risk" protein-based memory could not only leapfrog the data storage industry but also revive the national initiative in molecular electronics.

Intellectual Merit
This collaborative GOALI proposal between researchers of the University of California, Riverside (UCR), Florida International University (FIU), MagOasis LLC, and Western Digital Corporation (WDC) presents interdisciplinary research to study three-dimensional (3-D) magnetic recording, a promising and challenging near- and long-term solution to increasing the capacity of electronic and computer devices. Unlike 2-D alternatives, 3-D recording exploits advantages of using a 3rd spatial dimension to store information. The specific goals will include: (i) a study of different modes of 3-D recording, (ii) understanding the physics underlying write processes in 3-D systems, (iii) fabrication of 3-D media with three or more magnetic layers accessible for write/read processes, (iv) a basic study of 3-D media with a focus to understand thermal fluctuations in 3-D structures, (v) an investigation of new data coding channels to gain from the multilevel signal configuration in 3-D recording, and (vi) an industry-standard spinstand testing to demonstrate areal densities above 1 terabit/in2. One of the important research objectives will be to understand the physics of 3-D recording necessary for achieving effective areal densities substantially above 1 terabit/in2. The experimental study, involving (i) extensive fabrication via sputter deposition and combinatorial chemistry synthesis, ultra-high-density patterning via electron beam lithography (EBL), (ii) focused Kerr microscopy and ultra-high resolution magnetic force microscopy, (iii) measurements of heat propagation in 3-D, and (iv) a spinstand study to simulate recording systems, will be supported by numerical simulations to understand the micromagnetics in 3-D systems and a basic theoretical study to devise adequate multilevel data coding methods. Accordingly, the effort will follow a cross-disciplinary direction through involving experts in magnetic recording, materials science, micromagnetic modeling, and signal processing from both academia and industry. Particularly, the project will employ the complementing strengths of five co-investigators with a history of synergetic collaboration including (i) Sakhrat Khizroev at Florida International University (FIU) for Magnetic Recording and Nanofabrication, (ii) Alex Balandin at UCR for Heat Management at Nanoscale, (iii) Ilya Dumer at UCR for Data Coding, (iv) John Oti at MagOasis LLC for Micromagnetic Simulations, and (v) Rabee Ikkawi at Western Digital Corporation (WDC) for Disk Drive Integration and Spinstand Testing, respectively.

Broader Impacts
This project might have a significant impact on the data storage industry especially today when the progress in the multi-billion-dollar industry is facing a fundamental limit to scaling due to thermal instabilities in the recording media. The main targeted deliverable of the project is a cross-disciplinary basic study to demonstrate a record high information density over 1 terabit/in2 using the disruptive technology of 3-D magnetic recording. As one of the pioneering concepts in the broad area of 3-D devices, 3-D recording may pave a way to the new era of 3-D magneto-electronics and 3-D electronics applications in general3. The proposed educational component includes a new university-wide initiative to establish a channel for industry internships for both undergraduate and graduate level students. The connection to the industry will be secured through involvement of John Oti, President of MagOasis LLC, and Rabee Ikkawi, a Principal Engineer of Western Digital Corporation, as the industry Co-PI and Senior Personnel, respectively. UCR is one of America?s most ethnically diverse research institutions with a dominant Asian American body and 35% Hispanic enrollment. FIU is the largest Hispanic serving institution in the mainland U.S.A. The investigators commit to make every effort to assure diversity among the students who work on this project. In particular, they intend to do this in part by recruiting from the student chapters of the Society of Women Engineers, the National Society of Black Engineers, and the Society of Hispanic Professional Engineers, among others. In addition, the PIs have established a tradition of hosting local high-school students to give them tours of state-of-the-art research labs with the goal to attract students to become future engineers. Finally, the PIs intend to organize the next anticipated IEEE Nanoscale Device and System Integration (NDSI)-2012 conference to help broaden the research preparation of current students in the minority serving institutions and further attract talent with an emphasis on underrepresented students.

Program Director's Recommendation
1338922 Florida International (FIU); Rishe

The proposal requests Phase II funding for the Florida International University (FIU) to remain as an active site in the Center for Advanced Knowledge Enablement (CAKE). FIU at CAKE is the lead institution while Florida Atlantic University (FAU) Is a "Partner" site.

The faculty of the I/UCRC CAKE will carry out research in performance studies, benchmark evaluations, and the application of novel algorithms, routines, data models, network analyses and software tools to large-scale data sets. The research will be conducted by faculty at Florida International University (FIU), as well as the I/UCRC CAKE's ongoing affiliated sites, who are investigating a broad range of aspects of the science of data management and search. The Center, which will continue to be administratively hosted at FIU, expects to grow to include other domestic and foreign university partners.

The research proposed by the Center addresses challenges that cross scientific domains and vertical markets, as many industries are facing existential problems due to the sheer influx of data generated. The Center broadens participation of underrepresented groups in several ways. The investigators will Leverage their track record of involving FIU's predominantly Hispanic student population in research with programs such as 'affinity groups' that enable research performed by the graduate and undergraduate students to be shared with other students; the Center will expand opportunities of mentoring and graduating computer scientists from under-represented populations at the BS, MS, and PhD levels. As the I/UCRC CAKE continues to grow, the center will build a cohesive structure spanning multiple institutions, in part by enabling extended research visits at partner sites for faculty and doctoral students. The Center plans to include other US universities and international collaboration in the framework of its Latin American Grid Project, an existing NSF PIRE, and other work with European and Asian universities.

The human circulatory system can deliver a drug to every cell in the body; however, bringing a drug inside a tumor cell without affecting the healthy cells remains a formidable task. Availability of a technology capable of high-specificity delivery of anti-neoplastic drugs would be a breakthrough in cancer research. The objective of this research is to conduct basic in-vitro and in-vivo studies to understand the underlying physics of drug-loaded magneto-electric nanoparticles (MENs) at highly localized tumor sites. The engineering approach lies in increasing the porosity of the cell membrane, via application of a low-energy magnetic field, to allow the drug to penetrate inside the cancer cells without affecting the surrounding healthy cells. The proposed approach will form a basis of a novel external-field-controlled procedure to treat various cancers, including ovarian, breast and lung. An important goal of the project is to motivate students, especially underrepresented minorities at FIU and in South Florida, to pursue cross-disciplinary degrees at the intersection of nano-engineering and medicine. The interdisciplinary research team includes an electrical engineer, a gynecologic oncologist, a clinical pharmacologist and a cellular biologist.

In ovarian cancers, intraperitoneal delivery through a surgically implanted catheter has shown improved survival rates. However, catheter complications and toxicity have precluded widespread adoption of this technique. In this study, a new nanotechnology is proposed to take advantage of (i) the difference between the membrane electric properties of cancer and healthy cells, and (ii) the capability of magneto-electric nanoparticles (MENs) at body-temperature to serve as localized converters of a remotely supplied magnetic field into the MENs' intrinsic electric fields that can trigger local nano-electroporation effects. The technique allows to remotely control the electric fields in the vicinity of intravenously injected MENs-loaded drug and consequently to enable drug delivery with required specificity to the tumor cells. Electroporation will be used to deliver a drug inside the cytosol via application of high enough electric field to overcome the threshold required for increasing the porosity for drug penetration inside the cell. The required specificity is due to the lower threshold of the cancer cells being by at least a factor of two than that of the healthy cells. Scanning probe microscopy and comprehensive surface spectroscopy will be used to understand the pharmacokinetics and pharmacodynamics of the MENs' interaction with both the cancer and healthy cellular microenvironment under different field conditions. Ovarian cancer will be used as a model with nanoparticles core shell of cobalt iron titanate and barium titatnate as basic MENs in conjunction with paclitaxel as a popular mitotic inhibitor drug. Standard assays will be used to study the MENs' toxicity under different field conditions. A mouse animal model will be exploited to conduct in-vivo studies.

The broader impact/commercial potential of this project will go beyond wearable sensors. This project is expected to yield significant societal benefits on health and quality of life, as the proposed technology will be able to support the safe powering and communication of novel wireless systems that will enable next generation applications; including, implantable or wearable biomonitoring of senior people in assisted living, pacemakers, drug delivery, artificial organs, bionics for people with disabilities and injured military personnel, and novel treatments for cancer and brain disorders. This project is also expected to revolutionize other commercial applications, such as, wireless sensors for structural health monitoring and environmental monitoring. In addition, this project is expected to broaden broadening the participation of underrepresented groups through Senior Design projects on wireless powering and outreach efforts.

This Small Business Technology Transfer Research (STTR) Phase I project will generate the required technological knowledge for deriving the first miniaturized wireless power transfer systems, which can simultaneously and safely transmit power to and communicate with wearable devices and sensors, with unprecedented power transfer efficiency, bandwidth and alignment-insensitive characteristics. Therefore, this project is expected to have a significant impact on the development of new and/or conformal wearable battery-less devices that support novel biomonitoring, diagnostic techniques and therapies and enhancing our capabilities for disease prevention and treatment. This project is also expected to lead to the first generation of truly autonomous wireless implantable devices for various applications such as smart medicine activation, artificial organ enhanced performance and status monitoring.

The GOALI project at the intersection of engineering and medicine aims to address the following gap in the broad area of neurodegenerative diseases. Stimulation of the neural network by electric fields can repair the abnormal neural activity responsible for various neurodegenerative diseases such as Alzheimer's Disease (AD) and many others. Further, recently it has been shown that electric fields have fundamental effects on cell fate and neurogenesis. However, the existing approaches such as (1) direct deep-brain stimulation (DBS) by establishing direct electrical contact to the neural network and (2) less-invasive indirect transcranial magnetic stimulation (TMS) don't provide spatial and temporal resolutions required for adequate control of the neural network at the cellular level to effectively cure these diseases using electricity, without causing any devastating side effects. This project fills this gap by implementing a nanotechnology approach, according to which magnetoelectric nanoparticles (MENs) are used to combine the main advantages of electric and magnetic fields to enable wirelessly controlled high-efficacy, high-specificity and high-selectivity stimulation of selective regions in the brain to treat specific neurodegenerative diseases without any side effects. The potential applications are far-reaching into engineering electromagnetic and multiferroic nanoparticle-driven systems which could impact the emerging field of personalized precision medicine, cognitive neuroscience, neuroimaging, clinical neurology, and psychiatry. The proposed system can help reverse engineer the brain and thus open a pathway to fundamental understanding of the brain. An important component of the project is to motivate underrepresented minorities to pursue cross-disciplinary degrees at the intersection of engineering and medicine. A special emphasis will be made to attract local K-12 and undergraduate students to continue their research at FIU and Indiana University.

The GOALI proposal aims to conduct comprehensive studies to engineer magnetoelectric nanoparticles (MENs) based system for wireless stimulation of local regions deep in the brain to repair disease specific impediments. MENs can bridge local intrinsic electric fields deep in the brain with magnetic fields and thus enable an external control of local electric stimulation for repairing neural circuits locally. Like traditional magnetic nanoparticles, MENs can be used as image contrast agents in magnetic resonance imaging and navigated across the blood-brain barrier via application of magnetic field gradients. In addition, unlike traditional nanoparticles, MENs display an entirely new property due to the presence of a non-zero magnetoelectric (ME) effect. The ME effect, which exists due to coupled magnetostrictive and piezoelectric components, allows to efficiently couple intrinsic electric fields deep in the brain to magnetic fields which in turn can be wirelessly controlled from outside the skull. Thus, MENs allow to use d.c. and a.c magnetic fields for separating the two functions, (i) application of a d.c. magnetic field gradient for image-guided navigation of MENs across BBB and into a disease-specific local region(s) and (ii) application of an a.c. magnetic field to stimulate this local region(s) locally via inducing local a.c. electric fields, respectively. Based on the physics of metastable systems, using a system of electromagnets, the nanoparticles can be effectively maintained in a quasi-diamagnetic state and thus moved to any point deep in the brain for further local electric stimulation via application of a.c. magnetic fields. Due to the ME effect, the image provided by MENs not only contains structural information but also reflects a local electric field due to the neuronal activity. All these effects will be studied in vitro and in vivo using animal models to understand field-controlled local effects of MENs on the underlying mechanisms of activation of neurons and synapses, the cortical neuronal activity, neuronal excitability, and synaptic transmission.

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.

Part 1: Non-technical Description:<br/>The grant’s main objective is to conduct a basic experimental study to understand the feasibility of using a new class of intelligent materials known as magnetoelectric nanoparticles (MENPs) to create a revolutionary technology for high precision wireless deep brain stimulation. Owing to their quantum-mechanical properties, particularly the magnetoelectric effect, MENPs can serve as nanoscale multimodal hubs capable of combining strengths of different fields, while mitigating their weaknesses, to achieve wireless deep brain stimulation with a sub-mm spatial resolution in real time. To date, such capability has not been made possible by any other stimulation technology. Furthermore, by unlocking such unprecedented technology capabilities, MENPs promise to make significant impacts on two large application areas. First, they will allow to treat neurological disorders and diseases, e.g., Parkinson’s, Autism, Alzheimer’s, Major Depression, and others, as well as deadly brain tumors such as glioblastomas at the molecular level, wirelessly and with control levels never available before. Second, by paving a way to wireless brain-machine interface with a record high spatiotemporal resolution, MENPs will enable a wireless connection between the human and artificial intelligence (AI) with record-high spatial and temporal resolutions, thus allowing to create a powerful tool to understand the computing architecture of the human brain and reciprocally, create leapfrog advances in the state of AI. <br/><br/><br/>Part 2: Technical Description:<br/>Unlike any other nanoparticles known to date, MENPs display a non-zero magnetoelectric effect and thus offer a multimodal functionality to electrically, and wirelessly, stimulate neural activity of selected local regions across the entire brain with the spatial resolution in the sub-millimeter size range in real time. The functionality is multimodal because the magnetoelectric effect allows to simultaneously use a combination of remotely controlled magnetic fields, focused ultrasound waves or near-infrared light to generate a spatiotemporal pattern of the local electric field to achieve the required high precision stimulation. Owing to the hybrid approach (magnetics-ultrasound or magnetics-near-infrared) this multimodal application allows to enhance strengths of any of these field modes alone while mitigating their disadvantages. Integration of magnetic fields with the ultrasound and near-infrared modes will be comparatively studied to understand the pros and cons of these two hybrid approaches. In both cases, the magnetic field will be used to deliver most of the energy required to stimulate neurons, while the ultrasound wave or near-infrared light will be used as the second low-energy field mode to define the selected local stimulation region. The experiments using core-shell MENPs made of lattice-matched magnetostrictive core, e.g., CoFe2O4 (cobalt ferrite) and piezoelectric shell, e.g., BaTiO3 (barium titanite) will include two parts: (1) nanoprobe measurements to quantify the multimodal energy addition effects and tailor the key core-shell MENPs’ properties and (2) in vitro studies using hippocampus neuronal cell cultures to understand the interaction of the multimodal effects due to activation by multiple effects on neuronal firing (measured via Ca++ imaging). In addition, we will study the effects of different MENPs’ compositions and surface functionalization on the wirelessly controlled firing capabilities. The two hybrid modes, (i) magnetics-ultrasound and (ii) magnetics-near-infrared, respectively, will be comparatively studied from the perspectives of the required energy, the spatial resolution, the depth of penetration, and the penetration through the skull and the brain tissue. To achieve the aforementioned goals, the GOALI team is made of four experienced researchers with cross-disciplinary backgrounds including (i) a nanotechnology expert who co-pioneered MENPs for medical applications, (ii) a neuroscientist, (iii) a photonics innovator, and (iv) an industry co-investigator who is an accomplished signal processing expert and a co-pioneer (with the principal investigator) of MENPs.<br/><br/>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.