Gianluca Lazzi - US grants

The objective of this proposal is to study the feasibility of delivering ultra-high data rates up to 1 Gbits/s to a mobile, wireless node through advances in the design of compact antenna arrays, modulation and error control coding/joint decoding techniques, and signal processing under high data rate and limited computing power environments. The technologies emphasized in our work are (1) novel design methods for patch antenna arrays, (2) recursive, nonlinear decoder structures that employ iterative decoding techniques similar to Turbo decoding, and channel estimation algorithms that utilize preliminary, probabilistic information from the iterative decoders, and (3) computationally ecient adaptation algorithms for estimating and predicting time-varying channel characteristics as well as steering the antenna patterns for nulling the signals arriving from the interfering users in a network. As part of our work, we propose to design and prototype a laptop system that integrates all three components listed above. While our studies will be more general in nature, we plan to use spread spectrum multiple access systems as the base technology for much of the experimental phase
of the work.

0121389
Hughes

The explosive growth in demand for broadband wireless data services has underscored the importance of low-complexity, bandwidth-efficient communication techniques for multipath radio channels. Recent information theoretic results have demonstrated that deploying multiple antennas at both the transmitter and receiver can dramatically increase the capacity of wireless channels. In order to realize the full potential of this approach, it is important to develop new antenna designs and low-complexity signal processing techniques that more fully exploit the space-time structure of multi-input/multi-output radio channels.

The aim of this project is to improve the performance of wireless communication systems by jointly optimizing the antenna array geometry, coding and modulation, and receiver processing. Four general issues are addressed: (1) design of new antenna arrays inspired by information theory; (2) design of space-time constellations that achieve full diversity and preserve channel capacity; (3) low-complexity space-time coding methods based on multilevel serial concatenation; and (4) new scalable receiver architectures for joint iterative space-time decoding and array processing. The proposed research is an interdisciplinary effort in communications, signal processing, and RF antenna design. The ultimate goal of this work is to increase spectral efficiency and reduce the power requirements of wireless communication systems.

With advances in wireless communications, medicine, and biocompatible electronics, novel ideas to
seamlessly integrate information technology and bioelectromagnetics toward the development of wireless
implantable biomedical devices need to be explored. Bioelectromagnetic phenomena are intrinsic to the
vital function of all living tissues, and a thorough understanding of both the internal electromagnetic
fields and the coupling of external electromagnetic fields to the human body represent a challenge that
will significantly contribute to the development of new biomedical devices for the 21st century.
The objective of this proposal is to bring about fundamental advances toward the development of novel
wireless transcutaneous electromagnetic devices for biomedical applications by integrating in the same
framework macro- and micro-scale phenomena. The study will start from considering the development of
suitable antenna systems for power and data telemetry between units internal and external to the human
body, to reach the level of understanding how induced and spontaneous electrical signals can be
meaningfully used in the development of biomedical devices. Macro-scale interactions of exogenous and
endogenous electromagnetic fields in the human body will be interfaced with microbioelectromagnetic
modeling, with the focus on characterizing exposure and excited electrical activity at the cellular and
molecular level. Such studies will help in understanding and elucidating the mechanisms of interaction of
electromagnetic fields with biological tissues, with potential applications to neural responses to
electromagnetic excitations.
Full-wave Finite-Difference Time-Domain based numerical methods will be used for this complete
modeling effort, with integration of quasi-static methods for the low frequency modeling of neural
responses. Experimental systems to test the performance of the developed implantable wireless links will
be fabricated, while computational models of the neural responses will be validated through collaboration
with researchers at Johns Hopkins University.
The impact of the proposed research activity will extend from the development of a epiretinal prosthesis
to restore sight in over 10,000,000 visually impaired to the development of wireless devices for sensing
the daily evolution of cancer. Collaborations with the Johns Hopkins Wilmer Eye Institute and biomedical
companies are already in place to provide the necessary medical help and expertise.
This project will offer a unique research environment with strong interdisciplinary and multi-institutional
collaborations that will provide graduate and undergraduate students an unprecedented exposure to
innovative technologies for the 21st century. New educational approaches aimed to present a broader
system-oriented view of the role of electromagnetics and bioelectromagnetics in today's and tomorrow's
technology will be pursued to expose students early in their career to a new and timely perspective of
careers in engineering electromagnetics and bioelectromagnetics.

Intellectual Merit:
In this seed project, we will
1) prove the feasibility and realize a new class of microfabricated three-dimensional inductive coils for telemetry devices used in biomedical applications;
2) develop microantennas operating in the microwave frequency range for high data transmission rate implantable systems.

We will investigate several unique approaches to create the desired structures for low-frequencytelemetry links (coils) and dual frequency power/data telemetry links (coils and microantennas). These approaches will require both numerical investigation of the coils/antennas and experimental validation of the designed devices.

Broader Impact:
The proposed activity is the result of an interdisciplinary collaboration between
bioelectromagnetics and solid-state researchers. This activity will have an immediate impact on our students that will be exposed to diverse disciplines to develop the next generations' biomedical systems. We anticipate that the proposed SGER will initiate a larger program at NCSU that will use the combined strengths in the bioelectromagnetics and solid-state research areas toward the realization of a new generation of biomedical electronics devices.

ABSTRACT
0312696
Lazzi, Gianluca
North Carolina State

Most wireless communication systems currently employ arrays of single- or dual-polarized
antenna elements, each which is capable of measuring at most two components of the electromagnetic signal. Recent results in communication theory suggest that, in a rich scattering environment, the capacity of wireless links can be dramatically improved by employing co-located, co-polarized antennas that can detect and excite additional components of the electromagnetic field.

Intellectual Merit: The aim of this project is to improve the performance of wireless communications through the use of arrays of vector sensors that can detect or excite up to 6 components of the underlying electromagnetic field. This project is an interdisciplinary effort between radio frequency antenna design and communication theory. Four main issues are addressed: (a) a new class of compact, planar vector-sensor antennas suitable for wireless communication, (b) new computational tools for accurately predicting the performance of such antennas, (c) an information-theoretic study of the capacity of vector-sensor communication systems, in order to quantify their advantages and extract insights into array design, and (d) new modulation, error-control coding, and receiver architectures that exploit the additional
information provided by these antennas. The ultimate goal of this work is to more fully exploit the potential of wireless radio channels, and in the process reduce the power and bandwidth requirements of wireless communication.

Broader Impact: This project is a joint effort between two investigators with established track records in antennas and wireless communication and a successful history of collaboration. This research will have a direct impact on our undergraduate and graduate students by exposing them to an interdisciplinary view of antenna design and wireless communications, seen as an indivisible concept rather than as separate engineering disciplines. This activity further has the potential to significantly impact the next generation of commercial wireless systems, by offering new approaches to reducing power and bandwidth requirements, and by generating a wealth of new concepts in antenna and communication system design.

Recent research on multiple-input multiple-output (MIMO) communications has shown that deploying arrays at the transmitter and receiver can dramatically improve the capacity of wireless multipath channels. Since the physical size of a transceiver is often limited, increasing the number of array elements often requires closer inter-element spacing and leads to signal correlation and mutual coupling. Coupling can profoundly impact the received power, diversity and system capacity. Moreover, this impact depends essentially on aspects of the transceiver design, such as antenna matching and the dominant sources of noise.



Intellectual Merit: This project seeks to develop a systems-level perspective on the design of compact array transceivers for wireless communications. The aim is to understand how antennas, matching networks, amplifiers and communications algorithms interact to determine overall performance, and to jointly optimize the design of these interacting subsystems. Three issues are addressed: (1) channel models which incorporate diverse noise sources, transceiver design and interference from other users for both narrowband and broadband channels; (2) the impact of different noise sources and propagation environments on the fundamental performance limits of coupled MIMO systems, as well as on performance of specific diversity and multiplexing techniques; (3) information-theoretic design criteria to jointly optimize the array, matching, amplifiers and communications algorithms.



Broader Impacts: This multi-disciplinary project combines theoretical studies with experiments using an antenna testbed. The mix of theory and hardware demonstrations will provide opportunities for student participation at all levels. This work has the potential to significantly advance science and engineering by providing a more unified view of the RF front end and by developing new models, communications algorithms and matching techniques which may significantly improve wireless performance.

"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."

The objective of this research is to investigate microfluidic technology as a platform for highly flexible antennas and electronics. The approach is to fill flexible, elastomeric microchannels with a liquid metal that has unique rheological properties. These properties allow the liquid metal to maintain mechanical stability in the channels and to flow in response to deformation (stretching, flexing, wrapping) to ensure electrical continuity while providing significant tunability and conformability.

The proposed devices represent a significant improvement from conventional copper antennas, which cannot be stretched beyond ~2% strain without inducing irreversible damage. This collaborative project will have an impact on applications ranging from wireless devices to biomedical electronics. The research will provide a better understanding of the characteristics and limitations of the proposed systems, and will allow this technology to be incorporated into complex antenna architectures.

The proposed interdisciplinary research will benefit society by leading to advanced electronics that are (i) wearable, (ii) surface conformal, (iii) responsive to external stimuli, and (iv) durable / self-healing. Underrepresented students and undergraduates will be actively recruited for this project through established programs at NCSU. A prototype antenna will be developed as an outreach tool for presentations at the Engineering Open House and NCSU Undergraduate Research Symposium, which collectively attracts more than 1,500 high school and community college students and their parents to campus each year.

Recent neuroengineering research has demonstrated that motor function and sensing in patients that are affected by neurodegenerative diseases can be partially restored by means of electrical neurostimulation. However, electrode arrays currently used to replace endogenous electrical activation present several drawbacks, including exposure of metal contacts to conductive tissue, potential need for excessive charge density to achieve stimulation when electrode size is small, and lack of tolerance with respect to imperfect contact between the electrode contacts and the neural tissue.
The PIs have recently demonstrated that a new class of microcoils can effectively stimulate the peripheral nervous system, leading to the idea that magnetic microstimulators for implantable devices and neuroprostheses can be devised. Since the mechanisms of magnetic stimulation are centered on eddy currents and their gradients, coils do not need direct contact with the tissue and therefore they can be completely insulated, thus avoiding the possibility of material reactions with conductive neural or surrounding tissues. Further, arrays of coils can potentially offer more options to control the shape of the induced magnetic fields, and therefore eddy currents, and their operation is not affected by contact capacitance.

Intellectual Merit: The goals of the proposed work capitalize on our theoretical and experimental findings that contact magnetic stimulation of the nervous system is feasible, and investigate new classes of microcoils and magnetic stimulators that will be particularly suited for micromagnetic stimulation. Specifically, a major goal is to investigate coil geometries that allow control of the microcoil?s magnetic fields; this will increase the magnetic flux density levels well beyond those of traditional coils and alter the orientation of the fields in the proximity of the target neurons. Ferrite-backed microcoil arrays have the potential to provide increased field strength, sharp gradients, and control of the magnetic field needed for selective neurostimulation. In this work, the PIs investigate novel devices that could provide a paradigm shift compared to traditional electrical neurostimulators.

Broader Impacts: This work has the potential to offer a highly innovative solution to peripheral and central system neurostimulation devices. Providing an alternative solution to surface or penetrating electrodes could positively impact a number of implantable systems, which currently suffer from the significant drawbacks of electrical neural stimulation. Besides the important clinical impact, the proposed program offers unique opportunities to train engineering students in a highly interdisciplinary activity at the forefront of engineering technology and medical research. In addition to utilizing the proposed research activity in various existing programs designed to have a lasting impact on current and prospective undergraduate students, the proposed project will increase the interest of engineering students in the emerging field of neuroprosthetics and demonstrate the benefits of engineering to medicine. The PIs will provide additional learning opportunities targeted at K-12, 2-year, and 4-year feeder schools and colleges through outreach programs.

DESCRIPTION (provided by applicant): The end goal of this multiscale modeling research is to bridge the gap existing between three-dimensional, full- wave, macro-modeling of electrical and magnetic biointeractions (global modeling) and cellular-level modeling strategies. Our research team is composed of engineers, neuroscientists, biophysicists, surgeons, and computer scientists that are experts in all computational and experimental aspects necessary to fill the existing gaps in multi-scale modeling. This new multi-university effort to predict spatio-temporal distributions of active neurons based on current densities created by multi-electrode electrical stimulation depends on having a set of core models of molecular (receptor-channel kinetics), synaptic, neuron, and multi-neuron activity. These models and their inputs and outputs must be integrated into a global model of the extracellular media/matrix including relevant multi-electrode arrays. Successful modeling at these levels will allow hypotheses about space-time patterns of electrical stimulation to produce predictions about the number and distribution of activated inputs (based on known spatial distributions of afferent axons). The linked molecular, synaptic, neuron, multi-neuron, and global model will provide the basis for emerging predictions of the spatio-temporal distribution of active neurons and thus, the spatio-temporal distributions of spike train activity that encode all information in the nervous system. Our research effort will capitalize on our accomplishments in the realm of retinal and cortical prostheses, and use these as test beds for the multiscale predictive modeling methods that we will develop within the proposed activity.

Project Abstract The end goal of this multiscale modeling research is to bridge the gap existing between three-dimensional, full- wave, macro-modeling of electrical and magnetic biointeractions (global modeling) and cellular-level modeling strategies. Our research team is composed of engineers and neuroscientists that are experts in all computational and experimental aspects necessary to fill the existing gaps in multi-scale modeling. This multi-university effort to predict spatio-temporal distributions of active neurons based on current densities created by multi-electrode electrical stimulation depends on having a set of core models of molecular (receptor-channel kinetics), synaptic, neuron, and multi-neuron activity. These models and their inputs and outputs must be integrated into a global model of the extracellular media/matrix including relevant multi- electrode arrays. Successful modeling at these levels will allow hypotheses about space-time patterns of electrical stimulation to produce predictions about the number and distribution of activated inputs (based on known spatial distributions of afferent axons). The linked molecular, synaptic, neuron, multi-neuron, and global model will provide the basis for emerging predictions of the spatio-temporal distribution of active neurons and thus, the spatio-temporal distributions of spike train activity that encode all information in the nervous system. Further, we believe the proposed multiscale modeling framework constitutes an ideal platform capable of generating novel insights into the pathogenic mechanisms precipitating abnormal hippocampal function. Although the proposed research is focused on the hippocampal system, our effort will capitalize on our multiscale modeling accomplishments during the performance period of our original multiscale modeling U01 grant, in the realm of both retinal and cortical prostheses.

Project Summary - Abstract Retinal prosthetic devices that use electrical stimulation have been designed in attempt to restore some vision in patients with degenerative diseases, such as retinitis pigmentosa (RP) or age-related macular degeneration (AMD). These devices function by using electrodes to stimulate local regions of retina tissue, approximating spatiotemporal patterns for representing the image facing the patient, intending to induce a pixelated percept. This has proven effective and has led to the design of multiple different prosthetic devices. In this proposal, we will take what we have learned from modeling retinal connectomes and apply them to the modeling of patho-connectomes, or connectomics volumes constructed from pathological or neurally degenerating tissues. The Tg P347L rabbit retina proceeds irreversibly through phases of retinal degeneration, altering programming and remodeling the topology and circuitry of retina. We will develop a connectome-derived submodel of each of the four degenerated states of the rabbit retina, involving the construction of pathoconnectomes of cone to ganglion cell pathways in each stage of degeneration based on TEM images of diseased retina, and the translation of each pathoconnectome to a computational model. Each of the four models will be incorporated in a multiscale hybrid Admittance Method (AM)-NEURON computational method to characterize the impact of the degeneration on neural activation induced by both natural photoreceptors and stimulating electrodes, and compare it with previously obtained results with healthy or synthetically degenerated retina. An accurate model of the degenerated retina integrated in our multiscale solver, as will be developed in the proposed work, can prove an important tool to further improve our understanding of spontaneous neural activity of the retina and support the design of effective electrodes that can incorporate the neural and anatomical information of actual degenerated retina, a task that to the best of our knowledge has never been approached to date.

Retinal blindness, such as retinitis pigmentosa (RP), age-related macular degeneration (AMD), and glaucoma (POAG), is characterized by unrelenting neuronal death (photoreceptor loss in RP and AMD and ganglion cell loss in POAG). These prevalent blinding conditions account for a significant part of the estimated US$139 billion annual economic burden of vision disorders in the U.S. This group has, for the first time, shown that controlled microscale electromagnetic (EM) stimulation can lead to neuroprotective changes in the retina. The transformational vision of this project is to use non-invasive controlled electrical stimulation to induce genetic changes in the mammalian retina to slow down the progression of retinal blindness and perhaps even restore some level of the lost vision. The success of such an approach would spawn a whole new area in basic science, engineering, and medicine and in doing so develop new, innovative, cross-disciplinary educational programs critical to foster the next-generation of researchers of bioelectronic devices to affect protective genetic changes.


A number of mechanisms have been identified as to why neuronal death occurs in different retinal blinding disorders (e.g., genetic mutations in RP, lipid metabolism abnormalities and inflammation in AMD, and elevated intraocular pressure in POAG to name a few). This group has shown that controlled microscale electromagnetic (EM) stimulation can lead to epigenetic retinal changes with implications for neuroprotective changes. The hypothesis of this proposal is that neuroepigenetic and chromatin remodeling of the retina induced through controlled electrical stimulation is a key molecular determinant of neuroprotection and could prove to be pivotal for the treatment of certain retinal blindness conditions. The vision of this proposal is that the findings will demonstrate how stimulation using electromagnetic (EM) fields can be effectively adopted to slow or halt the progression of prevalent retinal diseases.

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.

The goal of the proposed effort is to develop and make available to the scientific community a modular, integrated, multiscale computational modeling framework that will allow the user to design safe and effective peripheral neurostimulators. The multiscale computational framework is based on the seamless integration of multiple computational modules/platforms particularly suited for integration: (a) a multi- resolution, frequency-domain, large-scale electromagnetic field modeling platform based upon our Admittance/Impedance Method (AM/IM) for the prediction of fields and currents induced in the neural tissue by arbitrary neurostimulators; (b) micron-resolution computational models of the bulk electrical and magnetic properties of axons and their excitation in peripheral nerve models of mammalians using NEURON software, coupled in space and time to the Admittance/Impedance Method; (c) a computational tool for the estimation of direct, electrically or magnetically-induced, tissue and neural damage due to arbitrary, user-defined, peripheral neurostimulators and waveforms and for the estimation of activity- based early axonal damage (EAD) based on correlation with experimentally observed damage in chronically implanted neurostimulators. The development of the proposed modules will provide the most complete predictive software framework available to assess acute and activity-based safety of peripheral neurostimulators due to parameters including electrode geometric::al features, charge density, charge per phase, frequency of stimulation and thermal increase. To the best of our knowledge, there is no computational method readily available that addresses both the effectiveness of the neurostimulator (modeling of the excitation in peripheral nerve models due to arbitrary electrode geometries and waveforms) and the safety of the neurostimulator both at the large-scale (electromagnetic tissue models of the human body based on high-resolution, dielectric properties- based, discretized computational models) and at micron-resolution (neural level). The proposed effort will consists of a) generation of computational models of peripheral nerves; b) development of the computational modules and platform; and c) experimental verification of the predictive capabilities of the computational models and platform.

This project proposes to use in silico simulations to engineer nanoscale, biocompatible, protective barrier that will enhance our first line of defenses - prevention of pathogenic infection from entering and infecting the host. The principal investigator aims to develop a topical method that will enhance protection against virus attachment onto the nasal and oral as well as conjunctival epithelial cells, while preserving normal physiology and biochemistry. The project team will use computer models to engineer delivery devices to produce the optimal particle characteristics to maximally prevent microbial infection. If successful, this project can lead to paradigm changing alternatives to reducing public health risk to air borne infections like COVID-19 and seasonal flu which may be associated with devastating effects on the United States and World economy. The proposed approach will be swiftly conducted to present realistic solutions that may be useable in the face of this COVID-19 pandemic as well as future flu viruses of similar magnitude.

This research will fundamentally contribute to modeling the interactions between viral membranes and nanoscale barriers. The production of an innovative nanoscale biodegradable barrier may reduce the socioeconomic and public health burden significantly by lowering the risk of viral infection during the flu season or pandemics. The project team comprise of an interdisciplinary team that include engineers, ophthalmologists, molecular biologist, virologist and pharmacologist to explore a problem that could have a tremendous impact on the way we respond to seasonal flu or pandemics. Besides the potential benefits to reduce COVID-19 and influenza related deaths in the US and worldwide, the proposed work will afford us the opportunity to train engineering and biomedical students in a highly interdisciplinary research activity.

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.

PROJECT SUMMARY / ABSTRACT Increasing evidence suggests that electrical stimulation may be efficacious for Alzheimer's disease (AD); however, mechanistic explanations in support of the potential effect of stimulating electric fields for the treatment of AD are almost completely lacking. Importantly, there are currently no multiscale computational platforms and connectomic models to use to predict the current spread in anatomically correct neural tissue and potential electrical damage to it due to DBS electrodes. This lack of predicting capabilities significantly hinders the further development of this technology, which is primarily subjected to empirical observations guiding the search for answers. The goal of the proposed effort is to develop and make available to the scientific community a modular, integrated, multiscale computational modeling framework, informed by and verified through in-vivo experimental studies, that facilitates the design of safe and effective deep brain stimulators (DBS) for AD. This computational platform comprises global models of the extracellular media, including multi-electrode arrays and neurostimulators in general, as well as neuron modeling, which will provide the basis for emerging predictions of safe CNS neurostimulation. The proposed effort leverages the computational modules and model discretization strategies being developed in a parent R01 dedicated to the development of predcitvive multiscale computational methods for the stimulation of the peripheral nervous system. The proposed supplement begins the much needed development of both models and paired computational platform toward the goal of offering to the AD research community a versatile and modular software package to address the uncertainties associated with DBS of forniceal and hippocampal tissue. This project is the beginning of the roadmap to develop predictive tools that can be used by the community to treat AD with DBS.

Despite enormous advances in recent years to develop neuroprosthetics to bypass damaged areas of the Central Nervous System (CNS), these devices fail to halt the progression of the underlying degenerative diseases for which they were designed. Moreover, there are no effective therapies for many of the neurodegenerative conditions that affect, for example, the eye or the brain, and the humanitarian and economic impact of blinding diseases and dementia are enormous, with underrepresented groups particularly impacted by these conditions. The goal of this project is to enable restoration of function to the CNS by therapies that promote the repair and regeneration of damaged neurons and neural networks instead of bypassing damaged areas. To achieve this goal of delaying vision loss and neural degeneration in dementia through devices this team brings together engineers, surgeons, neuroscientists and big data/imaging scientists.

This research team will devise and optimize, experimentally and computationally, the electrical stimulation waveform characteristics needed to reprogram damaged neural network morphologies; create, “first of its kind” complete mesoscale connectivity atlases of the global neural networks exposed to electric fields and field gradients; develop predictive multiscale computational models of neural activity in healthy, degenerated and electrically stimulated neural networks; and design and engineer programmable implantable electronic systems for the acute neurostimulation of the neural tissue. The utility of the tools developed in the proposed effort will be enhanced by end-users providing design input, thus facilitating fully integrated, mutually beneficial, sustained convergent collaborations that are needed to develop the therapeutic opportunities of the next generation.

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.

The Coronavirus Disease 2019 (COVID-19) pandemic has dramatically impacted the way humans live and has resulted in more than 6 million deaths worldwide. This project uses a topical barrier to enhance the defense capabilities of the lining found in the nose, which is a highly novel method to prevent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) infections. The aim of this EArly-concept Grant for Exploratory Research (EAGER) project is to engineer a nasal spray and new type of applicator that can deliver a special coating that prevents viral and microbial infection. This user-friendly approach, if further developed, has the potential to be effective in preventing SAR-CoV-2 variants from infecting humans. Moreover, the innovative barrier could reduce the risk of other airborne threats, e.g., could be rapidly employed during the flu seasons or new emerging pandemics. The in silico computational models developed can also be used to expedite the development of accurate and precise countermeasures. The planned studies will provide opportunities to train engineering and biomedical science students who work collaboratively through highly interdisciplinary (engineering, molecular biology, virology and pharmacology) research studies and will enhance ongoing education and outreach activities focused on attracting underrepresented minority groups into these areas of research.

The overall goal of this project is to engineer an innovative, biodegradable, nanobarrier (anti viral coating) that is safe and can be widely deployed to protect the public from SARS-CoV-2 infections. Although traditional approaches like vaccines, mask mandates, and social distancing are being used to prevent or reduce the spread of COVID-19, long-term compliance is a challenge. Therefore, a novel approach to infection prevention is urgently needed. This project proposes a user-friendly nanobarrier designed to prevent viral and microbial attachment and infection of epithelial cells by enhancing the defense capabilities of the mucocutaneous lining found in nasopharyngeal passages. The nanobarrier inactivates enveloped viruses by sequestering essential cholesterols required for viral attachment, infection, and transmission. This project has two major objectives: (1) to use 3D-simulation of the nasopharyngeal cavity to optimize the parameters (droplet and delivery product characteristics) to guide the engineering of an applicator for accurate deposition of the nanobarrier to areas most susceptible to COVID-19 infection, facilitating translation into preclinical models, and (2) evaluate the efficacy of the nanobarrier in a validated coronavirus mouse model. The final nanobarrier will be agnostic to SARS-CoV-2 variants and can be quickly rolled-out to effectively prevent infection. The simulation approach used in this project will serve as a platform to develop targeted interventions with optimized delivery into the nasopharyngeal cavity. Additionally, this project will expand knowledge and understanding of how SARS-CoV-2 variants infect as well as their susceptibility.

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.