Qi Wang, Ph.D. - US grants

Conventional parallelization strategies do not scale
well when the computational effort arises from the
need to simulate to long time spans, rather than from
large state space. Molecular Dynamics simulations
constitute an important class of applications where
this proves to be a bottleneck. The investigators
develop a new approach to parallelization of Molecular
Dynamics, which is based on the observation that
simulations typically occur in a context rich in data
from other related simulations. They use such data to
parallelize the time domain, which yields a more
scalable algorithm. This approach is based on the
observation that long time-spans are often encountered
in simulations with multiple time scales. The fine
scales are responsible for the large computational
effort. However, the important contribution of the
fine-scales is often to the effect they have on the
coarse scale. The investigators use reduced order
modeling to identify important coarse scale effects.
They use clustering and machine learning to
dynamically determine the relationship between the
simulation being performed and prior data. They use
ODE and controls theory for stability analysis,
uncertainty estimation, and system identification.

The investigators validate their techniques using a
variety of realistic applications in nano and bio-nano
materials. The importance of the applications chosen
arises from the fact that materials have historically
played a pivotal role in human progress. An indication
of their importance lies in the fact that eras of
human progress, such as the iron age and the bronze
age, are named after the materials that contributed to
such progress. Nano and bio-nano materials, designed
based on fundamental understanding at the atomic
scale, promise yet another revolution, leading to
products such as fuel efficient cars, disaster
resistant structures, and new ways of treating
diseases. The investigators' techniques remove an
important impediment to such developments.
Furthermore, the students involved obtain training in
interdisciplinary research. Inclusion of a
collaborator with a joint appointment at an HBCU
ensures that under-represented students too benefit
from this work.

DESCRIPTION (provided by applicant): Device to mechanically interrogate tissue and skin across research environments Relative changes in the tissue's response to mechanical deformation have been used for centuries to diagnose and classify diseases and often serve as surrogates for assessment of disease stage or progression. Pathological conditions such as arterial, venous, diabetic, lymphatic and collagen vascular disease are manifested in macroscopic and microscopic structural changes in the skin and soft tissues. Many devices have been designed to measure and describe the mechanical properties of skin in vivo and some devices have attained success in certain research environments. However, a remaining need exists for a device that is compatible with both lab-based and clinically-based research. Current device have not been proven useful for both types of research environments. In this project, we will develop a low-cost, portable technology, the mechanical interrogation of tissue and skin device (MITS), to quickly and accurately quantify the mechanical properties of the tissue and skin within a variety of healthcare research settings. Because skin and tissue research spans a wide range of clinical conditions, in this project we must focus on a few examples in order to develop MITS for versatile and wide ranging applications. Specifically, we will 1) Engineer the MITS hardware and software for multiple research applications and environments, 2) Model and optimize MITS performance using tissue phantoms, 3) Optimize MITS for use in animal (wound) and human (pressure ulcer and edematous limb) research utilizing an iterative design approach. The novelty of the MITS device is its small form factor, small area of interrogation, high bandwidth, and its readiness to utilize variable excitation patterns. While this project is focused on developing a versatile research instrument, the simplicity and small form factor of the MITS can form the basis for the development of a clinical diagnostic device. Since a design objective includes utility in a variety of clinical research environments, one can envision later development work to focus on clinical applications. The potential of having a clinical tool based upon the same technical principles of a research instrument would streamline the translation of research findings into clinical applications. PUBLIC HEALTH RELEVANCE (provided by applicant): The proposed research will develop a low-cost technology that can quickly and accurately report mechanical properties of the tissue and skin. This technology will help healthcare researchers in a variety of research settings in which pathological conditions, such as arterial, venous, diabetic, lymphatic and collagen vascular disease, are manifested in macroscopic and microscopic structural changes in the skin and soft tissues.

The principal investigators use mathematics and computation to model fluid-particle mixtures in which the individual particles are anisotropic (e.g., rod-like) and have their own propulsion mechanism. Examples arise in nature with suspensions of rod-like, flagella-propelled bacteria, in living cells where actin filaments provide structural integrity and molecular motors propel the filaments to achieve cellular function, and in high performance materials where catalytic nano-rods are suspended in a reactive solvent and propelled by chemical reactions. These systems share the remarkable feature of self-organization on scales in space and time far greater than those of the individual particles, translating to functionality across many scales. These diverse active particle-fluid systems have been previously modeled. Here the investigators undertake a unified theoretical and computational platform for such problems, which offers multiple benefits. A common mathematical structure reveals how these systems achieve their functional properties, informs which physical and chemical features allow the most efficient steering and optimization of the system toward desired properties, allows for a common computational platform, and allows one to incorporate additional degrees of freedom or perturb existing particle and fluid properties and predict their consequences. These advances have applications to enhance beneficial bacterial colonies and to disrupt harmful ones, to repair damaged cellular functions, and to design nano-composite materials with optimal properties. Graduate students are involved in the work of the project.

The principal investigators develop a modeling and computational platform for active, anisotropic fluids, unifying three apparently diverse fluid systems (catalytic nano-rod dispersions, swimming bacterial suspensions, and motor-driven actin filament gels) for which models, analysis, algorithms, and simulations have so far evolved independently. The mathematical platform unifies previous results, spans kinetic to continuum spatial and temporal scales, and identifies a common leading-order mathematical structure at each scale of description as well as the lower-order structure that distinguishes among different active, anisotropic fluids. This structure guides analysis and algorithm development toward an understanding of, and predictive control over, the remarkable observed behavior of these fluid systems. The project aims to distinguish sensitivity to particle dimensions, aspect ratio, concentration, and activation energy, with direct application to active nano-rod dispersions, actin filament gels, and bacterial suspensions in confined and free surface flows.

Non-technical Description
The initiative for Materials Assembly and Design Excellence in South Carolina (MADE in SC) promises to break new ground in advanced materials design. The project will combine computational and experimental methods to design materials with specific desirable properties. The project will advance fundamental knowledge of complex materials while simultaneously working toward the development of products with valuable commercial applications, such as improved lasers, water treatment, and regenerative medicine. The project will make major investments in South Carolina?s research capacity, acquiring state-of-the art instrumentation and computing capabilities and hiring seventeen new faculty researchers at institutions across the state. In parallel with its research agenda, MADE in SC will also work to improve Science, Technology, Engineering, and Mathematics (STEM) education capacity in South Carolina through college curriculum improvements and professional development activities for high school teachers.

Technical Description
MADE in SC materials development process will use a Materials Genome Initiative (MGI) framework, incorporating an iterative design loop wherein modeling and computation based on initial design constraints provide data that will inform experimental design. Imaging and data visualization of experimental results will lead to insights that can then drive additional modeling work, with the cycle continuing until an optimal solution is achieved. This MGI-based framework will depend on the resources of the Multiscale Modeling and Computational Core (MCC), which will be established as part of the project. The MCC will develop modeling capabilities appropriate across length scales (microscopic, mesoscopic, and continuum), and will support the application of these tools to the project?s major research thrusts: 1) hierarchical structures with controlled optical and magnetic properties; 2) stimuli-responsive polymeric materials; and 3) rational design of interactive biomaterials. These research efforts will advance fundamental understanding of the chemical and physical drivers of observed material properties while also realizing new materials with desirable properties for commercial applications.

The broader impact/commercial potential of this I-Corps project is the development of technology that accurately perceives details of tactile, auditory, and visual stimuli required for completing the tasks necessary for daily life and independent living. Impaired sensory processing may cause misperceptions and miscommunication that can be frustrating, debilitating, and dangerous. This technology rapidly modulates sensory processing and could provide an immediate benefit across many potential use cases. By restoring clear sensory processing, this technology seeks to facilitate a return to socializing, exercise, hobbies, and employment for many individuals who have withdrawn from those activities due to chronic sensory issues. An enhancement of sensory processing may improve the ability to communicate easily, ambulate safely, and handle objects with dexterity.<br/><br/>This I-Corps project is based on the development of a method of rapidly enhancing the accuracy and detail of sensory information processed in the brain via a noninvasive neuromodulation technique. In both animal and human studies, enhanced sensory processing translated to increased sensory acuity as evidenced by improved performance on sensory tasks. This technology includes wearable neural stimulation patches that could treat a variety of clinical causes of impaired sensory processing. This patches cause tonic activation of the locus coeruleus-norepinephrine (LC-NE) system in the brain and have resulted in a rapid enhancement of thalamic sensory processing. This NE-enhanced sensory processing state increased the perceptual sensitivity of awake animals performing sensory tasks. The vagus nerve can be stimulated noninvasively in humans by delivering electric current transcutaneously, providing an effective and safe method of neuromodulation. This novel bioelectronic method of using continuous tonic VNS provides sensory enhancement on-demand.<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.

This award supports the 48th annual Northeast Bioengineering Conference (NEBEC), a regional conference that is historically student-centered. The conference will be held at Columbia University, New York City, New York, April 23-24, 2022. This is the first in-person NEBEC conference after the COVID pandemic and provides an opportunity to undergraduate and graduate student researchers in the field of biomedical engineering to meet and present their research to their peers. The conference has been impactful because it allows students in the Northeast region who do not have the funding to attend a national biomedical engineering meeting to present their work to a broad audience. This opportunity will encourage students to pursue graduate school and pursue a STEM career. The award will support a reduction in registration fees for undergraduate students and postdoc fellows, thus making the conference even more affordable to early career scientists, especially financially disadvantaged students.

As a conference with a strong tradition for educating the next generation of undergraduate students, graduate students, and postdoctoral fellows in biomedical engineering, the 48th Northeast Bioengineering Conference at Columbia University will bring together a number of leaders in various bioengineering fields to inform and inspire students about progress and research opportunities in the biomedical engineering. The conference expects to attract more than 450 attendees from around the Northeast region of the United States, with 60% of which expected to be students. The Biomedical Engineering Society and IEEE Engineering in Medicine and Biology Society Student Chapters at different universities in the Northeast region are reaching out and encouraging participation by students, especially female and under-represented minority students from the region. Young Scientist Awards and New Innovator Award will be given to specifically support professional development of early career scientists. Themes of the presentations will include the following: Neural Engineering, Cellular and Molecular Bioengineering, Biomechanics, Tissue Engineering, Synthetic Biology, Computational Biology/Bioinformatics, Medical Devices, and Biophotonics / Biomedical Imaging. Additional sessions planned include a senior design competition, Future Bioengineer session, and a panel discussion about biomedical engineering education and research after COVID.

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.