CAREER: Tailoring Thermal Conductivity of Soft Magnetic Nanomaterials for Wireless Neuromodulation
This career research project provides the foundation for a long-term productive research program to investigate nanoscale transport phenomena principles for the development of a novel neuromodulation technology. This research explores fundamental questions of nanoscale heat and mass transport. and applies these findings to yield a completely new mechanism to transduce magnetic signals into biochemical stimulus utilizing hybrid nanomaterials. This research would (1) develop a completely new paradigm for precise control of neural activity. (2) provide the research community with a new platform for mapping brain circuits to improve our understanding of complex neural networks. (3) enable the on-demand localized release of therapeutics required for the next generation of bioelectronics medicines. and (4) accelerate the development of wireless neuromodulation technologies for the treatment of brain malfunctions. Finally. this proposal lays out the potential for this fundamental research to lead to not only pharmacological magnetothermal neuromodulation. but further to develop drug-free neuromodulation technologies utilizing soft magneto-mechanical and magneto-electrical approaches. Overview: The ability to evoke and inhibit neural activity on-demand is essential to understand basic biology of neural circuit dynamics. Critically. current techniques for the control of neural circuits lack of cell-type specificity or require implantable devices that are damaging to biological tissues. The PI has been working on developing neural modulation paradigms in which neural activity is remotely controlled through noninvasive alternating magnetic fields (AMFs). The developed technology uses magnetic nanoparticles (MNPs) selectively targeted to neuronal membranes to transduce magnetic fields into heat stimulus. The proposed work will design a soft magnetic nanomaterials platform to enable a stable pharmacological. non-toxic. targetable strategy for neuromodulation by transducing magnetic signals into biochemical stimulus. Objective 1 investigates the synthesis and characterization of biocompatible temperature-responsive polymer brushes. This objective will develop the relationship between polymer composition and thermodynamic properties that will allow the independent release of neurostimulators and neuroinhibitors. Objective 2 investigates polymer brushes coatings on MNPs surface for the entrapment of neuromodulatory compounds and its on-demand release. in multiple dosages. triggered by the hysteretic heat dissipation of MNPs under AMFs. We will develop the mechanistic relationships governing nanoscale heat and mass transport triggered by AMFs. Objective 3 designs a magnetothermal pharmacological paradigm for precise modulation of neural activity. This objective develops fundamental aspects of local neuromodulation to support development of magnetothermal pharmacological paradigms for precise control of neural circuits. Objective 4 integrates magnetothermal pharmacological modulation of neural activity into a Heat and Mass Transport program to enhance high school Physics Science education through a RET program. and Biotransport Phenomena undergraduate education by incorporating student-centered learning strategies. Broader Impacts: This project capitalizes on the synergy between fundamental research on the nanoscale transport processes involved in magnetothermal pharmacological neuromodulation and Biotransport Phenomena education. The PI will continue to improve the flipped undergraduate Biotransport Phenomena course by incorporating real-world problems and refining a unique superhero project that promotes lifelong learning and proved popular with students during the pilot. Based on prior research on active learning and challenge-based education. the proposed activities should increase student access. engagement. and performance in heat and mass transport phenomena training. To evaluate this. the PI will implement assessment of student learning in this course and compare the results to course transformations at other institutions. Using the RET mechanism. the PI will provide research access and training to three local high school teachers and create three developmentally appropriate standards-based high school lab activities and lessons. To broaden the impact and promote dissemination. these activities will be used to develop a summer professional development workshop for high school STEM teachers that will reach approximately 20 teachers and 2.000 local high school students in San Antonio. The PI will continue to recruit and mentor students underrepresented in engineering by serving as a Latina role model in academia.