GOALI: Magnetoelectric Nanoparticles As Multi-Field Controlled Devices for Activation of Brain Circuitry

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Part 1: Non-technical Description: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. Part 2: Technical Description: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.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.