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

第一部分：非技术性描述：该基金的主要目标是进行一项基础实验研究，以了解使用一种称为磁电纳米颗粒（MENP）的新型智能材料的可行性，为高精度无线脑深部刺激创造一种革命性技术。由于它们的量子力学特性，特别是磁电效应，电磁纳米颗粒可以作为纳米级多模式枢纽，能够结合不同领域的优势，同时减轻他们的弱点，实现无线深部脑刺激与亚毫米空间分辨率在真实的时间。迄今为止，任何其他增产技术都无法实现这种能力。此外，通过释放这种前所未有的技术能力，电磁纳米粒子有望对两大应用领域产生重大影响。首先，它们将允许治疗神经障碍和疾病，例如，帕金森氏症，自闭症，阿尔茨海默氏症，严重抑郁症等，以及致命的脑肿瘤，如胶质母细胞瘤在分子水平上，无线和控制水平前所未有。其次，通过为具有创纪录的高时空分辨率的无线脑机接口铺平道路，MENP将使人类和人工智能（AI）之间的无线连接具有创纪录的高空间和时间分辨率，从而允许创建一个强大的工具来理解人类大脑的计算架构，并在AI状态下实现跨越式发展。第二部分：技术描述：与迄今为止已知的任何其他纳米颗粒不同，电磁纳米颗粒显示出非零磁电效应，因此提供了多模态功能，以真实的时间以亚毫米尺寸范围内的空间分辨率以电和无线方式刺激整个大脑中选定局部区域的神经活动。该功能是多模态的，因为磁电效应允许同时使用远程控制的磁场、聚焦超声波或近红外光的组合来生成局部电场的时空图案，以实现所需的高精度刺激。由于混合方法（磁超声或磁近红外），这种多模式应用允许单独增强这些场模式中的任何一种的强度，同时减轻它们的缺点。将比较研究磁场与超声和近红外模式的集成，以了解这两种混合方法的优缺点。在这两种情况下，磁场将被用于传递刺激神经元所需的大部分能量，而超声波或近红外光将被用作第二低能量场模式以定义所选择的局部刺激区域。使用由晶格匹配的磁致伸缩核制成的核-壳型电磁纳米粒子的实验，CoFe 2 O 4（钴铁氧体）和压电外壳，例如，BaTiO 3（钛酸钡）将包括两个部分：（1）纳米探针测量，以量化多模态能量添加效应并定制关键的核-壳电磁纳米颗粒的特性，以及（2）使用海马神经元细胞培养物的体外研究，以了解由于对神经元放电的多种效应的激活而导致的多模态效应的相互作用（通过Ca++成像测量）。此外，我们将研究不同的电磁纳米粒子的组成和表面功能化对无线控制发射能力的影响。从所需能量、空间分辨率、穿透深度以及穿透颅骨和脑组织的角度，分别对两种混合模式（i）磁-超声和（ii）磁-近红外）进行比较研究。为了实现上述目标，GOALI团队由四名具有跨学科背景的经验丰富的研究人员组成，包括（i）共同开创医疗应用的MENP的纳米技术专家，（ii）神经科学家，（iii）光子学创新者，以及（iv）一位行业合作研究员，他是一位有成就的信号处理专家和合作先驱该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.