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

第1部分：非技术描述：赠款的主要目标是进行一项基本的实验研究，以了解使用一种被称为磁电纳米颗粒(MENPs)的新型智能材料来创造一种革命性的高精度无线脑深部刺激技术的可行性。由于其量子力学特性，特别是磁电效应，MENPs可以作为纳米级的多模式枢纽，能够结合不同领域的优势，同时减轻它们的弱点，以实现实时亚毫米空间分辨率的无线脑深部刺激。到目前为止，这种能力还没有通过任何其他刺激技术实现。此外，通过释放这种前所未有的技术能力，MENPs有望在两个大的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、严重抑郁症和其他，以及分子水平上的致命脑瘤，如胶质母细胞瘤，无线和以前从未获得过的控制水平。其次，通过铺平一条具有创纪录高时空分辨率的无线脑机接口的道路，MENPs将以创纪录的高时空分辨率在人类和人工智能(AI)之间实现无线连接，从而允许创建一个强大的工具来了解人脑的计算架构，反过来，创造AI状态的跨越式进步。第2部分：技术说明：与迄今已知的任何其他纳米粒子不同，MENPs显示出非零的磁电效应，因此提供了一种多模式功能，以电和无线的方式刺激整个大脑中选定局部区域的神经活动，空间分辨率实时达到亚毫米级。该功能是多模式的，因为磁电效应允许同时使用遥控磁场、聚焦超声波或近红外光的组合来产生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。将对磁场与超声波和近红外模式的集成进行比较研究，以了解这两种混合方法的优缺点。在这两种情况下，磁场将被用来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种低能场模式，以定义选定的局部刺激区。使用晶格匹配的磁致伸缩核心，例如CoFe2O4(钴铁氧体)和压电壳，例如BaTiO3(钛酸钡)制成的核壳MENPs将包括两部分实验：(1)纳米探针测量以量化多峰能量添加效应并调整关键的核壳MENPs的特性；(2)使用海马神经元细胞体外培养的研究，以了解通过多种影响激活神经元所引起的多峰效应之间的相互作用；以及(3)通过钙成像测量对神经元放电的影响。此外，我们还将研究不同的MENPs的组成和表面功能化对无线控制发射能力的影响。将分别从所需能量、空间分辨率、穿透深度以及穿透颅骨和脑组织的角度对两种混合模式，即(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，其中包括(I)一名共同开创医疗应用MENPs的纳米技术专家，(Ii)一名神经科学家，(Iii)一名光子学创新者，以及(Iv)一名行业合作调查员，他是一名有成就的信号处理专家，也是MENPs的共同先驱(与首席研究员一起)。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.