Collaborative Research: Magnetic mapping of bio-inspired clusters of iron oxide nanoparticles

人造氧化铁纳米颗粒对于标记人体内外的细胞和分子具有广泛的重要性。除了合成颗粒，许多生物体还产生天然存在的氧化铁纳米颗粒，称为铁蛋白，以储存和调节体内的铁。无论是人造的还是天然的，这些氧化铁纳米颗粒都具有磁化作用，可以用作生物环境中操纵或传感的工具。然而，纳米粒子往往聚集在复杂的生物环境中，聚集对其集体磁性的影响还没有很好的理解。这项工作的总体目标是探索纳米颗粒聚集和所得的磁性之间的关系。这项工作的发现可能用于设计基于磁性的传感工具，以更准确地跟踪生物系统中的铁纳米颗粒。该项目的数据还可以推进氧化铁颗粒的其他生物医学应用，例如它们在癌症治疗的磁热疗或医学成像的造影剂中的应用。除了推进生物磁性和纳米生物技术领域，该研究项目将通过为学生提供最先进的纳米颗粒合成和表征技术的研究经验，帮助培养下一代科学家和工程师，通过开发新的磁特性鉴定技术和扩大代表性不足的群体对科学的参与来加强研究和教育基础设施和工程活动。氧化铁纳米粒子由于其磁性特性已成为生物医学和生物纳米技术中的重要工具。这些包括合成的磁铁矿纳米颗粒（直径约5至10 nm），以及存在于铁蛋白（人体中最大的铁储存蛋白）中的天然存在的水铁矿核心（约5至8 nm）。确定这些氧化铁纳米颗粒在细胞和组织中的空间定位和定量对于健康领域的许多应用至关重要。到目前为止，我们表征氧化铁纳米颗粒的空间分布和数量的能力仅限于生物化学方法，如组织化学染色，这在很大程度上是定性的。磁敏检测为氧化铁纳米颗粒的表征提供了一种替代的、非破坏性的、无标记的和定量的手段。然而，在生物系统中，纳米颗粒通常以聚集体/簇的形式存在，这会影响它们的局部和全局磁性，并使磁信号的解释复杂化。该项目的目标是了解生物启发的氧化铁纳米颗粒的聚集如何影响其在许多长度尺度（纳米到微米尺度）上的磁性。具体而言，将使用一系列磁敏感技术研究单个颗粒之间以及较大颗粒簇之间的相互作用。生物衍生的颗粒簇以及人工工程聚集体将用于研究。这些包括合成的磁铁矿纳米颗粒和存在于铁蛋白中的天然存在的水铁矿核。在某些情况下，将使用模板引导组装来纳米制造簇，使得簇的几何参数（诸如尺寸、形状和颗粒间距离）可以系统地变化。将使用分析电子显微镜、磁力显微镜、超导量子干涉装置磁力测定和磁共振成像等技术对颗粒组装体进行表征。这项研究的结果将用于开发先进的基于磁性的计量学，用于定位和量化生物环境中氧化铁纳米颗粒的聚集体。理解聚类对磁特性的影响可以使定量组织磁检测方案用于映射组织切片中的铁沉积物。项目活动将通过为研究生和本科生提供多学科和机构间研究经验以及建立新的研究合作来完成。该项目还将包括扩大参与的外展工作，为当地学校的贫困中学生开发和提供工程概念的实践讲习班。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

Man-made iron oxide nanoparticles have widespread importance for labeling cells and molecules both inside and outside the human body. Besides synthetic particles, many organisms also generate naturally occurring iron oxide nanoparticles, known as ferritin, to store and regulate iron within their bodies. Whether man-made or natural, these iron oxide nanoparticles have a magnetization that can be used as a tool for manipulation or sensing in biological environments. However, nanoparticles often aggregate in complex bio-environments, and the effect of aggregation on their collective magnetic properties is not well understood. The overall objective of this work is to explore the relationship between nanoparticle clustering and resultant magnetic properties. Findings from this work can be potentially used to engineer magnetism-based sensing tools for more accurately tracking iron nanoparticles in biological systems. Data from this project can also advance other biomedical applications of iron oxide particles, such as their uses in magnetic hyperthermia for cancer therapy or as contrast agents for medical imaging. Besides advancing the field of bio-magnetism and nano-biotechnology, this research project will help train the next generation of scientists and engineers by providing research experience to students in state-of-the-art techniques for synthesis and characterization of nanoparticles, by enhancing infrastructure for research and education through the development of new techniques for magnetic characterization and by broadening participation of underrepresented groups in science and engineering activities. Iron-oxide nanoparticles have become crucial tools in biomedicine and bio-nanotechnology due to their magnetic behavior. These include synthetic magnetite nanoparticles (~5 to 10 nm in diameter), and naturally occurring ferrihydrite core (~ 5 to 8 nm) present in ferritin, the largest iron-storage protein in the human body. Determining the spatial localization and quantification of these iron-oxide nanoparticles in cells and tissues is critical for a number of applications in health. Thus far our ability to characterize the spatial distribution and quantity of iron oxide nanoparticles is limited to biochemical approaches like histochemical staining, which are largely qualitative. Magnetically sensitive detection offers an alternative, non-destructive, label free and quantitative means for characterization of iron-oxide nanoparticles. However, in biological systems, nanoparticles are often found in aggregates/clusters, which can impact their local and global magnetic properties and complicate interpretation of magnetic signals. The goal of this project is to understand how clustering of bio-inspired iron-oxide nanoparticles affect their magnetic properties across many length scales (nanometer to micrometer scale). Specifically, interactions between individual particles, as well as between larger clusters of particles, will be studied using a range of magnetically sensitive techniques. Biologically derived clusters of particles as well as artificially engineered aggregates will be used for the study. These include synthetic magnetite nanoparticles and naturally occurring ferrihydrite cores present in ferritin. In some cases, clusters will be nanofabricated using template guided assembly, so that geometric parameters of clusters such as size, shape, and interparticle distance can be varied systematically. Characterization of particle assemblies will be performed using techniques such as analytical electron microscopy, magnetic force microscopy, super-conducting quantum interference device magnetometry and magnetic resonance imaging. Results from this study will be used to develop advanced, magnetism-based metrology for localizing and quantifying aggregates of iron oxide nanoparticles in biological environments. An understanding of the effect of clustering on magnetic properties can enable quantitative histo-magnetic detection schemes for mapping iron deposits in tissue sections. The project activities will be accomplished by providing multidisciplinary and inter-institutional research experiences for graduate and undergraduate students and by establishing new research collaborations. The project will also include outreach efforts to broaden participation, by developing and offering hands-on workshops on engineering concepts to under-privileged middle school students at a local school.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.