Magnetic Particle Microscopy of Living Organisms

活体磁粉显微镜

• 批准号: 1310657
• 负责人: Pallavi Dhagat
• 金额: $ 45万
• 依托单位: Oregon State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1310657&HistoricalAwards=false
• 关键词: Magnetic; Particle; Microscopy; Living; Organisms

The goal of this project is to develop a new three-dimensional imaging technique, using magnetic nanoparticle tracers, to observe and study biological processes at the cellular and sub-cellular level in live organisms, tissue and cell cultures.Intellectual Merit:Advances in optical microscopy and imaging have transformed biology. However, the penetration depth of optical microscopy is limited due to the scattering and absorption of light within tissue. Thus, interrogating tissue and 3D cell cultures beyond (0.5 to 0.8) mm with high resolution and minimal photodamage from the required high-intensity illumination has been challenging. Magnetic fields, in contrast, penetrate biological samples without scattering or harm to the cells, providing the opportunity for a new imaging modality from magnetic nanoparticle microscopy as proposed here. Cells and cellular organelles may be labeled with magnetic nanoparticle tracers, which can then be imaged with high contrast and resolution. Magnetic nanoparticle microscopy is based on the principles of magnetic particle imaging (MPI). Briefly, a magnetic field distribution is established such that tracer particles everywhere within the sample except a small field free point are magnetically saturated. As a result, when an ac excitation field is applied, a response is elicited only from nanoparticles within the field free point. A 3D image of the nanoparticle concentration is constructed by scanning the field free point within the sample to spatially select the nanoparticles and measure their response inductively. Research on MPI has focused on the development of millimeter-scale resolution scanners with a field of view encompassing the whole human or small animal body. The proposed research seeks instead to scale magnetic particle imaging for sub cellular resolution. The experimental goal is to demonstrate 25 µm in a relevant biological specimen. A magnet field assembly will be implemented to provide the high field gradient needed for nearly two orders of magnitude finer resolution. The system hardware will be designed with low noise electronics to ensure maximal signal-to-noise ratio. Further, nanoparticle tracers of custom size and biocompatible coatings will be precision engineered with to meet the imaging requirements. A modular synthetic approach will allow the core and biocompatible coatings to be independently and systematically tailored, with exquisite control. Imaging capabilities will be demonstrated in embryonic zebrafish and verified via concurrent optical microscopy. Experiments proposed to qualify magnetic nanoparticle imaging will also advance ongoing research in identifying physical and chemical properties of nanoparticles that influence their uptake and thereby provide insight to their toxicity.Broader Impact: This project forges an interdisciplinary and inter-institutional collaboration, bridging engineering, chemistry and biology, to meet the need for an imaging technology to explore new scientific frontiers in microbiology and medicine. The successful demonstration of cellular and sub cellular resolution will establish a new means of microscopy, using magnetic nanoparticle tracers, to investigate cell behavior in optically opaque, living tissue. Beyond fundamental biology, this effort will advance synthesis techniques for precisely engineered nanoparticles and bring new insight to nanoparticle interactions with living systems. Further, it will lay the foundation for applications envisioned in medical imaging of clinical skin and breast cancer screening. The PIs will involve 2 graduate and 4 undergraduate students in research. The participating students will gain a well-rounded technical education acquiring not only expertise in their respective areas of specialization but also knowledge of methods and materials in complementary areas of research. Suitable sub-topics within the project will be integrated in to cross disciplinary and discipline-specific courses taught by the PIs. The research findings will be published in relevant high-impact journals and presented at regional, national and international technical meetings. In addition, as discussed in the data management plan, final data will be archived and made available to the public. The PIs will serve K-12 education by developing grade-level appropriate instruction materials in collaboration with elementary, middle and high school science teachers. The PIs will also participate in Science Pubs, an informal science education program to engage the public in discussion on the synthesis, applications and implications of nanoparticles in medicine and biology.

该项目的目的是使用磁性纳米颗粒示踪剂开发一种新的三维成像技术，以观察和研究活有机体，组织和细胞培养的细胞和亚细胞水平的生物学过程。启动性优点：光学显微镜和成像的进展转化了生物学。然而，由于组织内的光的散射和滥用，光学显微镜的穿透深度受到限制。这是挑战的，从所需的高强度照明受到高分辨率和最小的光损伤的询问已超过（0.5至0.8）毫米以上。相比之下，磁场可以穿透生物样品，而不会散射或对细胞造成伤害，从而为这里提出的磁性纳米颗粒显微镜提供了新的成像方式的机会。细胞和细胞细胞器可以用磁性纳米颗粒示踪剂标记，然后可以以高对比度和分辨率成像。磁性纳米颗粒显微镜基于磁颗粒成像（MPI）的原理。简而言之，建立了磁场分布，以使样品中各地的示踪剂颗粒除了小场自由点以外饱和。结果，当应用AC兴奋场时，仅从磁场自由点内的纳米颗粒引发响应。纳米颗粒浓度的3D图像是通过扫描样品中的场自由点以空间选择纳米颗粒并归纳测量其响应的3D图像。对MPI的研究重点是开发毫米级的分辨率扫描仪，其视野涵盖了整个人类或小动物的身体。拟议的研究旨在将磁性粒子成像扩展以进行亚细胞分辨率。实验目标是在相关的生物样品中证明25 µm。将实现磁铁场组件，以提供近两个分辨率近两个数量级所需的高场梯度。系统硬件将使用低噪声电子设备设计，以确保最大的信噪比。此外，将精确地设计自定义尺寸和生物相容性涂料的纳米颗粒示踪剂，以满足成像要求。模块化的合成方法将使核心和生物相容性涂层独立和系统地定制，并具有精美的控制。成像能力将在胚胎斑马鱼中证明，并通过并发光学显微镜进行验证。提议符合磁性纳米粒子成像的实验还将推进正在进行的研究，以识别影响其吸收的纳米粒子的物理和化学性质，从而对其毒性产生洞察力。BOADER的影响：该项目构成了跨学科和跨机构的跨机构和跨机构的协作，培养工程学，化学和生物学，以探索一项新的科学技术，以探索一项新的科学技术。细胞和亚细胞分辨率的成功证明将使用磁性纳米颗粒示踪剂建立一种新的显微镜方法，以研究光学不透明的活性组织中的细胞行为。除了基本生物学之外，这项工作还将推进精确设​​计的纳米颗粒的合成技术，并为与生活系统的纳米颗粒相互作用带来新的见解。此外，它将为在临床皮肤和乳腺癌筛查的医学成像中设想的应用奠定基础。 PI将涉及2名毕业生和4位本科生研究。参与的学生将获得一项全面的技术教育，不仅获得各自专业领域的专业知识，而且还获得了整个研究领域的方法和材料的知识。该项目内的合适子主题将集成到PIS教授的纪律和纪律特定课程。研究结果将在相关的高影响期刊上发表，并在地区，国家和国际技术会议上发表。此外，如数据管理计划中所述，最终数据将被存档并提供给公众。 PI将通过与小学，中学和高中科学老师合作开发适当的教学材料来为K-12教育提供服务。 PI还将参加科学酒吧，这是一项非正式的科学教育计划，旨在参与公众讨论纳米颗粒在医学和生物学中的综合，应用和含义。