Next Generation Neutron Diffraction Detector for Neuroscience

用于神经科学的下一代中子衍射探测器

• 批准号: 8248926
• 负责人: W B FELLER
• 金额: $ 15.06万
• 依托单位: NOVA SCIENTIFIC, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-24 至 2013-09-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8248926
• 关键词: Area; Axon; Benchmarking; Biological; Biology; Cells; Cellular biology; Collimator; Communities; Data Collection; Data Set; Demyelinating Diseases; Disease; Effectiveness; Electron Microscopy; Failure; Fatigue; Feasibility Studies; Future; Human; Image; Investigation; Knowledge; Laboratories; Leadership; Measurement; Measures; Medical; Membrane; Methods; Modeling; Mouse Strains; Multiple Sclerosis; Mus; Myelin; Myelin Sheath; Nerve; Nerve Fibers; Nerve Tissue; Nervous System Physiology; Neural Conduction; Neuraxis; Neurons; Neurosciences; Neutron Diffraction; Neutrons; Noise; Pattern; Performance; Perfusion; Peripheral Nervous System; Peripheral Nervous System Diseases; Phase; Physiological; Positioning Attribute; Property; Research; Research Personnel; Resolution; Sampling; Science; Screening procedure; Speed; Spinal cord injury; Stress; Structure; Techniques; Technology; Testing; Therapeutic; Therapeutic Agents; Time; Tissue Sample; Transgenic Mice; United States; Variant; Vertebrates; X ray diffraction analysis; X-Ray Diffraction; base; biological systems; design; detector; drug testing; imaging detector; improved; insight; instrument; instrumentation; leukodystrophy; mouse model; myelinopathy; next generation; programs; repaired; research study; structural biology; time use; tool

DESCRIPTION (provided by applicant): NOVA Scientific proposes to adapt a powerful new type of neutron diffraction instrumentation for biological applications, a neutron counting and imaging detector called the MCP/Medipix detector. The detector offers much higher spatial and timing resolution, as well as higher count rate capability (10-100 MHz) and dynamic range compared with existing neutron position-sensitive detectors. It was designed to provide state-of-the-art performance to match the higher neutron fluences of next generation of neutron scattering and imaging facilities. Although demonstrated successfully during the past year in other applications, this powerful new instrument has never been applied to research in cellular and structural biology. We propose for the first time to modify and employ it as new detector tool to elucidate biologically important structures by using it in neutron diffraction (ND). One highly promising biological system which could benefit would be myelin, the electrically insulating material that ensheathes the neuron axon; its integrity is critically important for the proper functioning of the nervous system. Myelin ultrastructure studies, traditionally carried out using electron microscopy and X-ray diffraction could be substantially enhanced by using a more powerful new type of neutron diffraction (ND) detector, particularly with the increasing availability of a variety of transgenic mice that model human demyelinating disorders. Myelin would be an ideal test case for demonstrating the MCP/Medipix detector, as it allows benchmarking of previous ND measurements carried out with 3He detectors. This will demonstrate that that the improved performance of the MCP/Medipix detector represents a major advance in the power of ND for cellular and structural biology. In Phase I neutron diffraction experiments will be carried out using mouse nerves for the first time anywhere, as there are numerous transgenic mice strains that mimic human myelinopathies in both the PNS and CNS. To accomplish this, assembly and integration of a neutron sensitive 40 mm MCP with a modified Medipix readout will be carried out, preparing it for high fluence neutron diffraction experiments on a biologically-oriented neutron diffractometer. Also a versatile and advanced perfusion cell will be constructed allowing deuteration of samples for enhanced contrast variation, and to minimize neutron scattering noise. Two ND diffraction test campaigns will be carried out with the MCP/Medipix detector. Different aspects of myelin ultrastructure will be illuminated to show feasibility of ND as an essential tool for answering specific questions about myelin structure and inter-membrane dynamics. A Phase II program would expand this initial feasibility study to build larger area format MCP/Medipix detectors with the addition of advanced neutron beam collimation, to obtain even greater neutron sensitivity and diffraction pattern resolution, as well as data collection speed and efficiency. Ultimately, the MCP/Medipix detector and collimator ND enhancement would be commercialized for the benefit of the biological ND community. PUBLIC HEALTH RELEVANCE: This project develops new laboratory instrumentation to increase the power of neutron diffraction (ND), a highly sophisticated technique with the potential to probe far deeper into the actual structure of myelin, the electrically insulating material that ensheathes central core of nerve fibers. The integrity of myelin is critically important for the proper functioning of the nervous system; demyelinating disorders such as multiple sclerosis (MS), certain peripheral neuropathies, and leukodystrophies are characterized by the progressive disruption and breakdown with partial or attempted re-formation of the highly ordered myelin sheath. The ability to accurately measure these extremely subtle features of myelin, enabled by the new NOVA Scientific/Medipix detector, will increase our knowledge about disease states, and will help to provide insight into developing therapeutic strategies for stabilizing normal myelin or remyelinating nerve fibers.

描述（由申请人提供）：NOVA Scientific建议将一种功能强大的新型中子衍射仪器用于生物应用，即称为MCP/Medipix探测器的中子计数和成像探测器。与现有的中子位置敏感探测器相比，该探测器具有更高的空间和时间分辨率，以及更高的计数率能力（10-100 MHz）和动态范围。它的设计目的是提供最先进的性能，以匹配下一代中子散射和成像设施的更高中子注量。虽然在过去的一年里在其他应用中得到了成功的证明，但这种强大的新仪器从未被应用于细胞和结构生物学的研究。我们首次提出修改和采用它作为新的探测器工具，以阐明生物重要的结构，通过使用它在中子衍射（ND）。 一个高度 一个有希望的生物系统，可能受益将是髓鞘，电绝缘材料的鞘神经元轴突;它的完整性是至关重要的正常运作的神经系统。传统上使用电子显微镜和X射线衍射进行的髓鞘超微结构研究可以通过使用更强大的新型中子衍射（ND）检测器来大大增强，特别是随着各种转基因小鼠模型人类脱髓鞘疾病的可用性不断增加。髓磷脂将是一个理想的测试案例，用于演示MCP/Medipix探测器，因为它允许基准以前的ND测量与3 He探测器进行。这将证明MCP/Medipix检测器性能的提高代表了ND在细胞和结构生物学方面的重大进步。 在第一阶段，中子衍射实验将首次在任何地方使用小鼠神经进行，因为有许多转基因小鼠品系在PNS和CNS中都模仿人类髓鞘病。为了实现这一目标，将进行中子敏感40 mm MCP与修改后的Medipix读数的组装和集成，为生物导向的中子衍射仪上的高通量中子衍射实验做好准备。此外，一个通用的和先进的灌注细胞将被构造允许氘化的样品增强对比度的变化，并尽量减少中子散射噪声。将使用MCP/Medipix检测器进行两次ND衍射测试活动。髓鞘超微结构的不同方面将被照亮，以显示ND作为回答髓鞘结构和膜间动力学的具体问题的重要工具的可行性。 第二阶段计划将扩大这一初步可行性研究，以建造更大面积的MCP/Medipix探测器，并增加先进的中子束准直，以获得更高的中子灵敏度和衍射图案分辨率，以及数据收集速度和效率。最终，MCP/Medipix探测器和准直器ND增强将商业化，以造福于生物ND社区。 公共卫生相关性：该项目开发了新的实验室仪器，以增加中子衍射（ND）的功率，这是一种高度复杂的技术，有可能更深入地探测髓鞘的实际结构，髓鞘是包裹神经纤维中央核心的电绝缘材料。髓鞘的完整性对于神经系统的正常功能至关重要;脱髓鞘疾病如多发性硬化症（MS）、某些周围神经病和脑白质营养不良的特征在于高度有序的髓鞘的部分或试图重新形成的进行性破坏和分解。通过新的NOVA Scientific/Medipix探测器，能够准确测量髓鞘的这些极其细微的特征，这将增加我们对疾病状态的了解，并有助于深入了解开发稳定正常髓鞘或髓鞘再生神经纤维的治疗策略。