MOLECULAR IMAGING OF BIOMATERIALS

生物材料的分子成像

• 批准号: 3421694
• 负责人: NICHOLAS WINOGRAD
• 金额: $ 28.45万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1995-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3421694
• 关键词: analytical chemistry; biomedical equipment development; chemical structure; cryoscience; imaging /visualization /scanning; ionization; ions; lasers; macromolecule; mass spectrometry; metals; method development; molecular biology; molecular size

This proposal concerns the development and application of a resource technology capable of direct imaging of biomolecules with extremely good spatial resolution and sensitivity. In the best case, the spatial resolution will approach 1000 Angstroms. Increased spatial resolution will be the direct result of an increased sensitivity gained via the use of laser-based multiphoton ionization techniques combined with a liquid metal ion source. This imaging molecular microprobe, which may be constructed largely with commercially available components, is predicted to exhibit a nearly 2 order of magnitude improvement in resolution over existing molecular imaging techniques. Molecular imaging will be carried out using a liquid metal ion source for ion and neutral desorption from prepared surfaces with subsequent laser-based multiphoton ionization and mass analysis by time-of-flight mass spectrometry. This combination of chemical methodologies is uniquely suited to provide quantitative chemical identification with high spatial resolution, or conversely, spatial resolution at the few micron level with extremely good concentration sensitivity. Both high resolution and low resolution applications are planned. Applications of this technology will involve at least nine investigators at Penn State Univ., SUNY Buffalo and NIH. These applications will include imaging haptens to identify colonies that have been genetically manipulated to produce catalytic antibodies. Moreover, chemical imaging will be used to examine molecules bound to clusters of neurotransmitter receptors on nerve cell membranes and experiments are proposed to quantitate peptidergic neurotransmitters in single vesicles exposed by freeze fracture. In addition, the molecular microprobe will be developed for imaging phospholipids in erythrocyte, sperm and nerve cells to correlate membrane structure with function. The technology proposed complements existing capabilities in optical and electron microscopy, provides an ability to identify chemical species with extremely high resolution, and promises to revolutionize our ability to carry out experiments requiring bioimaging.

该建议涉及资源的开发和应用 能够直接成像生物分子非常好的技术 空间分辨率和灵敏度。 在最好的情况下，空间 分辨率将接近1000埃埃斯特罗姆。空间分辨率增加 将是通过使用提高灵敏度的直接结果 基于激光的多光子电离技术与液体结合 金属离子源。 这个成像分子微探针，可能是 预测，主要用市售的组件构建 在分辨率上的分辨率提高了近2个数量级 现有的分子成像技术。 分子成像将被携带 使用液态金属离子源以离子和中性解吸 准备的表面具有随后的激光多光子电离和 通过飞行时间质谱法分析。 这种组合 化学方法论非常适合提供定量 具有高空间分辨率的化学识别，或相反 在几个微米级别的空间分辨率非常好 浓度灵敏度。 高分辨率和低分辨率 计划申请。 该技术的应用将涉及 宾夕法尼亚州立大学，纽约州立大学和NIH的至少九名调查员。 这些应用程序将包括成像触发，以识别殖民地 已通过遗传操纵以产生催化抗体。 此外，化学成像将用于检查与 神经细胞膜上神经递质受体的簇和 提出了实验来定量肽固定神经递质 通过冻结暴露的单囊泡。 另外，分子 微探针将用于成像红细胞中的磷脂， 精子和神经细胞将膜结构与功能相关联。 这 拟议的技术补充了光学和 电子显微镜提供了鉴定化学物种的能力 通过极高的分辨率，并承诺革新我们的能力 进行需要生物成像的实验。