SBIR Phase II: Novel platform for the preparation of samples for cryo-TEM imaging: capturing biomacromolecules repeatably in vitreous ice without artifacts

SBIR 第二阶段：用于制备冷冻 TEM 成像样品的新型平台：在玻璃体冰中重复捕获生物大分子，无伪影

• 批准号: 1951068
• 负责人: Michael Godfrin
• 金额: $ 74.47万
• 依托单位: NanoSoft, LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2022-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1951068&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Novel; platform

The broader impact of this Small Business Innovation Research (SBIR) Phase II project is a new way to prepare samples for life sciences research by addressing the major bottleneck in the associated workflow. The proposed work advances a new method to prepare biological samples for analysis to develop crisp, high-resolution 3D models of molecules. This will result faster acquisition of higher quality data and better 3D models of proteins and other cellular components, providing new insight into human biology and improvements to human health. The proposed project aims to solve the largest issues currently experienced in cryogenic Transmission Electron Microscopy (cryo-EM) sample preparation. Current sample preparation technologies are unreliable and require preparation of excess grids to acquire enough quality data for a 3D model of a biomacromolecule. Many grids are of poor quality and generate insufficient data for a high-resolution protein model; or samples may contain artifacts from interaction at the air/water interface, reducing the ultimate resolution. This Phase II project will advance an innovative design concept to repeatably prepare high quality samples with a blotless sample preparation technique. The proposed work will explore the trade space and optimize process parameters for image resolution, leading to an advanced prototype.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.

这个小企业创新研究 (SBIR) 第二阶段项目的更广泛影响是通过解决相关工作流程中的主要瓶颈，为生命科学研究准备样品的新方法。 这项工作提出了一种制备生物样品进行分析的新方法，以开发清晰、高分辨率的分子 3D 模型。这将导致更快地获取更高质量的数据以及更好的蛋白质和其他细胞成分的 3D 模型，从而为人类生物学和改善人类健康提供新的见解。拟议项目旨在解决目前低温透射电子显微镜 (cryo-EM) 样品制备中遇到的最大问题。目前的样品制备技术并不可靠，需要准备多余的网格才能为生物大分子的 3D 模型获取足​​够的质量数据。 许多网格质量较差，无法为高分辨率蛋白质模型生成足够的数据；或者样品可能含有空气/水界面相互作用产生的伪影，从而降低最终分辨率。 该二期项目将推进创新设计理念，通过无印迹样品制备技术可重复制备高质量样品。 拟议的工作将探索贸易空间并优化图像分辨率的工艺参数，从而产生先进的原型。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。