SBIR Phase I: CryoPREP-EM: Time-Resolved Sample Preparation for Single-Particle Cryo-Electron Microscopy (Cryo-EM)

SBIR 第一阶段：CryoPREP-EM：单颗粒冷冻电子显微镜 (Cryo-EM) 的时间分辨样品制备

• 批准号: 1820414
• 负责人: Trevor McQueen
• 金额: $ 22.5万
• 依托单位: Neptune Fluid Flow Systems LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2020-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1820414&HistoricalAwards=false
• 关键词: SBIR; Phase; CryoPREP; EM; Time

This Small Business Innovation Research Phase I project will evaluate the technical feasibility and commercial viability of a novel sample preparation method for cryo-EM (cryogenic electron microscopy) studies. As a rapidly growing technique in the structural biology field, the cryo-EM market as a whole is estimated to be more than $5 billion a year, with $500 million attributed to the sample preparation space. In spite of an overall revenue growth rate of more than 70% per year, cryo-EM sample preparation remains an area that has yet to see any major technological breakthroughs commercialized in the past decade. In fact, the current industry solution is reported to have a failure rate of 95%. By providing a sample preparation system that actually works, this Small Business Innovation Research (SBIR) Phase I project will significantly reshape the massive and rapidly expanding cryo-EM market and allow scientists to more readily collect detailed protein structures in their native state. This new knowledge on the molecular basis of cells and of life itself will be used to facilitate as well as accelerate the development of new pharmaceuticals as well as therapeutic treatments for diseases and thus greatly benefit human health in the long run.The intellectual merit of this project is the development of a cryo-EM sample preparation device built on the application of state-of-the-art microfluidic jet systems to deposit and vitrify protein solution on EM grids in milliseconds, which is at least 1000x faster than the current methods. Furthermore, it offers scientists the novel ability to control the thickness of the vitrified aqueous layer and, overall, more control over the sample vitrification process. With this new sample preparation device, a larger region of the cryo-EM grids will have intact protein molecules with the right layer thickness for structural determination, allowing researchers to save time and money in terms of both grid preparation and screening in a high-throughput manner. Currently, the proposed technology has not been tested nor used anywhere. Therefore, the first and foremost goal of this SBIR Phase I project is to better understand and well characterize the technical capabilities and limitations of this proposed innovation, with additional R&D work needed before product commercialization, which is expected in five years. The project will focus on defining and optimizing both the geometric and experimental setup in order to de-risk the technology.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.

这个小型企业创新研究阶段I项目将评估用于低温EM（低温电子显微镜）研究的新型样品制备方法的技术可行性和商业可行性。 作为在结构生物学领域的一种快速增长的技术，整个冷冻EM市场估计每年超过50亿美元，归因于样本准备空间的5亿美元。 尽管每年的总收入增长率超过70％，但冷冻EM样本制备仍然是一个尚未看到过去十年中任何主要的技术突破的领域。 实际上，据报道，当前的行业解决方案的故障率为95％。 通过提供实际有效的样品制备系统，这项小型企业创新研究（SBIR）I阶段项目将显着重塑大规模且迅速扩大的冷冻EM市场，并允许科学家更容易地收集其本土状态的详细蛋白质结构。 关于细胞和生命本身分子基础的新知识将用于促进和加速新药的发展以及对疾病的治疗治疗方法，因此从长远来看，该项目的智力优点是该项目的智力优点。毫秒，它比当前方法快至少1000倍。 此外，它为科学家提供了控制玻璃化水层厚度的新颖能力，总体而言，对样品玻璃化过程的控制更加控制。 使用这种新的样品制备设备，较大的冷冻EM网格区域将具有完整的蛋白质分子，其层厚度正确，可用于结构测定，从而使研究人员可以以高通量方式节省时间和金钱。 目前，拟议的技术尚未在任何地方进行测试或使用。 因此，该SBIR I阶段项目的第一个也是最重要的目标是更好地理解和很好地表征这项拟议创新的技术能力和局限性，并在产品商业化之前需要进行其他研发工作，这是预计在五年内。 该项目将着重于定义和优化几何和实验设置以降低技术。该奖项反映了NSF的法定任务，并且使用基金会的智力优点和更广泛的影响评估标准，被认为值得通过评估来获得支持。