SBIR Phase I: Widefield 3D Superresolution Microscopy Module

SBIR 第一阶段：宽场 3D 超分辨率显微镜模块

• 批准号: 1248873
• 负责人: Anurag Agrawal
• 金额: $ 15万
• 依托单位: Double Helix Optics Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1248873&HistoricalAwards=false
• 关键词: SBIR; Phase; Widefield; 3D; Superresolution

This Small Business Innovation Research Program (SBIR) Phase I project investigates the feasibility of a ground-breaking three-dimensional (3D) optical microscope with single-molecule sensitivity suitable for live cell studies and nanometer scale sensing. Several methods have recently shown resolution well beyond the optical diffraction limit, which restricts imaging to features larger than about 200 and 500 nm in the transverse and axial dimensions respectively. To date, these super-resolution techniques have been demonstrated in specialized labs but new developments are required to reach the fundamental limits on a regular basis at the typical biology lab. Therefore, this project focuses on fundamental technological developments to address the upcoming need for pervasive 3D superresolution single-molecule capabitlities. The instrument is based on a joint design of the illumination, optical response, data collection approach, and reconstruction algorithms for fluorescence imaging. The instrument makes use of tailored point spread functions that enable the determination of the 3D position of emitters with great precision, leading to better resolution and depth of field than competing methods. Preliminary laboratory experiments have shown 3D capability with resolutions below 20nm, which corresponds to one order of magnitude enhancement over most optical microscopes presently in use. The broader impact/commercial potential of this project addresses a major opportunity in an expanding biological instrumentation market. If successful, it will enable 3D superresolution imaging capability to many biological laboratories currently limited by past technologies. The feasibility plan opens up opportunities for an accelerated commercialization path by implementing a cost-effective flexible solution compatible with existing microscopes. The extensive availability of superresolution imaging will impact several fields of science and engineering including 3D biophysical and biomedical optical imaging. During the project the company will generate synergistic relationships to rapidly transfer the technology into applications. The company has established partnerships for testing the instrument in significant biological problems that are expected to contribute to a better understanding of diseases. From a broader perspective, this project will increase scientific technical capabilities by providing nanoscale optical imaging for everyday biological research, thereby strengthening US presence in the worldwide optical microscopy industry.

这项小型企业创新研究计划（SBIR）I期项目研究了具有适合活细胞研究和纳米尺度感测的单分子灵敏度的突破性三维（3D）光学显微镜的可行性。最近，几种方法显示了远远超出光学衍射极限的分辨率，这将成像限制在横向和轴向尺寸中的大约200和500 nm的特征。迄今为止，这些超分辨率技术已在专业实验室中得到证明，但是需要新的发展才能在典型的生物学实验室定期达到基本限制。因此，该项目侧重于基本技术发展，以满足即将到来的普遍3D超分辨率单分子帽子的需求。该仪器基于照明，光学响应，数据收集方法和用于荧光成像的重建算法的联合设计。该仪器利用量身定制的点扩散功能，使发射器的3D位置具有很高的精度，从而比竞争方法更好地分辨率和景深。初步实验室实验显示了3D能力，分辨率低于20nm，这对应于目前使用的大多数光学显微镜的一个数量级增强顺序。该项目的更广泛的影响/商业潜力解决了不断扩展的生物仪器市场的主要机会。如果成功，它将为许多当前受过去技术限制的生物实验室提供3D超分辨率成像能力。可行性计划通过实施与现有显微镜兼容的具有成本效益的灵活解决方案，为加速商业化路径开辟了机会。超分辨率成像的广泛可用性将影响科学和工程的几个领域，包括3D生物物理和生物医学光学成像。在项目期间，公司将产生协同关系，以将技术迅速转移到应用程序中。该公司建立了合作伙伴关系，以在重大生物学问题中测试该工具，这有望有助于更好地了解疾病。从更广泛的角度来看，该项目将通过为日常生物学研究提供纳米级光学成像来提高科学技术能力，从而增强我们在全球光学显微镜行业中的存在。