Light Engineering Module for Fast High-Resolution Whole-Cell Imaging

用于快速高分辨率全细胞成像的光工程模块

• 批准号: 10325024
• 负责人: WARREN COLOMB
• 金额: $ 73.84万
• 依托单位: DOUBLE HELIX OPTICS INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10325024
• 关键词: 3-Dimensional; Achievement; Address; Algorithms; Architecture; Brain; Cell physiology; Cells; Collaborations; Color; Colorado; Complex; Computer software; Custom; Data Collection; Degenerative Disorder; Detection; Development; Disease; Engineering; Extracellular Matrix; Feedback; Fiber Optics; Fluorescence; Heterogeneity; Image; Imaging Techniques; Institutes; Investigation; Laboratories; Lasers; Licensing; Light; Lighting; Masks; Methods; Microscope; Microscopy; Modality; Molecular; Neurons; Noise; Optics; Performance; Phase; Phototoxicity; Positioning Attribute; Protocols documentation; Readiness; Research; Resolution; Rights; Risk; Sampling; Scientist; Shapes; Signal Transduction; Signaling Molecule; Small Business Innovation Research Grant; Synapses; System; Techniques; Technology; Testing; Tetrapoda; Therapeutic; Thick; Thinness; Three-Dimensional Imaging; Time; Universities; Validation; anticancer research; base; bioimaging; brain research; cell growth; cell injury; cellular imaging; commercialization; cost effective; design; experimental study; flexibility; fluorescence imaging; imaging capabilities; imaging modality; improved; innovation; insight; instrument; live cell imaging; multimodality; novel; novel therapeutic intervention; phase 1 study; prototype; receptor; reconstruction; response; single molecule; stem cells; stress granule; temporal measurement; tumor; tumorigenesis; user-friendly

Summary This SBIR Phase II project is focused on the design refinement, development, and testing of a ground-breaking multidimensional multifunctional quantitative optical microscopy modular system suitable for live whole cell studies. The proposed Light Engineering modular system addresses the critical need for flexible imaging techniques to image live whole cells with low photodamage and phototoxicity while providing high spatial and temporal resolution as well as a large volumetric field of view. Despite extraordinary advances in optical microscopy, the availability of state-of-the-art commercial solutions has been slow to market, lacking in flexibility and ease of access. The modular instrument is based on an integrated design of the illumination, 3D optical response, data collection, and reconstruction algorithms for fluorescence imaging. Specifically, engineered 3D light excitation limits the background noise while reducing photodamage and phototoxicity. The engineered 3D point spread functions enable multiplex functionality including an extended depth of field imaging, high-sensitivity 3D localization of single-molecules or cellular heterogeneities, multi-color, and 3D imaging. As a result, the target performance outperforms the state of the art in terms of spatial/temporal resolution, signal-to-noise ratio, field of view, single-molecule localization precision, and ease of use. This project is targeted towards commercialization of a cost-effective modular solution that can be easily integrated with existing scientific microscopes. The commercial-ready prototype, will include a small footprint architecture, a set of novel optical phase masks for point spread function engineering and excitation shaping, a robust optomechanical design, and real-time experiment control software. Tests of the instrument in significant biomedical problems at partners’ labs will validate end-user acceptance and provide valuable feedback towards commercialization. The implications in biomedical imaging are far-reaching. For instance, the instrument would benefit the study of oncogenesis, owing to its degree of molecular sensitivity for detecting the spatial localization of receptors and other signaling molecules within the tumor/extracellular matrix. It would also empower the study of degenerative diseases where the instrument can help reveal their molecular origin and develop novel therapeutic strategies. The new imaging capabilities could also advance stem cell, cancer and brain research. Double Helix Optics is a startup company with exclusive licensing rights to the Light Engineering technology from the University of Colorado, as well as the novel Tetrapod and Multicolor PSF localization developments from Stanford University. The company, headquartered in the BioFrontiers Institute in Boulder, is optimally positioned to successfully bring this product to market.

总结 这个SBIR第二阶段项目的重点是设计改进，开发和测试一个突破性的 适用于活全细胞的多维多功能定量光学显微镜模块系统 问题研究拟议的光工程模块化系统解决了灵活成像的关键需求 本发明涉及一种成像活的全细胞的技术，其具有低的光损伤和光毒性，同时提供高的空间 时间分辨率以及大体积视场。 尽管光学显微镜取得了非凡的进步，但最先进的商业解决方案的可用性 市场化进程缓慢，缺乏灵活性和便利性。模块化仪器基于 照明、3D光学响应、数据收集和重建算法的集成设计， 荧光成像具体地，工程化的3D光激发限制了背景噪声，同时减少了噪声。 光损伤和光毒性。设计的3D点扩展功能可实现多路复用功能 包括扩展的景深成像、单分子或细胞的高灵敏度3D定位， 不均匀性、多色和3D成像。因此，目标性能优于最新技术水平 在空间/时间分辨率、信噪比、视场、单分子定位精度 和易用性。 该项目的目标是实现具有成本效益的模块化解决方案的商业化， 与现有的科学显微镜相结合。商业化的原型，将包括一个小的足迹， 体系结构，一套新颖的光学相位掩模的点扩散函数工程和激励整形， 稳健的光机设计和实时实验控制软件。仪器的显著性测试 合作伙伴实验室的生物医学问题将验证最终用户的接受程度，并提供有价值的反馈， 商业化 在生物医学成像的影响是深远的。例如，该文书将有助于研究 肿瘤发生，由于其检测受体空间定位的分子敏感性程度， 肿瘤/细胞外基质内的其他信号分子。这也将使研究退化性 该仪器可以帮助揭示其分子起源并开发新的治疗策略的疾病。 新的成像能力还可以推进干细胞、癌症和大脑研究。 Double Housing Optics是一家初创公司，拥有来自英国的光工程技术的独家许可权。 科罗拉多大学，以及小说四足动物和多色PSF本地化的发展，从 斯坦福大学。该公司总部位于博尔德的BioFrontiers研究所， 成功地将这一产品推向市场。