Light engineering module for fast high-resolution whole-cell imaging

总结 这个小企业创新研究（SBIR）第一阶段项目的重点是设计，开发， 测试一个突破性的多维多功能定量光学显微镜模块， 活细胞研究该模块将利用光工程，以实现快速高灵敏度，低噪音，高， 分辨率测量低至单分子水平，同时提供宽的体积视场。 尽管光学显微镜正在进行革命，但最先进的商业解决方案的可用性 一直以来，市场发展缓慢，缺乏灵活性，难以获得和负担得起。 所提出的仪器是基于照明，3D光学响应，数据集成设计 收集和荧光成像的重建算法。具体来说，工程3D光激发 限制了背景噪声，同时降低了光损伤和光毒性。3D点的工程 扩展功能实现多路复用功能，包括扩展景深、高灵敏度3D 单分子或细胞异质性的定位、多色和3D成像。集成系统 将使重建具有卓越的切片能力。因此，目标性能指标， 在学术实验室最近的研究演示的支持下， 空间/时间分辨率、信噪比、视场和易用性。 这个SBIR项目的目标是实现一个具有成本效益的解决方案的商业化，可以很容易地集成 现有的科学显微镜。将从第一阶段原型开发的商业模块将 包括小覆盖区结构、用于点扩展函数工程一组新颖的光学相位掩模 和激励整形、稳健的光学机械设计以及实时实验控制软件。的测试 在合作伙伴实验室解决重大生物医学问题的仪器将验证最终用户的接受程度，并提供 对商业化有价值的反馈。 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。 新的成像能力可以进一步帮助干细胞和大脑研究。 Double Housing Optics是一家初创公司，拥有成熟的记录和光的独家许可权。 来自科罗拉多大学的工程技术，以及新颖的四足和多色PSF 来自斯坦福大学的本地化发展。该公司总部设在美国的生物前沿研究所（BioFrontiers Institute）。 博尔德，是最佳的定位，成功地将这一产品推向市场。

Summary This Small Business Innovation Research (SBIR) Phase I project is focused on the design, development, and testing of a ground-breaking multidimensional multifunctional quantitative optical microscopy module suitable for live whole cell studies. The module will utilize Light Engineering to achieve fast high-sensitivity, low-noise, high- resolution measurements down to the single-molecule level while providing wide volumetric field of view. In spite of the ongoing revolution in optical microscopy, the availability of state-of-the-art commercial solutions has been slow to market, lacking in flexibility, ease of access and affordability. The proposed 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 photo-damage and photo-toxicity. The engineering of the 3D point spread function enables multiplex functionality including an extended depth of field, high-sensitivity 3D localization of single-molecules or cellular heterogeneities, multi-color, and 3D imaging. The integrated system will enable reconstruction with superb sectioning capability. As a result, the target performance metrics, supported by recent research demonstrations in academic labs, outperform the state of the art in terms of spatial/temporal resolution, signal-to-noise ratio, field of view, and ease of use. This SBIR project is targeted towards commercialization of a cost-effective solution that can be easily integrated with existing scientific microscopes. The commercial module, to be developed from the Phase I 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 further assist in stem cell and brain research. Double Helix Optics is a startup company with a proven record and 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.