SBIR Phase II: Real-time Active Image Stabilization for Microscopy

这个小型企业创新研究（SBIR）第二阶段项目将开发和商业化一个集成系统，以主动稳定光学显微镜，以满足当今尖端成像方法所需的精度。生物科学中的显微镜在几个方面都取得了根本性的进展。 “超分辨率”（SR）技术绕过了分辨率的衍射极限，一度被认为是不可逾越的，并承诺在分子水平上成像细胞生物学的结构和过程的能力。 这将在理解细胞内部运作方面带来深刻的进步。 然而，在广泛使用SR技术的道路上仍然存在重大的相互关联的障碍：（1）它们在技术上具有挑战性，（2）实施成本高;（3）它们对显微镜平台提出了物理要求，这不是设计来满足的。 这些需求中最重要的是SR方法需要控制生物样品的移动和具有纳米精度的显微镜系统的稳定性。 这种商业化的集成系统专门设计用于解决这些问题并消除这些障碍。 它使用一个3轴，压电驱动的纳米定位平台来控制样品的运动，并积极保持系统的稳定性，使用图像作为这种稳定性的参考点。该项目更广泛的影响/商业潜力在于使SR方法对工作生物学家常规有用。这些“改变游戏规则”的工具将促进我们对疾病病理学分子基础的理解，并使针对其治疗的方法更加精确。 新的见解将从分子病毒学和更安全，更有效的疫苗的发展，神经元信号和学习和记忆的分子机制。 事实上，很难想象细胞生物学领域不会受到这些新兴SR技术的影响。这些方法的先驱之一将它们比作哈勃望远镜：它们使人们能够看到以前无法看到的东西。 这一类比更进一步：目前只有一台哈勃望远镜，并且由于常规使用的技术和经济障碍，目前很少有具有SR能力的成像系统。 虽然SR方法以尖锐的方式暴露了显微镜的物理限制，但其稳定性和图像采集要求并不独特。 因此，这种商业系统将有更广泛的用途：它还将使任何长期成像实验的焦点稳定性和纳米尺度的分子跟踪成为可能。

This Small Business Innovation Research (SBIR) Phase II project will develop and commercialize an integrated system to actively stabilize an optical microscope to the precision required by today's cutting-edge imaging methods. Microscopy in the biological sciences is undergoing radical advancement on several fronts. "Super-Resolution" (SR) techniques circumvent the diffraction limit on resolution once thought to be insurmountable, and promise the ability to image the structures and processes of cell biology at the molecular level. This will usher in profound advancements in the understanding of the inner-workings of the cell. However, significant interrelated barriers remain in the path towards widespread use of SR techniques: (1) they are technically challenging and (2) expensive to implement; and (3) they place physical demands on the microscope platform it was not designed to meet. Foremost of these demands is that SR methods require control over the movement of the biological sample and the stability of the microscope system with nanometer precision. This commercialized integrated system is designed specifically to address these issues and remove these barriers. It uses a 3-axis, piezo-driven nanopositioning stage to control sample motion and actively maintains the stability of the system using the image as the reference point for this stability.The broader impact/commercial potential of this project lies in making SR methods routinely useful to working biologists. These "game-changing" tools will advance our understanding of the molecular bases of disease pathologies, and enable far more exacting methods aimed at their treatments. The new insights will range from those in molecular virology and the development of safer and more effective vaccines, to the molecular mechanisms of neuronal signaling and learning and memory. In fact, it is hard to imagine an area of cell biology that will not be impacted by these emerging SR techniques. One of the pioneers of these methods has likened them to the Hubble telescope: they enable people to see things they simply could not see before. This analogy goes further: there is only one Hubble telescope, and currently very few SR-capable imaging systems, due to both the technical and economic barriers to their routine use. And while SR methods expose the physical limitations of microscopes in an acute manner, their stability and image acquisition requirements are not unique. Thus, this commercial system will be much more broadly useful: it will also enable focal-stability and molecular tracking at the nanometer-scale for any long-term imaging experiment.