SBIR Phase I: Affordable Three-dimensional Microscopic Imaging

这个小企业创新研究第一阶段项目将通过使用电子控制的聚焦元件，提供价格合理的三维（3D）显微成像。科学家们渴望观察完整的、活的细胞或动物体内快速发生的生物现象。荧光标记的最新进展显著改善了药物传递的跟踪和细胞膜动态事件的观察。然而，实验室通常需要昂贵的扫描显微镜，如共聚焦或双光子，具有三维荧光成像能力来观察这些事件。拟议中的技术将增加3D、高分辨率成像的可及性，从而促进科学的进步。它还将提高图像采集的速度，减少标本的光漂白和光损伤，扩展纵向研究能力，减少敏感样品的搅拌和损伤。它有望在生物现象、物理现象和新的荧光成像方式方面带来新的发现。直接潜在市场的价值是5000万美元。该技术还有望通过提供高速和灵活的焦点控制，使制造或机器视觉的3D成像系统、小型化光盘采集、共聚焦和双光子显微镜、光学相干断层扫描和内窥镜成像系统受益。这个项目的智力价值集中在展示一种新的3D，高分辨率成像技术的可行性。该项目包括微机电反射镜的开发和一种新的光学机械设计。总电子对焦控制能力直到最近才变得可用。因此，最好地利用这些元素的标准光学设计实践并不存在。该项目的目标有三个方面：1)推进变焦元件的光学设计方法，2)开发一种新的光学机械设计，以及3)进一步发展微机电系统（MEMS）反射镜技术。第一阶段的研究和开发将确定光机械设计和MEMS镜像性能的可行性，以满足3D生物成像需求，成本低于当前可用技术的四分之一。技术成果将包括分析新的光学机械设计和MEMS反射镜的特性。

This Small Business Innovation Research Phase I project will provide affordable, three-dimensional (3D) microscopic imaging through the use of an electronically-controlled, focusing element. Scientists desire to observe biological phenomena in intact, living cells or animals that occur on fast time scales. Recent advances in fluorescent markers have significantly improved tracking of drug delivery and observation of dynamic events in cell membranes. However, laboratories often need expensive scanning microscopes, such as confocal or two-photon, with 3D fluorescent imaging capability to observe such events. The proposed technology will increase accessibility of 3D, high-resolution imaging, thereby enabling advancements in science. It will also improve the speed of image acquisition, reduce photobleaching and photodamage of specimens, extend longitudinal studies capabilities, and reduce agitation and damage of sensitive samples. It is expected to lead to new discoveries with regard to biological phenomena, physical phenomena, and novel fluorescent imaging modalities. The value of the immediate addressable market is $50 million. The technology also promises to benefit 3D imaging systems for manufacturing or machine vision, miniaturized optical disk pick-ups, confocal and two-photon microscopes, optical coherence tomography, and endoscopic imaging systems by providing high speed and agile focus control.The intellectual merit of this project centers on the demonstration of the feasibility of a novel 3D, high-resolution imaging technology. The project includes development of microelectromechanical mirrors and a novel optomechanical design. Gross electronic focus control capability has only recently become available. As such, standard optical design practices to best utilize these elements do not exist. The goals of this project are three fold: 1) to advance optical design methods for varifocus elements, 2) to develop a novel optomechanical design, and 3) to further microelectromechanical systems (MEMS) mirror technology. The research and development to be undertaken in Phase I will determine feasibility of the optomechanical design and of the MEMS mirror performance to meet 3D biological imaging needs at a cost less than one quarter of currently available technology. Technical results will include analysis of the new optomechanical design and characterization of the MEMS mirrors.