SBIR Phase I: Wavefront Microscopy: A low-cost implementation of high-quality microscopic phase imaging for bioscience teaching and training

该小型企业创新研究(SBIR)第一阶段项目旨在为标准显微镜开发一种低成本、易用的图像传感附件，提供相位成像功能。传感器芯片本身的特殊处理取代了这种专门的显微镜技术通常所需的大块光学功能。开发这种设备必须解决的主要挑战涉及当前可用的传感器芯片在像素大小和传感器噪声方面的基本限制。这项研究的目标是开发创新的软件算法，以在现有的传感器芯片上实现所提出的技术。这将涉及分离相邻传感器元件的贡献，以最大限度地提高分辨率和最小化串扰。然后，我们将根据标准分辨率目标以及用于低水平教学实验室练习的感兴趣的土壤微生物样本来评估这些设备。最后，该团队将开发一个互动软件平台，将该设备整合到教育环境中。首席调查员预计将开发一种功能设备，在图像平面上的分辨率至少为11微米，串扰限制在5%，能够在40倍以上的放大倍数下进行衍射限制成像。该项目的更广泛的影响/商业潜力可以总结如下。这项建议描述了一种简单的方法，使显微镜用户能够获得高质量的相位成像，以查看透明样品。这对许多细分市场都很重要，特别是研究、临床和工业细分市场。成像设备不使用必须由训练有素的显微镜专家仔细对准的光学部件，只需拧紧显微镜的相机端口即可。由于所需的制造程序很简单，这种设备可以低成本开发，用于以有限预算运行的教学和培训实验室。数字图像显示在可供多名学员或实习生同时查看的屏幕上。此外，这种新型图像传感器能够显示比任何标准相位成像显微技术更多的信息，潜在地使新的研究方向或新的临床诊断成为可能。目前的市场机会既包括销售带有新显微镜的此类设备，替换现有的阶段组件，也包括大量安装基础(目前正在使用的显微镜)，我们的设备可以进行改造。由于显微镜上的摄像头端口是标准化的，所以这次改造不会带来技术挑战。

This Small Business Innovation Research (SBIR) Phase I project aims to develop a low-cost, easy-to-use, image sensing attachment for standard microscopes that provides phase imaging capabilities. The functionality of the bulk optics typically required for such a specialized microscopy technique is replaced by special processing of the sensor chip itself. The major challenges that must be addressed to develop such a device involve the fundamental limitations of currently available sensor chips in terms of both pixel size and sensor noise. The objective of this research is to develop innovative software algorithms to implement the proposed technology on available sensor chips. This will involve separating the contributions of adjacent sensor elements with the goal of maximizing resolution and minimizing cross-talk. We will then evaluate the devices based on a standard resolution target as well as samples of microscopic soil-borne organisms of interest for low-level teaching laboratory exercises. Finally, the team will develop an interactive software platform for integrating the device in an educational setting. The Principal Investigator anticipates the development of a functional device with a resolution of at least 11 µ in the image plane and cross-talk limited to 5% that is capable of diffraction-limited imaging at magnifications above 40x.The broader impact/commercial potential of this project can be summarized as follows. This proposal describes a simple method that allows microscope users to gain access to high-quality phase imaging for viewing transparent samples. This is important for a number of market segments, specifically research, clinical, and industrial segments. Instead of using optical components that must be carefully aligned by a highly trained microscopist, the imaging device simply screws onto the camera port of a microscope. Since the required fabrication procedures are straightforward, this device can be developed at low-cost for use in teaching and training labs that operate on limited budgets. Digital images are displayed on a screen that can be viewed by multiple students or trainees at one time. Additionally, this novel image sensor is capable of displaying more information than any standard phase imaging microscopy technique, potentially enabling new research directions or new clinical diagnostics. The current market opportunity includes both the sale of such devices with new microscopes, replacing existing phase components, as well as a large amount of installed base (microscopes currently in use) to which our device can be retrofit. Since the camera port on microscopes is standardized, this retrofit does not pose technical challenges.