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

这项小型企业创新研究（SBIR）第一阶段项目旨在开发一种低成本、易于使用的标准显微镜图像传感附件，提供相位成像能力。这种专门的显微镜技术通常需要的大块光学的功能被传感器芯片本身的特殊处理所取代。开发这种设备必须解决的主要挑战涉及当前可用传感器芯片在像素大小和传感器噪声方面的基本限制。本研究的目的是开发创新的软件算法，以实现在可用的传感器芯片上提出的技术。这将涉及分离相邻传感器元件的贡献，目标是最大化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对低水平教学实验室练习感兴趣的微观土壤传播生物样本评估这些设备。最后，该团队将开发一个交互式软件平台，将该设备集成到教育环境中。首席研究员期望开发一种功能设备，其成像平面分辨率至少为11µ，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。该项目的广泛影响/商业潜力可概括如下：本提案描述了一种简单的方法，允许显微镜用户获得高质量的相位成像，以观察透明样品。这对许多细分市场都很重要，特别是研究、临床和工业领域。这种成像设备无需使用光学元件，而必须由训练有素的显微镜专家仔细校准，只需将其固定在显微镜的相机端口上即可。由于所需的制造过程很简单，这种设备可以以低成本开发，用于预算有限的教学和培训实验室。数字图像显示在屏幕上，可由多名学生或学员同时查看。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镜技术更多的信息，潜在地实现新的研究方向或新的临床诊断。目前的市场机会包括销售这些设备与新的显微镜，取代现有的相位组件，以及大量的安装基础（目前使用的显微镜），我们的设备可以进行改造。由于显微镜上的相机端口是标准化的，这种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.