SBIR Phase I: Instrumentation for In-situ CLEM (Correlated Light and Electron Microscopy)

这个小型企业创新研究(SBIR)第一阶段项目将展示用于电子和离子显微镜的光学显微镜附件的科学和技术可行性，使原位亮场和荧光显微镜能够同时进行电子或离子成像/处理。这直接解决了相关光学和电子显微镜(CLEM)领域的一个关键机会，这是在结构生物学中广泛应用的一个基本应用，以促进对健康和疾病的了解。光学显微镜提供低倍的概览，荧光成像识别罕见的细胞和事件(但只揭示信号的位置和强度)，而电子显微镜提供高分辨率来研究与荧光信号相关的超微结构。相关显微镜架起了这些方法从微米到纳米分辨率的不同长度尺度的桥梁，并提供了荧光图像中缺失的细节。这项研究的更广泛影响广泛应用于材料、食品科学和纳米技术，包括一种戏剧性的新的生物学调查能力，有助于加快癌症治疗、药物发现和蛋白质组研究等应用的发展步伐。它可以通过一个简单的附件在广泛存在的SEM和FIB平台上以低成本展开。这促进了新的研究创新。原位Clem的显著准确性和节省的时间可以加快研究，使临床研究和药物开发的生物标记物能够更快地发现和开发。FDA估计，仅在临床试验前预测药物失败的能力提高10%，就可以为每种药物节省1亿美元的开发成本。

This Small Business Innovation Research (SBIR) Phase I project will demonstrate the scientific and technical feasibility of an optical microscope accessory for electron and ion microscopes to enable in situ brightfield and fluorescence microscopy simultaneously with electron or ion imaging/processing. This directly addresses a critical opportunity in the area of correlative light and electron microscopy (CLEM), a fundamental application applied broadly in structural biology for advancing understanding of health and disease. Light microscopy provides low magnification overviews, fluorescence imaging identifies rare cells and events (but reveals only signal location and intensity), and electron microscopy provides high resolution to study ultrastructure associated with the fluorescent signal. Correlative microscopy bridges the different length scales of these methods from micron to nanometer resolution and provides the detail missing in fluorescence images.The broader impacts of this research are widely applicable to materials, food science, and nanotechnology and include a dramatic new capability for biological investigation that contributes to advancing the pace of development in applications such as cancer treatment, drug discovery and proteomics research. It can be fanned out at low cost through a simple accessory on broadly existing SEM and FIB platforms. This promotes new research innovations. The significant accuracy and time savings with in situ CLEM can speed research, enabling faster discovery and development of biomarkers for clinical research and drug development. The FDA estimates that just a 10% improvement in the ability to predict drug failures before clinical trials could save US$100 million in development costs per drug.