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

SBIR 第一阶段：原位 CLEM（相关光学和电子显微镜）仪器

• 批准号: 0945896
• 负责人: Cheryl Hartfield
• 金额: $ 15万
• 依托单位: Omniprobe
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0945896&HistoricalAwards=false
• 关键词: SBIR; Phase; Instrumentation; situ; CLEM

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.

这个小企业创新研究（SBIR）第一阶段项目将展示电子和离子显微镜的光学显微镜配件的科学和技术可行性，以实现原位明场和荧光显微镜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，CLEM是结构生物学中广泛应用的一个基本应用，用于促进对健康和疾病的理解。光学显微镜提供低放大率概览，荧光成像识别罕见细胞和事件（但仅显示信号位置和强度），电子显微镜提供高分辨率以研究与荧光信号相关的超微结构。相关显微镜将这些方法从微米到纳米分辨率的不同长度尺度连接起来，并提供荧光图像中缺失的细节。这项研究的更广泛影响广泛适用于材料、食品科学和纳米技术，包括一种引人注目的生物学研究新能力，有助于推进癌症治疗、药物发现和蛋白质组学研究等应用的发展步伐。它可以通过广泛存在的SEM和FIB平台上的简单配件以低成本散开。这促进了新的研究创新。原位CLEM的显著准确性和时间节省可以加速研究，从而能够更快地发现和开发用于临床研究和药物开发的生物标志物。FDA估计，在临床试验前预测药物失败的能力只要提高10%，就可以为每种药物节省1亿美元的开发成本。