Microsystems imaging system for epithelial-derived cancer heterogeneity

项目摘要/摘要 大多数人类癌症起源于中空器官和导管的上皮组织。出现的癌症 使用内窥镜检查可以防止自发地从这一薄层高度代谢活跃的组织中 准确定位和切除发生在大粘膜表面的癌前病变。我们将组成一个 工程学院和医学院之间的生物工程研究伙伴关系(BRP 密歇根大学开发了一种有针对性的内窥镜成像策略。这是一种健壮的，特征很好的 该解决方案将能够快速监测由中空器官中的上皮表达的癌症生物标记物。 我们将把柔性光纤广域荧光内窥镜的原型尺寸从 3.6到2.4毫米。薄膜PZT材料具有较高的工作密度，将用于减小尺寸和 在保持高性能的同时满足扫描仪的包装要求。单独的扫描仪支路将是 被驱动以执行随机访问控制，从而可以突出显示任意区域以最大化信令比 噪波比、对比度和帧速率。我们将优化一组针对细胞表面靶标的多肽 在上皮来源的癌症中早期表达。这些多肽将被FITC、Cy5和 IRDye800，分别用于体内多路传输成像。这些荧光团的激发温度分别为488、647和785 Nm，光谱互不重叠。特异性结合将在体外使用细胞进行验证 以及体外培养的人类标本。我们将验证2.4 mm宽视场的活体成像性能 荧光内窥镜在结直肠癌临床前移植瘤模型中的应用 有机化合物。这些癌前病变外观平坦而细微，并表达分子靶点。 遗传异质性在人类患者中所见的水平上具有代表性。 成功完成这些目标将产生一个原型仪器和多肽板，可以 未来将进行临床翻译，为研究和医学界提供新的成像工具 在中空器官中早期发现癌症。这项高度协作的工作将由一个多学科的 由工程师、生物化学家和分子生物学家组成的团队，将由TD Wang领导，他是 基于多肽的显像剂和柔性纤维仪器的发展，以及KR Oldham， 微系统技术。

Project Summary/Abstract Most human cancers originate within the epithelium of hollow organs and ducts. Cancers that arise spontaneously from this thin layer of highly metabolically active tissue can be prevented using endoscopy to accurately localize and resect pre-malignant lesions that arise within large mucosal surfaces. We will form a Bioengineering Research Partnership (BRP) between the College of Engineering and the Medical School at the University of Michigan to develop a targeted endoscopic imaging strategy. This robust, well-characterized solution will enable rapid surveillance of cancer biomarkers expressed by the epithelium in hollow organs. We will scale down the dimensions of a prototype flexible fiber wide-field fluorescence endoscope from 3.6 to 2.4 mm. Thin-film PZT materials have high work density and will be used to reduce the size and packaging requirements for the scanner while maintaining high performance. Individual scanner legs will be actuated to perform random access control whereby arbitrary regions can be highlighted to maximize signal-to- noise ratio, contrast, and frame rate. We will optimize a panel of peptides specific for cell surface targets expressed early in epithelial-derived cancers. The peptides will be fluorescently-labeled with FITC, Cy5, and IRDye800, respectively, for multiplexed in vivo imaging. These fluorophores are excited at 488, 647, and 785 nm, respectively, and the spectra are non-overlapping. Specific binding will be validated using cells in vitro and human specimens ex vivo. We will verify the in vivo imaging performance of the 2.4 mm wide-field fluorescence endoscope in a pre-clinical model of colorectal cancer using implanted human adenoma organoids. These pre-cancerous lesions are flat and subtle in appearance, and express molecular targets with genetic heterogeneity at levels representative of those seen in human patients. Successful completion of these aims will result in a prototype instrument and peptide panel that can be clinically translated in the future to provide the research and medical community with new imaging tools for early cancer detection in hollow organs. This highly collaborative effort will be performed by a multi-disciplinary team of engineers, biochemists, and molecular biologists, and will be led by TD Wang, an expert in the development of peptide-based imaging agents and flexible fiber instruments, and by KR Oldham, an expert in microsystems technology.