Microsystems imaging system for epithelial-derived cancer heterogeneity

用于上皮源性癌症异质性的微系统成像系统

• 批准号: 10428365
• 负责人: Kenn R Oldham
• 金额: $ 58.07万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10428365
• 关键词: Affinity; Antibodies; Appearance; Area; Binding; Biochemistry; Biology; Biomedical Engineering; Biopsy; Caliber; Cancer Model; Carcinoma; Cell surface; Cells; Clinic; Clinical; Clinical Research; Colon; Colonic Adenoma; Colorectal Cancer; Communities; Development; Devices; Dimensions; Disease; Distal; Duct (organ) structure; Endoscopes; Endoscopy; Engineering; Epidermal Growth Factor Receptor; Epithelial; Excision; Fiber; Film; Fluorescein-5-isothiocyanate; Fluorescence; Future; Genetic Heterogeneity; Human; Image; Imaging Device; Imaging technology; Immunocompromised Host; Implant; In Vitro; Individual; Kinetics; Label; Leg; Length; Lesion; Light; Malignant Neoplasms; Mechanics; Medical; Metabolic; Michigan; Molecular; Molecular Target; Mucous Membrane; Mus; NOD/SCID mouse; Noise; Optics; Organ; Organoids; Pathway interactions; Patients; Peptides; Performance; Physicians; Pre-Clinical Model; Procedures; Protein Fragment; Research; Scanning; Screening for cancer; Serrated Adenoma; Signal Transduction; Specificity; Specimen; Surface; Technology; Thinness; Time; Tissues; Translating; Tubular Adenoma; Universities; Work; adenoma; base; cancer biomarkers; cancer heterogeneity; clinical application; clinically relevant; college; contrast imaging; cost; cyanine dye 5; density; design; experience; flexibility; fluorophore; imaging agent; imaging modality; imaging system; immunogenic; in vivo; in vivo imaging; instrument; lead titanate zirconate; medical schools; microsystems; millimeter; multidisciplinary; multiplexed imaging; peroxiredoxin I; pre-clinical; premalignant; prevent; protein aminoacid sequence; prototype; tumor

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.

项目总结/摘要 大多数人类癌症起源于中空器官和导管的上皮内。出现的癌症 可以使用内窥镜检查来防止这种高度代谢活性组织的薄层自发地产生， 准确定位和切除大粘膜表面内出现的癌前病变。我们将组建一个 生物工程研究伙伴关系（BRP）之间的工程学院和医学院在 密歇根大学开发一种有针对性的内窥镜成像策略。这种强大的，特征良好的 该解决方案将能够快速监测中空器官中上皮细胞表达的癌症生物标志物。 我们将缩小尺寸的原型柔性光纤宽视场荧光内窥镜， 3.6薄膜PZT材料具有高的工作密度，将用于减小尺寸， 扫描仪的封装要求，同时保持高性能。单个扫描仪腿将 被致动以执行随机接入控制，由此可以突出显示任意区域以最大化信号对 噪声比、对比度和帧速率。我们将优化一组针对细胞表面靶点的肽 在上皮来源的癌症中早期表达。肽将用FITC、Cy 5和 IRDye 800，分别用于多路复用体内成像。这些荧光团在488、647和785激发 nm，并且光谱不重叠。将使用体外细胞验证特异性结合 和离体人类样本。我们将验证2.4 mm宽视场的体内成像性能 荧光内窥镜在使用植入的人腺瘤的结直肠癌临床前模型中的应用 类有机体这些癌前病变在外观上是平坦和微妙的，并且表达分子靶点， 在人类患者中观察到的水平代表遗传异质性。 这些目标的成功完成将导致一个原型仪器和肽面板，可以 在未来的临床翻译，为研究和医学界提供新的成像工具， 中空器官的早期癌症检测。这项高度合作的工作将由一个多学科 工程师，生物化学家和分子生物学家组成的团队，并将由TD Wang领导，他是 肽基显像剂和柔性纤维仪器的开发，以及KR奥尔德姆， 微系统技术