CANCER MOLECULE ANALYSIS BY AOTF MULTISPECTRAL IMAGING

通过 AOTF 多光谱成像进行癌症分子分析

• 批准号: 6335312
• 负责人: DANIEL L FARKAS
• 金额: $ 13.86万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6335312
• 关键词: biomedical equipment development; flow cytometry; fluorescent dye /probe; ionophores; microscopy; optics; spectrometry

DESCRIPTION: (Provided by applicant) The importance of cancer research and the inherent complexity of its challenges make it very important to design strategic, innovative approaches. Investigating the accumulation of multiple abnormalities per cell at the molecular level has prognostic value in cancer research. We propose to develop the capability to study this issue with optimal quantitative ability, discrimination and throughput by (a) focusing our proprietary technologies towards the goal of this solicitation; (b) developing the next-generation imaging cytometry instrument, able to bypass previous imitations; (c) raising the much needed optics/hardware/software /biology/clinical application continuum to a new level. We will concentrate on the imaging of 5-10 molecular species simultaneously within the same cancer cell, with a new approach and instrument that we propose to develop, based on our previous advances in acousto-optic technologies and multispectral imaging. The aims are largely technologic, but their implementation will allow us to (a) elucidate critical sequences of genetic evolutionary changes in solid tumors that are responsible for increasing cancer aggressiveness; (b) identify the steps in the sequence that are most closely associated with cellular acquisition of the capacity to metastasize, and (c) develop a practical overall approach for the timely performance of relevant measurements on individual tumors, analysis of the data, and characterization of each tumor with respect to the degree of its advancement along its particular genetic evolutionary pathway, so that this information can be used for prognosis and adjuvant treatment planning. The ultimate clinical challenge is the elimination of false negatives and false positives in diagnostics, leading to individually optimized treatment and very significant savings. The technological task specifically addressed is the design and development of the ability to quantitative simultaneously, in the same cell, a sufficiently large number of molecular species to enable a qualitative leap in diagnosis and treatment. The emphasis is on fluorescence, due to its very high specificity for labeling intracellular features, and the central new technology is acousto-optic tunable filters, a tool whose use in microscopic imaging we perfected and patented. Specific aims include (1) the building of a prototype instrument with the desired new functionality; (2) the implementation of a second, more user-friendly workstation in our cancer research laboratories; (3) the thorough testing of the latter instrument in experiments focusing on molecular-level prognostic factors for tumor progression within single cells of individuals' tumors, and (4) the development of a productized customizable version of the instrument embodying the new technology, multispectral imaging, ready for use on an array of problems by other researchers. A collaborative, multidisciplinary team is proposed for implementation of these goals.

描述：（申请人提供） 癌症研究的重要性及其固有的复杂性 挑战使得设计战略性的创新办法非常重要。 研究了每个细胞的多个异常的累积， 分子水平在肿瘤研究中具有预后价值。我们建议发展 以最佳的定量能力来研究这个问题的能力， 通过（a）专注于我们的专有技术 （B）开发下一代 成像细胞仪，能够绕过以前的模仿;（c）提高 急需的光学/硬件/软件/生物学/临床应用 连续到一个新的水平。我们将专注于5-10个分子的成像， 同时在同一个癌细胞内的物种，用一种新的方法， 我们建议开发的工具，基于我们以前的进展， 声光技术和多光谱成像。目标主要是 技术，但其实施将使我们能够（a）阐明关键 实体瘤中的遗传进化变化序列， 用于增加癌症侵袭性;（B）识别序列中的步骤 与细胞获得能力最密切相关的， （c）制定一个切实可行的全面办法， 对单个肿瘤进行相关测量， 数据，以及每个肿瘤相对于其 沿着其特定的遗传进化路径前进， 这些信息可用于预后和辅助治疗计划。的 最终的临床挑战是消除假阴性和假阴性。 积极的诊断，导致个性化优化治疗， 显著的节省。具体涉及的技术任务是 设计和开发的能力，以定量的同时，在 同样的细胞，足够多的分子种类，使一个 诊断和治疗的质的飞跃。重点是荧光， 由于其对标记细胞内特征具有非常高的特异性， 核心的新技术是声光可调谐滤波器，这种工具可以用于 我们完善并申请了专利的显微成像技术。具体目标包括：（1） 建立具有所需新功能的原型仪器;（2） 在癌症中心设立第二个更方便使用电脑工作站 （3）对后一种仪器进行彻底的测试， 肿瘤分子水平预后因子实验 个体肿瘤的单细胞内的进展，以及（4） 开发产品化的可定制版本的仪器， 新技术，多光谱成像，准备用于阵列， 其他研究人员的问题。一个多学科的协作团队， 为实现这些目标。

项目成果

Automated quantification of DNA demethylation effects in cells via 3D mapping of nuclear signatures and population homogeneity assessment.

• DOI: 10.1002/cyto.a.20740
• 发表时间: 2009-07
• 期刊: CYTOMETRY PART A
• 影响因子: 3.7
• 作者: Gertych, Arkadiusz;Wawrowsky, Kolja A.;Lindsley, Erik;Vishnevsky, Eugene;Farkas, Daniel L.;Tajbakhsh, Jian
• 通讯作者: Tajbakhsh, Jian