Develop extremely-high-yield (5-10x conventional methods) tissue microarray techn

开发极高产量（5-10倍传统方法）组织微阵列技术

• 批准号: 8648567
• 负责人: William Scott Crawford
• 金额: $ 22.43万
• 依托单位: ARRAY SCIENCE, LLC
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-08 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8648567
• 关键词: Air; American; Automation; Big Data; Biological; Calibration; Cancer Diagnostics; Cell Culture Techniques; Computers; Data; Defect; Devices; Diagnosis; Diagnostic tests; Documentation; ERBB2 gene; Elements; Future; Goals; Heating; Histocompatibility Testing; Histologic; Histology; Image; Image Analysis; Immunohistochemistry; Laboratories; Legal patent; Light; Liquid substance; Marketing; Measurement; Mechanics; Methods; Microarray Analysis; Microscope; Microtomy; Morphologic artifacts; Outcome; Output; Paraffin; Pathologist; Pattern; Phase; Placenta; Preparation; Procedures; Process; Production; Public Health; Quality Control; Research; Resolution; Sampling; Scanning; Science; Services; Slice; Slide; Solid; Source; Standardization; Surveys; Suspension substance; Suspensions; Techniques; Technology; Temperature; Testing; Tissue Donors; Tissue Embedding; Tissue Microarray; Tissue Sample; Tissues; Tonsil; Validation; Variant; Waxes; anticancer research; base; cancer diagnosis; college; commercialization; comparative; design; feeding; improved; instrument; interest; malignant breast neoplasm; malignant stomach neoplasm; myometrium; novel; portability; pressure; programs; public health relevance; research and development; research clinical testing; retinal rods; success; tumor; virtual; wasting

DESCRIPTION (provided by applicant): We (Array Science, LLC) propose to perform detailed research and development of our patent-pending method and instrument for high-yield production of tissue microarrays (TMAs). Our approach to TMA production is novel in leveraging the liquid phase of standard histologic embedding media such as paraffin, and in so doing we achieve unprecedented levels of utilization of precious biological tissue sources. The outcome of this technique has proven highly beneficial in cancer diagnostics, where it has produced over 1.3 million TMA sections for on-slide controls in a major immunohistochemistry (IHC) laboratory, and in IHC proficiency testing, where we have achieved new levels of yield as a supplier to the College of American Pathologists. Whereas conventional TMA production methods yield 100-300 slides per TMA block, our method routinely produces 1500 slides per TMA block, with highly reduced levels of waste of source tissue. Theoretical yield is still up to twice our currenty achieved level, with two essential elements necessary for repeatably achieving maximum yields and realizing the full potential benefits of our method. First, a deeper understanding is required of the thermal-fluid dynamics and tissue mechanics that underly our method and dictate the success of a high-yield TMA block in histology. Concurrently and in light of this improved understanding, design changes to the instrument are required that will handle fluid and heat flow somewhat differently than in our instruments to date. Automation and computer control of several specific functions in the instrument are an important part of the effort, and will serve asa technical bridge between Phase I and Phase II. In the proposed research, a systematic study will be performed to recover half to all of the remaining available yield, utilizing (a) microCT scanning for non-destructive TMA block testing ("virtual histology") combined with automated image analysis to correlate TMA section flaws with artifacts of the TMA block building process; (b) method and instrument refinements to better control the fluid and solid mechanics of the two-phase block building process; (c) automation of the Array Science process for improved uniformity and portability of the technology to new users. The versatility of the Array Science method will also be systematically studied as regards tissue source preparations, from conventional (FFPE block coring) methods, to highly fragmented solid tissue in liquid suspension, to the use of cell culture material. Quantitative comparative analyses of microCT slice images and micrographs of their corresponding histologic sections, and section yield measurements in histology, hold promise as a novel and powerful validation of microCT as a nondestructive "virtual histology" to achieve definitive conclusions about sensitivity and control of the high-yield TMA construction method.

描述（由申请人提供）：我们（Array Science, LLC）建议对我们正在申请专利的方法和仪器进行详细的研究和开发，以高产地生产组织微阵列（TMA）。我们的 TMA 生产方法在利用标准组织学包埋介质（例如石蜡）的液相方面是新颖的，这样我们就实现了珍贵生物组织来源的前所未有的利用水平。事实证明，这项技术的成果在癌症诊断方面非常有益，它已在主要免疫组织化学 (IHC) 实验室中生成了超过 130 万个 TMA 切片，用于玻片上对照；在 IHC 能力测试中，我们已实现了新的产量水平作为美国病理学家学院的供应商。传统的 TMA 生产方法每个 TMA 块可生产 100-300 个载玻片，而我们的方法通常每个 TMA 块可生产 1500 个载玻片，从而大大减少了源组织的浪费水平。理论产量仍然高达我们目前达到的水平的两倍，为了可重复地实现最大产量和实现我们方法的全部潜在优势，有两个必要的要素。首先，需要对热流体动力学和组织力学有更深入的了解，它们是我们方法的基础，并决定了组织学中高产 TMA 块的成功。同时，鉴于这种加深的理解，需要对仪器进行设计更改，以与我们迄今为止的仪器有所不同的方式处理流体和热流。仪器中几个特定功能的自动化和计算机控制是这项工作的重要组成部分，并将成为第一阶段和第二阶段之间的技术桥梁。在拟议的研究中，将进行一项系统研究，利用 (a) microCT 扫描进行非破坏性 TMA 块测试（“虚拟组织学”），并结合自动图像分析来关联 TMA 切片，以恢复一半到全部剩余可用产量TMA 区块构建过程的缺陷； (b) 改进方法和仪器，以更好地控制两相砌块建造过程的流体和固体力学； (c) 阵列科学过程的自动化，以提高该技术对新用户的一致性和可移植性。还将系统地研究 Array Science 方法在组织源制备方面的多功能性，从传统的（FFPE 块取芯）方法，到液体悬浮液中高度破碎的固体组织，再到细胞培养材料的使用。对 microCT 切片图像和相应组织切片的显微照片进行定量比较分析，以及组织学中的切片产量测量，有望成为 microCT 作为无损“虚拟组织学”的新颖而有力的验证，以得出关于高灵敏度和控制的明确结论。 -产量TMA构建方法。