Multiplexed Ovarian Cancer Microfluidic Tissue Microarray

多重卵巢癌微流控组织微阵列

• 批准号: 8648455
• 负责人: Benjamin Delbert Brooks
• 金额: $ 22.5万
• 依托单位: CARTERRA, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8648455
• 关键词: Adoption; Affect; Animal Model; Antineoplastic Agents; Area; Biocompatible Materials; Biological Assay; Cell Adhesion; Cell Communication; Cell Culture Techniques; Cell surface; Cells; Cessation of life; Characteristics; Clinic; Clinical; Colony-Forming Units Assay; Controlled Study; Custom; DNA; Detection; Diagnosis; Disease; Disease model; Docking; Drug Combinations; Drug Delivery Systems; Early identification; End Point Assay; Engineering; Epithelial ovarian cancer; Future; Goals; Head; Immunohistochemistry; Individual; Intention; Investigation; Legal patent; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of ovary; Medicine; Methods; Microfluidics; Microscope; Modeling; Mus; Organ; Outcome; Ovarian Tissue; Pathology; Patients; Pharmaceutical Preparations; Phase; Play; Preclinical Drug Evaluation; Printing; Proteins; Publications; Reaction; Regimen; Research; Research Personnel; Risk; Slice; Spottings; Staging; Surface; Surface Plasmon Resonance; Survival Rate; System; Technology; Testing; Therapeutic; Therapeutic Agents; Tissue Microarray; Tissues; Toxic effect; Toxicity Tests; Translating; Treatment Protocols; United States; Woman; base; cancer diagnosis; chemotherapeutic agent; clinical application; combinatorial; digital; fluorescence microscope; improved; in vivo; innovation; instrument; killings; molecular recognition; mortality; novel; product development; prototype; public health relevance; research study; screening; shear stress; tissue culture; tool; tumor; tumor progression

Project Summary We propose an instrument system for automated, multiplexed cell- and tissue-based experiments (i.e. tissue microarrays) called the Microfluidic Flow Cell Array (MFCA). The MFCA consists of a microfluidic flow cell array integrated with an inverted fluorescent microscope, allowing the observation of 48 flow chambers simultaneously or an individual chamber at higher magnification. The proposed instrument will be used to novel cell- and tissue-based assays in a highly parallel manner that are otherwise difficult to perform. Our goal is to build a platform for producing a tissue microarray that maintains many of the characteristics found in cells in vivo and allows for the investigation of cell-surface, cell-cell, and especially tumor-stroma interactions, cell toxicity studies, and tissue toxicity studies in a multiplexed fashion. As a Phase I application, this proposal's focus is ovarian cancer tissue slice toxicity testing to determine the optimal chemotherapeutic agents for a specific patient (i.e. personalized treatment based on the tissue reaction); however, multiple applications can be envisioned beyond ovarian cancer including: combinatorial cell stimulation, toxicity, or therapeutic assays, stem cell screening and differentiation control studies, multiplexed primary cell assays, biomaterials screening, shear stress and cell adhesion studies, and combinatorial immunohistochemistry. This platform approach and simple integration with a microscope will allow for adoption and adaptability for researchers worldwide. The following hypotheses and specific aims have been identified to prove the feasibility of integrating the microfluidic flow cell array technology with an inverted fluorescent microscope for cell and tissue based assays. Specific Aim 1. Translate end point assays for existing tissue culture approaches including the MTT Assay and digital pathology to the MFCA. Specific Aim 2. Engineer the MFCA printhead to minimize impact of the printhead docking onto the tissue culture slice. Specific Aim 3. Optimize drug delivery of different therapeutic agents in the MFCA channels using to the mouse ovarian tissue slice and compare to existing tissue culture approaches.

项目摘要 我们提出了一种仪器系统，用于自动化，多路复用的细胞和组织为基础的 微流控流动池阵列（MFCA）是一种新型的微流控实验（即组织微阵列）。MFCA 由集成有倒置荧光显微镜的微流控流动池阵列组成， 允许同时观察48个流动室或在更高温度下观察单个室 倍率所提出的仪器将用于新的细胞和组织为基础的测定， 这是以其他方式难以执行高度并行的方式。我们的目标是建立一个平台 产生组织微阵列，其保持体内细胞中发现的许多特征， 并允许研究细胞-表面、细胞-细胞，特别是肿瘤-基质 相互作用、细胞毒性研究和组织毒性研究。作为相位 本人申请，本提案的重点是卵巢癌组织切片毒性试验的确定， 用于特定患者的最佳化疗剂（即，基于患者的个体化治疗）。 组织反应）;然而，可以设想卵巢癌以外的多种应用 包括：组合细胞刺激、毒性或治疗测定、干细胞筛选和 分化对照研究，多重原代细胞测定，生物材料筛选，剪切 应激和细胞粘附研究以及组合免疫组织化学。这个平台 方法和与显微镜的简单集成将允许采用和适应性， 全世界的研究人员。 确定了以下假设和具体目标，以证明 将微流控流动池阵列技术与倒置荧光显微镜相结合， 基于细胞和组织的测定。 具体目标1.为现有的组织培养方法翻译终点检测，包括 MTT测定和MFCA的数字病理学。 具体目标2。设计MFCA打印头，以最大限度地减少打印头对接到 组织培养切片。 具体目标3。优化MFCA通道中不同治疗剂的药物递送 并与现有的组织培养方法进行比较。