Microfluidic Platform for Cancer Cell Culture and Analysis

用于癌细胞培养和分析的微流控平台

• 批准号: 7622604
• 负责人: Philip J Lee
• 金额: $ 29.1万
• 依托单位: CELLASIC CORPORATION
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2011-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7622604
• 关键词: Address; Area; Automation; Biological Assay; Bioreactors; Breast Cancer Cell; Cancer Biology; Cancer cell line; Cell Culture Techniques; Cell physiology; Cells; Collaborations; Complex; Conditioned Culture Media; Consumption; Data Quality; Diagnosis; Dose; Drug Exposure; Engineering; Environment; Epithelial Cells; Extracellular Matrix; Fibroblasts; Goals; Gray unit of radiation dose; Human; In Vitro; Individual; Institutes; Kinetics; Laboratories; Letters; Life; Liquid substance; MEKs; Malignant Neoplasms; Methods; Microfabrication; Microfluidic Microchips; Microfluidics; Operative Surgical Procedures; Optics; Pathway interactions; Patients; Perfusion; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phenotype; Process; Property; Pump; RNA Interference; Reagent; Research; Robotics; Sampling; Schedule; Screening for cancer; Screening procedure; Small Business Innovation Research Grant; Solutions; Staging; Stromal Cells; System; Systems Analysis; Technology; Therapeutic; Time; Toxic effect; Work; base; cancer cell; commercial application; cost; design; flexibility; improved; in vivo; innovation; instrument; instrumentation; nanolitre; nanolitre scale; novel; pressure; programs; prototype; response; scale up; shear stress; tool

DESCRIPTION (provided by applicant): This Phase II SBIR proposes to develop a microfluidic cell culture and analysis platform for the in vitro screening of cancer cells. The end result of this research will be to deliver a fully functional system (automated instrument and disposable microfluidics) that can be used in both research and pharmaceutical labs. This will be validated and applied to the research underway at our collaborating institute for the purpose of profiling the Raf-MEK-ERK pathway in a panel of ~60 breast cancer cell lines for improved prediction of therapeutic response. The microfluidic platform will provide key advantages over the current cell based screening technology (96-well plate based), including: 1) improved handling of small cell samples (micoliters per array), 2) the ability to design more relevant microenvironments for phenotype analysis, 3) enabling multiplexed continuous flow experimentation, and 4) 10X-100X reduction of time and cost for cell culture automation. In addition, the platform is designed such that application specific microfluidic arrays can be utilized with a single system, increasing the flexibility and impact of the technology. The first major aim of this project will be to engineer an automated microfluidic screening platform. The main tasks are to optimize the design of the Phase I prototype, scale-up to a 384 well format, and refine the control system for high throughput operation. Three key innovations developed in our previous work will be further expanded to complete this aim: 1) the design of microfluidic networks and perfusion barriers to better approximate in vivo culture conditions, 2) the use of a pneumatic pressure driven manifold for multiplexed, non-wetted pumping of nanoliter volumes, and 3) the fabrication process that enables formatting the microfluidic arrays to SBS standards, making it compatible with current 96 and 384 well robotic screening instrumentation. The second major aim will be to apply this system to the cancer cell screening program at our collaborating institute. This will address areas where microfluidic technology can offer enabling benefits not possible with existing tools. Specific applications include: 1) flow based drug exposure, 2) cell invasion assay, 3) 3D ECM culture, 4) medium conditioning by stromal cells, and 5) integration with RNAi methods.

描述（由申请人提供）：该II期SBIR提出开发用于癌细胞体外筛选的微流体细胞培养和分析平台。这项研究的最终结果将是提供一个功能齐全的系统（自动化仪器和一次性微流体），可用于研究和制药实验室。这将被验证并应用于我们合作研究所正在进行的研究，目的是在一组约60种乳腺癌细胞系中分析Raf-MEK-ERK通路，以改善治疗反应的预测。 微流控平台将提供优于当前基于细胞的筛选技术（基于96孔板）的关键优势，包括：1）改进小细胞样品的处理（微升/阵列），2）设计用于表型分析的更相关微环境的能力，3）实现多路连续流实验，以及4）细胞培养自动化的时间和成本减少10 - 100倍。此外，该平台的设计使得特定应用的微流体阵列可以与单个系统一起使用，从而增加了该技术的灵活性和影响力。 该项目的第一个主要目标是设计一个自动化微流体筛选平台。主要任务是优化第一阶段原型的设计，扩大到384井格式，并完善高通量操作的控制系统。我们在以前的工作中开发的三个关键创新将进一步扩展，以完成这一目标：1）设计微流体网络和灌注屏障以更好地接近体内培养条件，2）使用气动压力驱动的歧管用于纳升体积的多路复用、非润湿泵送，以及3）能够将微流体阵列格式化为SBS标准的制造工艺，使其与当前的96和384井机器人筛选仪器兼容。 第二个主要目标是将该系统应用于我们合作研究所的癌细胞筛查项目。这将解决微流体技术可以提供现有工具无法实现的好处的领域。具体应用包括：1）基于流动的药物暴露，2）细胞侵袭测定，3）3D ECM培养，4）基质细胞的培养基调节，和5）与RNAi方法的整合。