An Integrated Incubator-Microscope for Cell Manipulation and Measurement

细胞操作和测量使发现基本机制(例如，机械转导和细胞间通讯)和实际应用(例如，治疗学的药物筛选)成为可能。这些实验涉及机器人细胞操作、延时细胞成像和细胞的电气/机械表征，时间从几小时到几周不等，在此期间，严格控制实验环境(温度、二氧化碳和湿度)对于确保适当的细胞状态和数据的有效性至关重要。 这个RTI应用需要一个培养箱显微镜，它将与我们定制开发的机器人细胞操作系统组件和这个申请者团队正在开发的几个使能微设备阵列集成在一起，形成一个独特的平台，在长期延时细胞成像、生物物理细胞测量、机器人细胞操作和细胞培养的机械/电气刺激期间保持严密的环境条件。集成的仪器将使这支研究团队能够开发和验证创新的机器人和微设备技术，并利用这些技术做出新的发现。利用集成仪器，我们将进行机器人细胞操作，以高通量测量心肌细胞的缝隙连接功能和药物筛选；用于表征心肌细胞搏动频率、节律和收缩能力的细胞生物物理学；以及具有所需组织特性的组织形成的动态机械刺激和反馈控制。 我们的总部基地将使用所要求的设备来构建和运行他们的创新系统和设备，并收集有效的单元数据和系统/设备性能指标。这些设备将用于培养大量博士后和研究生，他们将获得微纳米技术、生物医学仪器、临床心脏病学、细胞物理学和机械生物学方面的技能。

Cell manipulation and measurement enable the discovery of fundamental mechanisms (e.g., mechanotransduction and cell-cell communication) and practical applications (e.g., drug screen for therapeutics). The experiments involve robotic cell manipulation, time-lapsed cell imaging, and electrical/mechanical characterization of cells, and are performed over a period from hours to weeks, during which strict control of the experimental atmosphere (temperature, CO2, and humidity) is critical for ensuring proper cell status and the validity of data. This RTI application requests an incubator-microscope, which will be integrated with our custom-developed robotic cell manipulation system components and several enabling microdevice arrays under development by this team of applicants, forming a unique platform to maintain tight environmental conditions during long-term time-lapsed cell imaging, biophysical cell measurement, robotic cell manipulation, and mechanical/electrical stimulation of cell culture. The integrated instrument will enable this team of researchers to develop and validate innovative robotics and microdevice technologies and employ these technologies to make new discoveries. With the integrated instrument, we will pursue robotic cell manipulation for high-throughput gap junction function measurement on cardiomyocytes and drug screen; cell biophysics for characterizing cardiomyocytes’ beating rate, rhythm, and contractility; and dynamic mechanical stimulation and feedback control of tissue formation with desired tissue properties. Our HQPs will use the requested equipment to build and operate their innovative systems and devices and gather valid cell data and system/device performance metrics. The equipment will be used to train a high number of postdocs and graduate students who will gain skills in micro-nanotechnologies, biomedical instrumentation, clinical cardiology, cell physics, and mechanobiology.