Biosensor to measure microscopic cell function

描述（由申请人提供）：这是一个修改后的应用程序。这个第一阶段STTR提案的广泛，长期目标是证明开发一种新型的光电生物传感器的可行性，用于微观应用，以允许同时集成光子和电子信号，用于全面的时间推移显微镜应用。光学显微镜在评估信号转导对细胞膜功能的影响方面的灵敏度有限。光学显微镜无法检测低纳米水平的细胞膜位移，其特异性受到微米水平观察到的微观变化的潜在过度解释的限制。因此，需要在独立方法的上下文中正确地解释光信号。相比之下，电子传感器具有在低纳米水平测量细胞表面细胞膜功能的分辨率，但具有有限的细胞内空间分辨率。与爱荷华州州立大学合作，CET Inc.将开发一种新型的光电生物传感器，该生物传感器将以透射电子显微镜的分辨率以非破坏性方式测量培养细胞中的几个功能参数。该传感器将联合收割机结合电子和光学信号的互补强度。这项研究的结果是证明利用第二阶段提案的可行性，该提案将导致传感器设计，软件和硬件开发以及图像分析和信号处理的进一步发展，以提供有关培养活细胞信号转导的全面信息。该商业产品将为细胞显微镜工作者提供一个全面的平台。该STTR的第一阶段的具体目标是：（1）制造一种光电传感器，该传感器可以定量和动态地测量细胞粘附和运动性，而不会发生电极信号退化;（2）实验验证该传感器在短时间和长时间内对细胞没有固有毒性;（3）验证传感器不妨碍来自相位、DIC和荧光显微镜的光子信号。

DESCRIPTION (provided by applicant): This is a revised application. The broad, long-term objectives of this Phase I STTR proposal is to demonstrate feasibility in developing a novel optical-electronic biosensor for microscopic applications to permit simultaneous integration of photonic and electronic signals for comprehensive time-lapsed microscopy applications. Optical microscopy has limitations in sensitivity to evaluate the impact of signal transduction on cell-membrane function. Light microscopy is unable to detect cell-membrane displacement at the low nanometer level, and its specificity is limited by the potential over-interpretation of observed microscopic changes at the micron level. Thus, optical signals need to be properly interpreted within the contexts of an independent method. In contrast, electronic sensors have the resolution to measure cell surface cell membrane function at the low nanometer level but have limited intracellular spatial resolution. In collaboration with Iowa State University, CET Inc. will develop a novel, optical-electronic biosensor that will measure several functional parameters in cultured cells in a nondestructive fashion with a resolution of transmission electron microscopy. This sensor will combine the complementary strengths of electronic and optical signals. The outcome of this research is to demonstrate feasibility that will leverage a Phase II proposal that leads to further developments in sensor design, software and hardware development and image analysis and signal processing to provide comprehensive information on signal transduction in cultured living cells. The commercial product will provide a comprehensive platform for cell microscopists. The specific objectives for Phase I of this STTR are: (1) fabricate an optical-electronic sensor that can quantitatively and dynamically measure cell adhesion and motility without electrode signal degradation; (2) experimentally validate that the sensor is not inherently toxic to cells over both short and long time periods; (3) validate that the sensor does not impede the photonic signals from phase, DIC, and fluorescent microscopy.