IIBR Instrumentation: Multiscale Multiplex Nanomechanical Stimulus and Sensing of Living Cells on 3D-Cell Culture

罗格斯大学（Rutgers）和新泽西州立大学（State University of New Jersey）开发了一种传感平台，可以实现活细胞的快速、宽带纳米机械制图。通过将该传感平台与扫描探针显微镜（SPM）相结合，可以绘制三维（3D）细胞培养中多个细胞随时间流逝的纳米力学演化图。这种传感平台可以作为各种生物学研究的有力工具，更好地了解组织重塑过程中分子信号与生物力学物理之间的关系。该项目的研究成果将通过专利申请、技术演示和在生物会议上的介绍以及期刊出版物等方式传播。我们将联合举办暑期工作坊，向研究生和本科生介绍纳米/生物机械传感。罗格斯大学成熟的项目，如罗格斯女工程师协会，将在本科和研究生阶段招募代表性不足的学生，包括女性和非裔美国人，并通过开放的实验室参观，向初高中学生伸出援手。该项目的研究目标是实现3d细胞培养物的多种纳米力学测量，包括多个细胞的快速和宽带纳米力学特性制图，精确力控制的机械刺激和细胞戳戳，以及细胞的同时机械刺激和机械测量。本研究目标将通过以下四个目标来实现：(1)。设计并制造了一个具有四自由度运动（两个平移和两个旋转）的纳米机械臂，并将其集成到配备倒置光学显微镜的SPM系统中。(二)。设计并制造了一个多自由度的纳米定位平台来操纵悬臂探头，并将其集成到SPM系统中；(3)。将开发一套算法，将上述两个机械手与SPM系统集成，以实现所需的细胞刺激和测量功能；和(IV)。新的传感平台将通过植物生物学和细胞生物学基准实验中3D细胞培养的时间流逝粘弹性映射进行演示和评估。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

An award is made to Rutgers, the State University of New Jersey to develop a sensing platform to achieve rapid, broadband nanomechanical mapping of live cells. By integrating this sensing platform with a scanning probe microscope (SPM), time-elapsed nanomechanical evolutions of multiple cells on a three-dimensional (3D) cell culture can be mapped. Such a sensing platform can be used as a powerful tool in various biology studies to gain a better understanding of the correlation between molecular signaling and biomechanical physics in tissue remodeling. The research outcomes of this project will be disseminated through patent applications, technical demonstration and presentation in biological conferences, and journal publications. Joint summer workshops will be organized to introduce nano/bio-mechanical sensing to both graduate and undergraduate students. Well-established programs at Rutgers such as the Rutgers Society for Women Engineers will be leveraged to recruit under-represented students including women and African American at both undergraduate and graduate levels, and to reach out to middle- and high- school students through open lab-tours. The research goal of this project is to achieve a wide variety of nanomechanical measurements of a 3D-cell culture, including rapid and broadband nanomechanical property mapping of multiple cells, mechanical stimulus and cell poking with precision force control, and simultaneous mechanical stimuli and mechanical measurement of cells. This research goal will be accomplished through the following four objectives: (I). A nano-manipulator with four degree-of-freedom (DOF) motions (two translational and two rotational) will be designed and built, and then integrated to a SPM system equipped with an inverted optical microscope. (II). A multi DOF nano-positioning stage will be designed and built to manipulate a cantilever probe, and integrated to the SPM system; (III). A suite of algorithms will be developed to integrate the above two manipulators with the SPM system to fulfill the desired cell stimuli and measurement functions; and (IV). The new sensing platform will be demonstrated and evaluated through time-elapsed viscoelasticity mapping of 3D cell culture in plant biology and cell biology benchmark experiments.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.