Mechanial Phenotyping of Cells: Haptics-Enabled Atomic Force Microscopy

该奖项的研究目标是探索使用原子力显微镜(AFM)与触觉(触觉)反馈相结合的新方法来机械地表型和监测单个细胞。为了实现这一点，该项目的主要任务之一将是开发一种磁悬浮触觉反馈设备，具有接近零摩擦和足够的保真度，使用户能够感觉到？单个细胞。此外，在原子力显微镜研究中，我们将监测不同类型细胞对局部和全局反应的硬度。对于整体硬度的测量，我们将使用改进的AFM悬臂，这样顶端的球的直径将明显大于细胞的直径。我们将使用局部测量来了解每种类型细胞在细胞表面不同位置的硬度变化。我们将使用赫兹接触模型来量化局部和全局细胞探测任务中细胞的机械响应。这样的研究将帮助我们建立细胞机械性能的数据库。将触觉反馈与原子力显微镜相结合，并了解触觉设备在机械表型细胞中的有效性是该项目的最终目标。如果成功，这项研究将导致开发针对胚胎干细胞分化的改进方法，用于诊断和治疗目的，并监测细胞对环境刺激的反应。此外，使用触觉功能的AFM系统来表征细胞将提高我们对谱系确定的知识，以及我们控制定向分化用于治疗目的的能力。由于多能人类胚胎干细胞在治疗疾病(如心脏病、帕金森氏症、S和脊髓损伤)方面具有很强的治疗潜力，我们预计我们提出的方法将有助于使这一进展可行。

The research objective of this award is to investigate novel approaches for using Atomic Force Microscopy (AFM), combined with haptic (sense of touch) feedback, to mechanically phenotype and monitor individual cells. To enable this, one of the primary tasks in this project will be to develop a magnetically levitated haptic feedback device with near zero friction and sufficient fidelity so that a user can ?feel? individual cells. Furthermore, in the AFM studies, we will monitor the stiffness of the different cell types for both local and global responses. For global stiffness measurements, we will use modified AFM cantilevers whereby the diameter of the ball at the tip will be significantly larger than that of the cell. We will use localized measurements to understand the variation in the stiffness at various locations on the cell surface for each type of cell. We will use the Hertz contact model to quantify the mechanical response of the cell for local and global cell probing tasks. Such studies will help us to create a database of the mechanical properties of the cells. Combing haptic feedback with the AFM and understanding the effectiveness of the haptic device in mechanically phenotyping cells is the end-goal of this project. If successful, this research will lead to the development of improved methods of targeting embryonic stem cell differentiation for diagnostic and therapeutic purposes and monitoring cellular responses to environmental stimuli. Additionally, the use of haptics-enabled AFM system to characterize cells will advance our knowledge of lineage determination and our ability to control directed differentiation for therapeutic purposes. Since pluripotent human embryonic stem cells have a strong potential for therapeutic use in treatment of disease (e.g., heart disease, Parkinson?s, and spinal cord injuries), we envision our proposed approach will help to make that advancement feasible.