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Iterative Control Approach to High-Speed Force-Distance Curve Measurement Using AFM for Biological Applications

机译:用于生物应用的AFM高速力距离测量的迭代控制方法

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Since its invention, atomic force microscopy (AFM) has been used in a wide variety of biological studies, from the topography imaging to the interactions of both subcell molecular (i.e., DNA and protein) and cell membranes. Particularly, the force-curve measurement using AFM has become a powerful tool to study the biophysical and/or biochemical properties of single bimolecular and single cell, at unprecedented spatial and force resolution. However, currently the temporal resolution of AFM force curve measurement is limited by its low operation speed. For example, studies such as the time-dependence of the unfolding force of a titin domain, and the time-dependence of the unbinding force of a single DNA strand, are still limited to the low-speed range when using force-curve measurement. Large temporal distortions also occur during the force-volume imaging of a live cell when mapping the force-curve distribution across the cell membrane, because of the large time lapse between the force-curve acquired at the first and the last sample point. In this article, a novel inversion-based iterative control technique is proposed to dramatically increase the speed of forcecurve measurements. The experimental results are presented to show that by using the proposed control technique, the speed of force-curve measurements can be significantly increased (over 60 times) --- with no loss of spatial resolution. This control technique, demonstrated on a commercial AFM platform with a conventional cantilever, can be easily automated with guaranteed performance.
机译:由于本发明以来,原子力显微镜(AFM)已被用于各种各样的生物学研究,从地形成像到亚壳分子(即DNA和蛋白)和细胞膜的相互作用。特别地,使用AFM的力曲线测量已经成为研究单个双分子和单细胞的生物物理和/或生化特性,以前所未有的空间和力分辨率研究的强大工具。然而,目前AFM力曲线测量的时间分辨率受其低操作速度的限制。例如,在使用力曲线测量时仍然限于低速范围,例如术曲线域的展开力的时间依赖性以及单个DNA链的未粘附力的时间依赖性。当在映射细胞膜穿过细胞膜时的力曲线分布时,在直播电池的力量成像期间也发生大的时间变形,因为在第一和最后一个采样点中获取的力曲线之间的较大时间流逝。在本文中,提出了一种新的基于反演的迭代控制技术,从而显着提高了Forcurve测量的速度。提出了实验结果表明,通过使用所提出的控制技术,力曲线测量的速度可以显着增加(超过60次) - - 没有空间分辨率损失。在具有传统悬臂的商用AFM平台上演示的这种控制技术可以通过保证性能轻松自动化。

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