Adaptive-scanning, near-minimum-deformation atomic force microscope imaging of soft sample in liquid: Live mammalian cell example?

Abstract

In this paper, an adaptive-scanning mode (ASM) of atomic force microscopy (AFM) with near-minimum deformation is proposed for imaging live biological samples in liquid. Due to the intrinsic softness of life science samples, conventional contact mode (CM) topography imaging is rather slow (scan rate <; 0.2 Hz) as significant sample deformation caused by the tip-sample interaction occurs when the imaging speed increases. Such a low speed CM is not only time consuming, but also incapable of capturing dynamic evolution of life science samples. The proposed ASM approach addresses these challenges by combining an online adaptive-scanning speed optimization to accommodate the sample topography variation and tip-sample interaction force for the lateral sample deformation minimization with a gradient based deflection set-point optimization scheme along with a data driven iterative feedforward control approach for the vertical sample deformation minimization. The ASM technique was experimentally validated through imaging live human prostate cancer cells. Compare to the conventional CM imaging, the ASM technique was able to increase the imaging speed over eight times while preserving the topography details of the live cells and substantially lowering the tip-sample interaction force.