Nanomanipulation of biological samples using a compact atomic force microscope under scanning electron microscope observation

Abstract

We introduce a compact nanomanipulator that can be operated inside the sample chamber of a scanning electron microscope (SEM) for biological sample manipulation. The design of the nanomanipulator is based on that of an atomic force microscope (AFM). A self-sensitive cantilever is used to realize the compact body and thus it is possible to put a pair of the standalone AFM units on the sample stage in the SEM chamber. Using this system, we accomplished nanodissection of biological samples as well as AFM imaging under SEM observation. We then fabricated the surface of a rat renal glomerulus by scan-scratching and succeeded in making a small hole on the wall of a blood capillary. As a result, it was possible to observe the internal structure of the capillary, which had been hidden beneath the surface wall. Furthermore, using two AFM units on the sample stage of the SEM, we successfully dissected the lens fiber cells taken from a rat eye in a multi-probe operation using the two cantilevers. This system is expected to become a very useful tool for micro- and nanometer-scale anatomy and engineering applications.