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

Futoshi Iwata¹, Yuya Mizuguchi, Hideyuki Ko

¹Department of Mechanical Engineering, Shizuoka University, Hamamatsu 432-8561, Japan. tmfiwat@ipc.shizuoka.ac.jp

Journal of Electron Microscopy

|November 4, 2011

Summary

We developed a compact nanomanipulator for scanning electron microscopes (SEM) enabling precise biological sample manipulation. This atomic force microscope (AFM)-based system allows nanodissection and imaging within the SEM, revealing hidden structures.

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Area of Science:

Biotechnology
Microscopy
Nanotechnology

Background:

Biological sample manipulation requires high precision at the nanoscale.
Existing tools may have limitations in integrated microscopy environments.

Purpose of the Study:

To introduce a compact nanomanipulator for in-situ biological sample manipulation inside a scanning electron microscope (SEM).
To demonstrate the system's capability for nanodissection and atomic force microscopy (AFM) imaging under SEM observation.

Main Methods:

The nanomanipulator design is based on atomic force microscopy (AFM) principles, utilizing a self-sensitive cantilever for a compact form factor.
Two standalone AFM units were integrated onto the sample stage of an SEM.
Techniques demonstrated include nanodissection, AFM imaging, scan-scratching, and multi-probe operations.

Main Results:

Successful nanodissection and AFM imaging of biological samples within the SEM.
Fabrication of a rat renal glomerulus surface via scan-scratching, creating a hole in a blood capillary wall.
Observation of the internal capillary structure previously obscured by the surface wall.
Multi-probe dissection of rat eye lens fiber cells using two cantilevers.

Conclusions:

The developed compact nanomanipulator system enables precise manipulation and imaging of biological samples inside an SEM.
This technology facilitates detailed micro- and nanometer-scale anatomical studies and engineering applications.
The system's ability to reveal hidden internal structures and perform complex dissections offers significant potential for biological research.