Atomic force microscopy (AFM) has great potential as a tool for structural
biology, a field in which there is increasing demand to characterize larger
and more complex biomolecular systems. However, the poorly characterized s
ilicon and silicon nitride probe tips currently employed in AFM limit its b
iological applications. Carbon nanotubes represent ideal AFM tip materials
due to their small diameter, high aspect ratio, large Young's modulus, mech
anical robustness, well-defined structure, and unique chemical properties.
Nanotube probes were first fabricated by manual assembly, but more recent m
ethods based on chemical vapor deposition provide higher resolution probes
and are geared towards mass production, including recent developments that
enable quantitative preparation of individual single-walled carbon nanotube
tips [J. Phys. Chem. B 105 (2001) 743]. The high-resolution imaging capabi
lities of these nanotube AFM probes have been demonstrated on gold nanopart
icles and well-characterized biomolecules such as IgG and GroES. Using the
nanotube probes, new biological structures have been investigated in the ar
eas of amyloid-beta protein aggregation and chromatin remodeling, and new b
iotechnologies have been developed such as AFM-based haplotyping. In additi
on to measuring topography, chemically functionalized AFM probes can measur
e the spatial arrangement of chemical functional groups in a sample. Howeve
r, standard silicon and silicon nitride tips, once functionalized, do not y
ield sufficient resolution to allow combined structural and functional imag
ing of biomolecules. The unique end-group chemistry of carbon nanotubes, wh
ich can be arbitrarily modified by established chemical methods, has been e
xploited for chemical force microscopy, allowing single-molecule measuremen
ts with well-defined functionalized tips. (C) 2001 Elsevier Science Ltd. Al
l rights reserved.