Biomedical Engineering Reference
In-Depth Information
Fig. 7.15. AFM height images of different structures made by nanoparticle binding to DNA. Left:
nanowires made by non-specific (electrostatic) binding to 'combed' or straightened DNA; top:
sparse nanoparticle coating; bottom: denser coating. Middle: non-specific binding (sugar-DNA
phosphate backbone) of glyconanoparticles to DNA [123]. Both DNA and small nanoparticles are
visible. Right: probing the action of a biosensor: measuring specificity of binding of DNA-sensing
nanoprobes to their targets. Although the nanoparticles are much larger than the DNA, both can be
clearly seen. Grey arrows show non-specific binding events, while white arrows show specific
binding events. In total, 70% of binding was found to be specific [534]. Reproduced with permission
from [547] (left).
in fact no other technique can simultaneously observe both species. There have been a
number of examples shown where complexes were observed between various nanoparti-
cles and proteins or DNA using AFM [493, 539-545]. The case of oligonucleotide-DNA
complexes is one where AFM can perform a special role. This is because DNA molecules
have many potential binding sites for nanoparticles; the AFM's high spatial resolution can
be used to distinguish between them. In many examples, the interactions are rather non-
specific; the nanoparticles are designed to interact with any DNA sequence. This is
particularly useful to build a nanowire using the DNA as a template [542, 546, 547].
However, if the nanoparticles are modified with short sequences of single stranded DNA
(ssDNA), they can specifically recognize and hybridize with target sequences in the DNA
(or RNA ) target [534, 548]. This can form the basis of a biosensor for molecular diagnosis
of disease; the mechanism of action of the biosensor can be determined by observation of
the complexes of the nanoparticles with target DNA by AFM [485]. Example images
showing this are given in Figure 7.15. This is one of a number of methods of specifically
targeting certain DNA sequences with nanoparticles that have been illustrated by AFM
[534, 549]. Figure 7.16 shows some examples of imaging nanoparticle-DNA interactions.
7.2.5 Electrical measurements of nanostructures with AFM
One of the most active areas in nanotechnology is the search for new electronic
materials that, based on a bottom-up fabrication approach, could be used to replace
today's lithography-based electronics. As well as these applied studies, the study of the
fundamental optical and opto-electronic properties of nanomaterials is a very important
