Nanotechnology-Enabled Sensors

7.5 Nano-sensors based on Nucleotides and DNA 455
tionalized by controlling the self-assembly process. As an example of the
latter, a network of DNA-streptavidin conjugates can be effectively transformed
into supramolecular DNA-streptavidin nanocircles as shown in
(Fig. 7.66 – 4) by thermal treatment (Fig. 7.66). 151 Since the endogeneous
protein molecule within the DNA-streptavidin nanocircles allows for the
convenient attachment of other functional molecules, potential applications
of such nanostructures obviously include their use as molecular tools in
novel immunological assays. 152
In addition, functional analogues of the conjugates described above can
be obtained from the use of streptavidin covalently functionalized with a
single-stranded oligonucleotide. These DNA-streptavidins (as shown in
Fig. 7.66 – 6) are synthesized from 5'-thiol-modified oligonucleotides and
streptavidin using hetero-bispecific cross-linkers, such as sulfosuccinimidyl-4(p-maleimidophenyl)-butyrate
(Fig. 7.66). 152
The covalently bound oligonucleotide moiety in (Fig. 7.66 – 6) provides
a specific recognition domain for the complementary nucleic acid sequence
in addition to the four native biotin-binding sites. Thus, it can be
used as a versatile molecular adaptor in a variety of applications, ranging
from the assembly of nanostructured protein arrays (Fig. 7.66) to the generation
of laterally-microstructured protein biochips. 146 It is possible to use
such DNA-protein biochips as decoding and sensing tools. Such standard
biochips decrease the cost of development of devices and also standardize
the process. With such biochips it is also possible to fabricate mixed
arrays.
7.5.6 DNA Conjugates with Inorganic Materials
DNA can be combined with many chemical functional groups. For example,
single-stranded DNA can be attached to electrically-active molecular
elements such as metal clusters, fullerenes or certain molecular
switches. 153 In 1997, Mirkin’s group at Northwestern University in Evanston,
Illinois, showed that free-floating target DNA strands with complementary
DNA linked to gold nanoparticles are detectable (Fig. 7.67). 154
When the target strands bind to the gold-bound complementary strands,
they pack the gold particles closer together. That changes the color which
the particles reflect, creating a simple color-based detector for specific
DNA sequences. They showed that the hybridization was facilitated by
freezing and then thawing the solutions, and that the denaturation of these
hybrid materials showed transition temperatures over a narrow range that
allowed differentiation of a variety of imperfect targets. The transfer of the
hybridization mixture to a reverse-phase silica plate resulted in a blue color