Biomedical Engineering Reference
In-Depth Information
The delta F508 mutation site in the cystic fibrosis (a common fatal genetic diseases
among the population of Europe and the U.S.) transmembrane receptor gene has been
distinguished using this approach. As shown in Figure 12.25
,
the SiNWs operating as a
gate in the FET device were functionalized with PNA via intervening avidin protein layer,
and a microfluidic system was used to deliver a DNA sample. The specific conductance
changes due to PNA-DNA hybridization could be obtained from the time-dependent con-
ductance recorded following introduction of wild-type and the mutant DNA samples
using the same FET device. The system allowed effective and selective detection of DNA
as low as ca. 10 fM without labeling and in real time. Small protein molecule inhibition of
ATP binding to a tyrosine kinase (ABI) has been analyzed using a similar approach as
monitoring the conductance of SiNW FET devices with ABI linked to the NW surface. The
binding event and inhibition affinities (such as inhibition constants) can be directly elec-
trically detected, which suggests that the approach could serve as a technology platform
for drug discovery [196].
The latest advances in the production of well-controlled aligned NW arrays have
accelerated the application of NWs in biosensor technology. Nanowire array has been
performed on specific antibody-functionalized gates of FET biosensors for virus detec-
tion, and the influenza A virus can be selectively detected by measuring conductance
changes (Figure 12.26) [170]. Arrays of SiNW devices were defined by using photoli-
thography with Ni metal contacts on silicon substrates with an oxide layer. The specific
antibody receptor for influenza A was covalently linked to the surfaces of SiNWs. The
conductance changes due to the binding or unbinding in the presence of the virus have
been observed but not the other kinds of viruses, thus confirming the selectivity and
specificity of the system.
Based on the approach using NW-based FET devices, rather than metal oxide film or
polycrystalline metal film, indium tin oxide NW and silver NW-based sensors have also
been successfully used to detect NO
2
and NH
3
vapor with high sensitivity at room tem-
perature [197,198].
Conducting polymers such as Ppy are more easily incorporated with biomolecules in a
single step during polymer synthesis rather than the multiple steps for synthesis of sur-
face-modified SiNWs and CNTs. The physical properties and biocompatibility have
allowed conducting polymer NWs to emerge as another promising material in the devel-
opment of biosensors [199,214]. Single and multiple individually addressable Ppy and
polyaniline NWs of controlled dimension and location have been generated by
electrodeposition within a channel between two electrodes on the surface of a silicon
wafer. The source-drain resistance increased significantly with the binding of the biotin-
conjugated DNA oligo with avidin-functionalized Ppy NWs. Further sensitivity enhance-
ment can be obtained by adjusting theNW's conductivity to a value closer to the lower
range of semiconductors.
In contrast to these electrical methods, NWs can also be used for optical biosensor
development because of their size- and shape-dependent optical properties. Metal sub-
micron wire (Au/Ag) barcodes have been used in conjunction with traditional flores-
cent assays for DNA detection, where the barcode makes possible multiplexed
detection [200]. A novel strategy for DNA hybridization studies based on measuring
either UV or fluorescence properties of gold nanorods has been demonstrated
[201,202]. DNA probe-functionalized gold nanorods show decreased fluorescence
when they are mixed with complementary oligonucleotide-functionalized gold
nanorods (Figure 12.27). The fluorescence properties of gold nanorods open up a new
perspective for the use of gold nanorods as an alternative tag in fluorescence-based
detection assays [202].
