Biomedical Engineering Reference
In-Depth Information
Fig. 7.24
DNA hybridization on microcantilever. (
a
) Scanning electron micrograph of a micro-
fabricated silicon cantilever array; (
b
) each cantilever is functionalized on one side with a different
oligonucleotides (
red
or
blue
); (
c
) after injection of the first complementary oligonucleotide
(
green
), hybridization occurs on the cantilever that provides the matching sequence
(
red
),
increasing the differential signal
x; (
d
) injection of the second complementary oligonucleotide
(
yellow
) causes the cantilever functionalized with the second oligonucleotide (
blue
)tobend
(Reprinted from Ref. [
104
] with permission from AAAS)
work in two modes: static deflection mode and dynamic resonance mode [
103
]. The
cantilever-based DNA detection was initiated by Fritz and coworkers in 2000 [
104
].
The sensor translated DNA hybridization signal into a nanomechanical bending
(Fig.
7.24
). They performed in situ monitoring of the differential deflection signals
between two DNA oligonucleotides, which suggested that multiplexed detection can
be accomplished by cantilever system [
105
]. The hybridization of a 12 mer DNA
at a concentration of 400 nM generated a 16 nm deflection, which corresponded
to a surface stress of 5 mN
m
1
or an actuation force of
300 pN. They further
demonstrated the ability to discriminate single-base mismatch, which is desired by
the application of SNP. Later, the same group demonstrated the use of cantilever
arrays for the nanomechanical analysis of multiple differential gene expression
without amplification or labeling at picomolar level in complex sample [
106
].
Fabricating thinner cantilevers will enhance the molecular sensitivity further
(nanomolar level using thickness of 1
m[
105
]; picomolar level using thickness
of 0.45
m[
106
]), and integrating arrays into microfluidic channels will reduce
the amount of sample required significantly, which may be the most important
challenge for the realization of POCT. Burg and coworkers reported a series of
works that realized weighing of single nanoparticles, single bacterial cells, and
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