Biomedical Engineering Reference
In-Depth Information
insulating surface is required. Liquid phase silane based chemistries are the most
commonly used technique to functionalize individual nanopores in such insulating
membranes [
66
,
93
]. While these surface chemistries have been characterized in
detail on planar surfaces, questions still remain as to the exact packing density,
molecular orientation and thickness of SAM's in a highly confined environment that
is a nanopore. In addition, nanopores formed via TEM decompositional sputtering
processes typically exhibit high surface roughness, high surface curvature and a non-
stoichiometric material composition due to selective material sputtering as observed
in SiO
2
coated Si
3
N
4
nanopores [
97
,
98
], further complicating the nanopore functiona-
lization process. In these cases it is vital to thoroughly oxidize the surface through an
extensive O
2
plasma treatment or a liquid based treatment in 1:3 H
2
O
2
:H
2
SO
4
.Using
such a process, Wanunu et al. showed a change in the pH response of Si
3
N
4
nanopore
functionalized with various amine terminated silane chemistries in comparison to
non-functionalized Si
3
N
4
nanopores [
93
]. Ionic conductance measurements were
used to monitor in-situ the formation of the SAM in the nanopore and to calculate
the thickness of the molecular layer directly attached to the internal surface of the
nanopore. The calculated values suggested the upright orientation of the attached
molecules on the nanopore surface. Note, in this specific example, the entire mem-
brane containing the nanopore was functionalized with the silane chemistry.
For certain applications however, it may be desirable to functionalize only the
nanopore region itself. For example, in applications where the analyte of interest
is present only at very low concentrations, a functionalized membrane may reduce
the detection limits of the nanopore due to delocalized binding events on the
membrane surface between immobilized receptors and the target species, without
yielding detectable changes in the output signal [
37
]. In addition, receptors
immobilized on the membrane may themselves modulate the conductance of the
nanopore, even in the absence of the target species. Hofler et al. showed via
coarse-grained molecular dynamics simulations that DNA anchored on the mem-
brane surface can electrically gate the nanopore if bound sufficiently close to the
pore opening [
34
]. A localized nanopore functionalization process was explored
by Nilsson et al. and involved the localized deposition of a tetraethylorthosilicate
(TEOS) based oxide ring around the nanopore [
66
]. A focused ion beam was used
to decompose the TEOS precursor near the Si nanopore surface, thereby reducing
the diameter of the pore to a final diameter of between 25 and 30 nm. DNA probes
were immobilized in the nanopore via a silane based chemistry thereby introducing
local chemical functionality at the entrance of the nanopore without functionalizing
the remainder of the Si membrane. SAM coatings may also help to reduce the
speed of polymer translocation through nanopores. Kim et al. derivatized Al
2
O
3
nanopore surfaces with aminopropyltriethoxysilane (APTES) resulting in a posi-
tively charged surface in pH 6.0 buffer, attractive to anionic dsDNA [
46
,
48
]. The
resulting strong electrostatic polymer-pore interactions enabled the detection of
short dsDNA molecules that are typically under the detection limits of conventional
solid-state nanopore sensors. In addition to SAM coatings, highly functional lipid
bilayer coatings on nanopores are also possible [
91
], permitting the potential
integration with sensitive biological nanopore channels.
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