Biomedical Engineering Reference
In-Depth Information
Fig. 13.3
a
-hemolysin
structure
permit the protein to tolerate modifications without losing functionality (i.e., still
having the ability to form a channel in a lipid bilayer after the protein is
engineered). Additionally, the relatively large
HL pore, and hence, the large
single-channel conductance facilitates current recording. For example, the wild-
type and engineered versions of the transmembrane protein pore in
a
HL have been
used as stochastic sensing elements for the identification and quantification of a
wide variety of substances [
1
], including metal ions [
7
,
8
], anions [
9
], organic
molecules [
10
], reactive molecules [
11
], enantiomers [
12
], terrorist agents [
13
-
16
],
DNA [
17
-
24
], peptides [
3
,
25
-
28
], and proteins [
29
-
32
]. Whereas this work is
of obvious interest, a major challenge to the transition of protein pore technology to
deployable sensors for extended usage is the fragility and the long-term stability of
the biological membranes.
In light of the above limitation of natural pores, efforts are underway to construct
robust pores in other materials, e.g., polymer and solid inorganic membranes
[
33
-
37
]. Although the fabricated artificial nanopores improve the fragility aspect
of the protein pore and they can function in a variety of extreme conditions,
including voltage, temperature, and solvent variations, the following two issues
have, to date, severely limited the practical application of the artificial pore
approach. First, unlike the protein pore, it is very difficult, time-consuming, and
requires specialized expensive equipment to prepare artificial pores with reproduc-
ible pore size. Therefore, the current signatures for a given analyte (e.g., amplitude
and residence time) may change significantly from pore to pore, thus making the
statistical analysis of the data extremely difficult and non transferable from lab to
lab and even one sensor to another in the same lab. Second, the currently available
artificial pore technology provides a very poor resolution due to the lack of surface
functionalities [
2
], although it should be noted that the most recent study showed
a
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