Stochastic Detection of Terrorist Agents and Biomolecules in a Biological Channel - Nanopores: Sensing and Fundamental Biological Interactions - page 317

that it was possible to impart solid-state nanopores with selectivity and chemical
functions [ 38 - 40 ]. This allows only large molecules such as DNA to be detected by
using the electrophoretic effect to drive these molecules through the pore [ 33 ].
Furthermore, the poor resolution provided by the artificial pore makes it extremely
difficult to characterize the current signatures of different large molecules, thus not
permitting differentiation of molecules that differ slightly in composition.
There are also other efforts to overcome the fragility aspect of the protein pore.
For example, carbon nanotubes have been tested as an alternative to the protein
pore [ 41 , 42 ]. However, in addition to the surface functionality problem noted
above, it is currently not possible to reproducibly fabricate single-walled nanotubes
of specified length and pore size. Another nanopore approach, called hybrid nano-
pore system, attempts to combine the advantage of the protein pore technology
(i.e., the ease of engineering the nanopore with numerous functions, and having an
identical pore size) and that of artificial pore approach (i.e., robustness). For
example, it has been suggested that natural protein pores could be placed in
artificial membranes [ 43 ], or located in etched inorganic nanotubes [ 44 ]. Although
inherently appealing, the relative lack of results to date makes it impossible to
gauge the long-term effectiveness of this approach at this point in time.
The recent advance in the protein-based nanopore technology has shown great
promise to transition the nanopore sensor from pure academic curiosity to deploy-
able use as a laboratory or clinical tool for routine sensor applications. For example,
it has been demonstrated that a single

HL pore embedded in a planar phospholipid
bilayer could be sandwiched between two agarose gel layers in situ, which may be
transported, stored, and used repeatedly [ 45 ]. Furthermore, it was reported that the
lipid bilayer supported by a glass nanopore membrane was very stable and could last
for at least 2 weeks [ 46 ]. Thus, the issue regarding the fragility and the long-term
stability of the lipid bilayer, i.e., the major hurdle of utilizing the protein pore
method for extended usage could be overcome. More recently, Zhao and co-workers
have demonstrated that an array of protein pores modified with a variety of surface
functions could be used to construct a pattern-recognition stochastic sensor [ 47 ].
This nanopore sensor array technique allows identification of a target analyte from a
mixture and the potential for simultaneous detection of multiple analytes.
A thorough overview of various aspects of nanopore stochastic sensing technology
was recently provided in an excellent review article by Howorka and Siwy [ 48 ]. In this
chapter, we will first briefly introduce planar bilayer recording, and then summarize
the recent advances pertinent to the stochastic detection of terrorist agents and
biomolecules in a biological channel.

a

13.2 Planar Bilayer Recording

Protein pore-based stochastic sensing experiments are usually performed in a
two-compartment chamber device similar to that as shown in Fig. 13.4 , where the
cis and trans compartments are separated by a hydrophobic film (e.g., Teflon) having