ATOMIC FORCE MICROSCOPY FOR MEDICINE - Life at the Nanoscale: Atomic Force Microscopy of Live Cells - page 423

et al. 28 pioneered the concept that biomolecular binding
events yield forces and deformations that might be detected and recognized
by appropriately selective sensing nanostructures, leading to new
approaches to multiplexed molecular recognition ( Fig. 20.5 ).
Primary examples of such devices are micro- or nanocantilevers, which
delect and change resonant frequencies as a result of afinity binding e.g.,
nucleic acid hybridization or proteomic binding events occurring on their
free surfaces. A nanocantilever is a thin silicon nitride (typically 1 μm
thick, 500 μm long, 100 μm wide) projection attached to a microchip. The
cantilevers' surfaces are covered with a layer of receptor probes with a
speciic binding afinity to target sequence. Because of the extreme thinness
of the probe, any adjacent bindings of probes to target molecules would
cause the cantilever to locally bend at those binding sites through steric
and charge interactions. The resulting bending could then be measured
dynamically through the change in resonance frequency in response to the
added mass, or statically through the delection of a laser beam in response to
bending. The biochemically induced surface stress was shown to directly and
speciically transduce molecular recognition into nanomechanical responses
in a cantilever array. Cantilevers in an array were functionalized with a
selection of oligonucleotides of variable lengths. The differential delection
of the cantilevers was found to provide a true molecular recognition signal,
despite large nonspeciic responses of individual cantilevers. Hybridization
of complementary oligonucleotides shows detection of a single-base
mismatch between two 12-mer oligonucleotides ( Fig. 20.5 ) . The nanometre-
sized cantilevers, being extremely sensitive and able to detect single
molecules of DNA or proteins, also provide fast and sensitive detection for
cancer-related molecules. Other applications include microcantilevers to
detect single nucleopeptides in a 10-mer DNA target oligonucleotide without
the use of extrinsic luorescent or radioactive labeling. 29,30 Quantitation of
prostate serum albumin at clinically signiicant concentrations has also
been demonstrated. 29 Nanocantilevers possess extraordinary multiplexing
capability. 31 In future, fabrication of arrays of cantilevers may allow the
simultaneous reading of proteomic proiles or the entire proteome.
Based on similar concept, silicon nanowires can be engineered to detect
molecular markers of cancer cells in microluidic channel devices. Because
of their tiny size (20-100 nanometres wide), they exhibit special properties
such as superconductivity, and extremely high sensitivity to outside electric
ields. Nanowires can be coated with a probe such as an antibody that
binds to a target protein. Proteins that bind to the antibody can change the
nanowire's electrical conductance, and this can be measured by a detector.

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Each nanowire may bear a different antibody or oligonucleotide, a short
stretch of DNA that can be used to recognize speciic RNA sequences or