403
14 Quantitative Analysis of disease Biomarkers using …
particles with thin layers of the desired material, followed by selective removal of
the colloidal templates through calcination or wet chemical etching. these particles
show strong enhancement effects from individual particles because of their ability
to localize the surface electromagnetic fields through the pinholes in the hollow
particle structures. Y. Xia and co-workers [29, 30] developed a simple and versatile
route for the synthesis of metal nanostructures with well-defined hollow interiors
using a replacement reaction between the surface of a nanoscale template and an
appropriate salt precursor solution. C. E. talley and co-workers [31] also synthesized hollow gold nanospheres (hgNs) using cobalt nanoparticles as templates and
investigated their SERS application feasibility. According to their experimental results, the homogeneity of the hgNs leads to a nearly 10-fold improvement in signal
consistency over standard silver substrates commonly used in SERS applications.
Encapsulated SERS probes, in which the central metal core and label molecule
are encapsulated by a shell, have also been developed. For example, silica-encapsulated SERS nanoparticles were first reported by R. g. Freeman and co-workers [32]
and commercialized by oxonica. J. Choo and co-workers [33] developed silvercoated gold hybrid nanoprobes. gold nanoparticles are superior to other nanoparticles in terms of long-term stability; however, the SERS enhancement effect of
silver is 100–1000 times greater than that of gold. thus, gold particles were coated
with silver for maximum SERS enhancement.
metal nanomaterials with different morphologies have also been used as SERS
nanoprobes. Recently, rod-shaped nanoparticles have been introduced as powerful
imaging probes for biomedical applications. gold nanorods (gNRs) have two surface
plasmon bands: a short-wavelength band near 520 nm and a long wavelength band
in the near-infrared region. the long-wavelength band has much greater absorption
intensity because of the longitudinal oscillation of the conduction-band electrons
[34]. Furthermore, the gold nanorod aggregates also show stronger SERS enhancement effects than gold nanosphere aggregates because of the increase in density of
junction points caused by their large surface area. the aspect ratio of gold nanorods
can be controlled through the synthetic process, and it provides an opportunity to
tune the surface plasmon band to obtain the maximum signal enhancement [35–38].
SERS targeting nanoprobes should always contain Raman reporter molecules
to create a known source of the SERS spectrum for the molecule in question. the
internal modes of the reporter molecules adsorbed to the nanoparticle surface can
be used as diagnostic signals of a specific biomarker in blood serum. In particular,
different reporter molecules can be applied to multiplex SERS detection. Because
SERS peaks are narrower than fluorescence peaks, it is possible to create many
distinct and simultaneously quantifiable SERS probes. It is also very important to
functionalize the surface of the nanoparticles to selectively attach the nanoprobes
to specific biomarkers in blood serum. For this purpose, antibodies or other biomolecules should be conjugated to the gold nanoparticle surface. Preparing stable
biomolecule-gold nanoparticle complexes depends on several interactions: (a) electrostatic attraction between the negatively-charged nanoparticles and the abundant
positively-charged sites on the biomolecule, (b) hydrophobic adsorption of biomolecules on the metal surface, and (c) covalent bonding between free thiol groups and
nanoparticles. Among these conjugation methods, covalent attachment of molecules
14 Quantitative Analysis of disease Biomarkers using …
particles with thin layers of the desired material, followed by selective removal of
the colloidal templates through calcination or wet chemical etching. these particles
show strong enhancement effects from individual particles because of their ability
to localize the surface electromagnetic fields through the pinholes in the hollow
particle structures. Y. Xia and co-workers [29, 30] developed a simple and versatile
route for the synthesis of metal nanostructures with well-defined hollow interiors
using a replacement reaction between the surface of a nanoscale template and an
appropriate salt precursor solution. C. E. talley and co-workers [31] also synthesized hollow gold nanospheres (hgNs) using cobalt nanoparticles as templates and
investigated their SERS application feasibility. According to their experimental results, the homogeneity of the hgNs leads to a nearly 10-fold improvement in signal
consistency over standard silver substrates commonly used in SERS applications.
Encapsulated SERS probes, in which the central metal core and label molecule
are encapsulated by a shell, have also been developed. For example, silica-encapsulated SERS nanoparticles were first reported by R. g. Freeman and co-workers [32]
and commercialized by oxonica. J. Choo and co-workers [33] developed silvercoated gold hybrid nanoprobes. gold nanoparticles are superior to other nanoparticles in terms of long-term stability; however, the SERS enhancement effect of
silver is 100–1000 times greater than that of gold. thus, gold particles were coated
with silver for maximum SERS enhancement.
metal nanomaterials with different morphologies have also been used as SERS
nanoprobes. Recently, rod-shaped nanoparticles have been introduced as powerful
imaging probes for biomedical applications. gold nanorods (gNRs) have two surface
plasmon bands: a short-wavelength band near 520 nm and a long wavelength band
in the near-infrared region. the long-wavelength band has much greater absorption
intensity because of the longitudinal oscillation of the conduction-band electrons
[34]. Furthermore, the gold nanorod aggregates also show stronger SERS enhancement effects than gold nanosphere aggregates because of the increase in density of
junction points caused by their large surface area. the aspect ratio of gold nanorods
can be controlled through the synthetic process, and it provides an opportunity to
tune the surface plasmon band to obtain the maximum signal enhancement [35–38].
SERS targeting nanoprobes should always contain Raman reporter molecules
to create a known source of the SERS spectrum for the molecule in question. the
internal modes of the reporter molecules adsorbed to the nanoparticle surface can
be used as diagnostic signals of a specific biomarker in blood serum. In particular,
different reporter molecules can be applied to multiplex SERS detection. Because
SERS peaks are narrower than fluorescence peaks, it is possible to create many
distinct and simultaneously quantifiable SERS probes. It is also very important to
functionalize the surface of the nanoparticles to selectively attach the nanoprobes
to specific biomarkers in blood serum. For this purpose, antibodies or other biomolecules should be conjugated to the gold nanoparticle surface. Preparing stable
biomolecule-gold nanoparticle complexes depends on several interactions: (a) electrostatic attraction between the negatively-charged nanoparticles and the abundant
positively-charged sites on the biomolecule, (b) hydrophobic adsorption of biomolecules on the metal surface, and (c) covalent bonding between free thiol groups and
nanoparticles. Among these conjugation methods, covalent attachment of molecules