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2.2.3 Water Solubility
In a reverse microemulsion, the hydrolysis and polymerization of the silicate
precursor occur in the water droplet, therefore, to dope dyes in the silica nanopar-
ticles they must be water soluble. However, a number of organic dye molecules are
hydrophobic, requiring modifications prior to doping. Several methods are avail-
able to link a hydrophobic dye molecule to a water soluble group. A simple and
effective example is to link a hydrophilic dextran to the dye molecules [ 8 ]. This
modification can greatly enhance the water solubility of hydrophobic dye mole-
cules, but will increase the cost of resultant DDSNs.
In summary, a suitable association between dye molecules and the silica matrix
is necessary for synthesis of DDSNs. Without the presence of chemical bonds or
electronic interactions, the dye molecules will leak out from silica nanoparticles
through the silica pores [ 22 ]. Such DDSNs will provide unstable florescence signals
and cannot be used as a labeling agent in bioanalysis. Meanwhile, water solubility is
critical for a dye molecule when using a reverse microemulsion method to make the
DDSNs.
2.3 Configurations of DDSNs
Several different configurations of DDSNs have been reported. At the beginning,
most DDSNs were designed with a single type of dye molecules homogeneously
doped inside the silica nanoparticles [ 5 , 8 , 58 ]. These nanoparticles, as labeling
materials, were successfully applied to bioanalysis and bioimaging. At the present,
DDSNs contain multiple dye molecules [ 21 , 60 - 62 ], have different configurations
[ 6 , 13 , 14 , 27 , 28 ], and multiple functions [ 15 , 19 , 37 , 43 ]. These new designs
extend the range of DDSN applications.
2.3.1 Doping Multiple Dye Molecules
The purpose of doping multiple types of dye molecules in a silica nanoparticle is
to simultaneously emit fluorescence signals at different wavelengths under a single
excitation source. Different sizes of quantum dots made from the same materials
can emit fluorescence at different wavelengths using a single excitation wave-
length. Like quantum dots, DDSNs can also produce multiple-colored fluorescence
if multiple dyes are doped into a silica nanoparticle. A series of dual-DDSNs were
designed by doping tris(2,2 0 -bipyridyl)osmium(II)bis(hexafluoro-phosphate) (Os
(bpy) 3 2+ ) and Ru(bpy) 3 2+ into silica nanoparticles with various dye molar ratios
[ 21 ]. When excited at a single wavelength of 488 nm, the two emission spectra from
Ru(bpy) 3 2+ and Os(bpy) 3 2+ have no overlap. Their emission peaks are at 610 nm
(Ru(bpy) 3 2+ ) and 710 nm (Os(bpy) 3 2+ ), respectively. By changing their molar ratios
of the two dye molecules, the resultant DDSNs displayed different colors. These
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