In recent years, molecular barcodes have become an exciting new
class of multiplexed detection and aid in identification of many
biomolecules for high-throughput screening of biological
samples. 1,2 Fluorescent dyes, quantum dots, striped metallic
particles, photonic crystals, rare earth doped glasses, and so on,
have all been used as encoding elements of molecular barcodes to
detect a broad variety of analytes in gene expression, clinical
diagnosis, drug screening and drug discovery. 3–9 Within the
context of molecular barcoding, optical barcoding technology
based on fluorophore-encoded microbeads is the most suitable
for application in high-throughput multiplexed detection due to
their simplicity in both encoding and detection. 10 Compared with
traditional molecular dyes, fluorescent quantum dots (QDs),
offering unique photochemical and photophysical properties
such as narrow emission spectra, broad excitation bandwidth,high quantum yields, resistance to photobleaching, and the
possibility of exciting all colors at the same wavelength, have
been proved to be ideal fluorophores for barcoding. Combining
different-sized and hence different-colored QDs with different
concentrations (and thus intensities) into polymeric beads,
multiplex QD-encoded microbeads with unique spectral barc-
odes can be achieved that are capable of reading thousands or
even millions of genes, proteins and small-molecule compounds
at a time. 11 Consequently, both the formation of monodispersed
polymeric microbeads and the precise variation of colors and
intensities of QDs have become the central issues in QD-based
spectral barcoding technology, at which extensive investigations
have been directed. At present, most of the methods to incor-
porate QDs into microbeads for encoding are mainly based on
the swelling technique 11 and layer-by-layer assembly strategy. 12
In these methods, the formation of microbeads and the strategy
of spectral barcoding have been accomplished via separated
two-stage processes. Technologies to encapsulate QDs into
microbeads during the bead synthesis are also developed for
polymerizable QD encapsulation. 13,14 However, these processes
are lengthy, and yet result in broadly dispersed microbead size
distribution. Some efforts are being focused on the mass
production of robust and reproducible QD-barcodes bydeveloping new microfabrication techniques and microreaction
techniques.
An emerging technique that shows great potential for the
synthesis of microparticles with controlled size, shape,
morphology and composition is droplet-based microfluidics. 15
Droplet-based microfluidics focuses on creating and manipu-
lating discrete droplets with the use of immiscible phases inside
microdevices. This method can produce highly monodisperse
droplets with diameters ranging from a few microns up to several
hundred microns, at the rate of a few hundred to several thou-
sand per second. 16 By combining the emulsification of monomers
or oligomers, bybreaking up their liquid threads in droplets, with
on-chip (or off-chip) solidification of these droplets by means of
chemical and physical crosslinking, droplet-based microfluidic
systems provide a novel route for the synthesis and fabrication of
monodisperse polymer particles.
Depending on the specific device geometry and flow parame-
ters, a wide variety of materials including gels, polymers, and
polymers doped with functional additives have been used to
produce solid, hollow, and multicored, asymmetric, and irregu-
larly shaped polymer microparticles with droplet-based
microfluidics. 17–22 Several groups have reported the production
of QD-doped microparticles accomplished with droplet-based
microfluidic systems. 16,23–26 Fluorescent poly-tripropyleneglycol
diacrylate microspheres doped with CdSe QDs were prepared
in a microfluidic flow-focusing device based on photo-
polymerization in the collaborative work of Whitesides, Stone,
and Kumacheva. 16 Both Weitz et al. 23 and Lee et al. 24 showed
that the microfluidic technologies are useful to produce mono-
disperse temperature-sensitive poly-N-isopropylacrylamide
microgels. 19 nm PEG-modified QDs and mercaptoacetic-acid
capped QDs, used as example materials, were incorporated into
their obtained microgels, respectively. Chang et al. 25 reported the
microfluidic assisted preparation of poly( DL -lactide-co-glycolide)
(PLGA) microcapsules encapsulated with CdSe/ZnS QDs. The
PLGA polymer solution containing the CdSe/ZnS QDs was
flow-focused into droplets, followed by a separate solvent
evaporation process for the formation of QD-doped PLGA
microspheres. Yang et al., 26 using a similar approach as Chang, 25
created multi-functional polycaprolactone microcapsules incor-
porating CdTe QDs, Fe 3 O 4 superparamagnetic nanoparticles
and tamoxifen anticancer drugs. All of the above have revealed
the potential of droplet-based microfluidics for the preparation
of QD-doped microparticles. It provides an op