Web Release Date: May 16,
Dual Magnetic-/Temperature-Responsive Nanoparticles for Microfluidic Separations and Assays




and
Department of Bioengineering, University of Washington, Seattle, Washington 98195, CIRIMAT, UMR 5085 CNRS-UPS-INP, 118 route de Narbonne, 31062 Toulouse Cedex 09, France, and ICMCB, UPR 9048 CNRS, Université de Bordeaux I, 87 Avenue du Docteur Schweitzer, 33608 Pessac Cedex, France
Received August 28, 2006
In Final Form: February 16, 2007

Abstract:
A stimuli-responsive magnetic nanoparticle system for diagnostic target capture and concentration has been developed
for microfluidic lab card settings. Telechelic poly(N-isopropylacrylamide) (PNIPAAm) polymer chains were synthesized
with dodecyl tails at one end and a reactive carboxylate at the opposite end by the reversible addition fragmentation
transfer technique. These PNIPAAm chains self-associate into nanoscale micelles that were used as dimensional
confinements to synthesize the magnetic nanoparticles. The resulting superparamagnetic nanoparticles exhibit a
-Fe2O3
core (~5 nm) with a layer of carboxylate-terminated PNIPAAm chains as a corona on the surface. The carboxylate
group was used to functionalize the magnetic nanoparticles with biotin and subsequently with streptavidin. The
functionalized magnetic nanoparticles can be reversibly aggregated in solution as the temperature is cycled through
the PNIPAAm lower critical solution temperature (LCST). While the magnetophoretic mobility of the individual
nanoparticles below the LCST is negligible, the aggregates formed above the LCST are large enough to respond to
an applied magnetic field. The magnetic nanoparticles can associate with biotinylated targets as individual particles,
and then subsequent application of a combined temperature increase and magnetic field can be used to magnetically
separate the aggregated particles onto the poly(ethylene glycol)-modified polydimethylsiloxane channel walls of a
microfluidic device. When the magnetic field is turned off and the temperature is reversed, the captured aggregates
redisperse into the channel flow stream for further downstream processing. The dual magnetic- and temperature-responsive nanoparticles can thus be used as soluble reagents to capture diagnostic targets at a controlled time point
and channel position. They can then be isolated and released after the nanoparticles have captured target molecules,
overcoming the problem of low magnetophoretic mobility of the individual particle while retaining the advantages
of a high surface to volume ratio and faster diffusive properties during target capture.
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