Novel Fabrication Strategies for Multifunctional Hydrogel Microparticles.
fabrication strategies for poly (ethylene glycol) (PEG) -based microparticles and their
utility for exploiting the advantages of viral nanotemplates and DNA oligonucleotides
are presented in this dissertation: 1. Nucleic Acid Hybridization Assembly of Viral
Nanotemplates on Microparticles A flow lithography technique known as stop-flow
lithography (SFL) was used to fabricate ... read moremicroparticles with discrete regions for sample
identification and patterned assembly of functionalized tobacco mosaic virus (TMV)
nanotemplates. TMV nanotemplates were programmed with linker DNA, complementary to the
probe DNA in the assembly region of the microparticles. The hybridization-based assembly
yielded specific, programmable, and spatially selective assembly of TMV nanotemplates on
encoded hydrogel microparticles and demonstrates a novel high throughput route to create
multiplexed and multifunctional viral-synthetic hybrid microentities. 2. Microparticles
Containing Functionalized Viral Nanotemplates Functionalized viral assemblies were
uniformly distributed throughout hydrogel microparticles by direct embedding with a
microfluidic flow-focusing device and UV photopolymerization. Fluorescence and confocal
microscopy images showed uniform distribution of the TMV nanotemplates. Microparticles
containing TMV-templated palladium (Pd) nanoparticles exhibited catalytic activity for
the dichromate reduction reaction. The results reveal that microparticles provide a
stable and simple-to-handle carrier for TMV nanotemplates and address a critical
challenge of 3D assembly of functionalized viral hybrid nanomaterials. 3. DNA-Conjugated
Microparticles via Replica Molding (RM) DNA-conjugated microparticles were fabricated
using a soft-lithographic batch processing-based technique, known as RM. A humidity
controlled environment was found to minimize the negative effects of rapid evaporation
and ensure uniformity across batch fabricated microparticles. It was also found that
PEG-diacrylate concentration effects hybridization and target DNA penetration depth.
Additionally, the effects of probe DNA and photoinitiator concentration on target DNA
hybridization and particle formation were examined. Finally, sequence-specificity and
responsiveness down to single nanomolar concentrations was determined. The results
demonstrate a simple, robust, and scalable batch procedure for manufacturing highly
uniform hybridization assay particles in a well-controlled manner. Additionally, this
work illustrates a novel batch fabrication technique, which offers advantages over the
traditional, continuous (microfluidic) fabrication methods for DNA-conjugated
microparticles. Together, these results identify multiple simple and well-controlled
fabrication strategies for PEG-based, functional hydrogel microparticles, which
contribute to the advancement and application of functional
Thesis (Ph.D.)--Tufts University, 2011.
Submitted to the Dept. of Chemical and Biological Engineering.
Advisor: Hyunmin Yi.
Committee: Daniel Ryder, Da vid Kaplan, and Patrick Doyle.
Keywords: Chemical Engineering, Chemistry, and Nanotechnology.read less
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