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					                                            Research Projects

     The focus of the research group of Julian Zhu is on the development of new polymer materials with
advanced applications in the biomedical and pharmaceutical fields. These materials include amphiphilic
polymers in self-assembled systems, new polymeric nanoparticles for biosensor applications, degradable
polymers for controlled release device, new dental resins based on natural compounds and solid supports
for combinatorial syntheses. We have established interdisciplinary collaborations with researchers in the
biomedical and industrial fields to insure rapid progress in our research and direct feedback on the
performance of the materials.

        (1) New block copolymers with self-assembling properties. New amphiphic copolymers with be
made by the new controlled polymerization techniques. We explore the use of controlled radical
polymerization methods to prepare new block copolymers with a well-defined structures. This will avoid
the stringent conditions required for the traditional ionic polymerization methods and expand to
momoners that are previously unaccessible. The most used controlled radical polymerization methods
include nitroxyl-mediated polymerization (NMP), atomtransfer radical polymerization (ATRP), and more
recently, reversible addition-fragmentation chain transfer polymerization (RAFT). RAFT polymerization
seems the best suited for polymerizing acrylamide derivatives and has been used in the preparation of new
di- and tri-block copolymers with multiple thermosensitive properties. The aggregation of these polymers
can be studied by various physico-chemical means, especially the imaging techniques. We will explore
the use of these polymers as rheology modifiers and controlled release vehicles.
        Natural compounds such as bile acids and cholesterol are known to self-assemble in the body in
the formation of cells and emulstions. We have used the ATRP method to modify the amphiphilicity of
these molecules, especially the grafting of short hydrophilic chains that are designed to be neutral, anionic
or cationic. The aggregation of such molecules are being studied by NMR, AFM, light scattering and
electronic microscopy. In collaboration with Dr. Guy Cloutier of Notre Dame Hospital of Montreal, we
are using the star-shaped polymers based on pegylated cholic acid to study the aggregation of red blood
cells and the rheological peroperties of human serum. This work has direct application in the ultrasonic
imaging of cells as well as in the treatment of cardiovascular abnormalities.

        (2) Biosensors: The development of biosensors is driven by a growing need for accurate and rapid
detection of biochemical species for diagnostics and sensing purposes. The central objective of this project
is to develop new devices that can be used as biosensors for diagnostics and therapeutics and to find and
improve means of detecting biochemical agents for the prevention of biochemical contamination,
environmental hazards, and safety and security threat. The ideal detection device should be free-standing
and automated with integrated sample housing and biosensing elements. Our effort is focused on the
design, synthesis and characterization of several classes of new polymers as biosensing materials. The
polymers will be tested and refined for their intended applications. Through physico-chemical studies of
the polymers, we intend to gain a better understanding of the structure-property relationships of the
polymers and of the specific interactions between the hydrogel-support systems and the agents to be
detected, especially the interaction and interference related to the pragmatic materials applicability. We
have already carried out a test of the principle with the model receptor-ligand systems chosen. We will
focus on ligand-receptor molecular recognition interactions since this will serve as the basis for
immunoassay and antigen sensing devices. With our expertise in the synthesis of hydrogels, biochemistry
and device design and fabrication, the project should be feasible within the term of the project. The
ultimate goal of the proposed project is to develop highly sensitive molecular recognition-based sensors
that selectively detect targets and provide a rapid quantitative readout. Among the factors to be considered
for the development of the biosensors are selectivity, sensitivity, robustness and sample preparation.
        (3) New dental resins. The use of composites in restorative dentistry has sparked widespread
research into the development of an ideal material with specific thermal, aesthetic, and mechanical
properties. However, the shortcomings of such materials include low biocompatibility, mechanical
properties, and resistance to wear. The purpose of this study is to evaluate multi-methacrylate derivatives
of cholic acid (a bile acid) as replacements for the rigid monomers currently used in the organic phase of
dental composites. It is our hypothesis that the rigid steroid backbone, natural occurrence in the human
digestive tract, and multiple chemical odification sites of bile acids make them ideal candidates for the
preparation of biocompatible materials with tailored physical properties. While other monomer candidates
have been put forth over the years by various research groups, the novelty of this work lies in the fact that
the molecules released from the composite through wear in the mouth should be biocompatible and not
have the adverse health effects known for typical commercial monomers (as well as their degradation
products). In the present study we assess the reactivity of monomers derived from cholic acid and test the
thermo-mechanical properties of polymers, co-polymers, and composites prepared from the latter. Results
indicate that materials prepared from certain cholic acid derivatives possess thermo-mechanical properties
similar to those of typical commercial materials. This indicates that derivatives of cholic acid may
potentially be viable replacements for typical commercial dental monomers. We have measured the
mechanical properties of these materials. We also develop new methods to monitor the degree of curingin
such resins.

        (4) Anti-aggregation with quantum dots nano-assembly in conjugated polymers. Light
emitting conjugated polymers are a new class of materials with similar optical properties to those of
inorganic semi-conductors. Their low synthesis cost and ease of processing make them extremely good
candidates for applications in flat panel and large surface display technologies. However, low
photoluminescence quantum yield in the solid state caused by aggregation quenching of the excited state
is an important limiting factor that has hindered industrial applications. In order to solve this problem,
many different strategies have been developed, focusing on the chemical modification of the main
conjugated chain with bulky side groups or end-capping agents, but the charge transport properties of the
materials are greatly impaired by such modifications. In collaboration with Dr. M.T. Nguyen of ADS,
Inc, we have made negatively-charged CdTe quantum dots to efficiently counterbalance the p-stacking in
such conjugated polymers,. The high surface area of quantum dots maximizes the ionic interactions with
the polyelectrolytes at relatively low loading levels. The photophysical properties of these assemblies
were studied by UV-visible and fluorescence spectroscopy and correlated to the level of aggregation in
the conjugated polymer. Such an efficient displacement of p-stacking by competitive positive interactions
constitutes the first example of positive aggregation modulation.

        (5) Biodegradable polymers. Biodegradable materials are now used in a wide range of
therapeutic applications ranging from drug delivery to tissue engineering. The physical and mechanical
properties of the materials play an important role in the determination of their potential use. The two main
classes of synthetic biodegradable polymers are polyesters and polyanhydrides. To improve the
biocompatibility and to achieve fine tuning of degradabilty of such materials, we have introduced natural
compounds such as bile acids into such polymers. Research in this area focuses on the development of
novel synthetic routes to degradable polymers based on bile acids. For the synthesis of polyanhydrides,
polycondensation of novel bile acid dimers is being studied under both molten and dilute conditions. In
the case of polyesters, we have chosen an emerging polymerization technique: entropy driven ring
opening polymerisation. This technique requires macrocyclic monomers to be used and therefore allows
large and rigid moieties to be incorporated in the polymer backbone. Moreover, the ring opening nature of
this polymerisation makes it suitable for reaching high molecular weights without the use of large
quantities of toxic coupling agents. These polymers are tested as drug carriers in the treatment of tumors
and as bone tissue replacement materials.
         (6) Polymer support in combinatorial synthesis. With the rapid development of combinatorial
synthesis in pharmaceutical industry, more specialized functional polymers are needed as supports for
solid phase synthesis or as scavengers for undesired products to simplify the isolation and purification
procedures. The nature of the polymer support and the functional groups is of crucial importance in such
applications. Research in this area ongoing within our group focuses on the development of crosslinked
polymers with high loading of various functional groups levels and with good swellability in aqueous
media and in organic solvents. Moreover, large and uniform-sized polymer beads are synthesized via
ascension polymerization for the one bead-one compound application in combinatorial synthesis of
libraries of compounds. Some of the polymers have been tested with our collaborators in organic
chemistry and in industry.