Dr. John L. Brash

Overview

1. Biotechnology and Biomaterials
A major theme of our studies is the interfacial behaviour of proteins which is of great importance in biotechnology, diagnostics, and medical devices. Many of the products of biotechnology are genetically engineered proteins – e.g. insulin and growth factors. Processing presents unique problems due to the instability of these complex macro-molecules. For example, chromatography involving interaction of the proteins with solid surfaces is often used in final purification but can lead to molecular distortion and a biologically inactive, even though pure, product. An example in the medical devices field is blood compatible materials for arterial grafts, blood pumps and heart valves. A major unsolved problem here is blood coagulation/thrombosis believed to be initiated by the adsorption of plasma proteins to the surface of the implant. In these contexts we are studying the adsorption of a range of proteins using tube flow, serum replacement(equivalent to CSTR), and packed column experiments in conjunction with radio labelled proteins. Media range from buffered solutions to blood. Specific interests are the kinetics,equilibria and reversibility of adsorption and changes in the structure and biologic function of adsorbed proteins. A prime objective is to correlate specific interactions with surface properties, e.g. wettability, electric charge, chemical composition. Materials for study, mostly polymers, are synthesized in the laboratory or are acquired from collaborating research groups around the world.

2. Polymerization and Polymer Characterization
This work is on condensation polymerization and is mainly concerned with segmented polyurethanes, a versatile class of thermoplastic elastomers. Objectives are to improve understanding of structure-property relationships, to develop methods for “tailoring” surface properties, and to develop “bioactive” polyurethanes having specific biological activity. An example of the latter are surfaces which will activate the fibrinolytic (clot dissolving system) in blood.

3. Modification of Surfaces for Biotechnology Applications
Surface modification of materials is of considerable current interest in biotechnology applications such as biosensors and diagnostic devices. In general one wants to keep the bulk properties of the material intact while tailoring the surface to impart properties such as resistance to fouling or binding of a specific molecule from a contacting biofluid. We are developing a program in this area based on two approaches: (a) gas plasma treatment of polymer surfaces, (b) chemical grafting (c) modification of surfaces via exploitation of gold-thiol chemistry. In the latter, the surface is coated with a thin film of gold which is then treated with appropriate thiolates to give the desired properties. In some cases the resulting layers have unique properties through ordering and self assembly.