We have prepared a swellable templated copolymer that selectively recognizes theophylline in the presence of caffeine, a compound that differs from theophylline by a single methyl group. The copolymer includes 10 to 20 mole-% recognition monomer and 5 mole-% crosslinker. The rest is N-isopropylacrylamide or n-propylacrylamide. This polymer undergoes a thermal phase transition, coming out of solution above the thermal phase transition temperature. Molecular recognition occurs above the thermal phase transition. We have demonstrated response to theophylline below 0.1 micromolar at room temperature and neutral pH. These copolymers are stable and easily prepared in large quantities. They offer new possibilites for designing sensors and actuators for biomedical applications. They can be used for continuous sensing of drugs or endogenous compounds. They can be employed as actuators in drug delivery systems. They can potentially be used for chemically triggered delivery of trapped compounds. This application has two specific aims. The first specific aim is to synthesize a copolymer that selectively recognizes glutamine and to incorporate this material into a sensor that is capable of in situ monitoring of glutamine in fermentation broths. Two sensing schemes are proposed. One involves measuring changes in the turbidity of membranes consisting of copolymer microspheres embedded in a hydrogel. Turbidity changes because swelling and shrinking changes copolymer refractive index. The turbidity can be measured remotely through optical fibers using components developed for optical telecommunications. The second involves incorporating donor and acceptor fluorophores into the copolymer at levels such that swelling and shrinking change the extent of fluorescence resonance energy transfer, leading to a change in the ratio of donor to acceptor fluorescence. The second is to demonstrate the feasibility of chemically triggered delivery of trapped target molecules under physiological conditions. The trigger molecule will be theophylline. The rate of release of fluorescent target molecules will be monitored as a function of time for different release conditions. ? ? ?
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