Systematic Optimization of Fluorogenic ARGET ATRP toward Rapid and Oxygen-Tolerant Analyte Detection

Sensitive analyte detection requires the rapid amplification of small molecular interactions into observable macro readouts. Fluorogenic activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) afford real-time, visible fluorescence generation as a function of polymerization initiator (or analyte) concentration, as dark, nonfluorescent monomers reveal their fluorescence upon incorporation into the growing polymer chain. Though encouraging, the practicality of the initially developed fluorogenic ARGET ATRP platform is severely limited by long reaction times and the sensitivity to oxygen, precluding its development for bioanalyte detection applications. This paper describes a systematic optimization study to probe the effect of several fluorogenic ARGET ATRP reaction variables, evaluating the effects of surfactant, catalyst loading, halide salt, and reaction solvent on fluorescence generation. Combining the effects of optimized individual reaction components affords a significant increase in both the rate and magnitude of fluorescence generation and renders the optimized platform tolerant to ambient oxygen, able to reliably detect initiator or model analyte when conducted in open air. Taken together, these dramatic strides in the optimization of fluorogenic ARGET ATRP open the door to applications for rapid bioanalyte detection.