Synthesis and Characterization of a Micelle-Based pH Nanosensor with an Unprecedented Broad Measurement Range

A new cross-linked micelle pH nanosensor design was investigated. The nanosensor synthesis was based on self-assembly of an amphiphilic triblock copolymer, poly(ethylene glycol)- b -poly(2-amino ethyl methacrylate)- b - poly(coumarin methacrylate) (PEG- b -PAEMA- b -PCMA), which was synthesized by isolated macroinitiator atom transfer radical polymerization. Micelles were formed by PEG- b -PAEMA- b -PCMA self-assembly in water, giving micelles with an average diameter of 45 nm. The PCMA core was employed to utilize coumarin-based photoinduced cross-linking in the core of the micelles, which was performed by UV irradiation (320 nm < λ < 500 nm), and the progress of the cross-linking was monitored by UV spectroscopy. The formed cross-linked core–shell–corona micelle was converted into ratiometric pH nanosensors by binding the pH-sensitive fluorophores oregon green 488 and 2′,7′-bis-(2-carboxyethyl)-5-(and-6) carboxyfluorescein and a reference fluorophore Alexa 633 to the PAEMA shell region of the micelles. Fluorescence measurements show that these pH nanosensors are sensitive in a surprisingly broad pH range of 3.4–8.0, which is hypothesized to be due to small differences in the individual fluorophores’ local environement. It was found that the utilization of self-organization principles to form the nanoparticles, followed by cross-linking to ensure sensor integrity, provides a fast and highly flexible method that can be utilized in a broad range of nanosensor designs.