Covalent incorporation of metalloporphyrin in luminescent polymer dot transducer for continuous glucose monitoring

Luminescent dye-doped polymer dots (Pdots) have been demonstrated for various biosensing applications. However, the dye doping strategy may suffer from dye aggregation and dye leaching issues which limit the long-term sensor performance. Here, we show that covalent incorporation of metalloporphyrin in polyfluorene backbone for continuous glucose monitoring. The resulting polymer was used to develop luminescent Pdots transducer that overcome the dye-aggregation problem. We characterized the spectroscopic properties of the metalloporphyrin covalently-linked Pdots, which showed reduced batch-to-batch variation, enhanced intra-particle energy transfer, and improved luminescence stability as compared to the metalloporphyrin-doped Pdots. After bioconjugation with glucose oxidase (GOx), the oxygen-sensitive phosphorescence is highly sensitive to glucose variations. The metalloporphyrin-linked Pdots transducer showed good performance in long-term continuous glucose monitoring in mouse models. This work demonstrates that covalent incorporation of porphyrin dyes in Pdots transducer is a reliable strategy to improve their stability and reproducibility for long-term continuous glucose monitoring in vivo.