A biocompatible hydrogel-coated fiber-optic probe for monitoring pH dynamics in mammalian brains in vivo

The pH dynamics plays an important role in maintaining the homeostasis of the brain and is related to a variety of brain diseases. Yet, there are many challenges in designing long-term implanted probes to accurately detect weak pH changes in vivo in real time. Here, we report the first biocompatible hydrogel-coated fiber optic probe (HCFOP) for monitoring pH dynamics at high precision in brains of freely moving mice, to the best of our knowledge. The novel HCFOP is prepared by covalently linking hydrogel-coated silica multimode fiber to hydrogel fiber, which embeds pH-sensitive fluorescence microspheres. Based on fluorescence ratio detection, the pH sensor has a dynamic range from 3.0 to 9.0, and a resolution of 0.0014 pH units in the super sensitive range of pH 7.0–8.0, with good reproducibility, reversibility, and stability. During cerebral ischemia, we detect a decrease of pH by ∼0.5 after ∼15 mins in mouse brains. During epileptic seizure, we detect a decrease of pH by ∼0.3 after ∼1 h in the hippocampus. This biocompatible HCFOP provides a unique solution for assessing minor changes in pH of the brain microenvironments, thus holds great promises in neuroscience study.