A SERS Optophysiological Probe for the Real-Time Mapping and Simultaneous Determination of the Carbonate Concentration and pH Value in a Live Mouse Brain

To have a profound understanding of the physiological and pathological processes in a brain, both chemical and electrical signals need to be recorded, but this is still very challenging. Herein, micrometer- to nanometer-sized SERS optophysiological probes were created to determine both the CO ₃ ²⁻ concentration and the pH in live brains and neurons because both species play important roles in regulating the acid–base balance in the brain. A ratiometric SERS microarray of eight microprobes with tip sizes of 5 μm was established and used for the first time for real-time mapping and simultaneous quantification of CO ₃ ²⁻ and pH in a live brain. We found that both the CO ₃ ²⁻ concentration and the pH value dramatically decreased under ischemic conditions. The present SERS technique can be combined with electrophysiology without cross-talk to record both electrical and chemical signals in brains. To deepen our understanding of the mechanism of ischemia on the single-cell level, a SERS nanoprobe with a tip size of 200 nm was developed for use in a single neuron.