Novel Self-Calibrating Amperometric and Ratiometric Electrochemical Nanotip Microsensor for pH Measurement in Rat Brain.

Brain pH has been proven to be a key factor in maintaining normal brain function. The relationship between local pH fluctuation and brain disease has not been extensively studied due to lack of the accurate in situ analysis technology. Herein, we have for the first time proposed a voltammetric pH sensor by measuring the ratio of current signals instead of the previously reported potential based on the Nernst equation. Single-walled carbon nanotubes (CNT) were first self-assembled on the electrode surface of a carbon-fiber nanotip electrode (CFNE). Then, poly-o-phenylenediamine (PoPD) molecules were deposited as pH-responsive molecules through in situ electrochemical polymerization. The compact CFNE/CNT/PoPD exhibited a good redox process with the on-off-on ratiometric electrochemical response to pH ranging from 4.5 to 8.2, providing self-correction for in situ pH detection. Thus, the proposed sensor enabled the accurate measurement of pH with excellent selectivity even in the presence of proteins or electroactive species. In addition, the sensor showed high repeatability, reproducibility, and reversibility in measuring pH and even demonstrated good stability when it was exposed to air for 5 months. Finally, we successfully detected the fluctuation of pH in rat brains with cerebral ischemia and rat whole blood. Overall, this research not only provides a good tool for the detection of rat brain pH but also provides a new strategy for further designing nanosensors for intracellular or subcellular pH.