In Vivo Measurement of Calcium Ion with Solid-State Ion-Selective Electrode by Using Shelled Hollow Carbon Nanospheres as a Transducing Layer

In vivo monitoring of extracellular calcium ion (Ca2+) is of great importance due to its significant contributions in different (patho)physiological processes. In this study, we develop a potentiometric method with solid-state ion-selective electrodes (ISEs) for in vivo monitoring of the dynamics of the extracellular Ca2+ by using hollow carbon nanospheres (HCNs) as a transducing layer and solid contact to efficiently promote the ion-to-electron transduction between an ionophore-doped solvated polymeric membrane and a conducting substrate. We find that the use of HCNs essentially improves the stability of the signal response and minimizes the potential drift of the as-prepared ISEs. With three-shelled HCNs (3s-HCNs) as the transducing layer, we fabricate a solid-state Ca2+-selective microelectrode by forming a Ca2+-selective membrane with calcium ionophore II as the recognition unit, 2-nitrophenyl octyl ether as the plasticizer, sodium tetrakis[3,5-bis(trifluoromethyl)phenyl] borate as the ion exchanger, and polyvinyl chloride polymeric as the matrix onto the 3s-HCN-modified carbon fiber electrodes. The as-prepared electrode shows a high stability and a near Nernst response of 28 mV/decade toward Ca2+ over a concentration range from 10(-5) to 0.05 M as well as a good selectivity against species endogenously existing in the central nervous system. With these properties, the electrode is used for real-time recording of the dynamics of extracellular Ca2+ during spreading depression induced by electrical stimulation, in which the extracellular Ca2+ in rat cortex is found to decrease by 50.0 +/- 7.5% (n = 5) during spreading depression. This study essentially offers a new platform to develop solid-state ISEs, which is particularly useful for in vivo measurements of metal ions and pH in live rat brain.