Real-time Tracking and Sensing of Cu⁺ and Cu²⁺ with a Single SERS Probe in the Live Brain: Toward Understanding Why Copper Ions Were Increased upon Ischemia

The imbalance of Cu⁺ and Cu²⁺ in the brain is closely related to neurodegenerative diseases. However, it still lacks of effective analytical methods for simultaneously determining the concentrations of Cu⁺ and Cu²⁺. Herein, we created a novel SERS probe (CuSP) to real-time track and accurately quantify extracellular concentrations of Cu⁺ and Cu²⁺ in the live brain. The present CuSP probe demonstrated specific ability for recognition of Cu⁺ and Cu²⁺ in a dual-recognition mode. Then, a microarray consisting of 8 CuSP probes with high tempo-spatial resolution and good accuracy was constructed for tracking and simultaneously biosensing of Cu⁺ and Cu²⁺ in the cerebral cortex of living brain. Using our powerful tool, it was found that that the concentrations of Cu²⁺ and Cu⁺ were increased by ≈4.26 and ≈1.80 times upon ischemia, respectively. Three routes were first discovered for understanding the mechanisms of the increased concentrations of Cu⁺ and Cu²⁺ during ischemia.