A Single Biosensor for Evaluating the Levels of Copper Ion and L ‐Cysteine in a Live Rat Brain with Alzheimer's Disease

Copper ion (Cu 2+ ) and L ‐cysteine (CySH) are closely correlated with physiological and pathological events of Alzheimer’s Disease (AD), however the detailed mechanism is still unclear, mainly owing to a lack of accurate analytical methods in live brains. Herein, we report a single biosensor for electrochemical ratiometric detection of Cu 2+ and CySH in live rat brains with AD. N , N ‐di‐(2‐picoly)ethylenediamine (DPEA) is first synthesized for specific recognition of Cu 2+ to form a DPEA–Cu 2+ complex. This complex shows high selectivity for CySH owing to the release of Cu 2+ from the complex through CySH binding to Cu 2+ center. In parallel, 5′‐MB‐GGCGCGA‐SH‐3′ (HS‐DNA‐MB, MB=Methylene Blue) is designed as an inner‐reference for providing a built‐in correction to improve the accuracy. As a result, combined with the amplified effect of Au nanoleaves, our single ratiometric biosensor can be successfully applied in real‐time detection of Cu 2+ and CySH in the live rat brains with AD. To our knowledge, this is the first report on the accurate concentrations of Cu 2+ and CySH in live rat brains with AD.