Cascade-heterogated proton nanotransistors for multiplex pH-interval imaging

The pH in organisms is strictly regulated within an appropriate range for homeostasis, and many pathological processes often result in pH dysregulation to distinct intervals that serves as targets for diagnosis and treatment. Thus, a mechanism of selective and gating response for different proton levels in an integrated nanodevice is needed to report acidic biological environments with specific pH dynamic ranges. Here we report the design of band-pass light-up nanokits (BLINK) with pH heterogating capacity in opposite directions to achieve selective reporting of the acidic intervals (minimum to 0.25 pH unit) of pathophysiological environments. The proton heterogated property of BLINK integrates ultra-fast (<15 ms) and cascade nanophase transition of transistor-like polymeric modules and tandem FRET relay between encoded fluorophores, permitting the selective transformation of acidic extracellular or intracellular signals to exponentially amplified fluorescence readout without introducing the signals outside the targeted pH ranges. This study offers a valuable tool for pH sensing, and paves the way for the development of interval-based optical imaging technology.