Fig. 1: Schematic illustration of BLINK design for pH-interval imaging.
From: Cascade-heterogated proton nanotransistors for multiplex pH-interval imaging
a scheme of BLINK nanotransistor with binary OFF-ON-OFF response as compared to traditional OFF-ON-OFF small molecular probes. Transition of BLINK from OFF1 to ON is triggered at pHt1, while the transition from ON to OFF2 occurs when pH value drops to pHt2. Thus, BLINK[t2, t1] could selectively target specific pH-interval between pHt1 and pHt2 with a narrow resolution of 0.25 pH unit. However, OFF-ON type pH probe would provide biased signals of pH lower than the targeted pH window. As for dual-pH-responsive molecular probes, they require a very wide range of 4–6 pH units to achieve OFF-ON-OFF transition. b based on the concept of cascade-heterogated nanotransistor, BLINKs with distinct pHt1 and pHt2 exhibit the selective amplification of acidic extracellular tumor microenvironmental signals (pHe ~6.5–6.9) rather than the pH signals from bloodstream and endocytic organelles upon nanoparticle internalization. For the imaging of acidic endocytic organelles, BLINKs with optimized pHt1 and pHt2 keep OFF at pH higher than pHt1 and lower than pHt2, while the nanoparticles are turned ON in the unique pH ranges of early endosome (pHi ~6.0–6.5), late endosome (pHi ~5.5–6.0), and lysosome (pHi ~4.5–5.5) without any crosstalk.
