Photoactivated sensors offer a safe, low-power alternative to thermal sensors, yet their performance against trace concentrations of weakly reactive biomarkers is fundamentally crippled by the rapid energy loss of photogenerated carriers via electron relaxation into band-edge. This process limit the number of electrons available for sensing. Here, we overcome this limitation by introducing a new principle: non-equilibrium hot-electron-mediated chemoresistance. Our quantum-engineered CdSe@CdS-Au ternary hetero`structure is expressly designed to win the kinetic race against relaxation. Compared with two-tip gold domains governed by cooled electron transfer, the multi-site specific Au structure enhances electron transfer rates by 86-fold into 1.60×1012 s-1 with efficiencies of 99%, indicates ballistic hot-electron injection from the semiconductor into multi-site Au nanodomains prior to relaxation, as verified by femtosecond transient absorption spectroscopy. Functionalization with 4-bromobenzenethiol enables selective detection of trans-2-nonenal at 0.70 ppb—a new benchmark in optical sensors and chemoresistive sensors. Furthermore, a portable six-channel UV-activated sensor chip based on this principle demonstrates a 97.9% diagnostic accuracy in simulated exhaled breath, showcasing a transformative pathway toward non-invasive screening of non-small cell lung cancer.
