For the first time, a novel smart biosensor with hybrid sensor/memory/CMOS poly-Si nanowire technology has been developed. Special designed oxide-nitride-oxide composite dielectric underneath 50nm nanowire realizes an electrically Vth-adjustable sensor to compensate device variation. The detections of pH, hydrogen peroxide and DNA are demonstrated using various functionalized receptors. A substrate-ionic coupling operation of the buried-channel field-effect sensor exhibits superior pH sensitivity (V th shift > 100mV/pH) beyond Nernst limitation. The built-in memory of nanowire devices possess steady electrically Vth adjustment (Vth programming/erasing window > 2V), enable portable physiology monitoring and in-situ recording. In this work, we report a fully CMOS-compatible technique for Lab-on-Chip biosensor application.