High-sensitivity polycrystalline silicon (poly-Si) nanowire field-effect transistor (NW FET) pH sensors using top-down and self-aligned fabrication approaches involving the conventional complementary metal-oxide-semiconductor (CMOS) process are reported. For the top-down NW FET, the shrinkage due to reoxidation enables the nanowire width to be scaled to 40nm without requiring the use of extra lithography equipment, and this improves the electrical uniformity and the performance of the sensors. The surface-ionic coupling operation of this buried-channel field-effect sensor exhibits superior pH sensitivity (threshold voltage shift > 100 mV/pH) as compared to the surface-channel ion-sensitive FET (ISFET). In addition, we report a novel method for fabricating self-aligned, vertical-channel, poly-Si nanowire sensors. The resulting 65-nm self-aligned vertical-channel poly-Si device was found to be feasible for independent-gate bias control, thus enabling its possible integration in very-large-scale integration (VLSI) circuits. Both the abovementioned approaches enable the manufacture of nanowire devices on a large-scale integrated (LSI) circuit using only CMOS manufacturing processes; this provides a high sensitivity, compact and cost-efficient biosensor systems-on-a-chip application.