Field-effect sensors have been applied extensively to numerous biomedical applications. To develop biosensor arrays in large scale, integration with signal-processing circuits on a single chip is crucial for avoiding wiring complexity and reducing noise interference. This paper proposes and compares two CMOS-compatible processes that allow open-gate, field-effect transistors (OGFETs) to be fabricated at the die level. The polygates of transistors are removed to maximize the transconductance. The CMOS compatibility further facilitates the monolithic integration with circuitry. Based on images and electrical measurements taken at different stages of the post-CMOS processes, a more feasible and reliable process is identified. The robustness of the fabricated OGFETs against the micromachining process and against moisture is further examined and discussed. Finally, the capability of the OGFETs in detecting ion concentrations, biomolecules, and electrophysiological signals is demonstrated.