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This paper presents an integrated, protein-based, biosensor that can be scaled to form high-density, multi-analyte sensor arrays physically integrated on a signal conditioning circuit die. A fully scalable, post-CMOS-compatible, three-electrode interface to biochemical sensors has been developed. A silicon substrate electrode system, consisting of Ti/Au working and auxiliary electrodes and a Ti/Au/Ag/AgCl reference electrode has been adapted to biomimetic sensors. The functional Ag/AgCl reference electrode is isolated from the environment using a Nafion cation-exchange membrane to extend operation lifetime. To complete the sensor structure, lipid bilayers have been deposited in passivation layer openings formed over individual working electrodes using a special tethering molecule. Total internal reflection microscopy (TIRFM) studies were done to confirm that a wide range of proteins, such as dehydrogenase enzymes and ion channels, can then be embedded into the lipid bilayers. These results verify the potential to form highly selective recognition elements with direct physical connection to readout electronics on the supporting silicon substrate.