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The opportunity to integrate microfluidic devices with CMOS instrumentation is attractive to many biological and biomedical sensor applications. However, the packaging of CMOS circuitry for use within a liquid environment remains as an open challenge. This paper presents a robust and reliable packaging scheme for on-CMOS biosensors that is uniquely capable of providing both electrical insulation of a CMOS chip in a liquid environment and also protection from chemical and biological agents. In particular, this is the first reported CMOS packaging scheme capable of surviving harsh piranha solution that is needed to clean the surface of on-chip gold electrodes before final biointerface formation. The post-CMOS fabrication process is described for a 3×3mm2 CMOS die. Photos of a packaged CMOS biosensor array chip and electrochemical measurements in potassium ferrocyanide demonstrate proper operation of the device. The redox peak separation of on-chip electrodes was measured at 0.1V.