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Amperometric chemical sensing systems implemented in deep-submicron processes can meet the dimensional and functional requirements for bio-implantable and remote sensing applications. The low-voltage nature of these processes, however, limits the functionality of the sensor's electronic interface, the potentiostat. A new, fully-differential (FD) potentiostat that mitigates these problems is presented. The FD potentiostat was implemented in TSMC's 0.18 μm CMOS process and experimentally verified. The circuit maintains full functionality while operating at half the supply voltage of standard architectures. Analytes of biological and environmental importance are chemically analyzed using the FD potentiostat. Results indicate that the FD potentiostat enables system-on-chip sensor technology which may one day lead to pervasive sensing.