Mixed signal complementary metal oxide semiconductor (CMOS )technology has become a popular research area for integrated biosensing applications. However, while modern CMOS processes, through the fulfillment of Moore’s Law, realize decreasing minimum sizing, this is accompanied by a lessening power supply. Further, the inherent physical noise still remains the same. This trend leads to poor signal to noise ratios, and dynamic range performance being a significant challenge to sensitive and accurate low power biosensing. The application of information theory to circuits has been introduced to model various topologies. These topologies include chopper stabilized amplifiers, active pixel sensors, and single photon avalanche diodes [1–6]. By using circuit design methodologies based on information theory, it is possible to create mixed signal systems that can operate at lower power, while efficiently transmitting information in the presence of high intrinsic physical and environmental noise. The methodology and its implications in this chapter were previously presented as part of .