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Substrate noise coupling in integrated circuits (ICs) is the process by which interference signals in the form of voltage and current glitches cause parasitic currents to flow in the silicon substrate to various parts of the IC. The source of such glitches and parasitic currents could be from the switching noise of high speed digital clocks on the same chip. In RF and mixed signal ICs the switching noise is coupled to sensitive analog and RF nodes in the IC causing degradation in performance that could severely impact the yield. Thus, overcoming substrate coupling is a key issue in successful “system on chip” first-pass integration where RF and mixed signal blocks, high speed digital I/O interface are integrated with digital signal processing algorithms on the same chip. This is particularly true as we move to sub-90 nanometer system on chip integration. In this book a substrate aware design flow is built, calibrated to silicon and used as part of the design and validation flows to uncover and fix substrate coupling problems in RF ICs. The flow is used to develop a comprehensive RF substrate noise isolation design guide to be used by RF designers during the floor planning, circuit design and validation phases. This will allow designers to optimize the design, maximize noise isolation and protect sensitive analog/RF blocks from being degraded by substrate noise coupling