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A novel macromodeling congruent compact-cell methodology is introduced for full-wave investigations of multi-layered inhomogeneous structures containing elements that differ significantly in their scale and doping profiles. The proposed approach is implemented on the hybrid transverse waves formulation (TWF) leading to important complexity reduction in term of memory requirement and number of unknowns without sacrificing accuracy, thanks to scale analysis. The validity of the compact-cell methodology is demonstrated through numerous realistic RFIC examples including the effects on signal integrity of deep-trench (DT) isolation techniques. Results obtained using the compact-cell methodology are successfully compared to full (regular refined)-simulation results, to commercial design tool results and to measurement data. The approximation of cascade elements classically used in circuit approaches is discussed and its validity is investigated in regard to the compact-cell scale parameter.