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A non-conformal domain decomposition method (DDM) is proposed to investigate signal integrity (SI) of high-speed interconnects on multi-scale, multi-layer printed circuit board (PCB) in this paper. The accuracy and robustness of the proposed method is first demonstrated by analysis of a 4-layer differential pair. Then we studied a 14-layer 16 traces interconnect model to demonstrate the efficiency of the method. Eye diagrams of the two models are studied for time domain SI.