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A methodology for constructing circuit-level mismatch models and performing yield optimization is presented for CMOS analog circuits. The methodology combines statistical techniques with direct investigation of circuit behavior, and achieves model simplification and computational efficiency while ensuring sufficient accuracy. The circuit-level mismatch model can be used in performance characterization and yield estimation, both important in providing information for circuit reliability analysis. The proposed yield optimization technique consists of constructing and refining a yield model over the designable parameters, and ensures fast convergence to the global optimal design. The experimental results on two representative circuits confirm the efficiency and effectiveness of the proposed method.