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In this paper, CASCADE, a standard supercell-based design methodology, its supporting automated design flow, and associated design tools, are presented for 3D implementations of a class of interconnect-heavy application-specific very large-scale integrated circuits. In CASCADE, a system is first partitioned and synthesized using standard 2D design tools to a set of supercells with the same height and varying widths. With this, the 3D design is reduced to 3D supercell placement and 3D-via assignment. A congestion-driven simulated-annealing method is used to find a 3D placement of supercells to minimize the total wire length, the longest wire length, and the number of 3D vias and routing density. To efficiently estimate the routing density of a 3D grid space within the optimization loop, a simple probabilistic congestion model with an incremental congestion computation has been developed. Once the supercell placement is fixed, the problem of assigning 3D vias to accomplish minimal 2D routing densities and uniform 3D-via distribution is solved by an efficient min-cost-max-flow method. The proposed methods have been implemented and tested on a set of ISPD98 circuit benchmarks. Experimental results have shown that the proposed congestion-driven 3D supercell placement and flow-based 3D-via-assignment tools have yielded satisfactory placement with small-area, low-congestion, short-wire-length, few, and uniformly distributed 3D vias. Furthermore, an excellent correlation between routing-density estimation by our model and the actual routing performed by a commercial router has been observed. We have applied the proposed 3D design methodology, tools, and flows to tape out an over 4-million-gate low-density parity-check decoder in a three-tier 0.18- fully depleted silicon-on-insulator 3D CMOS process manufactured by MIT Lincoln Laboratory. The postlayout simulation of this DRC-clean layout design showed an about ten times improvement on the power-delay-area product compared t- o a 2D implementation in the same process.