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Lab-on-a-chip (LoC) devices are a class of microfluidic chip-based systems that show a great deal of promise for complex chemical and biological sensing and analysis applications. An approach for full-custom LoC design, which leverages optimal design techniques and system-on-a-chip (SoC) physical design methods, is being developed. Both physical design of the chip and microfluidic performance are simultaneously considered to obtain complete LoC layouts. The proposed approach is demonstrated by designing multiplexed capillary electrophoresis (CE) separation microchips. The authors believe that this approach provides a foundation for future extension to LoC devices in which many different complex chemical operations are performed entirely on-chip.