Biochips based on digital microfluidics offer a powerful platform for massively parallel biochemical analysis such as clinical diagnosis and DNA sequencing. Current full-custom design techniques for digital microfluidic biochips do not scale well for increasing levels of system integration. Analogous to classical VLSI synthesis, a top-down system-level design automation approach can shorten the biochip design cycle and reduce human effort. We present here an overview of a system-level design methodology that includes architectural synthesis and physical design. The proposed design automation approach is expected to relieve biochip users from the burden of manual optimization of bioassays, time-consuming hardware design, and costly testing and maintenance procedures. Categories and Subject Descriptors B.7.2 [Integrated Circuits]: Design Aids. General Terms Algorithms, Performance, Design, Reliability