Microfluidic biochips promise to revolutionize biosensing and clinical diagnostics. As more bioassays are executed concurrently on a biochip, system integration and design complexity are expected to increase dramatically. This problem is also identified by the 2003 ITRS document as a major system-level design challenge beyond 2009. We focus here on the automated design of droplet-based microfluidic biochips. We present a synthesis methodology that unifies operation scheduling, resource binding, and module placement for such “digital” biochips. The proposed technique, which is based on parallel recombinative simulated annealing, can also be used after fabrication to bypass defective cells in the microfluidic array. A real-life protein assay is used to evaluate the synthesis methodology. Categories and Subject Descriptors B.7.2 B.7.3 [Integrated Circuits]: Design Aids, Reliability and Testing. General Terms Algorithms, Performance, Design, Reliability Keywords Synthesis, placement, ...