Due to inherent reconfigurable capability, digital microfluidic biochips (DMFBs) have been a prime platform for critical medical diagnosis, real time bioassays, and lab-on-chip experiments. However, dependability is an urgent need to decide the correct outcome from a bioassay execution. To make a DMFB dependable in high frequency applications, a single electrode must not be frequently used as it may result in over-actuation problem. An over-actuated cell degrades over time and results a failure. Current fluid-level synthesis method only considers in minimizing the total completion time of the assay. Besides, recent technologies use abundant re-execution and perform costly online synthesis whenever such a fault is discovered. Two papers address the dependability issue and propose a placement solution. Here, we present a complete fluid-level synthesis to prepare binding, scheduling, placement, and routing solutions for a given bioassay. The concerned problem is proved to be NP-complete. A dynamic programming formulation is followed to obtain a solution in pseudo-polynomial time. Several benchmarks are used to evaluate the proposed method. © Springer Nature Singapore Pte Ltd 2017.