Microfluidic biochips are replacing the conventional biochemical analyzers, and are able to integrate on-chip all the necessary functions for biochemical analysis. The “digital” biochips are manipulating liquids as discrete droplets on a two-dimensional array of electrodes. Basic microfluidic operations, such as mixing and dilution, are performed on the array, by routing the corresponding droplets on a series of electrodes. So far, researchers have assumed that these operations are executed on virtual rectangular devices, formed by grouping several adjacent electrodes. One drawback is that all electrodes are considered occupied during the operation execution, although the droplet uses only one electrode at a time. Moreover, the operations can actually be performed by routing the droplets on any sequence of electrodes on the microfluidic array. Hence, in this paper, we eliminate the concept of virtual devices and allow the droplets to move on the chip on any route during operation execution. Thus, the synthesis problem is transformed into a routing problem. We develop an algorithm based on a Greedy Randomized Adaptive Search Procedure (GRASP) and we show that routing-based synthesis leads to significant improvements in the application completion time compared to traditional synthesis based on virtual devices. However, the disadvantage of the routing-based approach is that it may contaminate larger areas of the biochip, when synthesizing applications containing liquids which may adsorb on the surface of the microfluidic array. We have extended the GRASP-based algorithm to consider contamination avoidance during routing-based synthesis. Several real-life examples and synthetic benchmarks are used to evaluate the proposed approaches.