Droplet-based Digital Microfluidic Biochips (or DMFBs) are now being the prime platform for a number of point of care diagnostics, clinical studies, and sample preparations. Several design optimization methods exist at the fluid-level that automate the tasks of a DMFB. However, in high frequency applications, its performance heavily deteriorates in the order of degrading electrodes producing incorrect outcomes. Vague results may also be generated if cross contamination during droplet routing is not avoided. We define a DMFB to be safe if it is capable of handling reliability and also free from cross contamination. Alongside, as the fluid-level of DMFBs comprises several tasks that altogether introduces design cycles and leads to higher cost, a low-cost platform is urgently required. This paper proposes a fluid-level design for DMFBs that considers the above facts together. A graph model has been used to tackle them. An exact algorithm is presented. The obtained results are validated with several benchmarks. © 2018 IEEE.