Sample preparation, as a key procedure in many biochemical protocols, mixes various samples and/or reagents into solutions that contain the target concentrations. Digital microfluidic biochips (DMFBs) have been adopted as a platform for sample preparation because they provide automatic procedures that require less reactant consumption and reduce human-induced errors. However, traditional DMFBs only utilize the (1:1) mixing model, i.e., only two droplets of the same volume can be mixed at a time, which results in higher completion time and the wastage of valuable reactants. To overcome this limitation, a next-generation micro-electrode-dot-array (MEDA) architecture that provides flexibility of mixing multiple droplets of different volumes in a single operation was proposed. In this paper, we present a generic multiple-reactant sample preparation algorithm that exploits the novel fluidic operations on MEDA biochips. Simulated experiments show that the proposed method outperforms existing methods in terms of saving reactant cost, minimizing the number of operations, and reducing the amount of waste.