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Digital microfluidic biochips are being increasingly used for biotechnology applications. The number of control pins used to drive electrodes is a major contributor to fabrication cost for disposable biochips in a highly cost-sensitive market. Most prior work on pin-constrained biochip design determines the mapping of a small number of control pins to a larger number of electrodes according to the specific schedule of fluid-handling operations and routing paths of droplets. Such designs are therefore specific to the bioassay application, hence sacrificing some of the flexibility associated with digital microfluidics. We propose a design method to generate an application-independent pin-assignment configuration with a minimum number of control pins. Layouts of a commercial biochip and laboratory prototypes are used as case studies to evaluate the proposed design method for determining a suitable pin-assignment configuration. Compared with previous pin-assignment algorithms, the proposed method can reduce the number of control pins and facilitate the “general-purpose” use of digital microfluidic biochips for a wide range of applications.