Abstract. Recent emergence of microfluidic technology has imparted a profound impact on the implementation of miniaturized healthcare chips and systems. In this review article, we will elaborate on several algorithmic challenges that arise while realizing biochemical protocols on a digital microfluidic (DMF) lab-on-a-chip. In particular, we will focus on certain design automation issues of sample preparation, dilution gradient generation, layout planning, and testing of DMF biochips.