Abstract. Due to their emergence as an efficient platform for pointof-care clinical diagnostics, digital-microfluidic biochips (DMFBs) have received considerable attention in recent years. They combine electronics with biology, and they integrate various bioassay operations, such as sample preparation, analysis, separation, and detection. In this chapter, we first present an overview of digital-microfluidic biochips. We next describe emerging computer-aided design (CAD) tools for the automated synthesis and optimization of biochips from bioassay protocols. The chapter includes solutions for fluidic-operation scheduling, module placement, droplet routing, and pin-constrained chip design. We also show how recent advances in the integration of sensors into a DMFB can be exploited to provide cyberphysical system adaptation based on feedback-driven control.