Digital microfluidics chip with integrated intra‐droplet magnetic bead manipulation

Electrowetting-on-dielectric (EWD) droplet actuation has been used widely in handling liquid in small quantities in many biological applications (Fair et al. 2007; Miller and Wheeler 2009; Boles et al. 2011; Welch et al. 2011). The droplet is manipulated by applying voltage to EWD electrodes buried beneath an insulator (Fair et al. 2007; Boles et al. 2011; Welch et al. 2011). Many droplet functions have been studied over the years, and those functions include the dispensing, actuation, merging and splitting of droplets (Walker et al. 2009). Different droplet handling functions can be combined and used repeatedly. Those functions can be used together to achieve certain droplet manipulation sequences. Hence, EWD enables the handling of liquid to be programmable and reconfigurable (Fair 2007). These characteristics make EWD technology particularly suitable for integrated systems. To design a complete system for biological applications, it is required to have more than just liquid handling functions. One such function is magnetic actuation, which is used to manipulate magnetic bead for protocols such as molecular separation for purification. Magnetic beads, especially superparamagnetic beads, have been widely used in biological applications. The size of magnetic beads used in such applications is typically in the micrometre to nanometre range, and beads are used to separate molecules from a mixture of biological samples (Alexiou et al. 2006; Cho et al. 2007b; Mach et al. 2013). In such applications, the magnetic beads’ surface is modified to allow for binding to specific molecules. After target molecules have attached to the beads, the beads will then be placed in a high magnetic field gradient environment and be trapped together with the bound molecules. Washing is then applied to the magnetic beads. After Abstract This paper demonstrates an integrated device combining both EWD droplet actuation and intra-droplet magnetic bead manipulation. Magnetic bead manipulation is achieved by using current-carrying wires acting as microelectromagnets. The current wire structure is capable of segregating and separating magnetic beads within a droplet. By adjusting the amount of current in the wire structure, high segregation efficiency within the droplet is shown and the separation of two kinds of beads is realized within a distance of 65 μm. The EWD droplet actuation function and the magnetic bead separation function can be operated independently, which provides flexibility when designing operation protocols. The current wire structure is embedded in an EWD electrode without affecting droplet actuation. The vertical structure of the device and its fabrication process are also the same as a normal EWD device. Magnetic bead segregation efficiency of 96.8 % was achieved for 2.8-μm beads that were collected over a distance of 65 μm during a 20-s current pulse. Droplet splitting is shown to allow complete separation of beads into one of the two daughter droplets. And, intra-droplet separation of 1and 2.8-μm beads was demonstrated over an average distance of 65 μm. This experiment shows the feasibility of performing separation in droplets with a complex mixture of multiple beads, each having different magnetic contents.