Design and optimization of 3D digital microfluidic biochips for the polymerase chain reaction

A digital microfluidic biochip (DMFB) is an attractive technology platform for revolutionizing immunoassays, clinical diagnostics, drug discovery, DNA sequencing, and other laboratory procedures in biochemistry. In most of these applications, real-time polymerase chain reaction (PCR) is an indispensable step for amplifying specific DNA segments. In recent years, three-dimensional (3D) DMFBs that integrate photodetectors (i.e., cyberphysical DMFBs) have been developed. They offer the benefits of smaller size, higher sensitivity and quicker time-to-results. However, current DMFB design methods target optimization in only two dimensions, hence they ignore the 3D two-layer structure of a DMFB. Moreover, these techniques ignore practical constraints related to the interference between on-chip device pairs, the performance-critical PCR thermal loop, and the physical size of devices. In this paper, we describe an optimization solution for a 3D DMFB, and present a three-stage algorithm to realize a compact 3D PCR chip layout, which includes: (i) PCR thermal-loop optimization; (ii) 3D global placement based on Strong-Push-Weak-Pull (SPWP) model; (iii) constraint-aware legalization. Simulation results for four laboratory protocols demonstrate that the proposed approach is effective for the design and optimization of a 3D chip for real-time PCR.