Synthesis of Reconfigurable Flow-Based Biochips for Scalable Single-Cell Screening

Single-cell screening is used to sort a stream of cells into clusters (or types) based on prespecified biomarkers, thus supporting type-driven biochemical analysis. Reconfigurable flow-based microfluidic biochips (RFBs) can be utilized to screen hundreds of heterogeneous cells within a few minutes, but they are overburdened with the control of a large number of valves. To address this problem, we present a pin-constrained RFB design methodology for single-cell screening. The proposed design is analyzed using computational fluid dynamics simulations, mapped to an RC-lumped model, and combined with intervalve connectivity information to construct a high-level synthesis framework, referred to as cell sorter using multiplexed control (Sortex). Simulation results show that Sortex significantly reduces the number of control pins and fulfills the timing requirements of single-cell screening.