High-level synthesis of digital microfluidic biochips

Abstract

Microfluidic biochips offer a promising platform for massively parallel DNA analysis, automated drug discovery, and real-time biomolecular recognition. Current techniques for full-custom design of droplet-based “digital” biochips do not scale well for concurrent assays and for next-generation system-on-chip (SOC) designs that are expected to include microfluidic components. We propose a system design methodology that attempts to apply classical high-level synthesis techniques to the design of digital microfluidic biochips. We focus here on the problem of scheduling bioassay functions under resource constraints. We first develop an optimal scheduling strategy based on integer linear programming. However, because the scheduling problem is NP-complete, we also develop two heuristic techniques that scale well for large problem instances. A clinical diagnostic procedure, namely multiplexed in-vitro diagnostics on human physiological fluids, is first used to illustrate and evaluate the proposed method. Next, the synthesis approach is applied to a protein assay, which serves as a more complex bioassay application. The proposed synthesis approach is expected to reduce human effort and design cycle time, and it will facilitate the integration of microfluidic components with microelectronic components in next-generation SOCs.

Force-Directed List Scheduling for Digital Microfluidic Biochips

“…We are aware of two heuristics, Modified List Scheduling (MLS) [11] and Path Scheduling (PS) [3], two genetic algorithms (GA-1, GA-2) [9][11], and two optimal integer linear programming (ILP) formulations [2][11].…”

“…MLS [11] is an efficient polynomial-time greedy heuristic that runs in O(nlogn) time, where n is the number of vertices in the graph. MLS augments the standard List Scheduling (LS) algorithm [1] with a rescheduling step that is invoked to increase the likelihood of achieving a legal schedule while meeting resource constraints.…”

Synchronization of Concurrently-Implemented Fluidic Operations in Pin-Constrained Digital Microfluidic Biochips

“…Based on the schedule derived from architectural synthesis [11], a bioassay is implemented by performing several groups of fluidic operations at different time spans. All the fluidic operations within one group are concurrently implemented by applying their corresponding pin-actuation sequences at the same time.…”

“…These advances in technology serve as a powerful driver for research on computer-aided design (CAD) tools for the design of such chips. Architectural synthesis, physical design, and dropletrouting methods have been developed for the automated design of such chips that can execute laboratory protocols [11]- [16].…”

Ultra-Portable Smartphone Controlled Integrated Digital Microfluidic System in a 3D-Printed Modular Assembly

“…Microfluidics is one of the promising platforms for developing portable devices that allow real-time screening and on-chip diagnosis [5,6]. In particular, the reconfigurable architecture of digital microfluidic (DMF) systems permits the real-time change of fluidic protocols on the same chip, which cannot be achieved in conventional continuous flow systems [7][8][9][10][11][12]. Although several attempts have been made to introduce continuous microfluidic operations inside portable devices [13,14], few studies have focused on developing portable DMF platforms [15][16][17].…”