Integrated droplet routing in the synthesis of microfluidic biochips

Abstract

Microfluidic biochips are revolutionizing many areas of biochemistry and biomedical sciences. Several synthesis tools have recently been proposed for the automated design of biochips from the specifications of laboratory protocols. However, only a few of these tools address the problem of droplet routing in microfluidic arrays. These methods typically rely on post-synthesis droplet routing to implement biochemical protocols. Such an approach is not only time-consuming, but it also imposes an undue burden on the chip user. Moreover, post-synthesis droplet routing does not guarantee that feasible droplet pathways can be found for area-constrained biochip layouts; non-routable fabricated biochips must be discarded. We present a droplet-routing-aware automated synthesis tool for microfluidic biochips. Droplet routability, defined as the ease with which droplet pathways can be determined, is estimated and integrated in the synthesis flow. The proposed approach allows architectural-level design choices and droplet-routing-aware physical design decisions to be made simultaneously. We use a large-scale protein assay as a case study to evaluate the proposed synthesis method.

A fast routability- and performance-driven droplet routing algorithm for digital microfluidic biochips

“…The dynamic reconfigurability inherent in DMFBs allows different droplet routes to share cells on the microfluidic array during different time intervals. Unlike traditional VLSI routing, in addition to routing path selection, the droplet routing problem needs to address the issue of scheduling droplets under the practical constraints imposed by the fluidic property and the timing restriction of the synthesis result [12,13].…”

Fast Online Synthesis of Digital Microfluidic Biochips

“…Several papers, however, solve some of these problems together, using iterative improvement heuristics [15], [27], [28], [33], [35], whose runtime is prohibitive. These approaches address problems that can arise when one stage of synthesis does not consider the next.…”

“…The objective for most placers is to pack as many concurrent operations/modules into as little area as possible. Several direct-addressing placement and unified scheduling-placement algorithms [27], [28], [33], [35] use simulated annealing, which run in minutes or tens of seconds; in contrast, our online flow completes in tens of milliseconds.…”

Cross-Contamination Avoidance for Droplet Routing in Digital Microfluidic Biochips

“…A number of techniques have been proposed in the literature to solve the droplet-routing problem for digital microfluidics [5], [9], [14]- [16]. These methods are based on concepts such as path-planning for robots, prioritized A * search, network flow, integrated synthesis-and-routing, etc.…”

“…Discrete droplets of nanoliter volumes can be manipulated using electrowetting in a "digital" manner under clock control on a two-dimensional array of electrodes ("unit cells"). Synthesis and droplet-routing methods have been developed recently for the design of microfluidic biochips [3], [5], [9], [10], [12]- [16].…”