A top-down synthesis methodology for flow-based microfluidic biochips considering valve-switching minimization

Abstract

Designs of flow-based microfluidic biochips have emerged as a popular alternative for laboratory experiments because they replace conventional biochemical paradigms on a chip. As the applications are becoming more complicated, a flowbased microfluidic biochip requires more valves to manipulate the sample flow for the large-scale and concurrent experiments. However, current synthesis methodologies still use full-custom and bottom-up procedures to synthesize a biochip. These manual steps are time consuming and would lead to dispensable valve-switching. According to recent studies, frequent switching of the valves may reduce the reliability. To minimize the valve-switching activities, we propose a top-down synthesis methodology for flow-based microfluidic biochip. We develop a set-based minimum cost maximum flow (SMCMF) resource binding algorithm and an incremental cluster expansion (ICE) placement algorithm in architecture-level and physical-level synthesis, respectively. The experimental results show that our methodology not only makes significant reduction of valve-switching amount but also diminishes the application completion time for both real-life applications and a set of synthetic benchmarks.

Scheduling and Fluid Routing for Flow-Based Microfluidic Laboratories-on-a-Chip

“…2) Reliability-aware Application Mapping: Tseng et al [30], [31] developed a greedy resource binding technique that tries to minimize the number of fluid transfers. Their objective was to improve LoC reliability by minimizing the amount of valve switching required to execute the assay; in principle, this technique could also improve performance by reducing both the routing overhead and the number of rinsing steps that are needed to remove contamination.…”

Recent developments in microfluidic large scale integration

“…A second effort is an ongoing research project carried out at the Technical University of Denmark [43][44][45][46], with supporting efforts from researchers in Taiwan and Japan [47][48][49], which provides an algorithmic skeleton of an end-to-end design flow for mLSI chips. Starting from a high-level description of a biological protocol, algorithms are presented to: first, derive a graph-based representation of an mLSI chip that can execute the protocol [45,[47][48][49]; second, automatically synthesize the protocol onto a graph-based representation of an mLSI chip [43,44]; third, physically place components in the flow layer, and route control channels between them [45]; and fourth, automatically generate the control layer [46].…”

“…Starting from a high-level description of a biological protocol, algorithms are presented to: first, derive a graph-based representation of an mLSI chip that can execute the protocol [45,[47][48][49]; second, automatically synthesize the protocol onto a graph-based representation of an mLSI chip [43,44]; third, physically place components in the flow layer, and route control channels between them [45]; and fourth, automatically generate the control layer [46]. Although complete in principle, this work has not yet been used to design a real-world mLSI chip that has been fabricated.…”

Microfluidic very large-scale integration for biochips: Technology, testing and fault-tolerant design

“…This is followed by the physical synthesis of the flow layer, i.e., placement of components and routing of flow channels while following the design rules. Researchers have proposed placement algorithms [29]- [31] for the flow layer, routing approaches for the flow layer [29], [32], as well as integrated approaches for the placement and routing [29].…”

“…Next, the given biochemical application is mapped onto this biochip architecture and the optimized schedule for its execution is generated (the "Application Mapping" box). Researchers have started to propose approaches to the application mapping and scheduling [31], [33], [34]. Based on the schedule, the control information (which valves to open and close at what time and for how long) can now be extracted.…”