Harnessing the Granularity of Micro-Electrode-Dot-Array Architectures for Optimizing Droplet Routing in Biochips

In this article, we consider the problem of droplet routing for Microelectrode-Dot-Array (MEDA) biochips. MEDA biochips today provide a host of useful features for droplet movement by making it possible to manoeuvre droplets at a much finer granularity and with significantly increased flexibility. More precisely, MEDA biochips support more degrees of freedom in navigation and volumetric manipulation such as diagonal movement, droplet reshaping, and fractional-level split-and-merge. This helps improve routing of droplets on microfluidic grids—in particular, when the space available on the grid is limited or blocked by obstacles. In this work, we discuss how these improved capabilities can be utilized in the realization of the desired routes on those biochips. To this end, we introduce a routing method that utilizes satisfiability solvers and guarantees the generation of optimal solutions, considering the set of MEDA operations we model. This significantly improves the state of the art, since previously proposed solutions either (1) relied on heuristics and, hence, were not able to guarantee the optimum or (2) only considered a subset of the MEDA features. The solution proposed in this work includes a formulation of all MEDA features, which, as illustrated by examples, allows for the determination of routing solutions with smaller completion times. Experimental evaluations confirm these findings.

[1]  Ansuman Banerjee,et al.  Correctness Checking of Bio-chemical Protocol Realizations on a Digital Microfluidic Biochip , 2014, 2014 27th International Conference on VLSI Design and 2014 13th International Conference on Embedded Systems.

[2]  Robert Wille,et al.  A general and exact routing methodology for Digital Microfluidic Biochips , 2015, 2015 IEEE/ACM International Conference on Computer-Aided Design (ICCAD).

[3]  Philip Brisk,et al.  Exploring speed and energy tradeoffs in droplet transport for digital microfluidic biochips , 2014, 2014 19th Asia and South Pacific Design Automation Conference (ASP-DAC).

[4]  Chen-Yi Lee,et al.  An Intelligent Digital Microfluidic Processor for Biomedical Detection , 2015, J. Signal Process. Syst..

[5]  Robert Wille,et al.  Exact design of digital microfluidic biochips , 2018 .

[6]  Krishnendu Chakrabarty,et al.  Cross-contamination avoidance for droplet routing in digital microfluidic biochips , 2009, 2009 Design, Automation & Test in Europe Conference & Exhibition.

[7]  Krishnendu Chakrabarty.  Design Automation and Test Solutions for Digital Microfluidic Biochips , 2010, IEEE Transactions on Circuits and Systems I: Regular Papers.

[8]  A. Manz,et al.  Revisiting lab-on-a-chip technology for drug discovery , 2012, Nature Reviews Drug Discovery.

[9]  D. Weitz,et al.  Single-cell analysis and sorting using droplet-based microfluidics , 2013, Nature Protocols.

[10]  Paul Pop,et al.  Towards droplet size-aware biochemical application compilation for AM-EWOD biochips , 2015, 2015 Symposium on Design, Test, Integration and Packaging of MEMS/MOEMS (DTIP).

[11]  Fei Su,et al.  Unified high-level synthesis and module placement for defect-tolerant microfluidic biochips , 2005, Proceedings. 42nd Design Automation Conference, 2005..

[12]  Tsung-Wei Huang,et al.  A fast routability- and performance-driven droplet routing algorithm for digital microfluidic biochips , 2009, 2009 IEEE International Conference on Computer Design.

[13]  Hsie-Chia Chang,et al.  A field-programmable lab-on-a-chip with built-in self-test circuit and low-power sensor-fusion solution in 0.35μm standard CMOS process , 2015, 2015 IEEE Asian Solid-State Circuits Conference (A-SSCC).

[14]  Yi-Wen Lu,et al.  Field-programmable lab-on-a-chip based on microelectrode dot array architecture. , 2014, IET nanobiotechnology.

[15]  Samuel K Sia,et al.  Microfluidics and point-of-care testing. , 2008, Lab on a chip.

[16]  Tsung-Wei Huang,et al.  Voltage-Aware Chip-Level Design for Reliability-Driven Pin-Constrained EWOD Chips , 2014, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

[17]  Zhongkai Chen,et al.  Droplet routing in high-level synthesis of configurable digital microfluidic biochips based on microelectrode dot array architecture , 2011 .

[18]  Krishnendu Chakrabarty,et al.  High-level synthesis for micro-electrode-dot-array digital microfluidic biochips , 2016, 2016 53nd ACM/EDAC/IEEE Design Automation Conference (DAC).

[19]  Vijay Srinivasan,et al.  Development of a digital microfluidic platform for point of care testing. , 2008, Lab on a chip.

[20]  D. Beebe,et al.  The present and future role of microfluidics in biomedical research , 2014, Nature.

[21]  Daniel Teng,et al.  Digital microfluidic operations on micro-electrode array architecture , 2011, 2011 6th IEEE International Conference on Nano/Micro Engineered and Molecular Systems.

[22]  Robert Wille,et al.  Exact routing for digital microfluidic biochips with temporary blockages , 2014, 2014 IEEE/ACM International Conference on Computer-Aided Design (ICCAD).

[23]  Krishnendu Chakrabarty,et al.  Integrated Droplet Routing in the Synthesis of Microfluidic Biochips , 2007, 2007 44th ACM/IEEE Design Automation Conference.

[24]  Robert Wille,et al.  Scalable One-Pass Synthesis for Digital Microfluidic Biochips , 2015, IEEE Design & Test.

[25]  Hung-Ming Chen,et al.  Multi-level droplet routing in active-matrix based digital-microfluidic biochips , 2018, 2018 23rd Asia and South Pacific Design Automation Conference (ASP-DAC).

[26]  Robert Wille,et al.  Exact one-pass synthesis of digital microfluidic biochips , 2014, 2014 51st ACM/EDAC/IEEE Design Automation Conference (DAC).

[27]  Krishnendu Chakrabarty,et al.  Digital microfluidic biochips: A vision for functional diversity and more than moore , 2010, 2010 IEEE/ACM International Conference on Computer-Aided Design (ICCAD).

[28]  Fei Su,et al.  Digital Microfluidic Biochips - Synthesis, Testing, and Reconfiguration Techniques , 2006 .

[29]  Jason P. Gleghorn,et al.  Microfluidic scaffolds for tissue engineering. , 2007, Nature materials.

[30]  Robert Wille,et al.  Exact routing for micro-electrode-dot-array digital microfluidic biochips , 2017, 2017 22nd Asia and South Pacific Design Automation Conference (ASP-DAC).

[31]  David Z. Pan,et al.  A High-Performance Droplet Routing Algorithm for Digital Microfluidic Biochips , 2008, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

[32]  Ansuman Banerjee,et al.  Flexible Droplet Routing in Active Matrix–Based Digital Microfluidic Biochips , 2018, ACM Trans. Design Autom. Electr. Syst..

[33]  Fei Su,et al.  Droplet Routing in the Synthesis of Digital Microfluidic Biochips , 2006, Proceedings of the Design Automation & Test in Europe Conference.