Hardware Design and Fault-Tolerant Synthesis for Digital Acoustofluidic Biochips

A digital microfluidic biochip (DMB) is an attractive platform for automating laboratory procedures in microbiology. To overcome the problem of cross-contamination due to fouling of the electrode surface in traditional DMBs, a contactless liquid-handling biochip technology, referred to as acoustofluidics, has recently been proposed. A major challenge in operating this platform is the need for a control signal of frequency 24 MHz and voltage range $\pm 10/\pm 20$ V to activate the IDT units in the biochip. In this paper, we present a hardware design that can efficiently activate/de-activated each IDT, and can fully automate an bio-protocol. We also present a fault-tolerant synthesis technique that allows us to automatically map biomolecular protocols to acoustofluidic biochips. We develop and experimentally validate a velocity model, and use it to guide co-optimization for operation scheduling, module placement, and droplet routing in the presence of IDT faults. Simulation results demonstrate the effectiveness of the proposed synthesis method. Our results are expected to open new research directions on design automation of digital acoustofluidic biochips.

[1]  Dimos Poulikakos,et al.  Acoustophoretic contactless transport and handling of matter in air , 2013, Proceedings of the National Academy of Sciences.

[2]  Krishnendu Chakrabarty,et al.  Multitarget Sample Preparation Using MEDA Biochips , 2020, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

[3]  Ali K Yetisen,et al.  Commercialization of microfluidic devices. , 2014, Trends in biotechnology.

[4]  Vamsee K. Pamula,et al.  Development of automated enzymatic assays for NAGLU, GALNS, ARSB and TPP1 for high throughput newborn screening using digital microfluidics , 2018 .

[5]  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).

[6]  Philip Brisk,et al.  Rapid online fault recovery for cyber-physical digital microfluidic biochips , 2015, 2015 IEEE 33rd VLSI Test Symposium (VTS).

[7]  Po-Hsun Huang,et al.  Digital acoustofluidics enables contactless and programmable liquid handling , 2018, Nature Communications.

[8]  Krishnendu Chakrabarty,et al.  Structural Test and Functional Test for Digital Acoustofluidic Biochips , 2019, 2019 IEEE International Test Conference (ITC).

[9]  Shawn Walker,et al.  Modeling the fluid dynamics of electrowetting on dielectric (EWOD) , 2004, Journal of Microelectromechanical Systems.

[10]  Philip Brisk,et al.  Performance Improvements and Congestion Reduction for Routing-Based Synthesis for Digital Microfluidic Biochips , 2017, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

[11]  Ramesh Karri,et al.  Programmable Daisychaining of Microelectrodes to Secure Bioassay IP in MEDA Biochips , 2020, IEEE Transactions on Very Large Scale Integration (VLSI) Systems.

[12]  Xinyu Liu,et al.  Magnetic timing valves for fluid control in paper-based microfluidics. , 2013, Lab on a chip.

[13]  Krishnendu Chakrabarty,et al.  Synthesis of Error-Recovery Protocols for Micro-Electrode-Dot-Array Digital Microfluidic Biochips , 2017, ACM Trans. Embed. Comput. Syst..

[14]  Yici Cai,et al.  Control-fluidic codesign for paper-based digital microfluidic biochips , 2016, 2016 IEEE/ACM International Conference on Computer-Aided Design (ICCAD).

[15]  Ramesh Karri,et al.  Execution of provably secure assays on MEDA biochips to thwart attacks , 2019, ASP-DAC.

[16]  Krishnendu Chakrabarty,et al.  Design Tools for Digital Microfluidic Biochips: Toward Functional Diversification and More Than Moore , 2010, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

[17]  C. Kim,et al.  An integrated digital microfluidic chip for multiplexed proteomic sample preparation and analysis by MALDI-MS. , 2006, Lab on a chip.

[18]  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).

[19]  Tsung-Yi Ho,et al.  Module Placement under Completion-Time Uncertainty in Micro-Electrode-Dot-Array Digital Microfluidic Biochips , 2018, IEEE Transactions on Multi-Scale Computing Systems.

[20]  Krishnendu Chakrabarty,et al.  Acoustohydrodynamic tweezers via spatial arrangement of streaming vortices , 2021, Science Advances.

[21]  V. Bahadur,et al.  An energy-based model for electrowetting-induced droplet actuation , 2006 .

[22]  Jeong‐Yeol Yoon,et al.  Preventing Biomolecular Adsorption in Electrowetting-Based Biofluidic Chips. , 2003, Analytical chemistry.

[23]  Krishnendu Chakrabarty,et al.  Sample preparation for multiple-reactant bioassays on micro-electrode-dot-array biochips , 2019, ASP-DAC.

[24]  Peter R. C. Gascoyne,et al.  Dielectrophoresis-based sample handling in general-purpose programmable diagnostic instruments , 2004, Proceedings of the IEEE.

[25]  Richard B. Fair,et al.  Digital microfluidics: is a true lab-on-a-chip possible? , 2007 .

[26]  Richard L. Church,et al.  Finding shortest paths on real road networks: the case for A* , 2009, Int. J. Geogr. Inf. Sci..

[27]  Krishnendu Chakrabarty,et al.  Contactless, programmable acoustofluidic manipulation of objects on water. , 2019, Lab on a chip.