Digital microfluidic biochips: Recent research and emerging challenges

Microfluidic biochips are replacing the conventional biochemical analyzers, and are able to integrate on-chip all the basic functions for biochemical analysis. The “digital” microfluidic biochips (DM-FBs) are manipulating liquids not as a continuous flow, but as discrete droplets on a two-dimensional array of electrodes. Basic mi-crofluidic operations, such as mixing and dilution, are performed on the array, by routing the corresponding droplets on a series of electrodes. The challenges facing biochips are similar to those faced by microelectronics some decades ago. To meet the challenges of increasing design complexity, computer-aided-design (CAD) tools are being developed for DMFBs. This paper provides an overview of DMFBs and describes emerging CAD tools for the automated synthesis and optimization of DMFB designs, from fluidic-level synthesis and chip-level design to testing. Design automations are expected to alleviate the burden of manual optimization of bioassays, time-consuming chip designs, and costly testing and maintenance procedures. With the assistance of CAD tools, users can concentrate on the development and abstraction of nanoscale bioassays while leaving chip optimization and implementation details to CAD tools.

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

[2]  Yao-Wen Chang,et al.  Cross-contamination aware design methodology for pin-constrained digital microfluidic biochips , 2010, Design Automation Conference.

[3]  J. Gross,et al.  Graph Theory and Its Applications , 1998 .

[4]  Krishnendu Chakrabarty,et al.  Functional testing of digital microfluidic biochips , 2007, 2007 IEEE International Test Conference.

[5]  Paul Pop,et al.  Synthesis of biochemical applications on digital microfluidic biochips with operation variability , 2010, 2010 Symposium on Design Test Integration and Packaging of MEMS/MOEMS (DTIP).

[6]  Krishnendu Chakrabarty,et al.  Defect-Tolerant Design and Optimization of a Digital Microfluidic Biochip for Protein Crystallization , 2010, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

[7]  Sachin S. Sapatnekar,et al.  Handbook of Algorithms for Physical Design Automation , 2008 .

[8]  K. Chakrabarty,et al.  Towards fault-tolerant digital microfluidic lab-on-chip: Defects, fault modeling, testing, and reconfiguration , 2008, 2008 IEEE Biomedical Circuits and Systems Conference.

[9]  Fei Su,et al.  Reconfiguration Techniques for Digital Microfluidic Biochips , 2005 .

[10]  N. Gershenfeld,et al.  Microfluidic Bubble Logic , 2006, Science.

[11]  R. Fair,et al.  Electrowetting-based actuation of droplets for integrated microfluidics. , 2002, Lab on a chip.

[12]  Krishnendu Chakrabarty,et al.  Droplet-trace-based array partitioning and a pin assignment algorithm for the automated design of digital microfluidic biochips , 2006, Proceedings of the 4th International Conference on Hardware/Software Codesign and System Synthesis (CODES+ISSS '06).

[13]  K. Chakrabarty,et al.  Ensuring the operational health of droplet-based microelectrofluidic biosensor systems , 2005, IEEE Sensors Journal.

[14]  R. Fair,et al.  A scaling model for electrowetting-on-dielectric microfluidic actuators , 2009 .

[15]  Fei Su,et al.  Testing and Diagnosis of Realistic Defects in Digital Microfluidic Biochips , 2007, J. Electron. Test..

[16]  Christian Ejdal Sjøgreen Synthesis of Biochemical Applications with Operation Variability on Digital Microfluidic Biochips , 2011 .

[17]  Krishnendu Chakrabarty,et al.  Synchronization of washing operations with droplet routing for cross-contamination avoidance in digital microfluidic biochips , 2010, Design Automation Conference.

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

[19]  Fei Su,et al.  Microfluidics-Based Biochips: Technology Issues, Implementation Platforms, and Design-Automation Challenges , 2006, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

[20]  Fei Su,et al.  Architectural-level synthesis of digital microfluidics-based biochips , 2004, IEEE/ACM International Conference on Computer Aided Design, 2004. ICCAD-2004..

[21]  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.

[22]  Guido Groeseneken,et al.  Charge trapping in SiO 2 /HfO 2 gate dielectrics: comparison between charge-pumping and pulsed I D -V G , 2004 .

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

[24]  Krishnendu Chakrabarty,et al.  Broadcast electrode-addressing for pin-constrained multi-functional digital microfluidic biochips , 2008, 2008 45th ACM/IEEE Design Automation Conference.

[25]  Krishnendu Chakrabarty,et al.  Digital Microfluidic Logic Gates and Their Application to Built-in Self-Test of Lab-on-Chip , 2010, IEEE Transactions on Biomedical Circuits and Systems.

[26]  Yao-Wen Chang,et al.  ILP-based pin-count aware design methodology for microfluidic biochips , 2009, 2009 46th ACM/IEEE Design Automation Conference.

[27]  C. Kim,et al.  Direct-Referencing Two-Dimensional-Array Digital Microfluidics Using Multilayer Printed Circuit Board , 2008, Journal of Microelectromechanical Systems.

[28]  Stuart Allan,et al.  Nanotechnology in the news , 2006 .

[29]  Krishnendu Chakrabarty,et al.  Co-optimization of droplet routing and pin assignment in disposable digital microfluidic biochips , 2011, ISPD '11.

[30]  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.

[31]  Yao-Wen Chang,et al.  BioRoute: A Network-Flow-Based Routing Algorithm for the Synthesis of Digital Microfluidic Biochips , 2008, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

[32]  Toshinori Munakata,et al.  Micro/nanofluidic computing , 2007, CACM.

[33]  Tsung-Wei Huang,et al.  Progressive network-flow based power-aware broadcast addressing for pin-constrained digital microfluidic biochips , 2011, 2011 48th ACM/EDAC/IEEE Design Automation Conference (DAC).

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

[35]  K. Chakrabarty,et al.  Module placement for fault-tolerant microfluidics-based biochips , 2004, ACM Trans. Design Autom. Electr. Syst..

[36]  Fei Su,et al.  Test Planning and Test Resource Optimization for Droplet-Based Microfluidic Systems , 2004, Proceedings. Ninth IEEE European Test Symposium, 2004. ETS 2004..

[37]  H. Verheijen,et al.  REVERSIBLE ELECTROWETTING AND TRAPPING OF CHARGE : MODEL AND EXPERIMENTS , 1999, cond-mat/9908328.

[38]  Z. Bao-qi On Graph Theory and Its Application , 2007 .

[39]  Krishnendu Chakrabarty,et al.  Parallel Scan-Like Test and Multiple-Defect Diagnosis for Digital Microfluidic Biochips , 2007, IEEE Transactions on Biomedical Circuits and Systems.

[40]  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.

[41]  Tsung-Wei Huang,et al.  A contamination aware droplet routing algorithm for digital microfluidic biochips , 2009, 2009 IEEE/ACM International Conference on Computer-Aided Design - Digest of Technical Papers.

[42]  Krishnendu Chakrabarty,et al.  Integrated control-path design and error recovery in the synthesis of digital microfluidic lab-on-chip , 2010, JETC.

[44]  Paul Pop,et al.  Tabu search-based synthesis of dynamically reconfigurable digital microfluidic biochips , 2009, CASES '09.

[45]  K. Chakrabarty,et al.  Design and optimization of a digital microfluidic biochip for protein crystallization , 2008, 2008 IEEE/ACM International Conference on Computer-Aided Design.

[46]  R. Fair,et al.  Low Voltage Electrowetting-on-Dielectric Platform using Multi-Layer Insulators. , 2010, Sensors and actuators. B, Chemical.

[47]  Yao-Wen Chang,et al.  Placement of defect-tolerant digital microfluidic biochips using the T-tree formulation , 2007, JETC.

[48]  Tsung-Wei Huang,et al.  A network-flow based pin-count aware routing algorithm for broadcast electrode-addressing EWOD chips , 2010, 2010 IEEE/ACM International Conference on Computer-Aided Design (ICCAD).

[49]  Tsung-Wei Huang,et al.  A two-stage ILP-based droplet routing algorithm for pin-constrained digital microfluidic biochips , 2010, ISPD '10.

[50]  A. I. Drygiannakis,et al.  On the connection between dielectric breakdown strength, trapping of charge, and contact angle saturation in electrowetting. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[51]  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).