Integrated and real-time quantitative analysis using cyberphysical digital-microfluidic biochips

Considerable effort has recently been directed towards the implementation of molecular bioassays on digital-microfluidic biochips. However, today's solutions suffer from the drawback that multiple sample pathways are not supported and on-chip reconfigurable devices are not efficiently exploited. To overcome this problem, we present a spatial-reconfiguration technique that incorporates resource-sharing specifications into the synthesis flow. This technique is combined with cyberphysical integration to develop the first design-automation framework for quantitative gene expression. The proposed framework is based on a real-time resource-allocation algorithm that responds promptly to decisions about the protocol flow received from a firmware layer. Simulation results show that our adaptive framework efficiently utilizes on-chip resources to reduce time-to-result without sacrificing the chip's lifetime.

[1]  Martin A. Brooke,et al.  Progress in Chip-Scale Photonic Sensing , 2009, IEEE Transactions on Biomedical Circuits and Systems.

[2]  M. D. Chamberlain,et al.  A digital microfluidic method for multiplexed cell-based apoptosis assays. , 2012, Lab on a chip.

[3]  Krishnendu Chakrabarty,et al.  Error Recovery in Cyberphysical Digital Microfluidic Biochips , 2013, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

[4]  Haig Norian Integrated CMOS Polymerase Chain Reaction Lab-on-chip , 2014 .

[5]  Pui-In Mak,et al.  An intelligent digital microfluidic system with fuzzy-enhanced feedback for multi-droplet manipulation. , 2013, Lab on a chip.

[6]  Fei Su,et al.  High-level synthesis of digital microfluidic biochips , 2008, JETC.

[7]  Kai Hu,et al.  Fault detection, real-time error recovery, and experimental demonstration for digital microfluidic biochips , 2013, 2013 Design, Automation & Test in Europe Conference & Exhibition (DATE).

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

[9]  Paul Pop,et al.  Redundancy optimization for error recovery in digital microfluidic biochips , 2015, Des. Autom. Embed. Syst..

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

[11]  X. Gidrol,et al.  An EWOD-based microfluidic chip for single-cell isolation, mRNA purification and subsequent multiplex qPCR. , 2014, Lab on a chip.

[12]  S. Bustin,et al.  Quantification strategies in real-time PCR , 2008 .

[13]  Krishnendu Chakrabarty,et al.  Design and Optimization of a Cyberphysical Digital-Microfluidic Biochip for the Polymerase Chain Reaction , 2015, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

[14]  Andreas G. Boudouvis,et al.  Manifestation of the connection between dielectric breakdown strength and contact angle saturation in electrowetting , 2005 .

[15]  T. G. Mitchell,et al.  Multiplexed real-time polymerase chain reaction on a digital microfluidic platform. , 2010, Analytical chemistry.

[16]  Kristin C. Scott,et al.  Uncoupling of Genomic and Epigenetic Signals in the Maintenance and Inheritance of Heterochromatin Domains in Fission Yeast , 2012, Genetics.

[17]  Philip Brisk,et al.  A field-programmable pin-constrained digital microfluidic biochip , 2013, 2013 50th ACM/EDAC/IEEE Design Automation Conference (DAC).

[18]  Philip Brisk,et al.  Fast Online Synthesis of Digital Microfluidic Biochips , 2014, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

[19]  James L. Van de Vreugde,et al.  A solvent replenishment solution for managing evaporation of biochemical reactions in air-matrix digital microfluidics devices. , 2015, Lab on a chip.

[20]  Yao-Wen Chang,et al.  Placement of digital microfluidic biochips using the T-tree formulation , 2006, 2006 43rd ACM/IEEE Design Automation Conference.

[21]  Tsung-Wei Huang,et al.  A Network-Flow Based Pin-Count Aware Routing Algorithm for Broadcast-Addressing EWOD Chips , 2011, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

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

[23]  Jeong-Bong Lee,et al.  Machine vision for digital microfluidics. , 2010, The Review of scientific instruments.