A cyberphysical synthesis approach for error recovery in digital microfluidic biochips

Droplet-based “digital” microfluidics technology has now come of age and software-controlled biochips for healthcare applications are starting to emerge. However, today's digital microfluidic biochips suffer from the drawback that there is no feedback to the control software from the underlying hardware platform. Due to the lack of precision inherent in biochemical experiments, errors are likely during droplet manipulation, but error recovery based on the repetition of experiments leads to wastage of expensive reagents and hard-to-prepare samples. By exploiting recent advances in the integration of optical detectors (sensors) in a digital microfluidics biochip, we present a “physical-aware” system reconfiguration technique that uses sensor data at checkpoints to dynamically reconfigure the biochip. A re-synthesis technique is used to recompute electrode-actuation sequences, thereby deriving new schedules, module placement, and droplet routing pathways, with minimum impact on the time-to-response.

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

[2]  Martin A. Brooke,et al.  Integrated detectors for embedded optical interconnections on electrical boards, modules, and integrated circuits , 2002 .

[3]  H Becker,et al.  Microfluidics: a technology coming of age. , 2008, Medical device technology.

[4]  Joel H. Parks,et al.  Protein fluorescence measurements within electrospray droplets , 2001, Journal of the American Society for Mass Spectrometry.

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

[6]  Tsung-Wei Huang,et al.  A Two-Stage Integer Linear Programming-Based Droplet Routing Algorithm for Pin-Constrained Digital Microfluidic Biochips , 2011, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

[7]  William Thies,et al.  Biocoder: A programming language for standardizing and automating biology protocols , 2010, Journal of biological engineering.

[8]  W Bialek,et al.  Protein dynamics and reaction rates: mode-specific chemistry in large molecules? , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Robert W. Dutton,et al.  An Analytical Algorithm for Placement of Arbitrarily Sized Rectangular Blocks , 1985, 22nd ACM/IEEE Design Automation Conference.

[10]  R. Fair,et al.  A digital microfluidic biosensor for multianalyte detection , 2003, The Sixteenth Annual International Conference on Micro Electro Mechanical Systems, 2003. MEMS-03 Kyoto. IEEE.

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

[12]  Krishnendu Chakrabarty,et al.  Integrated Control-Path Design and Error Recovery , 2013 .

[13]  Paul Pop,et al.  Routing-based synthesis of digital microfluidic biochips , 2010, CASES '10.

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

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

[16]  Uri M. Ascher,et al.  Model and solution strategy for placement of rectangular blocks in the Euclidean plane , 1988, IEEE Trans. Comput. Aided Des. Integr. Circuits Syst..

[17]  Tsung-Wei Huang,et al.  A Contamination Aware Droplet Routing Algorithm for the Synthesis of Digital Microfluidic Biochips , 2010, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

[18]  Agnelo Furtado,et al.  Measurement of green fluorescent protein concentration in single cells by image analysis. , 2002, Analytical biochemistry.

[19]  Lin Luan,et al.  Optical Detection Heterogeneously Integrated With a Coplanar Digital Microfluidic Lab-on-a-Chip Platform , 2007, 2007 IEEE Sensors.

[20]  Robert Sedgewick,et al.  Algorithms in c, part 5: graph algorithms, third edition , 2001 .

[21]  J. Todd,et al.  Evaluation of single nucleotide polymorphism typing with invader on PCR amplicons and its automation. , 2000, Genome research.

[22]  Mineo Kaneko,et al.  VLSI/PCB placement with obstacles based on sequence-pair , 1997, ISPD '97.

[23]  V. Weekman,et al.  Chemical Reaction Engineering , 1974 .

[24]  Jack Zhou,et al.  Chemical and Biological Applications of Digital-Microfluidic Devices , 2007, IEEE Design & Test of Computers.