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Algorithmic Challenges in Digital Microfluidic Biochips: Protocols, Design, and Test

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Applied Algorithms (ICAA 2014)

Part of the book series: Lecture Notes in Computer Science ((LNPSE,volume 8321))

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Abstract

Recent emergence of microfluidic technology has imparted a profound impact on the implementation of miniaturized healthcare chips and systems. In this review article, we will elaborate on several algorithmic challenges that arise while realizing biochemical protocols on a digital microfluidic (DMF) lab-on-a-chip. In particular, we will focus on certain design automation issues of sample preparation, dilution gradient generation, layout planning, and testing of DMF biochips.

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References

  1. Fair, R.B.: Digital Microfluidics: Is a True Lab-on-a-Chip Possible? Microfluid. Nanofluid. 3, 245–281 (2007)

    Article  Google Scholar 

  2. Sista, R., Hua, Z., Thwar, P., Sudarsan, A., Srinivasan, V., Eckhardt, A., Pollack, M., Pamula, V.: Development of a Digital Microfluidic Platform for Point of Care Testing. Lab-on-a-Chip 8(12), 2091–2104 (2008)

    Article  Google Scholar 

  3. Abdelgawad, M., Wheeler, A.R.: The Digital Revolution: A New Paradigm for Microfluidics. Advanced Materials 21, 920–925 (2009)

    Article  Google Scholar 

  4. Chakrabarty, K., Xu, T.: Digital Microfluidic Biochips: Design and Optimization. CRC Press (2010)

    Google Scholar 

  5. Bohringer, K.F.: Modeling and Controlling Parallel Tasks in Droplet-Based Microfluidic Systems. IEEE Transactions on COMPUTER-AIDED DESIGN of Integrated Circuits and Systems 25(2), 334–344 (2006)

    Article  Google Scholar 

  6. Yuh, P.H., Yang, C.L., Chang, Y.W.: BioRoute: A Network-Flow-Based Routing Algorithm for the Synthesis of Digital Microfluidic Biochips. IEEE Transactions on COMPUTER-AIDED DESIGN of Integrated Circuits and Systems 27(11), 1928–1941 (2008)

    Article  Google Scholar 

  7. Cho, M., Pan, D.Z.: A High-Performance Droplet Routing Algorithm for Digital Microfluidic Biochips. IEEE Transactions on COMPUTER-AIDED DESIGN of Integrated Circuits and Systems 27(10), 1714–1724 (2008)

    Article  Google Scholar 

  8. Maftei, E., Pop, P., Madsen, J.: Tabu Search-based Synthesis of Dynamically Reconfigurable Digital Microfluidic Biochips. In: Proc. of the CASES, pp. 195–204 (2009)

    Google Scholar 

  9. Lin, C.C.Y., Chang, Y.W.: ILP-Based Pin-Count Aware Design Methodology for Microfluidic Biochips. In: Proc. of the DAC, pp. 258–263 (2009)

    Google Scholar 

  10. Datta, S., Joshi, B., Ravindran, A., Mukherjee, A.: Efficient Parallel Testing and Diagnosis of Digital Microfluidic Biochips. ACM Journal on Emerging Technologies in Computing Systems 5(2), 1–17 (2009)

    Article  Google Scholar 

  11. Xiao, Z., Young, E.F.: Droplet-Routing-Aware Module Placement for Cross-Referencing Biochips. In: Proc. of the ISPD, pp. 193–199 (2010)

    Google Scholar 

  12. Lin, C.C.Y., Chang, Y.W.: Cross-Contamination Aware Design Methodology for Pin-Constrained Digital Microfluidic Biochips. IEEE Transactions on COMPUTER-AIDED DESIGN of Integrated Circuits and Systems 30(6), 817–828 (2011)

    Article  MathSciNet  Google Scholar 

  13. Hsieh, Y.L., Ho, T.Y., Chakrabarty, K.: A Reagent-Saving Mixing Algorithm for Preparing Multiple-Target Biochemical Samples Using Digital Microfluidics. IEEE Transactions on COMPUTER-AIDED DESIGN of Integrated Circuits and Systems 31(11), 1656–1669 (2012)

    Article  Google Scholar 

  14. Luo, Y., Chakrabarty, K., Ho, T.Y.: Error Recovery in Cyberphysical Digital Microfluidic Biochips. IEEE Transactions on COMPUTER-AIDED DESIGN of Integrated Circuits and Systems 32(1), 59–72 (2013)

    Article  Google Scholar 

  15. Thies, W., Urbanski, J.P., Thorsen, T., Amarasinghe, S.: Abstraction Layers for Scalable Microfluidic Biocomputing. Natural Computing 7(2), 255–275 (2008)

    Article  MATH  MathSciNet  Google Scholar 

  16. OpenWetWare (October 2009), http://openwetware.org/wiki/Protocols

  17. BioCoder: A Programming Language for Biology Protocols, Microsoft Research India (December 2009), http://research.microsoft.com/en-us/um/india/projects/biocoder/

  18. Bio-Protocols: http://www.bio-protocol.org/

  19. Fair, R.B., Srinivasan, V., Ren, H., Paik, P., Pamula, V.K., Pollack, M.G.: Electrowetting-Based On-Chip Sample Processing for Integrated Microfluidics. In: Technical Digest. IEEE International Electron Devices Meeting (IEDM 2003), pp. 32.5.1–32.5.4 (December 2003)

    Google Scholar 

  20. Pollack, M.G., Fair, R.B., Shenderov, A.D.: Electrowetting-based Actuation of Liquid Droplets for Microfluidic Applications. Applied Physics Letters 77, 1725–1726 (2000)

    Article  Google Scholar 

  21. Brassard, D., Malic, L., Normandin, F., Tabrizian, M., Veres, T.: Water-oil Core-shell Droplets for Electrowetting-based Digital Microfluidic Devices. Lab-on-a-Chip 8, 1342–1349 (2008)

    Article  Google Scholar 

  22. Cho, S.K., Moon, H., Kim, C.J.: Creating, Transporting, Cutting, and Merging Liquid Droplets by Electrowetting-based Actuation for Digital Microfluidic Circuits. Journal of Microelectromechanical Systems 12(1), 70–80 (2003)

    Article  Google Scholar 

  23. Fouillet, Y., Jary, D., Chabrol, C., Claustre, P., Peponnet, C.: Digital Microfluidic Design and Optimization of Classic and New Fluidic Functions for Lab on a Chip Systems. Microfluidics and Nanofluidics 4(3), 159–165 (2008)

    Article  Google Scholar 

  24. Paik, P., Pamula, V.K., Fair, R.B.: Rapid Droplet Mixers for Digital Microfluidic Systems. Lab-on-a-Chip 3, 253–259 (2003)

    Article  Google Scholar 

  25. Paik, P., Pamula, V.K., Pollack, M.G., Fair, R.B.: Electrowetting-based Droplet Mixers for Microfluidic Systems. Lab-on-a-Chip 3, 28–33 (2003)

    Article  Google Scholar 

  26. Herold, K.E., Rasooly, A.: Lab-on-a-Chip Technology (vol. 1): Fabrication and Microfluidics. Caister Academic Press (August 2009)

    Google Scholar 

  27. Kim, C., Lee, K., Kim, J.H., Shin, K.S., Lee, K.J., Kim, T.S., Kang, J.Y.: A Serial Dilution Microfluidic Device using a Ladder Network Generating Logarithmic or Linear Concentrations. Lab-on-a-Chip 8(3), 473–479 (2008)

    Article  Google Scholar 

  28. Lee, K., Kim, C., Ahn, B., Panchapakesan, R., Full, A.R., Nordee, L., Kang, J.Y., Oh, K.W.: Generalized Serial Dilution Module for Monotonic and Arbitrary Microfluidic Gradient Generators. Lab-on-a-Chip 9, 709–717 (2009)

    Article  Google Scholar 

  29. Ren, H., Srinivasan, V., Fair, R.B.: Design and Testing of an Interpolating Mixing Architecture for Electrowetting-Based Droplet-On-Chip Chemical Dilution. In: Proc. of the International Conference on Solid-State Sensors, Actuators and Microsystems (TRANSDUCERS), pp. 619–622 (2003)

    Google Scholar 

  30. Griffith, E.J., Akella, S., Goldberg, M.K.: Performance Characterization of a Reconfigurable Planar-Array Digital Microfluidic System. IEEE Transactions on COMPUTER-AIDED DESIGN of Integrated Circuits and Systems 25(2), 345–357 (2006)

    Article  Google Scholar 

  31. Urbanski, J.P., Thies, W., Rhodes, C., Amarasinghe, S., Thorsen, T.: Digital Microfluidics using Soft Lithography. Lab-on-a-Chip 6(1), 96–104 (2006)

    Article  Google Scholar 

  32. Jebrail, M.J., Wheeler, A.R.: Digital Microfluidic Method for Protein Extraction by Precipitation. Journal of Analytical Chemistry 81, 330–335 (2009)

    Article  Google Scholar 

  33. Roy, S., Bhattacharya, B.B., Chakrabarty, K.: Optimization of Dilution and Mixing of Biochemical Samples using Digital Microfluidic Biochips. IEEE Transactions on COMPUTER-AIDED DESIGN of Integrated Circuits and Systems 29(11), 1696–1708 (2010)

    Article  Google Scholar 

  34. Roy, S., Bhattacharya, B.B., Chakrabarty, K.: Waste-Aware Dilution and Mixing of Biochemical Samples with Digital Microfluidic Biochips. In: Proc. of the IEEE/ACM Design, Automation and Test in Europe (DATE) Conference, pp. 1059–1064 (2011)

    Google Scholar 

  35. Cira, N.J., Ho, J.Y., Dueck, M.E., Weibel, D.B.: A self-loading microfluidic device for determining the minimum inhibitory concentration of antibiotics. Lab Chip 12, 1052–1059 (2012)

    Article  Google Scholar 

  36. Sugiura, S., Hattori, K., Kanamori, T.: Microfluidic serial dilution cell-based assay for analyzing drug dose response over a wide concentration range. Analytical Chemistry 82(19), 8278–8282 (2010)

    Article  Google Scholar 

  37. Wang, S., Ji, N., Wang, W., Li, Z.: Effects of non-ideal fabrication on the dilution performance of serially functioned microfluidic concentration gradient generator. In: Nano/Micro Engineered and Molecular Systems (NEMS), pp. 169–172 (2010)

    Google Scholar 

  38. Dertinger, S.K.W., Chiu, D.T., Jeon, N.L., Whitesides, G.M.: Generation of gradients having complex shapes using microfluidic networks. Analytical Chemistry 73(6), 1240–1246 (2001)

    Article  Google Scholar 

  39. Jang, Y.H., Hancock, M.J., Kim, S.B., Selimovic, S., Sim, W.Y., Bae, H., Khademhosseini, A.: An integrated microfluidic device for two-dimensional combinatorial dilution. Lab Chip 11, 3277–3286 (2011)

    Article  Google Scholar 

  40. Bhattacharjee, S., Banerjee, A., Ho, T.Y., Chakrabarty, K., Bhattacharya, B.B.: On producing linear dilution gradient of a sample with a digital microfluidic biochip. In: International Symposium on Electronic System Design, ISED (to appear, 2013)

    Google Scholar 

  41. Roy, S., Bhattacharya, B.B., Ghoshal, S., Chakrabarty, K.: A High-Throughput Dilution Engine for Sample Preparation on Digital Microfluidic Biochips. IET Computers & Digital Techniques (IET-CDT), 9 pages (September 2013)

    Google Scholar 

  42. Huang, J.D., Liu, C.H., Chiang, T.W.: Reactant Minimization during Sample Preparation on Digital Microfluidic Biochips using Skewed Mixing Trees. In: Proc. of IEEE/ACM ICCAD, pp. 377–384 (2012)

    Google Scholar 

  43. Bhattacharjee, S., Banerjee, A., Ho, T.Y., Chakrabarty, K., Bhattacharya, B.B.: Eco-friendly sample preparation with concentration gradient on a digital microfluidic biochip. In: International Conference on Eco-friendly Computing and Communication Systems, ICECCS (to appear, 2013)

    Google Scholar 

  44. Roy, S., Bhattacharya, B.B., Chakrabarti, P.P., Chakrabarty, K.: Layout-Aware Solution Preparation for Biochemical Analysis on a Digital Microfluidic Biochip. In: Proc. of the VLSID, pp. 171–176 (2011)

    Google Scholar 

  45. Roy, S., Chakrabarti, P.P., Kumar, S., Bhattacharya, B.B., Chakrabarty, K.: Routing-Aware Resource Allocation for Mixture Preparation in Digital Microfluidic Biochips. In: IEEE ISVLSI, pp. 1–6 (2013)

    Google Scholar 

  46. Bhattacharjee, S., Banerjee, A., Bhattacharya, B.B.: Sample preparation with multiple dilutions on digital microfluidic biochips. IET Computers & Digital Techniques (IET-CDT), 1–10 (2013)

    Google Scholar 

  47. Mitra, D., Roy, S., Chakrabarty, K., Bhattacharya, B.B.: On-chip sample preparation with multiple dilutions using digital microfluidics. In: Proc. of the IEEE International Symposium on VLSI (ISVLSI), pp. 314–319 (August 2012)

    Google Scholar 

  48. Chiang, T.W., Liu, C.H., Huang, J.D.: Graph-Based Optimal Reactant Minimization for Sample Preparation on Digital Microfluidic Biochips. In: Proc. of the IEEE VLSI-DAT, pp. 1–4 (2013)

    Google Scholar 

  49. Mitra, D.: Studies in High-Throughput and Reliable Assay Operations on Digital Microfluidic Biochips. PhD thesis, Bengal Engineering and Science University, Shibpur, India (2012)

    Google Scholar 

  50. Chakrabarty, K., Su, F.: Digital Microfluidic Biochips: Synthesis, Testing and Reconfiguration Techniques. CRC Press (2007)

    Google Scholar 

  51. Mitra, D., Ghoshal, S., Rahaman, H., Chakrabarty, K., Bhattacharya, B.B.: Test planning in digital microfluidic biochips using improved eulerization techniques and the Chinese postman problem. In: IEEE Asian Test Symposium (ATS), pp. 111–116 (2010)

    Google Scholar 

  52. Mitra, D., Ghoshal, S., Rahaman, H., Chakrabarty, K., Bhattacharya, B.B.: Test planning in digital microfluidic biochips using efficient eulerization techniques. Journal of Electronic Testing: Theory and Applications 27(5), 657–671 (2011)

    Article  Google Scholar 

  53. Su, F., Hwang, W., Mukherjee, A., Chakrabarty, K.: Testing and diagnosis of realistic defects in digital microfluidic biochips. Journal of Electronic Testing: Theory and Applications 23(2-3), 219–233 (2007)

    Article  Google Scholar 

  54. Xu, T., Chakrabarty, K.: Fault modeling and functional test methods for digital microfluidic biochips. IEEE Transactions on Biomedical Circuits and Systems 3(4), 241–253 (2009)

    Article  Google Scholar 

  55. Xu, T., Chakrabarty, K.: Functional testing of digital microfluidic biochips. In: International Test Conference (ITC), pp. 1–10 (2007)

    Google Scholar 

  56. Mitra, D., Ghoshal, S., Rahaman, H., Bhattacharya, B.B., Majumder, D.D., Chakrabarty, K.: Accelerated functional testing of digital microfluidic biochips. In: IEEE Asian Test Symposium (ATS), pp. 295–300 (2008)

    Google Scholar 

  57. Zhao, Y., Chakrabarty, K.: On-line testing of lab-on-chip using digital microfluidic compactors. In: IEEE International On-Line Testing Symposium, pp. 213–218 (2008)

    Google Scholar 

  58. Zhao, Y., Chakrabarty, K.: Pin-count-aware online testing of digital microfluidic biochips. In: IEEE VLSI Test Symposium (VTS), pp. 111–116 (2010)

    Google Scholar 

  59. Mitra, D., Ghoshal, S., Rahaman, H., Chakrabarty, K., Bhattacharya, B.B.: On-line error detection in digital microfluidic biochips. In: IEEE Asian Test Symposium (ATS), pp. 332–337 (2012)

    Google Scholar 

  60. Fair, R.B., Khlystov, A., Tailor, T.D., Ivanov, V., Evans, R.D., Griffin, P.B., Srinivasan, V., Pamula, V.K., Pollack, M.G., Zhou, J.: Chemical and Biological Applications of Digital-Microfluidic Devices. IEEE Design & Test of Computers 24(1), 10–24 (2007)

    Article  Google Scholar 

  61. Zhao, Y., Chakrabarty, K.: Cross-contamination avoidance for droplet routing in digital microfluidic biochips. In: IEEE/ACM Design, Automation and Test in Europe (DATE), pp. 1290–1295 (2009)

    Google Scholar 

  62. Mitra, D., Ghoshal, S., Rahaman, H., Chakrabarty, K., Bhattacharya, B.B.: On residue removal in digital microfluidic biochips. In: Great Lakes Symposium on VLSI (GLSVLSI), pp. 391–394 (2011)

    Google Scholar 

  63. Mitra, D., Ghoshal, S., Rahaman, H., Chakrabarty, K., Bhattacharya, B.B.: Automated path planning for washing in digital microfluidic biochips. In: IEEE International Conference on Automation Science & Engineering (CASE), pp. 115–120 (2012)

    Google Scholar 

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Bhattacharya, B.B., Roy, S., Bhattacharjee, S. (2014). Algorithmic Challenges in Digital Microfluidic Biochips: Protocols, Design, and Test. In: Gupta, P., Zaroliagis, C. (eds) Applied Algorithms. ICAA 2014. Lecture Notes in Computer Science, vol 8321. Springer, Cham. https://doi.org/10.1007/978-3-319-04126-1_1

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  • DOI: https://doi.org/10.1007/978-3-319-04126-1_1

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