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Abstract

The amount of Deoxyribonucleic acid (DNA) strands available in the biological sample is a major limitation for many genomic bioanalyses [1–4]. For example, in the study of gene dosage in tumor DNA by comparative genomic hybridization, the analysis procedure requires several hundred nanograms of DNA strands for fluorescent labeling [2]. It is difficult to obtain such a large amount of DNA strands directly from biological samples. To overcome this problem, the polymerase chain reaction (PCR) technique is used as the first step for these bioanalyses to amplify (replicate) the initial DNA strands [2, 3, 5]. Based on the categories of operations involved, the procedure of genomic analysis can be divided into three separate stages [6]. The first stage is sample preparation for PCR; the second stage is amplification of the DNA strands; after DNA amplification, the third stage includes the subsequent operations, such as mixing the droplet that contains DNA strands with other reagent droplets, detecting the concentration of intermediate product droplets, and the hybridization of the amplified DNA sequences [4].

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References

  1. Y. Luo, B. Bhattacharya, T.-Y. Ho and K. Chakrabarty, “Optimization of polymerase chain reaction on a cyberphysical digital microfluidic biochip”, Proc. IEEE/ACM International Conference on Computer-Aided Design, pp. 622–629, 2013.

    Google Scholar 

  2. J. Lage, J. Leamon, T. Pejovic, S. Hamann, M. Lacey, D. Dillon, et. al, “Whole genome analysis of genetic alterations in small DNA samples using hyperbranched strand displacement amplification and array-GH”, Genome Res. Issue 13, pp. 294–307, 2003.

    Google Scholar 

  3. J. Berthier, Micro-Drops and Digital Microfluidics, Norwich, NY: William Andrew, 2008.

    Google Scholar 

  4. I. Erill, S. Campoy, J. Rus, L. Fonseca, A. Ivorra, Z. Navarro, J. Plaza, J. Aguilo, and J. Barbe, “Development of a CMOS-compatible PCR chip: comparison of design and system strategies”, Journal of Micromechanics and Microengineering, Volume 14, Number 11, pp. 1–11, 2014.

    Google Scholar 

  5. C. Zhang and D. Xing, “Miniaturized PCR chips for nucleic acid amplification and analysis: latest advances and future trends”, Nucleic Acids Research, Vol. 35, No. 13, pp. 4223–4237, 2007.

    Article  Google Scholar 

  6. D. Brassard, L. Malic, C. Miville-Godin, F. Normandin, and T. Veres, “Advanced EWOD-based digital microfluidic system for multiplexed analysis of biomolecular interactions”, IEEE International Conference on Micro Electro Mechanical Systems (MEMS), pp. 153–156, 2011.

    Google Scholar 

  7. D. Jary, A. Chollat-Namy, Y. Fouillet, J. Boutet, C. Chabrol, G. Castellan, D. Gasparutto, and C. Peponnet, “DNA repair enzyme analysis on EWOD fluidic microprocessor”, Proceedings of the NSTI-Nanotech Conference, vol. 2, pp. 554–557, 2006.

    Google Scholar 

  8. K. Chakrabarty and F. Su, Digital Microfluidic Biochips: Synthesis, Testing, and Reconfiguration Techniques, Boca Raton, FL: CRC Press, 2006.

    Book  Google Scholar 

  9. Y. Luo, K. Chakrabarty, and T.-Y. Ho, “Dictionary-based error recovery in cyberphysical digital-microfluidic biochips”, Proc. IEEE/ACM International Conference on Computer-Aided Design, pp. 369–376, 2012.

    Google Scholar 

  10. R. Liu, J. Yang, R. Lenigk, J. Bonanno, and P. Grodzinski, “Self-contained, fully integrated biochip for sample preparation, polymerase chain reaction amplification, and DNA microarray detection”, Anal. Chem., Issue 76, pp. 1824–1831, 2004.

    Google Scholar 

  11. L. Malic, T. Veres, and M. Tabrizian, “Detection of DNA hybridization on a configurable digital microfluidic biochip using SPR imaging”, International Conference on Miniaturized Systems for Chemistry and Life Sciences, pp. 829–831, 2008.

    Google Scholar 

  12. L. Malic, T. Veres, and M. Tabrizian, “Two-dimensional droplet-based surface plasmon resonance imaging using electrowetting-on-dielectric microfluidics”, Lab on a Chip, Issue 9, pp. 473–475, 2009.

    Google Scholar 

  13. K. Choi, A. Ng, R. Fobel, and A. Wheeler, “Digital microfluidics”, Annual Review of Analytical Chemistry, Vol. 5, pp. 413–440, 2012.

    Article  Google Scholar 

  14. M. Shamsi, K. Choi, A. Ng, A. Wheeler, “A digital microfluidic electrochemical immunoassay”, Lab on a Chip, Issue 14, pp. 547–554, 2014.

    Google Scholar 

  15. S. Koster, F. Angile, H. Duan, J. Agresti, A. Wintner, C. Schmitz, A. Rowat, C. Merten, D. Pisignano, A. Griffiths. and D. Weitz, “Drop-based microfluidic devices for encapsulation of single cells”, Lab on a Chip, vol. 8, pp. 1110–1115, 2008.

    Article  Google Scholar 

  16. R. Daniel, M. Dines, and H. Petach, “The denaturation and degradation of stable enzymes at high temperatures”, Biochem J., vol. 317, Issue 1, pp. 1–11, 1996.

    Google Scholar 

  17. F. Ji, M. Juntunen, and I. Hietanen, “Evaluation of electrical crosstalk in high-density photodiode arrays for X-ray imaging applications”, Nuclear Instruments and Methods in Physics Research, volume 610, issue 1, pp. 28–30, 2009.

    Google Scholar 

  18. R. Evans et al., “Optical detection heterogeneously integrated with a coplanar digital microfluidic lab-on-a-chip platform”, Proc. IEEE Sensors Conf., pp. 423–426, Oct. 2007.

    Google Scholar 

  19. S. Koester, L. Schares, C. Schow, G. Dehlinger, and R. John, “Temperature-dependent analysis of Ge-on-SOI photodetectors and receivers”, IEEE International Conference on Group IV Photonics, pp. 179–181, 2006.

    Google Scholar 

  20. C. Zhang and D. Xing, “Single-molecule DNA amplification and analysis using microfluidics”, Chem Rev., Issue. 110, vol. 8, pp. 4910–4947, 2010.

    Google Scholar 

  21. D. Woide, A. Zink, and S. Thalhammer, “Technical note: PCR analysis of minimum target amount of ancient DNA”, Am J Phys Anthropol, volume 142, Issue 2, pp. 321–327, 2010.

    Google Scholar 

  22. J. Webster, M. Burns, D. Burke, and C. Mastrangelo, “Monolithic capillary electrophoresis device with integrated fluorescence detector”, Anal Chem., volume 73, Issue 7, pp. 1622–1626, 2001.

    Google Scholar 

  23. U.-C. Yi and C.-J. Kim, “Soft printing of droplets pre-metered by electrowetting”, Sensors and Actuators A: Physical, Volume 114, Issues 2–3, pp. 347–354, 2004.

    Google Scholar 

  24. I. Erill, S. Campoy, J. Rus, L. Fonseca, A. Ivorra, Z. Navarro, J. Plaza, J. Aguilo, and J. Barbe, “Development of a CMOS-compatible PCR chip: comparison of design and system strategies”, Journal of Micromechanics and Microengineering, Volume 14, Number 11, pp. 1–11, 2004.

    Google Scholar 

  25. M. Garey and D. Johnson, Computers and Intractability: A Guide to the Theory of NP-Completeness. W.H. Freeman & Company, 1979.

    Google Scholar 

  26. P. Bhowmick, A. Biswas, B. Bhattacharya, “ICE: The isothetic convex envelope of a digital object”, International Conference on Computing: Theory and Applications, pp. 219–223, 2007.

    Google Scholar 

  27. S. Roy, B. Bhattacharya, P. Chakrabarti, and K. Chakrabarty, “Layout-aware solution preparation for biochemical analysis on a digital microfluidic biochip”, Proc. IEEE International Conference on VLSI Design, pp. 171–176, 2011.

    Google Scholar 

  28. Y.-L. Hsieh, T.-Y. Ho, and K. Chakrabarty, “Design Methodology for Sample Preparation on Digital Microfluidic Biochips”, IEEE International Conference on Computer Design, pp. 189–194, 2012.

    Google Scholar 

  29. Y. Luo, K. Chakrabarty, and T.-Y. Ho, “Design of cyberphysical digital-microfluidic biochips under completion-time uncertainties in fluidic operations”, pp. 44–50, Proc. IEEE/ACM Design Automation Conference, 2013.

    Google Scholar 

  30. P. Paik, V. Pamula, and R. Fair, “Rapid droplet mixers for digital microfluidic systems”, Lab on a Chip, vol. 3, pp. 253–259, 2003.

    Article  Google Scholar 

  31. P. Paik, V. Pamula, M. Pollack, and R. Fair, “Electrowetting-based droplet mixers for microfluidic systems”, Lab on a Chip, vol. 3, Issue 1, pp. 28–33, 2003.

    Article  Google Scholar 

  32. E. Bolton, G. Sayler, D. Nivens, J. Rochelle, S. Ripp, and M. Simpson, “Integrated CMOS photodetectors and signal processing for very low-level chemical sensing with the bioluminescent bioreporter integrated circuit”, Sens Actuators B Chem, vol. 85, Issue 1, pp. 179–185, 2002.

    Article  Google Scholar 

  33. P. Paik, V. Pamula and R. Fair, “Rapid droplet mixers for digital microfluidic systems”, Lab on a Chip, vol. 3, pp. 253–259, 2003.

    Article  Google Scholar 

  34. (Optimase Master Mix Calculator) http://www.mutationdiscovery.com/md/MD.com-/screens/optimase/MasterMixCalculator.jsp?action=none

  35. Y.-L. Hsieh, T.-Y. Ho and K. Chakrabarty, “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, vol. 31, pp. 1656–1669, 2012.

    Article  Google Scholar 

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Luo, Y., Chakrabarty, K., Ho, TY. (2015). Optimization of On-Chip Polymerase Chain Reaction. In: Hardware/Software Co-Design and Optimization for Cyberphysical Integration in Digital Microfluidic Biochips. Springer, Cham. https://doi.org/10.1007/978-3-319-09006-1_5

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  • DOI: https://doi.org/10.1007/978-3-319-09006-1_5

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