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Oil-Encapsulated Nanodroplet Array for Bio-molecular Detection

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Abstract

Detection of low abundance biomolecules is challenging for biosensors that rely on surface chemical reactions. For surface reaction based biosensors, it require to take hours or even days for biomolecules of diffusivities in the order of 10−10−11 m2/s to reach the surface of the sensors by Brownian motion. In addition, often times the repelling Coulomb interactions between the molecules and the probes further defer the binding process, leading to undesirably long detection time for applications such as point-of-care in vitro diagnosis. In this work, we designed an oil encapsulated nanodroplet array microchip utilizing evaporation for pre-concentration of the targets to greatly shorten the reaction time and enhance the detection sensitivity. The evaporation process of the droplets is facilitated by the superhydrophilic surface and resulting nanodroplets are encapsulated by oil drops to form stable reaction chamber. Using this method, desirable droplet volumes, concentrations of target molecules, and reaction conditions (salt concentrations, reaction temperature, etc.) in favour of fast and sensitive detection are obtained. A linear response over 2 orders of magnitude in target concentration was achieved at 10 fM for protein targets and 100 fM for miRNA mimic oligonucleotides.

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References

  1. Accardo, A., et al. In Situ X-ray Scattering Studies of Protein Solution Droplets Drying on Micro- and Nanopatterned Superhydrophobic PMMA Surfaces. Langmuir 26(18):15057–15064, 2010.

    Article  CAS  PubMed  Google Scholar 

  2. Benn, J. A., et al. Comparative modeling and analysis of microfluidic and conventional DNA microarrays. Anal. Biochem. 348(2):284–293, 2006.

    Article  CAS  PubMed  Google Scholar 

  3. Chen, X. M., et al. Evaporation of droplets on superhydrophobic surfaces: surface roughness and small droplet size effects. Phys. Rev. Lett. 109(12):116101, 2012.

  4. Cui, M., et al. Cell-free circulating DNA: a new biomarker for the acute coronary syndrome. Cardiology 124(2):76–84, 2013.

    Article  CAS  PubMed  Google Scholar 

  5. Dash, S., and S. V. Garimella. Droplet Evaporation Dynamics on a Superhydrophobic Surface with Negligible Hysteresis. Langmuir 29(34):10785–10795, 2013.

    Article  CAS  PubMed  Google Scholar 

  6. De Angelis, F., et al. Breaking the diffusion limit with super-hydrophobic delivery of molecules to plasmonic nanofocusing SERS structures. Nat. Photonics 5(11):683–688, 2011.

    Article  Google Scholar 

  7. Du, X. L., et al. Enhancing DNA Detection Sensitivity through a Two-Step Enrichment Method with Magnetic Beads and Droplet Evaporation. Anal. Lett. 43(9):1525–1533, 2010.

    Article  CAS  Google Scholar 

  8. Gentile, F., et al. Superhydrophobic Surfaces as Smart Platforms for the Analysis of Diluted Biological Solutions. ACS Appl. Mater. Interfaces 4(6):3213–3224, 2012.

    Article  CAS  PubMed  Google Scholar 

  9. Hanash, S. M., S. J. Pitteri, and V. M. Faca. Mining the plasma proteome for cancer biomarkers. Nature 452(7187):571–579, 2008.

    Article  CAS  PubMed  Google Scholar 

  10. Huang, S. Q., et al. Microvalve and micropump controlled shuttle flow microfluidic device for rapid DNA hybridization. Lab. Chip 10(21):2925–2931, 2010.

    Article  CAS  PubMed  Google Scholar 

  11. Kulinich, S. A., and M. Farzaneh. Effect of contact angle hysteresis on water droplet evaporation from super-hydrophobic surfaces. Appl. Surf. Sci. 255(7):4056–4060, 2009.

    Article  CAS  Google Scholar 

  12. Lange, J., et al. miRNA biomarkers from blood—a promising approach for minimally invasive diagnostic testing. Geburtshilfe Frauenheilkd. 70(2):137–141, 2010.

    Article  CAS  Google Scholar 

  13. Li, J., et al. Enhancing deoxyribonucleic acid (DNA) detection sensitivity through microconcentration on patterned fluorocarbon polymer surface. Anal. Chim. Acta 571(1):34–39, 2006.

    Article  CAS  PubMed  Google Scholar 

  14. Li, Y. C., et al. DNA detection on plastic: surface activation protocol to convert polycarbonate substrates to biochip platforms. Anal. Chem. 79(2):426–433, 2007.

    Article  CAS  PubMed  Google Scholar 

  15. Li, C. Y., et al. Rapid discrimination of single-nucleotide mismatches based on reciprocating flow on a compact disc microfluidic device. Electrophoresis 30(24):4270–4276, 2009.

    Article  CAS  PubMed  Google Scholar 

  16. Malic, L., T. Veres, and M. Tabrizian. Biochip functionalization using electrowetting-on-dielectric digital microfluidics for surface plasmon resonance imaging detection of DNA hybridization. Biosens. Bioelectron. 24(7):2218–2224, 2009.

    Article  CAS  PubMed  Google Scholar 

  17. Malik, A., et al. Is mitochondrial DNA content a potential biomarker of mitochondrial dysfunction? Mitochondrion 13(5):481–492, 2013.

  18. Markou, A., et al. Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non-small cell lung cancer by quantitative real-time RT-PCR. Clin. Chem. 54(10):1696–1704, 2008.

    Article  CAS  PubMed  Google Scholar 

  19. Mitchell, P. S., et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc. Natl. Acad. Sci. U.S.A. 105(30):10513–10518, 2008.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Noerholm, M., et al. Polymer microfluidic chip for online monitoring of microarray hybridizations. Lab. Chip 4(1):28–37, 2004.

    Article  CAS  PubMed  Google Scholar 

  21. Pappaert, K., et al. Enhancement of DNA micro-array analysis using a shear-driven micro-channel flow system. J. Chromatogr. A 1014(1–2):1–9, 2003.

    Article  CAS  PubMed  Google Scholar 

  22. Rifai, N., M. A. Gillette, and S. A. Carr. Protein biomarker discovery and validation: the long and uncertain path to clinical utility. Nat. Biotechnol. 24(8):971–983, 2006.

    Article  CAS  PubMed  Google Scholar 

  23. Schuler, T., et al. A disposable and cost efficient microfluidic device for the rapid chip-based electrical detection of DNA. Biosens. Bioelectron. 25(1):15–21, 2009.

    Article  PubMed  Google Scholar 

  24. Seabrook, R. B., et al. MicroRNA MiR-205 is downregulated during normal lung development. Am. J. Respir. Crit. Care Med. 183:A4211, 2011.

  25. Situma, C., et al. Fabrication of DNA microarrays onto poly(methyl methacrylate) with ultraviolet patterning and microfluidics for the detection of low-abundant point mutations. Anal. Biochem. 340(1):123–135, 2005.

    Article  CAS  PubMed  Google Scholar 

  26. Spindler, K., D. Danish, and C. C. G. S. Circulating free DNA, mutation detection and predictive biomarker potential. Eur. J. Cancer 48:13–13, 2012.

  27. Wang, L., and P. C. H. Li. Gold nanoparticle-assisted single base-pair mismatch discrimination on a microfluidic microarray device. Biomicrofluidics 4(3):032209, 2010.

  28. Wang, L., and P. C. H. Li. Microfluidic DNA microarray analysis: a review. Anal. Chim. Acta 687(1):12–27, 2011.

    Article  CAS  PubMed  Google Scholar 

  29. Wang, G. K., et al. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur. Heart J. 31(6):659–666, 2010.

    Article  PubMed  Google Scholar 

  30. Wei, C. W., et al. Using a microfluidic device for 1 μl DNA microarray hybridization in 500 s. Nucleic Acids Res. 33(8):e78, 2005.

  31. Yu, M. Circulating cell-free mitochondrial DNA as a novel cancer biomarker: opportunities and challenges. Mitochondrial DNA 23(5):329–332, 2012.

    Article  CAS  PubMed  Google Scholar 

  32. Zampetaki, A., and M. Mayr. Analytical challenges and technical limitations in assessing circulating MiRNAs. Thromb. Haemost. 108(4):592–598, 2012.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Modern Optical Technologies & Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory of Advanced Optical Manufacturing Technologies & MOE Key Laboratory of Modern Optical Technologies, Soochow University, Suzhou, 215006, China

    Wen Qiao

  2. Department of Electrical and Computer Engineering, Jacobs School of Engineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0407, USA

    Wen Qiao, Junlan Song & Yu-Hwa Lo

  3. Materials Science and Engineering Program, University of California San Diego, La Jolla, CA, 92093-0418, USA

    Tiantian Zhang

  4. Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093-0412, USA

    Tony Yen

  5. Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, 92093-0365, USA

    Ti-Hsuan Ku

  6. Department of Biology, Lamar University, Beaumont, TX, 77710, USA

    Ian Lian

Authors
  1. Wen Qiao
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  2. Tiantian Zhang
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  3. Tony Yen
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  4. Ti-Hsuan Ku
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  5. Junlan Song
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  6. Ian Lian
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  7. Yu-Hwa Lo
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Corresponding author

Correspondence to Yu-Hwa Lo.

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Associate Editor Tingrui Pan oversaw the review of this article.

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Qiao, W., Zhang, T., Yen, T. et al. Oil-Encapsulated Nanodroplet Array for Bio-molecular Detection. Ann Biomed Eng 42, 1932–1941 (2014). https://doi.org/10.1007/s10439-014-1039-z

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  • DOI: https://doi.org/10.1007/s10439-014-1039-z

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