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3D printed microfluidic devices with immunoaffinity monoliths for extraction of preterm birth biomarkers

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Abstract

Preterm birth (PTB) is defined as birth before the 37th week of pregnancy and results in 15 million early deliveries worldwide every year. Presently, there is no clinical test to determine PTB risk; however, a panel of nine biomarkers found in maternal blood serum has predictive power for a subsequent PTB. A significant step in creating a clinical diagnostic for PTB is designing an automated method to extract and purify these biomarkers from blood serum. Here, microfluidic devices with 45 μm × 50 μm cross-section channels were 3D printed with a built-in polymerization window to allow a glycidyl methacrylate monolith to be site-specifically polymerized within the channel. This monolith was then used as a solid support to attach antibodies for PTB biomarker extraction. Using these functionalized monoliths, it was possible to selectively extract a PTB biomarker, ferritin, from buffer and a human blood serum matrix. This is the first demonstration of monolith formation in a 3D printed microfluidic device for immunoaffinity extraction. Notably, this work is a crucial first step toward developing a 3D printed microfluidic clinical diagnostic for PTB risk.

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References

  1. World Health Organization. Preterm birth. In: Fact sheets. WHO. 2018. http://www.who.int/mediacentre/factsheets/fs363/en/. Accessed 3 Jul 2018.

  2. Centers for Disease Control and Prevention. Preterm birth. In: Maternal and infant health. CDC. 2018. https://www.cdc.gov/reproductivehealth/maternalinfanthealth/pretermbirth.htm. Accessed 3 Jul 2018.

  3. Behrman RE, Butler AS. Preterm birth: causes, consequences, and prevention. Washington DC: National Academies Press; 2007.

    Google Scholar 

  4. Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet. 2012;379:2162–72.

    Article  PubMed  Google Scholar 

  5. Roberto R, Sudhansu KD, Susan JF. Preterm labor: one syndrome, many causes. Science. 2014;345:760–5.

    Article  CAS  Google Scholar 

  6. Esplin MS, Merrell K, Goldenberg R, Lai Y, Iams JD, Mercer B, et al. Proteomic identification of serum peptides predicting subsequent spontaneous preterm birth. Am J Obstet Gynecol. 2011;204:391.e8.

    Article  CAS  Google Scholar 

  7. Sahore V, Sonker M, Nielsen AV, Knob R, Kumar S, Woolley AT. Automated microfluidic devices integrating solid-phase extraction, fluorescent labeling, and microchip electrophoresis for preterm birth biomarker analysis. Anal Bioanal Chem. 2018;410:933–41.

    Article  CAS  PubMed  Google Scholar 

  8. Sonker M, Parker EK, Nielsen AV, Sahore V, Woolley AT. Electrokinetically operated microfluidic devices for integrated immunoaffinity monolith extraction and electrophoretic separation of preterm birth biomarkers. Analyst. 2018;143:224–31.

    Article  CAS  Google Scholar 

  9. Nielsen AV, Nielsen JB, Sonker M, Knob R, Sahore V, Woolley AT. Microchip electrophoresis separation of a panel of preterm birth biomarkers. Electrophoresis. 2018;39:2300–7.

    Article  CAS  PubMed  Google Scholar 

  10. Chin CD, Linder V, Sia SK. Commercialization of microfluidic point-of-care diagnostic devices. Lab Chip. 2012;13:2118–34.

    Article  CAS  Google Scholar 

  11. Sonker M, Sahore V, Woolley AT. Recent advances in microfluidic sample preparation and separation techniques for molecular biomarker analysis: a critical review. Anal Chim Acta. 2017;986:1–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Núñez O, Nakanishi K, Tanaka N. Preparation of monolithic silica columns for high-performance liquid chromatography. J Chromatogr A. 2008;1191:231–52.

    Article  CAS  PubMed  Google Scholar 

  13. Knob R, Sahore V, Sonker M, Woolley AT. Advances in monoliths and related porous materials for microfluidics. Biomicrofluidics. 2016;10:032901–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Andjelković U, Tufegdžić S, Popović M. Use of monolithic supports for high-throughput protein and peptide separation in proteomics. Electrophoresis. 2017;38:2851–69.

    Article  CAS  PubMed  Google Scholar 

  15. Svec F, Lv Y. Advances and recent trends in the field of monolithic columns for chromatography. Anal Chem. 2015;87:250–73.

    Article  CAS  PubMed  Google Scholar 

  16. Tetala KKR, Vijayalakshmi MA. A review on recent developments for biomolecule separation at analytical scale using microfluidic devices. Anal Chim Acta. 2016;906:7–21.

    Article  CAS  PubMed  Google Scholar 

  17. Buchmeiser MR. Polymeric monolithic materials: syntheses, properties, functionalization and applications. Polymer. 2007;48:2187–98.

    Article  CAS  Google Scholar 

  18. Masini JC, Svec F. Porous monoliths for on-line sample preparation: a review. Anal Chim Acta. 2017;964:24–44.

    Article  CAS  PubMed  Google Scholar 

  19. Yang W, Sun X, Wang HY, Woolley AT. Integrated microfluidic device for serum biomarker quantitation using standard addition or a calibration curve. Anal Chem. 2009;81:8230–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yang W, Yu M, Sun X, Woolley AT. Microdevices integrating affinity columns and capillary electrophoresis for multibiomarker analysis in human serum. Lab Chip. 2010;10:2527–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Svec F. Porous polymer monoliths: amazingly wide variety of techniques enabling their preparation. J Chromatogr A. 2010;1217:902–24.

    Article  CAS  PubMed  Google Scholar 

  22. Dziomba S, Araya-Farias M, Smadja C, Taverna M, Carbonnier B, Tran NT. Solid supports for extraction and preconcentration of proteins and peptides in microfluidic devices: a review. Anal Chim Acta. 2017;955:1–26.

    Article  CAS  PubMed  Google Scholar 

  23. Pandey C, Augustine S, Kumar S, Kumar S, Nara S, Srivastave S, et al. Microfluidics based point-of-care diagnostics. Biotechnol J. 2018;13:1700047.

    Article  CAS  Google Scholar 

  24. Nge PN, Rogers CI, Woolley AT. Advances in microfluidic materials, functions, integration, and applications. Chem Rev. 2013;113:2550–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Erickson D, Li D. Integrated microfluidic devices. Anal Chim Acta. 2004;507:11–26.

    Article  CAS  Google Scholar 

  26. Hu J, Cui X, Gong Y, Xu X, Gao B, Wen T, et al. Portable microfluidic and smartphone-based devices for monitoring of cardiovascular diseases at the point of care. Biotechnol Adv. 2016;34:305–20.

    Article  PubMed  Google Scholar 

  27. Yazdi AA, Popma A, Wong W, Nguyen T, Pan Y, Xu J. 3D printing: an emerging tool for novel microfluidics and lab-on-a-chip applications. Microfluid Nanofluid. 2016;20:50.

    Article  Google Scholar 

  28. Berman B. 3-D printing: the new industrial revolution. Bus Horiz. 2012;55:155–62.

    Article  Google Scholar 

  29. Stansbury JW, Idacavage MJ. 3D printing with polymers: challenges among expanding options and opportunities. Dent Mater. 2016;32:54–64.

    Article  CAS  PubMed  Google Scholar 

  30. Beauchamp MJ, Nordin GP, Woolley AT. Moving from millifluidic to truly microfluidic sub-100-μm cross-section 3D printed devices. Anal Bioanal Chem. 2017;409:4311–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Shallan AI, Smejkal P, Corban M, Guijt RM, Breadmore MC. Cost-effective three-dimensional printing of visibly transparent microchips within minutes. Anal Chem. 2014;86:3124–30.

    Article  CAS  PubMed  Google Scholar 

  32. Anciaux SK, Geiger M, Bowser MT. 3D printed micro free-flow electrophoresis device. Anal Chem. 2016;88:7675–82.

    Article  CAS  PubMed  Google Scholar 

  33. Anderson KB, Lockwood SY, Martin RS, Spence DM. A 3D printed fluidic device that enables integrated features. Anal Chem. 2013;85:5622–6.

    Article  CAS  PubMed  Google Scholar 

  34. Sochol RD, Sweet E, Glick CC, Venkatesh S, Avetisyan A, Ekman KG, et al. 3D printed microfluidic circuitry via multijet based additive manufacturing. Lab Chip. 2016;16:668–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Lee KG, Park KJ, Seok S, Shin S, Kim DH, Park JY, et al. 3D printed modules for integrated microfluidic devices. RSC Adv. 2014;4:32876–80.

    Article  CAS  Google Scholar 

  36. Lee JM, Zhang M, Yeong WY. Characterization and evaluation of 3D printed microfluidic chip for cell processing. Microfluid Nanofluid. 2016;20:1–15.

    Article  CAS  Google Scholar 

  37. Gong H, Beauchamp M, Perry S, Woolley AT, Nordin GP. Optical approach to resin formulation for 3D printed microfluidics. RSC Adv. 2015;5:106621–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Gong H, Bickham BP, Woolley AT, Nordin GP. Custom 3D printer and resin for 18 μm × 20 μm microfluidic flow channels. Lab Chip. 2017;17:2899–909.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Beauchamp MJ, Gong H, Woolley AT, Nordin GP. 3D printed microfluidic features using dose control in X, Y, and Z dimensions. Micromachines. 2018;9:326-1-326-12.

    Article  Google Scholar 

  40. Sahore V, Kumar S, Rogers CI, Sonker M, Jensen JK, Woolley AT. Pressure-actuated microfluidic devices for electrophoretic separation of pre-term birth biomarkers. Anal Bioanal Chem. 2016;408:599–607.

    Article  CAS  PubMed  Google Scholar 

  41. Gong H, Woolley AT, Nordin GP. 3D printed high density, reversible, chip-to-chip microfluidic interconnects. Lab Chip. 2018;18:639–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Gong H, Woolley AT, Nordin GP. High density 3D printed microfluidic valves, pumps, and multiplexers. Lab Chip. 2016;16:2450–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

The authors acknowledge support from the National Institutes of Health (R01 EB006124 and R15 GM123405-01A1). A.V.N. and M.J.B. thank the BYU Department of Chemistry and Biochemistry for financial support from a Roland K. Robins Fellowship, and H.M.A acknowledges Taif University for financial support.

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Correspondence to Adam T. Woolley.

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The authors declare that they have no conflicts of interest.

Research involving human participants

Human blood serum samples were obtained from commercial sources; human subjects work has been approved under IRB no. E18401.

Additional information

Published in the topical collection Ultrasmall Sample Biochemical Analysis with guest editors Ryan Kelly and Ying Zhu.

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Parker, E.K., Nielsen, A.V., Beauchamp, M.J. et al. 3D printed microfluidic devices with immunoaffinity monoliths for extraction of preterm birth biomarkers. Anal Bioanal Chem 411, 5405–5413 (2019). https://doi.org/10.1007/s00216-018-1440-9

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  • DOI: https://doi.org/10.1007/s00216-018-1440-9

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