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Paper-based cell culture microfluidic system

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Abstract

In the past decades, glass/PDMS-based microfluidic systems have been rapidly developed to provide homogenous and stable microenvironment for culturing cells. Although these excellent demonstrations involve much simplified operations than traditional cell culture protocol, but they are still not readily accessible to untrained personnel and not appropriate to operate in conventional biological laboratories. In this work, cellulose filter papers were used for the substrates of the cell culture microfluidic system, which provides a convenient tool for cell-based assay. A paper was patterned with culture areas and channels by wax printing technique. Medium or tested substance can be passively perfused to the culture areas. Analyses of cyto-compatibility, cell proliferation, cell morphology, and cell chemosensitivity were performed to confirm the possibility of the paper-based system. The culture system could provide a platform for a wide range of cell-based assays with applications in drug screening and quantitative cell biology. This work demonstrated a paper-based cell culture microfluidic system and the system is inexpensive, disposable, and compatible to the existing culture facility.

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References

  1. Abbot, A. Cell culture: biology’s new dimension. Nature 424, 870–872 (2003).

    Article  Google Scholar 

  2. Cukierman, E., Pankov, R., Stevens, D.R. & Yamada, K.M. Taking cell-matrix adhesions to the third dimension. Science 294, 1708–1712 (2001).

    Article  CAS  Google Scholar 

  3. Huh, D., Hamilton, G.A. & Ingber, D.E. From 3D cell culture to organs-on-chips. Trends Cell Biol. 21, 745–754 (2011).

    Article  CAS  Google Scholar 

  4. Benya, P.D. & Shaffer, J.D. Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell 30, 215–224 (1982).

    Article  CAS  Google Scholar 

  5. Lei, K.F. Microfluidic systems for diagnostic applications: a review. JALA 17, 330–347 (2012).

    CAS  Google Scholar 

  6. Kim, L., Toh, Y.C., Voldman, J. & Yu, H. A practical guide to microfluidic perfusion culture of adherent mammalian cells. Lab Chip 7, 681–694 (2007).

    Article  CAS  Google Scholar 

  7. Hung, P.J. et al. A novel high aspect ratio microfluidic design to provide a stable and uniform microenvironment for cell growth in a high throughput mammalian cell culture array. Lab Chip 5, 44–48 (2005).

    Article  CAS  Google Scholar 

  8. Lei, K.F., Wu, M.H., Hsu, C.W. & Chen, Y.D. Realtime and non-invasive impedimetric monitoring of cell proliferation and chemosensitivity in a perfusion 3D cell culture microfluidic chip. Biosens. Bioelectron. 51, 16–21 (2014).

    Article  CAS  Google Scholar 

  9. Kim, L., Vahey, M.D., Lee, H.Y. & Voldman, J. Microfluidic arrays for logarithmically perfused embryonic stem cell culture. Lab Chip 6, 394–406 (2006).

    Article  CAS  Google Scholar 

  10. Martinez, A.W., Phillips, S.T. & Whitesides, G.M. Diagnostics for the developing world: microfluidic paper-based analytical devices. Anal. Chem. 82, 3–10 (2010).

    Article  CAS  Google Scholar 

  11. Mao, X. & Huang, T.J. Microfluidic diagnostics for the developing world. Lab Chip 12, 1412–1416 (2012).

    Article  CAS  Google Scholar 

  12. Liu, B., Du, D., Hua, X., Yu, X.Y. & Lin, Y. Paperbased electrochemical biosensors: From test strips to paper-based microfluidics. Electroanalysis 26, 1214–1223 (2014).

    Article  CAS  Google Scholar 

  13. Li, X., Ballerini, D.R. & Shen, W. A perspective on paper-based microfluidics: Current status and future trends. Biomicrofluidics 6, 011301 (2012).

    Article  Google Scholar 

  14. Martinez, A.W., Philips, S.T., Wiley, B.J., Gupta, M. & Whitesides, G.M. FLASH: A rapid method for prototyping paper-based microfluidic devices. Lab Chip 8, 2146–2150 (2008).

    Article  CAS  Google Scholar 

  15. Carrilho, E., Martinez, A.W. & Whitesides, G.M. Understanding wax printing: A simple micropatterning process for paper-based microfluidics. Anal. Chem. 81, 7091–7095 (2009).

    Article  CAS  Google Scholar 

  16. Songjaroen, T., Dungchai, W., Chailapakul, O. & Laiwattanapaisal, W. Novel, simple and low-cost alternative method for fabrication of paper-based microfluidics by wax dipping. Talanta 85, 2587–2593 (2011).

    Article  CAS  Google Scholar 

  17. Lu, Y., Shi, W., Jiang, L., Qin, J. & Lin, B. Rapid prototyping of paper-based microfluidics with wax for low-cost, portable bioassay. Electrophoresis 30, 1497–1500 (2009).

    Article  CAS  Google Scholar 

  18. Li, X., Tian, J., Nguyen, T. & Shen, W. Paper-based microfluidic devices by plasma treatment. Anal. Chem. 80, 9131–9134 (2006).

    Article  Google Scholar 

  19. Zhao, W., All, M.M., Aguirre, S.D., Brook, M.A. & Li, Y. Paper-based bioassays using gold nanoparticle colorimetric probes. Anal. Chem. 80, 8431–8437 (2008).

    Article  CAS  Google Scholar 

  20. Delaney, J.L., Hogan, C.F., Tian, J. & Shen, W. Electrogenerated chemiluminescence detection in paperbased microfluidic sensors. Anal. Chem. 83, 1300–1306 (2011).

    Article  CAS  Google Scholar 

  21. Dungchai, W., Chailapakul, O. & Henry, C.S. Use of multiple colorimetric indicators for paper-based microfluidic devices. Anal. Chim. Acta 674, 227–233 (2010).

    Article  CAS  Google Scholar 

  22. Park, T.S., Baynes, C., Cho, S.I. & Yoon, J.Y. Paper microfluidics for red wine tasting. RSC Adv. 4, 24356–24362 (2014).

    Article  CAS  Google Scholar 

  23. Ellerbee, A.K. et al. Quantifying colorimetric assays in paper-based microfluidic devices by measuring the transmission of light through paper. Anal. Chem. 81, 8447–8452 (2009).

    Article  CAS  Google Scholar 

  24. Dungchai, W., Chailapakul, O. & Henry, C.S. Electrochemical detection for paper-based microfluidics. Anal. Chem. 81, 5821–5826 (2009).

    Article  CAS  Google Scholar 

  25. Davaji, B. & Lee, C.H. A paper-based calorimetric microfluidics platform for bio-chemical sensing. Bios. Bioelectron. 59, 120–126 (2014).

    Article  CAS  Google Scholar 

  26. Zang, D., Ge, L., Yan, M., Song, X. & Yu, J. Electrochemical immunoassay on a 3D microfluidic paperbased device. Chem. Commun. 48, 4683–4685 (2012).

    Article  CAS  Google Scholar 

  27. Nie, Z. et al. Electrochemical sensing in paper-based microfluidic devices. Lab Chip 10, 477–483 (2009).

    Article  Google Scholar 

  28. Cheng, C.M. et al. Paper-based ELISA. Angew. Chem. Int. Ed. 49, 4771–4774 (2010).

    Article  CAS  Google Scholar 

  29. Murdock, R.C. et al. Optimization of a paper-based ELISA for a human performance biomarker. Anal. Chem. 85, 11634–11642 (2013).

    Article  CAS  Google Scholar 

  30. Wang, H.K. et al. Cellulose-based diagnostic devices for diagnosing serotype-2 dengue fever in human serum. Adv. Healthc. Mater. 3, 187–196 (2013).

    Article  Google Scholar 

  31. Derda, R. et al. Paper-supported 3D cell culture for tissue- based bioassays. Proc. Natl. Acad. Sci. U.S.A. 106, 18457–18462 (2009).

    Article  CAS  Google Scholar 

  32. Derda, R. et al. Multizone paper platform for 3D cell cultures. PLoS ONE 6, e18940 (2011).

    Article  CAS  Google Scholar 

  33. Lei, K.F. & Huang, C.H. Paper-based microreactor integrating cell culture and subsequent immunoassay for the investigation of cellular phosphorylation. ACS Appl. Mater. Inter. 6, 22423–22429 (2014).

    Article  CAS  Google Scholar 

  34. Deiss, F. et al. Platform for high-throughput testing of the effect of soluble compounds on 3D cell cultures. Anal. Chem. 85, 8085–8094 (2013).

    Article  CAS  Google Scholar 

  35. Simon, K.A. et al. Polymer-based mesh as supports for multi-layered 3D cell culture and assays. Biomaterials 35, 259–268 (2014).

    Article  CAS  Google Scholar 

  36. Peppas, N.A., Hilt, J.Z., Khademhosseini, A. & Langer, R. Hydrogels in biology and medicine: From molecular principles to bionanotechnology. Adv. Mater. 18, 1345–1360 (2006).

    Article  CAS  Google Scholar 

  37. Tibbitt, M.W. & Anseth, K.S. Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol. Bioeng. 105, 655–663 (2009).

    Article  Google Scholar 

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Correspondence to Kin Fong Lei.

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Tao, F.F., Xiao, X., Lei, K.F. et al. Paper-based cell culture microfluidic system. BioChip J 9, 97–104 (2015). https://doi.org/10.1007/s13206-015-9202-7

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  • DOI: https://doi.org/10.1007/s13206-015-9202-7

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