BioChip Journal

, Volume 9, Issue 2, pp 97–104 | Cite as

Paper-based cell culture microfluidic system

  • Fang Fang Tao
  • Xia Xiao
  • Kin Fong LeiEmail author
  • I-Chi Lee
Original Article


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.


Paper-based microfluidics Filter paper Cell culture Cell proliferation Chemosensitivity 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Abbot, A. Cell culture: biology’s new dimension. Nature 424, 870–872 (2003).CrossRefGoogle Scholar
  2. 2.
    Cukierman, E., Pankov, R., Stevens, D.R. & Yamada, K.M. Taking cell-matrix adhesions to the third dimension. Science 294, 1708–1712 (2001).CrossRefGoogle Scholar
  3. 3.
    Huh, D., Hamilton, G.A. & Ingber, D.E. From 3D cell culture to organs-on-chips. Trends Cell Biol. 21, 745–754 (2011).CrossRefGoogle Scholar
  4. 4.
    Benya, P.D. & Shaffer, J.D. Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell 30, 215–224 (1982).CrossRefGoogle Scholar
  5. 5.
    Lei, K.F. Microfluidic systems for diagnostic applications: a review. JALA 17, 330–347 (2012).Google Scholar
  6. 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).CrossRefGoogle Scholar
  7. 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).CrossRefGoogle Scholar
  8. 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).CrossRefGoogle Scholar
  9. 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).CrossRefGoogle Scholar
  10. 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).CrossRefGoogle Scholar
  11. 11.
    Mao, X. & Huang, T.J. Microfluidic diagnostics for the developing world. Lab Chip 12, 1412–1416 (2012).CrossRefGoogle Scholar
  12. 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).CrossRefGoogle Scholar
  13. 13.
    Li, X., Ballerini, D.R. & Shen, W. A perspective on paper-based microfluidics: Current status and future trends. Biomicrofluidics 6, 011301 (2012).CrossRefGoogle Scholar
  14. 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).CrossRefGoogle Scholar
  15. 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).CrossRefGoogle Scholar
  16. 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).CrossRefGoogle Scholar
  17. 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).CrossRefGoogle Scholar
  18. 18.
    Li, X., Tian, J., Nguyen, T. & Shen, W. Paper-based microfluidic devices by plasma treatment. Anal. Chem. 80, 9131–9134 (2006).CrossRefGoogle Scholar
  19. 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).CrossRefGoogle Scholar
  20. 20.
    Delaney, J.L., Hogan, C.F., Tian, J. & Shen, W. Electrogenerated chemiluminescence detection in paperbased microfluidic sensors. Anal. Chem. 83, 1300–1306 (2011).CrossRefGoogle Scholar
  21. 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).CrossRefGoogle Scholar
  22. 22.
    Park, T.S., Baynes, C., Cho, S.I. & Yoon, J.Y. Paper microfluidics for red wine tasting. RSC Adv. 4, 24356–24362 (2014).CrossRefGoogle Scholar
  23. 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).CrossRefGoogle Scholar
  24. 24.
    Dungchai, W., Chailapakul, O. & Henry, C.S. Electrochemical detection for paper-based microfluidics. Anal. Chem. 81, 5821–5826 (2009).CrossRefGoogle Scholar
  25. 25.
    Davaji, B. & Lee, C.H. A paper-based calorimetric microfluidics platform for bio-chemical sensing. Bios. Bioelectron. 59, 120–126 (2014).CrossRefGoogle Scholar
  26. 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).CrossRefGoogle Scholar
  27. 27.
    Nie, Z. et al. Electrochemical sensing in paper-based microfluidic devices. Lab Chip 10, 477–483 (2009).CrossRefGoogle Scholar
  28. 28.
    Cheng, C.M. et al. Paper-based ELISA. Angew. Chem. Int. Ed. 49, 4771–4774 (2010).CrossRefGoogle Scholar
  29. 29.
    Murdock, R.C. et al. Optimization of a paper-based ELISA for a human performance biomarker. Anal. Chem. 85, 11634–11642 (2013).CrossRefGoogle Scholar
  30. 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).CrossRefGoogle Scholar
  31. 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).CrossRefGoogle Scholar
  32. 32.
    Derda, R. et al. Multizone paper platform for 3D cell cultures. PLoS ONE 6, e18940 (2011).CrossRefGoogle Scholar
  33. 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).CrossRefGoogle Scholar
  34. 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).CrossRefGoogle Scholar
  35. 35.
    Simon, K.A. et al. Polymer-based mesh as supports for multi-layered 3D cell culture and assays. Biomaterials 35, 259–268 (2014).CrossRefGoogle Scholar
  36. 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).CrossRefGoogle Scholar
  37. 37.
    Tibbitt, M.W. & Anseth, K.S. Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol. Bioeng. 105, 655–663 (2009).CrossRefGoogle Scholar

Copyright information

© The Korean BioChip Society and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Fang Fang Tao
    • 1
  • Xia Xiao
    • 1
  • Kin Fong Lei
    • 2
    • 3
    Email author
  • I-Chi Lee
    • 4
  1. 1.School of Electronic Information EngineeringTianjin UniversityTianjinChina
  2. 2.Graduate Institute of Medical MechatronicsChang Gung UniversityTaoyuan CityTaiwan
  3. 3.Department of Mechanical EngineeringChang Gung UniversityTaoyuan CityTaiwan
  4. 4.Graduate Institute of Biochemical and Biomedical EngineeringChang Gung UniversityTaoyuan CityTaiwan

Personalised recommendations