Skip to main content
SpringerLink
Log in

Microfluidic Systems and Organ (Human) on a Chip

  • Chapter
  • First Online:
Basic Concepts on 3D Cell Culture

Part of the book series: Learning Materials in Biosciences ((LMB))

What You Will Learn in This Chapter

In the previous chapters we learned how cells are cultivated in 3D and how the surrounding gel matrix is optimized. However, to achieve even higher physiologically relevant cell culture conditions, the surrounding environment must be controlled by emerging microfluidic systems. Thus, in the first part of this chapter we will learn about the tremendous benefits of microfluidic devices, their fabrication, and finally their implementation in novel and highly controlled biological and cell culture applications.

On this basis, the second part of this chapter will focus on the complete control of biochemical and biomechanical cell culture parameters, which results in sophisticated organ-on-a-chip systems. You will learn how the blood–tissue barrier and the minimal functional unit of an organ are reconstructed to mimic specific organ functions. Finally, the combination of several different organ-on-a-chip systems results in the so-called human-on-a-chip systems. Although these systems are still in its infancy, we will elaborate on first design concepts and point out their future role in drug development processes in industry.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 69.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 89.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Notes

  1. 1.

    Conversely, it should be noted that adsorption effects on channel walls also tend to increase. This is worth mentioning because adsorption can potentially lead to unwanted binding effects (e.g., with nonspecific proteins).

References

  1. Whitesides GM. The origins and the future of microfluidics. Nature. 2006;442:368–73. https://doi.org/10.1038/nature05058.

    Article  CAS  PubMed  Google Scholar 

  2. Pandey CM, Augustine S, Kumar S, et al. Microfluidics based point-of-care diagnostics. Biotechnol J. 2018;13:1700047. https://doi.org/10.1002/biot.201700047.

    Article  CAS  Google Scholar 

  3. Weibel DB, Whitesides GM. Applications of microfluidics in chemical biology. Curr Opin Chem Biol. 2006;10:584–91. https://doi.org/10.1016/j.cbpa.2006.10.016.

    Article  CAS  PubMed  Google Scholar 

  4. Whitesides GM, Ostuni E, Takayama S, Jiang X, Ingber DE. Soft lithography in biology and biochemistry. Annu Rev Biomed Eng. 2001;3(1):335–73.

    Article  CAS  Google Scholar 

  5. Siller IG, Enders A, Steinwedel T, et al. Real-time live-cell imaging technology enables high-throughput screening to verify in vitro biocompatibility of 3D printed materials. Materials (Basel). 2019;12:2125. https://doi.org/10.3390/ma12132125.

    Article  CAS  Google Scholar 

  6. Siller IG, Enders A, Gellermann P, et al. Characterization of a customized 3D-printed cell culture system using clear, translucent acrylate that enables optical online monitoring. Biomed Mater. 2020;15:055007. https://doi.org/10.1088/1748-605X/ab8e97.

    Article  CAS  PubMed  Google Scholar 

  7. Yeo LY, Chang H-C, Chan PPY, et al. Microfluidic devices for bioapplications. Small. 2011;7:12–48. https://doi.org/10.1002/smll.201000946.

    Article  CAS  PubMed  Google Scholar 

  8. Blazej RG, Kumaresan P, Mathies RA. Microfabricated bioprocessor for integrated nanoliter-scale sanger DNA sequencing. Proc Natl Acad Sci U S A. 2006;103:7240–5. https://doi.org/10.1073/pnas.0602476103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Aborn JH, El-Difrawy SA, Novotny M, et al. A 768-lane microfabricated system for high-throughput DNA sequencing. Lab Chip. 2005;5:669–74. https://doi.org/10.1039/b501104c.

    Article  CAS  PubMed  Google Scholar 

  10. Chin CD, Linder V, Sia SK. Commercialization of microfluidic point-of-care diagnostic devices. Lab Chip. 2012;12:2118–34. https://doi.org/10.1039/c2lc21204h.

    Article  CAS  PubMed  Google Scholar 

  11. Arshavsky-Graham S, Enders A, Ackerman S, et al. 3D-printed microfluidics integrated with optical nanostructured porous aptasensors for protein detection. Microchim Acta. 2021;188:67. https://doi.org/10.1007/s00604-021-04725-0

  12. Bahnemann J, Rajabi N, Fuge G, et al. A new integrated lab-on-a-chip system for fast dynamic study of mammalian cells under physiological conditions in bioreactor. Cell. 2013;2:349–60. https://doi.org/10.3390/cells2020349.

    Article  CAS  Google Scholar 

  13. Rajabi N, Bahnemann J, Tzeng T-N, et al. Lab-on-a-chip for cell perturbation, lysis, and efficient separation of sub-cellular components in a continuous flow mode. Sensors Actuators A Phys. 2014;215:136–43. https://doi.org/10.1016/j.sna.2013.12.019.

    Article  CAS  Google Scholar 

  14. Enders A, Siller IG, Urmann K, et al. 3D printed microfluidic mixers-a comparative study on mixing unit performances. Small. 2019;15:e1804326. https://doi.org/10.1002/smll.201804326.

    Article  CAS  PubMed  Google Scholar 

  15. Capretto L, Cheng W, Hill M, et al. Micromixing within microfluidic devices. Top Curr Chem. 2011;304:27–68. https://doi.org/10.1007/128_2011_150.

    Article  CAS  PubMed  Google Scholar 

  16. Nguyen N-T, Wu Z. Micromixers—a review. J Micromech Microeng. 2005;15:R1–R16. https://doi.org/10.1088/0960-1317/15/2/R01.

    Article  Google Scholar 

  17. Di Carlo D. Inertial microfluidics. Lab Chip. 2009;9:3038–46. https://doi.org/10.1039/b912547g.

    Article  CAS  PubMed  Google Scholar 

  18. Probst C, Grünberger A, Wiechert W, et al. Polydimethylsiloxane (PDMS) sub-Micron traps for single-cell analysis of bacteria. Micromachines (Basel). 2013;4:357–69. https://doi.org/10.3390/mi4040357.

    Article  Google Scholar 

  19. Grünberger A, Wiechert W, Kohlheyer D. Single-cell microfluidics: opportunity for bioprocess development. Curr Opin Biotechnol. 2014;29:15–23. https://doi.org/10.1016/j.copbio.2014.02.008.

    Article  CAS  PubMed  Google Scholar 

  20. Gao J, Yin X-F, Fang Z-L. Integration of single cell injection, cell lysis, separation and detection of intracellular constituents on a microfluidic chip. Lab Chip. 2004;4:47–52. https://doi.org/10.1039/b310552k.

    Article  CAS  PubMed  Google Scholar 

  21. Hung PJ, Lee PJ, Sabounchi P, et al. Continuous perfusion microfluidic cell culture array for high-throughput cell-based assays. Biotechnol Bioeng. 2005;89:1–8. https://doi.org/10.1002/bit.20289.

    Article  CAS  PubMed  Google Scholar 

  22. Gómez-Sjöberg R, Leyrat AA, Pirone DM, et al. Versatile, fully automated, microfluidic cell culture system. Anal Chem. 2007;79:8557–63. https://doi.org/10.1021/ac071311w.

    Article  CAS  PubMed  Google Scholar 

  23. Siller IG, Epping N-M, Lavrentieva A, et al. Customizable 3D-printed (co-)cultivation systems for in vitro study of angiogenesis. Materials (Basel). 2020;13:4920. https://doi.org/10.3390/ma13194290.

    Article  CAS  Google Scholar 

  24. Zhang J, Wei X, Zeng R, et al. Stem cell culture and differentiation in microfluidic devices toward organ-on-a-chip. Future Sci OA. 2017;3:FSO187. https://doi.org/10.4155/fsoa-2016-0091.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Marx U, Andersson TB, Bahinski A, et al. Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing. ALTEX. 2016;33:272–321. https://doi.org/10.14573/altex.1603161.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Cecchi E, Giglioli C, Valente S, et al. Role of hemodynamic shear stress in cardiovascular disease. Atherosclerosis. 2011;214:249–56. https://doi.org/10.1016/j.atherosclerosis.2010.09.008.

    Article  CAS  PubMed  Google Scholar 

  27. Zhang B, Radisic M. Organ-on-a-chip devices advance to market. Lab Chip. 2017;17:2395–420. https://doi.org/10.1039/c6lc01554a.

    Article  CAS  PubMed  Google Scholar 

  28. Zhang B, Korolj A, Lai BFL, et al. Advances in organ-on-a-chip engineering. Nat Rev Mater. 2018;3:257–78. https://doi.org/10.1038/s41578-018-0034-7.

    Article  Google Scholar 

  29. Zhang B, Montgomery M, Chamberlain MD, et al. Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis. Nat Mater. 2016;15:669. https://doi.org/10.1038/nmat4570.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Du Y, Li N, Yang H, et al. Mimicking liver sinusoidal structures and functions using a 3D-configured microfluidic chip. Lab Chip. 2017;17:782–94. https://doi.org/10.1039/c6lc01374k.

    Article  CAS  PubMed  Google Scholar 

  31. Domansky K, Inman W, Serdy J, et al. Perfused multiwell plate for 3D liver tissue engineering. Lab Chip. 2010;10:51–8. https://doi.org/10.1039/b913221j.

    Article  CAS  PubMed  Google Scholar 

  32. Lee PJ, Hung PJ, Lee LP. An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture. Biotechnol Bioeng. 2007;97:1340–6. https://doi.org/10.1002/bit.21360.

    Article  CAS  PubMed  Google Scholar 

  33. Hedaya MA. Basic pharmacokinetics, Pharmacy education series. 2nd ed. Hoboken: CRC Press; 2012.

    Google Scholar 

  34. Jang K-J, Mehr AP, Hamilton GA, et al. Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment. Integr Biol (Camb). 2013;5:1119–29. https://doi.org/10.1039/c3ib40049b.

    Article  CAS  Google Scholar 

  35. Musah S, Mammoto A, Ferrante TC, et al. Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip. Nat Biomed Eng. 2017;1:0069. https://doi.org/10.1038/s41551-017-0069.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Weinberg E, Kaazempur-Mofrad M, Borenstein J. Concept and computational design for a bioartificial nephron-on-a-chip. Int J Artif Organs. 2008;31:508–14. https://doi.org/10.1177/039139880803100606.

    Article  CAS  PubMed  Google Scholar 

  37. Sciancalepore AG, Sallustio F, Girardo S, et al. A bioartificial renal tubule device embedding human renal stem/progenitor cells. PLoS One. 2014;9:e87496. https://doi.org/10.1371/journal.pone.0087496.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kim S, LesherPerez SC, Kim BCC, et al. Pharmacokinetic profile that reduces nephrotoxicity of gentamicin in a perfused kidney-on-a-chip. Biofabrication. 2016;8:15021. https://doi.org/10.1088/1758-5090/8/1/015021.

    Article  Google Scholar 

  39. Ng CP, Zhuang Y, Lin AWH, et al. A fibrin-based tissue-engineered renal proximal tubule for bioartificial kidney devices: development, characterization and in vitro transport study. Int J Tissue Eng. 2013;2013:1–10. https://doi.org/10.1155/2013/319476.

    Article  Google Scholar 

  40. Homan KA, Kolesky DB, Skylar-Scott MA, et al. Bioprinting of 3D convoluted renal proximal tubules on perfusable chips. Sci Rep. 2016;6:34845. https://doi.org/10.1038/srep34845.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Maschmeyer I, Lorenz AK, Schimek K, et al. A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents. Lab Chip. 2015;15:2688–99. https://doi.org/10.1039/c5lc00392j.

    Article  CAS  PubMed  Google Scholar 

  42. Skardal A, Murphy SV, Devarasetty M, et al. Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform. Sci Rep. 2017;7:8837. https://doi.org/10.1038/s41598-017-08879-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Miller PG, Shuler ML. Design and demonstration of a pumpless 14 compartment microphysiological system. Biotechnol Bioeng. 2016;113:2213–27. https://doi.org/10.1002/bit.25989.

    Article  CAS  PubMed  Google Scholar 

  44. Tsamandouras N, Chen WLK, Edington CD, et al. Integrated gut and liver microphysiological systems for quantitative in vitro pharmacokinetic studies. AAPS J. 2017;19:1499–512. https://doi.org/10.1208/s12248-017-0122-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Abaci HE, Shuler ML. Human-on-a-chip design strategies and principles for physiologically based pharmacokinetics/pharmacodynamics modeling. Integr Biol (Camb). 2015;7:383–91. https://doi.org/10.1039/c4ib00292j.

    Article  Google Scholar 

  46. Wikswo JP, Block FE, Cliffel DE, et al. Engineering challenges for instrumenting and controlling integrated organ-on-chip systems. IEEE Trans Biomed Eng. 2013;60:682–90. https://doi.org/10.1109/TBME.2013.2244891.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Rogal J, Probst C, Loskill P. Integration concepts for multi-organ chips: how to maintain flexibility?! Future Sci OA. 2017;3:FSO180. https://doi.org/10.4155/fsoa-2016-0092.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Esch MB, King TL, Shuler ML. The role of body-on-a-chip devices in drug and toxicity studies. Annu Rev Biomed Eng. 2011;13:55–72. https://doi.org/10.1146/annurev-bioeng-071910-124629.

    Article  CAS  PubMed  Google Scholar 

  49. Zhang YS, Davoudi F, Walch P, et al. Bioprinted thrombosis-on-a-chip. Lab Chip. 2016;16:4097–105. https://doi.org/10.1039/c6lc00380j.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ayuso JM, Virumbrales-Munoz M, McMinn PH, et al. Tumor-on-a-chip: a microfluidic model to study cell response to environmental gradients. Lab Chip. 2019;19:3461–71. https://doi.org/10.1039/c9lc00270g.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Technical Chemistry, Leibniz University Hannover, Hannover, Germany

    Janina Bahnemann, Anton Enders & Steffen Winkler

Authors
  1. Janina Bahnemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anton Enders
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Steffen Winkler
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Janina Bahnemann .

Editor information

Editors and Affiliations

  1. Institute of Cell and Tissue Culture Technologies, University of Natural Resources and Life Sciences, Vienna, Austria

    Cornelia Kasper

  2. Institute of Cell and Tissue Culture Technologies, University of Natural Resources and Life Sciences, Vienna, Austria

    Dominik Egger

  3. Institute of Technical Chemistry, Leibniz University of Hannover, Hannover, Germany

    Antonina Lavrentieva

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Bahnemann, J., Enders, A., Winkler, S. (2021). Microfluidic Systems and Organ (Human) on a Chip. In: Kasper, C., Egger, D., Lavrentieva, A. (eds) Basic Concepts on 3D Cell Culture . Learning Materials in Biosciences. Springer, Cham. https://doi.org/10.1007/978-3-030-66749-8_8

Download citation

Publish with us

Policies and ethics

Search

Navigation