Skip to main content
Log in

Design Optimization of Liquid-Phase Flow Patterns for Microfabricated Lung on a Chip

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Microreactors experience significant deviations from plug flow due to the no-slip boundary condition at the walls of the chamber. The development of stagnation zones leads to widening of the residence time distribution at the outlet of the reactor. A hybrid design optimization process that combines modeling and experiments has been utilized to minimize the width of the residence time distribution in a microreactor. The process was used to optimize the design of a microfluidic system for an in vitro model of the lung alveolus. Circular chambers to accommodate commercial membrane supported cell constructs are a particularly challenging geometry in which to achieve a uniform residence time distribution. Iterative computational fluid dynamics (CFD) simulations were performed to optimize the microfluidic structures for two different types of chambers. The residence time distributions of the optimized chambers were significantly narrower than those of non-optimized chambers, indicating that the final chambers better approximate plug flow. Qualitative and quantitative visualization experiments with dye indicators demonstrated that the CFD results accurately predicted the residence time distributions within the bioreactors. The results demonstrate that such a hybrid optimization process can be used to design microreactors that approximate plug flow for in vitro tissue engineered systems. This technique has broad application for optimization of microfluidic body-on-a-chip systems for drug and toxin studies.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10

Similar content being viewed by others

References

  1. Adeosun, J. T., and A. Lawal. Numerical and experimental studies of mixing characteristics in a T-junction microchannel using residence-time distribution. Chem. Eng. Sci. 64:2422–2432, 2009.

    Article  CAS  Google Scholar 

  2. Campbell, C. J., and B. A. Grzybowski. Microfluidic mixers: from microfabricated to self-assembling devices. Philos. Trans. R. Soc. Lond. Ser. A 362:1069–1086, 2004.

    Article  Google Scholar 

  3. Cantu-Perez, A., S. Barrass, and A. Gavriilidis. Residence time distributions in microchannels: comparison between channels with herringbone structures and a rectangular channel. Chem. Eng. J. 160:834–844, 2010.

    Article  CAS  Google Scholar 

  4. Carlotto, S., I. Fortunati, C. Ferrante, P. Schwille, and A. Polimeno. Time correlated fluorescence characterization of an asymmetrically focused flow in a microfluidic device. Microfluid. Nanofluid. 10:551–561, 2011.

    Article  Google Scholar 

  5. Culbertson, C. T., S. C. Jacobson, and J. Michael Ramsey. Diffusion coefficient measurements in microfluidic devices. Talanta 56:365–373, 2002.

    Article  PubMed  CAS  Google Scholar 

  6. DeMello, A. J. Control and detection of chemical reactions in microfluidic systems. Nature 442:394–402, 2006.

    Article  PubMed  CAS  Google Scholar 

  7. Dutta, D., A. Ramachandran, and D. Leighton. Effect of channel geometry on solute dispersion in pressure-driven microfluidic systems. Microfluid. Nanofluid. 2:275–290, 2006.

    Article  Google Scholar 

  8. Esch, M. B., T. L. King, and M. L. Shuler. The role of body-on-a-chip devices in drug and toxicity studies. Annu. Rev. Biomed. Eng. 13:55–72, 2011.

    Article  PubMed  CAS  Google Scholar 

  9. Günther, A., M. Jhunjhunwala, M. Thalmann, M. A. Schmidt, and K. F. Jensen. Micromixing of miscible liquids in segmented gas–liquid flow. Langmuir 21:1547–1555, 2005.

    Article  PubMed  Google Scholar 

  10. Hartman, R. L., J. P. McMullen, and K. F. Jensen. Deciding whether to go with the flow: evaluating the merits of flow reactors for synthesis. Angew. Chem. Int. Ed. Engl. 50:7502–7519, 2011.

    Article  PubMed  CAS  Google Scholar 

  11. Hessel, V., H. Löwe, and F. Schönfeld. Micromixers—a review on passive and active mixing principles. Chem. Eng. Sci. 60:2479–2501, 2005.

    Article  CAS  Google Scholar 

  12. Hornung, C. H., and M. R. Mackley. The measurement and characterisation of residence time distributions for laminar liquid flow in plastic microcapillary arrays. Chem. Eng. Sci. 64:3889–3902, 2009.

    Article  CAS  Google Scholar 

  13. Huh, D., B. D. Matthews, A. Mammoto, M. Montoya-Zavala, H. Y. Hsin, and D. E. Ingber. Reconstituting organ-level lung functions on a chip. Science 328:1662–1668, 2010.

    Article  PubMed  CAS  Google Scholar 

  14. Inglesby, M. K., and S. H. Zeronian. Diffusion coefficients for direct dyes in aqueous and polar aprotic solvents by the NMR pulsed-field gradient technique. Dyes Pigments 50:3–11, 2001.

    Article  CAS  Google Scholar 

  15. Jamnongwong, M., K. Loubiere, N. Dietrich, and G. Hébrard. Experimental study of oxygen diffusion coefficients in clean water containing salt, glucose or surfactant: consequences on the liquid-side mass transfer coefficients. Chem. Eng. J. 165:758–768, 2010.

    Article  CAS  Google Scholar 

  16. Kola, I., and J. Landis. Can the pharmaceutical industry reduce attrition rates? Nat. Rev. Drug Discov. 3:711–716, 2004.

    Article  PubMed  CAS  Google Scholar 

  17. Nakagaki, M. The diffusion of dye solutions. Bull. Chem. Soc. Jpn. 23:104–107, 1950.

    Article  CAS  Google Scholar 

  18. Powers, D. E., J. R. Millman, S. Bonner-Weir, M. J. Rappel, and C. K. Colton. Accurate control of oxygen level in cells during culture on silicone rubber membranes with application to stem cell differentiation. Biotechnol. Prog. 26:805–818, 2010.

    Article  PubMed  CAS  Google Scholar 

  19. Rasband, W. S. ImageJ. Bethesda, Maryland: U.S. National Institutes of Health, 1997–2011.

  20. Ryu, G., J. S. Huang, O. Hofmann, C. A. Walshe, J. Y. Y. Sze, G. D. McClean, A. Mosley, S. J. Rattle, J. C. deMello, A. J. deMello, and D. D. C. Bradley. Highly sensitive fluorescence detection system for microfluidic lab-on-a-chip. Lab Chip 11:1664–1670, 2011.

    Article  PubMed  CAS  Google Scholar 

  21. Song, H., J. D. Tice, and R. F. Ismagilov. A microfluidic system for controlling reaction networks in time. Angew. Chem. Int. Ed. Engl. 115:792–796, 2003.

    Article  Google Scholar 

  22. Sung, J., and M. Shuler. Prevention of air bubble formation in a microfluidic perfusion cell culture system using a microscale bubble trap. Biomed. Microdevices 11:731–738, 2009.

    Article  PubMed  Google Scholar 

  23. Sung, J., and M. Shuler. In vitro microscale systems for systematic drug toxicity study. Bioprocess. Biosyst. Eng. 33:5–19, 2010.

    Article  PubMed  CAS  Google Scholar 

  24. Tamimi, A., E. B. Rinker, and O. C. Sandall. Diffusion coefficients for hydrogen sulfide, carbon dioxide, and nitrous oxide in water over the temperature range 293–368 K. J. Chem. Eng. Data 39:330–332, 1994.

    Article  CAS  Google Scholar 

  25. Znidarsic-Plazl, P., and I. Plazl. Steroid extraction in a microchannel system-mathematical modelling and experiments. Lab Chip 7:883–889, 2007.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grant W81XWH-10-1-0542 from the U. S. Army. The authors thank Richard Zotti at the CREOL Machine Shop at the University of Central Florida (UCF) for his assistance in production of the flow housings. This work was performed in part at the Cornell NanoScale Facility, a member of the National Nanotechnology Infrastructure Network, which is supported by the National Science Foundation (Grant ECS-0335765). Craig Finch thanks the Institute for Simulation and Training (IST) at UCF for donating computing time on the Stokes cluster, and IST and the NanoScience Technology Center at UCF for financial support.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to M. Shuler or J. Hickman.

Additional information

Associate Editor Jong Hwan Sung oversaw the review of this article.

C. Long and C. Finch contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Long, C., Finch, C., Esch, M. et al. Design Optimization of Liquid-Phase Flow Patterns for Microfabricated Lung on a Chip. Ann Biomed Eng 40, 1255–1267 (2012). https://doi.org/10.1007/s10439-012-0513-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-012-0513-8

Keywords

Navigation