Skip to main content
SpringerLink
Log in

High-throughput nanoscale lipid vesicle synthesis in a semicircular contraction-expansion array microchannel

  • Original Article
  • Published:
BioChip Journal Aims and scope Submit manuscript

Abstract

Towards potential applications in the field of nanomedicine, a new high-throughput synthesis method of lipid vesicles with tunable size as well as enhanced monodispersity is demonstrated using a semicircular contraction-expansion array (CEA) microchannel. Lipid vesicles are generated in the CEA microchannel by injecting lipids in isopropyl alcohol as a sample flow and phosphate buffered saline as a buffer flow, leading to spontaneous formation of lipid vesicles. In the CEA microchannel, Dean vortices cause three-dimensional (3D) lamination by continuously splitting and redirecting fluid streams, resulting in enhancement of fluid mixing. When considered only 3D laminating effect, it showed the best mixing efficiency in the range of flow rates of 12–15 mL/h. However, shear force effect also gives a strong influence on the formation of lipid vesicles, leading to the smallest size and uniform size distribution of lipid vesicles at a total flow rate of 18 mL/h. Consequently, from the interplay between high shear stress and 3D laminating effect, the lipid vesicles were generated with monodispersity and high throughput. The formation of lipid vesicles can be controlled with a total flow rate and a flow rate ratio between the sample and buffer fluids. The throughput of the lipid generation in the CEA microchannel was 10 times higher than previous works. In addition, the generated lipid vesicle populations were confirmed using a cryogenic transmission electron microscopy (cryo-TEM) technique.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jahn, A. et al. Microfluidic directed formation of liposomes of controlled size. Langmuir 23, 6289–6293 (2007).

    Article  CAS  Google Scholar 

  2. Hong, J.S. et al. Liposome-templated supramolecular assembly of responsive alginate nanogels. Langmuir 24, 4092–4096 (2008).

    Article  CAS  Google Scholar 

  3. Jahn, A., Vreeland, W.N., Gaitan, M. & Locascio, L.E. Controlled vesicle self-assembly in microfluidic channels with hydrodynamic focusing. J. Am. Chem. Soc. 126, 2674–2675 (2004).

    Article  CAS  Google Scholar 

  4. Huang, X.M. et al. Ultrasound-enhanced microfluidic synthesis of liposomes. Anticancer Res. 30, 463–466 (2010).

    CAS  Google Scholar 

  5. Gullotti, E. & Yeo, Y. Extracellularly activated nanocarriers: a new paradigm of tumor targeted drug delivery. Mol. Pharmaceut. 6, 1041–1051 (2009).

    Article  CAS  Google Scholar 

  6. Ishida, T., Harashima, H. & Kiwada, H. Liposome clearance. Bioscience. Rep. 22, 197–224 (2002).

    Article  CAS  Google Scholar 

  7. Xu, Q. et al. Preparation of monodisperse biodegradable polymer microparticles using a microfluidic flow-focusing device for controlled drug delivery. Small 5, 1575–1581 (2009).

    Article  CAS  Google Scholar 

  8. Traikia, M. et al. Formation of unilamellar vesicles by repetitive freeze-thaw cycles: characterization by electron microscopy and P-31-nuclear magnetic resonance. Eur. Biophys. J. Biophy. 29, 184–195 (2000).

    Article  CAS  Google Scholar 

  9. Tan, Y.C., Hettiarachchi, K., Siu, M. & Pan, Y.P. Controlled microfluidic encapsulation of cells, proteins, and microbeads in lipid vesicles. J. Am. Chem. Soc. 128, 5656–5658 (2006).

    Article  CAS  Google Scholar 

  10. Batzri, S. & Korn, E.D. Single bilayer liposomes prepared without sonication. Biochim. Biophys. Acta 298, 1015–1019 (1973).

    Article  CAS  Google Scholar 

  11. Maulucci, G. et al. Particle size distribution in DMPC vesicles solutions undergoing different sonication times. Biophys. J. 88, 3545–3550 (2005).

    Article  CAS  Google Scholar 

  12. Jahn, A. et al. Microfluidic mixing and the formation of nanoscale lipid vesicles. ACS Nano 4, 2077–2087 (2010).

    Article  CAS  Google Scholar 

  13. Valencia, P.M. et al. Single-step assembly of homogenous lipid — polymeric and lipid-quantum dot nanoparticles enabled by microfluidic rapid mixing. ACS Nano 4, 1671–1679 (2010).

    Article  CAS  Google Scholar 

  14. Ramachandran, S., Quist, A.P., Kumar, S. & Lal, R. Cisplatin nanoliposomes for cancer therapy: AFM and fluorescence Imaging of cisplatin encapsulation, stability, cellular uptake, and toxicity. Langmuir 22, 8156–8162 (2006).

    Article  CAS  Google Scholar 

  15. Abraham, S.A. et al. The liposomal formulation of doxorubicin. Method Enzymol. 391, 71–97 (2005).

    Article  CAS  Google Scholar 

  16. Gulsen, D., Li, C.C. & Chauhan, A. Dispersion of DMPC liposomes in contact lenses for ophthalmic drug delivery. Curr. Eye Res. 30, 1071–1080 (2005).

    Article  CAS  Google Scholar 

  17. Andresen, T.L., Jensen, S.S. & Jorgensen, K. Advanced strategies in liposomal cancer therapy: problems and prospects of active and tumor specific drug release. Prog. Lipid Res. 44, 68–97 (2005).

    Article  CAS  Google Scholar 

  18. Crosasso, P. et al. Preparation, characterization and properties of sterically stabilized paclitaxel-containing liposomes. J. Control. Release 63, 19–30 (2000).

    Article  CAS  Google Scholar 

  19. Sadava, D., Coleman, A. & Kane, S.E. Liposomal daunorubicin overcomes drug resistance in human breast, ovarian and lung carcinoma cells. J. Liposome Res. 12, 301–309 (2002).

    Article  CAS  Google Scholar 

  20. Pavelic, Z. et al. Development and in vitro evaluation of a liposomal vaginal delivery system for acyclovir. J. Control. Release 106, 34–43 (2005).

    Article  CAS  Google Scholar 

  21. Boonyasit, Y. et al. Passive micromixer integration with a microfluidic chip for calcium assay based on the arsenazo III method. BioChip J. 5, 1–7 (2011).

    Article  CAS  Google Scholar 

  22. Karnik, R. et al. Microfluidic platform for controlled synthesis of polymeric nanoparticles. Nano Lett. 8, 2906–2912 (2008).

    Article  CAS  Google Scholar 

  23. Stroock, A.D. et al. Chaotic mixer for microchannels. Science 295, 647–651 (2002).

    Article  CAS  Google Scholar 

  24. Lin, Y.C., Chung, Y.C. & Wu, C.Y. Mixing enhancement of the passive microfluidic mixer with J-shaped baffles in the tee channel. Biomed. Microdevices 9, 215–221 (2007).

    Article  Google Scholar 

  25. Hong, C.C., Choi, J.W. & Ahn, C.H. A novel inplane passive microfluidic mixer with modified Tesla structures. Lab Chip 4, 109–113 (2004).

    Article  CAS  Google Scholar 

  26. Lee, M.G., Choi, S. & Park, J.-K. Rapid laminating mixer using a contraction-expansion array microchannel. Appl. Phys. Lett. 95, 051902 (2009).

    Article  Google Scholar 

  27. Sudarsan, A.P. & Ugaz, V.M. Fluid mixing in planar spiral microchannels. Lab Chip 6, 74–82 (2006).

    Article  CAS  Google Scholar 

  28. Howell, P.B., Mott, D.R., Golden, J.P. & Ligler, F.S. Design and evaluation of a Dean vortex-based micromixer. Lab Chip 4, 663–669 (2004).

    Article  CAS  Google Scholar 

  29. Lee, M.G., Choi, S. & Park, J.K. Rapid multivortex mixing in an alternately formed contraction-expansion array microchannel. Biomed. Microdevices 12, 1019–1026 (2010).

    Article  CAS  Google Scholar 

  30. Zhang, H.W. et al. Assembly of plasmid DNA into liposomes after condensation by cationic lipid in anionic detergent solution. Biotechnol. Lett. 27, 1701–1705 (2005).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Bio and Brain Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea

    Jisun Lee, Myung Gwon Lee, Youn-Hee Park, Chaeyeon Song, Myung Chul Choi & Je-Kyun Park

  2. Department of Chemical and Biomolecular Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Korea

    Cheulhee Jung & Hyun Gyu Park

Authors
  1. Jisun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Myung Gwon Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cheulhee Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Youn-Hee Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chaeyeon Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Myung Chul Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hyun Gyu Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Je-Kyun Park
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Je-Kyun Park.

Additional information

These authors contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, J., Lee, M.G., Jung, C. et al. High-throughput nanoscale lipid vesicle synthesis in a semicircular contraction-expansion array microchannel. BioChip J 7, 210–217 (2013). https://doi.org/10.1007/s13206-013-7303-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13206-013-7303-8

Keywords

Search

Navigation