Skip to main content

Advertisement

SpringerLink
Log in

Local drug delivery with a self-contained, programmable, microfluidic system

  • Published:
Biomedical Microdevices Aims and scope Submit manuscript

Abstract

The development and optimization of many new drug therapies requires long-term local delivery with controlled, but variable dosage. Current methods for chronic drug delivery have limited utility because they either cannot deliver drugs locally to a specific organ or tissue, do not permit changes in delivery rate in situ, or cannot be used in clinical trials in an untethered, wearable configuration. Here, we describe a small, self-contained system for liquid-phase drug delivery. This system enables studies lasting several months and infusion rates can be programmed and modified remotely. A commercial miniature pump is integrated with microfabricated components to generate ultralow flow rates and stroke volumes. Solutions are delivered in pulses as small as 370 nL, with pulses delivered at any interval of 1 min or longer. A unique feature of the system is the ability to infuse and immediately withdraw liquid, resulting in zero net volume transfer while compounds are exchanged by mixing and diffusion with endogenous fluid. We present in vitro results demonstrating repeatability of the delivered pulse volume for nearly 3 months. Furthermore, we present in vivo results in an otology application, infusing into the cochlea of a guinea pig a glutamate receptor antagonist, which causes localized and reversible changes in auditory sensitivity.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Z. Chen, S.G. Kujawa, M.J. McKenna, J.O. Fiering, M.J. Mescher, J.T. Borenstein, E.E.L. Swan, W.F. Sewell, J. Control. Release 110, 1–19 (2005)doi:10.1016/j.jconrel.2005.09.003

    Article  Google Scholar 

  • C.E. Dubé, J.O. Fiering, M.J. Mescher, in Proc. IEEE Sensors, Orlando, (2002)

  • N. Galley, R. Klinke, W. Oertel, M. Pause, W.H. Storch, Brain Res. 64, 55–63 (1973)

    Article  Google Scholar 

  • M.C. Holley, Br. Med. Bull. 63, 157–169 (2002)

    Article  Google Scholar 

  • M.C. Holley, Drug Discovery Today 10, 1269–1282 (2005)

    Article  Google Scholar 

  • N. Inamura, A.N. Salt, Hear. Res. 61, 12–18 (1992)

    Article  Google Scholar 

  • D.A. LaVan, T. McGuire, R. Langer, Nat. Biotechnol. 21, 1184–1191 (2003)

    Article  Google Scholar 

  • T. Littman, R.P. Bobbin, M. Fallon, J.L. Puel, Hear. Res. 40, 45–53 (1989)

    Article  Google Scholar 

  • D. Maillefer, S. Gamper, B. Frehner, P. Balmer, H. van Lintel, P. Renaud, in Proc. MEMS 2001, 14th IEEE International Conf. on, Interlaken, Switzerland, 413–417 (2001)

  • D.M. Merfeld, W. Gong, J. Morrissey, M. Saginaw, C. Haburcakova, R.F. Lewis, IEEE Trans. Biomed Eng. 53, 2362–2372 (2006)

    Article  Google Scholar 

  • M.J. Mescher, C.E. Dube, M. Varghese, J.O. Fiering, in Proc. Micro Total Analysis Systems (MicroTAS), Squaw Valley CA, 947–950 (2003)

  • M.J. Mescher, C.E. Dube, J.O. Fiering, D.L. Fyler, E.S. Kim, M. Hansberry, J.T. Borenstein, J.J. Bernstein, E. Gragoudas, J. Miller, in Proc. Annual Meeting Society for Biomaterials, Pittsburgh (2006)

  • M.R. Prausnitz, Adv. Drug Deliv. Rev. 56, 581–587 (2004)

    Article  Google Scholar 

  • J.H. Prescott, S. Lipka, S. Baldwin, N.F.J. Sheppard, J.M. Maloney, J. Coppeta, B. Yomtov, M.A. Staples, J.T.J. Santini, Nat. Biotechnol. 24, 437–438 (2006)

    Article  Google Scholar 

  • S.Z. Razzacki, P.K. Thwar, M. Yang, V.M. Ugaz, M.A. Burns, Adv. Drug Deliv. Rev. 56, 185–198 (2004)

    Article  Google Scholar 

  • N. Roxhed, B. Samel, L. Nordquist, P. Griss, G. Stemme, in Proc. MEMS 2006, 19th International Conf. on, Istanbul, 414–417 (2006)

  • W.M. Saltzman, Drug Delivery: Engineering Principles for Drug Therapy (Oxford University Press, New York, 2001)

    Google Scholar 

  • J.T.J. Santini, M.J. Cima, R. Langer, Nature 397, 335–338 (1999)

    Article  Google Scholar 

  • J.T.J. Santini, A.C. Richards, R. Scheidt, M.J. Cima, R. Langer, Angew. Chem. Int. Ed. 39, 2396–2407 (2000)

    Article  Google Scholar 

  • M. Thorne, A.N. Salt, J.E. DeMott, M.M. Henson, O.W.J. Henson, S.L. Gewalt, The Laryngoscope 109, 1661–1668 (1999)

    Article  Google Scholar 

  • A.K. Wise, R. Richardson, J. Hardman, G. Clark, S. O'Leary, J Comp Neurol 487, 147–165 (2005)

    Article  Google Scholar 

Download references

Acknowledgments

We are grateful to Sarah Tao for her contributions. This research was made possible by grant number 5R01DC006848-03 from the National Institutes of Health, National Institute on Deafness and other Communication Disorders.

Author information

Authors and Affiliations

  1. Charles Stark Draper Laboratory, Cambridge, MA, USA

    J. Fiering, M. J. Mescher, E. E. Leary Swan, M. E. Holmboe & J. T. Borenstein

  2. Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    E. E. Leary Swan

  3. Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA, USA

    B. A. Murphy, Z. Chen, M. Peppi, W. F. Sewell & S. G. Kujawa

  4. Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USA

    Z. Chen, M. Peppi, W. F. Sewell, M. J. McKenna & S. G. Kujawa

  5. Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA

    Z. Chen, M. Peppi, W. F. Sewell, M. J. McKenna & S. G. Kujawa

  6. Program in Neuroscience, Harvard Medical School, Boston, MA, USA

    W. F. Sewell

  7. Department of Audiology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA

    S. G. Kujawa

  8. Harvard-MIT Program in Speech and Hearing Bioscience and Technology, Boston, MA, USA

    S. G. Kujawa

Authors
  1. J. Fiering
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. J. Mescher
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. E. Leary Swan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. E. Holmboe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B. A. Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Z. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Peppi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. W. F. Sewell
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M. J. McKenna
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. S. G. Kujawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. J. T. Borenstein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Fiering.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM1

(DOC 32.0 KB)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fiering, J., Mescher, M.J., Leary Swan, E.E. et al. Local drug delivery with a self-contained, programmable, microfluidic system. Biomed Microdevices 11, 571–578 (2009). https://doi.org/10.1007/s10544-008-9265-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10544-008-9265-5

Keywords

Search

Navigation