Biomedical Microdevices

, Volume 11, Issue 4, pp 861–867 | Cite as

A robust, electrochemically driven microwell drug delivery system for controlled vasopressin release

Article

Abstract

Micro-electro-mechanical-system (MEMS) based implantable drug delivery devices represent a promising approach to achieving more precise dosing, faster release and better localization of therapeutic compounds than is possible with existing technology. Despite recent advancements, there remain challenges in being able to build systems that enable active control over the dose rate and release time, in a robust, low power but simple to fabricate package. Here we demonstrate an implantable microreservoir device that enables delivery of dose volumes as high as 15 μl using an electrochemically based transport mechanism. This approach allows for a significant reduction in the amount of time required for drug delivery as well as reducing the dependence on the external physiological conditions. We present the overall design, operating principle and construction of the device, and experimental results showing the volume transport rate as a function of the strength of the applied electric field. The concentration profile vs. time, the power consumption, and ejection efficiency are also investigated. To demonstrate the medical utility of the device we also characterize the in-vitro release of vasopressin.

Keywords

Drug delivery Microfluidics Electrochemical reaction Vasopressin Microwell 

Supplementary material

Supplementary movie 1 Electrochemical transport of 15 μl of vasopressin directly into air for the case of an applied potential of 12 V (MPG 3620 kb)

Supplementary movie 2 Electrochemical transport of 15 μl of vasopressin into PBS buffer for the case of an applied potential of 12 V (MPG 3934 kb)

10544_2009_9303_MOESM3_ESM.doc (152 kb)
Supplementary Fig. S1Vasopressin spectrum by MALDI-TOF/TOF mass spectroscopy (A) Intensity profile for control experiment (B) The main vasopressin peak (~1.085 kD) remains after applying 12 V for 5 min (DOC 152 kb)

References

  1. A. Ahmed, C. Bonner, T.A. Desai, Biomed. Microdevices. 3, 89–96 (2001)CrossRefGoogle Scholar
  2. A. Ahmed, C. Bonner, T.A. Desai, J. Control, Release 81, 291–306 (2002)CrossRefGoogle Scholar
  3. W.H. Bickell, S.P. Bruttig, G.A. Millnamow, J. Obenar, C.E. Wade, Surgery 110, 529–536 (1991)Google Scholar
  4. M.C. Belanger, Y. Marois, J. Biomed. Mater. Res. 58, 467–477 (2001)CrossRefGoogle Scholar
  5. A.J. Chung, D. Erickson, Lab chip 9, 669–676 (2009)CrossRefGoogle Scholar
  6. A.J. Chung, D. Kim, D. Erickson, Lab. Chip. 8, 330–338 (2008)CrossRefGoogle Scholar
  7. R.M.C. Dawson, D.C. Elliott, W.H. Elliott, K.M. Jones, Data for Biochemical Research (Oxford University Press, Oxford, 1986), p. 31Google Scholar
  8. M.R. Dokmeci, J.A. von Arx, K. Najafi, Proc. Solid-State Sens. Act., Transducers 1, 283–286 (1997)CrossRefGoogle Scholar
  9. E.J. Fitzsimons, J. Sendroy, J. Biol. Chem. 236, 1595–1601 (1961)Google Scholar
  10. R.P. Frankenthal, D.J. Siconolfi, J. Electrochem. Soc. 129, 1192–1196 (1982)CrossRefGoogle Scholar
  11. A.C.R. Grayson, M.J. Cima, R. Langer, J. Biomed, Mater. Res. A 69A, 502–512 (2004a)CrossRefGoogle Scholar
  12. A.C.R. Grayson, M.J. Cima, R. Langer, Biomaterials 26, 2137–2145 (2005)CrossRefGoogle Scholar
  13. A.C.R. Grayson, R.S. Shawgo, A.M. Johnson, N.T. Flynn, Y.W. Li, M.J. Cima, R. Langer, Proc. IEEE 92, 6–21 (2004b)CrossRefGoogle Scholar
  14. S. Guo, T. Nakamura, T. Fukuda, K. Oguro, Proc. IEEE ICRA, 266-271 (1997)Google Scholar
  15. J.W. Judy, Smart Mat. Struct. 10, 1115–1134 (2001)CrossRefGoogle Scholar
  16. A.C. Krismer, V. Wenzel, W.G. Voelckel, P. Innerhofer, K.H. Stadlbauer, T. Haas, M. Pavlic, H.J. Sparr, K.H. Lindner, A. Koenigsrainer, Anaesthesist 54, 220–224 (2005)CrossRefGoogle Scholar
  17. D.A. LaVan, T. McGuire, R. Langer, Nat. Biotech. 21, 1184–1191 (2003)CrossRefGoogle Scholar
  18. Y.W. Li, H.L.H. Duc, B. Tyler, T. Williams, M. Tupper, R. Langer, H. Brem, M.J. Cima, J. Control, Release 106, 138–145 (2005)CrossRefGoogle Scholar
  19. H.G. Lienhart, K.H. Lindner, V. Wenzel, Curr. Opin. Crit. Care 14, 247–253 (2008)CrossRefGoogle Scholar
  20. K.H. Lindner, A.W. Prengel, E.G. Pfenninger, I.M. Lindner, H.U. Strohmenger, M. Georgieff, K.G. Lurie, Circulation 91, 215–221 (1995)Google Scholar
  21. M.B. Malay, J.L. Ashton, K. Dahl, S.A. Burchell, R.C. Ashton, R.R. Sciacca, J.A. Oliver, D.W. Landry, Critical Care Medicine 32, 1327–1331 (2004)CrossRefGoogle Scholar
  22. J.M. Maloney, S.A. Uhland, B.F. Polito, N.F. Sheppard, C.M. Pelta, J.T. Santini, J. Control, Release 109, 244–255 (2005)CrossRefGoogle Scholar
  23. G. Milles, C.J. Kouchk, H.G. Zacheis, Surgery 60, 434–442 (1966)Google Scholar
  24. D. Morales, J. Madigan, S. Cullinane, J. Chen, M. Heath, M. Oz, J.A. Oliver, D.W. Landry, Circulation 100, 226–229 (1999)Google Scholar
  25. A.B. Peitzman, B.G. Harbrecht, A.O. Udekwu, T.R. Billiar, K. Edward, R.L. Simmons, Curr. Probl. Surg. 32, 925–1002 (1995)CrossRefGoogle Scholar
  26. J.H. Prescott, S. Lipka, S. Baldwin, N.F. Sheppard, J.M. Maloney, J. Coppeta, B. Yomto, M.A. Staples, J.T. Santini, Nat. Biotech. 24, 437–438 (2006)CrossRefGoogle Scholar
  27. B.D. Ratner, A.S. Hoffman, F.J. Schoen, J.E. Lemons, Biomaterials science: An Introduction to Materials in Medicine (Academic, San Diego, 2004), pp. 296–304Google Scholar
  28. R.R. Richardson, J.A. Miller, W.M. Reichert, Biomaterials 14, 627–635 (1993)CrossRefGoogle Scholar
  29. I. Roberts, P. Evans, F. Bunn, I. Kwan, E. Crowhurst, Lancet 357, 385–387 (2001)CrossRefGoogle Scholar
  30. J.T. Santini, M.J. Cima, R. Langer, Nature 397, 335–338 (1999)CrossRefGoogle Scholar
  31. W.K. Schomburg, J. Vollmer, B. Bustgens, J. Fahrenberg, H. Hein, W. Menz, J. Micromech, Microeng. 4, 186–191 (1994)CrossRefGoogle Scholar
  32. G.W. Shaftan, C.J. Chiu, C. Dennis, C.S. Grosz, J. Cardiovasc, Surg. 5, 251–256 (1964)Google Scholar
  33. Y.S. Shin, K. Cho, S.H. Lim, S. Chung, S.J. Park, C. Chung, D.C. Han, J.K. Chang, J. Micromech, Microeng. 13, 768–774 (2003)CrossRefGoogle Scholar
  34. S.A. Stern, S.C. Dronen, P. Birrer, X. Wang, Ann. Emerg. Med. 22, 155–163 (1993)CrossRefGoogle Scholar
  35. W.G. Voelckel, K.G. Lurie, K.H. Lindner, T. Zielinski, S. McKnite, A.C. Krismer, V. Wenzel, Anesth. Analg. 91, 627–634 (2000)CrossRefGoogle Scholar
  36. G. Voskerician, M.S. Shive, R.S. Shawgo, H. von Recum, J.M. Anderson, M.J. Cima, R. Langer, Biomaterials 24, 1959–1967 (2003)CrossRefGoogle Scholar
  37. J.H. Yoo, C. Park, D.H. Hahm, H.J. Lee, H.M. Park, J. Vet, Medical Science 69, 755–758 (2007)Google Scholar
  38. J.D. Zahn, A. Deshmukh, A.P. Pisano, D. Liepmann, Biomed. Microdevices 6, 183–190 (2004)CrossRefGoogle Scholar
  39. R. Zengerle, J. Ulrich, S. Kluge, M. Richter, A. Richter, Sensor Actuat A-Phys. 50, 81–86 (1995)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Sibley School of Mechanical and Aerospace EngineeringCornell UniversityIthacaUSA

Personalised recommendations