Skip to main content
SpringerLink
Log in

A controlled-release microchip

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

Much previous work in methods of achieving complex drug-release patterns has focused on pulsatile release from polymeric materials in response to specific stimuli1, such as electric2,3,4,5 or magnetic6,7 fields, exposure to ultrasound7,8, light9 or enzymes10, and changes in pH11 or temperature12,13,14. An alternative method for achieving pulsatile release involves using microfabrication technology to develop active devices that incorporate micrometre-scale pumps, valves and flow channels to deliver liquid solutions15,16. Here we report a solid-state silicon microchip that can provide controlled release of single or multiple chemical substances on demand. The release mechanism is based on the electrochemical dissolution of thin anode membranes covering microreservoirs filled with chemicals in solid, liquid or gel form. We have conducted proof-of-principle release studies with a prototype microchip using gold and saline solution as a model electrode material and release medium, and we have demonstrated controlled, pulsatile release of chemical substances with this device.

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

Figure 1: A prototype microchip for controlled release showing the shape of a single reservoir.
Figure 2: Removal of an anode membrane to initiate release from a reservoir.
Figure 3: Pulsatile release of a single substance from a microchip device.
Figure 4: Pulsatile release of multiple substances from a single microchip device.

Similar content being viewed by others

References

  1. Kost, J. & Langer, R. Responsive polymeric delivery systems. Adv. Drug Delivery Rev. 6, 19–50 (1991).

    Article  CAS  Google Scholar 

  2. Kwon, I. C., Bae, Y. H. & Kim, S. W. Electrically erodible polymer gel for controlled release of drugs. Nature 354, 291–293 (1991).

    Article  ADS  CAS  Google Scholar 

  3. Bae, Y. H., Kwon, I. C. & Kim, S. W. in Polymeric Drugs and Drug Adminsitration (ed. Ottenbrite, R. M.) 98–110 (Am. Chem. Soc., Washington DC, (1994)).

    Book  Google Scholar 

  4. Miller, L. L. Electrochemically controlled release of drug ions from conducting polymers. Mol. Cryst. Liq. Cryst. 160, 297–301 (1988).

    Google Scholar 

  5. Hepel, M. & Fijalek, Z. in Polymeric Drugs and Drug Adminsitraiton (ed. Ottenbrite, R. M.) 79–97 (Am. Chem. Soc., Washington DC, (1994)).

    Book  Google Scholar 

  6. Edelman, E. R., Kost, J., Bobeck, H. & Langer, R. Regulation of drug release from polymer matrices by oscillating magnetic fields. J. Biomed. Mater. Res. 19, 67–83 (1985).

    Article  CAS  Google Scholar 

  7. Kost, J. & Langer, R. in Pulsed and Self-Regulated Drug Delivery (ed. Kost, J.) 3–16 (CRC, Boca Raton, (1990)).

    Google Scholar 

  8. Kost, J., Leong, K. & Langer, R. Ultrasound-enhanced polymer degradation and release of incorporated substances. Proc. Natl Acad. Sci. USA 86, 7663–7666 (1989).

    Article  ADS  CAS  Google Scholar 

  9. Mathiowitz, E. & Cohen, M. D. Polyamide microcapsules for controlled release. V. Photochemical release. J. Membr. Sci. 40, 67–86 (1989).

    Article  CAS  Google Scholar 

  10. Fischel-Ghodsian, F., Brown, L., Mathiowitz, E., Brandenburg, D. & Langer, R. Enzymatically controlled drug delivery. Proc. Natl Acad. Sci. USA 85, 2403–2406 (1988).

    Article  ADS  CAS  Google Scholar 

  11. Siegel, R. A., Falamarzian, M., Firestone, B. A. & Moxley, B. C. pH-controlled release from hydrophobic/polyelectrolyte copolymer hydrogels. J. Control. Release 8, 179–182 (1988).

    Article  CAS  Google Scholar 

  12. Bae, Y. H., Okano, T., Husu, R. & Kim, S. W. Thermo-sensitive polymers as on-off switches for drug release. Makromol. Chem. Rapid Commun. 8, 481–485 (1987).

    Article  CAS  Google Scholar 

  13. Hoffman, A. S., Afrassiabi, A. & Dong, L. C. Thermally reversible hydrogels: II. Delivery and selective removal of substances from aqueous solutions. J. Control. Release 4, 213–222 (1986).

    Article  CAS  Google Scholar 

  14. Okano, T., Bae, Y. H. & Kim, S. W. in Pulsed and Self-Regulated Drug Delivery (ed. Kost, J.) 17–45 (CRC, Boca Raton, (1990)).

    Google Scholar 

  15. Gravesen, P., Branebjerg, J. & Jensen, O. S. Microfluidics - a review. J. Micromech. Microeng. 3, 168–182 (1993).

    Article  ADS  CAS  Google Scholar 

  16. Shoji, S. & Esashi, M. Microflow devices and systems. J. Micromech. Microeng. 4, 157–171 (1994).

    Article  ADS  CAS  Google Scholar 

  17. Wolf, S. & Tauber, R. N. Silicon Processing for the VLSI Era Vol. 1 Process Technology (Lattice Sunset Beach, California, (1986)).

    Google Scholar 

  18. Jaeger, R. C. Introduction to Microelectronic Fabrication (Addison-Wesley, Reading, Massachusetts, (1988).

    Google Scholar 

  19. Frankenthal, R. P. & Siconolfi, D. J. The anodic corrosion of gold in concentrated chloride solutions. J. Electrochem. Soc. 129, 1192–1196 (1982).

    Article  CAS  Google Scholar 

  20. Merchant, B. Gold, the noble metal and the paradoxes of its toxicology. Biologicals 26, 49–59 (1998).

    Article  CAS  Google Scholar 

  21. Jiran, E. & Thompson, C. V. Capillary instabilities in thin, continuous films. Thin Solid Films 208, 23–28 (1992).

    Article  ADS  CAS  Google Scholar 

  22. Wu, B. M. in Microstructural Control During Three Dimensional Printing of Polymeric Medical DevicesThesis, 25–40 MIT((1997)).

    Google Scholar 

Download references

Acknowledgements

We thank A. Göpferich and M. Llabres for help in the early stages of the project, and K. Jensen, C. Thompson and R. Latanision for discussions about materials and electrochemical aspects of this project. All fabrication work was carried out at the Microsystems Technology Laboratory at MIT. This work was partially supported by the US NSF.

Author information

Authors and Affiliations

  1. Department of Chemical Engineering, and Engineering, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    John T. Santini Jr & Robert Langer

  2. Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Michael J. Cima

Authors
  1. John T. Santini Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael J. Cima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert Langer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert Langer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Santini, J., Cima, M. & Langer, R. A controlled-release microchip. Nature 397, 335–338 (1999). https://doi.org/10.1038/16898

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/16898

  • Springer Nature Limited

This article is cited by

Search

Navigation