A robust nanofluidic membrane with tunable zero-order release for implantable dose specific drug delivery

Daniel Fine, Alessandro Grattoni, Sharath Hosali, Arturas Ziemys, Enrica De Rosa, Jaskaran Gill, Ryan Medema, Lee Hudson, Milos Kojic, Miljan Milosevic, Louis Brousseau, Randy Goodall, Mauro Ferrari, Xuewu Liu

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

This manuscript demonstrates a mechanically robust implantable nanofluidic membrane capable of tunable long-term zero-order release of therapeutic agents in ranges relevant for clinical applications. The membrane, with nanochannels as small as 5 nm, allows for the independent control of both dosage and mechanical strength through the integration of high-density short nanochannels parallel to the membrane surface with perpendicular micro- and macrochannels for interfacing with the ambient solutions. These nanofluidic membranes are created using precision silicon fabrication techniques on silicon-on-insulator substrates enabling exquisite control over the monodispersed nanochannel dimensions and surface roughness. Zero-order release of analytes is achieved by exploiting molecule to surface interactions which dominate diffusive transport when fluids are confined to the nanoscale. In this study we investigate the nanofluidic membrane performance using custom diffusion and gas testing apparatuses to quantify molecular release rate and process uniformity as well as mechanical strength using a gas based burst test. The kinetics of the constrained zero-order release is probed with molecules presenting a range of sizes, charge states, and structural conformations. Finally, an optimal ratio of the molecular hydrodynamic diameter to the nanochannel dimension is determined to assure zero-order release for each tested molecule.

Original languageEnglish (US)
Pages (from-to)3074-3083
Number of pages10
JournalLab on a Chip
Volume10
Issue number22
DOIs
StatePublished - Nov 21 2010

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Chemistry(all)
  • Biomedical Engineering

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