Tailoring width of microfabricated nanochannels to solute size can be used to control diffusion kinetics Frank Martin a, * , Robbie Walczak a , Anthony Boiarski a , Michael Cohen a , Teri West a , Carlo Cosentino b , Mauro Ferrari c a iMEDD Inc., Columbus, OH, USA b Department of Experimental and Clinical Medicine, University of Catanzaro bMagna Gr&ciaQ, Catanzaro, Italy c Department of Internal Medicine, Ohio State University, Columbus, OH, USA Received 17 June 2004; accepted 28 September 2004 Abstract Top–down microfabrication techniques were used to create silicon-based membranes consisting of arrays of uniform channels having a width as small as 7 nm. The measurement of diffusion kinetics of solutes across these membranes under sink conditions reveals non-Fickian behavior as the nanopore width approaches the hydrodynamic diameter of the solute. Zero-order diffusion of interferon is observed at channel width of 20 nm, and the same phenomenon occurs with albumin and 13-nm-wide channels, whereas Fickian diffusion kinetics is seen at 26 nm and larger pore sizes. A prototypical drug delivery device is described that is fitted with a 13-nm nanopore membrane and loaded with radio-labeled BSA. Following subcutaneous implantation in rats, diffusion from the device provided prolonged levels of BSA in the blood. Such a nonmechanical device offers important advantages in drug delivery applications, including zero-order release and high loading capacity. D 2004 Elsevier B.V. All rights reserved. Keywords: Nanochannels; Nanopore membranes; Silicon membranes; Microfabrication 1. Introduction Fick’s laws of diffusion are usually adequate to describe the kinetics of solutes from a region of higher concentration to a region of lower concentration through a thin, semipermeable membrane. As the size of the membrane pores approaches that of the solute, however, unexpected effects can occur, which cause substantial deviations from the kinetics predicted by Fick’s laws. The diffusion of molecules in micro- porous media such as zeolites has led to experimental evidence of such unusual phenomena as molecular traffic control and single file diffusion (SFD; [1–6]). Theoretical treatments and simulations suggest that, in 0168-3659/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.jconrel.2004.09.024 * Corresponding author. E-mail address: fmartin@imeddinc.com (F. Martin). Journal of Controlled Release 102 (2005) 123 – 133 www.elsevier.com/locate/jconrel