E.I. Ozalp, S. Kim, V. Sundar, J-G Zhu, J.A. Weldon
Carnegie Mellon University,
Keywords: block copolymer, nanoporous membrane, drug delivery, simulation, nanofabrication
Summary:Nanoporous membranes have been recognized as promising candidates for drug delivery applications due to their small pore size and high surface-to-volume ratio1. The ultimate goal of smart drug delivery systems is to release a specific drug to a targeted location in the body at an externally controllable rate. However, in most nanoporous membrane drug delivery devices the drug delivery rate is controlled by diffusion through the nanopores, which is governed by the dimensions of the nanopore2,3. Since a majority of drug molecules have a net charge, applied electric fields could potentially allow for controlled diffusion4. Electrical control is possible when the size of the pore becomes comparable to the thickness of the electrical double layer. In this case, the electrical potential of the double layer extends significantly into the channel thereby controlling charged molecular diffusion inside of the nanochannel through electrostatic repulsion and attraction5. Consequently, a conductive nanoporous membrane structure with a thin insulating layer would effectively allow electrical gating thus enabling control of the diffusion of charged molecules through the nanochannel. In our previous work, we modeled the effect of membrane potential on the diffusion of charged molecules through silicon/silica nanochannels. We demonstrated through simulation that cylindrical nanochannel structures with chemically treated surfaces have the ability to control the diffusive transport with a small applied DC gate voltage6. If the diameter of the nanochannel gets too small (less than 5 nm), single file diffusion behavior occurs limiting the overall diffusion rate. Conversely, channel diameters larger than 100 nm require an unrealistically high control voltage. Our simulations showed that 20nm diameter nanochannels enable electrical gating with a low DC gate voltage. Hence, this work reports on the fabrication of an intrinsically conductive nanoporous membrane with adequate size of nanopores with high pore density (1011 pores per cm2) using self-assembling block copolymers. The nanochannels are ~ 25 nm in diameter and 50 nm in length, which is comparable to previous simulation condition. The nanochannels were fabricated into an amorphous silicon thin film sheathed by 2 nm of native oxide in order to enable gating. Poly (styrene-b-dimethyl siloxane) block copolymer was first used to generate a highly dense array of pillars; the pattern was then reversed and subsequently transferred into the amorphous silicon thin film. To predict the controllability of the fabricated nanoporous membrane structure, we analyzed gated molecular diffusion through simulation in nanochannels between two chambers with asymmetric concentrations of charged drug molecule. The modeled drug molecules are INFα-2b and leuprolide, which has -2 and +1 net formal charge. The gated nanochannel structures were modeled in the finite element software (COMSOL Multiphysics). The simulation results indicate that a fabricated membrane can alter the diffusion rate by many orders of magnitude under certain conditions with a ±1 volt gate voltage.