Electrically Gated Nanoporous Membranes for Smart Drug Delivery and Biomedical Devices

Advances in nanofabrication techniques have allowed producing fluidic channels of sub-100nm dimensions with a multitude of potential applications for biosensing, on-chip analytics, and drug delivery. The high surface to volume ratio of the nanoscale fluidic channel makes interfacial effects significant. The electrical double layer (EDL) is a charge distribution at the liquid-solid interface caused by the fixed surface charges and compensating counter-ions. When the dimension of the fluidic channel is comparable to the EDL thickness, known as the Debye length, an overlap of EDL is generated in the nanochannel. In the overlap of EDL, there exists an enrichment of counter-ions and the exclusion of co-ions that are caused by electrostatic interactions. This phenomenon is called the exclusion-enrichment effect and can be leveraged for new applications.
This thesis presents a novel conductive nanoporous membrane platform that is based on the electrical control of the diffusive transport of charged molecules through gated nanopores by altering the EDL with external gate voltage. An applied gate voltage controls the potential in the nanochannel. Molecules with the same charge as the channel potential are excluded from the nanochannel due to electrostatic repulsion, whereas molecules with opposite charge are enriched due to electrostatic attraction. Therefore, the diffusive flow of the charged molecules can be controlled by a single gate voltage without the need for high driving voltage. A thin insulating layer is needed to prevent current leakage.
A computational model (based on the Poisson-Nernst-Plank equation) of the single gated nanochannel was established to quantitatively predict the field-effect gating of the charged molecule transport through the nanochannel. We expected that the cylindrical nanochannel with a gate-insulator structure can alter the flux of the charged molecule through the nanochannel. Also, we investigated the effect of the surface charge plays a significant role.
Based on the results of the simulation, we developed a novel conductive nanoporous membrane and achieved electrical control and high flow at the same time. We sputter-deposited chromium (Cr) – gold (Au) – chromium (Cr) on top of the commercial anodic aluminum oxide nanoporous membrane. The exterior chromium layer was left to oxidize creating the insulation layer for the gate electrode. This membrane could regulate the diffusive transport of the timolol maleate (positively charged at pH 7.4) and the ethacrynic acid (negatively charged at pH 7.4) by applying a single DC gate voltage without the need for any other mechanism. The +2V gate voltage increased the transport rate of the ethacrynic acid, which is negatively charged at pH 7.4, by 337% and the -2V gate voltage decreased the transport rate by 48%. The transport rate of the timolol maleate, which is positively charged in pH 7.4, was decreased by 66% with +2V gate voltage and increased by 116% with -2V gate voltage. The effect of the surface charge of the AAO backbone structure on the controllability was also investigated. The removal of the surface charge increased the controllability of positively charged drug molecule and decreased the controllability of negatively charged drug molecule.
The novel conductive nanoporous membrane was utilized for the nanofluidic diode application. The charge polarities and densities of the nanopores can be regulated externally by the gate potential to change the ionic current rectification property of the device using chromium (Cr) conductive layer deposited directly on an AAO membrane. We developed the novel double gated nanoporous membrane structure for a biomimetic AND nanofluidic logic gate. The voltage-gated cation channel protein achieved precise control of the direction of the transmission by using two stacked gate structure in one channel protein. We modeled and tested the stacked gate structure with our conductive nanoporous membrane. This stacked structure is shown to act as an AND gate for charged molecule transport.
In-depth analysis of the gated diffusion between two chambers indicates that a conductive nanofluidic membrane has the potential for low power, electrically gated devices for implantable smart drug delivery applications such as the treatment of ocular diseases including glaucoma.