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Research Theme: Lipid Bilayers as Nano-Bio Interfaces

Lipid bilayers are a versatile model system for investigating the biochemistry of cell membranes, as well as a platform for biosensors, pharmaceutical screens and drug delivery. One widely-used configuration is a two-dimensional, planar bilayer, formed on solid or polymeric substrates and decorated with a wide-array of membrane-interacting biomolecules. We are interested in the development of novel techniques to manipulate and characterize such lipid bilayers both in vitro and in vivo through the use of nanofabricated features.

We have recently reported a new method for forming patterned lipid bilayers on solid substrates. In bubble collapse deposition (BCD), an air bubble is first "inked" with a monolayer of phospholipid molecules and then touched to the surface of a thermally oxidized silicon wafer and the air is slowly withdrawn. As the bubble shrinks, the lipid monolayer pressure increases. Once the monolayer exceeds the collapse pressure, it folds back on itself, depositing a stable lipid bilayer on the surface. These bilayer disks have lateral diffusion coefficients consistent with high quality supported bilayers. By sequentially depositing bilayers in overlapping areas, fluid connections between bilayers of different compositions are formed. Performing vesicle rupture on the open substrate surrounding this bilayer patch results in a fluid but spatially isolated bilayer. Very little intermixing was observed between the vesicle rupture and bubble-deposited bilayers.

We have also developed a novel system for chip-based drug delivery using small liquid volumes as a tool to studying cellular signaling processes. This hybrid system leverages the advantages of semiconductor nanofabrication with the sealing properties of lipid bilayers. The inorganic component of these devices is an array of pyramidal cavities connected to the surface of the silicon substrate by sub-micron pores. The cavities are loaded with a solution of interest and then sealed by occluding the pore with a lipid bilayer. The stability of these seals was found to depend strongly on pore size and, with pore diameters below 200nm, the seals were able to reliably retain dye in solution for a period of over four weeks at room temperature without vibration isolation. When desired, the seals could be rapidly opened by pulsed illumination with a standard microscope light. This release can be localized to a subset of the devices on a given substrate, opening one set of reservoirs while leaving those only tens of microns away unaffected. This system represents a simple, self-contained, biocompatible drug delivery system that affords the temporal and spatial resolution necessary to permit new work in the study of cellular and sub-cellular signaling processes.

Related Publications

Formation and Characterization of Fluid Lipid Bilayers on Alumina.
Morgan D. Mager, Benjamin Almquist and Nicholas A. Melosh. Langmuir. 24(22), 12734 (2008)

Lipid Bilayer Deposition and Patterning via Air Bubble Collapse.
Morgan D. Mager and Nicholas A. Melosh. Langmuir. 23(18), 9369 (2007)