Structural Studies of DNA–Cationic Lipid Complexes Confined in Lithographically Patterned Microchannel Arrays

We have used lithographically patterned microchannel arrays with channel widths ranging from 1 to 20 um, fabricated using electron beam lithography and reactive ion etching, in structural studies of DNA-cationic lipid complexes in confinement. Various techniques have been developed for loading these DNAmembrane complexes into the microchannels or to form the complexes in situ by sequentially depositing DNA and lipid solutions into the microchannels. Optical microscopy studies indicate that such complex formation is strongly influenced by the periodic channel structure even at channel widths much larger than the persistent length of the DNA molecules. Preliminary x-ray diffraction experiments conducted at Stanford Synchrotron Radiation Laboratory (SSRL) yielded only a weak signal from the lipid bilayers in the complexes. The use of a microfocused x-ray beam produced by the newly developed Bragg-Fresnel optics at a third-generation synchrotron facility may dramatically increase the signal-to-noise ratio and allow observation of orientational as well as positional ordering of DNA molecules induced by the microchannels. Structural control of the DNA-membrane complexes has a broad range of potential applications in gene probe technology and as mesoscopic biomolecular composites.