UC Davis

This thesis covers systemic nanomanufacturing efforts aimed at fabricating nano- and micro-structures containing lipids. In Chapter 3, a novel method for the controlled assembly of lipids is presented. The controlled assembly method utilizes an Atomic Force Microscopy (AFM)-based microfluidics system and relies on ultrafast evaporation rate and spatial confinement by the sub-femtoliter droplets. This enables the formation of lipid structures that deviate from the near-equilibrium state, such as ordered bilayers. In Chapter 4, AFM in conjunction with microfluidics delivery was utilized to produce three-dimensional (3D) lipid structures following a custom design. A variety of lipid 3D structures were successfully printed, including nanometer-thick disks, long linear spherical caps, three-layered stacking grids, and organizational chiral structures. Our high-resolution structural characterization reveals the spatial precision of the 3D nanoprinting in nanometers over the range of 0.5 mm. These results collectively demonstrate the promising potential of our designed technology and methodology for producing 3D structures ranging from the nanometer to continuum scale. In Chapter 5, the feasibility of one important application is demonstrated, i.e., the rehydration of the lipid constructs to form liposomes. While the thin film rehydration method has traditionally been used for liposome production, it typically requires post-rehydration handling for size and location selection. In contrast, this thesis work reports “in-situ” liposome production through the rehydration of lipid nanostructures, with demonstrated size control by varying the size of the lipid constructs. This investigation of the thesis work explores and demonstrates the possibility of programmable synthesis of biomimetic systems, including lipid bilayers, lipid nanoconstructs, and liposomes, all of which hold significant potential in material science, biomedical technology, and fundamental bio-research.