The delivery of therapeutic, detection and imaging agents for the diagnosis and treatment of cancer patients has improved dramatically over the years with the development of nano-carriers such as liposomes, micelles, dendrimers, biomolecules, polymer particles, and colloidal precipitates. While many of these carriers have been used with great success <i>in vitro</i> and <i>in vivo</i>, each suffers from serious drawbacks with regard to stability, flexibility, or functionality. To date, there has been no general particle fabrication method available that afforded rigorous control over particle size, shape, composition, cargo and chemical structure. By utilizing the method we has designed referred to as <b>P</b>article <b>R</b>eplication <b>I</b>n <b>N</b>on-wetting <b>T</b>emplates, or <b>PRINT</b>, we can fabricate monodisperse particles with simultaneous control over structure (<i>i.e.</i> shape, size, composition) and function (<i>i.e.</i> cargo, surface structure). Unlike other particle fabrication techniques, <b>PRINT</b> is delicate and general enough to be compatible with a variety of important next-generation cancer therapeutic, detection and imaging agents, including various cargos (e.g. DNA, proteins, chemotherapy drugs, biosensor dyes, radio-markers, contrast agents), targeting ligands (e.g. antibodies, cell targeting peptides) and functional matrix materials (e.g. bioabsorbable polymers or stimuli responsive matrices). <b>PRINT</b> makes this possible by utilizing low-surface energy, chemically resistant fluoropolymers as molding materials and patterned substrates to produce functional, harvestable, monodisperse polymeric particles.
The fabrication of nanometer size structures and complex devices for microelectronics is of increasing importance so as to meet the challenges of large-scale commercial applications. Soft lithography typically employs elastomeric polydimethylsiloxane (PDMS) molds to replicate micro- and nanoscale features. However, the difficulties of PDMS for nanoscale fabrication include inherent incompatibility with organic liquids and the production of a residual scum or flash layer that link features where the nano-structures meet the substrate. An emerging technologically advanced technique known as Pattern Replication in Non-wetting Templates (PRINT) avoids both of these dilemmas by utilizing photocurable perfluorinated polyether (PFPE) rather than PDMS as the elastomeric molding material. PFPE is a liquid at room temperature that exhibits low modulus and high gas permeability when cured. The highly fluorinated PFPE material allows for resistance to swelling by organic liquids and very low surface energies, thereby preventing flash layer formation and ease of separation of PFPE molds from the substrates. These enhanced characteristics enable easy removal of the stamp from the molded material, thereby minimizing damage to the nanoscale features. Herein we describe that PRINT can be operated in two different modes depending on whether the objects to be molded are to be removed and harvested (i.e. to make shape specific organic particles) or whether scum free objects are desired which are adhered onto the substrate (i.e. for scum free pattern generation using imprint lithography). The former can be achieved using a non-reactive, low surface energy substrate (PRINT: Particle Replication in Non-wetting Templates) and the latter can be achieved using a reactive, low surface energy substrate (PRINT: Pattern Replication in Non-wetting Templates). We show that the PRINT technology can been used to fabricate nano-particle arrays covalently bound to a glass substrate with no scum layer. The nanometer size arrays were fabricated using a PFPE mold and a self-assembled monolayer (SAM) fluorinated glass substrate that was also functionalized with free-radically reactive SAM methacrylate moieties. The molded polymeric materials were covalently bound to the glass substrate through thermal curing with the methacrylate groups to permit three dimensional array fabrication. The low surface energies of the PFPE mold and fluorinated glass substrate allowed for no flash layer formation, permitting well resolved structures.
We describe the use of multifunctional perfluoropolyethers as enabling materials in imprint lithography and metrology. Perfluoropolyethers (PFPEs) are a unique class of fluoropolymers that are liquids at room temperature that can be functionalized and cured to form transparent "PTFE-like" elastomers. These materials posses many favorable attributes relative to imprint lithography and other soft lithographic techniques including: chemical resistance, flexibility, incredibly low surface energies, high gas permeability, and UV transparency. Molds made from PFPE materials exhibit the favorable properties of both rigid and soft materials in that they are rapidly made and disposable, yet maintain the chemical resistance and performance of rigid materials such as quartz. We have previously demonstrated the use of such materials in patterning 70nm features with a precision of +/-1 nm. Herein, we further demonstrate the capability of these materials in the rapid patterning of dual damascene structures and other patterns. The chemical resistance of PFPE-based materials allows for the patterning of a variety of organic resins including etch resists, low-k dielectrics, and conducting polymers. Additionally, we demonstrate the utility of functional PFPEs in a novel metrology method. In this simple technique, the liquid PFPE precursor is poured onto a wafer with a given pattern and cured. When released from the wafer, the cured film possesses an exact negative replica of the original pattern. A variety of metrology and inspection methods can then be performed on the patterned, transparent film including microscopy and through-film optics which can reveal defects in the original pattern. Furthermore, the method is shown to be completely non-destructive to the original patterned wafer. We describe the use of this method in the metrology and inspection of a dual damascene pattern containing features which are difficult to characterize by other techniques.
Photocurable, liquid perfluoropolyethers (PFPEs) are ideal materials for high resolution (<100 nm) pattern transfer and imprint lithographic processes. PFPEs possess attributes of both elastomers and rigid materials, exhibit a remarkably low surface energy, mold extremely small features with high fidelity (minimal shrinkage), resist swelling by most organics, endure repetitive molding procedures, and out-perform routinely-used polydimethylsiloxane when replicating sub-micron sized features. We report nanoscale replicas of substrates, and the use of these replicas as molds, having features as small as 70 nm with no apparent loss of resolution.