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Micromachined needles have been shown to successfully transport biological molecules into the body with minimal invasiveness and pain, following the insertion of needles into the skin. The aim of this research is to demonstrate that micromachined hollow polymer needle arrays fabricated using UV lithography into micromolds, a potential batch-manufacturable process, can exhibit comparable insertion and injection performance to conventional hypodermic needles for drug delivery into skin. A dual-exposure-and-single-development process flow is proposed for the above-mentioned UV lithography into micromolds approach to construct a pyramidal-tip hollow microneedle array with an integral baseplate and fluidic manifold. The developed process ultimately resulted in the ability to fabricate a 10×10 array of hollow SU-8 microneedles measuring 825 μm in height, 400 μm in width, and possessing a lumen of 120 μm in diameter. The tip diameter of the microneedles ranges from 15 μm to 25 μm. The insertion force of single needles characterized using excised porcine skin as a substrate is 2.4±1.2 N. Nevertheless, the high insertion force of 2.4 N per needle may cause a significant concern when a large number of needles are required to insert into skin for drug delivery. Conventional hypodermic needles have two key structural characteristics: a sharp beveled tip and a large side-terminated lumen. Integration of these two key characteristics of hypodermic needles into microneedle design can potentially enhance microneedle performance. To reduce the insertion force and to incorporate the two key characteristics of hypodermic needles into the design of microneedles, a new needle tip design, namely the hypodermic-needle-like design, is presented. A 6×6 array of hypodermic-needle-like microneedles of 1 mm in height, approximate 350 μm in width, and with a lumen of 150 μm in diameter is demonstrated with successful insertion of the needle array into skin and an 85% lumen openness yield. The insertion force is significantly reduced by an order of magnitude with the new needle tip design and is 0.275±0.113 N per needle, comparable to that of hypodermic needles, i.e., 0.284±0.059 N. The hypodermic-needle-like microneedles exhibit a margin of safety of 180 for successful needle insertion into skin prior to needle fracture. A successful manual fluid injection into skin using single microneedle is demonstrated. The micromachined hypodermic-needle-like polymer needle arrays presented in this dissertation are fabricated using UV lithography into micromolds, a potentially batch-manufacturable process, and exhibit comparable insertion performance to conventional hypodermic needles. Injection capability into skin is also demonstrated with a hypodermic-needle-like microneedle, illustrating the utility of these devices.

Thesis (Ph. D.)--University of Texas at Austin, 2006. / Vita. Includes bibliographical references.

Thesis (M.S.)--Rochester Institute of Technology, 1988. / Typescript. Includes bibliographical references (leaves 94-95).

Thesis (Ph. D.)--University of Texas at Austin, 2005. / Supervisor: Chih-Kang Ken Shih. Vita. Includes bibliographical references.

Thesis (M. S.)--Mechanical Engineering, Georgia Institute of Technology, 2007. / King, William Paul, Committee Chair ; Henderson, Clifford L, Committee Co-Chair ; Gall, Ken, Committee Member.

A novel approach to microfabrication based on stereolithography was presented. This fabrication process is referred to as, ‘Exposure Controlled Projection Lithography’ (ECPL). In the ECPL process, incident radiation, patterned by a dynamic mask, passes through a transparent substrate to cure photopolymer resin. By controlling the amount of exposure, the height field of the cured film can be controlled. An ECPL system was designed and assembled. Factors affecting the accuracy of the ECPL process in fabricating micron shaped features were identified and studied. A real-time in-situ photopolymerization monitoring system was designed and assembled within the ECPL system to identify the sources of variations present in the system. Parts are fabricated from the ECPL process because of polymerization (or cross-linking) of monomer resin using light energy. Photopolymerization is a complex process involving coupling between several phenomena. This process was modeled by utilizing an understanding of the known polymerization reaction kinetics with incorporating the effects of oxygen inhibition and diffusion. A material response model and a simulation tool to estimate the shape of a cured part resulting from photopolymerization was created. This model was used to formulate a process-planning method to estimate the manufacturing process inputs required to cure a part of desired shape and dimensions. The process planning method was validated through simulations and experiments.

Over the last decades, integrated circuits have changed our everyday lives in a number of ways. Many common devices today taken for granted would not have been possible without this industrial revolution. Central to the manufacturing of integrated circuits is the photomask used to expose the wafers. Additionally, such photomasks are also used for manufacturing of flat screen displays. Microlithography, the manufacturing technique of such photomasks, requires complex electronics equipment that excels in both speed and fidelity. Manufacture of such equipment requires competence in virtually all engineering disciplines, where the conversion of geometry into pixels is but one of these. Nevertheless, this single step in the photomask drawing process has a major impact on the throughput and quality of a photomask writer. Current high-end semiconductor writers from Micronic use a cluster of Field-Programmable Gate Array circuits (FPGA). FPGAs have for many years been able to replace Application Specific Integrated Circuits due to their flexibility and low initial development cost. For parallel computation, an FPGA can achieve throughput not possible with microprocessors alone. Nevertheless, high-performance FPGAs are expensive devices, and upgrading from one generation to the next often requires a major redesign. During the last decade, the computer games industry has taken the lead in parallel computation with graphics card for 3D gaming. While essentially being designed to render 3D polygons and lacking the flexibility of an FPGA, graphics cards have nevertheless started to rival FPGAs as the main workhorse of many parallel computing applications. This thesis covers an investigation on utilizing graphics cards for the task of rendering geometry into photomask patterns. It describes different strategies that were tried and the throughput and fidelity achieved with them, along with the problems encountered. It also describes the development of a suitable evaluation framework that was critical to the process.

<p>During the past two decades, soft lithographic techniques that circumvent the limitations of photolithography have emerged as important tools for the transfer of patterns with sub-micron dimensions. Among these techniques, microcontact printing (uCP) has shown special promise. In uCP, an elastomeric stamp is first inked with surface-reactive molecules and placed in contact with an ink-reactive surface, resulting in pattern transfer in the form of self-assembled monolayers in regions of conformal contact. The resolution in uCP is ultimately limited to the diffusion of ink and the elastomechanical properties of the bulk stamping material. </p> <p>One way to improve resolution is to eliminate diffusion by using inkless methods for pattern transfer. Inkless catalytic-uCP uses a chemical reaction between a stamp-immobilized catalyst and surface bearing cognate substrate to transfer pattern in the areas of conformal contact. By using pre-assembled cognate surfaces, the approach extends the range of surfaces readily amenable to patterning while obviating diffusive resolution limits imposed by traditional uCP. </p> <p>In this thesis, we report two methods using inkless catalytic uCP: biocatalytic-uCP utilizes an immobilized enzyme as a catalyst whereas catalytic-uCP utilizes an immobilized small molecule as a catalyst, such as an acid or base. Both catalytic techniques demonstrate pattern transfer at the microscale while using unconventional, acrylate-based stamp materials. Previous results produced with catalytic-uCP have shown pattern transfer with sub-50 nm edge resolution. In this demonstration of catalytic-uCP, we use the technique to demonstrate a bi-layered patterning technique for H-terminated silicon, the foremost material in semi-conductor fabrication. This technique simultaneously protects the underlying silicon surface from degradation while a highly-reactive organic overlayer remains patternable by acidic-functionalized PU stamps. Lines bearing widths as small as 150 nm were reproduced on the reactive SAM overlayer, which would not be possible without circumvention of diffusion. Before and after patterning, no oxidation of the underlying silicon was observed, preserving desired electronic properties throughout the whole process. This bi-patterning technique could be extended to other technologically-relevant surfaces for further application in organic-based electronic devices and other related technologies.</p> / Dissertation

Nanotechnology has a steadily increasing impact on worldwide research and business activities. This work explores advanced micro/nano patterning approaches for molecular manipulation. The objectives are to (1) build a proper bridge from a few microns to the 100-10 nm range and below as well as to (2) combine “top-down” precise design with the “bottom-up” size scale to create designed surfaces, areas and volumes that can interact with molecules in a designed way. Three studies were designed and studied accordingly. The first investigation demonstrates that “top-down” Inclined Nanoimprinting Lithography (INIL) is able to produce three-dimensional (3-D) nanopatterns of varying heights in a single step. INIL reduces pattern's feature size from microns to nanometers. The degree of resulting nanopattern's asymmetry can be controlled by the magnitude of the inclination angle. Various 3-D nanostructures are successfully demonstrated including nanolines, nanocircles and nanosquares. The underlying INIL mechanism is investigated, which is primarily due to the induced shear force when the inclination angle is not zero. This leads to the anisotropic dewetting of polymer fluid and consequently asymmetric 3D nanopatterns of varying heights. INIL removes the need of preparation of expensive 3D nanotemplates or multiple template-to-substrate alignments. In addition, such 3-D structures are successfully transferred to silicon, silicone rubber and metal gold. INIL enables 3D nano-scale devices including angle-resolved photonic and plasmonic crystals. The second investigation demonstrates the success of “bottom-up” molecular imprinting of X-ray contrast agent iodixanol in polymer matrix. The synthetic tailor-made molecularly imprinted polymers (MIPs) are poly(4-vinylpyridine-co-ethylene glycol dimethacrylate) which possess specific binding sites induced by the template molecules of X-ray contrast agent iodixanol. It leads the feature size reduction from macromolecules to molecular scale. The properly imprinted binding sites also leads MIPs to have improved absorption capacity and efficiency for X-ray contrast agent iodixanol relative to non-imprinted polymers. The best binding capacity achieved from the optimized MIPs was 284 mg/g in aqueous solution, 8.8 times higher than that of the non-imprinted polymers. The best binding capacity obtained in sheep plasma was 232 mg/g, 4.5 times higher than the non-imprinted polymers. The factors that may affect the binding performance of MIPs in aqueous media are studied. The optimized MIPs are encouraging for biomedical implementations including dialysis and nanosensors. The third investigation of nanolithography-based molecular manipulation (NMM) explores a hybrid approach by combining “top-down” electron-beam lithography (EBL) with “bottom-up” surface initiated polymerization (SIP). It reduces the nanopattern's feature size to sub-10 nm and simultaneously tunes its surface chemistry through functional polymer brushes. The process has reduced process complexity and cost. The demonstrated prototype molecular manipulation templates have 3D surface nanostructures with sub-10 nm feature size and anisotropic surface functionalities. They mimic biocatalyst enzymes to “bottom-up” assemble nanoparticle targets at specific locations producing 3D nanostructures in a designated way. Various 3D synthetic nanostructures have been demonstrated including polystyrene “nanomushrooms” “nanospikes”, “nanofibers” and polystyrene-iron oxide “nanoflowers”. Potential applications of these synthetic 3D nanostructures can be improved therapeutic agents. This hybrid strategy realizes the integration of “top-down” design with “bottom-up” molecular scale to create designed nanopatterned surfaces that can interact with molecules in a designated way.