Titanium MEMS Technology Development for Drug Delivery and Microfluidic Applications

Doctor of Philosophy, Graduate Program in Mechanical Engineering
University of California, Riverside
Dr. Masaru P. Rao, Chairperson

The use of  microelectromechanical systems (MEMS)  technology in medical  and biological applications  has  Increased  dramatically  in the  past  decade  due to  the potential  for enhanced sensitivity,  functionality, and performance associated with the miniaturization of devices, as well as the market potential for low-cost, personalized medicine. However, the utility of such devices in clinical medicine is ultimately limited due to factors associated with prevailing micromachined materials such as silicon, which poses concerns of safety and reliability due to its intrinsically brittle properties,  making it prone to  catastrophic failure. Recent advances in titanium  (Ti)  micromachining provides  opportunity to create  devices with enhanced  safety due to its proven biocompatibility  and high  fracture  toughness, which  causes it to fail  by means  of graceful,  plasticity-based deformation.

Motivated by this  opportunity, we discuss  our efforts to advance  Ti MEMS technology through  the development of titanium-based microneedles (MNs) that seek to provide a safer, simpler, and more efficacious means of ocular drug delivery. We show that devices with in-plane geometry and
through-thickness fenestrations that serve as drug reservoirs for  passive delivery via  diffusive transport from fast-dissolving  coatings can be fabricated utilizing Ti DRIE. Our mechanical testing and finite element analysis results suggest that these devices possess  sufficient  stiffness reliable  corneal  insertion. MN  coating studies show  that fenestrated devices can increase drug carrying capacity by 5-fold, relative to solid MNs of identical shank geometry. Furthermore, using an ex vivo porcine cornea model, we  demonstration  that  through-etched  fenestrations  can  provide  a  protective  cavity  for  increasing delivering efficiency. Collectively, these results demonstrate the potential embodied in developing Ti MNs for effective, minimally invasive, and low-cost ocular drug delivery.

Additionally, we report the development of an anodic bonding  process that allows,  for the first time, high-strength joining of bulk Ti and glass substrates at the wafer-scale, without need for interlayers or adhesives. We demonstrate that uniform, full-wafer bonding can be achieved at temperatures as low as 250°C and that failure during burst pressure testing occurs via crack propagation through the glass, rather than the Ti/glass interface, thus demonstrating the robustness of the bonding. Moreover, using optimized  bonding  conditions,  we  demonstrate  the  fabrication  of  rudimentary  Ti/glass-based microfluidic  devices  at  the  wafer-scale,  and  their  leak-free  operation  under    pressure-driven  flow. Finally, we also  demonstrate the  monolithic integration of  nanoporous titanium dioxide within such devices, thus illustrating the promise embodied in Ti anodic bonding for future realization of robust  microfluidic  devices for  photocatalysis applications.  Together, these results demonstrate the potential embodied in utilizing Ti MEMS technology for the fabrication of novel drug delivery and microfluidic systems with enhanced robustness, safety, and performance.