Fabrication of Silicon Microneedles for Dermal Interstitial Fluid Extraction in Human Subjects

The goal of this project is to design and develop a fabrication process for silicon microneedle arrays to extract dermal interstitial fluid (ISF) from human skin. ISF is a cell- free, living tissue medium that is known to contain many of the same, clinical biomarkers of general health, stress response and immune status as in blood. However, a significant barrier to adoption of ISF as a diagnostic matrix is the lack of a rapid, minimally invasive method of access and collection for analysis. Microfabricated chips containing arrays of microneedles that can rapidly and painlessly access and collect dermal ISF for bioassay could greatly facilitate point-of-care diagnosis and health monitoring, especially in times of crisis or in austere environments, where drawing venous blood poses an unnecessary infection or biohazard risk. Two different fabrication methods were explored. The first method borrows from a previously reported dicing saw process, where a series of parallel and perpendicular cuts of partial depth are made into a thicker silicon wafer, creating arrays of square columns, which are subsequently sharpened into needles. The second method uses a new, entirely-DRIE process to create the arrays of columns. The columns are sharpened into needles using an isotropic wet etch method (HNA etch) which preferentially enhances etching at the tips and diminishes etching at the base, creating remarkably sharp, conical shaped needles capable of piercing skin. The needles contain holes that pass through the wafer to the opposite side, where they connect to a series of microfluidic channels that lead to a reservoir. The back of the wafer is bonded to glass, providing a hydrophilic cap to the channels, as well as a way to see into the device to detect whether the channels are filling with liquid. The fabrication procedures for both methods are presented, along with 2D- and 3D-rendered schematics for the final devices. Needle geometric shape is crucial to their ability to extract ISF. To determine the appropriate pre-sharpened etched shape, needle columns with a variety of different shapes were designed, produced, sharpened, and examined under a scanning electron microscope. The most promising shapes were selected for further processing and testing. Resulting chips were first bench tested to ensure capillary filling capability, and then tested for ISF collection from human skin. Microneedle arrays which were successfully demonstrated to extract ISF are presented, and the unsuccessful shapes are also shown in the interest of completion. Potential means for improving performance and future research directions are discussed