Titanium Micromachining Process Advancements for Optical Tissue Clearing
Optical Clearing Agents (OCAs) increase the transmittance of light through tissues, which represents a key step toward laser-based medical diagnostics and treatments. The stratum corneum is the key limitation to the transport of topically-applied OCA through the skin. While a bolus, subdermal injection overcomes the stratum corneum barrier, it can result in scarring and necrosis of the tissue; signifying a need for alternative drug delivery methods. One such alternative is the microneedle array, which can bypass the stratum corneum and overcome the low profusion of OCA by direct and evenly distributed injection into the tissue.
Current materials being used to fabricate microneedles, such as silicon, are non-ideal for intradermal drug delivery due to their non-optimal material properties. Titanium is a promising surrogate material in this regard, due to its excellent biocompatibility and fracture toughness. The recent development of Titanium Deep Reactive Ion Etching (TiDRIE) has enabled the fabrication of small-scale, titanium-based biomedical devices. However, this micromachining technique was developed for anisotropic deep etching, which limits microdevice design and complexity, but provides opportunity for improvements in sidewall profile control.
Herein, we explore two key objectives to the overall aim of increasing OCA efficacy through microneedle arrays. First, injection of OCA via a hypodermic needle array device is demonstrated to increase clearing efficacy in excised tissue in a proof-of-concept study. Next, multidimensional features were realized through the development and integration of profile control methods in TiDRIE that ultimately enabled the fabrication of the first dry etched out-of-plane bulk titanium microneedles.