2026 Theses Doctoral

Microneedle-Mediated Intracochlear and Intraocular Access for Precision Delivery and Diagnostics

Zhou, Chaoqun

Hearing loss is the most common sensory impairment in humans, and inner ear disorders are a major cause, leading to symptoms such as tinnitus, vertigo, and imbalance. The inner ear, which contains the cochlea, is embedded deep within the petrous portion of the temporal bone—one of the hardest bones in the body—making it difficult to access. Achieving safe, reliable, and precise access to the cochlea remains a longstanding challenge for both therapeutic delivery and diagnostic sampling. Conventional approaches, such as intravenous and intratympanic injections, are limited by the blood–cochlea barrier and by variable transport across the round window membrane (RWM), the only non-osseous portal connecting the middle ear to the inner ear. Direct intracochlear access offers improved precision but requires controlled perforation of the delicate RWM without causing structural damage or hearing loss.

In our research group, we have developed a suite of ultra-sharp microneedles using two-photon polymerization (2PP) lithography. These microneedles enable controlled perforation of the RWM and allow injection or aspiration of microliter-scale fluid volumes to and from the inner ear without measurable audiological or functional consequences.

In this thesis, I present advancements that further enable microneedle-mediated intracochlear delivery and diagnosis. To expand the range of materials and reduce microneedle dimensions, a pyrolysis protocol was developed to convert polymeric microneedles into high-carbon structures with enhanced mechanical properties. The potential of microneedle-based approaches for diagnosing endolymphatic hydrops was also demonstrated. In addition, an optimized dual-lumen microneedle was developed to enable simultaneous injection and aspiration, thereby minimizing pressure-induced damage during larger-volume delivery. A three-dimensional computational model was implemented to optimize lumen positioning and reduce aspiration of the injected substance. Experimental studies in vivo in guinea pig models were conducted to validate delivery performance and quantify percentage of aspirated injected substance. Furthermore, the application of 2PP-fabricated microneedles was extended beyond the inner ear to the eye, where microneedles were developed for retinal vessel cannulation and targeted ocular injections.