Hollow microneedle-based sampling and sensing of dermal interstitial fluid

Microneedle-based biosensing platforms have emerged as a promising alternative for blood-based health monitoring devices. Microneedles (MNs) can access the dermal interstitial fluid (ISF) in a painless and blood-free manner, enabling the detection of a wide range of biomarkers. Although in-skin biomarker monitoring using functionalized solid MNs remains attractive due to the challenging task of ISF sampling, there is growing attention toward the integration of biosensors into ISF sampling platforms. ISF sampling can be followed by measuring the biomarker level using the integrated biosensors. Recently, microfluidic-based biosensing devices have been incorporated with hollow MNs (HMNs) to enable the detection of target biomarkers in the collected dermal ISF. In this thesis, we report the development of HMN-based platforms integrated with microfluidic ISF collection chambers to provide the necessary contact between the sampled ISF and biosensors. Chapter one establishes a concise overview of recent advancements in the manufacturing of various HMNs and their integration into diverse biosensing devices. In chapter two, we demonstrate the integration of laser-drilled HMNs with a touch-activated vacuum source to enable continuous sampling of ISF with subsequent electrochemical sensing of glucose and pH levels. The wearable vacuum system leverages the self-recovery feature of the utilized elastomer to create the necessary negative pressure for ISF sampling. The developed touch-activated system shows ISF extraction rate of approximately 17 μL h-1 in vivo. We demonstrate the capacity of the developed platform in continuous health monitoring by measuring the glucose and pH levels in animal models. Chapter three presents our efforts in developing a hydrophilic 3D-printed HMN-based platform for measuring the pH and urea levels in the collected ISF using colorimetric techniques. Multichannel MNs are fabricated using high-precision projection micro stereolithography technology, followed by deposition of an oxide layer using plasma enhanced chemical vapor deposition (PECVD) to enhance the wettability of MNs for effective ISF collection. The oxide layer results in a significant decrease in water contact angle of the 3D-printed films from about 72° to 9°, rendering them superhydrophilic. The enhanced wettability of the surfaces leads to an improved liquid uptake capability of the MNs from agarose hydrogel and rat skin samples. We demonstrate the applicability of the developed approach by ex vivo colorimetric sensing of pH and urea. Overall, the devices developed offer promising advancements in technology and exhibit great promise for enhancing biomedical sensing and diagnostic applications.