Candidate: Hanjia Zheng
Date: December 8, 2026
Time: 1:00 PM
Location: Online
Supervisor: Mahla Poudineh
All are welcome!
Abstract:
Transdermal biosensing that interrogates skin interstitial fluid (ISF) for biomarker detection has great potential to advance healthcare, as ISF contains a diverse range of biomarkers relevant to physiological processes and disease progression and can support continuous monitoring. However, the development of continuous transdermal biosensing platforms has been hindered by challenges in sustained ISF sampling. Compared with conventional ISF sampling methods, microneedles (MNs) offer a simple, biocompatible, and minimally invasive platform for accessing ISF. Existing continuous biosensing platforms have often used solid or hollow MNs with sensing elements incorporated on or within the needles. By contrast, hydrogel microneedles (HMNs) facilitate rapid and sustained ISF sampling and support comfortable wear over prolonged periods. In this thesis, HMNs fabricated from methacrylated hyaluronic acid (MeHA) serves as a platform for ISF sampling and are integrated with different sensing approaches in wearable devices to detect biomarkers ranging from small molecules and nucleic acids to proteins.
The initial stage established a disposable, fluorescence-based platform for reagentless detection of a wide range of small molecules and proteins by immobilizing aptamers within the HMN matrix. This work demonstrated three capabilities of MeHA HMNs: rapid ISF collection, sufficient target diffusion, and simple chemical functionalization for the immobilization of biorecognition elements. The next stage introduced the Wearable Aptalyzer, an electrochemical aptamer-based (EAB) sensing platform that integrates HMNs with aptamer-functionalized sensing chips. Aptamers labeled with redox reporters translate target binding into electrical signals, enabling continuous monitoring of small metabolites. The platform tracked increases and decreases in glucose concentration and monitored lactate continuously for three days in live rats, establishing the HMN–chip interface as a practical foundation for continuous biomarker sensing. Building on this architecture, the Wearable Aptalyzer was extended to the Differential Aptalyzer, an HMN-based platform that integrates antibodies and aptamers for continuous protein monitoring. The mixed assay combines antibody-mediated target recognition with aptamer-based electrochemical readout. The sensing chip contains a baseline electrode that provides a reference for differential measurements and a test electrode that measures target-induced signal changes. Repeated pulse application regenerates the antibody capture interface for subsequent measurements. Together, these features support the tracking of changes in protein concentration. The Differential Aptalyzer has been validated for human cardiac troponin I detection and evaluated in a mouse model of coronary artery disease.
Together, these studies demonstrate the versatility of HMNs as an ISF sampling platform that can be integrated with different sensing approaches. The progression from single-use, fluorescence-based detection of small molecules, proteins, and miRNAs to continuous electrochemical monitoring of metabolites and the development of regenerable protein assays illustrates how different recognition and readout strategies can be incorporated into HMN systems.