Non-faradaic sensing of cardiac biomarkers from interstitial fluid using microneedle arrays

In recent years, microneedle-based biosensors have emerged as a promising technology for continuous and minimally invasive health monitoring. Various sensing methods, including electrochemical and optical approaches have been successfully integrated into these platforms. However, the integration of non-faradaic sensing methods into microneedle platforms remains limited. Non-faradaic sensing detects analyte-induced changes in interfacial capacitance without charge-transfer reactions, making it well-suited for developing label-free biosensors for cardiovascular health, where early and accurate biomarker detection is essential. To address this gap, this thesis presents a novel microneedle-based interdigitated electrode biosensor employing non-faradaic capacitive sensing principles to quantify cTnI directly from interstitial fluid (ISF). Fabrication of the microneedle capacitive patch was carried out using a reproducible process, followed by functionalization of the surface with anti-cTnI antibodies. The analytical output is expressed as the normalized capacitance change (%∆C/C), which improves the consistency of sensor responses. By relying on the intrinsic electrical double layer (EDL) phenomenon at the electrode–electrolyte interface, the sensor demonstrated effective detection capabilities validated through in vitro and in vivo characterization. The sensor exhibits a limit of detection of 3.27 pg/mL, and a total assay response time of less than 15 minutes. Also, to address the system integration challenges in wearable and implantable biosensors, the microneedle sensor is successfully integrated with a passive antenna enabling wireless and continuous monitoring. Furthermore, since the proposed platform operates in ISF, it is inherently affected by variations in its composition, both between individuals and within the same individual over time. Given that such fluctuations in ionic strength can influence both interfacial capacitance and overall sensor performance, a calibration correction method is introduced. This approach incorporates the effect of medium ionic resistivity on EDL capacitance changes through real time impedance measurement, thereby enhancing the robustness and reliability of biomarker quantification under diverse physiological conditions. The effectiveness of the proposed model in improving the accuracy of cTnI detection with the microneedle sensor was assessed through spike-and-recovery experiments. Collectively, this work advances the field of minimally invasive biosensing by offering an integrated, non-faradaic, microneedle-based solution with enhanced physiological adaptability and accuracy for the monitoring of cardiac biomarkers.