Minimally Invasive and in Situ Capacitive Sensing of Cardiac Troponin I from Interstitial Fluid

Abstract

Current diagnostic approaches for myocardial infarction (MI) rely on blood-based cardiac biomarker analysis by centralized instruments, often delaying timely clinical decisions. We present a microneedle-based capacitive biosensor (MiCaP) for in situ minimally invasive monitoring of cardiac troponin I (cTnI) in interstitial fluid (ISF) for point-of-care (POC) applications. MiCaP is a label-free biosensor operating based on nonfaradaic sensing by monitoring electric double layer capacitance at the microneedle-ISF interface. We extracted a simplified equivalent circuit model for MiCaP inserted into the skin, confirming that the measured capacitance variations originate from cTnI binding to surface-immobilized antibodies. MiCaP was fabricated by using a scalable process and functionalized with anti-cTnI antibodies. In vitro measurements showed a dynamic detection range of 10 pg/mL to 10 ng/mL, a limit of detection (LOD) of 3.27 pg/mL, and a total assay response time of less than 15 min. A spike-and-recovery test using cTnI-spiked human serum yielded a recovery accuracy exceeding 93%. In vivo studies in rats demonstrated ISF cTnI levels of 3 +/- 0.4 pg/mL in controls and 912 +/- 683 pg/mL in experimental animals, indicating an increasing trend consistent with serum concentrations measured using a clinical immunoassay. These results support the potential of MiCaP as a minimally invasive biosensing platform for cardiac biomarker monitoring, with possible extension to multiplexed ISF-based diagnostics in the POC.