Fabrication of molecularly imprinted nanoparticle based quartz crystal microbalance (QCM) sensors for angiotensi̇n-II detection from human serum

Angiotensin II (AngII) is a significant effector peptide of the renin-angiotensin system (RAAS) that serves as a growth factor, regulating cellular growth, fibrosis, and apoptosis. AngII plays a critical role in the pathophysiology of several diseases and disorders, including hypertension, cardiovascular diseases, and infections such as influenza and SARS-CoV-2. It is also being explored for its potential role in tumor progression. However, the spontaneous detection of AngII remains challenging due to its low physiological concentration, instability, and the complex nature of biological fluids. Molecular imprinting is a technique that enables the preparation of highly selective synthetic receptors that mimics the natural recognition sites for the molecule of interest. In this study, molecularly imprinted polymers (MIPs) were synthesized in nanoparticle form (~50 nm) and employed as recognition elements in quartz crystal microbalance (QCM) sensor chips for the selective detection of AngII. Following the synthesis and characterization of AngII-imprinted (AngII-MIP) and non-imprinted (NIP) nanoparticles, QCM-based sensors (AngII-MICqcm and NICqcm) were fabricated and used in kinetic binding studies. The AngII-MICqcm sensor demonstrated high sensitivity, with the ability to detect AngII at concentrations as low as 0.25 pg/mL. Selectivity tests using Angiotensin I (AngI) and vasopressin (Vasp) as competing molecules revealed selectivity ratios of 6.09 and 7.44 in favor of AngII, respectively. The calculated imprinting factor (IF) values were 5.58 for AngII, 3.67 for AngI, and 4.50 for Vasp, confirming the superior selectivity of the MIP-based sensor. Upon reusability test, it was found that after the 10th cycle, the QCM chip retained about 96% of its AngII adsorption capacity. Human serum samples were used in studies to detect AngII using the AngII-MICqcm chip. Even in this complex environment, the instrument was able to detect incredibly minute amounts of AngII (1 pg/mL).