Silane-Coupling Impelled Metal Oxide-MXene Proximity: An Electrochemical Probe for Tracking Enteral Histaminosis In Vitro

Allergic reactions trigger the release of histamine (HA) by immune cells when the body encounters allergens, such as pollen, dust, or certain foods. Besides its role in immune responses, HA also functions as a neurotransmitter released by neurons in the brain. The enzyme diamine oxidase (DAO) is mainly responsible for breaking down HA and deficiency in DAO can lead to histamine intolerance, known as enteral histaminosis, where the inability to metabolize histamine results in its accumulation, potentially causing allergic reactions, anaphylaxis, vertigo, Tourette syndrome, and other issues. To address this, there is a growing need for point-of-care (PoC) detection technologies capable of fast, accurate, and sensitive on-site HA detection. In this study, we developed a sensor by integrating Nb₂CT_x MXene with tungsten trioxide (WO₃) using silane linkage by 3-aminopropyl triethoxysilane (APTES), resulting in WO₃-APTES-Nb₂CT_x composite which was used as the electrode modifier on a flexible carbon yarn (CY) electrode. The density functional theory (DFT) analysis was employed to investigate the interaction of HA with WO₃-APTES-Nb₂CT_x and Nb₂CT_x and electron transport sites, providing a deeper understanding of the sensing mechanism. The sensing capability of the developed sensor was evaluated electrochemically, and the sensor demonstrated exceptional performance, including an ultralow detection limit of 432.4 pM with a broad detection range between 1 nM and 100 nM, as well as high selectivity for HA over other interfering molecules. The sensor performance is tested with human serum, sweat, and cerebrospinal fluid, highlighting its relevance for both physiological and clinical use. Moreover, the sensor successfully detected HA released from subcultured SH-SY5Y neuronal cells. Lastly, we developed a prototype named "HistoTrack" by repurposing a used pregnancy test kit into a disposable electrochemical sensor for on-site HA detection, paving a new way for plastic waste repurposing. This innovative, highly sensitive, and selective sensor marks a significant advancement in inflammation monitoring and offers great potential for broader medical and research applications.