Thus, a protocol based on chip treatment with HF in order to create secondary amine groups selectively onto silicon nitride was applied (Banuls et al., 2010). The biofunctionalized probes were immersed for 10 min in human serum sample and then for 5 min in goat anti-human IgG Fc specific antibody solution. Using a humanized rat antibody against SARS-CoV-2 RBD, a detection limit of 20 ng/mL was determined. Analysis of human serum samples indicated that the proposed sensor discriminated completely non-infected/non-vaccinated from vaccinated individuals, and the antibodies levels determined correlated well with those determined in the same samples by ELISA. These results demonstrated the potential of the proposed sensor to serve as an efficient tool for expeditious point-of-care testing. Keywords:Immersible sensor, Silicon nitride waveguides, Broad-band Mach-Zehnder interferometry, Label-free Amlodipine detection, SARS-CoV-2 antibody == Amlodipine Graphical abstract == == 1. Introduction == During the past two decades, the progress in micro/nano-fabrication techniques and in-depth understanding of photonic circuits has allowed the development of optical biosensing modules based on silicon Wisp1 substrates. These sensing modules Amlodipine take advantage of the fact that silicon-based photonic integrated circuits can be manufactured at high volume and relatively-low cost while there is possibility to fabricate multiple sensors on a single chip (Luan et al., 2018;Shakoor et al., 2019). In addition, the high refractive index contrast between silicon and silicon dioxide/silicon nitride or other surrounding media, facilitates light coupling and light guiding in curved waveguides thus enabling the label-free sensing of affinity interactions between an analyte and a receptor molecule in real-time with high detection sensitivity (Luan et al., 2018;Shakoor et al., 2019). Nonetheless, despite the impressive progress, very few of the existing silicon photonic integrated circuits have managed to escape laboratory settings and evolve to commercially available instruments which, however, are benchtop instruments not suitable for point-of-need Amlodipine applications. The main reason is that silicon inherently does not emit light and there is always the need to find a way to couple light in and out of the photonic chips. Thus, even though the chips themselves are miniaturized and compact, their driving and readout system requirements render their use in everyday life more or less impractical. The emergence of the COVID-19 pandemic revealed once more the need for point-of-care systems with high clinical sensitivity and specificity and minimal intervention from the user for detection of the virus or antibodies against it in biological samples (Mattioli et al., 2020). The latter application is very important in seroprevalence studies, which examine the SARS-CoV-2 infection spread in a community (Amanat et al., Amlodipine 2020;Eckerle and Meyer, 2020;Fotis et al., 2021;Jalkanen et al., 2021a), as well as the vaccination efficiency (Jalkanen et al., 2021b) and our understanding of the immunity progress over time (Okba et al., 2020). In this context, several approaches of serological testing based on lateral flow immunoassay (LFIA) or biosensors have been exploited for the point-of-care detection of total antibodies against SARS-CoV-2 in human serum. LFIAs are suitable for fast point-of-care as well as self-diagnostic tests due to their ease of use and short analysis time (Feng et al., 2020;Liu et al., 2020,2021;Roda et al., 2021;Wang et al., 2020;Wen et al., 2020). However, in most cases, they provide mainly qualitative results with sensitivity and specificity lower than those obtained by laboratory-based immunochemical methods (Lisboa Bastos et al., 2020). Biosensors on the other hand, could provide high detection sensitivity complimented by short turn-around times and ease-of-use (Antiochia, 2021). So far, several biosensing principles have been exploited for the detection of antibodies against SARS-CoV-2 in human serum, most of which are relying on optical (Cady et al., 2021;Dzimianski et al., 2020;Funari et al., 2020;Shaw et al., 2020;Steiner et al., 2020) or electrochemical transducers (Ali et al., 2020;Rashed et al., 2021;Torrente-Rodrguez et al., 2020;Yakoh et al., 2021). Regarding the SARS-CoV-2 protein used for detection of serum antibodies, most sensors rely on spike glycoprotein.