The SARS-CoV-2 coronavirus caused a pandemic three years ago, and although society became used to the virus, scientists never stopped investigating its interactions with the human body. The development and application of vaccines against this virus helped to control the unwanted reactions caused by Covid-19 disease. As new variants of the SARS-CoV-2 spike protein emerge, it is necessary to find ways to faster virus detection so new outbreaks can be avoided. Biological immunosensors can selectively and effectively detect various antigens or antibodies. Development of immunosensors that are sensitive to the SARS-CoV-2 spike protein could make monitoring of virus spread easier and fatal consequences could be avoided. The SARS-CoV-2 spike protein is one of the main proteins of the virus. The spike protein binds to the ACE2 receptor found on the human cells and triggers further spread of the virus in the body [1]. The immune system must react fast and synthesize specific antibodies to block the spike protein. To get better understanding of immune complex formation different SARS-CoV2 spike protein variants were chosen for our research and interactions with specific antibodies were investigated.
One of the methods used in this investigation was total internal reflection ellipsometry (TIRE). TIRE is an optical method which can be applied to thin layer optical properties' research. During the experiment, changes in the phase $ \Delta $ and the amplitude $ \Psi $ of light wave are measured and the index of refraction and dielectric constant of the material can be calculated. TIRE can be applied to the monitoring as it is very sensitive, non-destructive and label-free method, so biomolecules such as proteins do not lose their structure and activity [2].
Quartz crystal microbalance with dissipation (QCM-D) is a piezoelectric method using which the changes in frequency and dissipation are measured during real time biomolecules layer formation. QCM-D is a noninvasive, label-free method that can be used for measurements in liquids.
The combination of QCM-D with spectroscopic ellipsometry (SE) was applied to study SARS-CoV-2 coronavirus spike proteins and specific antibodies interactions. TIRE was used to find the most effective immobilization conditions for different spike proteins (wild, $ \alpha $ and $ \beta $ variants). SARS-CoV-2 spike proteins' interaction with specific antibodies were researched by QCM-D and SE methods combination and thermodynamical parameters of immune complex formation were calculated.