Such interactions could, otherwise, mislead the signal interpretation. Low cell density is also expected to minimize the appearance of TM0 waveguide mode which would significantly increase the complexity of the system under study. The second main objective of this study was to rigorously compare cell-induced signals for cSPR and LRSPR. This is of interest since LRSPR structures possess larger penetration depths, therefore the sensing electromagnetic fields can reach deeper into the cellular medium. Penetration depths for cSPR structures are of the order of 100–200 nm, whereas those of LRSPR are typically 500–1000 nm. On the other hand, cSPR has better angular sensitivity than LRSPR with respect to bulk refractive index changes. However, it has been recently reported that, in the case of bacterial detection, LRSPR is more sensitive than cSPR. To achieve a better understanding of the structureactivity relationship, a theoretical and experimental comparison of these two types of sensors is therefore provided in this study. Bridging this important knowledge gap will ultimately foster the application of SPR in the studies of microorganisms. This study has been carried out in order to improve the understanding of the effects of cells on plasmonic signal in SPR biosensing and ultimately towards achieving a detailed structureactivity relationship. The first aim was to assess the validity of simple models that have been used previously in the literature for related optical sensing schemes. For SPR configuration when Lprop is of the same dimension as that of the cell lateral size, the averaged-intensity model was found to provide a reasonably good prediction of SPR signals, taking in consideration some deviations in Rmin parameter. On the other hand, when Lprop is much larger than the cell dimensions the model needed is based on the fact that an effective RI is sensed by the plasmonic waves. The effective-RI model could describe the angular shifting experimentally measured in the calibration scheme although it did not describe accurately the spreading of cells of the sensors. The difference between the two schemes was attributed to the importance of the cell membrane configuration and its apparent weight in the EM sensing fields, thereby bringing the focus on the issue of penetration depth in addition to the propagation length in the studied systems. However, even when the angular shifting was correctly described, this model did not provided an accurate description of the parameters Rmin of the spectra, which can be related to scattering loss in the system. Indeed, the main Remdesivir source of discrepancy between the data and the models is thought to originate from the scattering losses of the plasmonic waves encountering scatterers.