Three-stage full-wave simulation architecture for in-depth analysis of microspheres in microscopy.

Over a decade, considerable development has been achieved in microsphere microscopy; the popularity of this method is attributable to its compatibility with biomedical applications. Although microscopy has been used extensively, insufficient analyses and simulation approaches capable of explaining the experimental observations have hampered its theoretical development. In this paper, a three-stage full-wave simulation architecture has been presented for the in-depth analysis of the imaging properties of microspheres. This simulation architecture consists of forward and backward propagation mechanisms, following the concept of geometric optics and strictly complying to wave optics at each stage. Three numerical simulation methods, including FDTD, NTFF, and ASPW, are integrated into this simulation architecture to encompass near-field and far-field behaviors and relieve the computational burden. We validated this architecture by comparing our simulation results with the experimental data provided in literature. The results confirmed that the proposed architecture exhibits high consistency both qualitatively and quantitatively. By using this architecture, we demonstrated the near-field effect of the samples on the resolution and provided evidence to explain the conflicts in literature. Moreover, the flexibility and versatility of the proposed architecture in modeling allow adaptation to various scenarios in microsphere microscopy. The results of this study, as an imaging analysis and system design platform, may facilitate the development of microsphere microscopy for biomedical imaging, wafer inspection, and other potential applications.