Imaging the cell membrane with surface plasmon resonance phase microscopy

Molecular interactions occurring on or near cell membrane surfaces are expected to have different properties from those occurring in bulk solutions. In order to analyze molecular interactions between the cell membrane with biomolecules having no additional fluorescence labeling, a microscope based on the integration of surface plasmon resonance (SPR) and common-path phase-shift interferometry (PSI) techniques is developed and used to study the cell adhesion and migration on the biosurfaces. The surface plasmons are excited by light via the attenuated total reflection method. The common-path PSI technique has features of long-term stability, even when subjected to external disturbances. Hence, the developed SPR phase microscope meets the requirements of real-time kinetic imaging. The proposed common-path SPR-PSI microscope demonstrates a detection limit of 2x10(-7) refractive index unit and a long-term phase stability of 2.5x10(-4) pi root mean square over four hours. The developed microscope is successfully applied to the real-time observation the live cell membranes with thrombomodulin proteins.