The present invention integrates the surface plasmon resonance and common-path phase-shift interferometry techniques to develop a microscope for measuring the two-dimensional spatial phase variation caused by biomolecular interactions on a sensing chip without the need for additional labeling. The common-path phase-shift interferometry technique has the advantage of long-term stability, even when subjected to external disturbances. Hence, the developed microscope meets the requirements of the real-time kinetic studies involved in biomolecular interaction analysis. The surface plasmon resonance microscope of the present invention using common-path phase-shift interferometry demonstrates a detection limit of 2x10<SUP>-7 </SUP>refractive index change, a long-term phase stability of 2.5x10<SUP>-4</SUP>pi rms over four hours, and a spatial phase resolution of 10<SUP>-3 </SUP>pi with a lateral resolution of 100 mum.
Surface plasmon resonance microscope using common-path phase-shift interferometry