An integrated spectro-microscopic system for multimodality imaging on a sample includes a reflected differential interference contrast (RDIC) microscope, a Raman spectroscope optically coupled with the RDIC microscope and a total internal reflection fluorescence/scattering (TIRF/TIRS) microscope optically coupled with the RDIC microscope such that the integrated spectro-microscopic system is capable of simultaneously acquiring both the RDIC images, the Raman spectra and TIRF/TIRS images on the same sample.