Band 3 which is the one of the most abundant membrane protein in red blood cell membrane. It is bound to the spectrin network via other proteins such as ankyrin, 4.1 or junctional complex. In addition to that literature suggests the presence of different sub populations of band 3. The spectrin mesh leads to the hexagonal compartments in red blood cell membrane. The arrangement of this skeleton network affects the stability and the size of the compartments. We discovered that spectrin compartment size and the band3 diffusion vary from normal to disease patient''s blood such as HbSS (Sickle cell anemia), HbSC (Sickle hemoglobin C disease), HbSBo (Sickle cell zero-beta-thalasamia), HbSB+ (Sickle cell beta-plus-thalasamia), HS (Hereditary Spherocytosis), and HPP (Hereditary Pyropoikilocytosis). HbSS has comparatively smaller compartment size and slow diffusion coefficient than normal blood cells. We have been able to show that by Single particle tracking (SPT) studies, which is investigated by video-enhanced TIR microscopy with 8ms temporal resolution, by labeling the band 3 with DIDS-Biotin linker bound to streptavidin Q-dots.