The discovery and utility of new methods based on different materials and chemical derivatisations for protein profiling of complex analytes is an ongoing field. This study includes the development, optimisation, validation and the application of a method based on the combined characteristics of physisorption and chemisorption of nano crystalline diamond (NCD) surfaces for serum profiling. Due to the expanded nano-structure, the numbers of potential binding sites are dramatically increased. For immobilised metal ion affinity chromatography (IMAC), diamond coated surfaces were derivatised with glycidyl methacrylate (GMA) under ultraviolet (UV) light at different wavelengths followed by further derivatisation with iminodiacetic acid (IDA) and loading with copper ions. This special kind of MALDI/TOF-MS, was termed as MELDI/TOF-MS (Material enhanced laser desorption ionization time of flight mass spectrometry), as it is based on various materials e.g. diamond, cellulose, silica and poly (glycidyl methacrylate/divinylbenzene). The diversity in the physical characteristics of these derivatised materials is responsible to get improved sensitivity, specificity, capacity and broad range of information. Human serum samples were assayed through MELDI/TOF-MS analysis to validate the capability, capacity, efficiency and reproducibility of the nano-structured diamond surfaces for protein profiling. Also the method was employed to search for the differences in human body fluids e.g. sera of different origin through matrix assisted laser desorption ionisation time of flight mass spectrometry (MALDI/TOF-MS).