The next generation of proteomic nanochips in biomarker discovery

As a potential source of diagnostic biomarkers for diseases at their early stage, the low-molecular weight (LMW) region of the blood proteome has gained increased interest recently. However, the presence of highly abundant proteins and the large dynamic range of serum/plasma proteins ultimately limit the sensitivity of the detection of low abundant species. In this study, we present a novel size-exclusion strategy based on nanoporous silica chips for the efficient removal of the high molecular weight proteins and for the specific isolation and enrichment of LMW species present in biological complex. We applied the Nanoporous Silica Chip Technology at the analysis of complex proteomic samples such as human serum and developed proteomic nanochips with different nanophase characteristics to specifically target the low molecular weight species present in the human circulating peptidome. Harvested peptides were analysed by MALDI-TOF and profiles consisting of more than 300 peaks in the range 800-20,000 m/z were generated. Tunable pore sizes, pore structure and surface chemistries were used as integrated "processors" for the recovery of LMW peptides and proteins. This approach will help in the selection of individualized therapeutic combinations that target the entire cancer-specific protein network, in the real-time assessment of therapeutic efficacy and toxicity, and in the rational modulation of therapy based on changes in the cancer protein network associated with prognosis and drug resistance.