Nanoporous silica chip technology for the early detection of diseases and the real time assessment of therapeutic efficacy
E. Tasciotti, X. Liu, A. Boumrani, T. Hu, L. Li, C. Chiappini, M. Ferrari
Univeristy of Texas Health Science Center - Houston, US
Keywords: porous silica, proteomics, proteome, low molecular weight, peptide, biomarker, early detection
Abstract:There is an intense interest in developing new biomarkers for diagnosis. The low-molecular weight (LMW) region of the blood proteome is an important source of diagnostic markers to be identified by matrix-assisted laser desorption (MALDI) mass spectrometry. In serum analysis, the interference of abundant proteins, limit the sensitivity of the MALDI detection of LMW biomarkers. We developed a size-exclusion strategy based on nanoporous silica chips (NSC) for the isolation of LMW species from complex biological mixtures. In the NSC, pore sizes and surface chemistries act as “processors” for the isolation of LMW species. We demonstrated the correlation between pore size and molecular cut-off. Reproducibility, sensitivity and protein profiles were assessed in relation to the physical and chemical properties of the NSC. We analyzed human serum with NSCs and developed chips to specifically target regions of the human LMW peptidome. Peptides harvested from serum were subjected to MALDI analysis and profiles consisting of more than 300 peaks in the range 800-20 000 m/z were generated. We envision that screenings based on our nanoporous silica chip technology might serve serve as a complement to histopathology, molecular imaging and other state of the art diagnostic techniques helping in the selection of individualized therapeutic.