Protein chips based on recombinant antibody fragments: A highly sensitive approach as detected by mass spectrometry

With the human genome in a first sequence draft and several other genomes b eing finished this year, the existing information gap between genomics and proteomics is becoming increasingly evident. The analysis of the proteome i s, however, much more complicated because the synthesis and structural requ irements of functional proteins are different from the easily handled oligo nucleotides for which a first analytical breakthrough already has come in t he use of DNA chips. In comparison with the DNA microarrays, the protein ar rays, or protein chips, offer the distinct possibility of developing a rapi d global analysis of the entire proteome. Thus, the concept of comparing pr oteomic maps of healthy and diseased cells may allow us to understand cell signaling and metabolic pathways and will form a novel base for pharmaceuti cal companies to develop future therapeutics much more rapidly. This report demonstrates the possibilities of designing protein chips based on special ly constructed, small recombinant antibody fragments using nanostructure su rfaces with biocompatible characteristics, resulting in sensitive detection in the 600-amol range. The assay readout allows the determination of singl e or multiple antigen-antibody interactions. Mass identity of the antigens, currently with a resolution of 8000, enables the detection of structural m odifications of single proteins.