Until recently, the identification of proteins in a tissue or a protein lysate has been limited by the availability of antibodies that recognise certain regions (epitopes) of a protein of interest. Antibodies have been and continue to be an important component of the armamentarium for protein research but they are not without limitations. While antibody arrays overcome the restriction to only one protein, ECM proteins tend to be under-represented in arrays. The main issues of antibody-based protein quantification, however, remain the same: (i) Usually only a small portion of the protein (epitope) is recognised by an antibody. Protein detection by antibodies relies on the presence of unmodified epitopes. In ECM proteins, however, common PTMs include hydroxylation, glycosylation or fragmentation. Due to epitope masking, ECM proteins may not be detectable by antibodies. (ii) Antibodies are often not commercially developed to target proteins in species beyond the commonly used mice and rats such as canine and porcine models for myocardial infarction,2,45,46 rabbit and goat models for studies involving atrial fibrillation9,47–49 and sheep as models of dilated cardiomyopathy.50 While some anti-human or anti-mouse antibodies will cross-react, many others will not recognize their target protein in different species or will display a high degree of non-specific binding. Vice versa, proteins in the bovine serum supplements of cell cultures can be detected not only in the conditioned media but also in the cell lysates.51