MINI-REVIEW Proteomic-based biomarker discovery for development of next generation diagnostics Akbar Khalilpour 1,2 & Tugba Kilic 1,2,3,4 & Saba Khalilpour 5 & Mario Moisés Álvarez 1,2 & Iman K. Yazdi 1,2,6 Received: 1 September 2016 /Revised: 22 November 2016 /Accepted: 25 November 2016 # Springer-Verlag Berlin Heidelberg 2016 Abstract In the post-genome age, proteomics is receiving significant attention because they provide an invaluable source of biological structures and functions at the protein level. The search for disease-specific biomarkers for diagnos- tic and/or therapeutic applications is one of the areas that pro- teomics is having a significant impact. Thus, the identification of a Bgood^ biomarker enables a more accurate early diagno- sis and prognosis of disease. Rapid advancements in mass spectrometry (MS) instrumentation, liquid chromatography MS (LCMS), protein microarray technology, and other protein profiling methodologies have a substantial expansion of our toolbox to identify disease-specific protein and peptide bio- markers. This review covers a selection of widely used prote- omic technologies for biomarker discovery. In addition, we describe the most commonly used approaches for diagnosis based on proteomic biomarkers and further discuss trends and critical challenges during development of cost-effective rapid diagnostic tests and microfluidic diagnostic systems based on proteomic biomarkers. Keywords Biomarker discovery . Proteomic . Diagnostic kits . Microfluidic systems Introduction Proteomics is one of the most potent methods in biomedical research, which enables identification and comprehensive char- acterization of cellular targets and understanding the mecha- nisms of actions for therapeutic agents and the main functional constituents of biochemical schemes, specifically proteins (Bhalla et al. 2010). Mining genomes and mapping proteomes, the protein complements to genomes in cell and tissue, are being applied to develop and evaluate novel protein targets. They have been fully explored to discover the mechanisms of action of compounds and to identify novel markers for diag- nostic and clinical uses (Veenstra and Smith 2003). Proteins expressed within a recognized proteome can be used to assess significant alterations in levels of biomarkers and their expres- sions in various pathological conditions. Proteomic profiling is expected to provide much needed insight into disease mecha- nisms and to bring forward therapeutic targeting candidates (Reisdorph et al. 2009; Seillier-Moiseiwitsch et al. 2002). The principal aim of current proteomics is to identify and character- ize potential biomarkers by addressing two aspects: functional and expression proteomics. Functional proteomics deals with characterization of proteins in organelles and complexes, while the latter deals with measuring protein-level fluctuations under given conditions or parameters. Indeed, expression proteomics can serve as a powerful tool to identify changes in protein * Akbar Khalilpour akhalilpour@bwh.harvard.edu 1 Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women’ s Hospital, Harvard Medical School, 65 Landsdowne Street, Rm. 265, Cambridge, MA 02139, USA 2 Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA 3 Department of Biomedical Engineering, Faculty of Engineering and Architecture, Izmir Katip Celebi University, 35620 Izmir, Turkey 4 Department of Biotechnology, Institute of Science, Ege University, 35100 Izmir, Turkey 5 Department of Pharmacological and Biomolecular Sciences (DiSFeB), Università degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy 6 Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02139, USA Appl Microbiol Biotechnol DOI 10.1007/s00253-016-8029-z