Fundamentals of protein separations: 50 years of nanotechnology, and growing

The separation of proteins in biology samples has long been recognized as an important and daunting endeavor that continues to have enormous impact on human health. Today's technology for protein separations has its origins in the early nanotechnology of the 1950s and 1960s, and the methods include immunoassays and other affinity extractions, electrophoresis, and chromatography. What is different today is the need to resolve and identify many low-abundance proteins within complex biological matrices. Multidimensional separations are the rule, high speed is needed, and the separations must be able to work with mass spectrometry for protein identification. Hybrid approaches that combine disparate separation tools (including recognition, electrophoresis, and chromatography) take advantage of the fact that no single class of separation can resolve the proteins in a biological matrix. Protein separations represent a developing area technologically, and understanding the principles of protein separations from a molecular and nanoscale viewpoint will enable today's researchers to invent tomorrow's technology.