Protein microchips in biomedicine and biomarker discovery.

Protein microarray technology is of high recent interest, especially for generating confirmatory and complementary information for transcriptomic studies. In this paper, the advantages, technical limitations, main application fields, and some early results of protein microarrays are reviewed. Today protein microchip technology is mostly available in the form of printed glass slides, bioaffinity surfaces, and tissue microarray (TMA)-based techniques. The advantages of glass slide-based microchips are the simplicity of their application and their relatively low cost. Affinity surface-based protein chip techniques are applicable to minute amounts of starting material (< 1 microg), but interrogation of these chips requires expensive instrumentation, such as mass spectrometers. TMAs are useful for parallel testing of antibody specificities on a broad range of histological specimens in a single slide. Protein microarrays have been successfully implemented for serum tumor marker profiling, cell physiology studies, and mRNA expression study verification. Some of the bottlenecks of the technology are protein instability, problems with nonspecific interactions, and the lack of amplification techniques to generate sufficient amounts of the lower abundance proteins. In spite of the current difficulties, protein microchips are envisioned to be available for routine biomedical and diagnostic applications provided that the ongoing technological developments are successful in improving sensitivity, specificity, and reducing costs.