Validation and quality control of protein microarray-based analytical methods

The microarray has emerged as an important format for simultaneous analysis of tens of thousands of substances present in a sample. Successful adaptation of microarray assays to clinical diagnostics will require particular attention to issues of quality control and quality assurance. Results of an assay can be compromised by a number of preanalytical factors including the quality of the reagents (e.g., the microarray and the detection reagents) and the integrity of the sample. Similarly, numerous factors in the analytical phase of a microarray assay, including changes in the reaction conditions and calibration, can contribute to inaccuracy and imprecision. Furthermore, a microarray combines many reagents or samples in a single device and therefore presents additional issues not usually encountered in discrete testing of a single analyte in a single sample. Various strategies (e.g., replicate analysis, array orientation control features, on-array controls, normalization) have been implemented to control and assess analytical factors that might compromise data generated from a microarray. The current range of measures taken to ensure the analytical accuracy and quality of data generated from protein microarrays is reviewed in the context of the lessons learned from DNA microarrays. The special considerations for protein microarrays as they transition from research into routine clinical analysis and the resulting quality control of clinical test results generated using such devices are discussed.