The detection of small molecule analytes (SMAs) is of great significance for food and drug testing, environmental monitoring, and disease diagnosis. However, the performance of commercially available SMA immunoassays is limited by their low sensitivity and specificity due to the competitive format, leaving significant room for improvement. In recent years, the application of noncompetitive immunoassays for the detection of SMAs has become a hot topic, especially with the rapid evolution of antibody development technology. The remarkable development and application of anti-immune complex (anti-IC) reagents targeting antigen-specific antibodies have garnered significant interest from researchers and diagnostic companies, particularly in the field of SMA detection. The discovery and development history of anti-IC antibodies, the advantages and limitations of different anti-IC reagent preparation methods, and the mechanisms of interaction between ICs and anti-IC antibodies are reviewed. A comprehensive overview of the application of anti-IC antibodies in SMAs assay, including pesticide residue detection, mycotoxin detection, and clinical testing, as well as current challenges and potential solutions in noncompetitive immunoassays, is also summarized to provide a reference for the rapid and accurate detection of SMAs.
© 2024 The Authors. Published by American Chemical Society.