Chemistry of Biotin-Streptavidin and the Growing Concern of an Emerging Biotin Interference in Clinical Immunoassays

Abstract

Overconsumption of biotin (5-100 mg daily) as a supplement by the general population poses a significant problem for clinical immunoassays (IAs) based on biotin-streptavidin (SA) interactions. This affinity pair has been exploited in immunoassays because of its avidity, sensitivity, specificity, and stability. The elevated biotin level in plasma varies from patient to patient, and its severe interference cannot easily be predicted and quantified. Thus, immunoassay manufacturers must investigate the biotin interference in the developed immunoassays to satisfy the threshold of 3510 ng/mL (14367 nM), as stipulated by the FDA. There is no concrete solution to circumvent the biotin interference without extra costs and technical difficulties, albeit different strategies have been attempted. They include the IA format with biotinylated reagents prebound to streptavidin, the removal of biotin from the specimen, sample treatment, and biotin interference-free assays. The general public has been instructed to stop taking biotin supplements for 48 h or even weeks before the test, depending on the specific test, dose, and frequency of biotin uptake. As lab-based techniques cannot accommodate an enormous number of public samples, a rapid analytical procedure for biotin is urgently needed to quantify for its interference in immunoassays.