An interdigitated electrode biosensor platform for rapid HLA-B*15:02 genotyping for prevention of drug hypersensitivity

Prevention of life threatening hypersensitivity reactions to carbamazepine is possible through pre-treatment screening of the associated HLA-B*15:02 risk allele. However, clinical implementation of screening is hindered by the high cost and slow turnaround of conventional HLA typing methods. We have developed an interdigitated electrode (IDE) biosensor platform utilizing loop mediated isothermal amplification (LAMP) that can rapidly detect the HLA-B*15:02 allele. DNA amplification is followed by solid-phase hybridization of LAMP amplicons to a DNA probe immobilized on the IDE sensor surface, resulting in a change in sensor impedance. The testing platform does not require DNA extraction or post-amplification staining, achieving sample-to-answer in 1 h and 20 min. The platform was tested on 27 whole blood samples (14 HLA-B*15:02 positive and 13 negative) with sensitivity of 92.9% and specificity of 84.6% when applying a cutoff of impedance change. Based on these characters the LAMP-IDE platform has potential to be further developed into point-of-care use to help overcome barriers in HLA-B*15:02 screening.