Triple signal biosensing platform for ultrasensitive and wide-range detection of HLA gene targets

Hyperthyroidism, a multifaceted endocrine disorder, is strongly associated with specific human leukocyte antigen (HLA) alleles, which also play a critical role in drug-induced complications such as agranulocytosis. Conventional HLA genotyping methods often face limitations in simultaneously achieving high accuracy, rapidity, and operational simplicity. To address these challenges, we developed a multimodal biosensing platform for the highly sensitive detection of alleles. This platform synergistically integrates three modalities. After molecular recognition, Electrochemiluminescence resonance energy transfer (ECL-RET) was employed using nanomaterials to generate ECL signals, Hybridization chain reaction (HCR) was incorporated to produce fluorescence signals, while nanozyme-mediated colorimetric reactions were coupled to generate visual signals. The combination of these strategies ensures exceptional sensitivity, specificity, and assay stability. Furthermore, spatial separation of the recognition and signal generation domains was implemented to minimize matrix interference from complex biological samples, significantly enhancing clinical applicability. This innovative approach establishes a novel paradigm for the precise analysis of HLA alleles, offering transformative potential for clinical diagnostics and advancing the frontiers of biosensing technologies.