Aggregation-Induced Emission Luminogen-Based Dual-Mode Enzyme-Linked Immunosorbent Assay for Ultrasensitive Detection of Cancer Biomarkers in a Broad Concentration Range

The enzyme-linked immunosorbent assay (ELISA) is one of the most commonly used methods for measuring antibodies and antigens in biological samples. However, developing new ELISAs with high detection sensitivity and broad detection dynamic ranges without resorting to complicated signal processing and equipment setups remains a challenge. In this work, we report a strategy to simultaneously improve the detection sensitivity and broaden the dynamic range by replacing the chromogenic reagents used in traditional ELISAs with an aggregation-induced emission luminogen (AIEgen). The developed AIE-ELISA could generate complementary absorbance and fluorescence signals with a linear detection range of 1.6-25,000 pg/mL. The application of this dual-mode AIE-ELISA in the detection of the prostate-specific antigen (PSA) realized a limit of detection of 1.3 pg/mL (3.78 × 10^-14 M) and dynamic range improvement of approximately 2 orders of magnitude compared to a single-mode ELISA, which enabled it to discriminate a minor PSA difference in a patient's serum. The simpler experimental operation, faster enzyme response speed, and better photostability of AIEgen than the traditional chromogenic reagents used in ELISAs showed that our developed AIE-ELISA holds great potential in the fields of immunoassay, immunohistochemistry, and immunocytochemistry.