Self-calibrated magnetic aptamer sensor with dual Lanthanide-assisted Time-resolved luminescence for high-sensitive detection of melanoma exosomal PD-L1

Highly sensitive detection of melanoma-derived exosomal PD-L1 plays a key role in non-invasive diagnosis of melanoma. Here, we proposed a self-calibrated magnetic aptamer sensor (sCMAS) for sensitive detection of melanoma exosomal PD-L1, using the dual lanthanide-assisted luminescence as well as the ratiometric fluorescent probe strategy to overcome limitations caused by systematic or environmental factors, thereby providing a more stable and liable detection output. Generally, the sCMAS employs the Tb-based nanoparticles (TbNps), which were immobilized on magnetic Fe3O4 microparticles, for stable luminescent reference signal report and the BHHCT-Eu3+ complex for detection signal report of the specific exosomal PD-L1 recognition. Particularly, the dual time-resolved luminescent elements were bridged through the PD-L1-responsive aptamer and its complementary DNA hybridization chain. Recognition of exosomes with the aptamer expelled the detection signal (BHHCT-Eu3+) only, leading to an exosome concentration-dependent liner increase of reference signal/detection signal ratio value in a broad concentration range (1.05 × 105–1.05 × 1010 particles/mL), and an extremely low calculated detection limitation of 1.88 × 102 particles/mL. Further, sCMAS allowed a rapid and efficient differentiation of the health samples from melanoma samples, even those early metastatic melanoma cases. Promisingly, this sCMAS developed in this work would provide a vast opportunity for future evaluation of tumor markers (exosomes, cells, proteins, etc.), and will provide a powerful tool in liquid biopsies.