Integrating aptasensor with an explosive mass-tag signal amplification strategy for ultrasensitive and multiplexed analysis using a miniature mass spectrometer

Mass probes attached with aptamers and mass tags offer excellent specificity and sensitivity for multiplexed detection, wherein the dissociation of mass tags from the mass probes is as important as their labeling. Herein, aggregation-induced emission luminogen (AIEgen)-tagged mass probes (AIEMPs) were established to analyze estrogens, which integrated aptasensor with an explosive mass-tag signal amplification strategy via a simple ultrasound-assisted emulsification of nanoliposomes. The AIEMPs were assembled by the hybridization of aptamer-modified Fe3O4 nanoparticles (Fe NPs@Apt) and nanoliposomes loaded with massive AIEgen mass tags and partially complementary DNA strands (AIE NLs@cDNA). The aptamer was preferentially and specifically bound to estrogen, resulting in the detachment of AIE NLs from AIEMPs. Subsequently, the AIEMPs were deposited with electrospray solvents for explosive release of mass tags. Using nanoelectrospray ionization mass spectrometry (nanoESI-MS), the AIEMP-based aptasensor achieved ultrasensitive analysis of estrogens with limits of detection of 0.168-0.543 pg/mL and accuracies in the range of 87.9-114.0%. Compared to direct nanoESI-MS detection, the AIEMP-based aptasensor provides a signal amplification of four orders of magnitude. Furthermore, the utilization of different AIEMPs enables multiplexed detection of three estrogens with a miniature mass spectrometer, showing promising potential for on-site detection. This work expands the diversity of mass-tagging strategy and provides a versatile mass probe-based aptasensor platform for routine MS detection of trace analytes.