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.

A novel mass probe-based aptasensor via integration with an efficient mass-tag signal amplification strategy was explored. This strategy is triggered by a convenient ultrasonic emulsification, allowing for the instant dissociation and release of massive AIEgen mass tags. Compared to direct nanoESI-MS detection, the AIEMP-based aptasensor achieved a significant enhancement in sensitivity. The aptasensor enabled the multiplexed detection of three estrogens using a miniature mass spectrometer. However, for enhanced practicality, further optimization of aptamer sequences and AIEgen mass tags, along with the mitigation of matrix effects, is necessary to refine the AIEMP-based aptasensor in subsequent experiments. By altering aptamer-AIEgen mass tag pairs, the AIEMP-based aptasensor can be extended to detect various targets. Moreover, this method has a high degree of environmental friendliness. This work is expected to expand the usage of mass probe-based aptasensor for MS detection in routine analysis.