Single-particle ICP-MS monitoring of aptamer-mediated nanoparticle aggregation for highly sensitive pancreatic polypeptide detection

A sensitive method for pancreatic polypeptide (PP) detection was developed by coupling aptamer-mediated gold nanoparticle (AuNP) aggregation with single-particle inductively coupled plasma mass spectrometry (spICP-MS). The assay uses a previously reported PP dual-aptamer pair to induce sandwich-type crosslinking of AuNP probes in the presence of PP. This aggregation increases the Au mass per detected event, producing a higher mass-equivalent spICP-MS signal for quantitative PP detection. Under optimized conditions, the assay exhibited a linear response from 50 pM to 2.5 nM, with a limit of detection of 13.3 pM (blank n = 3) and 10.3 pM (blank n = 10). The method showed good selectivity against structurally related peptides and abundant serum proteins. Satisfactory recoveries of 92.8%–108.8% were obtained in human serum samples, demonstrating its applicability to complex biological matrices. This work extends a dual-aptamer PP recognition system to an spICP-MS-based mass-equivalent readout and provides a sensitive approach for low-abundance peptide biomarker detection.