Advancements in Nanotags for Enhanced Mass Spectrometric Biosensors: Toward Next Generation Bioassay and Cytometry

Molecular spectroscopic bioassay and flow cytometry are mainstream methods for disease biomarker analysis, which gained great successes in the past. However, as rapid progresses of omics research, conventional spectroscopic methods often confront two thorny challenges. First, the molecular spectroscopic tags are often subject to spectral overlapping interference for complex multitarget analysis. Second, current bioanalytical strategies are constantly challenged by inadequate analytical sensitivity. Mass spectrometry, characterized by its high-throughput sampling method, inherent abundance of detection channels, diverse detection strategies, and high-resolution linear spectra, has been extensively utilized in biosensing and emerged as a potent tool for omics analysis. In this context, mass nanotags are considered beneficial tags to realize multiplex and sensitive analysis by mass spectrometric bioassay and mass cytometry. Nanoparticles are capable of integrating multiple mass labels in a single tag, which in turn results in high signal intensities in mass spectrometric analysis. Herein, this review summarizes strategies for the synthesis, design, and application of mass nanotags, providing a comprehensive overview of research on such mass spectrometric tags. In addition, this review describes the challenges and cutting-edge research results on the use of nanotags for mass spectrometry biosensing, providing insights into how mass nanotags could be more broadly applied to complex and challenging analytical tasks.