Metal Isotope-Tagged Nanomaterials for Mass Cytometry and Imaging: Advances and Biomedical Applications

Mass cytometry (cytometry by time-of-flight (CyTOF)) and imaging mass cytometry (IMC) are transformative technologies that combine flow cytometry principles with time-of-flight mass spectrometry (TOF-MS). By employing metal isotope-tagged antibodies instead of fluorophores, these techniques overcome spectral overlap limitations and enable high-dimensional, compensation-free analysis of complex biological systems at single-cell resolution. The performance of CyTOF and IMC critically depends on advanced nanomaterials labeled with stable metal isotopes, which are essential for improving sensitivity and multiplexing capacity. This review systematically discusses the design principles, synthesis methods, and functionalization strategies of mass-tagged nanomaterials tailored for CyTOF (e.g., cell suspension analysis) and IMC (e.g., spatial proteomics of tissue sections). We highlight their impactful applications in biomedicine, including proteomics, immunology, oncology, and neuroscience, emphasizing their roles in disease diagnosis, targeted drug development, and single-cell analysis. Despite these advancements, challenges such as nanomaterial biocompatibility, clinical scalability, and artificial intelligence (AI)-driven design are discussed, providing a roadmap for future research in personalized medicine and theranostics.