Luminescent Metal–Organic Framework Probes with Metallic and Fluorescent Dual-Properties for Mass Cytometry and Imaging

Mass cytometry (CyTOF) and imaging mass cytometry (IMC), as cutting-edge technologies in single-cell analysis, are capable of detecting more than 40 biomarkers simultaneously on a single cell. However, their sensitivity and multiparameter detection capabilities have been long constrained by the development of metal labeling materials. Meanwhile, as an imaging technique, IMC has suffered from a rather slow data acquisition rate. Here, we present a luminescent PCN-224-OH material that exhibits both fluorescent and mass dual-functionality and is enriched with Zr-OH^-/H₂O active sites. Without the additional need for complex postmodification or chemical coupling reactions, PCN-224-OH can be directly functionalized with antibodies/aptamers and poly(ethylene glycol) (PEG), resulting in the production of PCN-224-Ab-PEG or PCN-224-Apt-PEG probes. We demonstrated that PCN-224-Ab-PEG was compatible with commercial polymer-based probes but with superior sensitivity and specificity. Meanwhile, since PCN-224-Apt-PEG expressed both fluorescence and mass signals, we could adopt fluorescence signals for rapid tissue section scanning to swiftly identify the regions of interest (ROIs), and then adopt IMC for multiparameter imaging at the specific ROIs. The application of the PCN-224-Apt-PEG probe could significantly reduce the blind IMC scanning time by up to 90% and effectively compensate for IMC's low resolution. This study not only broadens the application scope of luminescent metal-organic frameworks but also offers a potentially novel toolbox for single-cell multiparameter detection.