Immune profiling and label-free detection of 2D MXenes at the single-cell and tissue level

There is a critical unmet need to image 2D materials within single cells and tissues. Here we propose a versatile label-free single-cell detection strategy based on mass cytometry. We use single-cell mass cytometry by time-of-flight (CyTOF), imaging mass cytometry, and multiplexed ion beam imaging by time-of-flight (MIBI-TOF) with three representative MXenes. Nb4C3, Mo2Ti2C3, and Ta4C3 were selected to ensure mass-detection within the range and to avoid overlap with currently available tags. We demonstrated their biocompatibility, detection, and quantification in 16 primary human immune cell subpopulations also showing the impact of MXene lateral size on the detection signal and cell binding. We report the biological and immune functional compatibility of MXenes. In vivo biodistribution experiments in mice using a mixture of MXenes revealed their presence in liver, blood, spleen, and lungs. Lastly, we applied MIBI-TOF to capture the presence of MXenes in different organs. The label-free detection of 2D materials by mass cytometry at the single cell level, on multiple subpopulations and in multiple organs in vivo opens exciting new opportunities in biomedicine.