Graphene quantum dots enhanced ToF-SIMS for single-cell imaging.

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) has shown promising applications in single-cell analysis owing to its high spatial resolution molecular imaging capability. One of the main drawbacks hindering progress in this field is the relatively low ionization efficiency for biological systems. The complex chemical micro-environment in single cells typically causes severe matrix effects, leading to significant signal suppression of biomolecules. In this work, we investigated the signal enhancement effect of graphene quantum dots (GE QDs) in ToF-SIMS analysis. A × 160 magnification of ToF-SIMS signal for amiodarone casted on glass slide was observed by adding amino-functionalized GE QDs (amino-GE QDs), which was significantly higher than adding previously reported signal enhancement materials and hydroxyl group-functionalized GE QDs (hydroxyl-GE QDs). A possible mechanism for GE QD-induced signal enhancement was proposed. Further, effects of amino-GE QDs and hydroxyl-GE QDs on amiodarone-treated breast cancer cells were compared. A significant signal improvement for lipids and amiodarone was achieved using both types of GE QDs, especially for amino-GE QDs. In addition, ToF-SIMS chemical mapping of single cells with better quality was obtained after signal enhancement. Our strategy for effective ToF-SIMS signal enhancement holds great potential for further investigation of drug metabolism pathways and the interactions between the cell and micro-environment.