Freeze-drying enhances ToF-SIMS imaging of biological tissues <i>via</i> structural and metabolic preservation

In the ToF-SIMS <i>in situ</i> analysis of mouse liver tissue, freeze-drying is superior to room-temperature drying and chemical fixation, minimizing lipid spillage while maintaining structural integrity. Freeze-drying preserves tissue structure with minimal lipid loss, whereas room-temperature drying leads to lipid spreading and chemical fixation results in background noise. Freeze-drying balances structural integrity, molecular preservation, and spectral clarity, making it the optimal ToF-SIMS prep method. Although the method was tested on lipid-rich liver tissue, it provides a framework for tissue specific preparation of ToF-SIMS.