Imaging with time-of-flight secondary ion mass spectrometry (TOF-SIMS) has been shown to be a powerful analytical tool for mapping the distribution of biologically relevant small molecules (<1000 Da) on a surface. To improve the success rate of sample preparation, a device was designed to cells freeze-fracture by using powerful magnets. Quantum dots (QDs) were used to observe the changes in the cell after freeze-fracture. Then, TOF-SIMS was employed to analyze the ionic and molecular distribution in the cells associated with the disease. Copyright © 2012 John Wiley & Sons, Ltd.