We present liquid-cell transmission electron microscopy (liquid-cell TEM) imaging of fixed and non-fixed prostate cancer cells (PC3 and LNCaP) with high resolution in a custom developed silicon nitride liquid cell. Fixed PC3 cells were imaged for 90–120 min without any discernable damage. High contrast on the cellular structures was obtained even at low electron doses (~2.5 e−/nm2 per image). The images show distinct structures of cell compartments (nuclei and nucleoli) and cell boundaries without any further sample embedding, dehydration, or staining. Furthermore, we observed dynamics of vesicles trafficking from the cell membrane in consecutive still frames in a non-fixed cell. Our findings show that liquid-cell TEM, operated at low electron dose, is an excellent tool to investigate dynamic events in non-fixed cells with enough spatial resolution (few nm) and natural amplitude contrast to follow key intracellular processes.
