Correlative imaging enabled by a microreactor SALVI, system for analysis at the liquid vacuum interface, is used to address the scientific challenge of spatially mapping chemical components and following dynamics of single cells in microchannels mimicking their native microenvironments. Application of SALVI permits in situ imaging by time-of-flight secondary ion mass spectrometry (ToF-SIMS), a vacuum-based surface technique. MCF-7 human breast cancer cell growth was monitored and confirmed by super resolution fluorescence microscopy, namely, structured illumination microscope (SIM) imaging; and cell changes were analyzed by direct probing of hydrated cells in a microfluidic channel using ToF-SIMS. MCF-7 cells were inoculated into the SALVI microchannel consisting of a silicon nitride (SiN) membrane and PDMS, incubated at 37 oC for 24 hr., and then fed with doxorubicin before SIM imaging. In subsequent ToF-SIMS analysis, an aperture of 2 µm in diameter was drilled through the SiN membrane to form a windowless detection area and permit direct imaging of biological surfaces. SALVI uses surface tension to hold the liquid within the aperture. Vacuum pressure can be maintained on the order of 10-7 Torr for continuous measurements for at least 8 hrs. SIM images confirmed that MCF-7 cells were successfully cultured; and doxorubicin was uptaken by cells and dispersed in the cytoplasm. Comparisons of ToF-SIMS m/z spectra among dried cancer cells, hydrated cells, and uninoculated medium show characteristic lipid fragments of cells. Depth profiling was used to provide time- and space-resolved chemical mapping of cells in their microenvironments. 2D and 3D ToF-SIMS images of representative fragments of hydrated cell will be presented and discussed for the first time. Principal component analysis of images was also conducted to evaluate the intrinsic similarities and discriminations among samples. Our results demonstrate the feasibility of in situ probing of cancer cells in the hydrated microenvironment using ToF-SIMS. Correlative imaging using SIM and ToF-SIMS provides information across different space scales for investigating cancer cell and drug interactions. In summary, SALVI has great potential for studying intracellular processes in the future.

Correlative imaging of cancer cell and drug interactions in the liquid microenvironment

249th National Meeting (2015)

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