RNA Detection

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  1. It is recommended to allow microemulsion bubbles to settle on
    the imaging surface (cover glass) for a few minutes before
    imaging.

  2. Microemulsions should be prepared fresh and used within
    hours after preparation.

  3. We have found that after microporation HeLa cells adhere
    faster and spread better on fibronectin-coated surfaces.

  4. To achieve high transfection efficiency and cell viability, it is
    critical that cells are well-spread and not overconfluent before
    being subjected to microporation experiments.

  5. The flask should be incubated at 37C for enough time to
    ensure all of the cells are fairly rounded and detached from the
    surface.

  6. To achieve high cell viability after microporation, gentle pipet-
    ting to minimize shearing of the cells is critical.

  7. The number of cells used per microporation is cell line-specific
    and may affect the transfection efficiency and viability. A
    detailed list of cell line and the number of cells to use per
    microporation can be found on the Neon transfection system
    website: https://www.thermofisher.com/us/en/home/life-
    science/cell-culture/transfection/transfection-selection-
    misc/neon-transfection-system.html.

  8. It is important to wash the cells with enough media to remove
    unincorporated probes, which can contribute to background
    fluorescence and hamper accurate fluorescence quantification.

  9. After every wash, it is recommended not to aspirate out the
    entire wash media as this risks aspirating out the loose cell pellet
    formed by the small number of cells.

  10. Prior to seeding the cells into the 8-well chamber, it is critical
    to wash the chamber with 1PBS to remove unbound fibro-
    nectin. Residual unbound fibronectin can inhibit cell attach-
    ment to the surface.

  11. We have found that taking multiple ROIs around the object
    gives more accurate assessment of the total background fluo-
    rescence within the object ROI.

  12. To determine the extent of MB nonspecific opening in cells
    based on fluorescence measurements acquired in solution and
    in cells, it is important to make sure that the emission proper-
    ties of the MB reporter dye and reference dye are the same in
    solution and in living cells. We have previous published a
    method for assessing the sensitivity of commercially available
    fluorophores to changes in environment [20].

  13. We have shown that the 2Me/PSLOOPMB was the most stable
    configuration in other cell types including HEK-293, Jurkat,


Optimizing Molecular Beacons 255
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