Home Pharmacology Clonogenic Cell Survival Assay (Colony Formation Assay)
Steps
  1. 1 Count cells and prepare suspension 00:54
  2. 2 Seed cells into culture plates 02:07
  3. 3 Treat cells with drug concentrations 02:25
  4. 4 Incubate plates for colony formation 02:53
  5. 5 Fix and stain colonies 03:31
  6. 6 Wash plates and count colonies 03:45
  7. 7 Analyze and plot results 04:03
Pharmacology YouTube (Curated Tutorials)

Clonogenic Cell Survival Assay (Colony Formation Assay)

Protocol
Difficulty
intermediate

Steps

1
Count cells and prepare suspension

Count cells from both wild-type and mutant cell lines using a counting chamber or automated system. Prepare a cell suspension with a defined concentration of 1000 cells per milliliter by diluting the appropriate volume of cell suspension in culture medium.

▶ 00:54
2
Seed cells into culture plates

Pipette 1 ml of the prepared cell suspension into each well of a 6-well plate to achieve equal cell density of 1000 cells per well. Allow cells to attach to the plate overnight.

▶ 02:07
3
Treat cells with drug concentrations

The following day, treat cells with increasing concentrations of the drug of interest, with two untreated control wells per cell line. Prepare technical duplicates for each treatment condition.

▶ 02:25
4
Incubate plates for colony formation

Incubate the seeded and treated plates for 7 to 14 days depending on cell line and compound, allowing single cells to proliferate into visible colonies.

▶ 02:53
5
Fix and stain colonies

Remove the medium and fix cells in 70% ethanol for 10 minutes. Allow plates to dry, then stain with crystal violet dye for several minutes to visualize colonies.

▶ 03:31
6
Wash plates and count colonies

Wash away the background stain with water so only the stained colonies remain clearly visible. Count the colonies in all technical duplicates and calculate averages.

▶ 03:45
7
Analyze and plot results

Set the untreated control to 100% and normalize all other conditions relative to the control. Plot the data to compare drug susceptibility between cell lines and determine treatment effects on cell survival.

▶ 04:03

🚨 Failure Case Library (7) + Submit your own case

severe
Plated too dense — colonies merge into one another
Many colonies fuse together so individual colonies cannot be counted reliably; counts will be over- or under-estimated.
💡 2 · ✓ 3
severe
Replicate dishes vary widely — conclusion is unsupported
Three replicates of the same group give very different colony counts. Showing only a representative image without statistics is misleading.
💡 4 · ✓ 4
moderate
Uneven colony sizes (large mixed with small)
Some colonies are very large while others are tiny — suggests cells were not properly singularized at seeding.
💡 3 · ✓ 3
moderate
Dirty background or uneven crystal violet staining
Staining shows blotches, smears, or uneven intensity across the dish — technical artifacts can be mistaken for real biological differences.
💡 4 · ✓ 4
moderate
"Halo" or edge-ring artifact around dishes
A ring of stain appears around the dish edge; cells aggregate at the periphery due to evaporation / meniscus effects.
💡 3 · ✓ 3
minor
Crystal violet stain is too light — colonies hard to see
Stained dish shows only very faint purple; colonies are hard to distinguish from background.
💡 3 · ✓ 3
minor
Plate scratches or impurities interfere with imaging
Imaging shows linear scratches, dust specks, or crystal violet precipitate that look like colonies or obscure them.
💡 3 · ✓ 3
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