Plating¶
Overview¶
Done after electroporation or chemical transformation.
Procedure¶
- Shake at 250 rpm for at least 1 hour at 37°C to allow the expression of the antibiotic resistance gene. Meanwhile, prewarm plates (cover side down) at 37C for 1 hour.
- If the plates contain a lot of moisture, place them cover side up and open the cover ~1/3 way to allow the plates to dry for 30-45 min.
- (Optional) To concentrate the cells, spin down for 2 min at 2400 g, then remove supernatant.
- Resuspend the cells by a gentle pipetting, then take 5-50 uL.
- Plate less for higher efficiency plasmids and vice versa.
- Plating:
- With a spreader (loop):
- Immerse the spreader in ethanol and use flame to sterilize it. Allow 10 s to cool, then touch agar at the edge of a plate (not touching the cells).
- Gently touch down the spreader and briefly and evenly spread the cells.
- Do not continue to spread until the sample has absorbed completely as this is lethal to cells.
- Rotating the plate might help.
- Before inverting the plates, allow the surplus liquid to absorb by leaving the plates on the bench for a few minutes.
- With beads: Add 10-20 beads, close the lid and rock the plate a few times.
- Beads spread cells more evenly and do not require ethanol/flame.
- This is particularly useful if spreading on multiple plates as you can shake them all at the same time by stacking them together.
- With a spreader (loop):
- Incubate at 37C overnight (cover side down; 15-18 h).
- Extend incubation time by 1-2 hours for larger colonies.
- If performing blue/white screening, place the plates at 4ºC for a few hours after the colonies have reached the desired size to enhance color development.
- Store the remaining transformation mix at +4°C. Additional cells may be plated out the next day, if desired.
Troubleshooting¶
- Few or no colonies:
- Test with a known plasmid, e.g., pUC19, if the cells are alive and the protocol is working.
- If not, check antibiotic choice and its concentration, media formulation and its stock, and incubation temperature.
- Make sure you're treating cells very gently. NEver vortex or mix vigorously. Resuspend by a gentle flick of gentle pipetting. Always keep them on ice. If thawed, do not place back to -70C as efficency might drop severalfold.
- Purify DNA form excess salts, EDTA, proteins that may impede vector and insert ligation.
- Test with a known plasmid, e.g., pUC19, if the cells are alive and the protocol is working.
- Small satellite colonies apprear:
- Plates were incubated for too long. Beta-lactamase is secreted by amp-resistant bacteria and eventually clear a zone around themselves from antibiotic where non-recombinants can grow.
- Antibiotic degraded (old plates or poured into too hot media)