Agarose gel electrophoresis¶
Overview¶
Agarose gel forms when a solution containing disaccharide of D-galactose and 3,6-anhydro-L-galactopyranose cools down below 35C and non-covalent bonds allow a porous structure to form (100-300 nm size pores). Best used with DNA fragments >100 bp.
(Source: Jiang et al., 2023)
Gel preparation¶
- Choose gel percentage based on the DNA size that you want to resolve and measure X g of agarose to make X% (w/v) agarose gel (usually 1 or 2%):
| Gel % | DNA size range (bp) |
|---|---|
| .5 | 1000 - 30000 |
| .8 | 800 - 12000 |
| 1.0 | 500 - 10000 |
| 1.5 | 200 - 3000 |
| 2.0 | 50 - 2000 |
- Mix agarose powder into 100 ml 1X TAE or TBE buffer in a microwavable flask (while shaking the flask) and let it hydrate for a minute or two.
- TBE: Best for smaller DNA fragments (<1500 bp), used with a higher voltage, can run for a longer time due to a higher buffering capacity
- TAE: Best for larger DNA fragments (>4000 bp), used with lower voltage, good for purification from gel.
- (Optional) Add 5 uL of SYBR Safe to prestain.
- Only for linear fragments because this dye acts as an intercalator and might alter plasmid migration, but should not affect linear fragments.
- Microwave for ~2 min until the agarose is completely dissolved (can do 30-45 sec, stop and swirl, and then continue towards a boil). Just put it in a microwave and heat until it starts to bubble and once it does, take it out and then swirl, and if some crystals are left then heat it for a bit more.
- Let agarose solution cool down to about 50°C (about when you can comfortably keep your hand on the flask), about 5 mins.
- Pour the agarose into a gel tray with the well comb in place. Make sure there are no bubbles – use a pipette tip to move them to the sides. Bubbles are most likely to appear near the comb.
- Place newly poured gel at 4°C for 10-15 mins OR let sit at room temperature for 20-30 mins, until it has completely solidified.
Running¶
- Put the gel tray into the gel tank.
- Fill gel box with 1X TBE (or TAE) until the gel is covered (important to use the same buffer).
- Add samples:
- 6 uL of sample with loading buffer: 1 uL TriTrack + 5 uL DNA (mix and spin down)
- 3 uL ladder (mix gently)
- Run at 100V for 1% agarose gel (40 min) or at 120V for 2% agarose (30 min)
- Rule of thumb: 5-10 V/cm of gel. Small size gel is 7 x 10 cm, so 35-70 V, but people just use 100V.
- It should start bubbling immediately.
- In a few minutes, you should see some bands
- At the end, the yellow die should be at the bottom of the well
- Proceed to staining.