OPTION 1 – Quick Protocol: Dilute the DNA with the necessary amount of water and then mix up and down gently with a wide bore P200 pipette tip 10 times. Place at 50°C for 20 minutes. Repeat the wide bore pipette gentle mixing and place at 50°C for another 20 minutes. Repeat the mixing and incubation a third time. At that point, most samples are homogeneous. You can verify by doing a nanodrop reading of DNA at the top of the solution and comparing to the reading of an aliquot at the bottom of the solution. If the readings are within 10%, the DNA is homogeneous.
OPTION 2 – Extended Protocol: Mix the DNA and then let it sit at room temperature overnight. That is usually enough though it can be sample dependent if the DNA is very long. The DNA lengths we prefer (50kb-500kb) should have increased viscosity relative to water at 100ng/µl but it should not be goopy or snotty. If it is highly viscous, it means the DNA is severely entangled and it will be challenging to carry out effective sample prep and separation of DNAs to run individually. We recommend the lower concentration because it is easier to disentangle the DNA.
