FAQ: I am having trouble dissolving my HMW DNA after isolation. Do you have any tips on increasing the solubility?

High molecular weight DNA (HMW DNA) is notoriously difficult to dissolve. When DNA samples are highly concentrated or contain ultra-high molecular weight DNA, dissolving it can be even more challenging. In general, the more DNA is compacted, the harder it is to get into solution. The glass beads employed in the Monarch HMW DNA Extraction Kits provide a large surface for the DNA to wrap around which generally serves to keep the DNA in an open conformation, making it easier to dissolve. However, solubility can still be an issue. Below are some tips to maximize the solubility of your DNA when working with the Monarch HMW DNA Extraction Kits:

  • Try to minimize the amount of time that the DNA is bound to the beads without liquid being present. After removing liquid from the beads, add the next buffer without delay. The longer the DNA is dried to the beads, the more compact the DNA will be and the more difficult it will be to dissolve later. 
  • When binding the DNA to the beads, do not invert the sample longer than recommended. The more time that the DNA wraps around the beads, the more compacted it will get, and the more difficult it will be to dissolve later.
  • Review our usage guideline, Homogenization of High Molecular Weight DNA (HMW DNA) Samples After Elution for more tips on homogenization of HMW DNA after elution.