How do I increase plasmid yield?

There are a number of things you can do to increase plasmid yield. Depending on the exact problem you’re experiencing, you may need to use a combination of techniques to improve plasmid yield. 

1. Input more raw material – If the plasmid yield is inadequate, the first thing to do is try increasing the volume of culture processed. Starting with a larger amount of culture is often all that’s needed to increase plasmid yield. This is because more volume means more cells, which translates to more plasmid. 
2. Optimize your bacteria – Differences between E. coli host strains can have an impact on plasmid yield. Not all bacterial strains are optimal for plasmid extraction. If you’re experiencing low yields, check the bacterial strain. You may need to include additional steps such as an extra wash step to optimize yield, or you may need to use a different strain altogether. 
3. Improve the culture media – Culture conditions have a major impact on plasmid yield. Optimal growth conditions may vary considerably among different plasmids and strains. While standard concentrations of LB broth and antibiotics work well enough for high copy plasmids, they may not work as well for low copy plasmids or slower growing strains. In this case, using a richer media or adding supplements can help improve the cell density, resulting in increased plasmid yield. 
4. Use optimal growth conditions – E. coli strains vary considerably in terms of their growth rate and final density. Some may require longer incubation times, different temperatures, more oxygenation, or faster shaking speeds. To increase plasmid yield, it’s important to ensure that you’re using growth conditions that are optimal for the strain you’re using.