Fully automated plasmid purification on Biomek i7

The automation of keystone procedures in DNA workflows are fundamental to achieve complete walk-away automation of DNA assembly and cloning workflows in high-throughput. With progress being made on the automation of gene assembly and the setup of miniaturized cloning reactions on acoustic liquid handlers in high throughput, the complete automation of workflows covering the complete process from in-house DNA synthesis to sequence verified plasmids appears within reach. Here we focus on one of the remaining challenges: automation-friendly implementation of plasmid purification from overnight bacterial cultures at scale. Protocols avoiding high-speed centrifugation steps based on magnetic bead purification have been reported but can suffer from impurities and high genomic DNA contamination. Here we explore a resin loaded tip approach and report on the Design of Experiment guided implementation on a Biomek i7 liquid handler. We find that using this approach, it is possible to fully automate the plasmid purification procedure in high-throughput format in a liquid handler alone, and optimize outputs of interest.