A linear programming-based strategy to save pipette tips in automated DNA assembly

Abstract

Laboratory automation and mathematical optimisation are key to improving the efficiency of synthetic biology research. While there are algorithms optimising the construct designs and synthesis strategies for DNA assembly, the optimisation of how DNA assembly reaction mixes are prepared remains largely unexplored. Here, we focus on reducing the pipette tip consumption of a liquid-handling robot as it delivers DNA parts across a multi-well plate where several constructs are being assembled in parallel. We propose a linear programming formulation of this problem based on the capacitated vehicle routing problem, along with an algorithm which applies a linear programming solver to our formulation, hence providing a strategy to prepare a given set of DNA assembly mixes using fewer pipette tips. The algorithm performed well in randomly generated and real-life scenarios concerning several modular DNA assembly standards, proving capable of reducing the pipette tip consumption by up to 61% in large-scale cases. Combining automatic process optimisation and robotic liquid-handling, our strategy promises to greatly improve the efficiency of DNA assembly, either used alone or in combination with other algorithmic methods.

Automation of yeast spot assays using an affordable liquid handling robot

“…The system developed in this study took about 25 min to spot four plates, while the experimental time when it was conducted by the human experimenter was about 30 min. To reduce the time that is required for the experiment, it would be best to optimize the movements [42] and dispensing speed of the OT-2 pipette and replace the single pipette with multichannel pipettes. The third is the quantification of the relative yeast growth.…”

A linear programming-based strategy to save pipette tips in automated DNA assembly

“…The proposed algorithm’s implementation in Python code is available via our open-access GitHub repository [ 15 ]. Our package offers Application Programming Interface solutions which allow users to incorporate our algorithm for pipette tip consumption minimization into existing DNA assembly pipelines for the Opentrons OT-2 liquid handler, namely DNA-BOT [ 2 ] and ‘OT2 Modular Cloning (MoClo) and Transformation in E. coli Workflow’ [ 11 ].…”