According to leaders in the synbio field, miniaturization is the next step for cost-cutting in gene construct assembly. For example, using acoustic liquid handling technology can scale down and streamline the process without compromising accuracy. The Labcyte Echo Liquid Handlers do just this by using acoustic waves to precisely move nano-droplets of primers into assays, without the need for tips.
Estimated to grow by as much as 35% annually for the next few years, the synthetic biology industry is predicted to be worth $11.8 billion by next year.
Yet with such a spike in demand, the quest to dramatically drop the cost of DNA synthesis is still raging with the rise of de novo assembly technologies.
“What has changed is the scale of synthesis and the efficiency of workflows for producing these pieces of DNA,” explained Chris Voigt, professor of biological engineering at MIT, in an interview with Drug Discovery World magazine. He noted that miniaturization will be as important as automation.
However, designing an instrument to use smaller volumes of construct material is no mean feat. Reducing assay volumes, whilst more efficient in cost and time, demands new forms of quality control optimization due to greater room for error.
This complex task has been achieved by the Labcyte Echo acoustic liquid handlers, which are now allowing many industry leaders, from Twist Bioscience to Ginkgo Bioworks, to lower costs and improve performance for synbio assembly.
Labcyte’s high-throughput Echo Liquid Handlers avoid any compromise in accuracy by precisely controlling transfer of nanoscale volumes through acoustic droplet ejection.
Its patented Dynamic Fluid Analysis (DFA) technology uses focused ultrasonic acoustic energy for contactless transfer of nanoliter-scale droplets of a broad range of aqueous solutions such as cDNA, siRNA vectors, proteins and crystallography reagents – without the need for tips.
With the obvious benefits of reduced cross-contamination and saved time, contactless transfer also means less reagent is lost due to tip adherence. Because of this, the Echo system can dramatically reduce the volume of assembly from the typical 10-20 microliters per well to as little as 2.5 nanoliters – a reduction of up to 100-fold.
(Image: Labcyte Inc.)
Miniaturized reactions not only cut costs, but they also lead to fewer dilution errors because more concentrated primer libraries generate a higher rate of simultaneous normalization of primers during pooling.
The Labcyte DFA technology is also less sensitive to reagent changes as it is an active process compared to single calibration points, permitting more consistent downstream experimental data.
Therefore, with the Echo Liquid Handler, there is a reduced amount of noise in the data produced, giving scientists greater resolution to spot small changes in the target organisms.
Eliminating the need for tips speeds up the process because there is no need to wash or replace them for each assembly. Calibration of the Echo Liquid Handler has been automated to further minimize hands-on time.
Compatible with both Gibson Assembly and Golden Gate cloning methods, the Echo Liquid Handler can rapidly pool oligos or DNA fragments from any well in a library plate to any well in a destination plate in less than a second.
Cumulatively these time savings add up. In a high-throughput setting, the Echo system can save up to 15 hours of lab work per run.
For example, David McClymont, Head of Automation at SynbiCITE – the synbio accelerator at Imperial College London – is using the Labcyte Echo 525 instrument to speed up the workflow and automation of DNA assembly.
“The Echo advanced liquid handling means that sub-nanoliter volumes of all ingredients can be added quickly, and in a specified order, so reactions can be run immediately,” McClymont explained.
Unleashing experimental design
With Echo Liquid Handlers, scientists can pursue more ambitious experimental designs.
For example, Linda D’Amore is Operational Manager at the GeneMill Foundry – part of the Centre for Genomic Research at the University of Liverpool. The Foundry is combining the Labcyte Echo instrument with the PacBio system to create a single miniaturized reaction step.
“The idea was to take all the constructs together, assuming they are different enough for multiplexing, [to have] a single reaction where the constructs are all in one pot,” D’Amore told SelectScience.
By designing DNA constructs in silico and then combining them with the Echo 525 Liquid Handler, the system streamlines this stage in preparation for next-generation sequence validation.
Other prominent members of the synbio community using the Labcyte Echo instruments include the Boeke Lab at New York University’s School of Medicine, which is studying synthetic retrotransposons – “jumping genes” – in yeast. And the Cai Lab at the Manchester Institute of Biotechnology is using the Echo technology to refine the pathway of construct design to fabrication in synthetic biology.
From genomic research and cell-based assays to drug discovery and personalized medicine, acoustic liquid handling technology is moving the industry toward more efficient and accurate high-throughput assay transfer.
You can read more on the Labcyte solutions for synbio HERE.
This article is sponsored by Labcyte0