Automated Microfluidic Systems for Gene Editing

Technologies such as CRISPR are being utilized on a daily basis in an ever growing number of research laboratories across the world, and it seems that the anticipated introduction of gene editing to the medical field may only be a stones throw away. Before this happens, however, techniques need to be optimized. Recently, Oxford Genetics and Sphere Fluidics announced a multi-partner collaboration to expedite the development of automated microfluidic systems for rapid and high-throughput gene editing in mammalian cells. We spoke with Emily Leproust, PhD, CEO of Twist Biosciences, and other collaborators from the partnership to discuss the background of this announcement and the need for automated systems in gene editing.

Molly Campbell (MC): Why are microfluidic systems essential for high-throughput gene editing?

Emily Leproust (EL): Microfluidic systems enable miniaturisation and multiplexing of gene editing experiments by carrying out manipulations at the single cell level. This also ensures instant generation of clonal, isogenic cell lines. 

MC: What challenges currently exist in high-throughput gene editing? 

EL: Oxford Genetics has extensive experience in developing automated cell engineering platforms, using liquid handling systems that provide robust, high-capacity gene editing capabilities. Concurrently, Oxford Genetics is looking to develop and integrate ‘next-gen’ approaches to manipulation of mammalian cell lines. While CRISPR has opened up the field of gene editing, and enabled researchers in academic and commercial labs, there are very significant challenges to fully automating these processes, particulary around transfection efficiency, enrichment of rare populations, and recovery of viable edited clonal lines. 

MC: Why is an automated system beneficial? How will the next-generation workflow overcome the current challenges faced in gene editing using microfluidic systems?

EL: Microfluidic systems miniaturize experiments, and allow them to run in parallel. This reduces cost and increases throughput. These systems also allow handling of sensitive cell lines, resulting in high efficiency clonal cell line generation, along with enrichment of rare populations. Finally, the ability to multiplex editing events facilitates CRISPR screening applications, used in the discovery of novel genetic drivers of disease.

MC: What does each partner bring to the collaboration?

EL: Oxford Genetics – Oxford Genetics brings a multi-disciplinary team to the collaboration with extensive expertise in CRISPR/gene editing, translational biology, and process automation/informatics system.

Sphere Fluidics – Sphere bring expertise around microfluidic system development, as exemplified by the current Cyto-Mine® platform for Biologics Discovery/Cell Line Development. This will be applied here in the context of developing a desktop gene editing platform.

Twist Bioscience  – Twist provides DNA synthesis at a scale otherwise unavailable, facilitating new avenues of research and biotechnology applications.

The University of Edinburgh – A leading academic partner with expertise in gene editing experimentation and translational contexts, particularly neural stem cell modification and brain cancer.

MC: Will the system vary greatly from currently used methods? If so, will there be training attached with the system?

EL: It will use standard gene editing techniques but at scale in single cells. The vision is for it to be a plug and play system - introducing the cells you want to modify and the gene editing reagents and the rest is done by the machine, including outputting sorted, modified cell lines. All this will be controlled by user-friendly software that will take a few hours training session to learn.

MC: How will the system advance the CRISPR research field?

EL: The ability to scale CRISPR research in this way will continue to enable responsible research that has the potential to improve health worldwide and contribute to development of treatments for deadly diseases. Additionally, high-throughput cell engineering will facilitate developments around personalized/stratified medicine. 

MC: How long do you predict the workflow will take to create? Is there an estimated timeline for when it will be available to the public?

EL: Sphere Fluidics has already carried out highly successful proof of concept experiments validating gene editing in their proprietary microfluidic picodroplet systems. It is anticipated that it will take about 9 months to complete the development of the initial automated platform, with the completed system commercially available in approximately 2 years. 

Emily Leproust was speaking to Molly Campbell, Science Writer for Technology Networks.