The Wellcome Sanger Institute is a world-leading genomics research institute that delivers insights into human, evolutionary and pathogen biology by using information from genome sequences to advance understanding of biology and improve health.
The Wellcome Sanger Institute approached eg, having been referred by an existing client. They wished to further automate the practice of in-situ sequencing, which allows RNA to be mapped to specific cellular locations in a tissue sample. Their advanced technique utilised their existing library of tissue samples mounted on microscope slides, upon which fluorescent labels would be applied manually, which in turn would bind to cells that are expressing certain genes or proteins. This process is repeated sequentially, whilst images are taken and overlayed, producing a single composite image mapping diverse tissue architecture right down to the cellular level.
The team at the Wellcome Sanger Institute were experiencing bottlenecks when it came to the process of exchanging, incubating and washing the multiple fluorescent reagents. Their process had limitations as there was no way to mount large samples into a flowcell without the risk of sample damage and the number of fluid exchange and incubation steps between each imaging step was inhibitive.
They therefore asked eg technology to identify an approach for mounting the samples in a flowcell, performing the perfusion of reagents and subsequently automating the entire process.
Engineering the Solution
Our team were quick to set up a programme of work for this project. Through start-up meetings, we discussed the specification in detail to ensure a common understanding of spatial (gen)omics, cyclic microscopy, multiplex sequencing and how each applied to the programme requirements as a whole. As such, a system requirements specification for the flowcell and fluid handling system was prepared highlighting the core functions and the longer-term product requirements.
The team then developed a flowcell concept design taking in to account likely fabrication techniques as well as fluid flow characteristics. The engineers had to effectively manage throughput and ensure that load fluid dead volumes were kept to a minimum. We therefore performed meticulous design calculations to assess likely flowrates, volumes, back pressures and glass deflections in the flowcell and generated an outline fluidic design for the fluid handling hardware. This helped to identify pumping and valving methods as well as flowcell interfaces and likely reagent storage schemes
Our team managed the project from specification writing and concept generation, through to risk analysis and delivery of proof of principal prototype. We were successful in developing a test rig which incorporated a fluidics system containing mounted flowcells designed to fit a 96 well plate format. The mounted flowcells were also thermally controlled to ensure the correct incubation parameters whilst being viewed with an integrated confocal microscope. The automated application of reagents enabled the utilisation of a superior microscope and allowed the Wellcome Sanger Institute to develop their protocols.
The Wellcome Sanger Institute were able to leverage our extensive design and development engineering expertise within fluid handling and microfluidics. As such, the developed multiplex sequencing has reduced the process time by 75% due to capability of activities occurring synchronously and a-synchronously.
“The work eg technology did was important in many respects. This project took place through the pandemic, when many genome labs were working to capacity, but our engineers were able to maintain momentum and create a prototype on which Sanger can further develop their procedure. This project is a nice example of science being enabled by engineering.”Andrew EdeCo-Founder & Director | eg technology
“Working with eg technology has significantly increased our work efficiency, both now and in the future. We were able to describe our application and trust the team at eg to define specifications, develop concepts, and deliver a prototype. This allowed our team to focus on our own areas of strength. The delivered instrument is able to adapt to new protocols and continues to increase the efficiency of our work through the automation that it provides.”Omer BayraktarGenome Research Ltd | The Wellcome Sanger Institute
Further examples of our work in LabTech and BioTech
Every project we work on is tailored to the needs of our clients. This extends to their privacy requirements and as such this selection of case studies includes those which our clients are happy for us to share. For more information, please get in touch.