- COVID-19 testing capacity in the U.K. was hampered by supply chain shortages
- Developing a reagent- and instrument-agnostic test required ability to randomize and track samples
- Developed high throughput workflows that can test 100s-1000s of samples in 24 hours
- Sped up the testing and validation of robot and reagent combinations
About the Project
Early on during the COVID-19 pandemic, supply chain shortages were hamstringing diagnostic efforts. Reagent allocation by the central government was limited to only 34,000 tests per week and often limited to a single reagent supplier and their specific testing platform.
Dr. Paul Freemont, Professor of Synthetic Biology and Co-Director of the London Biofoundry, witnessed his colleagues struggling to access reagents as early as February. He decided to co-opt a diagnostic assay developed by his graduate student Michael Crone to provide what was desperately needed: a robust, validated assay agnostic to reagents and liquid handling instruments. This would allow test centers to mix and match instruments and reagents as available and relieve bottlenecks due to supply shortages.
The Riffyn Nexus Solution
Using different combinations of instruments, robots, reagents, and experiment design and analysis software, Crone and his colleagues at the London Biofoundry quickly developed several open-access high throughput workflows for testing hundreds to thousands of samples with a 24-hour turnaround.
The biggest hurdles faced while testing different liquid handling robots and reagents were differences in capacity on the different liquid handling robots. Crone used Riffyn Nexus and JMP software to set up and track well randomizations and plate transfers to speed up the process of testing and validating each robot and reagent combination.
Track, analyze, and scale experiments without spreadsheet errors
For this assay to be agnostic, all the materials and instruments being tested need to be randomized across experiments. Crone used Riffyn Nexus to track samples and randomize their locations in qPCR plates for each assay. A file with a source-to-destination “map” was uploaded to the liquid handler to execute the physical transfer of the materials for qPCR assays. Assay results were then imported back to Riffyn Nexus to back-associate with the source samples, giving a complete chain of custody of samples, materials, methods, and metadata.
Once the assays were validated using VLPs, they were validated using patient samples, accessed via a collaboration with the U.K. National Health Service (NHS). The NHS immediately added Crone’s workflow to their assay suite, rapidly scaling testing capacity one weekend when over 600 samples were run in just under 12 hours — by only two people.
Scaling For The Future
Now, the NHS is in the process of buying more instrumentation so they can increase capacity to 3000 samples per day on robots running 24/7 using Crone’s assay workflow. To further raise testing capacity, the Biofoundry team is designing new workflows using Riffyn Nexus’ workflow design and sample tracking. This will facilitate the implementation of pooling approaches that will have a manifold impact on testing capacity.
Imperial College London used these Riffyn Nexus capabilities to enable:
- Well Randomization - Set up and track well randomization.
- Plate Transfers - Set up liquid handler to physically transfer samples.
- Seamless Data Import - Match qPCR results to sample in a single step.
- Rapid Data Analysis - Integrate with JMP using Riffyn API.
The results of this work were published in September in Nature Communications.
A pre-print of the Design and Implementation of An Adaptive Pooling Workflow for SARS-CoV-2 Testing in an NHS Diagnostic Laboratory can be downloaded here.
Read more of the story in this first-person account by Michael Crone.