Biofoundries are integrated platforms for the rapid design, construction, and testing of genetically reprogrammed organisms for biotechnology applications and research. In practice, their application to biotechnology and genetic engineering lies mainly in the expertise of the scientists that work within them. Physically, Biofoundries are suites of laboratory automation equipment that could, conceivably, be applied to numerous scientific workflows. For example, the Earlham Biofoundy has five main automated platforms: an automated cryostorage system that will deliver a 96 well plate populated with a user-specified array of any of the 80K tubes in its store; a liquid handling system that moves nanolitre droplets of reagents (or cells) using acoustic energy; two highly flexible multi-station micro-scale liquid handling systems, and an automated microfermentation platform for optimising, monitoring and sampling microbial cultures. Similar equipment can be found in labs that conduct high-throughput genotyping, or in pathology labs, including diagnostic facilities.
Automation Platforms at the Earlham BioFoundry
Last year, the Global Biofoundry Alliance (GBA) was established to coordinate activities across the Biofoundries that are popping up across the world. While there are similarities in the goals of Foundries and, to an extent, their facilities, the projects and expertise varies between Foundries. Across the Biofoundries a wide array of molecular biology and biochemical workflows have been miniaturised, scaled and automated. In addition, numerous software packages have been developed to aid the design and analysis of experiments.
The Logo and Objectives of the Global Biofoundry Alliance
Along with specialised workflows for specific projects, most Biofoundries have miniaturised and automated at least one type of parallel DNA assembly reaction (e.g. Golden Gate and Gibson Assembly) together with several other core molecular biology workflows such as DNA/RNA purification, PCR set-up etc. All Foundries are able to perform at least hundreds of such reactions each week, and some have projects that require throughputs of thousands, or even tens of thousands.
As SARS-CoV-2, the virus strain that causes COVID-19, began to spread across the globe, it became clear that the pathology labs in many countries did not have the necessary capacity to meet demand. Further, it became apparent that the global demands for reagents required for testing, particularly for specific brands of reagents, were outstripping supply. While a few Biofoundries with existing expertise or projects in diagnostics and infectious diseases have continued to work, unfortunately most Biofoundries have been shut down as they are not certified as diagnostics laboratories, and thus many automation platforms are sitting unused as Biofoundry staff moved to working from home.
However, the scientific community has responded astoundingly quickly with several inventive detection protocols being developed and published. It has also responded to support the infrastructures already approved for diagnostics. In Norwich, movable liquid-handling platforms were relocated from the Earlham Institute to the Norfolk and Norwich University Hospital to enable automation of the approved RNA-extraction protocol. At the time of writing, additional automation from the Earlham Biofoundry is being scoped for deactivation of virus on swabs and the preparation of reagents for the approved qPCR tests. The team at the London DNA Foundry have also relocated several automation platforms to their local hospitals to increase capacity in the capital. These automation platforms also require the presence of automation specialists to program and validate the workflows and to train new operators.
As pleased as we are to offer these small measures of assistance, there is a degree of frustration that the Biofoundries, filled with appropriate equipment for high throughput testing, are not enabled to do more. Interestingly, one of the exercises planned for the next meeting of the Global BioFoundries Alliance (previously planned for May 2020 in Canada), was to agree a series of activities that Biofoundries could undertake to address a Global Challenge such as emerging diseases. Sub-groups working on software, metrology and the development of the challenge were formed last year and had already began to formulate ideas.
Since the pandemic has taken hold, we have continued these discussions with the main question being "Can Biofoundries develop generalised workflows for biosecurity threats, and, if so, what needs to be done?"
Interestingly, the many discussions all seemed to boil back down to the same aims that were initially described as the core business of the GBA:
· To test the robustness of protocols across different platforms and locations
· To establish infrastructures and a community of practice that would enable the rapid transfer and benchmarking of protocols on new platforms and in new locations
· To establish and scale-up low-cost protocols, including those that can be performed on low-cost platforms
To these, Covid-19 has added:
· The need to validate protocols using locally-manufactured reagents, which obviously includes the ability to make and validate the quality of key reagents such as reverse-transcriptases
· A greater focus on the development of workflows on deployable automation platforms that can be relocated to the point-of-of need (e.g. approved diagnostic laboratories)
It is still unclear how much these current efforts will impact the current pandemic. But, this pandemic is highlighting some of the weak links in biosecurity and preparedness, showing us where we can and should focus our efforts to be able to deal with future challenges.
Written by Dr Nicola Patron, OpenPlant project leader.