A research team based at the University of Toronto, along with collaborators around the world, has demonstrated the effectiveness of bringing bioproduction of low-cost, robust reagents to laboratory research and diagnostics in remote or resource-limited settings.
Their paper, published in the journal Science Advances, describes hardware and molecular tools that bring the power of a handful of global biomanufacturing hubs to researchers on the ground, improving accessibility of life sciences research, empowering local innovation and improving research equity.
"For labs in low- and middle-income countries, access to critical lab bioreagents such as antibodies, enzymes and growth factors is a chronic problem," says Keith Pardee, an associate professor at U of T's Leslie Dan Faculty of Pharmacy, who led the research with colleagues around the world. "Shipping can take a long time, it's expensive and products often require a cold chain to retain their effectiveness.
"This research is in response to those challenges by bringing the production of these products into the hands of the researchers themselves."
Pardee and his team's research focuses on improving access to research and diagnostic tools in resource-limited settings. Over the past several years, Pardee's team has been developing synthetic biology and cell-free systems built around the molecular machinery responsible for the synthesis of proteins in living cells. These freeze-dried reagents can then be shipped without a cold chain. Adding water reactivates them for on-site and on-demand production of proteins such as antibodies and enzymes. To accompany this cell-free technology, the team has also been developing portable and adaptable hardware designed for small-batch biomanufacturing.
Building on this work, Pardee and his collaborators' latest research demonstrates the effectiveness of their cell-free protein synthesis and low-cost hardware in a variety of settings - from conventional labs to remote locations. Their cell-free systems and standardized protocols enabled researchers to produce a variety of protein-based products to support lab research.
Postdoctoral researcher Mohammad Simchi used these techniques to develop a 3D-printed hand-powered centrifuge. Other applications included high-value growth factors, a preclinical vaccine for SARS-CoV-2 and diagnostic tools for a number of clinically important pathogens.
"Our work shows that it is possible to produce high-value bioreagents on site, essentially anywhere," says Severino Jefferson Ribeiro da Silva, postdoctoral fellow in Pardee's lab and first author of the study. "Through this work, we demonstrated our tools across diverse international settings while maintaining performance comparable to commercial products."
Researchers tested tools in remote areas of Canada and internationally
Key to the research was testing the tools in different settings - in both Canada and internationally. In one case, da Silva tested the diagnostic tools for tick-borne pathogens and tuberculosis at a cottage in Ontario's Algonquin Highlands. In another, graduate student Quinn Matthews demonstrated local production of enzymes in the Yukon, including producing and purifying proteins using the cell-free system and a 3D-printed centrifuge on a mountain outside Whitehorse.
Collaborators in Chile, Brazil, Colombia and India also tested the systems. The strong international collaborations - involving regular and frequent meetings, international student exchanges and knowledge sharing - ensured the teams drew diverse perspectives to develop tools that would meet the needs and challenges of potential users.
Da Silva says the researchers got a taste of the challenges when packages containing critical reagents were sent between team members - only to be delayed for weeks or months in customs, or when other materials were damaged during transit.
"Those experiences highlighted how dependent many researchers and labs still are on fragile international supply chains. If a shipment is delayed, an entire project can stop," says da Silva. "This work makes it possible to reduce that dependency by enabling local production of key proteins directly at the point of need. The goal here is not to replace centralized manufacturing but to create more equitable and resilient distributed systems that can improve global access to biotechnology."
Pardee says the goal is for research labs in low- and middle-income countries or remote settings to have access to high-quality research tools and diagnostics through on-site biomanufacturing, which increases resilience to trade or supply chains disruptions. Ultimately, this would allow more countries to build their research capacity and address their local health-care needs.
"This work is really about access and scientific empowerment. Many labs worldwide have the expertise and ideas to conduct life sciences and applied science research, but they face major challenges to accessing key bioreagents and other essential materials," says da Silva. "In these cases, decentralized biomanufacturing could help reduce those barriers and enable more local innovation, making research and diagnostics more accessible globally."
