That’s because a team of researchers at the University of Ottawa’s Flow Chemistry Research Facility, within Centre for Catalysis Research and Innovation (CCRI), developed a new, more sustainable, and safer way to prepare large quantities of an essential ingredient used in test kit preparation to diagnose SARS-CoV-2 – and thereby address its global shortage.
We talked to Dr. Michael Organ, Professor in the Department of Chemistry and Biomolecular Sciences at the University of Ottawa and Director of the CCRI, to learn more.
Please tell us about this new technology.
“Testing for SARS-CoV-2 is done using a Polymerase Chain Reaction (PCR)-based test to detect the viral RNA. The PCR test kit contains probes that are prepared while attached to the surface of glass beads by a special non-nucleoside linker (see Figure below). This linker requires a series of chemical steps to make it from commercially available starting chemicals, and the key step has proven problematic.
Our team has developed a sustainable flow chemistry route for carrying out that key step.
COVID-19 is just one possible test target since the technology is applicable to many targets beyond the current application.”
What exactly is flow chemistry?
“Flow chemistry is the continuous synthesis of compounds travelling through a long tube, rather than in traditional large vats called ‘batch reactors’. The flow approach produces smaller amounts of material at a time but does so continuously over a longer period of time. Flow is more readily controlled and often leads to cleaner product mixtures that are easier to purify. It is referred to as a form of “sustainable manufacturing.” That is, you only make it as you need and use it right away – this avoids large and potentially dangerous (and expensive) chemical stockpiles of high-value material. Further, the flowed process can be stopped the minute something changes in the process and does not compromise the material already made. The batch approach carries the risk of losing an entire batch if something goes wrong, which may mean the loss of millions of dollars in the pharmaceutical sector, for example.”
Why was there a need to prepare the linker in large quantities?
“In light of the COVID-19 pandemic, there was an acute global shortage of this material due to the difficulties associated with its preparation.
Prior to COVID-19, the annual consumption of this chemical for such test kits has been in the kilogram per year range, and this is supplied by Toronto Research Chemicals (TRC) an LGC subsidiary in Toronto. Demand for this material has now increased to over 25 times the annual global consumption.
The technology developed at uOttawa can now produce multi kilograms of this material per month, allowing TRC to meet its global requirement. If the need for tests increases, the system could be run for a longer time to produce more material, or a second system could be set up and run in parallel.
This exercise has allowed TRC to consider moving other chemical preparations to flow, thereby making them safer and more controlled processes.”
How did you achieve that?
“Our group was one of the first academic groups to engage the production of small, organic molecules using flow. We have been developing various aspects of the technology for almost 20 years.
The chemistry involved in the TRC project is temperamental and must be, especially on larger scale, done with great care to ensure that the process is strictly controlled and safe.
We invented a flow reactor specifically tailored for this process to implement a tight set of operating conditions to control the synthesis of the key linker molecule, which is obtained from this process in high yield and purity, and in a safe manner.
Hundreds of grams of this precious material have been prepared at uOttawa in the Flow Chemistry Research Facility and sent to TRC, so that it can make its way into the COVID-19 test kits.
TRC has been a major fine chemical manufacturer for over 30 years and the world experts on manufacturing this particular compound. They know it well, how to purify, analyze, store, etc. They also have the established relationship with the end users that make the test kits through their supply chain.”
What are the next steps?
“The company has committed funding to support expanding the project. This will include moving more scale-up chemical processes at TRC, in Toronto, to flow.
Also, the Flow Facility at uOttawa is developing technology in artificial intelligence (AI). This will enable such chemical processes to be optimized using algorithms to reach the best possible set of reaction conditions with which to manufacture.
This is closely related to machine learning (ML), which includes the invention of ‘smart equipment’ that can perform operations in the absence of an operator. This will ultimately be linked wirelessly to the cell phones of chemists, for example, to monitor and control processes remotely.
The idea here is to lower the human footprint in the laboratory, which will not only benefit the current COVID-19 restrictions, but we believe that this could be the trigger for such a more permanent change in the labs of the future. This could have a considerable impact on Equity, Diversity and Inclusion (EDI) in the field of chemistry, as the possibility of carrying out chemical operations remotely would be helpful for people who can work effectively from home.”
The team leaders of this project include: Dr. Andrew Corbett (Director of Production Chemistry at TRC), Prof. Michael Organ (uOttawa CCRI Director), Dr. Debasis Mallik (uOttawa Flow Chemistry Manager in the CCRI), Dr. Aliakbar Mohammadzadeh (Mechanical Engineer, postdoctoral fellow, uOttawa), Dr. Sepideh Sharif (Synthetic Chemist, postdoctoral fellow, uOttawa), Dr. Jürgen Schulmeister (Synthetic Chemist, postdoctoral fellow, uOttawa), Dr. Volodymyr Semeniuchenko (Synthetic Chemist, Research Associate, uOttawa), Mr. Peter Zhang (Software Engineer, York University). Special thanks to Professor Arturo Macchi (Chemical Engineer, uOttawa).
The Organ Group has received funding from the Natural Sciences and Engineering Research Council (NSERC) for this project, as well as a MITACS COVID-19 grant, which matched funding provided by TRC.
About the Flow Chemistry Research Facility
The Flow Chemistry Research Facility within the CCRI, managed by Dr. Debasis Mallik ([email protected]), is equipped with state-of-the-art equipment for innovative research in sustainable manufacturing. The facility, which is built as an international hub for innovative academic-industrial partnerships through fundamental research in flow chemistry and analysis. Currently, collaborates with members of the university research community, as well as industrial leaders, who are building new tools for smart manufacturing (including AI) and process analytical technology (PAT).
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