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Author: Nicholas Kirkwood, University of Melbourne
As Australia continues to roll out the COVID-19 vaccine nationwide, and the threat of new and existing global variants is imminent, rapid testing remains essential for identification, contact tracing, and infection control.
With the support of our Australian collaborators, our research team is about to complete a one-year exploration of developing commercial quantities of locally sourced magnetic nanoparticles-a key missing component of a completely Australian-made COVID-19 test kit.
Although antibody tests (used in most Australian testing centers) can show who has been exposed and developed an immune response, polymerase chain reaction (PCR) testing is the gold standard for determining whether a person is currently infected.
Many Australians, and even many people around the world, are familiar with the "swab test" for COVID-19. "First wipe the back of your throat with a cotton swab, then go deep into the two nostrils-this is a strange and unpleasant sensation.
COVID testing: behind the scenes
The part you can't see occurs in the laboratory, where the technician analyzes the RNA in the sample-the genetic material of SARS-CoV-2-the virus that causes COVID-19.
A key part of the laboratory process is the separation of genetic material (called nucleic acid) from other biological material collected on the swab. This is achieved using magnetic silica nanoparticles.
These nanoparticles are usually only a few hundred nanometers (one millionth of a millimeter) in size and consist of a core of magnetic material encased in a thin silica (glass) shell, which is then added to a vial containing a swab solution .
A special salt is added to make all the nucleic acids in the swab reversibly adhere to the silica gel shell.
Because nanoparticles are magnetic, simple magnets can now be used to collect nucleic acids and separate them from all other unwanted biological materials in the swab.
The purified nucleic acid is then separated from the magnetic silica nanoparticles, and a PCR test is performed to check for the presence of any SARS-CoV-2 viral RNA.
However, when the pandemic hit, Australia did not produce magnetic silica nanoparticles, and because there were still no local producers, Australian test kit manufacturers had to source from overseas.
The global demand for these particles has increased significantly, driving up costs, disrupting the supply chain, and limiting the supply of magnetic beads from Australian swab test kit manufacturers.
The Australian government established a COVID test kit working group, which requested the help of our nanoscience laboratory in March 2020 to help produce magnetic silica particles locally and ensure a supply of at least 100,000 COVID tests per week .
But there are some problems.
First of all, commercial particles are produced overseas through a non-public proprietary method, so before we create an Australian supply, we need to come up with our own method to produce functional magnetic silica nanoparticles.
Fortunately, at the ARC Center of Excellence in Exciton Science, we have been committed to manufacturing magnetic nanoparticles for other applications, including quantum dot synthesis, so we can quickly design and test methods to make suitable products.
Local production during the pandemic
The second question is that it is 2020 and we are in Melbourne. Due to strict movement restrictions for most of the year, almost all faculty, staff and students cannot enter the University’s Parkville campus.
However, our team of researchers was allowed to occupy space in the largely deserted School of Chemistry to meet this important challenge.
The last issue is the issue of scale.
Each test kit requires approximately 5 micrograms of silica particles, so in order to meet 100,000 tests per week, our initial goal is to produce 500 grams of magnetic nanoparticles per week.
We have chemical expertise, but for a research laboratory that is accustomed to performing small reactions and producing less than 1 gram of product, we cannot use all the necessary equipment.
To understand how big the problem is, imagine being told in your kitchen to make enough spaghetti sauce for a thousand people.
In order to achieve a substantial increase in scale, we have established partnerships with several Australian companies, including Scaled Organics in Melbourne, and they have provided their pilot reactors to produce the amount of materials we need.
Then, Genetic Signatures, a Sydney-based COVID test kit manufacturer, was able to verify that each batch of nanoparticles is suitable for real COVID testing conditions.
We have also received support from the Monash Electron Microscopy Center and the Australian Synchrotron, who imaged commercial samples of nanoparticles and compared them with our test batches.
The response needs to be simple and relatively few steps to minimize costs and other scalability barriers.
After months of long and all-weather work, we identified, optimized, verified and expanded the synthesis of silica-coated magnetic nanoparticles.
But there is an obstacle.
We noticed that the color of the nanoparticle sample changed soon after synthesis, which prompted people to speculate that the crystal structure of the nanoparticle changed from magnetite (Fe₃O₄) to maghemite (Fe2O₃) over time.
Recognizing the importance of this project, the Australian Nuclear Science and Technology Organisation (ANSTO) provided us with the priority use of their equipment, the X-ray Absorption Spectroscopy (XAS) beamline of the Australian Synchrotron to solve this problem.
Since the two crystal structures are very similar, it is difficult to distinguish them, but X-ray absorption spectroscopy can easily distinguish them. From the results, we determined that one salt we added to the reaction mixture promoted the formation of one crystal structure, not the other (these results will be announced later).
We were then able to find the optimal salt concentration to produce magnetite, which is preferred because it is more magnetic than maghemite and functions better in finished nanoparticles.
In order to develop products that are compatible with similar foreign products, we have conducted more than 500 small batch experiments to optimize every element of production, including the thickness of the silica coating, reagent ratio and concentration, and even different purification methods.
After clinical testing, our nanoparticles will soon be available to provide magnetic silica nanoparticles for COVID-19 test kits made in Australia-because we will continue to meet the challenges of this unprecedented global health emergency. Further exploration. From thousands of small magnetic balls to 150,000 COVID-19 tests per week. Citation provided by the University of Melbourne: Manufacturing Nanoparticle Components for COVID-19 Testing Made in Australia (2021, August 20), November 2021 Retrieved from https://phys on the 12th. org/news/2021-08-nanoparticle-ingredient-australian-made-covid.html This document is protected by copyright. Except for any fair transaction for private learning or research purposes, no part may be copied without written permission. The content is for reference only.
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