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Adapted for Sars-Cov-2 in just 10 days, the diagnostic technology could be modified and deployed quickly in response to other future pandemics, the researchers said.
The device produces a result within about five minutes – at least three-times quicker than many lateral flow tests, which generally provide a result within 15-30 minutes.
“A rapid test means that you can open up travel much earlier in a future pandemic. You can screen people getting off of an aeroplane and determine whether they should quarantine or not. You could similarly screen people entering their workplace and so forth,” said Michael Strano, senior author of the study. “We do not yet have technology that can develop and deploy such sensors fast enough to prevent economic loss.”
The test was based on carbon nanotube sensor technology developed previously in Strano’s laboratory. The researchers identified a modified carbon nanotube capable of selectively detecting the viral proteins they were looking for, before testing it and incorporating it into a working prototype. This approach eliminated the need for antibodies or other reagents, which are time-consuming to generate, purify, and make widely available.
Carbon nanotubes – hollow, nanometre-thick cylinders made of carbon – naturally fluoresce when exposed to laser light. The researchers previously showed that by wrapping such tubes in different polymers, they could create sensors that respond to specific target molecules by chemically ‘recognising’ them.
The approach, known as Corona Phase Molecular Recognition (Cophmore), takes advantage of a phenomenon that occurs when certain types of polymers bind to a nanoparticle. Known as amphiphilic polymers, the molecules have hydrophobic regions that latch onto the tubes like anchors, and hydrophilic regions that form a series of loops extending away from the tubes. Those loops form a layer surrounding the nanotube. Depending on the arrangement of the loops, different types of target molecules can wedge into the spaces between them, altering the intensity or peak wavelength of fluorescence produced.
Researchers in Strano’s lab had already developed strategies that allowed them to predict which amphiphilic polymers would interact best with a particular target molecule, so they quickly generated a set of 11 strong candidates for Sars-Cov-2.
Within about 10 days of starting the project, the researchers had identified accurate sensors for both the nucleocapsid and the spike protein of the virus. During that time, they also incorporated the sensors into a prototype device with a fibreoptic tip that can detect fluorescence changes of the biofluid sample in real time. This eliminates the need to send the sample to a lab, which is required for the ‘gold standard’ PCR diagnostic test.
The device produces a result within about five minutes, and can detect concentrations as low as 2.4 picograms of viral protein per millilitre of sample. In more recent experiments after the new paper was submitted, the researchers reportedly achieved a ‘limit of detection’ lower than commercially available rapid tests.
The researchers also showed that the device could detect the Sars-Cov-2 nucleocapsid protein when it was dissolved in saliva, something that is usually difficult because saliva contains sticky carbohydrates and digestive enzymes that interfere with protein detection.
“This sensor shows the highest range of limit of detection, response time, and saliva compatibility even without any antibody and receptor design,” said Sooyeon Cho, lead author alongside Xiaojia Jin. “It is a unique feature of this type of molecular recognition scheme that rapid design and testing is possible, unhindered by the development time and supply chain requirements of a conventional antibody or enzymatic receptor.”
The team has filed for a patent on the technology, hoping that it could be commercialised for use as a Covid-19 diagnostic tool.
The research was published in Analytical Chemistry.
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