Nanoparticles could enable a more sensitive and durable rapid COVID-19 test

Rapid antigen tests can quickly and easily tell someone they are COVID-19 positive. However, since antibody-based tests are not very sensitive, they may not detect early infections with low viral loads. Today, researchers who report in ACS sensors have developed a rapid test that uses molecularly imprinted polymer nanoparticles, rather than antibodies, to detect SARS-CoV-2. The new test is more sensitive and works in more extreme conditions than antibody-based tests.

The reference test for the diagnosis of COVID-19 remains the reverse transcription-polymerase chain reaction (RT-PCR). Although this test is very sensitive and specific, it usually takes 1-2 days to get a result, is expensive, and requires special laboratory equipment and trained personnel. In contrast, rapid antigen tests are quick (15-30 minutes) and people can take them at home without training. However, they lack sensitivity, which sometimes results in false negatives. Additionally, the tests use antibodies against SARS-CoV-2 for detection, which cannot withstand wide temperature and pH ranges. Marloes Peeters and Jake McClements of Newcastle University, Francesco Canfarotta of MIP Diagnostics and their colleagues wanted to create an inexpensive, rapid, robust and highly sensitive COVID-19 test that uses nanomolecularly imprinted polymer particles (nanoMIPs) instead of antibodies.

The researchers produced nanoMIPs against a small fragment, or peptide, of the SARS-CoV-2 spike protein by creating molecular fingerprints, or molds, in the nanoparticles. These nanoscale binding cavities were appropriately sized and shaped to recognize and bind the imprinted peptide and, therefore, the entire protein. They attached the nanoparticles most strongly bound to the peptide to printed electrodes. After showing that nanoMIPs could bind to SARS-CoV-2, they developed a prototype 3D-printed device that detects virus binding by measuring temperature changes.

When the team added samples from seven patients’ nasopharyngeal swabs to the device, liquid dripped onto the electrode and the researchers detected a change in temperature for the samples that had previously tested positive for COVID-19 by RT-PCR. The test took just 15 minutes and preliminary results indicated it could detect 6,000 times less SARS-CoV-2 than a commercial rapid antigen test. Unlike antibodies, nanoMIPs withstood hot temperatures – which could give the test a longer shelf life in hot climates – and acidic pH – which could make it useful for monitoring SARS-CoV-2 in sewage and saliva samples. However, to prove that the test has a lower false-negative rate than existing rapid antigen tests, it must be tested on many other patient samples, the researchers say.

The authors acknowledge funding and support from Newcastle University, Rosetrees Trust, Wellcome Trust, MIP Diagnostics and the Scientific Research Fund.

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