Global efforts to combat the pandemic have shifted focus over the last two years, from the vaccine rollout to combating the many variants of concern that have emerged. Through it all, diagnostics have been pivotal in controlling the spread of COVID-19.
Most frontline diagnostics work by detecting antibodies against the coronavirus in patients’ serum. However, experts say such serological assays fall short in some areas, particularly accuracy. Xiaodi Su, Principal Scientist at A*STAR’s Institute of Materials Research and Engineering (IMRE), says the problem is that these tests often use full-length viral proteins as antibody targets.
This casts a net that’s too wide—the presence of related coronaviruses can trigger a false positive. Moreover, current gold standard tests require multiple steps and reagents, making them time-consuming and expensive.
Su and Lisa Ng, Executive Director of A*STAR Infectious Diseases Labs (ID Labs), led an initiative to develop faster, more reliable COVID-19 serological assays. To tackle this big challenge, the team turned to tiny, colour-changing spheres of gold nanoparticles, or AuNPs.
The researchers devised an innovative approach of coating the outer surface of these nanoparticles with short segments of viral proteins, known to bind to antibodies in the blood of COVID-19 patients. However, they had to cross a technical hurdle: getting the viral proteins to stick to the AuNPs proved challenging because of their incompatible surface charges.
“We overcame this difficulty by using a linker protein to first stabilise the nanoparticles; the charged epitopes could then be attached easily to the protein-stabilised nanoparticles,” Su explained.
After successfully formulating the AuNPs, the team incorporated nanoparticles into their newly developed assay. When exposed to the blood from a COVID-positive patient, the AuNPs bound to SARS-CoV-2-specific antibodies and clumped together. This in turn changed the colour of the solution, indicating a positive result in just 30 minutes.
In their study, the researchers outlined the advantages of their nanotechnology-powered test: it’s fast, cost-effective, doesn’t require specialised equipment for the test readout, and is remarkably sensitive and accurate.
The AuNPs could identify positive patient samples with 100% specificity and 83% sensitivity, thereby avoiding false positives from related coronaviruses and detecting even trace concentrations of antibodies at the early stages of infection.
Building on their achievement, the team plans to advance their innovation to handle even trickier applications, such as identifying viral variants.
“As our epitopes are well-conserved across the different variants of concern, it would also be worthwhile to assess the performance of this platform in patient samples infected with SARS-CoV-2 variants such as Delta and Omicron,” said Ng.
The A*STAR-affiliated researchers contributing to this research are from the A*STAR Infectious Diseases Labs (ID Labs) and the Institute of Materials Research and Engineering (IMRE).