Chung-Ang University Researchers Show A Gold-Paved Path Towards Faster COVID-19 Diagnosis

Researchers use gold nanoparticles to develop a new molecular diagnostic platform that considerably reduces the time required for COVID-19 detection

The RT-PCR test, the current diagnostic standard for COVID-19, is considerably time-consuming. To shorten the time required for SARS-CoV-2 detection, researchers have developed a nanotechnology-based platform called “SERS-PCR” using a “gold nanoparticle-internalized nanodimple” substrate. This new molecular diagnostic platform reduces the number of PCR cycles required to amplify and detect viral genes as compared to conventional RT-PCR, allowing more rapid diagnosis and helping in the mitigation of COVID-19 transmission.

The rapid spread of COVID-19, a disease caused by the SARS-CoV-2 virus, has created a public health crisis around the world. While vaccination campaigns are currently underway, early COVID-19 detection and isolation are key for controlling disease transmission and protecting vulnerable populations. The current standard for COVID-19 diagnosis is reverse transcriptase-polymerase chain reaction (RT-PCR), a technique in which viral genes are detected after they undergo multiples cycles of amplification. However, this technique is time-consuming, creating a testing backlog across diagnostic centers and leading to delayed diagnosis. Given the unpredictable nature of spikes in COVID-19 transmission, new approaches that allow faster diagnosis are the need of the hour.

Providing newfound hope is a recent study published in Biosensors and Bioelectronics, in which researchers from Korea and China have introduced a novel nanotechnology-based platform that can shorten the time required for COVID-19 diagnosis. Their surface-enhanced Raman scattering (SERS)-PCR detection platform — prepared using gold nanoparticles (AuNPs) in the cavities of Au ‘nanodimple’ substrates (AuNDSs) — can detect viral genes after only 8 cycles of amplification. That is almost one-third of the number required with conventional RT-PCR. This paper was made available online on October 31, 2021, and was published in volume 197 of the journal on February 1, 2022.

“Conventional RT-PCR is based on the detection of fluorescence signals, so 3–4 hours are required to detect SARS-CoV-2. This speed is not enough considering how rapidly COVID-19 spreads. We wanted to find a way to cut this time at least by half,” says Prof. Jaebum Choo, explaining the motivation behind the study. Fortunately, the answer was not too far. In a previous study published in 2021, Prof. Choo’s team had developed a novel detection platform in which high-sensitivity SERS signals are produced by AuNPs uniformly arranged in the cavities of AuNDSs through a technique called DNA hybridization. Based on this previous discovery, Prof. Choo and his team developed the novel SERS-PCR platform for COVID-19 diagnosis.

The newly developed SERS-PCR assay uses SERS signals to detect “bridge DNA” — small DNA probes that slowly break down in the presence of target viral genes. Therefore, in samples from patients positive for COVID-19, the concentration of bridge DNA (and therefore the SERS signal) continuously decreases with progressive PCR cycles. In contrast, when SARS-CoV-2 is not present in the sample, the concentration of bridge DNA and the resultant SERS signal remain unchanged. In this way, SARS-CoV-2 can be rapidly detected in patient samples.

The team tested the effectiveness of their system using two representative target markers of SARS-CoV-2, namely, the envelope protein (E) and RNA-dependent RNA polymerase (RdRp) genes of SARS-CoV-2. While 25 cycles were required for RT-PCR-based detection, the AuNDS-based SERS-PCR platform required only 8 cycles, considerably reducing the testing duration. “Although our results are preliminary, they provide an important proof-of-concept for the validity of SERS-PCR as a diagnostic technique. Our AuNDS-based SERS-PCR technique is a promising new molecular diagnostic platform that can considerably shorten the time required for gene detection compared to conventional RT-PCR techniques. This model can be further expanded by incorporating an automatic sampler to develop a next-generation molecular diagnostic system,” explains Prof. Choo.

Indeed, SERS-PCR could be an important tool in our arsenal against the COVID-19 pandemic. It could also create a paradigm shift in the field of molecular diagnostics, revolutionizing how we detect infectious diseases and tackle future epidemics.

Reference

Authors: Yixuan Wu 1, Hajun Dang 1, Sung-Gyu Park 2, Lingxin Chen 3, Jaebum Choo 1

Title of original paper: SERS-PCR assays of SARS-CoV-2 target genes using Au nanoparticles-internalized Au nanodimple substrates

Journal: Biosensors and Bioelectronics

DOI: https://doi.org/10.1016/j.bios.2021.113736

Affiliations:

1 Department of Chemistry, Chung-Ang University, Seoul, 06974, South Korea

2 Nano-Bio Convergence Department, Korea Institute of Materials Science KIMS, Changwon, 51508, South Korea

3 Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, 264003, China

About Chung-Ang University

Chung-Ang University is a private comprehensive research university located in Seoul, South Korea. It was started as a kindergarten in 1918 and attained university status in 1953. It is fully accredited by the Ministry of Education of Korea. Chung-Ang University conducts research activities under the slogan of “Justice and Truth.” Its new vision for completing 100 years is “The Global Creative Leader.” Chung-Ang University offers undergraduate, postgraduate, and doctoral programs, which encompass a law school, management program, and medical school; it has 16 undergraduate and graduate schools each. Chung-Ang University’s culture and arts programs are considered the best in Korea.

Website: https://neweng.cau.ac.kr/index.do

About Professor Jaebum Choo

Prof. Jaebum Choo is a Professor at the Department of Chemistry, Chung-Ang University. He obtained a PhD in Molecular Spectroscopy at the Texas A&M University. He was formerly the Director of the Center for Integrated Human Sensing System and Bionano Fusion Technology Program and is currently the Director of the Biomedical Diagnostics Research Center. His research interests include SERS, biosensors, micro-devices, and molecular spectroscopy. Currently, his focus is the development of ultrasensitive optical nano-sensor systems for rapid, sensitive, in vitro infectious disease diagnosis. In 2015, he was appointed as a Baik Nam Distinguished Professor owing to his outstanding academic contributions.