Scientists develop nanoparticle-based biosensing device for rapid and ultrasensitive detection of SARS-CoV-2

Scientists from the University of Michigan, USA, have recently developed a gold nanoparticle-based biosensing device for rapid and ultrasensitive detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in point-of-care settings. The study is currently available on the medRxiv* preprint server.

Study: Nano assembly of plasmonic probe-virus particles enabled rapid and ultrasensitive point-of-care SARS-CoV-2 detection. Image Credit: LuckyStep/Shutterstock

Background

Detection of SARS-CoV-2 RNA in respiratory specimens via reverse transcription-polymerase chain reaction (RT-PCR) is considered the gold standard for the diagnosis of coronavirus disease 2019 (COVID-19).

Although highly sensitive and specific, RT-PCR is expensive and time-consuming and requires trained personnel to perform the complex procedure. These factors make RT-PCR unsuitable for COVID-19 diagnosis in point-of-care settings.

In the current study, scientists have described the development of a nano assembly-based rapid and sensitive COVID-19 biosensor assay that does not require any sample processing.

Assay development

A hand-held biosensing device was developed in the study to rapidly and accurately detect and quantify SARS-CoV-2 particles in point-of-care settings. The assay involved only a single step of reagent–sample mixing that led to the spontaneous construction of an array of gold nanoparticles surrounding a virus particle via self-assembly.

Specifically, the assay contained antibody-conjugated gold nanoparticles as plasmonic nanoprobes that specifically bind to the spike protein of SARS-CoV-2, leading to the formation of self-assembled gold nanoparticle-virus hybrid nanostructure, which was termed the plasmo-virus particle .

The optical interaction between plasmo-virus particles induces strong multimode plasmonic coupling, leading to the generation of multiple localized surface plasmon resonance peaks. The intensities of these peaks differ with the number of viral particles present in the sample. Thus, the measurement of peak intensities allowed for quantifying virus particles in the sample with a low limit of detection.

The hand-held point-of-care biosensing device constructed in the study included a micro-optoelectronic unit with a biochip, a microcontroller, and a smartphone application software-driven data transfer unit.

The smartphone-operated device was used to perform nano assembly-based detection of SARS-CoV-2 in a small volume of viral transport medium, which is used to transfer the virus safely. Specifically, the device measures the variation of light transmission through the sample using a complementary metal oxide semiconductor photodetector.

The mode of action of the entire system involved mixing of plasmonic nanoprobe reagent solution with virus-containing medium, followed by loading of the mixture onto the biochip, insertion of the biochip into the integrated point-of-care biosensing device, and finally, the detection of photocurrent signal. Custom-made software was used for real-time monitoring of the signal via smartphone.

Diagnostic efficacy of the biosensing device

Different quantities of viral particles were used to determine the consistency of the biosensing device. Given that the plasmo-virus particle has multi-plasmonic modes at 532 nm and 780 nm wavelengths, the normalized photocurrent signal change was measured at these two wavelengths.

A standard multimode calibration curve was prepared using the photocurrent signal values, which showed that the biosensing device has high consistency in accurately quantifying SARS-CoV-2 particles with a low detection limit.

Different types of virus-containing media, including phosphate-buffered saline (PBS), saliva, and viral transport medium, were used to compare the limit of detection for these media. The findings revealed that the detection consistency of the biosensing device remains high, irrespective of the types of media used.

The device’s specificity was determined by measuring photocurrent signals for samples containing microphase, cowpea mosaic virus, SiO2 nanoparticles, or SARS-CoV-2 at different concentrations. The findings revealed that the device specifically detects SARS-CoV-2, indicating that SARS-CoV-2-targeting plasmonic nanoprobes do not cross-react with other particles tested.

Study important

The study describes the development and validation of a gold nanoparticle-viral particle assembly-based assay that consistently and accurately detects SARS-CoV-2 in point-of-care settings. The assay does not require laborious and time-consuming sample processing and can cost-effectively diagnose COVID-19 within 10 minutes.

The smartphone-operated hand-held biosensing device enables real-time monitoring of assay-generated signals in the presence of SARS-CoV-2 in clinically relevant samples.#

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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