Table 5.
Early research stage SARS-COV-2 detection strategies in the literature.
| Target | Method | Result | Ref |
|---|---|---|---|
| A new framework to predict COVID-19 using onboard smartphone sensors | Measurement of well-known disease symptoms (fever, fatigue, headache, nausea, dry cough, lung CT imaging features, and shortness of breath) through the sensors already embedded in smartphones (cameras, inertial sensors, microphone, and temperature sensor) | The proposed framework is expected to read the smartphone sensors' signal measurements to predict the grade of severity of pneumonia. Although the sensitivity is still a question, such systems can be useful to monitor and act on mass populations worldwide online. | Maghdid et al. (2020b) |
| An electrical probe to detect COVID-19 spike protein S1 | Receptor Binding Domain-modified graphene field-effect transistor was used to identify spike proteins | The sensor can capture S1 protein at a limit of detection down to 0.2 pM, in a real-time and label-free manner. The platform could also be used to screen high-affinity antibodies. Portable electrochemical measurement systems are widely available at low-cost, and thus FET principle may be quickly transformed into a biomedical instrument for on-site diagnosis, especially in rural areas. | Zhang et al. (2020) |
| An artificial intelligence tool (based on deep learning and transfer learning algorithms) to predict COVID-10 cases | Collection of X-rays and CT scan images from multiple sources and processing by simple convolution neural network (CNN) and modified the pre-trained Alex Net model. | The constructed models provide accuracy up to 98% via a pre-trained network and 94.1% accuracy by using the modified CNN. Such algorithms can be quite fast and effective for health and regulatory institutions to monitor the pandemic in real-time and obtain fast-track data of individuals who are at risk. | Maghdid et al. (2020a) |
| A field-effect transistor device for SARS-CoV-2 spike protein detection in clinical samples | The graphene sheets coated by SARS-CoV-2 spike protein-specific antibodies were used as the transducer for sensing the signal production | The sensor detected SARS-CoV-2 in culture medium (limit of detection [LOD]: 1.6 × 101 pfu/mL) and clinical samples (LOD: 2.42 × 102 copies/mL) | Seo et al. (2020) |
| RT-LAMP-coupled with Nanoparticles are suggested for COVID-19 diagnosing | The assay is based on two sets of LAMP primers against ORF1ab and N genes of the virus. The assay results were interpreted through the nanoparticles | The sensitivity was reported as 12 copies/reaction, and no cross-reactivity was generated from non-SARS-CoV-2 templates. The analytical sensitivity was 100% (33/33) in the clinically validated oropharynx swab samples, and the specificity was also 100% (96/96) when analyzed with samples from non-COVID-patients. RT-LAMP has rapidly become an efficient tool for viral gene detection because of faster reaction times and increased sensitivity. These systems can be an alternative to the existent RT-PCR method because RT-LAMP can also be incorporated with LFA technology for individual implementation (please see the previous sections). | (Zhu et al., 2020b) |
| A microfluidic ELISA technology for rapid (15–20 min) detection of viral IgG and viral S antigen | The portable, microfluidic-based ELISA array has 12 channels. The signal intensities of the microfluidic ELISA were measured with the chemiluminescent imaging method, using a CMOS camera. Multiple exposures with adjustable exposure time were applied to enhance the dynamic ranges of the ELISA | A candidate IgG with a high binding affinity towards the SARS-CoV-2 S1 protein was identified. The microfluidic ELISA platform was used for the detection of anti-S1 monoclonal antibodies. No clinical testing was performed. The current rapid antibody tests are mainly LFA-based, and many of them still rely on instruments for increased sensitivity. Although ELISA is also instrument-dependent, it can give high throughput results with better sensitivity. | Tan et al. (2020) |
| The selected gene sequences (RdRp, E gene, ORF1ab) from SARS-CoV- through nucleic acid hybridization | A dual-functional plasmonic biosensor combining the plasmonic photothermal (PPT) effect and localized surface plasmon resonance (LSPR) was proposed for COVID-19 diagnosis. The two-dimensional gold nano islands-modified with complementary DNA receptors was used to detect the selected viral sequences |
A reasonably low detection limit of 0.22 pM was reported. SPR instruments are quite sensitive in general and easy to operate in the laboratories. They only require chip or surface modification by antigens or antibodies. They, therefore, can be a good alternative to current diagnostic tools that are limited by RT-PCR instruments. | Qiu et al. (2020) |
| Reverse transcription loop-mediated isothermal amplification (RT-LAMP) methodology was reported for simultaneous SARS-CoV-2 RNA region detection (ORF1a and N regions) | ORF1a and N gene regions from SARS-CoV-2 RNA were targeted with the RT-LAMP system using China-CDC approved primers | 45 SARS-CoV-2 positive and 25 negative samples were employed in the study. The dual gene RT-LAMP assay was found to be 95% accurate in detecting positive cases and showed no cross-reactivity or false-positive results in non-COVID- 19 samples | Butt et al. (2020) |
| A portable Surface Plasmon Resonance (SPR)-based platform for SARS-CoV-2 specific antibody detection | The SPR chip surface was modified with the viral N proteins to be able to detect the antibodies against the nucleocapsid proteins of the virus in diluted human serum samples. An SPR sensor coated with a peptide monolayer and functionalized with SARS-CoV-2 nucleocapsid recombinant protein detected anti-SARS-CoV-2 antibodies in the nanomolar range. This bioassay was performed on a portable. |
SPR instrument used with undiluted human serum samples provided binding affinities in the nanomolar range. The results were collected within 15 min of sample/sensor contact. | Djaileb et al. (2020) |
| CRISPR, Cas12-based lateral flow assay for detection of SARS-CoV-2 from RNA extracts. | The platform performs RT-LAMP with RNA samples extracted from nasopharyngeal or oropharyngeal swabs in universal transport media (UTM). Then, selected SARS-CoV-2 sequences are detected by Cas 12 enzyme, and the cleavage of a reporter dye confirms the presence of the virus | The method was validated by employing contrived reference samples and 40 clinical samples from infected US patients. The results said to be comparable with the US CDC SARS-CoV-2 real-time RT-PCR assay. | Broughton et al. (2020) |
| SARS-CoV-2 spike protein detection in saliva | A built in- house electrochemical measurement platform (eCovSens) was used for the detection. The fluorine-doped tin oxide and the gold nanoparticle (signal amplifier)-based electrode was decorated with anti-spike monoclonal antibodies to monitor the change in the conductivity upon target binding | The limit of detection was reported as small as 90 fM for the spiked saliva samples. | Mahari et al. (2020) |
| One-pot detection of SARS-CoV-2 and | The assay platform, AIOD-CRISPR, was based on dual CRISPR-Cas12a components and the LAMP principles. The assays were conducted in one pot at one step and one temperature. | The optimized system was able to detect 1.2 copies of DNA targets, and 4.6 copies of RNA targets in 40 min without the need for a preamplification step. | Ding et al. (2020) |
| SARS- CoV-2 genome sequences | Nanopore target sequencing (NTS) platform was developed to detect novel coronavirus as well as previous respiratory viruses in a simultaneous manner in 6–10 h. | The NTS platform was compared with the approved qPCR for 61 samples from suspected clinical samples. The results demonstrated that the NTS could detect more positive cases. Besides, the mutated sequences can be found along with the other respiratory viruses present in the sample. The sequencing-based virus diagnosis strategies are quite rare but highly needed since the revealed genomic and proteomic elements of the virus form the basis for the current and future diagnosis tools. | (M. M. Wang et al., 2020) |
| SARS-CoV-2 nucleic acids: N1, N2, and N3 gene regions | The diagnosis system was based on the combined use of a portable mini PCR machine and a 96-well plate reader. EvaGreen dye was employed as an intercalator for fluorescent detection of the targeted regions. | The method detected ~625 to 2 × 105 DNA copies through direct PCR amplification, and the signal measurements were performed on a plate reader, which was proposed as a portable alternative for viral gene sequencing. | Gonzalez-Gonzalez et al. (2020) |