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Detection and Diagnosis of the New Coronavirus

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A special issue of Sensors (ISSN 1424-8220). This special issue belongs to the section "Biosensors".

Deadline for manuscript submissions: closed (10 June 2022) | Viewed by 104718

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Dr. Ajeet Kaushik

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Department of Natural Sciences, Division of Sciences, Arts & Mathematics (SAM), Florida Polytechnic University, Lakeland, FL 33805-8531, USA
Interests: functional materials; polymers; sensors; biosensors; nanomedicine drug delivery systems
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Hai-Feng (Frank) Ji

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Department of Chemistry, Drexel University, 3141 Chestnut Street, Disque 507, Philadelphia, PA 19104, USA
Interests: MEMS; microcantilever; FET; fluorescent; polythiophene; polyaniline; hydrogel; nanocomposites
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The World Health Organization (WHO) has declared the novel coronavirus 2019 (COVID-19) an international health emergency due to severity of infection progression which has led to the loss of over 3000 people as of 3 March 2020. This COVID-19 epidemic is becoming more serious due to its continuous spread globally and the unavailability of appropriate therapy and diagnostics systems. International health agencies are making serious efforts to manage the COVID-19 epidemic via exploring every aspect of therapy development with a special attention on investigating smart diagnostics tool needs for rapid and selective detection of the COVID-19 protein. Such diagnostics systems not only will make detection possible but will also generate the bio-informatics required to understand COVID-19 infection progression along with establishing a correlation between COVID-19 level and pathogenesis.

Efforts are being to make investigate biomarker specific to COVID-19 and required to develop vaccines, drug, therapies, and diagnostics system. In this direction, cryo-EM based studies have been performed to design crystal structure of COVID-19 to explore active and functional sites. Such of informatics is useful to design and develop vaccine, drugs, and therapeutics. Another potential approach to manage COVID-19 epidemic is to degrade virus structure in the air using photo-senstized nano-particle embadded filaters.

Keeping challenge of rapid and diagnostics at point-of-care, experts have suggested exploring nano-enabled sensing systems. The introduction of nanotechnology and advanced system packaging will be useful to design and develop miniaturized sensing systems which are recommended to perform diagnostics at point-of-care application. Rapid and POC diagnostics of COVID-19 will produce useful informatics, which can be shared with clinics through the Internet of Things (IoT) for quick analysis to prescribe therapy. Additionally, there is a potential scope to introduce artificial intelligence to analyze big data collected using IoT-assisted sensing systems for better understanding of the COVID-19 epidemic progression and relation of the COVID-19 level with pathogenesis and variabilities such as genome, age, race, gender, etc. Overall, smart detection and diagnostics of COVID-19 are a potential solution to manage the COVID-19 epidemic, even in personalized medicine.

Keeping this in view, this Special Issue welcomes research findings, technical notes, and full reviews addressing the aspects of smart sensing of COVID-19 for health wellness.

Prof. Dr. Ajeet Kaushik
Prof. Dr. Hai-Feng (Frank) Ji
Guest Editors

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Keywords

Diagnostics and detection of COVID-19
Smart sensors for early-stage diagnotics
Miniaturized COVID-19 sensors
Point-of-care diagnostics of COVID-19
Artificial intelligence for COVID-19 diseases management
Internet-of-Things-assisted approaches
COVID-19 disease management
Personalized approaches

Published Papers (11 papers)

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Research

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13 pages, 1324 KiB

Open AccessArticle

Molecular Beacon Assay Development for Severe Acute Respiratory Syndrome Coronavirus 2 Detection

by Josué Carvalho, Jéssica Lopes-Nunes, Joana Figueiredo, Tiago Santos, André Miranda, Micaela Riscado, Fani Sousa, Ana Paula Duarte, Sílvia Socorro, Cândida Teixeira Tomaz, Mafalda Felgueiras, Rui Teixeira, Conceição Faria and Carla Cruz

Sensors 2021, 21(21), 7015; https://0-doi-org.brum.beds.ac.uk/10.3390/s21217015 - 22 Oct 2021

Cited by 5 | Viewed by 3199

Abstract

The fast spread of SARS-CoV-2 has led to a global pandemic, calling for fast and accurate assays to allow infection diagnosis and prevention of transmission. We aimed to develop a molecular beacon (MB)-based detection assay for SARS-CoV-2, designed to detect the ORF1ab and S genes, proposing a two-stage COVID-19 testing strategy. The novelty of this work lies in the design and optimization of two MBs for detection of SARS-CoV-2, namely, concentration, fluorescence plateaus of hybridization, reaction temperature and real-time results. We also identify putative G-quadruplex (G4) regions in the genome of SARS-CoV-2. A total of 458 nasopharyngeal and throat swab samples (426 positive and 32 negative) were tested with the MB assay and the fluorescence levels compared with the cycle threshold (Ct) values obtained from a commercial RT-PCR test in terms of test duration, sensitivity, and specificity. Our results show that the samples with higher fluorescence levels correspond to those with low Ct values, suggesting a correlation between viral load and increased MB fluorescence. The proposed assay represents a fast (total duration of 2 h 20 min including amplification and fluorescence reading stages) and simple way of detecting SARS-CoV-2 in clinical samples from the upper respiratory tract. Full article

(This article belongs to the Special Issue Detection and Diagnosis of the New Coronavirus)

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12 pages, 4896 KiB

Open AccessCommunication

Automated ELISA On-Chip for the Detection of Anti-SARS-CoV-2 Antibodies

by Everardo González-González, Ricardo Garcia-Ramirez, Gladys Guadalupe Díaz-Armas, Miguel Esparza, Carlos Aguilar-Avelar, Elda A. Flores-Contreras, Irám Pablo Rodríguez-Sánchez, Jesus Rolando Delgado-Balderas, Brenda Soto-García, Diana Aráiz-Hernández, Marisol Abarca-Blanco, José R. Yee-de León, Liza P. Velarde-Calvillo, Alejandro Abarca-Blanco and Juan F. Yee-de León

Sensors 2021, 21(20), 6785; https://0-doi-org.brum.beds.ac.uk/10.3390/s21206785 - 13 Oct 2021

Cited by 12 | Viewed by 4236

Abstract

The COVID-19 pandemic has been the most critical public health issue in modern history due to its highly infectious and deathly potential, and the limited access to massive, low-cost, and reliable testing has significantly worsened the crisis. The recovery and the vaccination of millions of people against COVID-19 have made serological tests highly relevant to identify the presence and levels of SARS-CoV-2 antibodies. Due to its advantages, microfluidic-based technologies represent an attractive alternative to the conventional testing methodologies used for these purposes. In this work, we described the development of an automated ELISA on-chip capable of detecting anti-SARS-CoV-2 antibodies in serum samples from COVID-19 patients and vaccinated individuals. The colorimetric reactions were analyzed with a microplate reader. No statistically significant differences were observed when comparing the results of our automated ELISA on-chip against the ones obtained from a traditional ELISA on a microplate. Moreover, we demonstrated that it is possible to carry out the analysis of the colorimetric reaction by performing basic image analysis of photos taken with a smartphone, which constitutes a useful alternative when lacking specialized equipment or a laboratory setting. Our automated ELISA on-chip has the potential to be used in a clinical setting and mitigates some of the burden caused by testing deficiencies. Full article

(This article belongs to the Special Issue Detection and Diagnosis of the New Coronavirus)

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13 pages, 2134 KiB

Open AccessArticle

CovidArray: A Microarray-Based Assay with High Sensitivity for the Detection of Sars-Cov-2 in Nasopharyngeal Swabs

by Francesco Damin, Silvia Galbiati, Stella Gagliardi, Cristina Cereda, Francesca Dragoni, Claudio Fenizia, Valeria Savasi, Laura Sola and Marcella Chiari

Sensors 2021, 21(7), 2490; https://0-doi-org.brum.beds.ac.uk/10.3390/s21072490 - 03 Apr 2021

Cited by 15 | Viewed by 5595

Abstract

A new coronavirus (SARS-CoV-2) caused the current coronavirus disease (Covid-19) epidemic. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is used as the gold standard for clinical detection of SARS-CoV-2. Under ideal conditions, RT-qPCR Covid-19 assays have analytical sensitivity and specificity greater than 95%. However, when the sample panel is enlarged including asymptomatic individuals, the sensitivity decreases and false negatives are reported. Moreover, RT-qPCR requires up to 3–6 h with most of the time involved in RNA extraction from swab samples. We introduce CovidArray, a microarray-based assay, to detect SARS-CoV-2 markers N1 and N2 in the nasopharyngeal swabs. The method is based on solid-phase hybridization of fluorescently-labeled amplicons upon RNA extraction and reverse transcription. This approach combines the physical-optical properties of the silicon substrate with the surface chemistry used to coat the substrate to obtain a diagnostic tool of great sensitivity. Furthermore, we used an innovative approach, RNAGEM, to extract and purify viral RNA in less than 15 min. We correctly assigned 12 nasopharyngeal swabs, previously analyzed by RT-qPCR. Thanks to the CovidArray sensitivity we were able to identify a false-negative sample. CovidArray is the first DNA microarray-based assay to detect viral genes in the swabs. Its high sensitivity and the innovative viral RNA extraction by RNAGEM allows the reduction of both the amount of false-negative results and the total analysis time to about 2 h. Full article

(This article belongs to the Special Issue Detection and Diagnosis of the New Coronavirus)

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11 pages, 1788 KiB

Open AccessArticle

Rapid SARS-CoV-2 Detection Using Electrochemical Immunosensor

by Biljana Mojsoska, Sylvester Larsen, Dorte Aalund Olsen, Jonna Skov Madsen, Ivan Brandslund and Fatima AlZahra’a Alatraktchi

Sensors 2021, 21(2), 390; https://0-doi-org.brum.beds.ac.uk/10.3390/s21020390 - 08 Jan 2021

Cited by 152 | Viewed by 11849

Abstract

The outbreak of the coronavirus disease (COVID-19) pandemic caused by the novel coronavirus (SARS-CoV-2) has been declared an international public health crisis. It is essential to develop diagnostic tests that can quickly identify infected individuals to limit the spread of the virus and assign treatment options. Herein, we report a proof-of-concept label-free electrochemical immunoassay for the rapid detection of SARS-CoV-2 virus via the spike surface protein. The assay consists of a graphene working electrode functionalized with anti-spike antibodies. The concept of the immunosensor is to detect the signal perturbation obtained from ferri/ferrocyanide measurements after binding of the antigen during 45 min of incubation with a sample. The absolute change in the [Fe(CN)₆]₃−/⁴⁻ current upon increasing antigen concentrations on the immunosensor surface was used to determine the detection range of the spike protein. The sensor was able to detect a specific signal above 260 nM (20 µg/mL) of subunit 1 of recombinant spike protein. Additionally, it was able to detect SARS-CoV-2 at a concentration of 5.5 × 10⁵ PFU/mL, which is within the physiologically relevant concentration range. The novel immunosensor has a significantly faster analysis time than the standard qPCR and is operated by a portable device which can enable on-site diagnosis of infection. Full article

(This article belongs to the Special Issue Detection and Diagnosis of the New Coronavirus)

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26 pages, 21522 KiB

Open AccessReview

Human Body Performance with COVID-19 Affectation According to Virus Specification Based on Biosensor Techniques

by Mohammed Jawad Ahmed Alathari, Yousif Al Mashhadany, Mohd Hadri Hafiz Mokhtar, Norhafizah Burham, Mohd Saiful Dzulkefly Bin Zan, Ahmad Ashrif A Bakar and Norhana Arsad

Sensors 2021, 21(24), 8362; https://0-doi-org.brum.beds.ac.uk/10.3390/s21248362 - 15 Dec 2021

Cited by 3 | Viewed by 3725

Abstract

Life was once normal before the first announcement of COVID-19’s first case in Wuhan, China, and what was slowly spreading became an overnight worldwide pandemic. Ever since the virus spread at the end of 2019, it has been morphing and rapidly adapting to human nature changes which cause difficult conundrums in the efforts of fighting it. Thus, researchers were steered to investigate the virus in order to contain the outbreak considering its novelty and there being no known cure. In contribution to that, this paper extensively reviewed, compared, and analyzed two main points; SARS-CoV-2 virus transmission in humans and detection methods of COVID-19 in the human body. SARS-CoV-2 human exchange transmission methods reviewed four modes of transmission which are Respiratory Transmission, Fecal–Oral Transmission, Ocular transmission, and Vertical Transmission. The latter point particularly sheds light on the latest discoveries and advancements in the aim of COVID-19 diagnosis and detection of SARS-CoV-2 virus associated with this disease in the human body. The methods in this review paper were classified into two categories which are RNA-based detection including RT-PCR, LAMP, CRISPR, and NGS and secondly, biosensors detection including, electrochemical biosensors, electronic biosensors, piezoelectric biosensors, and optical biosensors. Full article

(This article belongs to the Special Issue Detection and Diagnosis of the New Coronavirus)

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26 pages, 3567 KiB

Open AccessReview

Biosensors as Nano-Analytical Tools for COVID-19 Detection

by Anchal Pradhan, Preeti Lahare, Priyank Sinha, Namrata Singh, Bhanushree Gupta, Kamil Kuca, Kallol K. Ghosh and Ondrej Krejcar

Sensors 2021, 21(23), 7823; https://0-doi-org.brum.beds.ac.uk/10.3390/s21237823 - 24 Nov 2021

Cited by 19 | Viewed by 6224

Abstract

Selective, sensitive and affordable techniques to detect disease and underlying health issues have been developed recently. Biosensors as nanoanalytical tools have taken a front seat in this context. Nanotechnology-enabled progress in the health sector has aided in disease and pandemic management at a very early stage efficiently. This report reflects the state-of-the-art of nanobiosensor-based virus detection technology in terms of their detection methods, targets, limits of detection, range, sensitivity, assay time, etc. The article effectively summarizes the challenges with traditional technologies and newly emerging biosensors, including the nanotechnology-based detection kit for COVID-19; optically enhanced technology; and electrochemical, smart and wearable enabled nanobiosensors. The less explored but crucial piezoelectric nanobiosensor and the reverse transcription-loop mediated isothermal amplification (RT-LAMP)-based biosensor are also discussed here. The article could be of significance to researchers and doctors dedicated to developing potent, versatile biosensors for the rapid identification of COVID-19. This kind of report is needed for selecting suitable treatments and to avert epidemics. Full article

(This article belongs to the Special Issue Detection and Diagnosis of the New Coronavirus)

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24 pages, 7063 KiB

Open AccessReview

COVID-19 Testing and Diagnostics: A Review of Commercialized Technologies for Cost, Convenience and Quality of Tests

by Ashler Benda, Lukas Zerajic, Ankita Ankita, Erin Cleary, Yunsoo Park and Santosh Pandey

Sensors 2021, 21(19), 6581; https://0-doi-org.brum.beds.ac.uk/10.3390/s21196581 - 01 Oct 2021

Cited by 38 | Viewed by 13417

Abstract

Population-scale and rapid testing for SARS-CoV-2 continues to be a priority for several parts of the world. We revisit the in vitro technology platforms for COVID-19 testing and diagnostics—molecular tests and rapid antigen tests, serology or antibody tests, and tests for the management of COVID-19 patients. Within each category of tests, we review the commercialized testing platforms, their analyzing systems, specimen collection protocols, testing methodologies, supply chain logistics, and related attributes. Our discussion is essentially focused on test products that have been granted emergency use authorization by the FDA to detect and diagnose COVID-19 infections. Different strategies for scaled-up and faster screening are covered here, such as pooled testing, screening programs, and surveillance testing. The near-term challenges lie in detecting subtle infectivity profiles, mapping the transmission dynamics of new variants, lowering the cost for testing, training a large healthcare workforce, and providing test kits for the masses. Through this review, we try to understand the feasibility of universal access to COVID-19 testing and diagnostics in the near future while being cognizant of the implicit tradeoffs during the development and distribution cycles of new testing platforms. Full article

(This article belongs to the Special Issue Detection and Diagnosis of the New Coronavirus)

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0 pages, 4348 KiB

Open AccessReview

An Analysis Review of Detection Coronavirus Disease 2019 (COVID-19) Based on Biosensor Application

by Bakr Ahmed Taha, Yousif Al Mashhadany, Mohd Hadri Hafiz Mokhtar, Mohd Saiful Dzulkefly Bin Zan and Norhana Arsad

Sensors 2020, 20(23), 6764; https://0-doi-org.brum.beds.ac.uk/10.3390/s20236764 - 26 Nov 2020

Cited by 59 | Viewed by 8845

Abstract

Timely detection and diagnosis are essentially needed to guide outbreak measures and infection control. It is vital to improve healthcare quality in public places, markets, schools and airports and provide useful insights into the technological environment and help researchers acknowledge the choices and gaps available in this field. In this narrative review, the detection of coronavirus disease 2019 (COVID-19) technologies is summarized and discussed with a comparison between them from several aspects to arrive at an accurate decision on the feasibility of applying the best of these techniques in the biosensors that operate using laser detection technology. The collection of data in this analysis was done by using six reliable academic databases, namely, Science Direct, IEEE Xplore, Scopus, Web of Science, Google Scholar and PubMed. This review includes an analysis review of three highlights: evaluating the hazard of pandemic COVID-19 transmission styles and comparing them with Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) to identify the main causes of the virus spreading, a critical analysis to diagnose coronavirus disease 2019 (COVID-19) based on artificial intelligence using CT scans and CXR images and types of biosensors. Finally, we select the best methods that can potentially stop the propagation of the coronavirus pandemic. Full article

(This article belongs to the Special Issue Detection and Diagnosis of the New Coronavirus)

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28 pages, 5070 KiB

Open AccessFeature PaperReview

Point-of-Care Diagnostics of COVID-19: From Current Work to Future Perspectives

by Heba A. Hussein, Rabeay Y. A. Hassan, Marco Chino and Ferdinando Febbraio

Sensors 2020, 20(15), 4289; https://0-doi-org.brum.beds.ac.uk/10.3390/s20154289 - 31 Jul 2020

Cited by 61 | Viewed by 11613

Abstract

Coronaviruses have received global concern since 2003, when an outbreak caused by SARS-CoV emerged in China. Later on, in 2012, the Middle-East respiratory syndrome spread in Saudi Arabia, caused by MERS-CoV. Currently, the global crisis is caused by the pandemic SARS-CoV-2, which belongs to the same lineage of SARS-CoV. In response to the urgent need of diagnostic tools, several lab-based and biosensing techniques have been proposed so far. Five main areas have been individuated and discussed in terms of their strengths and weaknesses. The cell-culture detection and the microneutralization tests are still considered highly reliable methods. The genetic screening, featuring the well-established Real-time polymerase chain reaction (RT-PCR), represents the gold standard for virus detection in nasopharyngeal swabs. On the other side, immunoassays were developed, either by screening/antigen recognition of IgM/IgG or by detecting the whole virus, in blood and sera. Next, proteomic mass-spectrometry (MS)-based methodologies have also been proposed for the analysis of swab samples. Finally, virus-biosensing devices were efficiently designed. Both electrochemical immunosensors and eye-based technologies have been described, showing detection times lower than 10 min after swab introduction. Alternative to swab-based techniques, lateral flow point-of-care immunoassays are already commercially available for the analysis of blood samples. Such biosensing devices hold the advantage of being portable for on-site testing in hospitals, airports, and hotspots, virtually without any sample treatment or complicated lab precautions. Full article

(This article belongs to the Special Issue Detection and Diagnosis of the New Coronavirus)

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Other

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10 pages, 1571 KiB

Open AccessLetter

Functionalized TiO₂ Nanotube-Based Electrochemical Biosensor for Rapid Detection of SARS-CoV-2

by Bhaskar S. Vadlamani, Timsy Uppal, Subhash C. Verma and Mano Misra

Sensors 2020, 20(20), 5871; https://0-doi-org.brum.beds.ac.uk/10.3390/s20205871 - 17 Oct 2020

Cited by 151 | Viewed by 9182

Abstract

The COronaVIrus Disease (COVID-19) is a newly emerging viral disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Rapid increase in the number of COVID-19 cases worldwide led the WHO to declare a pandemic within a few months after the first case of infection. Due to the lack of a prophylactic measure to control the virus infection and spread, early diagnosis and quarantining of infected as well as the asymptomatic individuals are necessary for the containment of this pandemic. However, the current methods for SARS-CoV-2 diagnosis are expensive and time consuming, although some promising and inexpensive technologies are becoming available for emergency use. In this work, we report the synthesis of a cheap, yet highly sensitive, cobalt-functionalized TiO₂ nanotubes (Co-TNTs)-based electrochemical sensor for rapid detection of SARS-CoV-2 through sensing the spike (receptor binding domain (RBD)) present on the surface of the virus. A simple, low-cost, and one-step electrochemical anodization route was used for synthesizing TNTs, followed by an incipient wetting method for cobalt functionalization of the TNTs platform, which was connected to a potentiostat for data collection. This sensor specifically detected the S-RBD protein of SARS-CoV-2 even at very low concentration (range of 14 to 1400 nM (nano molar)). Additionally, our sensor showed a linear response in the detection of viral protein over the concentration range. Thus, our Co-TNT sensor is highly effective in detecting SARS-CoV-2 S-RBD protein in approximately 30 s, which can be explored for developing a point of care diagnostics for rapid detection of SARS-CoV-2 in nasal secretions and saliva samples. Full article

(This article belongs to the Special Issue Detection and Diagnosis of the New Coronavirus)

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12 pages, 1902 KiB

Open AccessLetter

Development of a Portable, Ultra-Rapid and Ultra-Sensitive Cell-Based Biosensor for the Direct Detection of the SARS-CoV-2 S1 Spike Protein Antigen

by Sophie Mavrikou, Georgia Moschopoulou, Vasileios Tsekouras and Spyridon Kintzios

Sensors 2020, 20(11), 3121; https://0-doi-org.brum.beds.ac.uk/10.3390/s20113121 - 31 May 2020

Cited by 198 | Viewed by 22909

Abstract

One of the key challenges of the recent COVID-19 pandemic is the ability to accurately estimate the number of infected individuals, particularly asymptomatic and/or early-stage patients. We herewith report the proof-of-concept development of a biosensor able to detect the SARS-CoV-2 S1 spike protein expressed on the surface of the virus. The biosensor is based on membrane-engineered mammalian cells bearing the human chimeric spike S1 antibody. We demonstrate that the attachment of the protein to the membrane-bound antibodies resulted in a selective and considerable change in the cellular bioelectric properties measured by means of a Bioelectric Recognition Assay. The novel biosensor provided results in an ultra-rapid manner (3 min), with a detection limit of 1 fg/mL and a semi-linear range of response between 10 fg and 1 μg/mL. In addition, no cross-reactivity was observed against the SARS-CoV-2 nucleocapsid protein. Furthermore, the biosensor was configured as a ready-to-use platform, including a portable read-out device operated via smartphone/tablet. In this way, we demonstrate that the novel biosensor can be potentially applied for the mass screening of SARS-CoV-2 surface antigens without prior sample processing, therefore offering a possible solution for the timely monitoring and eventual control of the global coronavirus pandemic. Full article

(This article belongs to the Special Issue Detection and Diagnosis of the New Coronavirus)

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