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1.
ACS Appl Mater Interfaces ; 14(8): 10844-10855, 2022 Mar 02.
Article in English | MEDLINE | ID: covidwho-1692677

ABSTRACT

The widespread and long-lasting effect of the COVID-19 pandemic has called attention to the significance of technological advances in the rapid diagnosis of SARS-CoV-2 virus. This study reports the use of a highly stable buffer-based zinc oxide/reduced graphene oxide (bbZnO/rGO) nanocomposite coated on carbon screen-printed electrodes for electrochemical immuno-biosensing of SARS-CoV-2 nuelocapsid (N-) protein antigens in spiked and clinical samples. The incorporation of a salt-based (ionic) matrix for uniform dispersion of the nanomixture eliminates multistep nanomaterial synthesis on the surface of the electrode and enables a stable single-step sensor nanocoating. The immuno-biosensor provides a limit of detection of 21 fg/mL over a linear range of 1-10 000 pg/mL and exhibits a sensitivity of 32.07 ohms·mL/pg·mm2 for detection of N-protein in spiked samples. The N-protein biosensor is successful in discriminating positive and negative clinical samples within 15 min, demonstrating its proof of concept used as a COVID-19 rapid antigen test.


Subject(s)
Antigens, Viral/analysis , COVID-19/diagnosis , Coronavirus Nucleocapsid Proteins/analysis , Graphite/chemistry , Nanocomposites/chemistry , Zinc Oxide/chemistry , Antibodies, Immobilized/immunology , Antigens, Viral/immunology , Biosensing Techniques/instrumentation , Biosensing Techniques/methods , Coronavirus Nucleocapsid Proteins/immunology , Electrochemical Techniques/instrumentation , Electrochemical Techniques/methods , Electrodes , Humans , Immunoassay/instrumentation , Immunoassay/methods , Limit of Detection , Phosphoproteins/analysis , Phosphoproteins/immunology , Proof of Concept Study , SARS-CoV-2/chemistry
2.
Bioelectrochemistry ; 143: 107982, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1525699

ABSTRACT

The large-scale diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important for traceability and treatment during pandemic outbreaks. We developed a fast (2-3 min), easy-to-use, low-cost, and quantitative electrochemical biosensor based on carbon nanotube field-effect transistor (CNT-FET) that allows digital detection of the SARS-CoV-2 S1 in fortifited saliva samples for quick and accurate detection of SARS-CoV-2 S1 antigens. The biosensor was developed on a Si/SiO2 surface by CNT printing with the immobilization of a anti-SARS-CoV-2 S1. SARS-CoV-2 S1 antibody was immobilized on the CNT surface between the S-D channel area using a linker 1-pyrenebutanoic acid succinimidyl ester (PBASE) through non-covalent interaction. A commercial SARS-CoV-2 S1 antigen was used to characterize the electrical output of the CNT-FET biosensor. The SARS-CoV-2 S1 antigen in the 10 mM AA buffer pH 6.0 was effectively detected by the CNT-FET biosensor at concentrations from 0.1 fg/mL to 5.0 pg/mL. The limit of detection (LOD) of the developed CNT-FET biosensor was 4.12 fg/mL. The selectivity test was performed by using target SARS-CoV-2 S1 and non-target SARS-CoV-1 S1 and MERS-CoV S1 antigens in the 10 mM AA buffer pH 6.0. The biosensor showed high selectivity (no response to SARS-CoV-1 S1 or MERS-CoV S1 antigen) with SARS-CoV-2 S1 antigen detection in the 10 mM AA buffer pH 6.0. The biosensor is highly sensitive, saves time, and could be a helpful platform for rapid detection of SARS-CoV-2 S1 antigen from the patients saliva.


Subject(s)
Electrochemical Techniques/instrumentation , Nanotubes, Carbon/chemistry , SARS-CoV-2/chemistry , Spike Glycoprotein, Coronavirus/analysis , Antigens, Viral/analysis , Biosensing Techniques , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology
3.
Anal Bioanal Chem ; 414(3): 1313-1322, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1506326

ABSTRACT

Among the deadliest pandemics in history, coronavirus disease 2019 (COVID-19) has wreaked havoc on human lives, economies and public health systems worldwide. To temper its effects, diagnostic methods that are simple, rapid, inexpensive, accurate, selective and sensitive continue to be necessary. In our study, we developed an electrochemical biosensing platform based on gold clusters, mercaptoethanol, the spike protein of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antigen and bovine serum albumin-modified glassy carbon electrode able to detect the SARS-CoV-2 spike antibody. Moreover, during the detection of the SARS-CoV-2 spike antibody in spiked-real samples, the anodic signal of the produced biosensor at 0.85 V decreased as the amount of the SARS-CoV-2 spike antibody increased. Meanwhile, the recovery and relative standard deviation values for saliva and oropharyngeal swab samples were 97.73% and 3.35% and 102.43% and 4.63%, respectively. In 35 min, the biosensing platform could detect 0.03 fg/mL of the SARS-CoV-2 spike antibody in synthetic media and spiked-saliva or -oropharyngeal swab samples. The method thus issues a linear response to the SARS-CoV-2 spike antibody from 0.1 fg/mL to 10 pg/mL. The cross-reactivity studies with spike antigens of Middle East respiratory syndrome-coronavirus and influenza A and the antigen of pneumonia confirmed the excellent selectivity of the proposed method. The developed method was compared with the lateral flow immunoassay method in terms of sensitivity and it was found to be approximately 109 times more sensitive. Biosensing mechanism of the platform to the SARS-CoV-2 spike antibody.


Subject(s)
Antibodies, Viral/analysis , COVID-19 Serological Testing/instrumentation , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/analysis , Antibodies, Viral/immunology , Biosensing Techniques/instrumentation , COVID-19/immunology , Electrochemical Techniques/instrumentation , Equipment Design , Humans , Hydrogen Bonding , Models, Molecular , SARS-CoV-2/immunology , Saliva/virology , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/immunology
4.
ACS Appl Mater Interfaces ; 13(42): 49754-49761, 2021 Oct 27.
Article in English | MEDLINE | ID: covidwho-1475248

ABSTRACT

A reliable and sensitive detection approach for SARS-CoV 2 is essential for timely infection diagnosis and transmission prevention. Here, a two-dimensional (2D) metal-organic framework (MOF)-based photoelectrochemical (PEC) aptasensor with high sensitivity and stability for SARS-CoV 2 spike glycoprotein (S protein) detection was developed. The PEC aptasensor was constructed by a plasmon-enhanced photoactive material (namely, Au NPs/Yb-TCPP) with a specific DNA aptamer against S protein. The Au NPs/Yb-TCPP fabricated by in situ growth of Au NPs on the surface of 2D Yb-TCPP nanosheets showed a high electron-hole (e-h) separation efficiency due to the enhancement effect of plasmon, resulting in excellent photoelectric performance. The modified DNA aptamer on the surface of Au NPs/Yb-TCPP can bind with S protein with high selectivity, thus decreasing the photocurrent of the system due to the high steric hindrance and low conductivity of the S protein. The established PEC aptasensor demonstrated a highly sensitive detection for S protein with a linear response range of 0.5-8 µg/mL with a detection limit of 72 ng/mL. This work presented a promising way for the detection of SARS-CoV 2, which may conduce to the impetus of clinic diagnostics.


Subject(s)
Aptamers, Nucleotide/chemistry , Biosensing Techniques/methods , Metal-Organic Frameworks/chemistry , SARS-CoV-2/chemistry , Spike Glycoprotein, Coronavirus/analysis , Base Sequence , Biosensing Techniques/instrumentation , COVID-19/diagnosis , DNA/chemistry , Electrochemical Techniques/instrumentation , Electrochemical Techniques/methods , Electrodes , Gold/chemistry , Gold/radiation effects , Humans , Immobilized Nucleic Acids/chemistry , Light , Limit of Detection , Metal Nanoparticles/chemistry , Metal Nanoparticles/radiation effects , Pharynx/virology , Photochemical Processes , Porphyrins/chemistry , Spike Glycoprotein, Coronavirus/chemistry , Ytterbium/chemistry
5.
Mikrochim Acta ; 188(6): 199, 2021 05 26.
Article in English | MEDLINE | ID: covidwho-1245646

ABSTRACT

Since the COVID-19 disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) was declared a pandemic, it has spread rapidly, causing one of the most serious outbreaks in the last century. Reliable and rapid diagnostic tests for COVID-19 are crucial to control and manage the outbreak. Here, a label-free square wave voltammetry-based biosensing platform for the detection of SARS-CoV-2 in nasopharyngeal samples is reported. The sensor was constructed on screen-printed carbon electrodes coated with gold nanoparticles. The electrodes were functionalized using 11-mercaptoundecanoic acid (MUA) which was used for the immobilization of an antibody against SARS-CoV-2 nucleocapsid protein (N protein). The binding of the immunosensor with the N protein caused a change in the electrochemical signal. The detection was realised by measuring the change in reduction peak current of a redox couple using square wave voltammetry at 0.04 V versus Ag ref. electrode on the immunosensor upon binding with the N protein. The electrochemical immunosensor showed high sensitivity with a linear range from 1.0 pg.mL-1 to 100 ng.mL-1 and a limit of detection of 0.4 pg.mL-1 for the N protein in PBS buffer pH 7.4. Moreover, the immunosensor did not exhibit significant response with other viruses such as HCoV, MERS-CoV, Flu A and Flu B, indicating the high selectivity of the sensor for SARS-CoV-2. However, cross reactivity of the biosensor with SARS-CoV is indicated, which gives ability of the sensor to detect both SARS-CoV and SARS-CoV-2. The biosensor was successfully applied to detect the SARS-CoV-2 virus in clinical samples showing good correlation between the biosensor response and the RT-PCR cycle threshold values. We believe that the capability of miniaturization, low-cost and fast response of the proposed label-free electrochemical immunosensor will facilitate the point-of-care diagnosis of COVID 19 and help prevent further spread of infection.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Coronavirus Nucleocapsid Proteins/analysis , Electrochemical Techniques/methods , Immunoassay/methods , SARS-CoV-2/chemistry , Antibodies, Immobilized/immunology , Biosensing Techniques/instrumentation , Biosensing Techniques/methods , COVID-19 Testing/instrumentation , Carbon/chemistry , Coronavirus Nucleocapsid Proteins/immunology , Electrochemical Techniques/instrumentation , Electrodes , Fatty Acids/chemistry , Gold/chemistry , Humans , Immunoassay/instrumentation , Limit of Detection , Metal Nanoparticles/chemistry , Nasopharynx/virology , Phosphoproteins/analysis , Phosphoproteins/immunology , Sulfhydryl Compounds/chemistry
6.
Biosensors (Basel) ; 11(6)2021 May 24.
Article in English | MEDLINE | ID: covidwho-1243953

ABSTRACT

Despite collaborative efforts from all countries, coronavirus disease 2019 (COVID-19) pandemic has been continuing to spread globally, forcing the world into social distancing period, making a special challenge for public healthcare system. Before vaccine widely available, the best approach to manage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is to achieve highest diagnostic accuracy by improving biosensor efficacy. For SARS-CoV-2 diagnostics, intensive attempts have been made by many scientists to ameliorate the drawback of current biosensors of SARS-CoV-2 in clinical diagnosis to offer benefits related to platform proposal, systematic analytical methods, system combination, and miniaturization. This review assesses ongoing research efforts aimed at developing integrated diagnostic tools to detect RNA viruses and their biomarkers for clinical diagnostics of SARS-CoV-2 infection and further highlights promising technology for SARS-CoV-2 specific diagnosis. The comparisons of SARS-CoV-2 biomarkers as well as their applicable biosensors in the field of clinical diagnosis were summarized to give scientists an advantage to develop superior diagnostic platforms. Furthermore, this review describes the prospects for this rapidly growing field of diagnostic research, raising further interest in analytical technology and strategic plan for future pandemics.


Subject(s)
Biosensing Techniques/instrumentation , COVID-19 Testing/instrumentation , SARS-CoV-2/isolation & purification , Animals , Biosensing Techniques/methods , COVID-19 Testing/methods , Colorimetry/instrumentation , Colorimetry/methods , Electrochemical Techniques/instrumentation , Electrochemical Techniques/methods , Enzyme-Linked Immunosorbent Assay/instrumentation , Enzyme-Linked Immunosorbent Assay/methods , Equipment Design , Humans , Nucleic Acid Amplification Techniques/instrumentation , Nucleic Acid Amplification Techniques/methods , Point-of-Care Testing
7.
J Mater Chem B ; 9(23): 4608-4619, 2021 06 16.
Article in English | MEDLINE | ID: covidwho-1236100

ABSTRACT

Worldwide infections and fatalities caused by the SARS-CoV-2 virus and its variants responsible for COVID-19 have significantly impeded the economic growth of many nations. People in many nations have lost their livelihoods, it has severely impacted international relations and, most importantly, health infrastructures across the world have been tormented. This pandemic has already left footprints on human psychology, traits, and priorities and is certainly going to lead towards a new world order in the future. As always, science and technology have come to the rescue of the human race. The prevention of infection by instant and repeated cleaning of surfaces that are most likely to be touched in daily life and sanitization drives using medically prescribed sanitizers and UV irradiation of textiles are the first steps to breaking the chain of transmission. However, the real challenge is to develop and uplift medical infrastructure, such as diagnostic tools capable of prompt diagnosis and instant and economic medical treatment that is available to the masses. Two-dimensional (2D) materials, such as graphene, are atomic sheets that have been in the news for quite some time due to their unprecedented electronic mobilities, high thermal conductivity, appreciable thermal stability, excellent anchoring capabilities, optical transparency, mechanical flexibility, and a unique capability to integrate with arbitrary surfaces. These attributes of 2D materials make them lucrative for use as an active material platform for authentic and prompt (within minutes) disease diagnosis via electrical or optical diagnostic tools or via electrochemical diagnosis. We present the opportunities provided by 2D materials as a platform for SARS-CoV-2 diagnosis.


Subject(s)
Biosensing Techniques/instrumentation , Biosensing Techniques/methods , COVID-19 Testing/instrumentation , COVID-19 Testing/methods , COVID-19/diagnosis , Electrochemical Techniques/instrumentation , Electrochemical Techniques/methods , SARS-CoV-2/isolation & purification , COVID-19/mortality , Humans , Spectrum Analysis, Raman , Transistors, Electronic
9.
J Am Chem Soc ; 143(4): 1722-1727, 2021 02 03.
Article in English | MEDLINE | ID: covidwho-1065802

ABSTRACT

The development of new methods for direct viral detection using streamlined and ideally reagent-free assays is a timely and important, but challenging, problem. The challenge of combatting the COVID-19 pandemic has been exacerbated by the lack of rapid and effective methods to identify viral pathogens like SARS-CoV-2 on-demand. Existing gold standard nucleic acid-based approaches require enzymatic amplification to achieve clinically relevant levels of sensitivity and are not typically used outside of a laboratory setting. Here, we report reagent-free viral sensing that directly reads out the presence of viral particles in 5 minutes using only a sensor-modified electrode chip. The approach relies on a class of electrode-tethered sensors bearing an analyte-binding antibody displayed on a negatively charged DNA linker that also features a tethered redox probe. When a positive potential is applied, the sensor is transported to the electrode surface. Using chronoamperometry, the presence of viral particles and proteins can be detected as these species increase the hydrodynamic drag on the sensor. This report is the first virus-detecting assay that uses the kinetic response of a probe/virus complex to analyze the complexation state of the antibody. We demonstrate the performance of this sensing approach as a means to detect, within 5 min, the presence of the SARS-CoV-2 virus and its associated spike protein in test samples and in unprocessed patient saliva.


Subject(s)
Biosensing Techniques/methods , COVID-19 Testing/methods , COVID-19/virology , Electrochemical Techniques/methods , SARS-CoV-2/isolation & purification , Virion/isolation & purification , Biosensing Techniques/instrumentation , COVID-19 Testing/instrumentation , Electrochemical Techniques/instrumentation , Electrodes , Humans , Point-of-Care Testing , Saliva/virology
10.
Biosens Bioelectron ; 178: 113029, 2021 Apr 15.
Article in English | MEDLINE | ID: covidwho-1046559

ABSTRACT

The current COVID-19 pandemic caused by SARS-CoV-2 coronavirus is expanding around the globe. Hence, accurate and cheap portable sensors are crucially important for the clinical diagnosis of COVID-19. Molecularly imprinted polymers (MIPs) as robust synthetic molecular recognition materials with antibody-like ability to bind and discriminate between molecules can perfectly serve in building selective elements in such sensors. Herein, we report for the first time on the development of a MIP-based electrochemical sensor for detection of SARS-CoV-2 nucleoprotein (ncovNP). A key element of the sensor is a disposable sensor chip - thin film electrode - interfaced with a MIP-endowed selectivity for ncovNP and connected with a portable potentiostat. The resulting ncovNP sensor showed a linear response to ncovNP in the lysis buffer up to 111 fM with a detection and quantification limit of 15 fM and 50 fM, respectively. Notably, the sensor was capable of signaling ncovNP presence in nasopharyngeal swab samples of COVID-19 positive patients. The presented strategy unlocks a new route for the development of rapid COVID-19 diagnostic tools.


Subject(s)
Antigens, Viral/analysis , Biosensing Techniques/instrumentation , COVID-19 Testing/instrumentation , COVID-19/diagnosis , COVID-19/virology , Coronavirus Nucleocapsid Proteins/analysis , Coronavirus Nucleocapsid Proteins/immunology , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Electrochemical Techniques/instrumentation , Equipment Design , Feasibility Studies , Humans , Molecular Imprinting , Nasopharynx/virology , Pandemics , Phosphoproteins/analysis , Phosphoproteins/immunology , Polymers
11.
Sensors (Basel) ; 21(2)2021 Jan 08.
Article in English | MEDLINE | ID: covidwho-1016225

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.


Subject(s)
Biosensing Techniques/instrumentation , COVID-19 Testing/instrumentation , COVID-19/diagnosis , COVID-19/virology , Point-of-Care Testing , SARS-CoV-2/chemistry , Spike Glycoprotein, Coronavirus/analysis , Antigens, Viral/analysis , Biosensing Techniques/methods , COVID-19 Testing/methods , Dielectric Spectroscopy , Electrochemical Techniques/instrumentation , Electrochemical Techniques/methods , Enzyme-Linked Immunosorbent Assay/instrumentation , Enzyme-Linked Immunosorbent Assay/methods , Equipment Design , Graphite , Humans , Limit of Detection , Pandemics , Proof of Concept Study , Protein Subunits , SARS-CoV-2/immunology , Single Molecule Imaging/instrumentation , Single Molecule Imaging/methods , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Time Factors
12.
Biosens Bioelectron ; 176: 112905, 2021 Mar 15.
Article in English | MEDLINE | ID: covidwho-996666

ABSTRACT

Electrochemical biosensors combine the selectivity of electrochemical signal transducers with the specificity of biomolecular recognition strategies. Although they have been broadly studied in different areas of diagnostics, they are not yet fully commercialized. During the COVID-19 pandemic, electrochemical platforms have shown the potential to address significant limitations of conventional diagnostic platforms, including accuracy, affordability, and portability. The advantages of electrochemical platforms make them a strong candidate for rapid point-of-care detection of SARS-CoV-2 infection by targeting not only viral RNA but antigens and antibodies. Herein, we reviewed advancements in electrochemical biosensing platforms towards the detection of SARS-CoV-2 through studying similar viruses.


Subject(s)
Biosensing Techniques/instrumentation , COVID-19 Testing/instrumentation , COVID-19/diagnosis , Pandemics , SARS-CoV-2 , Antibodies, Viral/analysis , Antigens, Viral/analysis , Biosensing Techniques/methods , COVID-19/immunology , COVID-19/virology , COVID-19 Nucleic Acid Testing/instrumentation , COVID-19 Nucleic Acid Testing/methods , COVID-19 Serological Testing/instrumentation , COVID-19 Serological Testing/methods , COVID-19 Testing/methods , Electrochemical Techniques/instrumentation , Electrochemical Techniques/methods , Humans , Point-of-Care Testing , RNA, Viral/analysis , RNA, Viral/genetics , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
13.
Anal Chem ; 93(3): 1826-1833, 2021 01 26.
Article in English | MEDLINE | ID: covidwho-997756

ABSTRACT

Collection of nasopharyngeal samples using swabs followed by the transfer of the virus into a solution and an RNA extraction step to perform reverse transcription polymerase chain reaction (PCR) is the primary method currently used for the diagnosis of COVID-19. However, the need for several reagents and steps and the high cost of PCR hinder its worldwide implementation to contain the outbreak. Here, we report a cotton-tipped electrochemical immunosensor for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus antigen. Unlike the reported approaches, we integrated the sample collection and detection tools into a single platform by coating screen-printed electrodes with absorbing cotton padding. The immunosensor was fabricated by immobilizing the virus nucleocapsid (N) protein on carbon nanofiber-modified screen-printed electrodes which were functionalized by diazonium electrografting. The detection of the virus antigen was achieved via swabbing followed by competitive assay using a fixed amount of N protein antibody in the solution. A square wave voltammetric technique was used for the detection. The limit of detection for our electrochemical biosensor was 0.8 pg/mL for SARS-CoV-2, indicating very good sensitivity for the sensor. The biosensor did not show significant cross-reactivity with other virus antigens such as influenza A and HCoV, indicating high selectivity of the method. Moreover, the biosensor was successfully applied for the detection of the virus antigen in spiked nasal samples showing excellent recovery percentages. Thus, our electrochemical immunosensor is a promising diagnostic tool for the direct rapid detection of the COVID-19 virus that requires no sample transfer or pretreatment.


Subject(s)
COVID-19/diagnosis , Cotton Fiber , Electrochemical Techniques/methods , Immunoassay/methods , SARS-CoV-2/isolation & purification , Antibodies, Viral/immunology , Biosensing Techniques/instrumentation , Biosensing Techniques/methods , Carbon/chemistry , Coronavirus Nucleocapsid Proteins/chemistry , Coronavirus Nucleocapsid Proteins/immunology , Electrochemical Techniques/instrumentation , Electrodes , Gossypium/chemistry , Humans , Immobilized Proteins/chemistry , Immobilized Proteins/immunology , Immunoassay/instrumentation , Limit of Detection , Nanofibers/chemistry , Phosphoproteins/chemistry , Phosphoproteins/immunology , SARS-CoV-2/immunology
14.
Biosens Bioelectron ; 176: 112912, 2021 Mar 15.
Article in English | MEDLINE | ID: covidwho-987148

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is emerging as a global pandemic outbreak. To date, approximately one million deaths and over 32 million cases have been reported. This ongoing pandemic urgently requires an accurate testing device that can be used in the field in a fast manner. Serological assays to detect antibodies have been proven to be a great complement to the standard method of reverse transcription-polymerase chain reaction (RT-PCR), particularly after the second week of infection. We have developed a specific and sensitive immunosensor for immunoglobulin detection produced against SARS-CoV-2. Unlike other lateral flow-based assays (LFAs) involving the utilization of multiple antibodies, we have reported a label-free paper-based electrochemical platform targeting SARS-CoV-2 antibodies without the specific requirement of an antibody. The presence of SARS-CoV-2 antibodies will interrupt the redox conversion of the redox indicator, resulting in a decreased current response. This electrochemical sensor was proven effective in real clinical sera from patients with satisfactory results. In addition, the proposed format was also extended to antigen detection (the spike protein of SARS-CoV-2), which presents new possibilities for diagnosing COVID-19.


Subject(s)
Biosensing Techniques/instrumentation , COVID-19 Serological Testing/instrumentation , COVID-19/diagnosis , SARS-CoV-2/immunology , Antibodies, Viral/analysis , Antigens, Viral/analysis , Biosensing Techniques/methods , COVID-19/immunology , COVID-19/virology , COVID-19 Serological Testing/methods , Cross Reactions , Electrochemical Techniques/instrumentation , Electrochemical Techniques/methods , Equipment Design , Humans , Pandemics , Paper , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/analysis , Spike Glycoprotein, Coronavirus/immunology
15.
Molecules ; 25(24)2020 Dec 08.
Article in English | MEDLINE | ID: covidwho-967219

ABSTRACT

With the rise in public health awareness, research on point-of-care testing (POCT) has significantly advanced. Electrochemical biosensors (ECBs) are one of the most promising candidates for the future of POCT due to their quick and accurate response, ease of operation, and cost effectiveness. This review focuses on the use of metal nanoparticles (MNPs) for fabricating ECBs that has a potential to be used for POCT. The field has expanded remarkably from its initial enzymatic and immunosensor-based setups. This review provides a concise categorization of the ECBs to allow for a better understanding of the development process. The influence of structural aspects of MNPs in biocompatibility and effective sensor design has been explored. The advances in MNP-based ECBs for the detection of some of the most prominent cancer biomarkers (carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), Herceptin-2 (HER2), etc.) and small biomolecules (glucose, dopamine, hydrogen peroxide, etc.) have been discussed in detail. Additionally, the novel coronavirus (2019-nCoV) ECBs have been briefly discussed. Beyond that, the limitations and challenges that ECBs face in clinical applications are examined and possible pathways for overcoming these limitations are discussed.


Subject(s)
Electrochemical Techniques/methods , Metal Nanoparticles/chemistry , Point-of-Care Testing , Biomarkers, Tumor/analysis , Biosensing Techniques/instrumentation , Biosensing Techniques/methods , COVID-19 Testing/methods , Carbon/chemistry , Electrochemical Techniques/instrumentation , Equipment Design , Female , Humans , Male , Nanostructures/chemistry
16.
Biosens Bioelectron ; 172: 112750, 2021 Jan 15.
Article in English | MEDLINE | ID: covidwho-893621

ABSTRACT

Tremendous research and commercialization efforts around the world are focused on developing novel wearable electrochemical biosensors that can noninvasively and continuously screen for biochemical markers in body fluids for the prognosis, diagnosis and management of diseases, as well as the monitoring of fitness. Researchers in North America are leading the development of innovative wearable platforms that can comfortably comply to the human body and efficiently sample fluids such as sweat, interstitial fluids, tear and saliva for the electrochemical detection of biomarkers through various sensing approaches such as potentiometric ion selective electrodes and amperometric enzymatic sensors. We start this review with a historical timeline overviewing the major milestones in the development of wearable electrochemical sensors by North American institutions. We then describe how such research efforts have led to pioneering developments and are driving the advancement and commercialization of wearable electrochemical sensors: from minimally invasive continuous glucose monitors for chronic disease management to non-invasive sweat electrolyte sensors for dehydration monitoring in fitness applications. While many countries across the globe have contributed significantly to this rapidly emerging field, their contributions are beyond the scope of this review. Furthermore, we share our perspective on the promising future of wearable electrochemical sensors in applications spanning from remote and personalized healthcare to wellness.


Subject(s)
Biosensing Techniques/instrumentation , COVID-19 Testing/instrumentation , COVID-19/diagnosis , Wearable Electronic Devices , Biomarkers/analysis , Biosensing Techniques/history , Biosensing Techniques/trends , Blood Glucose/analysis , Blood Glucose Self-Monitoring/instrumentation , COVID-19 Testing/trends , Electrochemical Techniques/history , Electrochemical Techniques/instrumentation , Epidermis/chemistry , Equipment Design/history , Extracellular Fluid/chemistry , History, 21st Century , Humans , North America , Potentiometry/instrumentation , Saliva/chemistry , Sweat/chemistry , Tears/chemistry , Wearable Electronic Devices/history , Wearable Electronic Devices/trends
17.
Biosens Bioelectron ; 171: 112731, 2021 Jan 01.
Article in English | MEDLINE | ID: covidwho-866448

ABSTRACT

Rapid person-to-person transfer of viruses such as SARS-CoV-2 and their occasional mutations owing to the human activity and climate/ecological changes by the mankind led to creation of wrecking worldwide challenges. Such fast transferable pathogens requiring practical diagnostic setups to control their transfer chain and stop sever outbreaks in early stages of their appearance. Herein, we have addressed this urgent demand by designing a rapid electrochemical diagnostic kit composed of fixed/screen printed electrodes that can detect pathogenic viruses such as SARS-CoV-2 and/or animal viruses through the differentiable fingerprint of their viral glycoproteins at different voltage positions. The working electrode of developed sensor is activated upon coating a layer of coupled graphene oxide (GO) with sensitive chemical compounds along with gold nanostars (Au NS) that can detect the trace of viruses in any aquatic biological media (e.g., blood, saliva and oropharyngeal/nasopharyngeal swab) through interaction with active functional groups of their glycoproteins. The method do not require any extraction and/or biomarkers for detection of target viruses and can identify trace of different pathogenic viruses in about 1 min. The nanosensor also demonstrated superior limit of detection (LOD) and sensitivity of 1.68 × 10-22 µg mL-1 and 0.0048 µAµg.mL-1. cm-2, respectively, toward detection of SARS-CoV-2 in biological media, while blind clinical evaluations of 100 suspected samples furtherly confirmed the superior sensitivity/specificity of developed nanosystem toward rapid identification of ill people even at incubation and prodromal periods of illness.


Subject(s)
Betacoronavirus/isolation & purification , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Electrochemical Techniques/instrumentation , Pneumonia, Viral/diagnosis , Spike Glycoprotein, Coronavirus/analysis , Animals , Biosensing Techniques/instrumentation , COVID-19 , COVID-19 Testing , Electrodes , Equipment Design , Gold/chemistry , Graphite/chemistry , Humans , Limit of Detection , Metal Nanoparticles/chemistry , Pandemics , SARS-CoV-2
18.
Biosens Bioelectron ; 171: 112686, 2021 Jan 01.
Article in English | MEDLINE | ID: covidwho-813486

ABSTRACT

The diffusion of novel SARS-CoV-2 coronavirus over the world generated COVID-19 pandemic event as reported by World Health Organization on March 2020. The huge issue is the high infectivity and the absence of vaccine and customised drugs allowing for hard management of this outbreak, thus a rapid and on site analysis is a need to contain the spread of COVID-19. Herein, we developed an electrochemical immunoassay for rapid and smart detection of SARS-CoV-2 coronavirus in saliva. The electrochemical assay was conceived for Spike (S) protein or Nucleocapsid (N) protein detection using magnetic beads as support of immunological chain and secondary antibody with alkaline phosphatase as immunological label. The enzymatic by-product 1-naphtol was detected using screen-printed electrodes modified with carbon black nanomaterial. The analytical features of the electrochemical immunoassay were evaluated using the standard solution of S and N protein in buffer solution and untreated saliva with a detection limit equal to 19 ng/mL and 8 ng/mL in untreated saliva, respectively for S and N protein. Its effectiveness was assessed using cultured virus in biosafety level 3 and in saliva clinical samples comparing the data using the nasopharyngeal swab specimens tested with Real-Time PCR. The agreement of the data, the low detection limit achieved, the rapid analysis (30 min), the miniaturization, and portability of the instrument combined with the easiness to use and no-invasive sampling, confer to this analytical tool high potentiality for market entry as the first highly sensitive electrochemical immunoassay for SARS-CoV-2 detection in untreated saliva.


Subject(s)
Betacoronavirus/isolation & purification , Biosensing Techniques/instrumentation , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Saliva/virology , COVID-19 , COVID-19 Testing , Coronavirus Nucleocapsid Proteins , Electrochemical Techniques/instrumentation , Electrodes , Equipment Design , Humans , Immunoassay/instrumentation , Magnets/chemistry , Nucleocapsid Proteins/analysis , Pandemics , Phosphoproteins , SARS-CoV-2 , Sensitivity and Specificity , Soot/chemistry , Spike Glycoprotein, Coronavirus/analysis
19.
ACS Sens ; 5(9): 2747-2752, 2020 09 25.
Article in English | MEDLINE | ID: covidwho-740029

ABSTRACT

With the current intense need for rapid and accurate detection of viruses due to COVID-19, we report on a platform technology that is well suited for this purpose, using intact measles virus for a demonstration. Cases of infection due to the measles virus are rapidly increasing, yet current diagnostic tools used to monitor for the virus rely on slow (>1 h) technologies. Here, we demonstrate the first biosensor capable of detecting the measles virus in minutes with no preprocessing steps. The key sensing element is an electrode coated with a self-assembled monolayer containing the measles antibody, immobilized through an N-heterocyclic carbene (NHC). The intact virus is detected by changes in resistance, giving a linear response to 10-100 µg/mL of the intact measles virus without the need to label or process the sample. The limit of detection is 6 µg/mL, which is at the lower limit of concentrations that can cause infections in primates. The NHC-based biosensors are shown to be superior to thiol-based systems, producing an approximately 10× larger response and significantly greater stability toward repeated measurements and long-term storage. This NHC-based biosensor thus represents an important development for both the rapid detection of the measles virus and as a platform technology for the detection of other biological targets of interest.


Subject(s)
Antibodies, Immobilized/immunology , Benzimidazoles/chemistry , Biosensing Techniques/methods , Electrochemical Techniques/methods , Measles virus/isolation & purification , Antibodies, Immobilized/chemistry , Electrochemical Techniques/instrumentation , Electrodes , Gold/chemistry , Limit of Detection , Measles virus/immunology
20.
Biosens Bioelectron ; 166: 112431, 2020 Oct 15.
Article in English | MEDLINE | ID: covidwho-654767

ABSTRACT

Last few decades, viruses are a real menace to human safety. Therefore, the rapid identification of viruses should be one of the best ways to prevent an outbreak and important implications for medical healthcare. The recent outbreak of coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus which belongs to the single-stranded, positive-strand RNA viruses. The pandemic dimension spread of COVID-19 poses a severe threat to the health and lives of seven billion people worldwide. There is a growing urgency worldwide to establish a point-of-care device for the rapid detection of COVID-19 to prevent subsequent secondary spread. Therefore, the need for sensitive, selective, and rapid diagnostic devices plays a vital role in selecting appropriate treatments and to prevent the epidemics. During the last decade, electrochemical biosensors have emerged as reliable analytical devices and represent a new promising tool for the detection of different pathogenic viruses. This review summarizes the state of the art of different virus detection with currently available electrochemical detection methods. Moreover, this review discusses different fabrication techniques, detection principles, and applications of various virus biosensors. Future research also looks at the use of electrochemical biosensors regarding a potential detection kit for the rapid identification of the COVID-19.


Subject(s)
Betacoronavirus , Biosensing Techniques/instrumentation , Clinical Laboratory Techniques/instrumentation , Coronavirus Infections/diagnosis , Electrochemical Techniques/instrumentation , Pneumonia, Viral/diagnosis , Viruses/isolation & purification , Animals , Betacoronavirus/isolation & purification , Betacoronavirus/pathogenicity , COVID-19 , COVID-19 Testing , Coronavirus Infections/virology , Equipment Design , Humans , Metal Nanoparticles/chemistry , Metal Nanoparticles/ultrastructure , Microscopy, Electron, Scanning , Pandemics , Pneumonia, Viral/virology , Point-of-Care Testing , SARS-CoV-2 , Viruses/pathogenicity
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