Detection of SARS-CoV-2 Using Antibody–Antigen Interactions with Graphene-Based Nanomechanical Resonator Sensors
Ontology highlight
ABSTRACT:
SUBMITTER: Payandehpeyman J
PROVIDER: S-EPMC8189043 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The rapid spread of COVID-19 including recent emergence of new variants with its extreme range of pathologies create an urgent need to develop a versatile sensor for a rapid, precise, and highly sensitive detection of SARS-CoV-2. Herein, we report a microcantilever-based optical detection of SARS-CoV-2 antigenic proteins in just few minutes with high specificity by employing fluidic-atomic force microscopy (f-AFM) mediated nanomechanical deflection method. The corresponding antibodies against the target antigens were first grafted on the gold-coated microcantilever surface pre-functionalized with EDC-NHS chemistry for a suitable antibody-antigen interaction. Rapid detection of SARS-CoV-2 nucleocapsid (N) and spike (S1) receptor binding domain (RBD) proteins was first demonstrated at a clinically relevant concentration down to 1 ng/mL (33 pM) by real-time monitoring of nanomechanical signal induced by antibody-antigen interaction. More importantly, we further show high specific detection of antigens with nasopharyngeal swab specimens from patients pre-determined with qRT-PCR. The results take less than 5 min (swab to signal ≤5 min) and exhibit high selectivity and analytical sensitivity (LoD: 100 copies/ ml; 0.71 ng/ml of N protein). These findings demonstrate potential for nanomechanical signal transduction towards rapid antigen detection for early screening of SARS-CoV-2 and its related mutants.
| S-EPMC8445766 | biostudies-literature
Project description:The 2019 coronavirus pandemic remains a major public health concern. Neutralizing antibodies (nAbs) represent a cutting-edge antiviral strategy. We focus here on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV, and discuss current progress in antibody research against rampant SARS-CoV-2 infections. We provide a perspective on the mechanisms of SARS-CoV-2-derived nAbs, comparing these with existing SARS-CoV-derived antibodies. We offer insight into how these antibodies cross-react and cross-neutralize by analyzing available structures of spike (S) glycoprotein-antibody complexes. We also propose ways of adopting antibody-based strategies - such as cocktail antibody therapeutics against SARS-CoV-2 - to overcome the possible resistance of currently identified mutants and mitigate possible antibody-dependent enhancement (ADE) pathologies. This review provides a platform for the progression of antibody and vaccine design against SARS-CoV-2, and possibly against future coronavirus pandemics.
| S-EPMC7498231 | biostudies-literature
Project description:The ongoing outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) started in late 2019 and spread across the world, infecting millions of people, with over 3.3 million deaths worldwide. To fight back the virus, it is necessary to understand how the main structures work, especially those responsible for the virus infectivity pathogenicity. Here, using the most advanced atomic force microscopy techniques, SARS-CoV-2 viral particles were analyzed, with a special focus on their ultrastructure, adsorption conformation, and nanomechanical behavior. The results uncovered the aspects of the organization and the spatial distribution of the proteins on the surface of the viral particles. It also showed the compliant behavior of the membrane and ability to recover from mechanical injuries. At least three layers composing the membrane and their thickness were measured, protecting the virus from external stress. This study provides new insight into the ultrastructure of SARS-CoV-2 particles at the nanoscale, offering new prospects that could be employed for mapping viral surfaces. The understanding of the viruses' capacity to survive mechanical disruptions at any level and their ability to recover from such injuries can shed a light on the structure-function relationship and help us to find targets for drug action, especially for this virus that, to this day, has no course of treatment approved.
| S-EPMC8370120 | biostudies-literature
Project description:The massive global spread of the COVID-19 pandemic makes the development of more effective and easily popularized assays critical. Here, we developed an ultrasensitive nanomechanical method based on microcantilever array and peptide nucleic acid (PNA) for the detection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) RNA. The method has an extremely low detection limit of 0.1 fM (105 copies/mL) for N-gene specific sequence (20 bp). Interestingly, it was further found that the detection limit of N gene (pharyngeal swab sample) was even lower, reaching 50 copies/mL. The large size of the N gene dramatically enhances the sensitivity of the nanomechanical sensor by up to three orders of magnitude. The detection limit of this amplification-free assay method is an order of magnitude lower than RT-PCR (500 copies/mL) that requires amplification. The non-specific signal in the assay is eliminated by the in-situ comparison of the array, reducing the false-positive misdiagnosis rate. The method is amplification-free and label-free, allowing for accurate diagnosis within 1 h. The strong specificity and ultra-sensitivity allow single base mutations in viruses to be distinguished even at very low concentrations. Also, the method remains sensitive to fM magnitude lung cancer marker (miRNA-155). Therefore, this ultrasensitive, amplification-free and inexpensive assay is expected to be used for the early diagnosis of COVID-19 patients and to be extended as a broad detection tool.Electronic supplementary materialSupplementary material (experimental section, N gene sequences and all nucleic acid sequences used in the study, Figs. S1-S6, and Tables S1-S3) is available in the online version of this article at 10.1007/s12274-022-4333-3.
| S-EPMC9118818 | biostudies-literature
Project description:Ultrathin plasmonic metasurfaces have proven their ability to control and manipulate light at unprecedented levels, leading to exciting optical functionalities and applications. Although to date metasurfaces have mainly been investigated from an electromagnetic perspective, their ultrathin nature may also provide novel and useful mechanical properties. Here we propose a thin piezoelectric plasmonic metasurface forming the resonant body of a nanomechanical resonator with simultaneously tailored optical and electromechanical properties. We experimentally demonstrate that it is possible to achieve high thermomechanical coupling between electromagnetic and mechanical resonances in a single ultrathin piezoelectric nanoplate. The combination of nanoplasmonic and piezoelectric resonances allows the proposed device to selectively detect long-wavelength infrared radiation with unprecedented electromechanical performance and thermal capabilities. These attributes lead to the demonstration of a fast, high-resolution, uncooled infrared detector with ?80% absorption for an optimized spectral bandwidth centered around 8.8??m.
| S-EPMC4835539 | biostudies-literature
Project description:Single-molecule pH sensors have been developed by utilizing molecular imaging of pH-responsive shape transition of nanomechanical DNA origami devices with atomic force microscopy (AFM). Short DNA fragments that can form i-motifs were introduced to nanomechanical DNA origami devices with pliers-like shape (DNA Origami Pliers), which consist of two levers of 170-nm long and 20-nm wide connected at a Holliday-junction fulcrum. DNA Origami Pliers can be observed as in three distinct forms; cross, antiparallel and parallel forms, and cross form is the dominant species when no additional interaction is introduced to DNA Origami Pliers. Introduction of nine pairs of 12-mer sequence (5'-AACCCCAACCCC-3'), which dimerize into i-motif quadruplexes upon protonation of cytosine, drives transition of DNA Origami Pliers from open cross form into closed parallel form under acidic conditions. Such pH-dependent transition was clearly imaged on mica in molecular resolution by AFM, showing potential application of the system to single-molecular pH sensors.
| S-EPMC4239864 | biostudies-literature
Project description:Respiratory infections, like the current COVID-19 pandemic, target epithelial cells in the respiratory tract. Alveolar macrophages (AMs) are tissue-resident macrophages located within the lung. They play a key role in the early phases of an immune response to respiratory viruses. AMs are likely the first immune cells to encounter SARS-CoV-2 during an infection and their reaction to the virus will have a profound impact on the outcome of the infection. Interferons (IFNs) are antiviral cytokines and among the first cytokines produced upon viral infection. In this study, AMs from non-infectious donors are challenged with SARS-CoV-2. We demonstrate that challenged AMs are incapable of sensing SARS-CoV-2 and of producing an IFN response in contrast to other respiratory viruses, like influenza A virus and Sendai virus, which trigger a robust IFN response. The absence of IFN production in AMs upon challenge with SARS-CoV2 could explain the initial asymptotic phase observed during COVID-19 and argues against AMs being the sources of proinflammatory cytokines later during infection.
| S-SCDT-EMBOR-2020-51252V1 | biostudies-other
Project description:Early detection and identification of SARS-CoV-infected patients and actions to prevent transmission are absolutely critical to prevent another SARS outbreak. Antibodies that specifically recognize the SARS-CoV spike and nucleocapsid proteins may provide a rapid screening method to allow accurate identification and isolation of patients with the virus early in their infection. For this reason, we raised peptide-induced polyclonal antibodies against SARS-CoV spike protein and polyclonal antibodies against SARS-CoV nucleocapsid protein using 6x His nucleocapsid recombinant protein. Western blot analysis and immunofluorescent staining showed that these antibodies specifically recognized SARS-CoV.
| S-EPMC7111193 | biostudies-literature
Project description:RT-PCR is the gold standard to detect SARS-CoV-2, however, its capacity is limited. We evaluated an automated antigen detection (AAD) test, Elecsys SARS-CoV-2 Antigen (Roche, Germany), for detecting SARS-CoV-2. We compared the limit of detection (LOD) between AAD test, rapid antigen detection (RAD) test; SARS-CoV-2 Rapid Antigen Test (SD Biosensor, Korea), and in-house RT-PCR test. LOD results showed that the AAD test was 100 fold more sensitive than the RAD test, while the sensitivity of the AAD test was comparable to the RT-PCR test. The AAD test detected between 85.7% and 88.6% of RT-PCR-positive specimens collected from COVID-19 patients, false negative results were observed for specimens with Ct values >30. Although clinical sensitivity for the AAD test was not superior or comparable to the RT-PCR test in the present study, the AAD test may be an alternative to RT-PCR test in terms of turn-around time and throughput.
| S-EPMC8284070 | biostudies-literature
Project description:The current outbreaking of the coronavirus SARS-CoV-2 pandemic threatens global health and has caused serious concern. Currently there is no specific drug against SARS-CoV-2, therefore, a fast and accurate diagnosis method is an urgent need for the diagnosis, timely treatment and infection control of COVID-19 pandemic. In this work, we developed a field effect transistor (FET) biosensor based on graphene oxide-graphene (GO/Gr) van der Waals heterostructure for selective and ultrasensitive SARS-CoV-2 proteins detection. The GO/Gr van der Waals heterostructure was in-situ formed in the microfluidic channel through π-π stacking. The developed biosensor is capable of SARS-CoV-2 proteins detection within 20 min in the large dynamic range from 10 fg/mL to 100 pg/mL with the limit of detection of as low as ∼8 fg/mL, which shows ∼3 × sensitivity enhancement compared with Gr-FET biosensor. The performance enhancement mechanism was studied based on the transistor-based biosensing theory and experimental results, which is mainly attributed to the enhanced SARS-CoV-2 capture antibody immobilization density due to the introduction of the GO layer on the graphene surface. The spiked SARS-CoV-2 protein samples in throat swab buffer solution were tested to confirm the practical application of the biosensor for SARS-CoV-2 proteins detection. The results indicated that the developed GO/Gr van der Waals heterostructure FET biosensor has strong selectivity and high sensitivity, providing a potential method for SARS-CoV-2 fast and accurate detection.
| S-EPMC8719368 | biostudies-literature