skip to main content


This content will become publicly available on December 27, 2024

Title: Wearable MXene‐Graphene Sensing of Influenza and SARS‐CoV‐2 Virus in Air and Breath: From Lab to Clinic
Abstract

The rapidly expanding severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and its variants demand a continuous monitoring method through portable and wearable devices. Utilizing the rich surface chemistry and high chemical‐to‐electrical signal conversion of 2D MXene‐graphene heterostructure thin films, a field‐effect‐transistor (FET) sensor, which has a flexible substrate to be assembled onto the mask and combines with a Bluetooth system for wireless transmission is developed, to detect the influenza and SARS‐CoV‐2 viruses in air and breath. At first, the developed sensors are examined in the laboratory through direct contact with sensing targets in solution form. The results show a low limit of detection (LOD) of 1 fg mL−1for recombinant SARS‐CoV‐2 spike protein and 125 copies mL−1for inactivated influenza A (H1N1) virus with high specificity in differing recombinant SARS‐CoV‐2 spike protein and inactivated H1N1 virus. Then the sensors are tested under various simulated human breathing modes through controlled exposure to atomizer‐generated aerosols in an enclosed chamber and mask coverage. The results show the high sensitivity of the developed sensors under varying distances to the source, viral load, flow rate, and enclosed conditions. At last, clinical tests are carried out to demonstrate the robustness and potential field applications of the sensors.

 
more » « less
NSF-PAR ID:
10482499
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Advanced Materials Technologies
Volume:
9
Issue:
3
ISSN:
2365-709X
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract Rapid, inexpensive, and easy-to-use coronavirus disease 2019 (COVID-19) home tests are key tools in addition to vaccines in the world wide fight to eliminate national and local shutdowns. However, currently available tests for SARS-CoV-2, the virus that causes COVID-19, are too expensive, painful, and irritating, or not sufficiently sensitive for routine, accurate home testing. Herein, we employ custom-formulated graphene inks and aerosol jet printing to create a rapid electrochemical immunosensor for direct detection of SARS-CoV-2 spike receptor-binding domain (RBD) in saliva samples acquired noninvasively. This sensor demonstrated limits of detection that are considerably lower than most commercial SARS-CoV-2 antigen tests (22.91 ± 4.72 pg ml −1 for spike RBD and 110.38 ± 9.00 pg ml −1 for spike S1) as well as fast response time (∼30 min), which was facilitated by the functionalization of printed graphene electrodes in a single-step with SARS-CoV-2 polyclonal antibody through the carbodiimide reaction without the need for nanoparticle functionalization or secondary antibody or metallic nanoparticle labels. This immunosensor presents a wide linear sensing range from 1 to 1000 ng ml −1 and does not react with other coexisting influenza viruses such as H1N1 hemagglutinin. By combining high-yield graphene ink synthesis, automated printing, high antigen selectivity, and rapid testing capability, this work offers a promising alternative to current SARS-CoV-2 antigen tests. 
    more » « less
  2. In the context of continued spread of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 and the emergence of new variants, the demand for rapid, accurate, and frequent detection is increasing. Moreover, the new predominant strain, Omicron variant, manifests more similar clinical features to those of other common respiratory infections. The concurrent detection of multiple potential pathogens helps distinguish SARS-CoV-2 infection from other diseases with overlapping symptoms, which is significant for providing tailored treatment to patients and containing the outbreak. Here, we report a lab-on-a-chip biosensing platform for SARS-CoV-2 detection based on the subwavelength grating micro-ring resonator. The sensing surface is functionalized by specific antibody against SARS-CoV-2 spike protein, which could produce redshifts of resonant peaks by antigen–antibody combination, thus achieving quantitative detection. Additionally, the sensor chip is integrated with a microfluidic chip featuring an anti-backflow Y-shaped structure that enables the concurrent detection of two analytes. In this study, we realized the detection and differentiation of COVID-19 and influenza A H1N1. Experimental results indicate that the limit of detection of our device reaches 100 fg/ml (1.31 fM) within 15 min detecting time, and cross-reactivity tests manifest the specificity of the optical diagnostic assay. Furthermore, the integrated packaging and streamlined workflow facilitate its use for clinical applications. Thus, the biosensing platform presents a promising approach for attaining highly sensitive, selective, multiplexed, and quantitative point-of-care diagnosis and distinction between COVID-19 and influenza.

     
    more » « less
  3. Virus-like particles (VLPs) have been proposed as an attractive tool in SARS-CoV-2 vaccine development, both as (1) a vaccine candidate with high immunogenicity and low reactogenicity and (2) a substitute for live virus in functional and neutralization assays. Though multiple SARS-CoV-2 VLP designs have already been explored in Sf9 insect cells, a key parameter ensuring VLPs are a viable platform is the VLP spike yield (i.e., spike protein content in VLP), which has largely been unreported. In this study, we show that the common strategy of producing SARS-CoV-2 VLPs by expressing spike protein in combination with the native coronavirus membrane and/or envelope protein forms VLPs, but at a critically low spike yield (~0.04–0.08 mg/L). In contrast, fusing the spike ectodomain to the influenza HA transmembrane domain and cytoplasmic tail and co-expressing M1 increased VLP spike yield to ~0.4 mg/L. More importantly, this increased yield translated to a greater VLP spike antigen density (~96 spike monomers/VLP) that more closely resembles that of native SARS-CoV-2 virus (~72–144 Spike monomers/virion). Pseudotyping further allowed for production of functional alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2), and omicron (B.1.1.529) SARS-CoV-2 VLPs that bound to the target ACE2 receptor. Finally, we demonstrated the utility of pseudotyped VLPs to test neutralizing antibody activity using a simple, acellular ELISA-based assay performed at biosafety level 1 (BSL-1). Taken together, this study highlights the advantage of pseudotyping over native SARS-CoV-2 VLP designs in achieving higher VLP spike yield and demonstrates the usefulness of pseudotyped VLPs as a surrogate for live virus in vaccine and therapeutic development against SARS-CoV-2 variants.

     
    more » « less
  4. Abstract

    The SARS‐CoV‐2 pandemic caused a public health crisis throughout the world and highlighted the need for rapid and sensitive testing as a countermeasure. A sensitive and specific biosensor platform is developed for the detection of antigen and RNA of SARS‐CoV‐2, and its variant (B1.1.529). The demonstrated biosensor platform combines unique protein catalyzed capture bioreceptors (PCCs) for antigen capture and a chimeric (RNA‐DNA) probe for RNA detection using LwaCas13a collateral cleavage activity atop graphene field effect transistors (gFETs). The reported biosensor is able to differentiate unprocessed 104pfu m−1samples of SARS‐CoV‐2 from Influenza and Rhinovirus. The limit of detection (LOD) calculated for SARS‐CoV‐2 antigen is 103in buffer and 104PFU mL−1in 10% saliva, while LOD of ≈65 amcalculated for viral RNA isolate without amplification. To provide a high reliability of detection, the role of internal and external factors with respect to gate voltage is further analyzed by Principal Component Analysis (PCA). Based on PCA analysis, the authors are able to classify the samples as pathogen positive or negative (Y> 0: Positive for pathogen,Y< 0: Negative for pathogen). The reported platform can be quickly adapted for multi‐omics and multiplexed diagnosis of continuously evolving biothreats and global pandemics.

     
    more » « less
  5. Lee, Benhur (Ed.)
    ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 40 million people worldwide, with over 1 million deaths as of October 2020 and with multiple efforts in the development and testing of antiviral drugs and vaccines under way. In order to gain insights into SARS-CoV-2 evolution and drug targets, we investigated how and to what extent the SARS-CoV-2 genome sequence differs from those of other well-characterized human and animal coronavirus genomes, as well as how polymorphic SARS-CoV-2 genomes are generally. We ultimately sought to identify features in the SARS-CoV-2 genome that may contribute to its viral replication, host pathogenicity, and vulnerabilities. Our analyses suggest the presence of unique sequence signatures in the 3′ untranslated region (3′-UTR) of betacoronavirus lineage B, which phylogenetically encompasses SARS-CoV-2 and SARS-CoV as well as multiple groups of bat and animal coronaviruses. In addition, we identified genome-wide patterns of variation across different SARS-CoV-2 strains that likely reflect the effects of selection. Finally, we provide evidence for a possible host-microRNA-mediated interaction between the 3′-UTR and human microRNA hsa-miR-1307-3p based on the results of multiple computational target prediction analyses and an assessment of similar interactions involving the influenza A H1N1 virus. This interaction also suggests a possible survival mechanism, whereby a mutation in the SARS-CoV-2 3′-UTR leads to a weakened host immune response. The potential roles of host microRNAs in SARS-CoV-2 replication and infection and the exploitation of conserved features in the 3′-UTR as therapeutic targets warrant further investigation. IMPORTANCE The coronavirus disease 2019 (COVID-19) outbreak is having a dramatic global effect on public health and the economy. As of October 2020, SARS-CoV-2 has been detected in over 189 countries, has infected over 40 million people, and is responsible for more than 1 million deaths. The genome of SARS-CoV-2 is small but complex, and its functions and interactions with human host factors are being studied extensively. The significance of our study is that, using extensive SARS-CoV-2 genome analysis techniques, we identified potential interacting human host microRNA targets that share similarity with those of influenza A virus H1N1. Our study results will allow the development of virus-host interaction models that will enhance our understanding of SARS-CoV-2 pathogenesis and motivate the exploitation of both the interacting viral and host factors as therapeutic targets. 
    more » « less