Rapid diagnosis of COVID-19 via nano-biosensor-implemented biomedical utilization: a systematic review

Abstract

The novel human coronavirus pandemic is one of the most significant occurrences in human civilization. The rapid proliferation and mutation of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) have created an exceedingly challenging situation throughout the world's healthcare systems ranging from underdeveloped countries to super-developed countries. The disease is generally recognized as coronavirus disease 2019 (COVID-19), and it is caused by a new human CoV, which has put mankind in jeopardy. COVID-19 is death-dealing and affects people of all ages, including the elderly and middle-aged people, children, infants, persons with co-morbidities, and immunocompromised patients. Moreover, multiple SARS-CoV-2 variants have evolved as a result of genetic alteration. Some variants cause severe symptoms in patients, while others cause an unusually high infection rate, and yet others cause extremely severe symptoms as well as a high infection rate. Contrasting with a previous epidemic, COVID-19 is more contagious since the spike protein of SARS-CoV-2 demonstrates profuse affection to angiotensin-converting enzyme II (ACE2) that is copiously expressed on the surface of human lung cells. Since the estimation and tracking of viral loads are essential for determining the infection stage and recovery duration, a quick, accurate, easy, cheap, and versatile diagnostic tool is critical for managing COVID-19, as well as for outbreak control. Currently, Reverse Transcription Polymerase Chain Reaction (RT-PCR) testing is the most often utilized approach for COVID-19 diagnosis, while Computed Tomography (CT) scans of the chest are used to assess the disease's stages. However, the RT-PCR method is non-portable, tedious, and laborious, and the latter is not capable of detecting the preliminary stage of infection. In these circumstances, nano-biosensors can play an important role to deliver point-of-care diagnosis for a variety of disorders including a wide variety of viral infections rapidly, economically, precisely, and accurately. New technologies are being developed to overcome the drawbacks of the current methods. Nano-biosensors comprise bioreceptors with electrochemical, optical, or FET-based transduction for the specific detection of biomarkers. Different types of organic-inorganic nanomaterials have been incorporated for designing, fabricating, and improving the performance and analytical ability of sensors by increasing sensitivity, adsorption, and biocompatibility. The particular focus of this review is to carry out a systematic study of the status and perspectives of synthetic routes for nano-biosensors, including their background, composition, fabrication processes, and prospective applications in the diagnosis of COVID-19.

Fig. 1. Commonly used methods for the spotting of SARS-CoV-2 and COVID-19 prognosis. Reprinted (adapted) with permission from (ref. 15) copyright 2021, MDPI.

Fig. 2. Chronology of the different nano-biosensors developed for the detection of other virus strains. Reprinted (adapted) with permission from (ref. 20) copyright 2021, Wiley.

Fig. 3. Simple illustration of an immuno-biosensor manufactured by coating the graphene sheet of a FET with a clearly defined protein found in coronavirus spikes. Reproduced (adapted) from (ref. 30) copyright 2020, ACS.

Fig. 4. (a) Typical representation of ROS, (b) device for ROS detection, (c) ROS detected in different patients, and (d), (e) contrasted with a verified sample. (f) Red, orange, and green represent 800 μA, 490 μA, and ∼71 μA, respectively. Images produced by lung CT scanning (d, e, and f). Reprinted (adapted) with permission from (ref. 10) copyright 2021, Elsevier.

Fig. 5. (a) Functionalities of sensors, (b) different layers for operation purposes, and (c) the molecular structure of proposed nano-biosensors. Reprinted (adapted) with permission from (ref. 37) copyright 2021, Springer Nature.

Fig. 6. CNT-FET-based nano-biosensor and SARS-CoV-2 S1 detection process. Reprinted (adapted) with permission from (ref. 40) copyright 2022, Elsevier.

Fig. 7. (a) Structural and (b) functional representation of LFIA sensors. Reprinted (adapted) with permission from (ref. 48) copyright 2020, ACS.

Fig. 8. The procedure for the detection of IL-6 present in blood samples of patients by a paper-based biosensor with the help of a smartphone application. Reprinted (adapted) with permission from (ref. 49) copyright 2021, Elsevier.

Fig. 9. (a) Simple illustration of the surface of the nano-biosensor, (b) test procedure, and (c) the complete setup of the device. In the figure, HRP, dAb, and N protein stand for horseradish peroxidase, detection antibody, and nucleocapsid proteins, respectively. Reprinted (adapted) with permission from (ref. 51) copyright 2021, ACS.

Fig. 10. Schematic illustration of functionalized magnetic nanoparticles (a), mimetic SARS-CoV-2 (b), and MPS signals (c). Reprinted (adapted) with permission from (ref. 54) copyright 2021, ACS.

Fig. 11. Typical illustration of the structure and operation of magnetic nanoparticles-based nano-biosensors. Reprinted (adapted) with permission from (ref. 55) copyright 2021, Elsevier.

Fig. 12. SARS-CoV-2 detection utilizing a surface-enhanced Raman spectroscopy (SERS)-based aptasensor constructed on silver nanoparticles (AgNPs). Reprinted (adapted) with permission from (ref. 58) copyright 2022, Elsevier.

Fig. 13. Schematic depiction of the fabrication processes for the nanoprobes (A) and the electrochemical aptasensor for the capture and detection of 2019-nCov-NP (B). Reprinted (adapted) with permission from (ref. 59) copyright 2021, Elsevier.

Fig. 14. Plasmonic biosensors for detecting and identifying COVID-19. (a) Device configuration and sensing mechanism of the 3D plasmonic sensor. (b) A genetic algorithm (GA) program is used to optimize the metal structure, where “1” means nano-metal and “0” means no nano-metal. (c) The resonance position of the metal structure is designed to overlap the fingerprint vibration signals of the virus molecule, allowing the simultaneous enhancement and detection of COVID-19-induced absorption changes. Reprinted (adapted) with permission from (ref. 62) copyright 2021, ACS.

Fig. 15. Label-free detection of the SARS-CoV-2 pseudovirus with a nanoplasmonic sensor. (a) Schematic diagram of the nanoplasmonic resonance sensor for the determination of the SARS-CoV-2 pseudovirus concentration. (b) A photograph (middle) showing one piece of the Au nanocup array chip with a drop of water on top. Scanning electron microscopy image (left) showing the replicated nanocup array. Transmission microscopy image (right) showing that air and water on the device surface exhibit different colors; green and far-red pink, respectively. Reprinted (adapted) with permission from (ref. 63) copyright 2021, Elsevier.