Virus Detection: From State-of-the-Art Laboratories to Smartphone-Based Point-of-Care Testing

Abstract

Infectious virus outbreaks pose a significant challenge to public healthcare systems. Early and accurate virus diagnosis is critical to prevent the spread of the virus, especially when no specific vaccine or effective medicine is available. In clinics, the most commonly used viral detection methods are molecular techniques that involve the measurement of nucleic acids or proteins biomarkers. However, most clinic-based methods require complex infrastructure and expensive equipment, which are not suitable for low-resource settings. Over the past years, smartphone-based point-of-care testing (POCT) has rapidly emerged as a potential alternative to laboratory-based clinical diagnosis. This review summarizes the latest development of virus detection. First, laboratory-based and POCT-based viral diagnostic techniques are compared, both of which rely on immunosensing and nucleic acid detection. Then, various smartphone-based POCT diagnostic techniques, including optical biosensors, electrochemical biosensors, and other types of biosensors are discussed. Moreover, this review covers the development of smartphone-based POCT diagnostics for various viruses including COVID-19, Ebola, influenza, Zika, HIV, et al. Finally, the prospects and challenges of smartphone-based POCT diagnostics are discussed. It is believed that this review will aid researchers better understand the current challenges and prospects for achieving the ultimate goal of containing disease-causing viruses worldwide.

Keywords: biosensors; laboratory-based diagnostics; point-of-care testing; smartphones; virus.

Figure 1

The appeared of major events in popular infectious diseases. From top to bottom are digitally colorized transmission electron microscopic (TEM) or 3D particle structure images of various infectious viruses. Image of Adonavirus: https://commons.wikimedia.org/wiki/File:Adenovirus_3D_schematic.png. Image of HCV: https://commons.wikimedia.org/wiki/File:HCV.png. Image of Zika Virus: https://commons.wikimedia.org/wiki/File:Zika-chain-colored.png.

Figure 2

a) Immune response to virus infection, time points are approximate and could be changed depending on the different viruses. Protective immune responses of adaptive immune system to b) acutely cytopathic viruses and c) poorly cytopathic viruses. Reproduced with permission.^{[ 42 ]} Copyright 2006, Nature Publishing Group.

Figure 3

Laboratory‐based virus detection. Schematic diagram of the basic principle: a) ELISA. Reproduced with permission.^{[ 46 ]} Copyright 2016, Nexus Academic Publishers. b) electrochemical immunoassay. Reproduced with permission.^{[ 47 ]} Copyright 2018, Nature Publishing Group. c) RT‐PCR. Reproduced with permission.^{[ 48 ]} Copyright 2011, Elsevier.

Figure 4

POC virus diagnostic systems and equipment currently marketed. a) ID NOW influenza A & B 2 system (Abbott Co., Ltd). Reproduced with permission.^{[ 172 ]} Copyright 2022, Abbott. b) The m‐PIMA analyzer and m‐the PIMA HIV‐1/2 test cartridge (Abbott Co., Ltd). Reproduced with permission.^{[ 173 ]} Copyright 2022, Abbott. c) The GeneXpert System and the Xpert HIV‐1/HCV viral load test cartridge (Cepheid Co., Ltd). Reproduced with permission.^{[ 174 ]} Copyright 2022, Cepheid. d) R01 fluorescence immunoassay analyzer and Rapid test strip (Maccura Co., Ltd). Reproduced with permission.^{[ 175 ]} Copyright 2022, Maccura.

Figure 5

Built‐in functional modules in smartphones include the camera, ambient light sensor, distance sensor, gravity sensor, acceleration sensor, electrochemical module, magnetic sensor, barometric sensor, gyroscopes, global position system (GPS).

Figure 6

Smartphone‐based colorimetric biosensors for virus detection. a) The detection processes of the instrument‐free ZIKV POC test. Reproduced with permission.^{[ 90 ]} Copyright 2020, Elsevier. b) Smartphone combined with colloidal gold LFIAS for Ebola virus IgG detection. Reproduced with permission.^{[ 93 ]} Copyright 2018, American Chemical Society. c) A sample‐to‐answer, portable smartphone‐controlled system that integrated self‐driven LAMP microfluidic device for the detection of H1N1 virus. Reproduced with permission.^{[ 98 ]} Copyright 2019, Royal Society of Chemistry. d) Smartphone mediated paper‐based Dot ELISA system for HIV p24 antigen detection. Reproduced with permission.^[95] Copyright 2018, Elsevier.

Figure 7

Smartphone‐based fluorescence biosensors for virus detection. a) The design of the smartphone‐based fluorescent LFIAS platform for the detection of ZIKV NS1. Reproduced with permission.^{[ 113 ]} Copyright 2019, Elsevier. b) Overview of smartphone‐based fluorescence LFIAS reader design. Smartphone‐based LFIAS reader including a reflective light concentrator module, a fluorescence detector flow strip, and the test procedures of the purposedplatform. Reproduced with permission.^{[ 114 ]} Copyright 2016, Ivyspring International Publisher. c) Smartphone‐enabled LAMP box for analysis of Zika viruses with RT‐LAMP assay. Reproduced with permission.^{[ 124 ]} Copyright 2017, Nature Publishing Group. d) Workflow for the detection of SARS‐CoV‐2 using smartphone‐based imaging POC system. Reproduced with permission.^{[ 125 ]} Copyright 2020, National Academy of Sciences, USA. e) Schematic of a 3D‐printed smartphone fluorescence reader, and workflow of a saliva‐based on‐chip CRISPR‐FDS smartphone assay. Reproduced with permission.^{[ 135 ]} Copyright 2020, American Association for the Advancement of Science (AAAS).

Figure 8

Smartphone‐based electrochemical biosensors for virus detection. a) POC smartphone‐based potentiostat platform with CV to detect HCV. Reproduced with permission.^{[ 143 ]} Copyright 2016, Elsevier. b) System diagram and electrochemical principle for WBC count with DPV. Reproduced with permission.^{[ 145 ]} Copyright 2017, Elsevier. c) The SIC4341 circuit board diagram and the image of portable NFC Potentiostat, and the interface of POTEN_303 app. Reproduced with permission.^{[ 147 ]} Copyright 2021, Elsevier.

Figure 9

a,b) Smartphone‐based microscopy for virus disease diagnostics. a) Overview of the smartphone‐based microscopy utilizing quantum dot barcodes. The assay involves the addition of patient samples to a chip coated with microbeads and related optical principles. Reproduced with permission.^{[ 149 ]} Copyright 2015, American Chemical Society. b) SPIR microscopy and schematic of the experimental setup. Reproduced with permission.^{[ 150 ]} Copyright 2018, American Chemical Society. c–e) Smartphone integrated with other types of biosensors for virus disease diagnostics. c) 3D schematic of the CNN‐nanoparticle‐enabled smartphone for virus detection. Reproduced with permission.^{[ 152 ]} Copyright 2020, American Association for the Advancement of Science (AAAS). d) Image of GMR nanosensor chip on PCB, and essential components of the redesigned Eigen diagnosis platform. Reproduced with permission.^{[ 153 ]} Copyright 2019, Elsevier. e) Wearable RPA sensing system for rapid detection of HIV‐1 DNA is consisted of a fluorescence image box and PDMS‐based flexible chips. Reproduced with permission.^{[ 155 ]} Copyright 2019, Elsevier.