Recent Advances in DNA Nanotechnology-Enabled Biosensors for Virus Detection

Abstract

Virus-related infectious diseases are serious threats to humans, which makes virus detection of great importance. Traditional virus-detection methods usually suffer from low sensitivity and specificity, are time-consuming, have a high cost, etc. Recently, DNA biosensors based on DNA nanotechnology have shown great potential in virus detection. DNA nanotechnology, specifically DNA tiles and DNA aptamers, has achieved atomic precision in nanostructure construction. Exploiting the programmable nature of DNA nanostructures, researchers have developed DNA nanobiosensors that outperform traditional virus-detection methods. This paper reviews the history of DNA tiles and DNA aptamers, and it briefly describes the Baltimore classification of virology. Moreover, the advance of virus detection by using DNA nanobiosensors is discussed in detail and compared with traditional virus-detection methods. Finally, challenges faced by DNA nanobiosensors in virus detection are summarized, and a perspective on the future development of DNA nanobiosensors in virus detection is also provided.

Keywords: DNA nanotechnology; DNA origami; DNA tile; biosensors; virus detection.

Figure 2

Principles and applications of DNA aptamers for biosensing. (a) Secondary structure of the B4–25 aptamer obtained by the FOLD method [74]. Copyright 1990, Springer Nature. (b) The SELEX process consists of five main steps: binding, magnetic separation, elution, amplification, and conditioning [83]. Copyright 2015, American Chemical Society. (c) The schematic representation illustrates the structures of the typical antibodies, G4–SSA and G4–SSA target complement [84]. Copyright 2019, American Chemical Society. (d) Schematic of the CRISPR/Cas12a-derived electro-chemical sensor for ultrasensitive detection of SARS-CoV-2p [85]. Copyright 2022, Elsevier.

Figure 4

SERS DNA nanobiosensors for virus detection. (a) Schematic diagram of SERS biosensor for DENV gene by cascade enzyme-free signal amplification strategy of local catalytic hairpin assembly (LCHA) and hybridization chain reaction (HCR) [148]. Copyright 2020, Elsevier. (b) SERS-based design strategy for the SARS-CoV-2 label-free sensitive-sensor platform [150]. Copyright 2023, Elsevier.

Figure 5

SPR DNA nanobiosensors for virus detection. (a) Schematic diagram of SPR biosensors based on ESDRs and DDTs nanostructures for the detection of HIV-related DNA [158]. Copyright 2017, Elsevier. (b) Diagram of the AIV detection biosensor fabricated based on the LSPR method [159]. Copyright 2019, Elsevier. (c) Schematic of the mechanism of DENV detection by AuNPs and hairpin ssDNA–CdSeTeS QDs [160].

Figure 6

Fluorescence-based DNA nanobiosensors for virus detection. (a) Schematic representation of the working principle of the fluorescence DENV assay based on QD-CPs [171]. Copyright 2015, Elsevier. (b) The working principle of the fluorescence-based detection of HCV using the acpcPNA-immobilized PAD and ssDNA-specific fluorescence dye [173]. Copyright 2021, Elsevier. (c) Dimensional analysis and design concept of the DNA tile structure corresponding to the ED3 cluster on the DENV surface [175]. Copyright 2019, Springer Nature. (d) Schematic design concept and detection of DNA mesh structures binding to SARS-CoV-2 [31]. Copyright 2019, Springer Nature.

Figure 7

Electrochemical DNA nanobiosensors for virus detection. (a) Schematic image of the fabricated AIV detection biosensor [186]. Copyright 2019, Elsevier. (b) Schematic illustration of triplet nanostructure-mediated dendritic HCR for electrochemical detection of DENV [187]. Copyright 2021, Elsevier. (c) Schematic diagram of an electrochemical biosensor based on DNA tetrahedral nanostructures for the detection of H7N9 virus [188]. Copyright 2015, American Chemical Society.

Scheme 1

DNA nanotechnology-based optical and electrochemical DNA biosensors for virus detection.

Figure 1

Wireframe DNA tile self-assembled polyhedron. (a) The infinite 2D lattice is constructed separately using the multi-vertex branching DNA tile as the basic unit [43,45,46,47,48]. Copyright 2020, American Chemical Society. (b) Construction of wireframe polyhedral structures by hierarchical assembly of branching DNA tiles as basic units [48,49,50,51,52,53,54,55,56]. Copyright 2020, American Chemical Society. (c) Two-dimensional (2D) and three-dimensional (3D) lattices of composite 142 mesojunctions [57]. Copyright 2023, American Chemical Society. (d) 3D DNA motifs with two turns per helical axis [58]. Copyright 2022, Wiley-VCH. (e) Crystal packing of the sΔ247-WC 24 bp trigonal motif with GA/TC sticky ends showcasing the two diamond subunits [59]. Copyright 2022, Wiley-VCH.

Figure 3

The Baltimore classification of viruses [95]. (a) Description of a revised classification scheme for the seven major classes of viruses in the Baltimore classification system that highlights the transfer of genetic information from the nucleic acids of the viral endo-encapsulated genome to the mRNA. (b) The evolution of the Baltimore taxa and the original replicon pool is shown. Copyright 2021, American Society for Microbiology.

Figure 8

Impedance-based DNA nanobiosensors for virus detection. (a) Schematic representation of the construction and DNA hybridization stages of the oxidized-GCE-[AuNP-SiPy]/ZIKV1 biosensor [195]. Copyright 2019, Elsevier. (b) Schematic representation of different steps for the fabrication of electrochemical DNA biosensors [196]. Copyright 2018, Elsevier. (c) AuNT PC surface probe immobilization and hybridization of HPV-DNA target sequences with AuNT surface modifications and schematic diagrams [197]. Copyright 2019, Elsevier.