Electrochemical Aptasensing of SARS-CoV-2 Based on Triangular Prism DNA Nanostructures and Dumbbell Hybridization Chain Reaction

Abstract

Development of convenient, accurate, and sensitive methods for rapid screening of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection is highly desired. In this study, we have developed a facile electrochemical aptasensor for the detection of the SARS-CoV-2 S1 protein amplified by dumbbell hybridization chain reaction (DHCR). A triangular prism DNA (TPDNA) nanostructure is first assembled and modified at the electrode interface. Due to the multiple thiol anchors, the immobilization is quite stable. The TPDNA nanostructure also provides an excellent scaffold for better molecular recognition efficiency on the top single-strand region (DHP0). The aptamer sequence toward the SARS-CoV-2 S1 protein is previously localized by partial hybridization with DHP0. In the presence of the target protein, the aptamer sequence is displaced and DHP0 is exposed. After further introduction of the fuel stands of DHCR, compressed DNA linear assembly occurs, and the product can be stacked on the TPDNA nanostructure for the enrichment of electrochemical species. This electrochemical method successfully detects the target protein in clinical samples, which provides a simple, robust, and accurate platform with great potential utility.

Programmable Nanostructures Based on Framework-DNA for Applications in Biosensing

“…Unlike antibodies, aptamers—short strands of ssDNA or RNA binding to specific target molecules or substances—are robust, easily chemically synthesized, and modified, which has been utilized to recognize the differing protein morphologies of different viruses. As illustrated in Figure 3 b, a simple electrochemical aptamer sensor for detecting SARS-CoV-2 S1 protein had been established using the dumbbell hybridization chain reaction (DHCR) technique [ 92 ]. The aptamer sequence of the SARS-CoV-2 S1 protein was previously positioned by partial hybridization with the DHP0 of the triangular prismatic DNA (TPDNA) nanostructure.…”

“…; et al Accessible detection of SARS-CoV-2 through molecular nanostructures and automated microfluidics, 2021 , 194 , 113629, Copyright (2021), with permission from Elsevier). ( b ) Aptamer-mediated target recognition with the DHCR process for the detection of the virus [ 92 ]. (Reprinted from Analytical Chemistry , Jiang, Y.; Chen, X.; Feng, N.; Miao, P. Electrochemical Aptasensing of SARS-CoV-2 Based on Triangular Prism DNA Nanostructures and Dumbbell Hybridization Chain Reaction, 2022 , 94 , 14755–14760, Copyright (2022), with permission from the American Chemical Society).…”

Aptamer‐based strategies against SARS‐CoV‐2 viruses

“…In a different study, CoV2‐RBD‐1C as a recognition element was embedded in a triangular prism DNA (TPDNA) nanostructure to block the initiation sequence of dumbbell hybridization chain reaction (DHCR), thus constructing an electrochemical strategy for ultra‐sensitive detection of S protein [51] (Figure 3a). When the aptamer binds to the target, the DHCR is triggered to achieve a linear assembly of the compressed DNA on top of TPDNA, causing an amplified electrochemical response.…”

A cascade amplification strategy based on rolling circle amplification and hybridization chain reaction for ultrasensitive detection of pathogens

“…32 An initiator triggers continuous reactions between two hairpin probes to form long nicked polymeric DNA double helices in typical HCR. [33][34][35] Through a simple modication on the hairpin probes, various signal modes would be generated and could be detected by colorimetric, 36 uorescence, 37 and electrochemical chemiluminescence. 38 However, the sensitivity of HCR needs to be improved if it is to be applied to clinical diagnosis in the future.…”