Rapid Detection and One-Step Differentiation of Cross-Reactivity Between Zika and Dengue Virus Using Functional Magnetic Nanosensors

Abstract

Infection with the Zika virus (ZIKV) is an ongoing problem especially as accurate, cost-effective testing remains unresolved. In addition, coinfection occurs with both the Dengue virus (DENV) and ZIKV which leads to cross-reactivity between the flaviviruses and can result in false positives and inaccurate testing. This supports the current need for a simple assay that can detect Zika antibodies sensitively that at the same time can differentiate between cross-reactive antibodies. In this study, we developed customizable magnetic relaxation nanosensors (MRnS) conjugated to various ligands, which included ZIKV (ZENV, zika domain III and NS1) and DENV proteins for specific detection of cross-reactive Zika and Dengue antibodies. Binding interactions between functional MRnS and corresponding targets resulted in the change in spin−spin magnetic relaxation time (T2MR) of water protons, allowing for a rapid and simple means by which these interactions were detected and quantified. Our results show the detection of Zika antibodies within minutes at concentrations as low as 20 nM and display high specificity, reproducibility, and analytical sensitivity. Furthermore, a mixture of functional MRnS was used for the one-step simultaneous detection and differentiation of Zika and Dengue infections. These results demonstrate high specificity and sensitivity for the detection of ZIKV and DENV despite coinfections in both simple and complex media. Overall, our magnetic nanoplatform could be used as a rapid and sensitive assay for the detection of not only Zika-and Dengue-related testing but can be further applied to serological samples of any other pathogens.

Plasmon-Enhanced Bimodal Nanosensors: An Enzyme-Free Signal Amplification Strategy for Ultrasensitive Detection of Pathogens

“…Appearance of a visible line on the protein A/G test strip indicated that the antibody was successfully conjugated on GNPs (2) and MPnS (3, Figure E). Additionally, we used the spin–spin T2 magnetic relaxation (MR) diagnostic technique, as explained in the previous literature . In brief, binding of target analytes displaced water molecules, leading to measurable changes in the spin–spin magnetic relaxation time (ΔT2).…”

“…Additionally, we used the spin−spin T2 magnetic relaxation (MR) diagnostic technique, as explained in the previous literature. 59 In brief, binding of target analytes displaced water molecules, leading to measurable changes in the spin−spin magnetic relaxation time (ΔT2). This was observed with the MPnS measured at 102 ms and the MPnS-Ab increasing to 115 ms (Figure 2F).…”

A Portable, Integrated, Sample-In Result-Out Nucleic Acid Diagnostic Device for Rapid and Sensitive Chikungunya Virus Detection

“…However, these specific antibody/antigen-based assays show poor sensitivity in the first few days of infection, particularly during the acute phase. Clinical statistics show that anti-CHIKV lgM is only detectable from day 4 to day 7 of sickness, resulting in false-negative results [6]. Due to their higher sensitivity and specificity, molecular diagnostic techniques can detect viruses early in infection within the window period of pathogen-specific antibody/antigen detection [7].…”