Glycan-immobilized dual-channel field effect transistor biosensor for the rapid identification of pandemic influenza viral particles

Abstract

Pandemic influenza, triggered by the mutation of a highly pathogenic avian influenza virus (IFV), has caused considerable damage to public health. In order to identify such pandemic IFVs, antibodies that specifically recognize viral surface proteins have been widely used. However, since the analysis of a newly discovered virus is time consuming, this delays the availability of suitable detection antibodies, making this approach unsuitable for the early identification of pandemic IFVs. Here we propose a label-free semiconductor-based biosensor functionalized with sialic-acid-containing glycans for the rapid identification of the pandemic IFVs present in biological fluids. Specific glycans are able to recognize wild-type human and avian IFVs, suggesting that they are useful in discovering pandemic IFVs at the early stages of an outbreak. We successfully demonstrated that a dual-channel integrated FET biosensing system, which were modified with 6′-sialyllactose and 3′-sialyllactose for each gate area, can directly and specifically detect human H1N1 and avian H5N1 IFV particles, respectively, present in nasal mucus. Furthermore, to examine the possibility of identifying pandemic IFVs, the signal attributed to the detection of Newcastle disease virus (NDV) particles, which was selected as a prime model of a pandemic IFV, was clearly observed from both sensing gates. Our findings suggest that the proposed glycan-immobilized sensing system could be useful in identifying new pandemic IFVs at the source of an outbreak.

Recent advances and challenges in electrochemical biosensors for emerging and re-emerging infectious diseases

“…In addition, the assay responds specifically to SARS CoV-2 in presence of MERS CoV. Hideshima et al reported a glycan based FET biosensor which can detect both human H1N1 and avian H5N1 influenza viruses in nasal mucus [ 109 ]. Rapid detection in the wide concentration range 10 0.5 to 10 8.5 TCID 50 /mL was made possible by functionalizing the gate terminals with two different sialic acid containing glycans that recognize human and avian viruses respectively.…”

Field-Effect Sensors for Virus Detection: From Ebola to SARS-CoV-2 and Plant Viral Enhancers

“…To selectively recognize target biomolecules or bioparticles, the gate insulator surface is functionalized with respective receptors (e.g., antibodies, antigens or ssDNA). the electrostatic detection of various intact virus particles, including several subtypes of influenza A [H1N1 (Hideshima et al, 2019;Park et al, 2019), H3N2 (Shen et al, 2012), H5N1 (Hideshima et al, 2019), H5N2 (Chiang et al, 2012)], human immunodeficiency virus (HIV) (Kim et al, 2019), rotavirus (Liu et al, 2013), Ebola (Jin et al, 2019), and SARS-CoV-2 (Seo et al, 2020). For instance, a SiNW biosensor for the rapid (within minutes) and low-cost diagnosis of seasonal flu that could detect H3N2 viruses in clinical, exhaled breath condensate samples down to ∼3 × 10 4 particles/mL, was developed by Shen et al (2012).…”

Glycan Nanobiosensors

“…LOD for virus detection was 0.025 HAU, which was two orders of magnitude lower than with conventional rapid human influenza virus test kits [ 130 ]. A similar two-channel device based on a semiconductor interface for immobilization of α-2,6-sialylactose and α-2,3-sialylactose was used for the detection of human (H1N1) and avian (H2N1) influenza viruses [ 131 ]. The portable device connected to a mobile phone via Bluetooth could measure the interaction in a label-free format with the integration seen in real time ( Figure 17 ).…”

“…The portable device connected to a mobile phone via Bluetooth could measure the interaction in a label-free format with the integration seen in real time ( Figure 17 ). The device could detect influenza viruses at a concentration much lower than by using a device based on immunochromatography [ 131 ]. Another device for the detection of influenza relies on the compression of a polymer layer resulting in the induction of stress in the artificial layer causing a resonance frequency shift ( Figure 18 ) [ 132 ].…”