Highly sensitive detection of influenza virus by boron-doped diamond electrode terminated with sialic acid-mimic peptide

Abstract

The progression of influenza varies according to age and the presence of an underlying disease; appropriate treatment is therefore required to prevent severe disease. Anti-influenza therapy, such as with neuraminidase inhibitors, is effective, but diagnosis at an early phase of infection before viral propagation is critical. Here, we show that several dozen plaque-forming units (pfu) of influenza virus (IFV) can be detected using a boron-doped diamond (BDD) electrode terminated with a sialic acid-mimic peptide. The peptide was used instead of the sialyloligosaccharide receptor, which is the common receptor of influenza A and B viruses required during the early phase of infection, to capture IFV particles. The peptide, which was previously identified by phage-display technology, was immobilized by click chemistry on the BDD electrode, which has excellent electrochemical characteristics such as low background current and weak adsorption of biomolecules. Electrochemical impedance spectroscopy revealed that H1N1 and H3N2 IFVs were detectable in the range of 20-500 pfu by using the peptide-terminated BDD electrode. Our results demonstrate that the BDD device integrated with the receptor-mimic peptide has high sensitivity for detection of a low number of virus particles in the early phase of infection.influenza virus | boron-doped diamond electrode | sialic acid-mimic peptide | electrochemical impedance spectroscopy | click chemistry

Nanocrystalline diamond-glass platform for the development of three-dimensional micro- and nanodevices

“…After growth, NCD films can be processed to form two or three-dimensional suspended structures [11,12] and the surface of an NCD film can be functionalized with a variety of (bio)molecules for use in biosensors [13] and solar cells [14]. Due to these excellent properties, NCD based devices such as micromechanical resonators of high Q-factor [15,16], pressure sensors for harsh environments [17,18], tunable optical lenses [19], biosensors that, for example, can detect influenza [20,21], optically transparent electrodes [22,23], CO 2 reducing electrodes [24], superconducting quantum interference devices [25], and conducting atomic force microscope tips are being developed [26].…”

Recent trends in click chemistry as a promising technology for virus-related research

“…Recently, a boron-doped diamond (BBD) electrode clicked with sialic acid-mimic peptide, a common receptor of influenza viruses, was designed to capture influenza virions during the early stages of infection (Fig. 3b) (Matsubara et al, 2016). Using the BBD, 20-500 pfu of H1N1 and H3N2 virions can be detected, indicating that the BDD device integrated with the receptor-mimic peptide has high sensitivity in the early phase of infection (Matsubara et al, 2016).…”

“…3b) (Matsubara et al, 2016). Using the BBD, 20-500 pfu of H1N1 and H3N2 virions can be detected, indicating that the BDD device integrated with the receptor-mimic peptide has high sensitivity in the early phase of infection (Matsubara et al, 2016). The great advantage of this BBD is that the sialic acidmimic peptide is free from the risk of NA digestion (Matsubara et al, 2016).…”

“…The amount and size of the nanoclusters correlate with the target concentration and can be quantified using an optomagnetic readout method (Antunes et al, 2015). (b) The sialic acid-mimic peptide dimer was immobilized on the alkyne-terminated BDD electrode via a click reaction, and the capture of the influenza virus was detected electrochemically (Matsubara et al, 2016). (c) Biotin-modified capture DNA was linked on Streptavidin MagneSphere Paramagnetic Particles and hybridized with hepatitis B virus DNA, followed by hybridizing the target DNA with DNA-CuS particles to form a sandwich like structure (Yue et al, 2014).…”

Recent Progress in Electrochemical Biosensors for Glycoproteins

“…The sensors thus prepared show impedimetric response to Lens culinaris lectin with a detection limit of 5 ± 0.5 nM. A similar protocol for the formation of sialic acid SAMs on BDD electrodes has been reported, in which ethynylbenzene is first introduced on the BDD surface and, after deprotection, sialic acid-mimic peptide terminated with an azide group is immobilized via click reaction [78]. The BDD electrode is used for detecting influenza virus in the range of 20–500 plaque-forming units (pfu), based on the high affinity of influenza virus to sialic acid [79].…”