Ultrasensitive and Label-Free Detection of the Measles Virus Using an N-Heterocyclic Carbene-Based Electrochemical Biosensor

Abstract

With the current intense need for rapid and accurate detection of viruses due to COVID-19, we report on a platform technology that is well suited for this purpose, using intact measles virus for a demonstration. Cases of infection due to the measles virus are rapidly increasing, yet current diagnostic tools used to monitor for the virus rely on slow (>1 h) technologies. Here, we demonstrate the first biosensor capable of detecting the measles virus in minutes with no preprocessing steps. The key sensing element is an electrode coated with a self-assembled monolayer containing the measles antibody, immobilized through an N-heterocyclic carbene (NHC). The intact virus is detected by changes in resistance, giving a linear response to 10−100 μg/mL of the intact measles virus without the need to label or process the sample. The limit of detection is 6 μg/mL, which is at the lower limit of concentrations that can cause infections in primates. The NHC-based biosensors are shown to be superior to thiol-based systems, producing an approximately 10× larger response and significantly greater stability toward repeated measurements and long-term storage. This NHC-based biosensor thus represents an important development for both the rapid detection of the measles virus and as a platform technology for the detection of other biological targets of interest.

Electrochemical Generation of N‐Heterocyclic Carbenes for Use in Synthesis and Catalysis

“…In recent work, Birss and co-workers have demonstrated the use of an NHC decorated Au electrode for the electrochemical detection of the measles virus. [50] The NHC is covalently bonded to the measles antibody, creating a monolayer. The system is then used as an electrochemical biosensor.…”

Imidazolinium N-Heterocyclic Carbene Ligands for Enhanced Stability on Gold Surfaces

“…For example, recent reports have employed thiol-based ligands to develop patterned molecular films for site-specific immobilization of biomolecules, , to investigate host–guest complexation for surface detection of polycyclic aromatic hydrocarbons, and to tether aptamers on implantable electrochemical devices for in vivo diagnostics. , In 2014, Crudden and co-workers reported that N -heterocyclic carbene (NHC) ligands form stable, well-ordered, and self-assembled monolayers on crystalline gold that can, in many situations, exceed the performance of thiols. Since their initial work, multiple research groups have explored the capabilities of NHC-coated surfaces toward a variety of applications. − …”

Affinity Sensors for the Diagnosis of COVID-19

“…Incidentally, the application of antibody fragments seems to be a very promising approach for the development of sensors for the determination of virus proteins because it enables increasing the surface concertation of sites that are selective to virus proteins [125,126] There are some other researches dedicated to the development of biosensors with the potential application for the determination of SARS-CoV-2 infection, based on the antigen-antibody interactions. In order to exploit such interactions, an electrochemical biosensor based on electrode covered with a SAM and specific-antibodies against SARS-CoV-2 proteins, was designed [127].…”