COVID-19 Multisensor
Graphene sensor made it possible to make an express test for COVID-19
Oksana Borzenkova, N+1
Scientists have created a graphene-based biosensor for an express test for COVID-19. Such a test can be done independently at home and get the result in less than ten minutes. The work is published in the Matter magazine.
The presence of the virus and its effect on the body can be judged by different biomarkers. For example, the result of the immune system's response to the virus antigen is antibodies, and for each type of virus, the body produces specific antibodies. Depending on the stage of the disease, it can be immunoglobulin G (IgG) or immunoglobulin M (IgM). Other markers are the nucleocapsid protein, which plays a role in the assembly of new viral particles, and the C-reactive protein, which shows the severity of the disease. Currently, there are many methods for detecting these markers, one of which is electrochemical.
The electrochemical method of detecting molecules makes it possible to determine their concentration by changing the current flowing between the electrodes. One of the electrodes (working) acts as a substrate for the assembly of a biological structure that interacts with the detected markers. Depending on the concentration of the marker that is bound to the structure, the resistance changes, and hence the current between the electrodes. These important biological parts of the structure are called functional and can be of different types – direct (using one antibody), indirect (using two antibodies, one of which is labeled), sandwich type (the protein to be registered is located between two antibodies).
Sensor structure, on the left – for registration of C-reactive and nucleocapsid proteins, on the right – antibodies. Drawings from the article in Matter.
A team of scientists from the California Institute of Technology led by Wei Gao has developed and manufactured an electrochemical multisensor that can simultaneously measure four markers – IgG, IgM, C-reactive and nucleocapsid proteins. In their research, the authors focused on detecting the SARS-CoV-2 virus.
When connected to auxiliary electronics, the sensor can transmit data to the user's mobile phone wirelessly via Bluetooth.
The multisensor consists of four separate working pads-electrodes and a common electrode that encircles these pads. The entire functional structure of the sensor is located on working graphene electrodes and consists of a linker, antibodies and labeled antibodies. A linker is necessary to stabilize the graphene surface, and to bond with an antibody or other protein. To register the C-reactive and nucleocapsid proteins, the authors sewed an antibody to the linker that specifically bound to the desired protein, and then added another labeled antibody on top to amplify the signal.
This structure is called a "sandwich" and has a high sensitivity due to the presence of two antibodies. The structure for detecting IgG and IgM looks simpler and consists of a piece of the SARS-CoV-2 virus itself, with which the antibody binds, and a labeled antibody. Due to the presence of a second antibody, such a structure is called indirect.
The results of experiments on real biological fluids. Changing the current through the cathodes for (a) healthy and (b) sick subjects. (c) histograms comparing healthy and sick for each type of marker. (d), (e) comparison of results for blood plasma and saliva, (f) association of C-reactive protein level with the severity of the disease.
In search of the best configuration for measuring all four markers, the scientists tested different linkers and types of functional structures and showed that the selected set is optimal in terms of sensitivity and specificity. They tested the sensor for other similar viruses SARS-CoV and MERS-CoV to show its specificity to SARS-CoV-2.
In addition to measurements of markers diluted in buffer solution, the authors tested the sensor on real biological fluids – blood plasma and saliva. The results for plasma were more contrasting, but in both cases they were able to reliably determine the presence of the virus and assess the severity of the disease.
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