Introduction

The serum-neutralization test (SNT) represents the gold standard for assessing the immune response to a viral infection. It quantifies the activity of functional antibodies in in-vitro experiments with cell cultures and provides a realistic and reliable output of the immune protection, omitted by other assays based on antibody-antigen tests such as ELISA. Currently available SNT procedures allow to evaluate antibodies’ neutralizing effect only at the end of the experiment, require toxic reagents (i.e formaldehyde), involve a subjective element in the titration evaluation from specialized operators or require spectrophometric instrumentation. They also require biocontainment procedures and facilities that are often bulky and expensive, due to the biological risk of direct exposure to the virus/pathogen.

 

Technical features

The serum neutralisation test is based on the fact that the cultures or cell lines used in the neutralisation tests form a confluent monolayer, if healthy, which represents a physical barrier for ion transport. This barrier property can be electrically quantified as a trans-epithelial resistance (TEER). The invention implements current methods on organic electrochemical transistors that detect by electrical measurement the cytopathic effect of viruses induced in cell cultures in vitro, measuring TEER. This innovation would allow to place side by side/ replace the current tests with an objective measure, real-time, automated, making possible the application even on a large scale. The starting technology consists of a container of several multiwells, equipped (each) with at least one electronic reading device. The device is a biocompatible and semi-transparent organic electrochemical transistor (OECT). The cells are sown in the well creating a cellular layer and the device measures the resistance of that layer which depends on its integrity and the health of the cells themselves.

Possible Applications

• SNT for the identification of neutralizing antibodies produced against any viral species responsible for animal and human pathologies, for example Sars-CoV-2
• Test and development of drugs and vaccines, with definition of the optimal vaccination strategy

Advantages

• Objective, automatized, real-time measurement which can be read by non-specialized personnel, remotely, and provides for comparable standards  different laboratories
• Small and portable instrumentation, compatible with BSL 2/3/4 laboratories
• Can be used for neutralization tests in all animal species as it is not necessary to use Ab anti Ab species/specific
• Low cost and scalable, thuscan be used in massive testing