Infectious diseases pose a major threat to the world population. Over the last few decades we have seen an increase in the number of outbreaks , related to globalization and growth of the world population. Anticipation and control of rising epidemics has proven to be difficult with the technology which is currently available, especially in third-world countries. The Wageningen iGEM Team 2017 wants to improve this situation by introducing a novel, universal diagnostic tool. Mantis - Modular ANtigen-based Test for Infectious diseaseS -, is designed to be universal due to its modularity. This way we aim to introduce a widely applicable diagnostic to be implemented quickly when the need arises.
While there is a wide variety of infectious diseases, many of these cause similar symptoms, especially in the early stages of infection. Currently, there are no cheap diagnostics available which can give a reliable diagnosis to distinguish between these diseases. As a consequence, specific treatment for infected individuals is often not possible. Instead, curative methods are based on treatment with antibiotics, depending on symptoms displayed by the patient. This highlights the importance of proper diagnosis to prevent faulty treatment. As a solution, the Mantis diagnostic allows for all-round high specificity diagnosis, due to its modular technology.
The Mantis diagnostic can be easily adapted to new diseases due to the approach taken in its design. We make use of the antibody-like proteins called affinity bodies, which can be designed to have high affinity for specific targets. By altering the sequence of these proteins we can create affinity bodies that are specific for disease antigens such as chikungunya virus, Human African Trypanosomiasis and Zika virus. Bacterial strains capable of expressing these affinity bodies are used to detect specific disease antigens in the blood sample of the patient, resulting in generation of a visual signal. Only needing to interchange the affinity body, we created a modular system that is capable of detecting a wide variety of diseases.
At the foundation of the Mantis diagnostic lies the bacterial system capable of detecting disease antigens in the blood of the patient. These antigens can be bound by specifically designed affinity bodies. By coupling these affinity bodies to the Cpx bacterial receptor system, the generated signal is internalized. In the cell, this signal is transformed to a visual output by the transcription-less Bimolecular Fluorescence Complementation technology, directly coupled to the receptor system. This results in a fast and reliable way to diagnose whether the patient is healthy or not. Furthermore, when the aim is to detect diseases that are not very contagious, but pose a large health risk if untreated, the least amount of false negatives is desired. For that, we also designed a system that is more robust and able to detect antigens present in very low concentrations. This system is built using the same receptor system, combined to a novel quorum sensing approach.
While designing Mantis, we took the essential aspects (the so-called ASSURED criteria) for designing a point-of-care diagnostic into account . Not only did we aim for a fast, reliable and robust detection system, but we also identified important factors that influence the design of the device, its implementation and safety for the user. For this we reached out to specialists and stakeholders with years of experience in the diagnostic field. Combining all these aspects we created a diagnostic that could be implemented successfully in real-life situations to help diagnose patients in third-world countries.
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