Schematic view of the interaction between ACE2 Peptidase domain and SARS-CoV2 Spike protein
The SARS-CoV-2 biosensor prototype: a graphene field-effect transistor (GFET)
A schematic representation of the approach to read the signal coming from the Biosensor
Possible application of the Biosensor
Possible application of the Biosensor
The ViruSensing Teams
The problem your project solves The SARS-CoV-2 virus, discovered in December 2019 in the city of Wuhan in the Hubei province of China is a positive-strand RNA Betacoronavirus that is responsible for the current pandemic diffusion of atypical pneumonia called COVID-2019. Up to date, COVID-2019 pneumonia has killed more than 200,000 people all over the world. The sudden health emergency connected to the rapid spread of SARS-CoV-2 is endangering the health services and economy of many countries. Unfortunately, there are several aspects of the SARS-CoV-2 spread which are still unclear, such as key molecular mechanisms of the infection and the persistence of the virus in aerosol and on different surfaces.
Indoor Air and risk of infection Being the SARS-CoV-2 a respiratory virus, one important aspect of the COVID-2019 syndrome spread is related to the small respiratory droplets that are free to travel in the air, covering a quite large area and likely being the primary mode of virus transmission. To manage this aspect of the pandemic diffusion, most of the countries have adopted emergency procedures ranging from travel bans to lockdown useful to maximise social distancing. However, all of these precautions focus on the indoor environment of public places, where the risk of infection is the greatest, and may not be fully effective because of i) the airborne transmission through virus-carrying droplets, ii) the virus putative higher stability in indoor air and iii) a larger density of people. In light of this, a system able to detect the viruses travelling directly in the air would be highly desirable.
What it does
A virus magnet ViruSensing is a biosensor able to specifically trap SARS-CoV-2 from the respiratory droplet, by using an engineered version of the human ACE2 receptor, as a “magnet” for the whole virus particle. We replicate into a biosensor what normally happens in nature between the virus and its receptor. Differently from the standard method of testing (based on the identification of virus RNA through antibody-antigen reactions), ViruSensing identifies the whole virus particles and it will bring:
- more specificity and accuracy;
- detection of the real infective cases only (the presence of viral RNA does not imply infectivity);
- reduction of the problem with false positive/negative results;
- much lower cost since the production of antibodies is more complicated and expensive than the production of the receptor.
How we built it
We have started from the idea of replicating into a biosensor what normally happens in nature between the virus and its receptor. This project took advantage of a multidisciplinary team with different expertise, ranging from biology to physics and engineering. The combination of mathematical models and simulative approaches, such as molecular dynamics (MD), provided a strong theoretical basis for the realisation of a biotechnological prototype.
The initial idea for the prototype was to develop a graphene field-effect transistor (GFET) as a SARS-CoV-2 biosensor. This technology is composed of a graphene channel between two electrodes with a gate contact to modulate the electronic response of the channel. During the weekend we have thought about another possible approach of detection, that involves the labelling of the receptor ACE2 with a fluorophore, located in a different position compared to the binding site for the virus spike protein. In normal conditions, the fluorophore has a specific emission, easily detectable by a fluorescence spectrophotometer. Conversely, when the virus binds the receptor immobilized on the biosensor, it “masks” the fluorophore and then the fluorescent emission is not able to reach the detector, decreasing the measure of absorbance. We developed schemes and identified the experimental and engineering steps necessary for both the prototypes.
Next step has been to imagine where the biosensor could be installed, for example in those environments where the infecting viral dose may be high, such as hospital rooms. ViruSensig could be placed into a box in the air recirculation channels, where it could represent an effective system to “trap” the viruses and at the same time to reveal whether the environment is COVID-free or not. This would provide us with important information, that no other system currently available on the market is able to give. Furthermore, this biosensor chip could be installed on a portable device system (like a breathalyser) and could represent a new SARS-CoV-2 breath test, that will be specific, easy and rapid.
We combined the scientific progress with the innovation management know-how of both the team members and the mentors involved at the checkpoints, leading to a reliable and scalable innovation plan. The innovation process has been defined as a roadmap towards the realization of a physical engineered prototype, with an eye to the further steps necessary for industrialization of the product (reuse of already existing technologies, potential certification issues, issues when scaling from lab engineering to industrial process).
Challenges we ran into
During the Hackathon, the main challenge we stumbled upon was how to detect the interaction between the receptor and the spike protein of the virus, and therefore how to be able to translate the presence of the entire virus in the air into an easy and quick detectable signal.
Things we are proud of
Sharing different ideas and information have made this project a success, we are proud of what we did and we will continue to collaborate to make this idea a real device applicable in everyday life.
What we learned
The Hackathon has been a great opportunity to understand the meaning of teamwork. We have learned how to interact with each other to develop and make a simple idea possible to be realized. Some of us did not know each other before this experience, learning how to communicate, mixing the different personal skills brought the project to a solid level of applicability.
We will implement the roadmap towards the realization and testing of a physical engineered prototype (that is expected in one month) We need to identify and link with interested industrial partners (mainly biosensor manufacturers) and identify the steps towards the certification and industrialization of our prototype We need to further develop the business plan and find the right funding sources (business angels, direct EU grants, accelerators) The value of our solution goes far beyond the current COVID-19 crisis as the same approach could be applied to other viruses or other biological agents (like toxins) with relatively easy and cheap adaptations of the same approach (for most of viruses and toxins the mechanisms behind their binding with human cells and involved receptors are well-known)
Molecular Dynamics (MD) Collaborative co-design techniques