Silicon technologies against Covid-19

In the Clean Room of the Barcelona Microelectronics Institute (IMB-CNM-CSIC) scientists are developing devices for COVID-1 diagnostic sensors. This work is part of two projects: Convat , led by ICN2, and POC4CoV, co-led by the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC) and the IMB-CNM, CSIC.

It has hardly passed two months since the first wafers with prototypes of a photonic sensor for the detection of SARS-CoV-2  were produced in the Clean Room of the Barcelona Microelectronics Institute (IMB-CNM, CSIC), destinated to the European project CONVAT. This project is directed and coordinated by Professor Laura M. Lechuga, a CSIC researcher at the Catalan Institute of Nanoscience and Nanotechnology (ICN2). The Barcelona Microelectronics Institute of the National Microelectronics Centre (IMB-CNM, CSIC) participates in the project, associated as a Third Party to ICN2, and will develop and manufacture photonic devices.

CONVAT
The goal of CONVAT is to create a new photonic biosensor that can detect the SARS-CoV-2 coronavirus in 30 minutes. It has to be reliable enough to perform the test directly with a patient's sample without the need to send the sample to a centralized clinical laboratory.

In photonic devices, light is confined within a structure. Any interaction of the external medium with that structure produces changes in the propagation characteristics of the confined light. Carlos Domínguez, a CSIC researcher and co-director of the Chemical Transducers Group, explains that it can be compared to flat optical fibers through which light moves. "When some of the characteristics of the environment change, the properties of the light also change. This variation is what we use to measure." Professor Domínguez, of the IMB-CNM, leads the development of transducer devices for CONVAT, which are being manufactured in the Photonic Integration Platform, located in the Integrated Clean Room of Micro and nanofabrication of the IMB-CNM .
 
The structure of the transducers consists in a 340-nanometer layer of silicon nitride and two surrounding layers of 2000-nanometer silicon oxide. To obtain the layers, as well as their subsequent processing, the scientists use silicon microelectronic technologies.
 
In the area exposed to the external side a layer of biological compounds (enzymes, antigens, DNA molecules ...) is immobilized. These compounds can specifically recognize the searched molecule and the interaction with it triggers a variation in some parameter (temperature, density, refractive index ...), which in turn affects the propagation of light. This is how the molecule is detected, by the light intensity  changes.

This is basically how photonic transducers created by the IMB-CNM work. These devices were patented by the CSIC for Europe and several countries around the world. Now, in the CONVAT project, "the team of Prof. Laura Lechuga is modifying the photon transducer with a specific molecule (antibody) to selectively determine the SARS coronavirus, and afterwards will validate the final device."

The project will take two years although, but as the work does not start from scratch results are expected in less than a year. The technology could also quickly identify the type of coronavirus, and distinguish a SARS-CoV-2 infection from another coronavirus infection or a flu. In addition, the biosensor device will also be used for the analysis of different types of coronavirus present in reservoir animals, such as bats, to observe and monitor possible evolutions of these viruses, therefore preventing future infectious outbreaks in humans.
 
CONVAT is a cooperation project between Spain, Italy and France. In addition to the group of Prof. Lechuga, three other centers will participate in it: the group of Prof. Jordi Serra Cobo from the University of Barcelona (UB); the laboratory of Prof. Remi Charrel at the University of Marseille; and the laboratory of Dr. Antonino Di Caro, of the Italian National Institute of Infectious Diseases (INMI).

POC4CoV project
Silicon technology are also being applied for the development of other diagnostics kits for COVID-19, as a part of the POC4CoV project - Point-of-care tests for the rapid detection of SARS-CoV-2. Seven research groups are participating in this project, five of them belonging to CSIC centers: the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), the Barcelona Microelectronics Institute (IMB-CNM-CSIC) and the Aragon Institute of Materials Science (ICMA-CSIC).
 
Two devices to simultaneously and quickly detect several biomarkers of SARS-CoV-2 infection will be developed in the project POC4CoV. The devices will allow to know not only whether a patient is infected but also at what stage of the disease, enabling therefore to monitor the progress. Specific bioreagents (antibodies, peptides or DNA probes) will be used to detect biomarkers.
 
"The first one is an electrochemical device that incorporates an array of metal electrodes manufactured on silicon substrates using standard microfabrication technology in the Clean Room of the IMB-CNM. This array  is ​​attached to a single-use paper component, where different sections will have been established. In certain areas of the paper component some of the specific bioreagents will be embedded. previosly marked with an enzyme to generate the electrochemical signal ", explains professor M. Pilar Marco, researcher of the CSIC at the IQAC, and César Fernandez, researcher at the IMB-CNM. Both are coordinators of the project and lead, respectively, the group of Nanobiotechnology for the Diagnosis and the group of Chemical Transducers.
 
The patient's sample will be collected in tubes where the specific bioreagents will be immobilized in magnetic nanoparticles, which will allow their capture. Then, a drop of the magnetic particles will be added to the different sections of the paper component and the solution will move by capillarity to the area of ​​the electrodes, where the nanoparticles will be concentrated by the action of a magnetic field. With this we hope to obtain a higher signal and therefore a greater sensitivity, adds Pilar Marco. The device is very simple, similar to strip tests, and would be low cost, which will facilitate its wide use.
 
The second device involves the use of plasmonic nanostructures, functionalized with the same specific chemical bioreagents, which will identify biomarkers on a nitrocellulose substrate, by means of the heat generated when the are exposed to a  laser beam irradiation. "The sample is mixed with these plasmon probes and deposited at the end of the paper strip. The solution flows by capillarity through the paper to the detection area, where there is another specific immobilized bioreactive, which "The capture by affinity of the complexes formed with the biomarkers of infection. Signal amplification is achieved through the use of plasmonic nanoparticles and laser irradiation," says Pilar Marco. This device is similar to pregnancy tests, and it is also a low cost and easy to use.