Dissemination activities of CorDial-S

CorDial-S : un projet lillois de recherche sur le Covid-19 financé par l’Europe

La Commission européenne a sélectionné ce mois-ci 23 nouveaux projets de recherche sur le Covid-19 qu’elle soutiendra à hauteur de 128 millions d’euros dans le cadre de son programme-cadre Horizon 2020. Des équipes françaises sont impliquées dans 12 de ces projets, parmi lesquels le projet CorDial-S, coordonné par Sabine Szunerits (IEMN) et David Devos (CHU) qui vise à développer un « test de résonance plasmonique de surface portable et rapide pour le Covid-19 ». L’étude préliminaire de ce projet a d’ailleurs été soutenue dans le cadre de la task force lilloise de recherche sur le Covid-19.

French Team Awarded €2.3M to Develop SPR-Based Point-of-Care Test for SARS-CoV-2

NEW YORK – A consortium led by investigators at the University of Lille in France has been awarded €2.3 million ($2.7 million) to develop a surface plasmon resonance-based device for detecting SARS-CoV-2 at the point of care. The effort, called "Coronavirus diagnostics using surface plasmon resonance," or CorDial-S, is funded to run for the next 12 months.

The effort is one of 23 research projects selected as part of a new, €128 million EU package to combat COVID-19.

Sabine Szunerits, a professor of chemistry at the University of Lille, is the principal investigator on the project. She said the aim of CorDial-S is to apply expertise in surface plasmon resonance with magnetic particles to enrich the virus and to detect it using the optical device at the point of care. This could permit a faster, cheaper alternative to PCR, she said.

The envisioned device, no bigger than an 8 x 11-inch sheet of paper, could be used to rapidly detect the presence of SARS-CoV-2 in a sample, typically in about half an hour, and without the reagents that are necessary to carry out the current gold standard assay, real-time PCR.

"We wanted to develop a technique that has nothing to do with PCR, that doesn't use any chemicals used for PCR, because there [has been] a great shortage of chemicals available during the pandemic," said Szunerits. "SPR is not detecting any RNA," she noted. "This device will only detect the presence of the spiked protein around the virus, which means it is very direct."

To accomplish this, the investigators and their partners have worked to engineer nanobodies that they can immobilize directly on the surface of a surface plasmon resonance chip.

"This was actually the challenge of a lot of other detection techniques," Szunerits said. "While they might work, they are not as sensitive as PCR," she said. "This is more important if you want to get rid of nasal swab analysis, which is not so people friendly, and can use saliva instead." 

The technical challenge for Szunerits and her fellow researchers, however, was to detect small concentrations of spiked proteins. They managed to overcome this using SPR coupled with magnetic particles and nanobodies.

As Szunerits noted, CorDial-S involves other participants, both academic and commercial. In addition to investigators at the University Hospital Lille, a city of 230,000 people on the border with Belgium, researchers at the nearby Catholic University of Leuven in Belgium are taking part, as are scientists at Aix Marseille University in the south of France. According to Szunerits, the Belgian team is helping to build AI and data transfer capabilities.

In addition, there are three industry partners. Magnostics, a Dublin, Ireland-based firm;  PhotonicsSys, based in Israel; and Colmers MedTech, headquartered in Boissy-l'Aillerie, France.

Gil Lee, director and chair of the scientific advisory board at Magnostics, said that the company has been working on magnetic nanoparticle sensing for some time and has applied it in detecting HSV-1 on a lab-on-a-chip platform, work that was featured in the journal Nanoscale earlier this year. While he acknowledged that the SPR platform is a "fundamentally different approach," Magnostics is "confident it can apply the technology to SARS-CoV-2."

As part of its role in the project, Magnostics will produce magnetic particles, chemistries, and lab-on-chip technologies that will allow for the "rapid reaction, separation, and detection of the virus," Lee said. Szunerits said that they are also working on developing contained vials for the reactions to minimize the threat of contamination so that tests can be run at the point of care. "We will deactivate the virus, so you don't need to rely on [biosafety level 2] or L3 facilities," she said.

PhotonicsSys, meantime, will provide the instruments for detecting these particles. Ibrahim Abdulhalim, chief consultant for the Beersheba-based firm, said it has positioned its SPR H5 photonics instrument for use in miniaturized, point-of-care devices. He noted the device currently is less than 5 cm in height and weighs less than a kilogram.

"The specially developed substrates allow small and large bioentities to be detected," said Abdulhalim. "The miniature device can be easily integrated into other instruments so that several measurement modes can be combined with SPR measurement: miniature design, friendly graphic user interface, and integration with other inspection equipment."

As part of the project, he said the SPR H5 will be adapted to include more channels, to decrease the substrate size, as to lower the price of the instrument, which currently costs about $5,000. PhotonicsSys' engineers will also add an electromagnet to apply a magnetic field for dragging functionalized magnetic nanoparticles to the plasmonic surface. A future iteration of the device is also planned, he noted, one that will be 3 cm in height, and will contain all light sources and electronics, so that it can be operated wirelessly with a built-in screen. Szunerits said that an eight or 12-channel instrument is envisioned, one that can support parallel and faster screening.

"The idea is to put these types of devices in emergency rooms and ambulances, where in a short time you need an answer if the person has an infection, or if you can operate, for instance," said Szunerits. "It's not to replace PCR per se, but to have a supplementary device in the clinics."

The intention is to commercialize it too, and that is where Colmeris MedTech is assisting the team with regulatory and marketing questions. Currently, the idea is to create a company to offer the platform, and the investigators are seeking investment. They are also open to partnering with larger diagnostic companies.

Getting any new technology into the clinic isn't easy, especially as PCR is so entrenched in clinical labs. Szunerits noted that a quick turnaround time of 30 minutes, plus a relatively low cost of perhaps $15 per assay, could spur clinical adoption, as well as a comparable sensitivity to PCR.

"We will have to convince different stakeholders to be open to this new technology, and hospitals have to invest in the instrument, but it is not so expensive," she said, noting the cost could be halved depending on market uptake.

While technology development continues, the current platform prototype is already being assessed in a clinical trial at University Hospital Lille. David Devos, a professor of clinical pharmacology at the hospital, is responsible for trialing the test on the fly.

"Indeed, once the scientists set up a new nanobody or a new interface within CorDial-S, the new solution is directly tested the next few days in a virology lab receiving new samples daily from patients positive and negative for COVID-19," Devos said.

The hospital is already taking advantage of an authorized clinical trial for the test, as well as access to a biobank of samples. A second trial is set to commence already in October, which will involve other hospitals.

"Our very short-term goal is to improve the organization of care in order to avoid contaminations between [caregivers] and caretakers at hospitals and in the care structures," said Devos. "Finally, we will concomitantly develop the third step with a simple and easy-to-use test for everyone with an objective of urban mass screening," he said. This third trial of the test for surveillance in an urban setting is currently planned for early 2021.

'Positive outputs'

The EU announced its funding for CorDial-S as well as 22 other projects last week. These newly funded projects will support a variety of activities, from repurposing medical supplies, analyzing behavioral and socio-economic aspects of response to the pandemic, and enhancing research networks and collaboration.

The program is also funding new medical technologies, digital tools, and AI analytics with €55.2 million, and CorDial-S is one of several projects funded that are explicitly focused on developing a point-of-care test.

Other projects include: INNO4COV, which aims to boost innovation for COVID-19 diagnostics, prevention, surveillance, and is led by the INL International Iberian Nanotechnology Laboratory in Portugal; IRIS-COV, which aims to develop a point-of-care device for the disease and is led by researchers at the Foundation for Research & Technology – Hellas (FORTH) in Heraklion, Greece; and COVIRNA, which similarly will develop a new test to improve surveillance of COVID-19 patients, led by investigators at the Luxembourg Institute of Health.

Further information about these other projects is not yet available. Representatives for INL and FORTH did not respond to emails seeking comment. A spokesperson for LIH declined comment at this time. A representative for the European Commission similarly declined to discuss the projects beyond what is already public, as the actual grant agreements are not yet signed.

"For each project, funding, composition of the consortium and coordinating institution are subject to a final European Commission decision and signature of the Horizon 2020 Grant Agreement, which also triggers the first advance of funding," the spokesperson said. "However, the researchers can begin working immediately under the assumption that eligible costs will be reimbursed provided the grant agreement is eventually signed," she said. She noted that, as agreements are signed, more information about the projects will be made publicly available.

With so many new devices receiving EU funding with the potential to come onto the market, there is, of course, the question of whether the market can even accommodate so many new tests for SARS-CoV-2. Yet Szunerits said that the new point-of-care tests will be a valuable resource in the future for pandemics and outbreaks to come.

"All this effort that has been spent on COVID-19 sensors will have positive outputs for other diagnostics," Szunerits said. "We are already working in parallel on other viruses," she said. "In the end, we might be prepared for the COVID-21 crisis," she added. She noted the researchers have been trialing the device's use for influenza and proteins.

Méthodes diagnostiques du COVID-19

Poser rapidement le diagnostic de COVID-19 – récemment renommé COVID – avec le plus d’exactitude possible est la pierre angulaire du contrôle de la pandémie. Mais cette évidence partagée par tout un chacun se heurte au caractère véritablement multiforme de l’infection par le SARS-CoV2, appelée COVID-19 : à côté des formes restant totalement asymptomatiques, on observe en effet des formes légères ou pauci-symptomatiques, des formes modérées à sévères, ces dernières nécessitant des soins hospitaliers, et enfin des formes très graves nécessitant une admission en soins intensifs et une ventilation assistée. L’ensemble de ces manifestations de l’infection virale est susceptible de contribuer à la transmission du virus dans les collectivités. Parmi les tests diagnostiques qui nous permettent de confirmer le COVID, la réaction de transcription inverse suivie d’une réaction de polymérisation en chaîne quantitative en temps réel (RT-qPCR), et le test de diagnostic rapide basé sur la détection de l'antigène spécifique du SARS-CoV-2 sont deux méthodes utilisées dans la phase précoce des manifestations infectieuses. Les tests de détection des anticorps sériques (ELISA et test de flux latéral) sont utilisés dans la phase ultérieure et après la guérison. En l’absence de « test de référence » parfait, les sensibilités et spécificités respectives citées dans les différentes études doivent être considérées avec prudence et ne seront donc que brièvement commentées.

[1] Gala J.-L,; Nyabi O.; Durant J.-F,; Chibani N.; Bentahir M. Méthodes diagnostiques du COVID-19,
Louvain Médical, , Mai 2020 .