Periodic Reporting for period 1 - CorDial-S (PORTABLE AND FAST SURFACE PLASMON RESONANCE POINT-OF-CARE TEST FOR COVID-19)
Période du rapport: 2020-12-01 au 2022-03-31
The ability to control SARS-CoV-2, the virus that causes the highly contagious Coronavirus disease 2019 (COVID-19), relies on access to rapid and sensitive technologies that can detect the virus, and differentiate SARS-CoV-2 infections from infections with other viruses. Diagnosis of COVID-19 remains largely based on reverse transcription PCR (RT-PCR), which identifies the genetic material of the virus.
Yet, the impact of RT-PCR is hindered by slow delivery of results, with rapid testing based on enzyme-linked immunosorbent assays (ELISA) and lateral flow assays (LFA) technology often preferred as pre-screening methods with results available in 10-20 min. However, these approaches remain challenging due to the limited sensitivity of these sensing platforms. With a cycle threshold (Ct) cut off correlating to Ct = 28 in the best cases, concerns regarding the high frequency of false negative results raised research efforts in finding alternative strategies to real-time RT-PCR tests. One potential approach to detect SARS-CoV-2 is to use sensors comprised of specialized surfaces and chemicals that can detect changes in the properties of samples containing the virus.
The objective of CorDial-S was to bridge this gap though the development of a rapid (<15 min), sensitive (2000 viral particles per mL), selective, and inexpensive solution to address this medical need. The development of a point-of care testing device (POCT) based on the combination of different technologies for the screening of the presence/absence of the SARS-CoV-2 virus in nasal samples was targeted. It includes the use of COVID-19 specific nanobodies, their integrating into an optical sensing cartridge, the use of a portable sensing device and the incorporation of artificial intelligence elements. The project aimed in addition product optimization, and performance validation in a clinical setting, to enable completion of its technical file, and aim for declaration of conformity and affixing of CE mark. The integration of magnetic nanoparticles with high magnetic strength and modified with nanobodies for virus capture was aimed at in addition and proved to be of high complexity.
Yet, the impact of RT-PCR is hindered by slow delivery of results, with rapid testing based on enzyme-linked immunosorbent assays (ELISA) and lateral flow assays (LFA) technology often preferred as pre-screening methods with results available in 10-20 min. However, these approaches remain challenging due to the limited sensitivity of these sensing platforms. With a cycle threshold (Ct) cut off correlating to Ct = 28 in the best cases, concerns regarding the high frequency of false negative results raised research efforts in finding alternative strategies to real-time RT-PCR tests. One potential approach to detect SARS-CoV-2 is to use sensors comprised of specialized surfaces and chemicals that can detect changes in the properties of samples containing the virus.
The objective of CorDial-S was to bridge this gap though the development of a rapid (<15 min), sensitive (2000 viral particles per mL), selective, and inexpensive solution to address this medical need. The development of a point-of care testing device (POCT) based on the combination of different technologies for the screening of the presence/absence of the SARS-CoV-2 virus in nasal samples was targeted. It includes the use of COVID-19 specific nanobodies, their integrating into an optical sensing cartridge, the use of a portable sensing device and the incorporation of artificial intelligence elements. The project aimed in addition product optimization, and performance validation in a clinical setting, to enable completion of its technical file, and aim for declaration of conformity and affixing of CE mark. The integration of magnetic nanoparticles with high magnetic strength and modified with nanobodies for virus capture was aimed at in addition and proved to be of high complexity.
The goal of this study was to develop an optical biosensor in the form of a portable surface plasmon resonance (SPR) point-of-care device through a nanobody-modified SPR chip for the detection of SARS-CoV-2 in nasopharyngeal samples.
Seven Milestones have been identified including clinical trial authorization|regulatory acceptance| result of clinical (M1-3), and a finalized first prototype (M4), all achieved. The second prototype (M5) with machine learning algorithm (M6) was delivered in a different format. The prototype developed is a cartridge-based sensor chip with microfluidic cell integrated. The portable character was maintained and allowed to give a limit of detection of 10 pfu mL-1 for SARS-CoV-2 corresponding to Ct=32.5 and 5.9x10-4 to 1.9x108 viral copies mL-1. Quantitative and qualitative analysis was achieved via the use of a nanobody featuring high binding strength to the spike 1 glycoprotein of the SARS-CoV-2 viral envelope. The concept was validated on 200 nasopharyngeal samples, 100 positive and 100 negative as identified by real-time polymerase chain reaction (RT-PCR) tests, in a clinical study performed at CHU Lille. An 86% positive percentage agreement and a 76% negative percentage agreement, as compared to the gold standard RT-qPCR resulted. With the access to raw clinical data, machine learning (M6) methods have been applied to grasp the characteristics of SPR sensing curves and to estimate the cut-off value between positive and negative nasopharyngeal samples. Our study highlights that 1 min SPR sensogram data is sufficient to match the inferred results from 15 min sensing data.
M7, Declaration of conformity and CE marking remains pending. A technical file was established, but cost and time restrictions resulted that CE mark was not reached within the timelines of the project.
From the 26 deliverables, 3 deliverables could not be achieved or where achieved partially.
D3.5. Production of 1000 CoV@vials
D3.6 ISO13485 protocol for CoV@SPR, Production of 1000 microfluidic systems, 10 CoV@SPR-2 by PhotonicSys
D5.1 CE number
In summary, the exploitable results are as defined in the following
1. Cartride based sensing SPR
2. ISO1348 anti-SARS-CoV- magnetic beads for virus collection
3. Developed machine learning alogorythms
4. Framework of IVDMD Cordial-S regulatory network
5. Patent on magnetic SPR
Exploitation of ISO1348 anti-SARS-CoV- magnetic beads for virus collation will continue. The cartridge-based sensing SPR might be further exploited. Knowledge has been gained together, and we are at the cross-road to see how to move forward.
Seven Milestones have been identified including clinical trial authorization|regulatory acceptance| result of clinical (M1-3), and a finalized first prototype (M4), all achieved. The second prototype (M5) with machine learning algorithm (M6) was delivered in a different format. The prototype developed is a cartridge-based sensor chip with microfluidic cell integrated. The portable character was maintained and allowed to give a limit of detection of 10 pfu mL-1 for SARS-CoV-2 corresponding to Ct=32.5 and 5.9x10-4 to 1.9x108 viral copies mL-1. Quantitative and qualitative analysis was achieved via the use of a nanobody featuring high binding strength to the spike 1 glycoprotein of the SARS-CoV-2 viral envelope. The concept was validated on 200 nasopharyngeal samples, 100 positive and 100 negative as identified by real-time polymerase chain reaction (RT-PCR) tests, in a clinical study performed at CHU Lille. An 86% positive percentage agreement and a 76% negative percentage agreement, as compared to the gold standard RT-qPCR resulted. With the access to raw clinical data, machine learning (M6) methods have been applied to grasp the characteristics of SPR sensing curves and to estimate the cut-off value between positive and negative nasopharyngeal samples. Our study highlights that 1 min SPR sensogram data is sufficient to match the inferred results from 15 min sensing data.
M7, Declaration of conformity and CE marking remains pending. A technical file was established, but cost and time restrictions resulted that CE mark was not reached within the timelines of the project.
From the 26 deliverables, 3 deliverables could not be achieved or where achieved partially.
D3.5. Production of 1000 CoV@vials
D3.6 ISO13485 protocol for CoV@SPR, Production of 1000 microfluidic systems, 10 CoV@SPR-2 by PhotonicSys
D5.1 CE number
In summary, the exploitable results are as defined in the following
1. Cartride based sensing SPR
2. ISO1348 anti-SARS-CoV- magnetic beads for virus collection
3. Developed machine learning alogorythms
4. Framework of IVDMD Cordial-S regulatory network
5. Patent on magnetic SPR
Exploitation of ISO1348 anti-SARS-CoV- magnetic beads for virus collation will continue. The cartridge-based sensing SPR might be further exploited. Knowledge has been gained together, and we are at the cross-road to see how to move forward.
Expected impacts of the CorDial-S project according to the work program:
- To contribute to the public health preparedness and response in the context of the ongoing epidemic of COVID-19 and to ensure the availability of critical technologies and tools.
- To contribute to the acceptability, adoption, appropriateness, feasibility, fidelity, implementation cost, coverage, and sustainability of diagnosis and clinical management of patients and survivors of COVID-19.
- To contribute to proposing recommendations for changes that would allow a fast recovery and a better preparedness, including in the health care systems, for future health emergencies
- To accelerate the deployment of a matured health technology for the prevention and optimized treatment of the COVID-19 disease
Expected impacts of the CorDial-S project beyond the work program: The CorDial-S technologies will have a revolutionary impact on pandemic viral outbreaks due to its nanotechnological aspects in biology, chemistry and physics.
The CorDial-S sensing device goes beyond state-of-the art as it proposes a fast, high performing and low-cost diagnostic device for point-of-care testing, enabling early-state infection sensing with a response time of 10 min max, down to 1 min using machine learning. This PC device does not aim to replace RT-PCR-based testing but can be seen as an add-on diagnostic for fast decision making in clinical care.
- To contribute to the public health preparedness and response in the context of the ongoing epidemic of COVID-19 and to ensure the availability of critical technologies and tools.
- To contribute to the acceptability, adoption, appropriateness, feasibility, fidelity, implementation cost, coverage, and sustainability of diagnosis and clinical management of patients and survivors of COVID-19.
- To contribute to proposing recommendations for changes that would allow a fast recovery and a better preparedness, including in the health care systems, for future health emergencies
- To accelerate the deployment of a matured health technology for the prevention and optimized treatment of the COVID-19 disease
Expected impacts of the CorDial-S project beyond the work program: The CorDial-S technologies will have a revolutionary impact on pandemic viral outbreaks due to its nanotechnological aspects in biology, chemistry and physics.
The CorDial-S sensing device goes beyond state-of-the art as it proposes a fast, high performing and low-cost diagnostic device for point-of-care testing, enabling early-state infection sensing with a response time of 10 min max, down to 1 min using machine learning. This PC device does not aim to replace RT-PCR-based testing but can be seen as an add-on diagnostic for fast decision making in clinical care.