Rapid Multi-antigen COVID-19 Point-of-Care Antibody Test from a Pin-Prick Blood Sample
Lead Research Organisation:
University of Cambridge
Department Name: Engineering
Abstract
The aim is to develop a point-of-care (POC) device to determine the immune status of an individual to SARS-CoV-2 from a pin prick blood sample in under 10 minutes. The POC device have at its core a disposable, single sample cartridge containing an array of up to eight film bulk acoustic resonator (FBAR). FBAR sensors have the potential to significantly advance the state-of-the-art in COVID-19 testing as they offer a small form factor (each sensor has an active area of 100x300 micron on a 0.7 mm silicon die), high sensitivity, high dynamic range, economical manufacture at scale, and can measure binding of proteins from within whole blood samples without the need for lysis, centrifugation or other pre-processing.
The FBAR sensor array, encased in a single use cartridge together with integrated microfluidics, will simultaneously quantitate antibodies against multiple SARS-CoV-2 protein domains (S1, S2, receptor binding domain, N protein), as well as epitopes known to be critical for viral neutralisation. This multiplexed quantitation, together with the high sensitivity of the sensors and automated interpretation algorithms in a small form factor reader, will allow us to achieve the high specificity and sensitivity required by MHRA's target product profile for serology with tiny blood volumes at unprecedented speed.
The product would allow rapid quantitation of COVID-19 immune status as the COVID-19 outbreak persists. It would partner rapid RT-PCR based viral detection (e.g. Cepheid) as key tests directing infection control in healthcare and other settings where high transmission risk exists, democratising access to testing.
The FBAR sensor array, encased in a single use cartridge together with integrated microfluidics, will simultaneously quantitate antibodies against multiple SARS-CoV-2 protein domains (S1, S2, receptor binding domain, N protein), as well as epitopes known to be critical for viral neutralisation. This multiplexed quantitation, together with the high sensitivity of the sensors and automated interpretation algorithms in a small form factor reader, will allow us to achieve the high specificity and sensitivity required by MHRA's target product profile for serology with tiny blood volumes at unprecedented speed.
The product would allow rapid quantitation of COVID-19 immune status as the COVID-19 outbreak persists. It would partner rapid RT-PCR based viral detection (e.g. Cepheid) as key tests directing infection control in healthcare and other settings where high transmission risk exists, democratising access to testing.
| Description | The aim of this project was to develop a point-of-care (POC) device to determine the immune status of an individual to SARS-CoV-2 from a pin prick blood sample in under 10 minutes. The POC device would have at its core a disposable, single sample cartridge containing an array of up to eight film bulk acoustic resonator (FBAR) sensors. FBAR sensors have the potential to significantly advance the state-of-the-art in COVID-19 testing as they offer a small form factor (each sensor has an active area of 100×300 µm on a 0.7mm silicon die), high sensitivity, high dynamic range, economical manufacture at scale, and can measure binding of proteins from within whole blood samples without the need for lysis, centrifugation or other pre-processing. A key success of this project was the optimisation of the biochemical functionalisation of the FBAR devices for the detection of the antibodies and the virus. This required identification of key viral epitopes by investigating patterns of antigenicity. We also successfully integrated a microfluidic system around packaged FBAR sensors and developed methodologies for measurement and data extraction. Although we were idly to identify weak responses to targets, further work would have been required to move to a prototype system, which was hindered by supply chain difficulties at the time. Furthermore, the successful development of a vaccine has, for now, reduced the need for such a COVID test. However, the learning from this project on the use of FBAR sensors with complex fluids has been significant and the resulting know how will be applied to future projects. |
| Exploitation Route | Sorex Sensors is looking at the outcomes of the project and we are looking at applications of the technology for sensing in other complex fluids. |
| Sectors | Electronics Energy Healthcare |
| Description | Sorex Sensors Limited (sorexsensors.com) is a spin-out from the University of Cambridge, University of Warwick and the Polytechnic University of Madrid. Its core technology is the design of FBAR sensors and Sorex was a key collaborator on this project. A feature of the technology is the potential ability to operate in complex environments using the patented 'dual mode' FBAR device design. This project allowed significant knowledge gain by Sorex Sensors on the operation of FBAR devices in complex environments. One output from this is Sorex Sensors participation in an InnovateUK project ECLAIR. The lessons learned from this project gave new insight into how to analyse data from the dual mode devices and this was applied to the ECLAIR project with success, allowing the identification of complex gases at very low concentration levels. This is now being used in other projects buy Sorex Sensors as well, including a new project that is being put together in the agritech sector. |
| First Year Of Impact | 2022 |
| Sector | Aerospace, Defence and Marine,Agriculture, Food and Drink,Electronics,Energy |
| Impact Types | Economic |
| Title | Epitope libraries for SARS-COV-2 RBD |
| Description | We have validated the approach using a published nanobody against N-protein and been able to narrow down its binding site to small 10-amino acid peptide. The RBD library has also shown reproducible pattern of signal when screened against sera from mouse immunised with RBD. We have also started to screen antibody samples from vaccinated individuals with an aim to identify the most representative epitopes for possible inclusion in the FBAR array. We have also produced a panel of RBD mutants based on newly arise SARS-COV-2 variants and incorporated these into pair epitopes (original virus vs variant). All of these proteins are produced in biotinylated form, ready for incorporation to the FBAR sensors. |
| Type Of Material | Biological samples |
| Year Produced | 2021 |
| Provided To Others? | No |
| Impact | Too early for further impact. |
| Description | COVID Project Team |
| Organisation | Public Health England |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | Advancing the development of the underlying sensor and functionalisation technology for COVID testing. |
| Collaborator Contribution | Advice on the appropriate target biomarkers for rapid COVID testing from blood samples. |
| Impact | Ongoing project development. |
| Start Year | 2020 |