The INNOVA Attobench System
The INNOVA Attobench System is a benchtop instrument designed for use at point-of-care in clinics, hospitals, labs and pharmacies. It aims to profile patient blood in 7 minutes and with a small 10 µL sample, providing not just yes/no for a single biomarker but a quantified result for a panel of markers. In short, it allows the person’s clinical condition to be treated more precisely and systematically.
The technology is adaptable and can perform a different rapid, multiplexed biomarker test each day, depending on the test chip inserted. In the near future, the instrument will be able to perform not only tests for COVID-19 immunity, but also for liver function testing, for allergy screening, or for fertility monitoring, to name but a few, allowing users either to use multiple instruments every day or to use a single device with specific testing assigned to a day, according to the needs and patient throughput.
The technology behind: SPR (surface-plasmon resonance)
The benchtop uses a label-free particle plasmon resonance multiplexed array functionalised with capture molecules that provide analytical specificity to the target analyte. Thus target protein concentrations can be quantitatively measured from a 10 µL blood sample in 7 minutes (for up to 20 biomarkers).
The array incorporates gold nanoparticles illuminated in total-internal-reflection which is monitored in real time by a video camera. The spots are functionalised with proteins that provide the specificity for the target assays, as well as appropriate control spots and calibrated materials to provide a quantitative result in mg/L.
INNOVA Attobench System is the only benchtop system worldwide that provides a fully quantitative result in 7 minutes, with 10 µL of blood, giving an individualised level of COVID-19 immunity through 5 biomarkers. The test has a high sensitivity and specificity (sensitivity = 96%; specificity = 95%), and is CE marked and MHRA registered.
The need addressed
The INNOVA CovDImmune test was created based on three now undisputed facts demonstrating a need for a solution that determines personal immunity to COVID-19:
- Everyone responds uniquely to vaccination: As many as 1 in 4 persons are poor responders, developing few or no antibodies after vaccination.
- Antibody protection wanes over time: Antibody levels wane quickly in some and more slowly in others (in several weeks to several months).
- A growing concern exists to avoid overstimulation of immune system: Certain individuals carry a potential risk for autoimmune reactions if the immune system is overstimulated by boosters.
The outcomes
- Guide patients towards daily preventive measures with regards to COVID-19 (and ideally to bring peace of mind): with more advanced immunity scores, patients can be guided on risk management. With significant antibody levels less drastic measures may be possible (e.g., grandparents not seeing their grandchildren, people self-isolating themselves) while for low antibody levels managing high vulnerability by using cars instead of planes or trains for vacations, or wearing masks at work etc. may be important
- Help the patient make informed decisions on boosters: the patient can be guided on when a booster will be useful (from “now” to “hundreds of days”) and/or be directed to their GP in case high risk of immunity overstimulation is detected.
- Convince booster-sceptics by showing to them their own personal results.
- Follow-up precisely on more vulnerable patients or specific workforces, such as doctors, teachers, airline crews, or the elderly
- Conduct surveillance on immunity levels & predict possible outbreaks with centralized data
The biomarkers measured & the test results
The test allows a simultaneous measure of the concentration of antibodies to Nucleocapsid (N), Receptor Binding Domain (RBD), “Wild” Spike protein (S) and Spike Omicron (S Om), as well as CRP levels. The system provides measures for each protein, expressed in mg/L as a standard and easily interpretable unit.
- Comprehensive, with 5 markers (4 antibodies and CRP) to understand the level of immunity, where it comes from and underlying inflammation processes
- Explicit, with an estimated edge of immunity threshold; based on the S and S Om antibody response, and a predictive immunity threshold of 3.4mgL in the nasal mucosa
Beyond S and S(Om) that are well known, each biomarker (S, S(Om), RBD, N and CRP) brings its own layer of information to be interpreted by the HCP in the personal patient context:
- RBD is a part of the Spike protein. RBD antibodies have a neutralizing action and can block entry of the virus to cells by blocking the receptor binding domain where the virus binds to the cell surface marker (ACE2), while Spike antibodies normally have neutralizing and opsonizing actions. In some rare cases when a patient has high Spike antibody levels with low RBD antibody levels, it means the antibodies produced for Spike are opsonizing only: thus, even if the Spike antibody level is high, the patient is more likely to have a weaker immune response, and thus more likely to have infection.
- N antibodies have a non-neutralizing activity and is a marker of recent past infection. Recent studies suggest that it provides an additional protection if combined with other antibodies (but provide a limited protection alone). It is thus either an element of further reinsurance (e.g., for a patient with high level of antibodies overall including N from a past asymptomatic infection) or of warning (e.g., a patient that had COVID-19 and thinks they are protected, yet only N antibodies levels are elevated).
CRP is a marker of inflammation. A high level of CRP may mean it is not the best time to get a booster to avoid overstimulation of the immune system, even if other biomarkers are low. Interpretation of an elevated CRP level is important to be discussed with an HCP, as it may relate to an underlying condition that has not yet received diagnosis, particularly in the absence of an active infection, or known circumstances, such as a short-term reaction to BOTOX injection.
Liver disease
The liver is a key organ and a direct reflection of how we live our lives. As the effects of life choices accumulate, the liver can enter a pathway to Non-Alcoholic Fatty Liver Disease (NAFLD) leading to an endpoint of liver cirrhosis (NASH). Frequent monitoring of the fatty liver markers can help monitor progression of chronic conditions such as Type 2 diabetes, which may be reversible if fatty liver markers are detected and monitored at frequent intervals, alongside adaptive changes in lifestyle. This panel of biomarkers will provide an opportunity to influence lifestyle choices and improve preventive diabetes programmes.
Food allergies
Food allergies are at an all-time global high, with 1-10% of the population worldwide and 6-8% under 15 years old suffering food allergy, often with distressing effects and sometimes with dangerous consequences. Private testing tends to be very expensive and difficult to access in most geographies, often resulting in individuals experiencing years of symptoms before getting the answers they need.
Additionally, food allergies are an issue that scare parents in particular, a problem addressed by the INNOVA Attobench System, which uses a small blood volume, allowing infants to be tested before their first meal. An initial peanut/milk panel is in development using a small heelprick sample for babies. Eventually this panel will measure total IgG/IgE to the top 8 food allergies and provide a corresponding RAST score.
Precision fertility & hormone testing
More and more couples are considering childbirth later in life, and some need support in optimising conception. Others may also need support in managing hormone replacement therapy through the menopause in a much more precise and targeted manner. The panel for fertility will be designed to allow clinics and physicians to measure levels of several key hormones in the reproductive process, as part of the same test, allowing a rapid result to be obtained within the consultation. For those trying to conceive, this can allow conception to be optimised to the individuals, alongside hCG monitoring to follow child growth in the first trimester, and for those experiencing menopause, it may help with managing hormone replacement therapies.
INNOVA Attobench System is the only benchtop system worldwide that provides a fully quantitative result in 7 minutes, with 10 µL of blood, giving an individualised level of COVID-19 immunity through 5 biomarkers. The test has a high sensitivity and specificity (sensitivity = 96%; specificity = 95%), and is CE marked and MHRA registered.
The need addressed
The INNOVA CovDImmune test was created based on three now undisputed facts demonstrating a need for a solution that determines personal immunity to COVID-19:
- Everyone responds uniquely to vaccination: As many as 1 in 4 persons are poor responders, developing few or no antibodies after vaccination.
- Antibody protection wanes over time: Antibody levels wane quickly in some and more slowly in others (in several weeks to several months).
- A growing concern exists to avoid overstimulation of immune system: Certain individuals carry a potential risk for autoimmune reactions if the immune system is overstimulated by boosters.
The outcomes
- Guide patients towards daily preventive measures with regards to COVID-19 (and ideally to bring peace of mind): with more advanced immunity scores, patients can be guided on risk management. With significant antibody levels less drastic measures may be possible (e.g., grandparents not seeing their grandchildren, people self-isolating themselves) while for low antibody levels managing high vulnerability by using cars instead of planes or trains for vacations, or wearing masks at work etc. may be important
- Help the patient make informed decisions on boosters: the patient can be guided on when a booster will be useful (from “now” to “hundreds of days”) and/or be directed to their GP in case high risk of immunity overstimulation is detected.
- Convince booster-sceptics by showing to them their own personal results.
- Follow-up precisely on more vulnerable patients or specific workforces, such as doctors, teachers, airline crews, or the elderly
- Conduct surveillance on immunity levels & predict possible outbreaks with centralized data
The biomarkers measured & the test results
The test allows a simultaneous measure of the concentration of antibodies to Nucleocapsid (N), Receptor Binding Domain (RBD), “Wild” Spike protein (S) and Spike Omicron (S Om), as well as CRP levels. The system provides measures for each protein, expressed in mg/L as a standard and easily interpretable unit.
- Comprehensive, with 5 markers (4 antibodies and CRP) to understand the level of immunity, where it comes from and underlying inflammation processes
- Explicit, with an estimated edge of immunity threshold; based on the S and S Om antibody response, and a predictive immunity threshold of 3.4mgL in the nasal mucosa
Beyond S and S(Om) that are well known, each biomarker (S, S(Om), RBD, N and CRP) brings its own layer of information to be interpreted by the HCP in the personal patient context:
- RBD is a part of the Spike protein. RBD antibodies have a neutralizing action and can block entry of the virus to cells by blocking the receptor binding domain where the virus binds to the cell surface marker (ACE2), while Spike antibodies normally have neutralizing and opsonizing actions. In some rare cases when a patient has high Spike antibody levels with low RBD antibody levels, it means the antibodies produced for Spike are opsonizing only: thus, even if the Spike antibody level is high, the patient is more likely to have a weaker immune response, and thus more likely to have infection.
- N antibodies have a non-neutralizing activity and is a marker of recent past infection. Recent studies suggest that it provides an additional protection if combined with other antibodies (but provide a limited protection alone). It is thus either an element of further reinsurance (e.g., for a patient with high level of antibodies overall including N from a past asymptomatic infection) or of warning (e.g., a patient that had COVID-19 and thinks they are protected, yet only N antibodies levels are elevated).
CRP is a marker of inflammation. A high level of CRP may mean it is not the best time to get a booster to avoid overstimulation of the immune system, even if other biomarkers are low. Interpretation of an elevated CRP level is important to be discussed with an HCP, as it may relate to an underlying condition that has not yet received diagnosis, particularly in the absence of an active infection, or known circumstances, such as a short-term reaction to BOTOX injection.
Liver disease
The liver is a key organ and a direct reflection of how we live our lives. As the effects of life choices accumulate, the liver can enter a pathway to Non-Alcoholic Fatty Liver Disease (NAFLD) leading to an endpoint of liver cirrhosis (NASH). Frequent monitoring of the fatty liver markers can help monitor progression of chronic conditions such as Type 2 diabetes, which may be reversible if fatty liver markers are detected and monitored at frequent intervals, alongside adaptive changes in lifestyle. This panel of biomarkers will provide an opportunity to influence lifestyle choices and improve preventive diabetes programmes.
Food allergies
Food allergies are at an all-time global high, with 1-10% of the population worldwide and 6-8% under 15 years old suffering food allergy, often with distressing effects and sometimes with dangerous consequences. Private testing tends to be very expensive and difficult to access in most geographies, often resulting in individuals experiencing years of symptoms before getting the answers they need.
Additionally, food allergies are an issue that scare parents in particular, a problem addressed by the INNOVA Attobench System, which uses a small blood volume, allowing infants to be tested before their first meal. An initial peanut/milk panel is in development using a small heelprick sample for babies. Eventually this panel will measure total IgG/IgE to the top 8 food allergies and provide a corresponding RAST score.
Precision fertility & hormone testing
More and more couples are considering childbirth later in life, and some need support in optimising conception. Others may also need support in managing hormone replacement therapy through the menopause in a much more precise and targeted manner. The panel for fertility will be designed to allow clinics and physicians to measure levels of several key hormones in the reproductive process, as part of the same test, allowing a rapid result to be obtained within the consultation. For those trying to conceive, this can allow conception to be optimised to the individuals, alongside hCG monitoring to follow child growth in the first trimester, and for those experiencing menopause, it may help with managing hormone replacement therapies.
FAQ
The technology has been calibrated based on the NISTmAb antibody, which is a reference sample very well characterized in terms of concentration and mass.
The INNOVA Attobench System is based on the SPR technology that has been used successfully since decades; the INNOVA Attobench System being the result of more than a dozen years of research at the University of Exeter.
As for the INNOVA CovDImmune test, more information on science behind the test can be found in the publications below, the most recent are on pre-print servers. Other peer-reviewed articles are available upon request.
Fully Quantitative Measurements of Differential Antibody Binding to Spike Proteins from Wuhan, Alpha, Beta, Gamma, Delta and Omicron BA.1 variants of SARS-CoV-2: Antibody Immunity Endotypes. Philip H. James-Pemberton, Shivali Kohli, Jordan Twynham, Aaron C. Westlake, Alex Antill, Jade Hunt, Rouslan V. Olkhov, Andrew M. Shaw. Sep 2022 https://www.medrxiv.org/content/10.1101/2022.09.23.22280271v1.fulltext
Vaccine, Booster and Natural Antibody Binding to SARS-CoV-2 Omicron (BA.1) Spike Protein and Vaccine Efficacy. Philip H James-Pemberton, Mark W Helliwell, Rouslan V Olkhov, Shivali Kohli, Aaron C Westlake, Benjamin M Farrar, Ben J Sutton, Nicholas D Ager and Andrew M Shaw medRxiv. July 2022, 10.1101/2022.07.12.22277539 http://medrxiv.org/content/early/2022/07/15/2022.07.12.22277539
Fully Quantitative Measurements of the Antibody Levels for SARS-CoV-2 Infections and Vaccinations calibrated against the NISTmAb Standard IgG Antibody. Philip H James-Pemberton, Mark W Helliwell, Rouslan V Olkhov, Shivali Kohli, Aaron C Westlake, Benjamin M Farrar and Andrew Shaw medRxiv. July 2022, 10.1101/2022.07.12.22277533 http://medrxiv.org/content/early/2022/07/15/2022.07.12.22277533
Real-world evaluation of a novel technology for quantitative simultaneous antibody detection against multiple SARS-CoV-2 antigens in a cohort of patients presenting with COVID-19 syndrome. Analyst 2020, 145, 5638-5646
- For S and SO, different methodologies were used (based on vaccine efficacy, on Youden index, on the nasal mucosa threshold hypothesis and on comparison with other vaccines for respiratory diseases).
- For N, the threshold was calculated through samples of PCR- patients pre-pandemic and PCR+ patients recovering from COVID-19 using the Youden index allowing identification of the threshold optimised for good specificity and sensitivity.
- For CRP, 20mg/L was used as a known threshold of the inflammation marker.
Days of immunity are measured using the results for Spike and Omicron Spike proteins, assuming a 60-day half-life, and a nasal mucosa threshold of 3.4mg/L, rounded to the nearest month. The half-life of antibodies can vary among individuals 60-200 days, therefore a 60-day half-life was chosen to underpredict rather than overpredict an estimated ‘edge of immunity’. If a more precise estimate of antibody half-life wants to be known, a repeat of the test can be performed a few months apart (assuming no change to vaccination or infection history within this timeframe).
Nevertheless, should new variants change drastically in the future, and/or there is a significant change in the predicted nasal mucosa threshold, a new test with new variants and/or an updated threshold will be released and also go through the regulatory process.
The benchtop and the test are both powered by Attomarker’s science. Attomarker is a spin-out company from the University of Exeter, founded by Prof. Andrew Shaw.
