Tuesday, October 27, 2020

Novel Method Can Test the Efficacy of Antibacterial Drugs on Infectious Microbes

A rapid and simple method for testing the efficacy of antibacterial drugs on infectious microbes has been developed and validated by a team of Penn State researchers.

Antimicrobial resistant infection is one of the major threats to human health globally, causing 2.5 million infections and 35,000 deaths annually, with the potential to grow to 10 million deaths annually by 2050 without improved techniques for detection and treatment.

Several rapid testing techniques have been developed, but they do not live up to the reliability of the gold standard technology, which requires 18 to 24 hours for reliable results. In many cases, patients need to be treated with antibiotics in a crisis, leading clinicians to prescribe broad-spectrum antibiotics that may actually lead to greater drug resistance or unacceptable side effects.

Compared to other methods of detection, our method does not require complex systems and measurement setups. Its simplicity and low cost are among the advantages and coupling our technology to machine learning makes the accuracy of our method comparable to the gold standard method and much better than other rapid methods."

The team tested their method against three strains of bacteria, including a resistant strain, to prove its effectiveness in the lab. Upon further development and validation with a broader range of pathogens and antibiotics, their method can allow physicians to prescribe the minimum dosage of the necessary drug, called the minimum inhibitory concentration (MIC) in a timely fashion.

A phenomenon that other tests fail to account for is that bacteria may initially appear to be dead, but then can revive and multiply after many hours. The team's technology, augmented by machine learning, can predict whether the bacteria will revive or are actually dead, which is critical for accurate determination of the MIC value.

Their technique is called dynamic laser speckle imaging. Zhiwen Liu, professor of electrical engineering and the second corresponding author explains the technology: "The main advantages of our method are the speed and simplicity.

You shine a laser beam on the sample and get all of these light scattering speckles. We can then capture these images and subject them to machine learning analysis.

We capture a series of images over time, which is the dynamic part. If the bacteria are alive, you are going to get some motion, such as a small vibration or a little movement. You can get reliable, predictive results quickly, for example within one hour."

In addition to the immediate benefits provided to the patient, the lower concentration of drugs entering the water supply translates to less pollution to the environment, he says.

"One of the exciting aspects of this research has been its multidisciplinary nature. As an electrical engineer, I find it quite fascinating to work on designing and developing an optical diagnostic system as well as performing microbiology assays," said Keren Zhou, the co-lead first author on the paper and a Ph.D. student in electrical engineering.

His co-lead author, Ph.D. student Chen Zhou, added, "We plan to further develop our technique to a low-cost and portable platform, which would be especially beneficial for resource-limited settings."

In this work, the researchers also collaborated with Jasna Kovac, assistant professor of food science, to validate their findings with gold standard microbiology methods.

Journal reference: Zhou, K., et al. (2020) Dynamic Laser Speckle Imaging Meets Machine Learning to Enable Rapid Antibacterial Susceptibility Testing (DyRAST). ACS Sensors.

SQI Diagnostics Updates Clinical Progress on Novel COVID-19 Tests

SQI Diagnostics Inc., a precision medicine company that discovers, develops, manufactures and commercializes innovative rapid diagnostic testing for healthcare professionals, patients and consumers worldwide, today updated the Company's clinical development progress for its three novel Covid-19 tests, highlighted by confirmation from the U.S. FDA that Emergency Use Authorization (EUA) submission is acceptable for all three COVID diagnostic tests. SQI is accelerating the clinical development of its direct-to-consumer COVID-19 HOME Antibody Test, its COVID-19 RALI-dx™ Severity Triage Test and its COVID-19 RALI-fast™ Severity Triage Point-of-Care (POC) Test.

"We are currently advancing three important COVID-19 tests through clinical development with the intent to submit applications for Emergency Use Authorization to the FDA for all three, said Mr. Robert L. Chioini, Chief Executive Officer of SQI. Mr. Chioini further stated, "We believe our COVID-19 Antibody Home Collection Test will be differentiated by providing both speed and accuracy, delivering results in 24-48 hours with > 99% accuracy. Our COVID-19 Severity Triage Tests are unique because both have the potential to help save lives while reducing the burden and cost on healthcare systems. SQI is committed to our goal of making rapid diagnostic testing widely available to clinicians, patients, consumers and industry to help improve lives."

SQI's RALI-dx™ COVID-19 Severity Triage Test measures five critical biomarkers including IL-6 in approximately 50-minutes to help clinicians determine severe inflammatory response in patients with COVID-19 and whether they require hospital admission or not. SQI intends to submit RALI-dx for EUA to FDA in late Q4 2020. The RALI-dx™ COVID-19 Severity Triage Test is expected to be used primarily in hospital emergency departments upon FDA approval.

SQI's RALI-fast™ COVID-19 Severity Triage POC Test measures the key critical biomarker IL-6 in approximately 15-minutes to help clinicians determine severe inflammatory response in patients with COVID-19 and whether they require hospital admission or not. SQI intends to submit RALI-fast™ for EUA to FDA in late Q1 2021. The RALI-fast™ COVID-19 Severity Triage POC Test is expected to be used primarily in hospital emergency departments and urgent care centers upon FDA approval.

SQI's COVID-19 HOME Antibody Test identifies the presence of IgM, IgA and IgG antibodies of SARS-CoV-2 in individuals suspected to have been infected with COVID-19 and those wanting to know if they have been exposed. The test is > 99% accurate with results delivered conveniently in 24-48 hours. intends to submit its EUA to FDA in early Q1 2021. The COVID-19 HOME Antibody Test is expected to be used widely, including by school systems, businesses, sports teams, government and consumers at home.

Thursday, October 15, 2020

20/20 Launching First COVID-19 Rapid Antibody Test Authorized by FDA for Point-of-Care Use

20/20 BioResponse, a business unit of 20/20 GeneSystems, Inc., announced today that it is now accepting orders for the Assure COVID-19 IgG/IgM Rapid Test kits. These kits were the first to receive an emergency use authorization (EUA) from the FDA for point-of-care (POC) use with fingerstick blood samples on September 23. According to the FDA announcement “this authorization means that fingerstick blood samples can now be tested in POC settings like doctor’s offices, hospitals, urgent care centers and emergency rooms rather than having to be sent to a central lab for testing.” “Authorizing POC serology tests will enable more timely and convenient results for individuals who want to understand if they have previously been infected with the virus that causes COVID-19,” said FDA Commissioner Stephen M. Hahn, M.D.

The company is now accepting orders from pharmacies, urgent care centers, and doctor’s offices, especially those servicing first responders.

The test kits are rapid chromatographic immunoassays (configured like a home pregnancy test) to detect IgM and IgG antibodies to COVID-19 SARS-CoV-2 in blood, which is the cause of COVID-19. IgM antibody generally begins to rise within 1 week of initial infection and IgG typically appears about 14 days after infection.

“As vaccines begin to enter the market over the coming months, we believe there will be increasing demand by individuals and their healthcare providers for antibody tests,” said Michael Lebowitz, Ph.D., 20/20’s Chief Scientific Officer. “The presence of serum antibodies against an infectious agent may be an indicator of immunity against said agent. Until such time as the durability of the immune response is established, it will be important for both those who have had a prior infection as well as those who have received a vaccine to be monitored on a regular basis for the presence of antibodies. Such information can be used to suggest that an individual may benefit from a boost with the vaccine”.

20/20 also plans to conduct studies to validate the use of an at-home fingerstick blood collection device together with a quantitative antibody test awaiting an EUA from the FDA. Quantitative tests permit individuals to monitor changes in their antibody levels over time and may help assess susceptibility to future infections. The company, which specializes in developing machine learning algorithms associated with laboratory tests, will seek to build algorithms to help predict and quantify the strength and durability of immune response.

About 20/20 GeneSystems: 

20/20 GeneSystems, Inc. is a Rockville, MD based company focused on innovative diagnostics and detection products. In addition to the company’s blood tests for early cancer detection, 20/20 has also commercialized its patented BioCheck® detection kit to help fire departments and other emergency response organizations screen suspicious powders.

Monday, September 28, 2020

Vox Biomedical Receives NIH Award for Rapid COVID-19 Diagnostic Development

Vox Biomedical announced that it has received a supplemental award from the National Institute on Drug Abuse, part of the National Institutes of Health, to expand upon the breath analyzer technology, which it is developing for the detection of marijuana and opioids, to include a rapid, sensitive and accurate breath diagnostic test for COVID-19.  

The award calls for a biomarker discovery effort to determine the exhaled breath molecular species most suitable for use as a COVID-19 biomarker and methods of capture that can be implemented within the safety paradigm governing COVID-19 testing.  

Exhaled breath is a rich matrix of volatile organic compounds, or VOCs, originating from human metabolism as well as aerosol condensates and bacterial and viral species suspended in micro-water droplets and inflammatory products. Towards the end of developing a breath-based COVID-19 diagnostic, Vox Biomedical scientists will investigate biomolecules associated with the inflammatory and metabolic changes caused by COVID-19 infection. In addition, Vox Biomedical scientists will consult with Dr. Scott Lukas of McLean Hospital and Harvard Medical School to determine substance abuse molecules that can be simultaneously captured along with a COVID-19 biomarker in the exhaled breath. This effort will allow future studies to determine the effect of COVID-19 infection on substance abuse communities.

Upon identification of potential COVID-19 breath-based biomarkers detection, efforts will concentrate on breath collection and virus detection utilizing Vox’s current portable instrument design. An FDA regulatory approval strategy for such a COVID-19 diagnostic technique will be developed to aid in the rapid deployment of this diagnostic technique once validation of a COVID-19 biomarker has been established.

Diagnostic Tool for Coronavirus Being Developed by University of Warwick

Scientists at the University of Warwick have demonstrated that a potential diagnostic tool for detecting COVID-19 using sugars will work with a virus rather than just its proteins, a significant step in making it a viable test in future.

Coronavirus diagnostics currently require centralised facilities and collection/distribution of swabs and results are ‘next day’. A new diagnostic tool being developed by the University of Warwick and its partner Iceni Diagnostics may allow on-the-spot detection of Coronavirus infection, without facilities using a simple disposal device.

The researchers detailed their technique in a preprint paper announced earlier this year, but have now presented additional results in a paper for the journal ACS Central Science, published by researchers from the University of Warwick, University of Manchester and Iceni Diagnostics ltd based in Norwich. The new diagnostic tool uses glycans (sugars) to detect the virus, using a tool very similar to a home pregnancy test.

There is an urgent need for new diagnostics, especially those which give rapid results for screening of healthcare professions or for getting transportation, education and manufacturing hubs running again.

The diagnostic proof of principle has been demonstrated in initial studies, but the partnership is now searching for investment or philanthropic donors to take the concept forward.

Professor Matthew Gibson who holds a joint appointment between the Department of Chemistry and Warwick Medical School comments:

“Our team has now been able to show that this detection technique works with a ‘pseudotyped virus’; a safer to handle alternative which mimics SARS-COV-2. This further demonstrated that the diagnostic format can detect actual viruses not just the isolated proteins from its surface.

“The additional results have allowed us to fine-tune the system more, and learn more about how we can optimise the detection limits and exactly how a sample needs to be introduced to the device, which is crucial. Our next stage is patient samples and understanding how sensitive the device is and really thinking how it might be used alongside existing diagnostic tools.

“The rapid detection of the virus, for both healthcare and to enable society to return to normal is crucial. Our technology, developed through joint PhD student work with our industry partners, makes use of glyco-nanomaterials to detect a specific portion of the coronavirus. The technology is straightforward, and extremely low-cost as the kit is paper-based. The University retained lab-capacity for essential COVID research such as this ensuring we could fulfil the University’s mission to create new knowledge and innovative solutions.”

Professor Robert Field, co-founder and CEO of Iceni diagnostics, comments:

”It is great working with the fabulous talent in the Gibson team at Warwick. Combining our expertise has enabled us to move this project along rapidly - including initial clinical evaluation. We look forward to extending our working relationship with Warwick to explore diagnostics for other infectious diseases based on carbohydrates and glycopolymers”

Dr James Lapworth, Warwick Innovations, who is working with Professor Gibson to commercialise the technology, said:

“There is an urgent, global need to increase diagnostic testing capacity for Covid-19 infections. This new approach potentially offers significant benefits because it delivers a very rapid result and requires no specialist lab equipment or training to complete. The result is that people could determine very quickly whether they have a current infection and take appropriate action, for example to self-isolate.”

‘The SARS-COV‑2 Spike Protein Binds Sialic Acids and Enables Rapid Detection in a Lateral Flow Point of Care Diagnostic Device’ is published in ACS Central Science, DOI: 10.1021/acscentsci.0c00855 Link: https://dx.doi.org/10.1021/acscentsci.0c00855

The research and development of the new tool has been supported by grants from the BBSRC (BB/M01116X/1 and BB/S506783/1), EPSRC (EP/R511808/1), the University of Warwick and Iceni.

Evaluation of LamPORE Rapid Covid-19 Tests Show High Levels of Diagnostic Sensitivity

A team of scientists, including researchers from the University of Sheffield, have published their evaluation of a rapid, new Covid-19 testing technology, which has the potential to expand the type and scale of testing available.

LamPORE, a novel diagnostic platform for detecting SARS-CoV-2RNA, combines loop-mediated isothermal amplification with nanopore sequencing, meaning it has the potential to analyse thousands of samples per day on a single instrument.

Although preliminary, the results suggest high levels of diagnostic sensitivity in LamPORE which could mean an expansion to the scale of testing that could be offered in the future to help control the SARS-CoV-2 pandemic.

The collaboration between the University of Sheffield and colleagues at Public Health England Porton Down (PHE), Sheffield Teaching Hospitals NHS Foundation Trust and the University of Oxford, including support from the NIHR Oxford Biomedical Research Centre, evaluated the performance of LamPORE against RT-PCR - the most commonly-used laboratory test for Covid-19.

The team used RNA (Ribonucleic acid which is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes) extracted from two types of samples. Initially, mock samples formed of saliva from people without infection that had a known quantity of virus added to it, and subsequently nose and throat swabs from real Covid-19 patients collected during routine care at two UK hospitals - Oxford University Hospitals NHS Foundation Trust and Sheffield Teaching Hospitals NHS Foundation Trust.

The positive clinical specimens came mostly from patients with symptomatic infection, and among these LamPORE had a diagnostic sensitivity of 99.1 per cent (i.e. it was positive in 226 of 228 samples positive by RT-PCR).

Among negative clinical specimens, including 153 with other respiratory pathogens detected, LamPORE had a diagnostic specificity of 99.6 per cent (i.e. it was negative in 278 of 279

samples negative by RT-PCR). Overall, 1.4 per cent of samples produced an indeterminate result on first testing, and repeat LamPORE testing on the same RNA extract had a reproducibility of 96.8 per cent.

These results indicate that LamPORE has a similar performance to RT-PCR for the diagnosis of SARS-CoV-2 infection in symptomatic patients.

Dr Thushan de Silva, from the University of Sheffield’s Department of Infection, Immunity and Cardiovascular Disease, said: “These are preliminary but promising data that suggest LamPORE has the potential to expand the type and scale of SARS-CoV-2 testing that could be offered in the future.

“We are delighted to have partnered with collaborators in Oxford and Public Health England to help evaluate this novel diagnostic platform for SARS-CoV-2.”

Dr Cariad Evans, Consultant Virologist at Sheffield Teaching Hospitals NHS Foundation Trust and joint senior author of the published evaluation, said: “We are pleased to have contributed to this important evaluation. These are encouraging early findings and we are proud to have supported Public Health England and our academic partners in this essential Covid-19 research.”

Professor Helen McShane, Director of the NIHR Oxford BRC, said: “This is an excellent example of how NIHR funding to support academic–industrial collaborations can lead to the development of new tools to help us control the SARS-CoV-2 pandemic.”

Dr Steve Pullan, from Public Health England, Porton Down, said: “Our early data indicates LamPORE to be a credible alternative to conventional PCR -based diagnostics, which has the potential to provide further high-throughput testing capacity.”

TU Dublin Team to Develop Rapid Saliva-Based COVID Test

Researchers at Technological University (TU) Dublin have been awarded funding to develop a saliva-based COVID-19 test, which can detect the virus in a matter of minutes.

The project, known as AptaGold, will focus on developing a test that is suitable for use in a number of settings, is cost effective and is readily scalable.

According to AptaGold lead and medical scientist, Dr Steve Meaney of TU Dublin, current diagnostic tools are expensive as they rely on the use of genetic approaches and require equipment, reagents and trained diagnostic staff.

"The capacity of such laboratory-based test systems will always be a challenge. Our solution meets the urgent need for a cheap, on-the-spot and sample-to-result screening option, using an easily obtainable saliva sample.

"As specialised training or equipment is not required to complete the proposed new test, it might find use in workplaces, airports and other travel hubs, as well as in low-resource environments where there are insufficient laboratory services," he explained.

It is already well established that viral particles from SARS-CoV-2, the virus that causes COVID-19, are present in the saliva of infected individuals.

According to AptaGold co-lead and biochemist, Dr Niamh Gilmartin of TU Dublin, AptaGold is based on mixing patient saliva samples with specially selected DNA strands called aptamers.

"These strands are linked to tiny gold particles, and if COVID-19 virus proteins are present, these particles bunch up, leading to a visible colour change in minutes. Aptamers can be produced at a much lower cost than antibodies, so the production can be easily scaled up to meet demand in Ireland and abroad," she explained.

She emphasised that testing, isolating and contact tracing are all vital to stopping COVID-19 and timely, accurate results will significantly reduce these timelines and save lives.

"AptaGold is designed to be a first-line screening system for those who require immediate treatment and isolation, both in the healthcare sector and in the general population. By providing a simple and inexpensive near-patient test system, this approach will significantly reduce wait times for sample collection and test results," Dr Gilmartin noted.

The researchers believe that the rapid identification of infected patients will improve clinical decision making.

"The system can support rapid intervention and therefore, reduce the spread of infection. This is really relevant as we continue to open up the economy and society. Employees could take the test each morning to quickly find out if they should self-isolate or not and it could be helpful for people to manage their travel plans," Dr Meaney said.

AptaGold is a multi-agency project led by TU Dublin in collaboration with Dublin City University, Trinity College Dublin, St James's Hospital, Beaumont Hospital, the Royal College of Surgeons in Ireland and the National Clinical Programme for Pathology.

The funding was awarded as part of a rapid research response funding call published jointly by Science Foundation Ireland, Enterprise Ireland and the IDA.

New COVID-19 Diagnostic Test in French Clinical Trial

C4Diagnostics, Bertin Technologies, and Enalees announce the launch of their clinical trial of BEC-SARS-CoV-2 for humans, a diagnostic test for COVID-19, developed jointly with Pasteur Institute.

The BEC-SARS-CoV-2 for humans test has been submitted to the authorities in accordance with French regulations, the detection process has been validated and a clinical trial has been launched by the consortium in order to obtain CE-IVD marking by the end of September. In the meantime, the test is available as RUO. This diagnostic test relies on two technologies for the extraction of viral RNA and its rapid detection using RT-LAMP. Due to its portable format, it can detect SARSCoV-2 in human on site within 25 minutes (from collection to result) from a nasal or nasopharyngeal swab, with an endogenous control and two different target genes (in line with the World Health Organisation and the French Health Authority (HAS) recommendations).  

Laurent Thiery, CEO and co-founder of Enalees, said: "The BEC-SARS-CoV-2 for humans test kit is based on the Enalees test concept that we have been using for two years to detect and curtail the transmission of respiratory diseases, on site, in domestic animals such as horses. In particular, our rapid viral RNA extraction technique validated previously on test kits for animal diseases is at the core of this new test kit. In addition, this test also uses a rapid molecular diagnostic technology based on RTLAMP, used in all Enalees test kits and during previous health crises such as Ebola or Zika by Pasteur Institute. We have adapted our standardised and optimised sample preparation and analysis procedures for human SARS-CoV2 diagnostic test in time to help manage the current health crisis. BEC-SARS-CoV-2 for humans therefore provides a proven solution both in terms of performance and ease of use. This integrated approach highlights the benefits of the One Health approach, combining the best of human, animal, and environmental health."

Younes Lazrak, CEO of C4Diagnostics, added: "While waiting for an effective vaccine against COVID-19, we must expand and facilitate population screening. To cope with the current health crisis, a diagnostic test kit such as BEC-SARS-CoV-2 for humans is particularly suitable for scenarios where access to a diagnostic laboratory is difficult or even impossible, and/or where test results must be determined immediately for on-site testing of asymptomatic individuals who may be potential COVID-19 carriers. The ability to carry out field testing of people in a rapid, easy, and robust way is a major step forward for COVID-19 rapid screening campaigns. The results we have obtained are currently being tested in a prospective clinical trial led by Pasteur Institute in several clinical centres. The clinical data will confirm the sensitivity and specificity of our diagnostic test and we expect that BEC-SARS-CoV-2 for humans will receive its CE-IVD marking by the end of September.” 

Health Canada Approves Portable Human COVID-19 Testing Device that Delivers Results in 90 Minutes

Health Canada has granted approval for the Hyris bCUBE to be used as a medical device for COVID-19 human testing. As a portable device, the Hyris bCUBE provides onsite and accurate results in minutes. This timely approval arrives as Canadians face rising COVID-19 cases and it supports the testing capabilities of provincial programs to meet demand.

The Hyris bCUBE is a portable DNA-testing laboratory in a box, offering Point of Care (POC) testing wherever people are—anytime, anywhere. Controlled by any device with an internet connection, including a smartphone, the scientifically validated bCUBE analyzes test samples through a cloud-based platform that delivers accurate results in minutes.

The bCUBE was previously approved and used for surface testing. Now, with Health Canada's approval for human testing, more Canadians and businesses can access testing that is accurate, quicker and less invasive—wherever they are in the country. This is particularly significant for vulnerable or remote communities, businesses or industries, where access to onsite rapid testing is key.

Considered the "gold standard" according to the CDC and WHO's effective testing guidelines, the bCUBE deploys PCR (Polymerase Chain Reaction) technology that has demonstrated a 95%+ accuracy rate in clinical trials. Similar trials are currently underway with the FDA.

"The bCUBE is a small, portable genomic biotechnology that is ideal for onsite, immediate test results," confirms Dr. Steven Newmaster, University of Guelph Genomics Professor. "We have validated the bCUBE after using it for several years in the food and natural products industry to identify pathogens, microbes, animal and botanical species ingredients."

Songbird Life Science is the exclusive Canadian distributor of the Hyris bCUBE. Along with several DNA/RNA-identification technologies that Songbird can deploy to suit a space or community's specific requirements, the bCUBE is a key component to Songbird's risk-management consultancy services.

"Health Canada's approval of the Hyris bCUBE addresses big gaps in testing capability and accessibility for Canadians," says Deleo de Leonardis, co-founder of Songbird Life Science. "This is key to keeping the economy running and people safe, despite the ongoing pandemic. Test results in minutes is a game changer."

Hyris is a UK-based company producing bCUBEs in Italy and Germany in accordance with the strictest quality and engineering requirements. Interested businesses can purchase bCUBEs through the Songbird Life Science website. Songbird is currently working with government officials at all levels to assess how this technology can be best deployed to remote communities and other locations where the need for onsite COVID-19 testing with rapid results is especially urgent.

FDA Authorizes First Point-of-Care Antibody Test for COVID-19

The U.S. Food and Drug Administration recently issued an emergency use authorization (EUA) for the first serology (antibody) point-of-care (POC) test for COVID-19.

The Assure COVID-19 IgG/IgM Rapid Test Device was first authorized for emergency use by certain labs in July 2020 to help identify individuals with antibodies to SARS-CoV-2, indicating recent or prior COVID-19 infection.

That EUA has been reissued to authorize the test for POC use using fingerstick blood samples. This authorization means that fingerstick blood samples can now be tested in POC settings like doctor’s offices, hospitals, urgent care centers and emergency rooms rather than having to be sent to a central lab for testing.

“Authorizing point-of-care serology tests will enable more timely and convenient results for individuals who want to understand if they have previously been infected with the virus that causes COVID-19,” said FDA Commissioner Stephen M. Hahn, M.D.

“Until today, serology test samples were generally only able to be evaluated in a central lab, which can be time-consuming and use additional resources to transport samples and run the test. As more and more point-of-care serology tests are authorized, they will help conserve those resources and may help reduce processing time for other types of COVID-19 tests, as less time is spent on serology tests.”

Nearly 50 serology tests have been granted an EUA since the start of the pandemic. The Assure test is a lateral flow assay and is authorized for use with venous whole blood, serum, plasma and fingerstick whole blood. This serology POC test, unlike POC COVID-19 diagnostic tests, uses a blood sample from the fingertip to run the test.

The FDA wants to remind patients that it is unknown how long antibodies persist following infection and if the presence of antibodies confers protective immunity, so they should not interpret results from a serology test as telling them they are immune, or have any level of immunity, from the virus.

Due to these unknowns, the FDA is cautioning patients against using the results from these tests, or any serology test, as an indication that they can stop taking steps to protect themselves and others, such as stopping social distancing, discontinuing wearing masks or returning to work.

The FDA also wants to remind the public that serology tests should not be used to diagnose an active infection, as they only detect antibodies the immune system develops in response to the virus – not the virus itself. It is also important to remember that in a population with low prevalence, even high-performing antibody tests may produce as many or more false results as true results because the likelihood of finding someone who has been infected is very small. Thus, it is necessary to consider that the results from two serology tests may be needed to generate reliable results.

The Assure COVID-19 IgG/IgM Rapid Test Device is currently the only FDA authorized COVID-19 POC serology test and is available by prescription only. The FDA continues to work with test developers to expand access to COVID-19 testing.

Bosch Develops “World’s Fastest” PCR-Based Coronavirus Test

Bosch has developed a new rapid test for its Vivalytic analysis device to detect the SARS-CoV-2 pathogen. The test provides a reliable result in 39 minutes and is currently the fastest polymerase chain reaction (PCR) test worldwide. Bosch’s new rapid test is predestined for decentralized use in mobile test centers at freeway service stations or in airports. People who take the test can obtain a reliable result while at the testing site. Available now in Europe, the CE-approved test helps avoid time in quarantine, relieve laboratories, and make travel and work safer again. “One of the keys to fighting the coronavirus pandemic is to rapidly identify sources of infection. That’s why we focused on following up on our first coronavirus test with an even faster one,” says Dr. Volkmar Denner, chairman of the board of management of Robert Bosch GmbH. “This will now enable us to put people’s minds at ease even more quickly.”

The development of the new Bosch PCR singleplex test is part of a research and development project funded by the German Federal Ministry of Education and Research (BMBF). As the federal minister for education and research Anja Karliczek says, “I believe it’s important that people have clarity about their state of health as quickly as possible. In this respect, insights from science and research can bring people huge benefits. Over the next few months, we will be confronted with the particular challenge of having to test more people. The improved testing procedure developed by Bosch with the BMBF’s support has the potential to be a tremendous help with this complex job. The rapid improvement of our technological capabilities shows what innovative achievements German companies can deliver in times of crisis.”

The test has a sensitivity of 98 percent and a specificity of 100 percent. To develop it, the Bosch subsidiary Bosch Healthcare Solutions joined forces with the German biotechnology company R-Biopharm – a leading provider of highly sensitive manual PCR tests. PCR tests are considered the gold standard of test methods.

Bosch launched the first rapid test for its Vivalytic analysis device at the end of March, after just six weeks’ development. As a multiplex test, it simultaneously checks samples for the SARS-CoV-2 virus and nine other respiratory diseases in two and a half hours. The new, accelerated test is exclusively for SARS-CoV-2. “With our different coronavirus tests and variable analysis strategies, we open up a range of testing scenarios with a Vivalytic device – from screening all the way to supporting differential diagnosis for diseases with similar symptoms,” says Marc Meier, president of Bosch Healthcare Solutions GmbH. And development work is still in full swing at Bosch: As of early October 2020, it will be possible to simultaneously evaluate five samples in one test cartridge and at a comparable speed – a world first, according to the company. Bosch is thus increasing available testing capacity, enabling fully automated processing of more than 160 samples a day using a Vivalytic device. In addition, optimized software will in the next few weeks further reduce the time to result of the SARS-CoV-2 test on positive samples.

The advantages of Bosch’s rapid test lie not only in speedy analysis, but also in ease of use. A sample is taken from the patient’s nose or throat using a swab, and placed in the test cartridge. Then the test cartridge, which already contains all the reagents required for the test, is inserted into the Vivalytic device for automated analysis. The Vivalytic analysis device is designed to be user-friendly; medical staff require only brief training on how to operate it. The development of the Vivalytic system, which consists of an analysis device and test cartridges, grew out of a long-standing collaboration between Bosch’s corporate research and advance engineering and Bosch Healthcare Solutions.

By the end of the year, Bosch wants to reach capacity for one million tests. As demand for the analysis device and the rapid tests remains high, the company is working closely with its suppliers to maximize capacity and further increase supply.

ASU Receives Contract to Develop 20-Minute COVID-19 Saliva Test

As the world manages through the coronavirus pandemic, Arizona State University continues its work to discover and develop easier and more widespread COVID-19 testing to assist in managing the virus.

In May, researchers at ASU’s Biodesign Institute produced the Western United States’ first FDA-approved saliva-based COVID-19 test — one of only a handful available in the country — with test results delivered in 24–48 hours. Now, researchers are taking that work to the next level by building a new, portable saliva-based testing device that will deliver results in as little as 20 minutes. 

Also referred to as a point-of-need test, users will be able to easily provide a saliva sample on a computer chip that will quickly detect whether the virus is present. The project is being funded by $5.2 million in CARES Act dollars from the governor’s office and $860,000 from the Arizona Department of Health Services. The CARES Act was passed by Congress in March to support coronavirus relief, research and response efforts.

“Arizona State University continues to lead the way in developing new technologies to help us respond to COVID-19 and protect Arizona communities,” said Gov. Doug Ducey. “We’re excited to work with our university partners on expanding access to COVID-19 testing, including investing in ASU’s groundbreaking point-of-need test. I’m grateful to President Crow and everyone at ASU for their commitment to finding creative solutions in the fight against COVID-19.”

Six months ago, ASU pivoted one of its research labs at the Biodesign Institute into a Clinical Laboratory Improvement Amendments (CLIA)-approved testing laboratory. The university began COVID-19 testing for front-line health care workers, critical infrastructure and public safety personnel. With a $12 million investment from Ducey in July, the university was able to quickly scale and deploy testing sites across the state with tests available to the public at no cost. To date, more than 36,000 Arizonans have received testing free of charge through the ASU/state of Arizona partner testing sites, a portion of the more than 135,000 tests ASU has run in total.

Gov. Ducey pledged an additional $8 million of funds to support university testing efforts.

“We are of the view that this virus will be with us in some capacity for the foreseeable future; therefore, we need to develop the most sophisticated tools in order to help manage it,” said ASU President Michael M. Crow. “This work is emblematic of ASU’s mission — we’re here to help solve grand challenges for society and to be of service to the people of Arizona.”

ASU professors Mark Hayes, Jennifer Blain Christen and Alexander Green are leads on the new COVID-19 testing device.

The team sees the test’s impact on managing COVID-19 as threefold:

1. Distributed testing that is rapidly, conveniently and inexpensively available to anyone that needs it, for example in neighborhood drop-in clinics. 
2. A means of rapidly scaling testing across the state.
3. Flexible, rapid, convenient testing in workplaces or schools to ensure a safe environment .

“Ultimately, we want to produce something easy to use so anyone could ‘spit on a chip’ while waiting for results for a few minutes and then be cleared for everyday activities or events, or rapidly isolated or ID’d as infected,” said Hayes. 

The team’s interdisciplinary approach to building their prototype draws on a diverse group of specialists, who combined their expertise to make a difference during the pandemic. Hayes, with the ASU School of Molecular Sciences, is an expert in using tiny, liquid samples called microfluidics for biological analysis. Green, also with the ASU School of Molecular Sciences and ASU’s Biodesign Institute, designs biological sensors for detecting pathogens. Christen, of the Ira A. Fulton Schools of Engineering, develops handheld systems for thermal control and rapid optical readout of results. 

The new rapid saliva test detects the viral RNA and combines the ease of use and speed of the newly FDA-approved antigen tests with greater accuracy similar to PCR-based RNA tests. If the virus is detected, a strong, green fluorescent signal is generated on the device. Also, unlike the PCR method, which needs a few hours of time because of several steps performed at different temperature cycles, this device is being designed to have all of the reactions performed at the same temperature. 

A key point of the project will be mobility. Researchers envision a "plug and play" cartridge system that could be used by the ASU Biodesign Institute saliva-testing robotics system or implemented by practitioners without needing extensive training. By keeping the device small and portable, it can be rapidly employed and scaled in case of a surge in infection and done so locally and in a distributed fashion. 

The ultimate goal is to have these devices accessible in public places such as doctors’ offices, workplaces and other densely populated areas. Through early detection, preventative measures can minimize contact risk and ensure safe spaces. Christen said their goal is to “ensure that we are able to get the best detection possible … while making sure it is financially accessible.” 

Although the project is expected to generate working prototypes in six months and apply for FDA emergency-use authorization approval for COVID-19 testing, the team has already worked to align their technology with several companies for scalable production.

Thursday, September 10, 2020

UCal Irvine’s Rapid, Low-Cost COVID-19 Antibody Test Could be Available by Year’s End

A robust, low-cost imaging platform, utilizing lab-on-a-chip technology, and costing just a couple of hundred dollars, may be available for rapid coronavirus diagnostic and antibody testing throughout the United States by the end of the year. That’s belief of scientists at the University of California, Irvine (UCI) who developed the test that uses blood from a finger prick that test probes hundreds of antibody responses to 14 respiratory viruses, including SARS-CoV-2. Results are available in two to four hours.

The UCI team has already completed 5,000 tests in Orange County, and say the final goal is to be able to run 20,000 samples per unit a day. They suggest that identifying responses to viral infections with symptoms similar to those of COVID-19 will keep hospitals clear of patients with standard colds and flu. The researchers are partnering with UCI startups Velox Biosystems and Nanommune to scale up production of the TinyArray imager technology, and expect that the platform will be ready to deploy across the United States by the end of 2020. They are also working with scientists in Uruguay, Russia, and Thailand to develop similar systems.

“We need to test millions of people a day, and we’re very far from that,” said Per Niklas Hedde, PhD, a project scientist in pharmaceutical sciences and lead author of the team’s paper, which is published in Lab on a Chip. “This accurate testing platform enables public health officers to implement individualized mitigation strategies that are needed to safely reopen the country and economy.” The technology would also be great for a low-income country, he believes. “Because the device’s materials are cheap and easy to obtain, the platform is easy to manufacture and use in low-resource areas, making testing accessible on a world scale.”

Hedde, together with UCI colleagues, including Weian Zhao, Ph.D., Enrico Gratton, PhD, and Philip Felgner , PhD, reported on the TinyArray imager in a paper titled, “A modular microarray imaging system for highly specific COVID-19 antibody testing.”

It is well accepted that official infection numbers for COVID-19 are “widely underestimated,” the authors wrote. This is due to a combination of test shortages, limiting testing to people with symptoms, and the time-sensitive nature of RT-PCR, which depends on the presence of viruses and/or viral genetic material in respiratory tract mucosa. “Broad availability of highly specific, high-throughput, inexpensive serological testing can help manage COVID-19 over the coming months and years as it will be able to determine the true density of exposed, seropositive people to enable containment and mitigation measures to avoid formation of new COVID-19 hot spots,” they suggested.

“Massive” serological testing would aid in the development of strategies to help kickstart the economy, and help to minimize the risk of further waves of SARS-CoV-2 infection and death toll. “The implementation of broad testing for SARS-CoV-2 and for antibodies against the virus will be an essential step on the road to the successful implementation of efficient containment measures, and to help develop therapeutics and vaccines,” the authors pointed out. Understanding what antibodies are produced and how long they last will be key to developing an effective vaccine.

The system developed by the UCI researchers is based on a robust, inexpensive, 3D-printable portable imaging platform, the TinyArray imager, which they claim can be deployed immediately in areas with minimal infrastructure, to read the results of coronavirus antigen microarrays (CoVAMs) that contain a panel of antigens from respiratory viruses including SARS-CoV-2, SARS-1, and MERS.

The current CoVAM serology platform developed by the UCI team can measure antibody levels in blood serum samples tested against 67 antigens from 23 strains of 10 viruses that known to cause respiratory tract infections, and so can accurately discriminate between the viruses. New antigens can be included as a virus evolves, the team noted.

“Probing this large number of antigens simultaneously in a single test allows for much higher specificity, sensitivity, and information density than conventional antibody tests such as lateral flow assays (LIFAs),” they claimed. Currently, most antibody tests only check for one or two antigens. “Testing for reactivity against only one or two antigens is not always reliable as cross-reactivity can occur,” they pointed out. “The CoVAM test can tease out this cross-reactivity by taking a simultaneous snapshot of the relative serum reactivity against multiple, cross-species viral antigens … CoVAM is specifically designed for high-throughput serological studies on the scale of >100,000 samples with a minimal number of reagents, which will be critical to enable massive, repeated testing of large populations.

The TinyArray imager combines a 3D-printed prototype with an off-the-shelf LED and a small, 5-megapixel camera, and is used to read the microarrays by identifying markers for the antibodies simultaneously. The scientists say their tests showed the platform has the same accuracy as expensive imaging systems, but is portable enough to deploy anywhere. “To evaluate our imaging device, we probed and imaged coronavirus microarrays with COVID-19-positive and negative sera and achieved a performance on par with a commercial microarray reader 100x more expensive than our imaging device,” they wrote. The same device can also process the results of commonly used nose swab tests for SARS-CoV-2 so that patients can be tested for COVID-19 and its antibodies on a single platform.

“A month or two ago, testing was kind of regarded as the Wild West,” said Zhao, a professor of pharmaceutical sciences, adding that most SARS-CoV-2 antibody tests are “just not accurate.” Large-scale testing will determine what percentage of the population had COVID-19 but never showed symptoms, which will have a big impact on public health and reopening decisions. “What if it turns out that a larger percentage of the people in a community have already contracted the virus?” Zhao said. “This means you are closer to accomplishing herd immunity.”

The team plans to compare the TinyArray assay performance with other COVID-19 immunoassays, including ELISA technology. They suggest that previous work has demonstrated that microarrays can match or outperform ELISA for serological testing, and that the main advantages of microarrays over ELISA are higher information density and throughput. “Also, in our separate study, we show the highly quantitative nature of the CoVAM in measuring antibody reactivity for positive and negative sera, enabling our test to measure antibody titers and potentially infer patient immunity against SARS-CoV-2 infection,” they noted.

The team suggests that their platform could also be compatible with smartphone technology to speed analysis. “After imaging, microarray data could be uploaded for cloud-based analysis using a smartphone,” they wrote. “This capability will be especially important in the upcoming months as the disease is spreading to countries with minimal health care infrastructure and high population densities.”

“This work will enable large scale serosurveillance, which can play an important role in the months and years to come to implement efficient containment and mitigation measures, as well as help develop therapeutics and vaccines to treat and prevent the spread of COVID-19,” they concluded.

Rapid COVID-19 Test Uses Graphene-Enhanced Sensor to Produce Signal After Positively Identifying Viral Antigens

A new COVID-19 rapid test delivers accurate and reliable results in seconds using a graphene-enhanced sensor that produces a signal when exposed to COVID-19 viral antigens.

The graphene-enhanced sensor has been developed by Graphene Leaders Canada (GLC) Inc. (Alberta, Canada) together with its subsidiary GLC Medical (GLCM) Inc. for use in their Rapid COVID-19 Virus Detection Test Kit. The only of its kind saliva test eliminates the nasopharyngeal swab, all certified practitioner oversight requirements, does not require expensive equipment, and there is no cross handling which increases cross contaminations. GLCM's test directly detects the virus ensuring no false positive/negative results, unlike other tests which detect only the byproducts of infection and are therefore unreliable.

GLCM has completed development of the graphene-enhanced sensor used in the rapid test kit, which is an in-vitro diagnostic device that produces a signal when exposed to COVID-19 viral antigens. Following the achievement of the positive identification of the viral antigens, GLCM has commenced development of a functional prototype of the rapid-response test. GLCM's COVID-19 point-of-care test will offer a unique advantage over other tests as it detects the presence of the COVID-19 virus. GLCM's test has been developed to indicate a positive result only when the COVID-19 virus is present, allowing for direct and clear interpretation by the user. GLCM's rapid test is an "at the door" technology which is perfect before boarding a plane, entering a venue for a concert or sporting event, as it delivers instant results regaining confidences to bring us back to our "normal" before the pandemic. The company is advancing discussions with manufacturers and governments in several countries in order to facilitate production protocols reflective of their country's government regulatory compliance requirements.

"Graphene is the ideal sensing material. The 2D nature and conductive attributes of graphene make for an extremely sensitive material to detect any molecule," said Jason Deacon, Product Development Lead of GLC-GLCM. "I have investigated this principle extensively during my time at Cambridge University. At GLC-GLCM, we have made the surface highly specific to SARS-CoV-2 (COVID-19) to ensure that our rapid test will save lives. The study of 2D materials has been encased in academia for 15 years. Our team at GLC-GLCM believes that nanotechnology regarding 2D materials is critical to future technology and innovation, with graphene at the forefront".

"The success of this development offers the world a solution for COVID-19, and as our graphene is tailorable, we can offer a fast solution to future virus' in rapid modification of our graphene which will ensure we do not relive the major economic shutdown as experienced with COVID-19," said Donna Mandau, President & CEO for GLC-GLCM. "The inspiration for all of us at GLC-GLCM is to offer our graphene solutions for People and Planet. This rapid test brings family and friends together for times of joy free from fear of COVID-19. This test also brings family together in those times that we need to say good-bye to a loved one. No one should have to die alone again."

Thursday, August 27, 2020

Abbott's Fast, 15-Minute, Easy-to-Use COVID-19 Antigen Test Receives FDA Emergency Use Authorization

Abbott announced that the U.S. Food and Drug Administration (FDA) has issued Emergency Use Authorization (EUA) for its BinaxNOW™ COVID-19 Ag Card rapid test for detection of COVID-19 infection. Abbott will sell this test for $5. It is highly portable (about the size of a credit card), affordable and provides results in 15 minutes. BinaxNOW uses proven Abbott lateral flow technology, making it a reliable and familiar format for frequent mass testing through their healthcare provider. With no equipment required, the device will be an important tool to manage risk by quickly identifying infectious people so they don't spread the disease to others.

Abbott will also launch a complementary mobile app for iPhone and Android devices named NAVICA™. This first-of-its-kind app, available at no charge, will allow people who test negative to display a temporary digital health pass that is renewed each time a person is tested through their healthcare provider together with the date of the test result. Organizations will be able to view and verify the information on a mobile device to facilitate entry into facilities along with hand-washing, social distancing, enhanced cleaning and mask-wearing.

"We intentionally designed the BinaxNOW test and NAVICA app so we could offer a comprehensive testing solution to help Americans feel more confident about their health and lives," said Robert B. Ford, president and chief executive officer, Abbott. "BinaxNOW and the NAVICA app give us an affordable, easy-to-use, scalable test, and a complementary digital health tool to help us have a bit more normalcy in our daily lives."

In data submitted to the FDA from a clinical study conducted by Abbott with several leading U.S. research universities, the BinaxNOW COVID-19 Ag Card demonstrated sensitivity of 97.1% (positive percent agreement) and specificity of 98.5% (negative percent agreement) in patients suspected of COVID-19 by their healthcare provider within the first seven days of symptom onset.

"The massive scale of this test and app will allow tens of millions of people to have access to rapid and reliable testing," said Joseph Petrosino, Ph.D., professor and chairman, Molecular Virology and Microbiology, Baylor College of Medicine, whose labs have been leading efforts to provide COVID-19 testing for the college and Harris County. "With lab-based tests, you get excellent sensitivity but might have to wait days or longer to get the results. With a rapid antigen test, you get a result right away, getting infectious people off the streets and into quarantine so they don't spread the virus."

Under FDA EUA, the BinaxNOW COVID-19 Ag Card is for use by healthcare professionals and can be used in point-of-care settings that are qualified to have the test performed and are operating under a CLIA (Clinical Laboratory Improvement Amendments) Certificate of Waiver, Certificate of Compliance, or Certificate of Accreditation. Within these settings, the test can be performed by doctors, nurses, school nurses, medical assistants and technicians, pharmacists, employer occupational health specialists, and more with minimal training and a patient prescription.  

"Our nation's frontline healthcare workers and clinical laboratory personnel have been under siege since the onset of this pandemic," said Charles Chiu, M.D., Ph.D., professor of Laboratory Medicine at University of California, San Francisco. "The availability of rapid testing for COVID-19 will help support overburdened laboratories, accelerate turnaround times and greatly expand access to people who need it."

Currently, AdvaMed (The Advanced Medical Technology Association) estimates that test manufacturers are shipping about 1 million tests per day. Abbott will ship tens of millions of tests in September, ramping to 50 million tests a month at the beginning of October. The company has invested hundreds of millions of dollars since April in two new U.S. facilities to manufacture BinaxNOW at massive scale.

The BinaxNOW COVID-19 Ag Card can be used as a first line of defense to identify people who are currently infected and who should isolate themselves to help prevent the spread of the disease. It is intended for the qualitative detection of nucleocapsid protein antigen from SARS-CoV-2 in nasal swabs from individuals suspected of COVID-19 by their healthcare provider within the first seven days of symptom onset.

As a near-person rapid antigen test, BinaxNOW was engineered for point-of-care settings, near-patient, and not for reference labs. Patient samples should be tested immediately and should not be diluted in viral transport media.

NAVICA mobile app will help facilitate return to daily activities

Abbott is also offering a mobile app at no charge that will allow people to display their results obtained through a healthcare provider when entering facilities requiring proof of testing. The NAVICA app is optional and an easy-to-use tool that allows people to store, access and display their results with organizations that accept the results so people can move about with greater confidence. The app is supported by Apple and Android digital wallets and will be available from public app stores in the U.S.

"While BinaxNOW is the hardware that makes knowing your COVID-19 status possible, the NAVICA app is the digital network that allows people to share that information with those who need to know," said Ford. "We're taking our know-how from our digitally-connected medical devices and applying it to our diagnostics at a time when people expect their health information to be digital and readily accessible."  

If test results are negative, the app will display a digital health pass via a QR code, similar to an airline boarding pass. If test results are positive, people receive a message to quarantine and talk to their doctor. As they're required to do for all COVID-19 tests, healthcare providers in all settings will be required to report positive results to the CDC and other public health authorities, regardless of whether they use the app. The digital health pass is stored in the app temporarily and expires after the time period specified by organizations that accept the app.

The app's user interface is supported by a back-end digital infrastructure that is cloud-based, scalable and secure. It's been designed to support a very large number of users and enable access from anywhere. The app is not for contact tracing and only collects a person's first and last name, email address, phone number, zip code, date of birth and test results.

About the BinaxNOW COVID-19 Ag Card Test

The BinaxNOW COVID-19 Ag Card is an assay for the qualitative detection of specific antigens to COVID-19 in the human nasal cavity. A simple nasal swab is used to collect specimens from people suspected of having an active infection. No equipment is required to process samples or read test results. In addition, minimal chemical reagents are required, which lessens exposure to biohazardous materials and improves safety for those administering the test.

The BinaxNOW COVID-19 Ag Card is the sixth test that Abbott is launching in the U.S. to help fight the coronavirus pandemic. Abbott's tests are performed on its high-volume m2000™ and Alinity® m molecular laboratory systems; its ID NOW™ rapid molecular point-of-care platform; antibody tests for its high-throughput ARCHITECT® i1000SR and i2000SR and Alinity™ i laboratory instruments.

Abbott has provided more than 27 million COVID-19 tests in the U.S. to date, including 14 million detection tests and 13 million antibody tests.  

Thursday, August 20, 2020

LumiraDx Receives FDA Emergency Use Authorization for Point of Care COVID-19 Antigen Test

The FDA has authorized its third antigen test for the novel coronavirus, designed to provide fast and cost-efficient results at the point of care and in community settings.

Developed by London-based LumiraDx, the diagnostic operates similar to rapid tests for the flu—it detects fragments of specific proteins found within the SARS-CoV-2 virus, as opposed to molecular diagnostics that match up sequences of the virus’s RNA or antibody tests that gauge the body’s natural immune response.

The LumiraDx SARS-CoV-2 Ag Test is a microfluidic immunofluorescence assay for direct and qualitative detection of nucleocapsid proteins in nasal swab specimens from patients suspected of COVID-19. Used with the LumiraDx Instrument the Test delivers rapid results at the point-of-care.

Using a nasal swab, chemical solution, testing strip and reader, LumiraDx’s assay aims to deliver results on-site within 12 minutes. The company’s clinical studies have shown it to be 97.6% as accurate as high-throughput molecular tests, which may require shipping samples to a centralized laboratory and waiting days for results.

“Actionable diagnostic results at the point of care lead to better health outcomes,” CEO Ron Zwanziger said. “Now that the FDA EUA has been received, we are working with health systems, major retail clinics and employers to get our platform to healthcare providers quickly to utilize in their testing programs.”

LumiraDx said it aims to produce 2 million tests during the month of September before ramping up manufacturing to 10 million tests per month by the end of the year. The company also plans to submit an antibody test, run on the same instrument, to the FDA for emergency review.

Todos Medical Announces Positive Proof-of-Concept Data for Novel 10-Minute Point-of-Care Saliva-based Test Detecting Active SARS-CoV-2 Infection

Todos Medical Ltd., an in vitro diagnostics company focused on distributing comprehensive solutions for COVID-19 screening and diagnosis, and developing blood tests for the early detection of cancer and Alzheimer’s disease, today announced positive proof-of-concept data for its proprietary 10-minute rapid point-of-care saliva-based test for detecting active SARS-CoV-2 infections. Based on these data, the Company has initiated a multicenter clinical trial at Assuta Ashdod Hospital and Tel Aviv University in Israel to evaluate the clinical performance of the assay, and optimize product development prototypes for commercial scale-up.

This technology holds promise to provide a rapid result without the need for heating, expensive instrumentation, inconvenient sample collection or cold-chain logistics. As such, it may have applicability for self-testing at home, or where large numbers of people gather such as school, work, airports, etc.  Todos envisions developing both quantitative and qualitative tests based on the technology and intellectual property.  The Company is working to complete this initial clinical trial in the third quarter of 2020, with trial results and submissions to regulatory agencies worldwide in the fourth quarter of 2020.

“These data provide proof-of-concept for the 3C-Protease diagnostic approach in COVID-19 testing,” said Dr. Jorge Leon, consulting Chief Medical & Scientific Officer of Oncology and Infectious Disease for Todos. “The clinical trial in Israel will generate real-world data on how best to integrate this technology platform into products that can be deployed worldwide. We will now begin incorporating the software to analyze this assay into an application for use with mobile phones and various telemedicine platforms, so as to provide a more complete and efficient solution for COVID-19 testing and data reporting for all stakeholders.”

The proof-of-concept analytical performance data demonstrate that the assay is able to accurately detect the SARS-CoV-2 3C-Protease in human saliva samples spiked with recombinant 3C protease, and that the protease signal was specifically and significantly distinguishable from background protease activity present in normal saliva. The 3C-Protease is a coronavirus-derived protein that is required for viral replication and transmission to other cells and tissues. The 3C-Protease assay detects the presence of active viral replication specific to SARS-CoV-2, rather than host reactions to current or previous other coronavirus infections, or the detection of viral genetic fragments that continue to shed from patients who have recovered from COVID-19. As more people become infected and recover from COVID-19 worldwide, it is becoming increasingly important for a molecular assay to distinguish active, replicating SARS-CoV-2 virus from inactive, non-replicating SARS-CoV-2 genetic fragments.

Data on the importance of the 3C-Protease in coronaviruses was recently published in Science Translational Medicine, available here.  Patents covering the use of the 3C-Protease for the detection of the SARS-CoV-2 were filed in the first quarter in of 2020 by Todos’ joint venture partner NLC Pharma. The joint venture, named COVID Antigen Test Killer (CATK), is focused on the development of molecular diagnostic tests that are differentiated from currently available tests to enable point-of-care detection of the virus in its reproduction stage in minutes, as well as quantitative analysis of how quickly the virus is replicating, which is a measure of viral load. Assay data would give healthcare providers more meaningful information with which to triage patients with COVID-19.

“We are extremely pleased to have confirmed the usefulness of our 3C-Protease patented viral detection technology for COVID-19,” said Dr. Dorit Arad, Chief Scientific Officer of NLC Pharma. “With these data in hand, we see a clear path to apply our technology at large scale to provide widespread rapid, highly-sensitive molecular testing to make a difference in the rapid detection of active COVID-19. We believe this sets the stage for significant growth within our joint venture with Todos.”

Saturday, August 15, 2020

Quick and Affordable Saliva-based COVID-19 Test Developed by Yale Scientists Receives FDA Emergency Use Authorization

A saliva-based laboratory diagnostic test developed by researchers at the Yale School of Public Health to determine whether someone is infected with the novel coronavirus has been granted an emergency use authorization by the U.S. Food and Drug Administration (FDA).

 

The method, called SalivaDirect, is being further validated as a test for asymptomatic individuals through a program that tests players and staff from the National Basketball Association (NBA). SalivaDirect is simpler, less expensive, and less invasive than the traditional method for such testing, known as nasopharyngeal (NP) swabbing. Results so far have found that SalivaDirect is highly sensitive and yields similar outcomes as NP swabbing.  

 

With the FDA’s emergency use authorization, the testing method is immediately available to other diagnostic laboratories that want to start using the new test, which can be scaled up quickly for use across the nation — and, perhaps, beyond — in the coming weeks, the researchers said. A key component of SalivaDirect, they note, is that the method has been validated with reagents and instruments from multiple vendors. This flexibility enables continued testing if some vendors encounter supply chain issues, as experienced early in the pandemic.

 

“This is a huge step forward to make testing more accessible,” said Chantal Vogels, a Yale postdoctoral fellow, who led the laboratory development and validation along with Doug Brackney, an adjunct assistant clinical professor. “This started off as an idea in our lab soon after we found saliva to be a promising sample type of the detection of SARS-CoV-2, and now it has the potential to be used on a large scale to help protect public health. We are delighted to make this contribution to the fight against coronavirus.” The preprint on the development and validation of SalivaDirect was recently posted on medRxiv.

 

Development of SalivaDirect as a means of rapidly expanding SARS-CoV-2 testing was spearheaded this spring by Nathan Grubaugh and Anne Wyllie, assistant professor and associate research scientist, respectively, at Yale School of Public Health. After finding saliva to be a promising sample type for SARS-CoV-2 detection, they wanted to improve the method further. 

 

“With saliva being quick and easy to collect, we realized it could be a game-changer in COVID-19 diagnostics,” said Wyllie. With testing urgently needed, the Yale team was determined to decrease both testing times and costs, to make testing widely accessible.

 

“Wide-spread testing is critical for our control efforts. We simplified the test so that it only costs a couple of dollars for reagents, and we expect that labs will only charge about $10 per sample. If cheap alternatives like SalivaDirect can be implemented across the country, we may finally get a handle on this pandemic, even before a vaccine,” said Grubaugh. 

 

One of the team’s goals was to eliminate the expensive saliva collection tubes that other companies use to preserve the virus for detection. In a separate study led by Wyllie and the team at the Yale School of Public Health, and recently published on medRxiv, they found that SARS-CoV-2 is stable in saliva for prolonged periods at warm temperatures, and that preservatives or specialized tubes are not necessary for collection of saliva. 

 

The Jackson Laboratory for Genomic Medicine in Farmington, Connecticut, will partner with Yale to explore how to implement the test for a broader audience. The laboratory already analyzes patient samples for an RNA signature unique to that of SARS-CoV-2, the virus that causes COVID-19.  

 

“We must continue to invent and implement new ways to conduct SARS-CoV-2 testing faster, more economically and with greater accessibility, while maintaining acceptable test accuracy,” said Charles Lee, the laboratory’s director. “This method is an important next step toward this goal.”

 

Grubaugh and Wyllie said that they are not seeking to commercialize the method. Rather, they want the simplified testing method to help those most in need. Testing for SARS-CoV-2 has been a major stumbling block in the fight against the pandemic, with long delays and shortages of testing. Some experts have said that up to 4 million tests are needed per day; SalivaDirect provides one pathway toward that goal, the researchers said.

 

“Using SalivaDirect, our lab can double our testing capacity,” said Professor Chen Liu, chair of Yale Pathology, who oversaw the clinical validation of the study. 

 

“Dr. Liu and Yale Pathology Laboratory were instrumental in our application. We look forward to continuing to partner with them,” said Grubaugh. 

 

Liu will start offering SalivaDirect as a testing option in their CLIA-certified clinical laboratory in the coming days.

 

The related research was funded by the NBA, National Basketball Players Association, and a Fast Grant from the Emergent Ventures at the Mercatus Center, George Mason University.

Sunday, August 02, 2020

U of Arizona Aims to Provide Rapid Tests for Exposure to Biothreats, Including COVID-19

To better protect those serving on the front lines of battlefields or dealing with an event like the COVID-19 health crisis or potential future pandemics, scientists at the University of Arizona College of Medicine – Phoenix are leading an effort to develop a device that could easily, quickly and accurately detect pathogens and biological threats.

The college's Center for Applied Nanobioscience and Medicine is leading the effort, under an Other Transaction Agreement with the Defense Threat Reduction Agency, an agency within the U.S. Department of Defense. The contract, to provide about 3,000 devices, has a $9.5 million ceiling for three years.

Frederic Zenhausern, the center's director and interim co-chair of the Department of Basic Medical Sciences, and his team members, including associate professor Jian Gu, are creating the device in collaboration with scientists from the University of Nevada, Arizona State University, Duke University and Whitespace Enterprises, an Arizona-based startup founded by Zenhausern. The group is responsible for mass production of the technology.

"An individual in a combat zone or a first responder in the field could know within minutes if they have – or were exposed to – a serious pathogen or biothreat," Zenhausern said. "We want the brave individuals serving on the front lines to be safe, and this device potentially could prevent the next pandemic by providing rapid diagnostic testing for a broad range of threats, including coronaviruses."

The team is developing a vertical flow immunoassay diagnostic test that interfaces with a smartphone. Users would take a small finger prick of blood or a syringe of urine and then push the liquid onto a test strip. Essentially, the device would take a picture of that paper membrane, which would be analyzed and sent back to the users, telling them if they have been exposed to pathogens like anthrax, the plague-causing bacterium Yersinia pestis, or other bacteria and viruses.

Two major platforms for microbial diagnostics are available, including polymerase chain reaction tests, which look at the nucleic acid molecules of the organism, and antibody or immunoassay testing. The immunoassay test typically is color-coded, like a pregnancy test, and uses a lateral flow immunoassay method that involves a piece of paper upon which biofluid, such as blood or urine, is placed.

The biofluid would migrate along the paper and meet different antibodies to determine if an individual's body has produced an immune response to the virus, or if antigens could be detected. An antigen is a toxin or other foreign substance that induces an immune response in the body, especially production of antibodies. An interaction then occurs on the paper, signaling whether the individual has been exposed to the biothreat.

"Lateral flow immunoassay tests are limited to only a few antibodies and are not very sensitive or fast, but they are inexpensive and safe, which has made it a popular option in the past," Zenhausern said. "Through our device, we are combining the benefit of both platforms by increasing capabilities of looking at a much broader panel of disease signatures while significantly increasing the test sensitivity by orders of magnitude."

A vertical flow immunoassay test is when biofluids go toward and through the paper, not by capillarity along the surface of the test strip. This changes the mechanisms of fluidics and physics, which allows testing to look at multiple biomarkers for a wider range of pathogens, instead of just looking at one target biomarker.

"It's much faster and more sensitive," Zenhausern said, adding that this device would have more capabilities than currently available technology and could be applied to illnesses such as influenza, Ebola, COVID-19 or any other biological signature.

"Dr. Zenhausern's team at the University of Arizona Health Sciences and additional collaborators have worked tirelessly to take this idea from concept to production, and I am grateful for their dedication," said University of Arizona President Robert C. Robbins. "This research is an incredible example of how university research directly serves the community. By protecting first responders and others who have an increased likelihood of pathogen exposure, including those serving in combat zones, we can improve public health and prevent future outbreaks. I am immensely proud of our faculty who are spearheading this vital work and I am eager to see its impact."

Zenhausern said, due to the pandemic, a change in the health care delivery system will occur. "We will need to have rapid testing that is less invasive and more personalized."

A previous program, also sponsored by the Defense Threat Reduction Agency, successfully established design rules for the proposed vertical flow immunoassay platform technology, which will be scaled up for this product development project. This increase would encompass the U.S. Food and Drug Administration regulatory filing and delivery of thousands of devices. The Other Transaction Agreement contract also includes a subsequent production option for future commercialization and possible stockpiling through the Department of Defense.

The Other Transaction Agreement program is a partnership among several investigators and their teams, which have been collaborating for many years. These teams are led by world-renowned scientists such as David AuCoin at the University of Nevada Reno, Tuan Vo-Dinh at Duke University and Doug Montgomery at Arizona State University, as well as many industry partners.

The collaboration among most of these institutions began in 2016 after a $2 million Defense Threat Reduction Agency contract was awarded to study this technology and determine how it could be applied for the detection of Tier-1 bioagents in defense operations.


Singapore Scientists Develop COVID-19 Test Method that Delivers Results in 36 Minutes

Scientists at the Nanyang Technological University (NTU) have discovered a way to improve the speed of obtaining COVID-19 test results by up to four times.

The improved testing method for COVID-19 yields results in 36 minutes – about a quarter of the time required by existing gold-standard tests. The current testing method requires highly trained technical staff and can take a few hours before results are finalised.

NTU said the test can be done with portable equipment and could be deployed in the community as a screening tool.

Testing is a key part of the Singapore Government’s strategy to isolate and ring-fence COVID-19 cases to prevent large clusters from forming. Since Jul 1, individuals aged 13 and older who present with symptoms of acute respiratory infection will be tested for COVID-19 at first presentation to a doctor.

The new method, developed by scientists at NTU’s Lee Kong Chian School of Medicine, has demonstrated a way to improve “the speed, handling time and cost of COVID-19 laboratory tests”, the university said.

Currently, the most sensitive method of testing for the coronavirus is through a laboratory technique called polymerase chain reaction (PCR), where a machine amplifies genetic material by copying it over and over again so any trace of the coronavirus can be detected.

A big problem is purifying the ribonucleic acid (RNA) from other components in the patient sample – a process that requires chemicals that are now "in short supply worldwide”, NTU said.

“The method developed by NTU LKCMedicine combines many of these steps and allows direct testing on the crude patient sample, cutting down the turnaround time from sample-to-result, and removing the need for RNA purification chemicals,” the university added.

PCR tests have proven to be “a workhorse” for biological research but it has some drawbacks, said Mr Wee Soon Keong, who is the first author of the research paper that has been published in the scientific journal Genes.

“The process is fiddly and time-consuming. Our rapid COVID-19 test involves a single-tube reaction that reduces hands-on time and biosafety risk for lab personnel, as well as the likelihood for carryover contamination during the processing of samples,” he added.

The same method can also be used to detect other viruses and bacteria, including dengue. The number of dengue cases this year is set to surpass the 22,170 cases in 2013 – Singapore’s worst outbreak.

THE NEW METHOD

In PCR tests, the genetic material on the swab sample has to be extracted to remove substances in the sample that prevent the test from working. One example of an inhibitor is mucin, a main component of mucus.

The test designed by the NTU team uses the “direct PCR method”, but removes the need for RNA purification – a time-consuming and costly step.

“Instead, they added inhibitor-resistant enzymes and reagents targeting compounds that obstruct RNA amplification, such as mucin … these enzymes and reagents, which are commercially available, have high resistance to such compounds that otherwise inhibit PCR, rendering the test inaccurate," said NTU.

The biochemical mix of crude sample and inhibitor-resistant enzymes and reagents is placed into a single tube, which is inserted into a laboratory thermocycler, a machine used to amplify genetic material in PCR. After 36 minutes, results reveal whether there is any trace of COVID-19 “with confidence”.

The team also tested this method on a portable thermocycler, which can be deployed in low-resource settings and endemic areas, pointing to the possibility of having this test done in community healthcare settings by frontline healthcare workers.

Senior research fellow Dr Sivalingam Paramalingam Suppiah said: “By skipping the RNA extraction step with our direct-PCR method, we see cost savings on nucleic acid extraction kits, and avoid the problem of reagents in short supply when lab testing is ramped up and the demand increases globally.”

Associate Professor Eric Yap, leader of the research team, said the team is now trying to deploy such methods for routine diagnostics.

“We need to determine the actual utility and benefits in a real-world setting, and to understand if there are any trade-offs. When one bottleneck is removed, other challenges may emerge – like ensuring quality control, or reducing manual errors.

“Our goal is to develop ultrafast and automated tests that yield results in minutes, and that can be performed by healthcare workers in the clinic with similar accuracy and sensitivity as in specialised laboratories,” he added.

“This will allow us to take PCR testing out of conventional laboratories nearer to the point-of-care, and into the low-resource settings that need them the most.”

Megna Health Announces FDA EUA Approval of COVID-19 Antibody Combo Test Kit

Megna Health, a medical technology company focused on the development and manufacturing of diagnostic and healthcare products, announced that the Company has received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA) for its Rapid COVID-19 IgG and IgM Combo Test Kit.

Serology testing for COVID-19 is at an increased demand to better understand COVID-19 infections especially in asymptomatic patients or those who have recovered and developed antibodies. IgM antibodies are generally detectable in blood samples a couple of days after initial infection, and IgG antibodies follow later, then stay in circulation longer. Antibody tests could be even more important to the reopening decision-making process since antibody tests indicate a certain degree of immunity for future infection. In contrast, diagnostic PCR tests can indicate the presence of viral material during infection and will not indicate if a person was infected and subsequently developed antibodies to prevent future infections.

Megna’s Rapid Antibody Test Kit is lateral flow based immune assay. It tests both IgM and IgG antibodies against the COVID-19 virus with only a drop of blood sample (less than 5uL) and reports result in less than 15 minutes. In addition to studies in 411 patients, Megna’s Rapid Antibody Test Kit has also been validated independently by NIH/NCI (National Cancer Institute). It demonstrated sensitivity of 100 percent both combined (IgM/IgG) and IgG antibody.

“Our antibody kit is a first among combo (IgM and IgG) antibody test kits approved and manufactured in U.S. with such sensitivity,” said Eric Hill, Head of Marketing at Megna Health. “Simultaneous detection of IgM and IgG provides more important information to assess stage of infection and degree of immunity than individual assay alone.” 

Fluidigm Announces GnomeDX Files for FDA EUA for Rapid Turnaround RT-PCR COVID-19 Test Utilizing Biomark HD Platform

Fluidigm Corporation, an innovative biotechnology tools provider with a vision to improve life through comprehensive health insight, today announced that Gnome Diagnostics, LLC (GnomeDX), a leading pharmacogenomics testing company, is utilizing Fluidigm® microfluidics technology and reagents in a test developed to detect the SARS‑CoV‑2 virus, which causes COVID-19.

The Rapid Turnaround Real-Time RT-PCR™ COVID-19 Test, which can be performed via oropharyngeal, nasopharyngeal and nasal swab, is intended to meet growing testing needs for patients, health care workers and other critical populations across central Ohio. GnomeDX has filed for Emergency Use Authorization (EUA) for its extraction-free GnomeDX RT-PCR COVID-19 Test from the U.S. Food and Drug Administration (FDA).

“Supporting our first responders and their patients are among key goals of our test development program,” said Vicky Amann, Vice President for Lab Operations at GnomeDx. “Our CLIA certified genomics lab is ideally suited to this challenge, and we are committed to support our community in any way we can to respond to the pandemic.”

“GnomeDX selected the Fluidigm integrated fluidic circuit technology, reagents and workflow because they provide high-performance sample throughput that is unmatched by microwell plate-based PCR assays for the SARS-CoV-2 virus,” Amann added.

GnomeDX is a high-complexity lab certified under the Clinical Laboratory Improvement Amendments (CLIA) in the United States and eligible under FDA guidance to create its own diagnostic tests for COVID-19. GnomeDX has validated a workflow using assays developed by the Centers for Disease Control and Prevention designed to be run on the Fluidigm Biomark™ HD system.

Because sample collection methods for the test include oropharyngeal and nasal swabs, it does not require invasive nasopharyngeal collection.

COVID-19 testing on the Biomark HD platform provides throughput and cost advantages that reduce the impact of capacity‑constrained supply chains. Fluidigm’s microfluidics technology enables processing of more samples per batch and uses a fraction of expensive testing reagents per sample as compared to more traditional, microwell plate-based PCR technology.

“We believe a significant increase in testing capacity remains critical to an effective global response to the COVID-19 crisis,” said Chris Linthwaite, President and CEO of Fluidigm. “As governments, medical institutions and private labs look for solutions, speed, scale and automation are paramount. Since the beginning of the pandemic, we have been supporting labs around the world as they build out testing infrastructure that meets these important criteria.

“The Biomark HD platform can generate as many as 6,000 test results per day on a single instrument. More and more labs are adopting the Fluidigm model of COVID-19 testing, which offers much-needed high-throughput capability per system. We also support multiple approaches to sample collection, having recently filed for Emergency Use Authorization from the FDA for an extraction-free saliva-based test to detect COVID-19.

“We are honored to have been chosen by GnomeDX to provide a platform for its COVID-19 test to provide critically needed testing capacity in central Ohio.”

In early June, Fluidigm filed for Emergency Use Authorization with the FDA for an extraction-free saliva-based test to detect the SARS‑CoV‑2 virus. The test was developed in collaboration with scientists at the McDonnell Genome Institute and the Department of Genetics at the Washington University School of Medicine in St. Louis.

With respect to the Fluidigm test, Fluidigm has filed for Emergency Use Authorization with the FDA. The test has been validated by Fluidigm, but the FDA’s independent review of this validation is pending. The FDA may require additional data, validation and/or testing, and may not ultimately provide authorization for EUA requests. An EUA, if granted, does not constitute FDA clearance or approval, but would allow use by authorized laboratories only while the EUA is in effect.