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.”