Monday, June 22, 2020

Virginia Commonwealth University Researchers Develop Extremely Rapid Experimental COVID-19 Test

Early diagnosis and isolation of patients with COVID-19 is a keystone for controlling the pandemic. While testing capacity has grown, quick turnaround for patient results remains critical.

To address this need, Rebecca Martin, Ph.D., a research member at VCU Massey Cancer Center, developed an extremely rapid experimental molecular diagnostic assay that decreases the amount of time required to diagnose COVID-19.

"When results can be obtained in just a few minutes, diagnosis and treatment can be provided on the initial care visit without sending samples to a central lab," said Martin, an assistant professor in the Department of Microbiology and Immunology at the VCU School of Medicine. "This methodology could provide accurate disease diagnostics on-site."

The project was enabled by a grant from the VCU COVID-19 Rapid Research Funding Opportunity, sponsored by the Office of the Vice President for Research and Innovation and the C. Kenneth and Dianne Wright Center for Clinical and Translational Research. The initiative was established to quickly pivot or expand research addressing the impact of the COVID-19 pandemic on the health system and the community.

Martin worked with VCU M.D.-Ph.D. students Jared Farrar and Joseph Lownik to develop the test by using recent methods of fast nucleic acid amplification to screen for SARS-CoV-2, the causative virus for COVID-19.

Their method is combined with rapid RNA extraction to allow for a total detection time of 3.5 minutes from swab to diagnosis. Compared to conventional testing, this new methodology is significantly faster, making the turnaround time minutes rather than hours.

"[Polymerase chain reaction], a common methodology in research and clinical laboratories, is slow, but sensitive," Martin said. "Antigen-based testing is fast, but not very sensitive. Our technique is both fast and sensitive."

Martin's work builds on research previously conducted by Farrar and Carl Wittwer, M.D., Ph.D., at the University of Utah that demonstrated that PCR—which can produce many copies of a DNA sequence from a small sample—can be performed in 15 to 60 seconds.

"By utilizing the principles of Extreme PCR, our test is currently the fastest described molecular diagnostic test for COVID-19 to our knowledge," Martin said. "Additionally, our technology can be easily multiplexed unlike other rapid molecular diagnostic methods."

Martin has filed provisional patent applications for this technology. She will also need to obtain Food and Drug Administration approval before the tests can be used on patients.

Her laboratory prototype is currently not practical for testing with patients at the point of care but proves that molecular diagnostic testing for COVID-19 can be done much faster than what current modalities are capable of doing.

For the next steps in their research, Martin and her team will work with the VCU Health System to test their prototype on patient samples as well as apply for funding for building a point-of-care prototype.

"We look forward to collaborating with the industry to develop an implementation for use in the clinic for COVID-19 diagnostics, as well as syndromic pathogen panels that can be used in testing for many different respiratory pathogens," she said.

Genetworx Laboratories Announces New COVID-19 Antibody Test with 99.8 Percent Specificity

Genetworx Laboratories, a leading innovative molecular diagnostic testing laboratory, announced today that the company is now performing COVID-19 antibody testing, in addition to diagnostic testing, for the virus. The Virginia-based company stated that it is providing the new antibody blood test in response to the demand from physicians' offices, emergency management providers, government, assisted living entities, and employers all over the United States. The Genetworx Total Antibody (IgM & IgG) test is 99.8% specific and 100% sensitive.

In addition to the new antibody test, the company further announced a comprehensive instant notification system implemented recently in which patients (who opt in) are notified of their test results immediately – for both antibody and diagnostic testing clients. Once Genetworx receives a patient's sample, the test is performed, and results are available through a patient or physician portal, or via text and voice messaging, within 24-48 hours.

Test results were previously sent directly to providers or third-party contractors. However, now, patients themselves can choose to receive their Genetworx COVID-19 test results automatically by text message or through a new interactive voice response telephone messaging system using a personal cellphone. Additionally, test results can be provided online through a patient portal. A certificate of proof of a test result will also be able to printed through the new online portal for employees as they return to work.

"We understand how important COVID-19 test results are to our patients so Genetworx invested in a system allowing rapid notification so that patients can have a diagnosis in the soonest time possible -- immediately after the Laboratory reads the results—usually within 24-48 hours of receipt of the sample," explained William Miller, CEO of Genetworx and a 20-year veteran of the molecular diagnostic laboratory testing industry. "Like all laboratories in the US, we saw a significant increase in volume recently and have worked tirelessly to implement the new system and be as responsive as possible to our patients and providers," he said.

The Genetworx antibody test, like the diagnostic test, is in the 99th percentile for accuracy and has emergency use authorization from the U.S. Food and Drug Administration. COVID-19 antibody tests utilize a patient's blood sample to detect the presence of specific antibodies to show a past infection with the virus. Nearly all immune competent individuals will develop an immune response following SARS-CoV-2 infection. Like infections with other pathogens, a COVID-19 infection creates IgM and IgG antibodies, which are the most useful for assessing antibody response. A patient's physician and the Centers for Disease Control guidelines will help determine the appropriate response to antibody test results.

Miller says that the last few months have been a once-in-a-lifetime experience for him and his staff.

"It's been very exciting for us to work together and play an important role in battling the coronavirus pandemic. Our company is proud that we pivoted quickly and repurposed part of our facilities back in March in order to conduct widespread COVID-19 testing with a 99 percent accuracy rate. Although it was challenging to keep up with the demand and to innovate in order to get both physicians and patients the information they need at the accuracy level required by the pandemic, Genetworx invested in our patients and, with this new rapid notification system and antibody test for our clients, we can assist the nation in moving forward through the pandemic and back to work."

Genetworx was founded to provide pharmacogenomic DNA genotyping to help provide patients with the right medications, at the right dose, and lower overall healthcare expenditures while delivering the best health outcome. The company is a fully integrated CAP/CLIA certified high complexity molecular diagnostic laboratory.

In 2017, the company was purchased by the national substance use disorder treatment network, Recovery Centers of America ("RCA"). Recovery Centers of America operates seven evidence-based addiction treatment facilities in Massachusetts, Pennsylvania, New Jersey and Maryland and is expanding to Chicago, Indianapolis, and Pittsburgh to meet the growing need for substance use disorder services.

InDevR Delivers Commercial Multiplex Coronavirus SeroAssay Kit and Testing Services for Vaccine Development

InDevR, Inc., a leader in novel analytical technologies that support the development and production of vaccines and biotherapeutics, announced commercial availability of its COVID-19 serology test kits. InDevR's VaxArray Coronavirus SeroAssay leverages the Company's established VaxArray platform to deliver a rapid quantitative test that can simultaneously screen for antibody responses to the spike proteins of SARS-CoV-2, SARS-CoV-1, MERS, and all four endemic coronaviruses in both animal and human samples. The serological test kit is designed to streamline the development of SARS-CoV-2 vaccine candidates by enabling measurements of pre-immunization status of clinical study participants, post-immunization antibody levels, and any potential induced cross-protection against other coronaviruses. The VaxArray Coronavirus SeroAssay uses ~200x less antigen per test than a typical ELISA, which is critical during a time when supplies of antigens are limited.  

Based on a clinical validation study involving over one hundred specimens and conducted in collaboration with Children's Hospital in Denver, the assay exhibits 100% clinical specificity and 98% sensitivity. Quantitative results with low limits of detection and multiple answers from a single <10 µL aliquot are more informative. This new tool will undoubtedly enable higher quality research and provide a deeper understanding of immunity.  InDevR also offers Testing Services to alleviate additional vaccine development bottlenecks.

Kathy Rowlen, CEO of InDevR, further noted that "In addition to the improvements in speed, usability, and information content relative to traditional ELISA immunoassays, we believe our VaxArray CoV SeroAssay can be used as a standardized benchmarking tool for the many organizations pursuing SARS-CoV-2 vaccine candidates. Higher quality comparisons of baseline antibody levels and immune responses across thousands of clinical study samples collected during the coming months will help accelerate the identification of the most promising vaccine candidates."

"The InDevR Coronavirus SeroAssay helped us to rapidly gain insight into various formulations of our COVID-19 vaccine candidates, providing us with an understanding of IgG response to SARS-CoV2 spike antigen produced from various sources and cross-reactivity with other CoVs. The information provided from the assay helped to guide decisions in our continuing work on development of a SARS-CoV-2 candidate vaccine. We found the correlation with our microneutralization measurements interesting and we look forward to pursuing this link further," noted Kentucky BioProcessing President, Hugh Haydon.

The VaxArray CoV SeroAssay is based on InDevR's VaxArray platform, a microscale multiplexed immunoassay that is already used by the world's largest vaccine manufacturers to streamline development and characterization of seasonal influenza vaccines, with applications to a range of other vaccines currently under development in collaboration with the Bill & Melinda Gates Foundation. The portfolio of VaxArray products delivers highly sensitive and quantitative measurements in a fraction of the time required for traditional characterization methods, thus reducing vaccine development timelines and manufacturing costs.

Thursday, June 18, 2020

FDA Revokes Emergency Use Authorization for Chembio Antibody Test

On June 17, 2020, the U.S. Food and Drug Administration revoked the emergency use authorization (EUA) of the Chembio Diagnostic System, Inc. (Chembio) DPP COVID-19 IgM/IgG System, a SARS-CoV-2 antibody test, due to performance concerns with the accuracy of the test. Antibody tests, a type of serological test, can help provide information on a person’s and population’s exposure to COVID-19.

As such, has deleted this serology test from its comprehensive list of EUAs.

“Since the beginning of the COVID-19 public health emergency, the FDA has balanced the urgent need for access to diagnostic and antibody tests with providing a level of oversight that helps to ensure accurate tests are being deployed,” said Jeff Shuren, M.D., director of FDA’s Center for Devices and Radiological Health. “By continuing to monitor authorized tests and emerging scientific evidence, we are able to make changes when appropriate – including taking action when a test’s benefits no longer outweigh its risks. Through these efforts, we are able to help assure that FDA-authorized tests meet the needs of the American public.”

The Chembio antibody test was one of the first antibody tests authorized by the FDA during the COVID-19 public health emergency. At the time of authorization, based on the information that Chembio submitted to the FDA at that time, the agency concluded that the test met the statute’s “may be effective” standard for emergency use authorization, and that the test’s known and potential benefits outweighed its known and potential risks.

As the FDA has learned more regarding the capability for performance of SARS-CoV-2 serology tests during the pandemic, and what performance is necessary for users to make well-informed decisions—through both the continued review and authorization of serology tests as well as through a research partnership with the National Institutes of Health’s National Cancer Institute (NCI)— the FDA was able to develop general performance expectations for these tests, which are listed in our serology templates.

Data submitted by Chembio as well as an independent evaluation of the Chembio test at NCI showed that this test generates a higher than expected rate of false results and higher than that reflected in the authorized labeling for the device. Under the current circumstances of the public health emergency, it is not reasonable to believe that the test may be effective in detecting antibodies against SARS-CoV-2 or that the known and potential benefits of the test outweigh the known and potential risks of the test, including the high rate of false results. Moreover, the risk to public health from the false test results makes EUA revocation appropriate to protect the public health or safety. As such, the FDA decided to revoke the emergency use authorization of the Chembio test, and this test may not be distributed.

The FDA will continue to monitor the performance of tests marketed in the U.S. and take actions, as appropriate, including modifying its policies.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Thursday, June 04, 2020

Digid Seeks FDA Approval for its Rapid Coronavirus Antigen Test Based on Cantilevers and Monoclonal Antibodies

At the Helmholtz Centre for Infection Research (HZI), scientists have succeeded for the first time in detecting SARS-CoV-2 viruses using the revolutionary Cantisense(TM) technology from Digital Diagnostics AG. Application for approval of the Digid Cantisense(TM) SARS-CoV-2 Test by the FDA has been submitted. Delivery of the first point-of-care tests is planned for July.

At the high-security laboratory of the Helmholtz Centre for Infection Research (HZI) in Braunschweig, Germany, the revolutionary Cantisense(TM) technology of the German health technology company Digital Diagnostics AG was used for the first time to successfully detect SARS-CoV-2 viruses in high measuring accuracy in test liquids.

In contrast to PCR testing, the new test provides a clear electronic "YES" or "NO" information within a few minutes, saving precious time in the diagnosis. What's more, the Digid Cantisense(TM) SARS-CoV-2 Test directly detects the presence of the virus while other rapid tests only recognize antibodies.

Konstantin Kloppstech, CTO at Digital Diagnostics, says: "Recent test series at the HZI high-security laboratory have shown that SARS-CoV-2 viruses can be detected directly using our Cantisense technology and without the need for PCR or further sample processing. This is a scientific breakthrough. We have coated cantilevers with a capture layer of highly specific monoclonal antibodies, which can reliably bind SARS-CO-2 viruses in the test fluid."

Constantin von Gersdorff, CEO of Digital Diagnostics, said: "The next step will be to initiate clinical studies with patient samples. To this end, we have already established international collaborations with leading hospitals."

With Digid's test kit, the measurement results are transmitted wirelessly from a sensor hub to a mobile device. By connecting to a secure analytics platform, the sensor data can be augmented with further data and processed anonymously for research and diagnostic applications.

Due to its measurement speed and the highly reliable results, the test is particularly suitable to support the containment of the current SARS-CoV-2 pandemic. The test offers the possibility of simple and rapid testing of patients and medical staff as an alternative to laboratory tests and enables reliable identification of infected persons within minutes. The possible areas of application therefore also include screening for access control at airports and railway stations, hospitals and specially protected areas (such as retirement homes) as well as for companies who want to ensure that their production runs smoothly and safely.

Digital Diagnostics has applied for approval of the Digid Cantisense(TM) SARS-CoV-2 Test by the US Food and Drug Administration (FDA). Digid aims to provide millions of units by July 2020. A further scaling of capacities is planned in the short term. The experts at Digital Diagnostics are also working at full speed to further develop the technology and to adapt the point-of-care testing procedure for use by consumers at home.

Atrys is Developing a Point of Care Graphene Technology-Based Biosensor to Detect COVID-19

Atrys Health, in collaboration with researchers from the Complutense University of Madrid and the University of Granada, is already working on the development of a portable diagnostic device “Point of Care” (tests from which the result is obtained immediately) based on graphene technology, which will allow detection with high reliability and in less than 15 minutes of COVID-19.

This kit, called RAP-ID19 will combine the advantages of the two techniques that have been most used so far for the diagnosis of the disease: on the one hand, the high specificity and sensitivity of the PCR (Polymerase Chain Reaction) technique; and, secondly, the speed of diagnosis and the need for specialized personnel of the RADTs (rapid antigen detection tests).

This will be achieved thanks to the graphene technology (GFET) used in its development, which allows making highly sensitive and instantaneous measurements using small amounts of sample thanks to the high electronic conductivity of graphene. In this sense, GFET-Point of Care biosensors represent a complete alternative for the massive, fast and reliable detection of COVID-19 due to its high sensitivity, specificity, speed, easy use, handling safety, as well as portability.

Another advantage of this Atrys device will be that end users will not be limited to testing by highly qualified professionals of the Health System, so it could be implemented as a detection tool in nursing homes; work and educational centers; airports, railway and bus stations.

Finally, by using a quantitative method, RAP-ID19 will allow quantifying the amount of virus, that is, the patient’s viral load, a factor potentially influencing the evolution of patients.

Financing of the SUPERA COVID-19 Fund

The project, which has an estimated duration of nine months, has been one of the seven selected within the SUPERA COVID-19 Fund of the Banco de Santander and Conference of Rectors of Spanish Universities.

The consortium that will carry out the RAP-ID19, with extensive experience in all the scientific aspects of this proposal and close prior collaboration, will receive financial assistance from the SUPERA COVID-19 Fund to develop the project and achieve a potentially marketable device.

Researchers Develop 1-Minute Electro-Optical Test to Identify COVID-19 Carriers

Ben-Gurion University of the Negev's Prof. Gabby Sarusi has developed a one-minute electro-optical test of nose, throat, or breath samples that will identify both asymptomatic and affected carriers of the COVID-19 virus in under one minute with greater than 90% accuracy.

Each test kit will cost approximately $50, which is far less costly than standard, laboratory-based polymerase chain reaction (PCR) tests. The BGU test is based on an electro-optical system that detects and identifies biological samples.

It does not require a lab environment so it can be deployed at critical locations such as airports, border crossings, stadiums, and other environments, as well as healthcare facilities where rapid testing is required.

Initial clinical trials completed with the Israel Defense Ministry on more than 150 Israelis had a better than 90% success rate. The ongoing trials will compare samples from COVID-19 patients with samples of patients with other diseases to detect the presence as well as the specific stage of COVID-19 infection.

"Right from the beginning of the trials, we received statistically significant results in line with our simulations and actual PCR tests that were conducted in parallel," says Prof. Sarusi, deputy head of research at the School of Electrical and Computer Engineering and a faculty member of the Electro-Optical Engineering Unit at BGU.

"We are now validating the robustness of the test and preparing to submit for FDA accelerated approval."

How does the test work?

"We asked ourselves, since this virus is just like a nano-particle or a quantum dot with a diameter between 100nm to 140nm in terms of its size and electrical properties, can we detect it using methods from the world of physics, photonics and electrical engineering," says Prof. Sarusi. "We discovered that the answer is yes; this virus resonates in the THz frequency, and spectroscopy in these frequencies reveals it promptly."

PCR coronavirus test kits are based on amplifying and identifying the viral RNA/DNA sequences and therefore depend on costly reagents in short supply and biochemical reactions that can be affected by heat and humidity.

PCR-based kits take hours, and in many cases days, to yield results and require logistically complicated shipping and handling of sensitive and infectious biological samples and can only be performed at points of care.

The new method is based on the change in the resonance in the THz spectral range imposed by the coronavirus through THz spectroscopy performed on the electronic chip designed by Prof. Sarusi and his team. This spectral range has been employed in recent decades for the fast detection and identification of biological samples.

Particles from a simple breath test or throat and nose swabs, currently used for other tests, are placed on a chip with a dense array of tens of thousands of metamaterial sensors that were designed specifically for this purpose.

The system then analyzes the biological sample and provides an accurate positive/negative result within a minute via a cloud-connected system.

The point-of-care device automatically records the results into a database that can be shared by authorities, making it easier than ever to track the course of the virus, as well as triage and treat patients.

"The world needs rapid, less expensive and widespread COVID-19 detection and this one will be ready to deploy in Israel in just weeks," says Doug Seserman, chief executive officer of the New York City-based American Associates, Ben-Gurion University of the Negev.

"BGU is working in many areas from vaccines to psychological support to mitigate the effects of this pandemic."

The new test is just one of more than 50 initiatives funded with grants as part of the BGU COVID-19 Response Effort. These each require financial support, and AABGU has announced its commitment to raise emergency funds, enabling BGU to participate fully in the world's efforts at mitigation and containment.

Source: American Associates, Ben-Gurion University of the Negev

Team to Develop Breathalyzer-Like Diagnostic Test for COVID-19

A research team led by Pirouz Kavehpour, professor of mechanical and aerospace engineering in the UCLA Samueli School of Engineering, is developing an inexpensive and fast breathalyzer-like diagnostic tool to test for the novel coronavirus that causes COVID-19.

“Unfortunately, the COVID-19 pandemic has exposed a critical weakness in health care security infrastructure, which is a substantial deficiency in our capabilities to conduct rapid, simple, point-of-care diagnostic and environmental sample collection and testing,” said Kavehpour, who is the principal investigator on the research. Kavehpour’s team has received a one-year, $150,000 research grant from the National Science Foundation.

“The goal in this research is to develop cheap, massively deployable, rapid diagnostic and sentinel systems for detecting respiratory illness and airborne viral threats,” said Kavehpour.

The design could also be altered to detect other infectious diseases and airborne viral threats by continuously monitoring the air of indoor environments, such as hospitals, schools and airports, for the presence of the dangerous levels of virus.

The concept is based on an environmental water condensation technology developed by Kavehpour and his research group. They have applied for a patent for the design.

Although similar in use to breathalyzer tests designed to check blood alcohol levels, which use infrared light to measure blood alcohol levels, the method behind the COVID-19 diagnostic test is different. For the coronavirus test, a person would exhale into the device for about a minute. Water vapor from their breath would condense on a special plate. Live virus and virus RNA could then be screened by using fluorescent genetic tags that light up if the virus is present. It could take about 10 minutes to show results.

If the design is successful and meets all federal criteria, test kits could be in production as early as fall 2020, said Kavehpour, who is also a professor of bioengineering.

Other UCLA investigators on the project include Ali Alshehri, a doctoral student in mechanical and aerospace engineering; Rob Candler, professor of electrical and computer engineering; Nasim Annabi, assistant professor of chemical and biomolecular engineering; and Dr. Paul Krogstad, professor of pediatrics, pediatric infectious diseases, and molecular and medical pharmacology at the David Geffen School of Medicine at UCLA.

Other members of the team are Jeff Ruberti and Sara Rouhanifard, of Northeastern University; and Jonathan Rothstein, of the University of Massachusetts, Amherst.

University of Toronto Researchers Develop Rapid, Sensitive Antibody Test for COVID-19

Researchers from the University of Toronto are developing a rapid blood test that can detect if a person has previously been infected with SARS-CoV-2 – information many countries say is critical to ease physical distancing measures and restart their economies.

“Until we have a valid drug treatment strategy or vaccine against COVID-19, we will have to perform mass blood testing in our corresponding countries,” says Igor Stagljar, a professor of biochemistry and molecular genetics in the Faculty of Medicine and the Donnelly Centre for Cellular and Biomolecular Research who leads the effort with support from the Toronto COVID-19 Action Fund.

“These serological tests will be the only way we can reliably determine the extent of viral spread and identify those individuals who are able to safely return to work.”

Serological tests look for antibodies in blood that are produced by the body to fight infection. Antibodies are protein molecules that bind and neutralize foreign proteins, known as antigens, that come from viruses and other pathogens.

According to the plan outlined by the federal COVID-19 Immunity Task Force, at least one million serological tests will be carried out over the next two years to help gauge how many Canadians have been exposed to the novel coronavirus.

Health Canada recently announced it approved the first serological test for COVID-19. However, concerns have been raised over the ability of some methods to detect potentially low antibody levels in people who were recently infected or suffered mild or no symptoms.

“Ideally, we want to have a test that is very fast, low cost and accurate,” says Stagljar, whose team is working to achieve just that.

The U of T team’s test, which works in under an hour, involves dousing a blood sample with purified SARS-CoV-2 proteins so that antibodies can bind to them. The viral proteins are engineered to carry pieces of a fluorescent protein that can only be reconstituted if antibodies are present in a chemical reaction that produces a flash of light – a positive result – that is detected by a plate reader instrument.

The test also employs a new technology called SIMPL, which stands for split intein mediated protein ligation, developed by Stagljar’s team and described in a study published recently in the journal Nature Communications. SIMPL helps strengthen the contact between antibodies and viral proteins to increase test sensitivity.

“We originally devised SIMPL to study interactions between proteins in living cells, however, we quickly realized that the technology could be adapted to dramatically improve the sensitivity of a COVID-19 serological assay” says Zhong Yao, a senior research associate in Stagljar’s lab who is responsible for both the COVID-19 and SIMPL projects.

The prototype lab test can detect different types of antibodies such as immunoglobulinM and immunoglobulinG that can help distinguish how long ago an infection occurred. IgM antibodies are produced first and are relatively short-lived, while IgG antibodies come later and linger in the bloodstream to confer longer-lasting immunity. While is still unclear how long the immunity to COVID-19 lasts, serological tests will help answer this.

“Our goal is to detect IgM and IgG antibodies in only 10 microliters of blood,” says Stagljar.

Having validated their test with purified antibodies, the team are now calibrating it for the detection of variable antibody levels in patient blood samples. “We should know in four months if it’s working or not.”

Stagljar is collaborating with Samira Mubareka, an assistant professor in the department of laboratory medicine and pathobiology in the Faculty of Medicine who is at Sunnybrook Health Sciences Centre, and Mario Ostrowski, a professor in the departments of medicine, immunology and laboratory medicine and pathobiology who is at St. Michael’s Hospital. James Rini, a professor of molecular genetics and biochemistry in U of T’s Faculty of Medicine, is also involved in the research.

The new SIMPL method locks interacting proteins together to help capture transient protein interactions in cells that could not be detected with other methods. It can also be applied across different types of human cells and to study interactions that occur in different cellular compartments.

Aside from the antibody test, Stagljar is applying SIMPL for cancer drug discovery. One project is looking for small molecules that can inhibit protein interactions involving disease variants of the KRAS protein, which is mutated in a third of all cancers. The project has received funding from the Cancer Research Society, FACIT Oncology Fund, Genome Canada and Toronto Innovation Acceleration Partners, a public-private partnership supporting academic research commercialization and previously known as Mars Innovation.

Source: University of Toronto News

GoDx Uses Point-of-Care Test to Rapidly Diagnose Gut, and COVID-19 Pathogens

GoDiagnostics, or GoDx, was formed with the vision to “democratize diagnostics” so that all people can more quickly learn about infections that make them sick.

The founder and chief executive officer of GoDx, Chang Hee Kim, and his team are in the process of gaining regulatory approval of their two diagnostics tests — GutChecker and CoronaChecker.

Kim founded the company to combat deaths related to diarrhea-inducing gut pathogens. With between millions of annual deaths, diarrhea is the second leading cause of death in children under age 5 worldwide. Furthermore, founders have identified an unmet need for quick, inexpensive and effective diagnostics tests in the health care system. GoDx is tackling this need head on.

Traditionally, such pathogen diagnostic tests would take several days to yield a result because samples have to be sent to a lab. In many cases, that isn’t enough time to effectively treat a potentially life-threatening pathogen. Most pathogen detection tests are also expensive and require instruments, costly machinery and plenty of time in order to yield accurate results – resources not readily available to many clinics around the world.

The GoDx tests under review is a rapid diagnostic that doesn’t need machines, instruments or even a laboratory, and can yield results in roughly 30 minutes.

This non-invasive diagnostic method works by amplifying pathogen DNA and RNA through a process called isothermal nucleic acid amplification. This process uses enzymes to amplify pathogen DNA and RNA, which replaces the need for heat and time required by most traditional diagnostic tests.

After 20 to 30 minutes, a practitioner will test for gastrointestinal pathogens by transferring the amplified DNA or RNA to a paper strip which will identify a positive or negative result for a specific pathogen.

“Think of it like a pregnancy test,” Kim said.

GoDx plans to bring GutChecker to developing countries most affected by diarrheal pathogens.

The company initially used this point-of-care technology for the GutChecker test for GI pathogens with a $3 million Small Business Innovation Research SBIR grant funding from the National Center for Advancing Translational Sciences of the National Institutes of Health.

With the rise of the coronavirus pandemic, GoDx is also developing a fast-tracked FDA emergency test called CoronaChecker to detect the SARS-CoV-2 virus which causes the COVID-19 disease. For this test, saliva or nasopharyngeal samples will be used.

“There is an urgent need for coronavirus testing at (volumes that are) currently unmet,” Kim said. “We were already working on the technology to find [gastrointestinal] pathogens… We already had our base platform.”

GoDx’s instrument-free tests make rapid diagnostics available to hospitals and labs that do not already have the specific and expensive instruments required for the current FDA emergency tests. GoDx also hopes to develop an at-home CoronaChecker test by the end of the year. Amid the current crisis, GoDx is prioritizing the rapid development of CoronaCheck over GutChecker.

Kim projects the company still has about a year and a half of development ahead for the GutChecker rapid diagnostic test.

Kim obtained his Ph.D. from CALTECH in biochemistry, a Howard Hughes Medical Institute postdoctoral fellowship at Harvard with Nobel Laureate Dr. Jack Szostak, and has a background in diagnostics and genomics. While GoDx originated in California in 2017, the company more recently made the move to Madison.

“We love the supportive startup environment here,” Kim noted.

Kim thanked Madison-based Merlin Mentors for mentorship support, and noted the company also received funding from the Wisconsin Economic Development Corporation through the Center for Technology Commercialization.

GoDx is among the finalists for the 2020 Wisconsin Governor’s Business Plan Contest, which will end at the Wisconsin Entrepreneurs’ Conference in June.

Mexico's National Polytechnic Institute Develops 15-Minute Test That Detects COVID in Asymptomatic Patients

A portable device for detection of the COVID-19 that provides a response in 15 minutes and that would avoid going to a hospital and coming into contact with seriously ill patients was designed by researchers from National Polytechnic Institute (IPN) from Mexico.

The device can be connected to the cell phone and indicate the result in real time to the doctor, via email.

The diagnostic method recommended by the World Health Organization (WHO) is the molecular test known as reverse transcriptase and chain reaction of the polymerase (RT-PCR, for its acronym in English), which reveals the presence of genetic material of the virus.

But its application is limited by the cost and the requirement of specialized facilities.

In a statement the IPN reported that a team of researchers from the Department of Biotechnology and Bioengineering of the Center for Research and Advanced Studies (Cinvestav) developed the apparatus.

The device works under the technique of reverse transcription coupled to the isothermal amplification Loop-mediated (RT-LAMP), to do the ‘in situ’ detection of the SARS-CoV-2 virus.

In such a way that “if a person has an active infection with the new coronavirus, detection by RT-LAMP generates a result in approximately 15 minutes, since it exponentially amplifies (generates multiple copies) a viral gene in a specific way,” he explained. the team led by researcher Roberto Ruiz Medrano.

In the note it was explained that unlike the conventional RT-PCR technique, where “the sample is subjected to different temperature cycles”, in which Cinvestav researchers propose, “a device is used that allows the detection mixture of the virus at 65 degrees centigrade. “

They specified that “by not requiring sophisticated equipment, RT-LAMP can be performed at the site where the patients to be diagnosed are located.”

They stressed that this technique has already been used internationally for the detection of various pathogens, both plant and animal and human.

Ideal for asymptomatic patients

According to researcher Beatriz Xoconostle Cázares, who along with Brenda Vargas Hernández and Brenda Vargas Hernández also participate in the project, the development of the RT-LAMP test started in January of this year.

The specialist said that the implementation of this type of rapid tests “would be ideal for asymptomatic patients or with mild symptoms, the same as having this diagnostic option, they would not need to go to hospitals with seriously ill patients ”.

He said that this would also allow them to recover at home and isolate themselves in order to limit the spread of the new coronavirus and recalled that since the transmission of the pathogen that causes COVID-19 can occur through infected people but do not show symptoms , “Identifying the virus carriers is a relevant aspect” to contain the advance of this infectious agent.

“By limiting infections, mutations in the genetic material of the virus could be avoided, since these changes can diversify variants of this pathogen (more aggressive or less) and make its control more complex,” said the researcher.

About the equipment for the RT-LAMP test, the expert said that it is portable and contains a resistance similar to that of an iron, responsible for maintaining a constant temperature of 65 degrees Celsius.

The aforementioned device is connected through the Android system to a cell phone, it has a special program that indicates the progress of the detection process in real time and at the end the result can be sent via email to the treating doctor.

The Quick test Developed by Cinvestav researchers, it is ready and the next step is to request its validation before the Institute of Epidemiological Diagnosis and Reference (InDRE), once this happens, hospitals and authorized laboratories will be able to apply it.

Team to Develop a New Physics-based Technology for COVID-19 Detection

One of the most challenging aspects of the COVID-19 pandemic has been the lack of testing needed to detect and trace infections—and without adequate testing, government officials do not have the data they need to make the best possible decisions in the interest of public health.

In addition to being in short supply, most tests use biochemicals that are expensive and difficult to produce, require long turnaround times for test results and produce a high number of false negative results—meaning that some people who test negative might still be infected and unknowingly spread the disease. And although newer testing methods that detect antibodies in the blood, based on the so-called ELISA method, are rapidly coming online, scientists and physicians question their efficacy.

NAU professor Miguel José Yacamán, a physicist and materials scientist in the Center for Materials Interfaces in Research and Applications (¡MIRA!), has assembled an interdisciplinary team to develop a new test technology that promises to overcome all these challenges. The project, “Development of a New Test for SARS-CoV-2 using Single Molecule Surface Enhanced Raman Spectroscopy,” was recently awarded a $200,000 grant from the National Science Foundation’s Rapid Response Research (RAPID) funding program supporting virus-related research. Although the team has one year to develop the new test, José Yacamán plans to achieve this goal even sooner.

The team will develop the new test by applying concepts from physics, not biochemistry, José Yacamán explains. They will focus on recent discoveries in the emerging fields of nanotechnology, plasmonic nanoparticles and 2D materials (similar to graphene).

“The project team will use non-traditional techniques to detect virus in infected patients. We will develop an alternative method based on recent advances in physics related to the interaction of light with matter,” he said.

The method, Single Molecule Surface Enhanced Raman Spectroscopy (SM-SERS), will detect the S proteins of the SARs-Cov-2 virus, which participate in infection at the cellular level. “The ability of SM-SERS to detect as little as one molecule of protein will enable healthcare professionals to detect infection early and follow up with patients who recover from the illness.”

The principal investigator of the project, José Yacamán will work in collaboration with two ¡MIRA! colleagues, associate professor Andy Koppisch, a biochemist, and associate professor of practice Rob Kellar, a biomedical engineer; and with Regents’ Professor Paul Keim, a microbial geneticist, and professor Dave Wagner, a disease ecologist, both with NAU’s Pathogen and Microbiome Institute (PMI).In his previous work, José Yacamán has used surface-enhanced Raman spectroscopy to detect glycoproteins and sialic acid as a method of testing for breast cancer, which is now in the final approval stage for commercial use.

“In the case of the SARS-CoV-2 virus, it was a natural extension to apply the same techniques,” he said, “but it will require the expertise of our PMI colleagues, who are growing the SARS-CoV-2 virus in their labs, to succeed.”

Keim, PMI executive director, said, “Major advances in science almost always occur at the interface between disciplines, and this is a great example. I think that this work between ¡MIRA! and PMI could be a game changer in our fight against COVID-19.”

“This project is a joint effort between researchers in ¡MIRA! and PMI,” said ¡MIRA! director and professor Jennifer Martinez. “It shows the power of interdisciplinary work for creating new ideas and new funding opportunities—and, most importantly, the importance of having centers of excellence to drive new research for NAU.”

“If successful, our research will be the first step in developing a method based on physics that will be fast and inexpensive, with high sensitivity and specificity and low percentage of false negatives,” said Yacaman. “This test will be a much more precise and reliable method to detect infections.”

“It is conceivable that once we’ve developed this test, portable Raman equipment can be used widely in many different populations; for instance, in rural or remote communities or in point-of-care stations in schools, factories, community centers and so on, in addition to traditional testing sites,” he said.

“Once widespread testing is under way, further analysis of the SM-SERS data will help scientists understand changes on the virus proteins and help develop antiviral drugs.”

Source: Northern Arizona University

Sherlock’s CRISPR SARS-CoV-2 Rapid Diagnostic Gets FDA Emergency Use Approval

Earlier this month, CRISPR engineering biology company Sherlock Biosciences announced it had received Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA) for its Sherlock CRISPR SARS-CoV-2 test kit for the detection of the virus that causes COVID-19.

“While it has only been a little over a year since the launch of Sherlock Biosciences, today we have made history with the very first FDA-authorized use of CRISPR technology, which will be used to rapidly identify the virus that causes COVID-19,” said Rahul Dhanda, co-founder, president and CEO of Sherlock Biosciences in a press release. “We are committed to providing this initial wave of testing kits to physicians, laboratory experts and researchers worldwide to enable them to assist frontline workers leading the charge against this pandemic.”

The kit, which provides results in roughly one hour, is the first FDA EUA for the use of CRISPR technology in a diagnostic. While the test kits are not currently available, the company said it is scaling up production and will announce its plans for distribution of the kits in the coming weeks.

The diagnostic has been designed to be used in CLIA certified laboratories and is based on the technology—Specific High-sensitivity Enzymatic Reporter unlocking (SHERLOCK)—that gives the company its name. The test works via the programming of a CRISPR molecule designed to detect the genetic signature of the SARS-CoV-2 virus, using specimens obtained via a nasal swab, nasopharyngeal swab, oropharyngeal swab or bronchoalveolar lavage. If the signature is found, the CRISPR enzyme is activated and releases a detectable signal.

“When our lab collaborated with Dr. Feng Zhang’s team to develop SHERLOCK, we believed that this CRISPR-based diagnostic method would have a significant impact on global health,” said James J. Collins, co-founder and board member of Sherlock. “Development of the SARS-CoV-2 test kits has shown that SHERLOCK technology is not only faster than what we’re seeing with real-time PCR test kits; it is more precise, providing true positive and true negatives with 100 percent accuracy in patient samples. During what is a major healthcare crisis across the globe, we are heartened that the first FDA-authorized use of CRISPR will aid in the fight against this global COVID-19 pandemic.”

Access to rapid diagnostics is critical for combating this pandemic and is a primary focus for Sherlock Biosciences co-founder and board member, David R. Walt, Ph.D., who co-leads the Mass General Brigham Center for COVID Innovation.

“SHERLOCK enables rapid identification of a single alteration in a DNA or RNA sequence in a single molecule,” said Dr. Walt. “That precision, coupled with its capability to be deployed to multiplex over 100 targets or as a simple point-of-care system, will make it a critical addition to the arsenal of rapid diagnostics already being used to detect COVID-19.”

US Germ Warfare Research Leads to New Rapid Covid-19 Test

Scientists working for the US military have designed a new Covid-19 test that could potentially identify carriers before they become infectious and spread the disease.

In what could be a significant breakthrough, project coordinators hope the blood-based test will be able to detect the virus’s presence as early as 24 hours after infection – before people show symptoms and several days before a carrier is considered capable of spreading it to other people. That is also around four days before current tests can detect the virus.

The test has emerged from a project set up by the US military’s Defense Advanced Research Projects Agency (Darpa) aimed at rapid diagnosis of germ or chemical warfare poisoning. It was hurriedly repurposed when the pandemic broke out and the new test is expected to be put forward for emergency use approval (EUA) by the US Food and Drug Administration (FDA) within a week.

“The concept fills a diagnostic gap worldwide,” the head of Darpa’s biological technologies office, Dr Brad Ringeisen, stated, since it should also fill in testing gaps at later stages of the infection. If given FDA approval, he said, it had the potential to be “absolutely a gamechanger”.

While pre-infectious detection would improve the efficiency of test-and-trace programmes as governments worldwide relax lockdowns, Darpa cautioned that it must wait until after FDA approval is given and the test can be put into practise for evidence of exactly how early it can pick up the virus.

“The goal of research is to develop and validate an early host blood response diagnostic test for Covid,” Prof Stuart Sealfon, who leads the research team at Mount Sinai hospital in New York, said in an email.

He said the testing approach, which looks at the body’s response as it fights Covid-19, should produce earlier results than current nose-swab tests that hunt for the virus itself. “Because the immune response to infection develops immediately after infection, a Covid signature is expected to provide more sensitive Covid infection diagnosis earlier.”

The research behind the development of the tests will eventually be made public, with the collaborating teams from medical schools at Mount Sinai, Duke University and Princeton expected to publish online, allowing scientists around the world to trial similar methods.

“We are all extremely excited. We want to roll this test out as quickly as we can, but at the same time share with others who might want to implement in their own countries,” said Dr Eric Van Gieson, who set up Darpa’s epigenetic characterization and observation (Echo) programme last year to diagnose biological warfare victims, and has redirected it to focus on Covid-19. Epigenetics looks at a set of controls on genes that can respond to the environment.

Hope that the test might pick up carriers before they become infectious is based on previous research into other viruses, though Sealfon said this remained “unknown” for Covid-19.

“We have evidence that diagnosis happens in the first 24 hours for influenza and an adenovirus,” Van Gieson said. “We are still in the midst of proving that with Covid-19. That said, we should know very soon after EUA.” He sees potential for the US to carry out up to a million tests a day, starting with 100,000 daily in May.

The test would up the possibility of isolating pre-infectious cases and closing down transmission chains. It could also dramatically reduce quarantine periods for people exposed to Covid-19 spreaders, allowing them to go back to work within days. “It could have exceptional demand,” said Chris Linthwaite, the chief executive of Fluidigm, a California life-sciences technology company that is part of the project, who believes frequent testing can help manage workforces as they return to offices, warehouses and factories.

The UK government announced plans two weeks ago to restart a contact-tracing programme that was abandoned early in the outbreak. Britain’s stated target was 100,000 tests a day by the end of April. France announced on Tuesday that it would test 700,000 people a week, including those without symptoms.

Other countries such as South Korea, Australia and New Zealand already have efficient tracing systems, but they would be boosted if carriers could be detected early.

Darpa experts also see potential to improve protocols for protecting health care workers and others in high-risk jobs, as well as those in relatively self-contained or isolated communities such as care homes and prisons or onboard ships.

The test uses the same polymerase chain reaction (PCR) machines used for checking nasal swabs from people suspected of having the virus. “It’s a simple tweak,” said Van Gieson. “The infrastructure is already there.”

Limitations on use are similar to those already faced by countries such as Britain and depend on PCR capacity, stocks of chemical reagents and logistics. Results can take an hour, or longer if samples must be sent away to laboratories.

Like the viral test, the new blood test hunts for a type of molecule called RNA. In this case it is messenger RNA (mRNA). “Target mRNA is part of the immune response to viral infection,” Sealfon said. “mRNA expression levels really do adjust due to the presence of Covid-19. Understanding the immune response is key to fighting Covid-19.”

Covid-19 is thought to incubate for about five days, at which stage people are assumed to become infectious. That is also when the virus can be detected by current nose swab tests. “They do the job, they just don’t tell you someone is sick until maybe four days after this [new test],” said Van Gieson.

The research shows accuracy levels above 95%. “This is something that will need to be constantly monitored as it will inevitably change up or down,” Van Gieson said.

Blood samples are harder to collect than nose swabs, but may be more reliable. Swab testing can be difficult because it requires taking a sample from deep inside the nose.

“It can throw up a lot of false negatives,” said Prof Lawrence Young of Warwick University, adding that recent studies showing low reliability were probably due to poor swab sampling. “I’ve been very concerned by pictures on the television of drive-in testing. Something you could measure reliably in blood could be a good thing.”

Young was unwilling to comment further until the Mount Sinai-led team published its research. Most were concerned about potential problems with accuracy and practicality. Blood collection is a potential limitation, since drive-in centres are not usually equipped to do this. One millilitre of blood – a fifth of a teaspoon – is needed.

The research team is expected to publish the mRNA sequence, allowing others to create the so-called “primer” required. A similar approach was taken when the genetic sequence of the virus itself was released by China in January, allowing tests to be developed rapidly in South Korea and elsewhere.

Source: The Guardian