HiberGene’s tests are based on LAMP technology. Can you explain the principles of this technology and how the tests work?
Technology Networks recently spoke to Dr Gary Keating, Chief Technical Officer at Hibergene Diagnostics, to learn more about LAMP technology and the advantages it could offer for COVID-19 testing. Gary also discussed some of the challenges faced when developing diagnostics and how the COVID-19 pandemic has impacted diagnostic design and manufacturing.
Throughout the COVID-19 pandemic, testing for active infection has been a crucial tool to help to control the spread of the SARS-CoV-2 virus, enabling the identification of infected individuals and subsequent isolation and contact tracing.
Most current diagnostic tests that detect SARS-CoV-2 genetic material are PCR-based, due to its high sensitivity and specificity. However, the method can be expensive, slow, and requires sophisticated equipment and well-trained personnel, making it unsuitable for point-of-care use.
Molecular tests based on alternative methods such as Loop-mediated Isothermal Amplification (LAMP) are being developed, which could offer a low-cost, fast and portable way to detect SARS-CoV-2 infection.
Anna MacDonald (AM): For readers that may not be familiar with HiberGene Diagnostics, could you tell us a little about the company history and mission?
Gary Keating (GK): HiberGene has been developing, manufacturing and selling molecular diagnostic tests from its Dublin site since late 2014. Our first product was a test for bacterial meningitis (the first and only non-invasive test which painlessly screens young children from throat swabs). We’ve followed that up with 12 other tests for critical infectious diseases, all of which utilize simple sample preparation techniques to deliver rapid accurate results with minimal facility and staff training requirements. Our range includes tests for hospital acquired infections, respiratory viruses, STIs and important maternal/neonatal health applications.
AM: HiberGene’s tests are based on LAMP technology. Can you explain the principles of this technology and how the tests work?
GK: LAMP (which is an acronym for Loop-mediated Isothermal Amplification) is a single tube technique for the amplification of DNA. It provides a low cost alternative to polymerase chain reaction (PCR) technology to detect certain diseases.
It involves the design of assay primers and use of a strand-displacing polymerase to allow rapid amplification at a constant temperature without the need for thermal cycling (required for PCR).
A typical LAMP reaction mix contains 6 primers which target 8 regions on the bacterial or viral genome.
AM: What advantages does this approach offer over other molecular diagnostics such as PCR-based testing?
GK: Simply speaking, LAMP provides a highly specific, low cost, fast and portable test for pathogenic bacteria/viruses.
Due to the large number of binding sites on target DNA/RNA, the LAMP method is inherently highly specific. The isothermal nature of the reaction means that no thermal cycling is required, facilitating the use of a small, portable, analyzer like HiberGene’s HG Swift.
LAMP reactions very rapidly generate large quantities of amplified material when pathogenic bacteria/viruses are present in the patient sample; typically time to positive result is 15-25 mins from the start of the reaction, a detection speed which outstrips standard automated PCR.
In addition, the ready-to-use freeze-dried LAMP reagents used in HiberGene tests are highly resistant to inhibition, allowing samples to be used without extraction. The standard sample handling protocol for most of our 13 CE-marked infectious disease tests involves simple dilution and heat treatment steps for crude samples including stool, respiratory and genital swabs , before addition to the reaction mix.
AM: HiberGene’s platform can distinguish between different infections from a single patient sample. Can you explain how this is achieved and the benefits it offers?
GK: Our LAMP technology uses highly specific fluorescent probes to differentiate between amplification of individual targets in our “combo” assays.
Using the sensitive two-channel fluorescent detector in our HG Swift instrument, we can distinguish between chlamydia and gonorrhoea infection in a urine sample, or between Flu A and Flu B in a respiratory swab, allowing clinicians to treat appropriately and quickly. Performing, for example, a Flu test and a COVID-19 test in parallel from the same sample within a single instrument run allows the laboratory to run a “mini-panel” for critical respiratory.
Performing multiple infection tests from the same sample reduces the number of tests a patient must have, time taken to diagnosis and this in turn facilitates a cost saving.
AM: You have recently entered a partnership with RocDoc Health Check. Can you tell us more about the partnership and its aims?
GK: As the COVID pandemic progressed, HiberGene began assessing an opportunity to provide a test service to businesses and individuals. We saw a synergy with RocDoc given that they operate a Primary Care Centre in Ashbourne and they frequently set up and operate mobile hospitals and labs throughout Ireland and the UK, and HiberGene provides fast molecular diagnostics for COVID and Flu.
RocDoc provide patient medical / clinical assessment and now offers a COVID test service to the public and to potential corporates, at their drive-thru test centre in Ashbourne and off site by sending out a swab team or their mobile lab as needed.
AM: What are the biggest challenges when developing diagnostics?
GK: It’s critical to have comprehensive design inputs from customers to ensure that the right products are being developed. For an IVD manufacturer, this means understanding the requirements of a large range of individual stakeholders, from the laboratory technician who runs the test to the lab manager who runs the testing facility, through the procurement staff who purchase test instrumentation and kits, and including the physician who orders the test. It’s also critically important to understand the clinical guidelines around each disease: the best test in the world will struggle for adoption if it involves a sample type or measurement technique which isn’t aligned with the guidelines.
AM: How has the COVID-19 pandemic impacted diagnostic design and manufacturing?
GK: As with all other businesses, the implementation of COVID-19 restrictions and work practices has obviously had a practical impact. In terms of product mix, the demand for COVID molecular testing has led to a decline in usage of other products across the globe. On the other hand, the huge focus on COVID testing in the news cycle has brought the critical importance of clinical diagnostics to the forefront of public consciousness. The fast-tracking of COVID-19 publications and the open sharing of information has been key in allowing companies like HiberGene to rapidly develop and bring to market tests which meet the clinical requirements. This experience is sure to leave a legacy of greater flexibility and innovation across the industry.
Gary Keating was speaking to Anna MacDonald, Science Writer for Technology Networks.