Swab, swoosh, splat. During the pandemic, many of us got used to using lateral flow tests to check if we were infected with Covid-19 or were likely to infect others. But despite the gag-inducing testing routines of the pandemic thankfully fading into memory, we may not have seen the back of those small diagnostic cartridges.
Boots UK recently launched finger-prick lateral flow tests (LFTs) to detect levels of vitamin D, iron or cholesterol in people’s blood, as well as an influenza test. Trials of LFTs to rapidly diagnose strokes are under way, and the type of sample that can be loaded on to these tests is expanding rapidly, from fingerprint sweat or river water to cat vomit.
LFTs are designed to rapidly detect a molecule of interest without the need for specialised, costly equipment, by incorporating highly specific antibodies into a plastic cartridge. These bind to the target and trigger a colour change if it is present, usually resulting in a red or blue line in the device’s reading window.
The first commercial LFT, the Clearblue pregnancy test, was launched in the late 1980s and, until Covid hit, such urine-based pregnancy tests were their primary application. However, the pandemic has ushered in a new era of innovation for these tests.
“First of all, there’s a much wider awareness – not only with the general public but the scientific community – of lateral flow, and treating it as a more serious alternative to laboratory testing,” said Dr Chris Hand, the chair and co-founder of Abingdon Health, which develops and manufactures LFTs on behalf of other companies.
“People are starting to understand the benefit of being able to test on site or at the point of care, that you can do the next stage of whatever process you’re doing immediately.”
Thanks to the pandemic, the capacity to manufacture these tests has also expanded hugely, while the experience of self-testing means most people are familiar and comfortable with this technology.
“The beauty of lateral flows is that they are easy to use but also easy for people to understand: you put a sample here, and a line means positive; no line is negative,” said Gonzalo Ladreda, the chief executive of UpFront Diagnostics, which is developing LFTs for early stroke detection.
Because of this, not to mention the innate flexibility of the technology, the number of potential applications is expanding rapidly.
“Most things you want to measure, you can measure with lateral flow,” Hand said. Tests are being developed or launched to detect microbial contaminants in aircraft fuel, disease-causing organisms such as E.coli in river water, or concussion in contact sports. In July, the UK’s first range of LFTs for pets was launched, capable of detecting the 12 most common infections in cats and dogs.
Advances in the materials used in LFTs are also opening up the possibility of testing additional substances – such as faeces, milk or sweat, or plant material such as leaves or roots – in increasingly smaller volumes. For instance, Cambridge-based Intelligent Fingerprinting has developed LFTs that can detect drugs including cannabis, cocaine and opiates in fingerprint sweat; they are already being used to test employees and job candidates in safety-critical industries.
A big growth area is healthcare. Besides early stroke detection, UK trials of two LFTs to detect the deadly bloodstream infection sepsis are getting started. The first, Neutrocheck, is designed to be used at home by patients whose immune systems have been weakened through chemotherapy, and who are therefore at high risk of sepsis.
Currently, such patients are advised to attend hospital if they are experiencing even mild signs of infection, to check that their levels of infection-busting immune cells – called neutrophils – are high enough. While awaiting the results, they are usually injected with antibiotics as a precaution, even though most are fine and don’t need to be in hospital at all. This puts pressure on the NHS and is stressful and inconvenient for patients.
“If you’re in your final month of life and you’re trying to deliver your bucket list, you don’t want to spend 12 hours waiting in an emergency department to be told to go home,” said Dr Ron Daniels, an NHS intensive care consultant and founder and chief medical officer of the UK Sepsis Trust. It has been supporting development of the Neutrocheck device in the hope that it could identify which patients genuinely need to attend hospital and which could remain at home.
Whereas LFTs typically measure dissolved substances or tiny viral particles, Neutrocheck captures and quantifies much larger neutrophils, as well as a blood protein called C-reactive protein that is associated with infection.
A separate device called Septiloop detects whether immune cells in the blood have recently been exposed to bacteria. It is designed for use by emergency departments to identify early signs of sepsis in patients who are not yet showing symptoms. A trial to investigate the economic impact of this test on the NHS is expected to begin within months.
The ability to rapidly identify high-risk patients or the likely cause of their symptoms could also be particularly valuable in lower-income countries, where laboratory infrastructure may be weak or nonexistent and patients’ nearest hospital many hours away.
Daniels believes LFTs could help to counter the growing threat posed by antimicrobial resistance. Giving antibiotics to patients who don’t need them, or won’t respond to them, is contributing to this problem. Yet, because laboratory tests often take days to return a result, doctors often err on the side of caution and prescribe these drugs. “I think there are huge opportunities for LFTs to identify which patients with symptoms of infection require antibiotics and which don’t,” Daniels said.
Further innovations are coming. “One of the advantages of lateral flow is that it can multiplex, so you can measure different things at the same time,” said Umaima Ahmad, the chief executive and co-founder of 52 North, which developed Neutrocheck. “We’re currently measuring two things but we could definitely look at incorporating five or six things across a single device.”
Abingdon is working on reducing the amount of single-use plastic associated with these tests. “We’re looking at using more sustainable material in the cassettes, including paper-based systems or biodegradable plastics,” Hand said.
Even so, there may be challenges ahead. Useful as rapid diagnostic tests might be, Daniels said: “I think we have to recognise that the quality of lateral flow tests is not as high as that of laboratory tests, and so we have to make sure that we integrate them into clinical systems in a careful way.”
Prof Kamila Hawthorne, the chair of the Royal College of GPs, said: “While the use of self-testing kits, including lateral flow tests, can have benefits for patient care, it’s vital that a thorough pilot and evaluation is undertaken before any wider roll-out of self-testing initiatives takes place in the NHS.”
She urged similar caution about consumer tests for hormonal or nutritional deficiencies, or infections. “With the risk of false positives and negatives, and no offer of an interpretation of the results or aftercare, self-testing kits can mean patients experience a significant amount of stress and anxiety – prompting them to seek guidance from their GP to interpret any results,” she said. “This not only negatively impacts our patients but it can also intensify the enormous pressures that GPs and their teams are currently under.”
Daniels said there is little incentive for hospital laboratories – which control testing budgets – to support the incorporation of LFTs into hospital workflows, when they could manage quality control more easily with lab-based tests. Also, whereas funding is available to support innovations in specific disease areas, “there isn’t really any innovation budget available to deliver more general service change,” he said.
“I’m a moderately senior intensive care clinician but if I decided I wanted to buy these lateral flow tests, I would have no budget available to me.”
– Guardian
