As countries work to contain the Covid-19 pandemic, the need for effective diagnostic testing has been front and center. Accurate, accessible testing is a precondition for the population’s gradual return to normal — or, most likely, a new normal.
Diagnostics companies have mobilized their resources and readied tens of tests, sometimes within weeks. In the face of the health emergency, the U.S. Food and Drug Administration and other regulatory bodies have lowered their standards and granted “Emergency Use Authorizations” for some of the tests. Since mid-March, companies including GenMark, BioFire, Cepheid, and Mesa Biotech have received approvals for their microfluidic-based rapid molecular testing for SARS-CoV-2, the pathogen that causes Covid-19. A new dynamic of innovation is emerging around the world, and it seems obvious that there will be a before and after Covid-19.
“The pandemic will certainly leave its mark on the way we work, produce, and live in society,” Sébastien Clerc, technology and market analyst in microfluidics, sensing, and actuating at Yole Développement (Lyon, France), told EE Times Europe. The structure of the diagnostics industry will change as it intensifies its R&D activity and continues to consolidate. Overall, the microfluidics market will grow at a CAGR of 11.7% to US$17.4 billion in 2024, Yole predicts.
The Covid-19 test protocol includes a real-time reverse-transcription polymerase chain reaction (RT-PCR) test of a person’s saliva or nasal sample and may currently take several days to yield results. A rapid test can help contain the number of unnecessary visits to health clinics and save lives by reducing the spread of the virus. Researchers are looking to apply microfluidic chips in coronavirus test protocols.
Microfluidics is a multidisciplinary field involving engineering, physics, biochemistry, and nanotechnology. It deals primarily with the behavior, precise control, and handling of geometrically confined fluids on a small (typically sub-millimetric) scale, in a context in which capillarity governs mass transport.
Microfluidic technology thus proves to be very suitable for the definition of the test structure used in many fields of biological research and has the potential to offer rapid diagnostic tools.
In a typical approach using a microfluidic chip, a small volume of fluid is injected in micron-scale channels by using a pump, allowing precise control of the microenvironment to reduce mass and heat transfer times. It thus requires smaller samples and less reagant, enabling greater efficiency at a lower cost compared with conventional methods.
Different types of pumps precisely move liquid inside the chip at a rate of 1 μL/ minute to 10,000 μL/minute. The form factor is usually transparent and measures 1 cm to 10 cm in length. The thickness ranges are from about 0.5 mm to 5 mm.
The flow of liquids through the channel network can be induced by various systems, such as pressure regulators, syringes, and hydrostatic pressure. Microfluidic units are used to measure molecular diffusion coefficients, fluid viscosity, pH, and required chemical coefficients. Microfluidic PCR chips have already been used to detect viruses and bacteria and could offer excellent functionality in the RT-PCR workflow for diagnosing Covid-19.
Microfluidic approaches have several advantages over other conventional solutions: faster reaction times, higher sensitivity, better temperature control, automation, and easier parallelization with microelectromechanical system (MEMS) solutions.
The choice of materials and manufacturing methods for microfluidic devices is determined by their final applications. The first material used for microfluidics was silicon, with chips built using the established processes of the microelectronics industry, but silicon was quickly replaced by glass and then polymers. Polymers offer the right solution because they are cheaper, are robust, and involve faster fabrication processes. Polydimethylsiloxane is the most common material used for microfluidic devices because of its optical transparency, biocompatibility, elasticity, and simple manufacturing process (soft lithography).
Lifting the lockdown
The sooner a patient is taken care of, the better the chances of recovery. Given the virulence of Covid-19, those battling the pandemic are in a race against time, and companies have mobilized resources to cut the time to diagnostic test results from days to hours to minutes, all while increasing throughput. Abbott Laboratories’ ID Now, Roche Molecular Systems’ Cobas, and Cepheid’s Xpert Xpress are rapid point-of-care (PoC) molecular assays for Covid-19 detection. Cepheid’s test has the capacity to process multiple samples simultaneously; the Cobas and ID Now platforms can handle only one sample at a time.
“The problem with PoC platforms is that the throughput of patient tests is very low,” said Clerc. “These platforms can handle between one and eight samples at a time. Even though tests are ultra-fast, [yielding results] in 15 to 30 minutes, only a few patients can be tested per hour.” Lifting the lockdown, however, requires a massive testing program “on the order of hundreds of millions of tests per week.” Supplementing the molecular tests will be serological tests to verify the presence or absence of SARS-CoV-2 antibodies in blood samples.
A key challenge in the exit plan will be to identify people who have had an asymptomatic or mild form of the virus. In those cases, molecular tests aren’t needed, said Clerc. “If the patient has contracted the virus but is in remission or has fought it, the molecular test will not be able to detect it. A serological test will be needed to measure the response of the patient’s immune system to the virus.” Those tests are simpler and do not necessarily require microfluidic technologies.
Complicating matters, it is not yet known whether immunity to the virus lasts weeks, months, or years. “It’s too early to tell,” said Clerc, “but we do know that patients develop immunity, and if we can detect it through mass screening of the population, we’ll be able to ease restrictions.”
Preparing for the after-crisis
The availability of established technologies has helped companies move faster with Covid-19 diagnostic testing. Lessons learned from the 2002 SARS outbreak have guided the development of Covid-19 identification and detection solutions. Lessons learned during the Covid-19 outbreak will result in a call for more versatile diagnostic solutions to prevent and manage future epidemics.
Tools that provide accuracy, ease of use, and automation are essential for health professionals. The holy grail for diagnostics, Clerc noted, would be a small box capable of performing any kind of test in minutes. Such multimodal platforms could address immunoassays, clinical chemistry, cytometry, and molecular diagnostics with the same instrument, at the point of care.
Portability and affordability are also important. Only one instrument would be purchased to run hundreds of different tests, in parallel or not, on that platform. “Consider a doctor’s office or a pharmacy; there is usually not enough room for several instruments,” said Clerc. Extending the subject to pandemics affecting developing countries, he added that “it is not convenient to transport multiple machines and install them under a tent to perform different types of tests.” Companies such as Qorvo Biotechnologies, Bosch Healthcare, Truvian Sciences, and Boehringer Ingelheim Mobinostics are working on solutions to address those scenarios.
Once an automated platform has been developed, the next challenge is designing a cost-effective microfluidic cartridge able to run various types of tests on the same footprint. “A microfluidic cartridge is dedicated to one type of test, and different types of tests need to be developed,” said Clerc. “A company can develop two to three tests per year, but there are hundreds to develop.” That’s where collaborations and acquisitions make sense.
In the health-care industry, barriers on the road to success are high, and acquisitions are often the best solution to remain competitive. In the past decade, large diagnostics companies such as bioMérieux, Roche, and Qiagen have acquired promising microfluidic technologies through the purchase of small or mid-sized companies. Market consolidation has accelerated to the extent that a group of about 15 players now accounts for more than 75% of the market. “Large companies do not take the risk of technical development and prefer to invest in already-developed technologies,” said Clerc.
At the same time, an acquisition by a larger company can provide startups with an established distribution network and improved logistics support. IQuum (Roche), BioFire Diagnostics (bioMérieux), and STAT-Dx (Qiagen) are good examples of microfluidic technology developers whose approaches took off once the companies were acquired.
But collaboration remains the fastest way to develop microfluidic tests. Bosch Healthcare, for instance, has teamed with Randox Biosciences and R-Biopharm to develop tests to implement on its Vivalytic platform. “If we look ahead two or three years and if we reach a dozen partnerships, that’s potentially two or three additional tests per partnership per year,” said Clerc. “This is starting to provide an extended range of tests for users.”