Popularly known as ‘dipsticks’, lateral flow assays (LFAs) have long been a standard point-of-care testing system, and continue to grow in popularity, especially in developing countries.
These disposable, paper-based diagnostic devices are inexpensive, readily available, have a long shelf life, and they’re fast, typically delivering results in under 20 minutes. They’re also easy to use at home, most commonly for pregnancy tests but also now for COVID.
“These tests have been extremely popular for years, mainly because they are so simple to use. You don’t send anything to the lab or clinic because these tests don’t require any external equipment to operate. This is an advantage,” said engineering researcher Fatih Sarioglu at the Georgia Institute of Technology. “But there also is a disadvantage. There are limitations to what they can do.”
Sarioglu and his team are overcoming the limitations of LFAs with development of a flow control technology, turning these simple tests into complex biomedical assays.
Their research is outlined in two papers in Science Advances and ACS Sensors. One explains the development of their technology and the other applies the technology in a toolkit to diagnose SARS-CoV-2, as well as influenza.
LFAs make use of capillary liquid flow to detect analytes. Sarioglu explained that conventional LFAs are not practical for performing multi-step assays – capillary flow precludes them from coordinating a complex process involving the application of multiple reagents in a specific sequence with specific delays in between.
The researchers describe a technique to control capillary flow by imprinting roadblocks on a laminated paper with water insoluble ink. The blocked liquid flow is thus manipulated into a void formed at the interface of the ink-infused paper and the polymer tape laminate. By modifying the roadblocks, the researchers can essentially set the time it takes for a void to form – creating timers that hold capillary flow for a desired period.
“By strategically imprinting these timers, we can program the assays to coordinate different capillary flows,” said Sarioglu, professor in the School of Electrical and Computer Engineering. “That enables multiple liquids to be introduced, and multistep chemical reactions, with optimal incubation times – so, we can perform complex, automated assays that otherwise would normally have to be performed in laboratories. This takes us beyond the conventional LFA.”
For the user, the new dipstick test works the same way as the reliable standard – a sample is added at one end and the results present themselves minutes later in living color(s) at the other end. Sarioglu and his colleagues simply enhanced and expanded the process in between.
Basically, they drew patterns on paper – a dipstick – and created immunoassays that rival other diagnostic tests requiring labs and extra equipment, in the effective detection of pathogenic targets like Zika virus, HIV, hepatitis B virus, or malaria, among others.
The paper in ACS Sensors describes a PCR-based point-of-care toolkit based on the lab’s flow technology. The assay is programmed to run a sequence of chemical reactions to detect SARS-CoV-2 and/or influenza A and influenza B. A traditionally labour-intensive genetic assay can now be done on a disposable platform which will enable frequent, on-demand self-testing, filling a critical need to track and contain outbreaks.
The lab is studying the technology’s application for other assays targeting other pathogens, with plans to publish in the coming months. Sarioglu is optimistic about the work’s potential.
“We believe this flow technology research will have widespread impact,” he said. “This kind of dipstick test is so commonly used by the public for biomedical testing, and now it can be translated into other applications that we do not traditionally consider to be cut out for these simple tests.”
Source: Georgia Institute of Technology