New Flow Control Technology Turns Simple COVID-19 Dipstick Tests into Complex Biomedical Assays

A team of researchers attempting to overcome the limitations of dipsticks have developed a flow control technology that can turn these simple tests into complex biomedical assays.

The researchers at the Georgia Institute of Technology (Atlanta, GA, USA) have applied the new technology in a toolkit to diagnose the novel coronavirus, as well as influenza. Lateral flow assays - LFAs, often called ‘dipsticks’ - have been a standard point-of-care testing platform for decades, and keep growing in popularity, especially in developing countries. These disposable, paper-based diagnostic devices are affordable, widely available, have a long shelf life, and they’re fast, typically delivering test results in less than 20 minutes. They’re also easy to use at home. The user adds a few drops of a sample - saliva, blood, or urine, for instance - to one end of the dipstick, and within minutes reads the results at the other end.

Image: Fully assembled liquid flow assay developed in the Sarioglu lab (Photo courtesy of Allison Carter)

The technology has been widely used to determine the presence or absence of biomarkers in humans, as well as contaminants in water or food. Most commonly, LFA technology is used for at-home pregnancy tests. And more recently, LFA technology has been used successfully in at-home tests for COVID-19. Recognizing the widespread popularity and practicality of dipsticks, particularly in resource-limited settings, the research team are overcoming those limitations with development of a flow control technology, turning these simple tests into complex biomedical assays.

LFAs utilize capillary liquid flow to detect analytes - capillary flow is the process of liquid passing through a narrow passageway (like a capillary); analytes are substances or chemicals of interest, such as an antibodies or proteins, in an analytical procedure (like an LFA). According to the researchers, conventional LFAs are not practical for performing multi-step assays - capillary flow prevents them from coordinating a complex process that includes the application of multiple reagents in a specific sequence with specific delays in between. In their recently published studies, the team describes 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.

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. The researchers have 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 researchers also tested 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 (severe respiratory syndrome-coronavirus 2) and/or influenza A and influenza B. A traditionally labor-intensive genetic assay can now be done on a disposable platform which will enable frequent, on-demand self-testing, thereby filling a critical need to track and contain outbreaks. The team is studying the technology’s application for other assays targeting other pathogens, with plans to publish in the coming months. The researchers are optimistic that the work will have implications in the current healthcare challenge with COVID-19, and beyond.

“We believe this flow technology research will have widespread impact,” said engineering researcher Fatih Sarioglu, who runs the Biomedical Microsystems Laboratory at the Georgia Institute of Technology. “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.”

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Georgia Institute of Technology