By Deborah Borfitz
November 24, 2020 | A pair of researchers at Rice University have developed a disposable, microneedle-based biosensing platform capable of detecting malaria infection from protein biomarkers in dermal interstitial fluid. The system not only eliminates the need for finger pricks or blood draws, but also requires no manual processing and has no electronic components—making it potentially well-suited to resource-limited settings, as a point-of-care test performed at doctors’ offices and health clinics, and as a screening tool for home use by the general public.
So says Peter Lillehoj, associate professor of mechanical engineering at Rice University and co-author of a proof-of-concept study on the bandage-like device that published in Microsystems and Nanoengineering (DOI: 10.1038/s41378-020-00206-1). Its co-developer is Xue Jiang, a Rice postdoctoral researcher.
The idea is this: A sticky patch gets applied to the forearm, where dermal interstitial fluid flows in through 16 hollow microneedles shallowly penetrating the skin. If an embedded antibody-based lateral-flow test strip senses the protein biomarker for malaria, Plasmodium falciparum histidine-rich protein 2 (PfHRP2), two readout lines turn red to indicate a positive result, Lillehoj explains.
One of the two lines serves as a control to verify the test was performed correctly and the device is functioning properly, he says. If only the control line is red, that’s a confirmed negative result.
In the recent study, the device detected PfHRP2 at concentrations as low as 8 ng/mL, Lillehoj notes. Each test can be completed in under 20 minutes.
The device was tested on porcine cadavers, since pig skin is anatomically and biochemically similar to human skin, Lillehoj says. Specificity testing involved measurements with samples spiked with other biomarkers for malaria to verify that they did not generate a positive result.
Clinical testing in patients is planned once the concentration of PfHRP2 in the interstitial fluid of malaria patients is determined. Sensitivity and specificity testing will be compared to the gold standard enzyme-linked immunosorbent assay test for the PfHRP2 biomarker. Lillehoj says he expects taking measurements of the biomarker in humans to be less challenging than in the previously frozen pig cadavers.
The researchers applied the device to their own forearms to conclude it delivered a relatively pain-free test, “like putting tape on your skin and then peeling it off,” says Lillehoj. Prior studies have also found that the size and tip geometry of the microneedles used in the device have been associated with pain levels of one-fourth to one-tenth that of a finger prick or a traditional hypodermic needle.
Testing Options
Only in the past decade has the diagnostic potential of interstitial fluid been recognized and actively explored, says Lillehoj. It will likely take a few years for clinic-ready tests to start emerging, especially if there is already an established alternative based on the collection of blood, saliva, urine, or other bodily fluid.
But interstitial fluid is known to contain a large diversity of proteins and metabolites, much like what is found in blood serum. Multiple researchers have demonstrated that glucose is detectable at similar levels in interstitial fluid and blood, for example, which Lillehoj expects will translate into new testing options for diabetics in the near future.
Perhaps more immediately, the new disposable patch could be adapted to detect COVID-19, he adds. If it turns out that the novel coronavirus behaves like the seasonal flu, such tests would be needed indefinitely.
In general, biomarkers in interstitial fluid for specific infectious diseases are not well understood, he continues. But ultimately, the microneedle-based skin patch could be a modality for the differential diagnosis of malaria and another infectious disease with similar symptoms. Its test strip would only need a third readout line.
Lateral flow strips typically look at one disease-specific biomarker using a single test strip, and occasionally two or three simultaneously. The main concern is the added complexity in interpreting results with more readout lines, particularly in resource-limited settings, says Lillehoj.
Rapid diagnostic tests such as the microneedle-based patch can be manufactured in bulk quantities for less than a dollar a piece, he says, which is an important consideration in developing countries. The actual market price will of course depend on the target audience, but even with a reasonable markup should not cost more than a few dollars per test.