Blood draws are no fun.
They hurt. Veins can burst, or even roll -- like they're trying to avoid the needle, too.
Oftentimes, doctors use blood samples to check for biomarkers of disease: antibodies that signal a viral or bacterial infection, such as SARS-CoV-2, the virus responsible for COVID-19; or cytokines indicative of inflammation seen in conditions such as rheumatoid arthritis and sepsis.
These biomarkers aren't just in blood, though. They can also be found in the dense liquid medium that surrounds our cells, but in a low abundance that makes it difficult to be detected.
Engineers at the McKelvey School of Engineering at Washington University in St. Louis have developed a microneedle patch that can be applied to the skin, capture a biomarker of interest and, thanks to its unprecedented sensitivity, allow clinicians to detect its presence.
The technology is a low cost, easy for a clinician or patients themselves to use, and could eliminate the need for a trip to the hospital just for a blood draw.
The research, from the lab of Srikanth Singamaneni, the Lilyan & E. Lisle Hughes Professor in the Department of Mechanical Engineering & Material Sciences, was published online on Jan. 22 in the journal Nature Biomedical Engineering.
In addition to the low cost and ease of use, these microneedle patches have another advantage over blood draws, perhaps the most important feature for some: "They are entirely pain-free," Singamaneni said.
Finding a biomarker using these microneedle patches is similar to blood testing. But instead of using a solution to find and quantify the biomarker in blood, the microneedles directly capture it from the liquid that surrounds our cells in the skin, which is called dermal interstitial fluid (ISF). Once the biomarkers have been captured, they're detected in the same way -- using fluorescence to indicate their presence and quantity.
ISF is a rich source of biomolecules, densely packed with everything from neurotransmitters to cellular waste. However, to analyze biomarkers in ISF, the conventional method generally requires the extraction of ISF from the skin. This method is difficult and usually, the amount of ISF that can be obtained is not sufficient for analysis. That has been a major hurdle for developing microneedle-based biosensing technology.
Another method involves direct capture of the biomarker in ISF without having to extract ISF. Like showing up to a packed concert and trying to make your way up front, the biomarker has to maneuver through a crowded, dynamic soup of ISF before reaching the microneedle in the skin tissue. Under such conditions, being able to capture enough of the biomarker to see using the traditional assay isn't easy.
But the team has a secret weapon of sorts: "plasmonic-fluors," an ultrabright fluorescence nano label. Compared with traditional fluorescent labels, when an assay was done on microneedle patch using plasmonic-fluor, the signal of target protein biomarkers shined about 1,400 times as bright and become detectable even when they are present at low concentrations.
"Previously, concentrations of a biomarker had to be on the order of a few micrograms per milliliter of fluid," Zheyu (Ryan) Wang, a graduate student in the Singamaneni lab and one of the lead authors of the paper, said. That's far beyond the real-world physiological range. But using plasmonic-fluor, the research team was able to detect biomarkers on the order of picograms per milliliter.
"That's orders of magnitude more sensitive," Ryan said.
These patches have a host of qualities that can make a real impact on medicine, patient care, and research.
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