Innovative Pain-Free Microneedle Patch with Unprecedented Sensitivity Can Test for Level of Antibodies Against COVID-19

A nearly pain-free microneedle patch developed by researchers can be applied to the skin, capture a biomarker of interest and, thanks to its unprecedented sensitivity, allow clinicians to detect the presence of antibodies that signal a viral or bacterial infection, such as SARS-CoV-2.

Engineers at the McKelvey School of Engineering at Washington University in St. Louis (St. Louis, MO, USA) have developed the technology which is 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. In addition to the low cost and ease of use, these microneedle patches are also entirely pain-free.

Oftentimes, doctors use blood samples to check for biomarkers of disease: antibodies that signal a viral or bacterial infection, such as SARS-CoV-2; 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 low abundance that makes it difficult to be detected. Finding a biomarker using 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 the cells in skin, which is called dermal interstitial fluid (ISF). Once the biomarkers have been captured, they are 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, conventional method generally requires extraction of ISF from 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.

To address the issue, the team used “plasmonic-fluors,” an ultrabright fluorescence nanolabel. 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. These patches have a host of qualities that can make a real impact on medicine, patient care and research. They would allow providers to monitor biomarkers over time, particularly important when it comes to understanding how immunity plays out in new diseases. For example, researchers working on COVID-19 vaccines who need to know if people are producing the right antibodies and for how long could use the patch to see whether a person has antibodies against COVID-19 and at what level. Also, EMTs could use a microneedle patch to test for troponin, the biomarker that indicates myocardial infarction, instead of having to get to the hospital and have blood drawn.

For people with chronic conditions that require regular monitoring, microneedle patches could eliminate unnecessary trips to the hospital, saving money, time and discomfort.

“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.”

“We’ll have to determine clinical cutoffs,” that is, the range of biomarker in ISF that corresponds to a normal vs. abnormal level,” said Srikanth Singamaneni, the Lilyan & E. Lisle Hughes Professor in the Department of Mechanical Engineering & Materials Sciences. “We’ll have to determine what levels of biomarker are normal, what levels are pathological.” And his research group is working on delivery methods for long distances and harsh conditions, providing options for improving rural healthcare.

“But we don’t have to do all of this ourselves,” added Singamaneni. “Instead, the technology will be available to experts in different areas of medicine. We have created a platform technology that anyone can use,” he said. “And they can use it to find their own biomarker of interest.”

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