No more diagnostic needles for testing? Engineers develop an almost painless micro-needle patch

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Engineers at the McKelvey School of Engineering at Washington University in St. Louis have developed a needle patch that can be applied to the skin to capture a biomarker of interest from the interstitial fluid and allow clinicians to detect its presence with unprecedented sensitivity. Credit: Sisi Cao

The almost painless micro-needle patch can find antibodies and more in the liquid between the cells.

Blood draws are not fun.

They hurt. The veins can explode, or they can even roll, just as they are trying to avoid the needle.

Doctors often use blood samples to find biomarkers of disease: antibodies that indicate a virus or bacterial infection, such as SARS-CoV-2, responsible for the virus COVID-19, or cytokines that are indicative of inflammation seen in situations such as rheumatoid arthritis and sepsis.

These biomarkers are not only in the blood. They can also be found in the dense liquid medium that surrounds our cells, but in the small abundance that makes detection difficult.

So far.

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, with unprecedented sensitivity, allowed clinicians to detect its presence.

The technology is low cost, easy to use by clinicians or patients themselves, and could eliminate the need to travel to the hospital to draw blood.

The research, by Srikanth Singamaneni, Lilyan & E. Lisle Hughes, a professor in the Department of Mechanical Engineering and Materials Science, was published online on January 22, 2021, in the journal. Biomedical Engineering of Nature.

In addition to their low cost and ease of use, these micro-needle patches have another advantage over blood draw, perhaps the most important feature for some: “They are almost painless,” Singamaneni said.

Finding a biomarker using these micro-needle patches is similar to blood tests. Instead of using a solution to find and quantify a blood biomarker, microneedles capture it directly from the fluid that surrounds our cells in the skin, which is the interstitial skin fluid (ISF). Once the biomarkers are captured, they are detected in the same way, using fluorescence to indicate their presence and quantity.

ISF is a rich source of biomolecules, packed densely from neurotransmitters to cell debris. However, in the study of ISF biomarkers, conventional methods typically require the extraction of ISF from the skin. This method is difficult and the number of ISFs that can normally be obtained is not sufficient for the study. This has been a major obstacle to the development of biosensitivity technology based on microneedles.

Another method involves capturing the biomarker directly in the ISF without having to extract the ISF. Like presenting to a crowded concert and trying to deal with it, the biomarker has to maneuver through a crowded and dynamic ISF soup before it reaches the skin’s micro-scratches. Under such conditions, it is not easy to capture enough biomarkers using traditional testing.

But the group has some sort of secret weapon: “plasmonic fluoride,” an ultra-light fluorescence nanotag. Compared to traditional fluorescent labels, when a study was performed using plasmonic fluorine on a microneedle patch, the signal of the target biomarker proteins had a brightness greater than 1,400 times the brightness and can be detected even when they are in low concentrations.

“Previously, the concentrations of a biomarker had to be in the order of a few micrograms per milliliter of fluid,” said Zheyu (Ryan) Wang, a graduate of Singamaneni Laboratory and one of the lead authors of the paper. That is beyond the physiological range of the real world. But using plasmonic fluoride, the research team was able to detect biomarkers in the order of picograms per milliliter.

“That’s a more sensitive order of magnitude,” Wang said.

These patches have a number of characteristics that can have a real impact on medicine, patient care, and research.

Providers will be able to control biomarkers over time, which is especially important when it comes to understanding how immunity behaves in new diseases.

For example, researchers working with COVID-19 vaccines need to know if people are producing the right antibodies and for how long. “Let’s put a patch on it,” Singamaneni said, “and let’s see if that person has antibodies against COVID-19 and at what level.”

Or in emergencies, “when someone complains of chest pain and is taken to the hospital by ambulance, we hope that the patch can be applied at that time,” said Jingyi Luan, a recently graduated student. Singamaneni from the lab and one of the main authors of the article. Instead of having to go to the hospital and draw blood, EMTs can use a microneedle patch to study troponin, a biomarker that indicates myocardial infarction.

For people with chronic illnesses that require regular monitoring, micro-needle patches can eliminate unnecessary trips to the hospital, saving you money, time, and discomfort – a lot of discomfort.

The patches are almost painless. “About 400 microns penetrate the skin tissue,” Singamaneni said. “They don’t even touch the sensory nerves.”

In the laboratory, the use of this technology may limit the number of animals required for research. Sometimes research requires several measurements in a row to detect the flow and discharge of biomarkers, for example, to monitor the progression of sepsis. Sometimes that means a lot of small animals.

“We could significantly reduce the number of animals needed for these studies,” Singamaneni said.

The implications are huge – and Singamaneni’s lab wants to make sure they are all studied.

There is a lot of work to be done, he said: “We will need to determine the clinical incisions,” which is the level of biomarkers in the ISF, both normal and abnormal. “We need to determine what levels of biomarkers are normal, what levels are pathological.” And his research team is working on methods for long-distance delivery and harsh conditions, offering opportunities to improve rural health.

“But we don’t have to do all of that ourselves,” he told Singamanen. Instead, it will be available to experts in different fields of medicine.

“We have created platform technology that anyone can use,” he said. “And they can use it to find their own biomarker of interest.”

We don’t have to do all this ourselves

Singamaneni and Erica L. Scheller, assistant professors of medicine in the Division of Bone and Mineral Diseases at the School of Medicine, worked together to investigate the concentration of biomarkers in local tissues.

The current approach to this assessment requires the isolation of local tissues and does not allow for continuous and continuous inspection. Singamaneni and Scheller are developing a better platform for long-term monitoring of local biomarker concentration.

Working together

Srikanth Singamaneni, Lilyan E. Lisle Hughes Professor of Mechanical Engineering and Materials Science and Jai S. Rudra, an assistant professor in the Department of Biomedical Engineering, worked together to study cocaine vaccines, which work by blocking the ability of cocaine. into the brain.

Current candidates for this vaccine do not provide lasting results; they often require encouragement. Singamanenik and Rudra wanted a better way to determine when the effects of the vaccine diminished. “We have shown that we can use patches to understand whether people are still producing the necessary antibodies,” he told Singamaneni. “There’s no need to draw blood.”

References: Zheyu Wang, Jingyi Luan, Anushree Seth, Lin Liu, Minli You, Prashant Gupta, Priya Rathi, Yixuan Wang, Sisi Cao, Qisheng Jiang, Xiao Zhang. Rohit Gupta, Qingjun Zhou, Jeremiah J. Morrissey, Erica L. Scheller, Jai S. Rudra and Srikanth Singamaneni, January 22, 2021, Biomedical Engineering of Nature.
DOI: 10.1038 / s41551-020-00672-y

This research was supported by the National Science Foundation (CBET-1900277) and the National Institutes of Health (R01DE027098, R56DE027924, R01CA141521, R21DA036663, R21CA236652).

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