Blood draw is not fun.
They hurt. Veins can burst, or even roll – like trying to avoid the needle as well.
Doctors often use blood samples to look for biomarkers of diseases: antibodies that indicate a viral or bacterial infection, such as SARS-CoV-2, the virus responsible for COVID-19, or cytokines that indicate inflammation seen in conditions such as rheumatoid arthritis. and sepsis.
However, these biomarkers do not just lie in blood. They can also be found in the dense liquid medium that surrounds our cells, but in a low amount that makes it difficult to be detected.
Until now.
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SingamaneniEngineers at the McKelvey School of Engineering at Washington University in St. Louis. Louis, has developed a microneedle stain that can be applied to the skin, capture an interesting biomarker and, thanks to unprecedented sensitivity, allow clinicians to detect its presence.
The technology is inexpensive, easy for clinicians or patients to use, and it can eliminate the need for a trip to the hospital, just for blood supply.
The research from the laboratory of Srikanth Singamaneni, the Lilyan & E. Lisle Hughes Professor in the Department of Mechanical Engineering and Materials Science, was published online on January 22 in the journal Nature Biomedical Engineering.
In addition to the low cost and ease of use, these microneedle stains have another advantage over blood draws, perhaps the most important feature of some: ‘They are almost painless,’ Singamaneni said.
It is similar to blood testing to find a biomarker using these microneedle stains. But instead of using a solution to find and quantify the biomarker in blood, the microneedles capture it directly from the fluid that surrounds our cells in the skin, 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 debris. To analyze biomarkers in ISF, it is usually necessary for ISF to be extracted from the skin by the conventional method. This method is difficult and usually the amount of ISF that can be obtained is not sufficient for analysis. This was a major obstacle to the development of microneedle-based biosensation technology.
Another method involves direct incorporation of the biomarker into ISF without withdrawing ISF. Like showing up at a packed concert and trying it out, the biomarker has to maneuver through a crowded, dynamic soup of ISF before it reaches the microneedle in the skin tissue. In such circumstances, it is not easy to capture enough of the biomarker to see how the traditional test is used.
But the team has a secret weapon of sorts: ‘plasmonic fluorine’, an ultra-bright fluorescence nanolabel. Compared to traditional fluorescent labels, when a test was done on a microneedle stain with plasmonic fluorine, the signal from protein biomarkers shone about 1400 times as bright and perceptible, even when present at 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 student in the Singamaneni Laboratory and one of the lead authors of the article. This is far beyond the physiological scope of the real world. But using plasmonic fluorine, the research team was able to detect biomarkers in the order of picograms per milliliter.
“It’s more sensitive,” Wang said.
These spots have a number of characteristics that can have a significant impact on medicine, patient care and research.
This will allow providers to monitor biomarkers over time, especially when it comes to understanding immunity in new diseases.
For example, researchers working on COVID-19 vaccines need to know if humans are producing the right antibodies and for how long. “Let’s put a patch on,” Singamaneni said, “and let’s see if the person has antibodies against COVID-19 and at what level.”
Or in an emergency: “If someone complains of chest pain and they are taken to the hospital in an ambulance, we just hope every now and then, the patch can be applied,” said Jingyi Luan, a student who has just graduated, said. of the Singamaneni Laboratory and one of the principal authors of the paper. Instead of having to go to the hospital and have blood drawn, EMTs can use a microneedle stain to test for troponin, the biomarker that indicates myocardial infarction.
For people with chronic conditions that need to be monitored regularly, microneedle patches can eliminate unnecessary trips to the hospital, saving money, time and inconvenience – a lot of inconvenience.
The spots are almost painless. “They go about 400 microns deep into the intestinal tissue,” Singamaneni said. “They do not even touch nerves.”
In the laboratory, the use of this technology can limit the number of animals needed for research. Sometimes research requires several consecutive measurements to capture the ebb and flow of biomarkers – for example, to monitor the progression of sepsis. Sometimes it means very small animals.
“We can significantly reduce the number of animals required for such studies,” Singamaneni said.
The implications are huge – and Singamaneni’s laboratory wants to make sure it’s all investigated.
There is a lot of work to be done, he said: ‘We need to determine clinical cut-off points,’ the range of biomarkers in ISF that correspond to a normal versus abnormal level. “We will have to determine which levels of biomarker are normal, which levels are pathological.” And its research team is working on delivery methods for long-distance and difficult conditions, and offers options for improving rural health care.
“But we do not have to do all this ourselves,” Singamaneni said. Instead, the technology will be available to experts in various medicines.
“We’ve created a platform technology that everyone can use,” he said. “And they can use it to find their own biomarker of interest.”