After getting the mice to generate IL-6, Singamaneni’s team could simply rinse off the patches and analyze them directly. They performed ultrasensitive diagnostic tests by mixing the microneedles with plasmon fluorine, a fluorescent dye solution containing nanoparticles designed to bind to IL-6. If these biomarkers were present, the glossy nanotags would adhere to them, causing the patch to glow.
The team reported that they were successful in tracking elevated IL-6 levels in their mice and detecting cytokine concentrations below 1 picogram per milliliter. It’s a millionth one millionth of one gram, per gram of water – 790 times more sensitive than without using plasmonic fluoride.
For diseases like malaria, in which a parasite releases specific proteins, doctors only need evidence of one type of biomarker to make a diagnosis. But you need more biomarkers to conclusively diagnose complex conditions such as cancer. Thus, the detection of IL-6 in mice was not so much a demonstration of a diagnosis as the proof that Singamaneni microneedles could measure biomarkers with extreme sensitivity.
According to Mousavi, the advance opens a door for the young estate. “Now we can actually use this tool to understand what’s going on with the interstitial fluid and how we’re going to be able to use it to address health or medical issues,” she says. “I think this has the potential to be a game changer.”
“I was surprised,” says Xue Jiang, a mechanical engineer at Rice University not involved in the study, who is developing microneedles. to detect malaria infections in economically developing countries like Malawi. “It’s amazing that they can improve the detection limit so much.”
While Mousavi applauds the combination of micro-needles and plasmonic fluorides as an important tool, she and Jiang both point out that the technology still relies on laboratory equipment to analyze the biological premium of the matrix. Laboratory testing reduces accessibility in low-income areas, compared to inexpensive home testing. “It would be so cool if there was a way to actually eliminate this laboratory need,” Mousavi says.
Prausnitz and Singamaneni also imagine that one day the process of analyzing biomarker measurements from the tables could be automated for home use by anyone following chronic disease. “So no expertise is needed to operate it,” Prausnitz says. “Put the patch on, take it off, stick it in the device.”
Prausnitz notes that Singamaneni’s technology is still in its infancy, but he is cautiously optimistic about what that might mean for his own work. Although he was not involved in this study, the two plan to collaborate on an accessible diagnosis of tuberculosis, which kills more than a million people a year.
And in the home state of Singamaneni, Andhra Pradesh, India, a mysterious chronic kidney disease called Uddanam nephropathy is endemic. This gave him a personal connection with the mission of simpler, faster and more precise diagnoses; he hopes that one day accessible biosensors will help people keep tabs on their kidney condition like others do with diabetes. “Maybe people can actually take the intervention that is needed to minimize the loss of kidney function and, of course, the loss of life,” he says. (His team is currently adapting their range to search for biomarkers relevant to kidney disease.)
Still, Prausnitz acknowledges, the interstitial fluid remains a somewhat mysterious stew. It will be necessary to link diseases to specific biomarkers – and their concentrations in the skin – before the technology can move from the lab to the homes.
“We cannot do this for all diseases, all biomarkers,” Singamaneni admits. “But at least if we firmly establish the methodology, we hope that others can actually take advantage of it and apply it to their own biomarkers, their diseases of interest.
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