A soft, flexible device that sticks on skin to capture sweat and measure sweat chloride may help doctors diagnose cystic fibrosis in infants, according to new data published online March 31 in Science Translational Medicine. But not everyone is convinced the device is the right approach for an important clinical diagnosis.
That said, the technology might also be used to help clinicians monitor how older patients with cystic fibrosis respond to treatment and allow for sweat testing outside of clinical settings, the researchers suggest.
Known as a microfluidic sweat sticker, the device may have advantages in terms of cost, comfort, and reliability in collecting enough sweat, relative to rigid collection systems, said senior study author John A. Rogers, PhD, director of the Querrey Simpson Institute for Bioelectronics at Northwestern University in Evanston, Illinois.
Rogers and colleagues compared the sweat sticker to the Macroduct Sweat Collection System, a rigid device currently used for sweat tests. They conducted sweat testing with both devices in 51 children and adults aged 2 months to 51 years, once on each arm. Thirty-three of the participants had cystic fibrosis.
For each test, pilocarpine iontophoresis initiated a sweat response, and sweat collection took about 30 minutes. On average, the sweat sticker collected 74 µl of sweat, whereas the Macroduct system collected 58 µl. In three instances, the Macroduct system did not collect enough sweat for testing.. No such instances occurred with the sweat sticker.
In addition, the results indicate that the sweat sticker and commercial chloridometers can provide comparable accuracy in assessing sweat chloride, the researchers report.
Although sweat testing is well established, there are challenges with existing, rigid devices, commented Aaron S. Chidekel, MD, director of the Cystic Fibrosis Care Center at Nemours/Alfred I. duPont Hospital for Children in Wilmington, Delaware.
“It is hard to get that gadget, which is kind of like a wristwatch, around the wrist of a wiggly baby and then keep a tight enough seal for 30 minutes,” said Chidekel, who was not involved in the research.
Even under ideal circumstances, the device sometimes does not collect enough sweat, he said.
“That is a challenge for the family, as you can imagine, because cystic fibrosis is a scary concept for new parents,” Chidekel told Medscape Medical News. Newborn screening for cystic fibrosis may have a high rate of false positives, and when screening indicates that a child might have cystic fibrosis, it is important to conduct a sweat test to resolve the uncertainty and start treatment, if necessary, as soon as possible, he said.
“Anything that can improve the timeliness, accuracy, and simplicity of the diagnosis of cystic fibrosis, particularly in very young babies, is an important advance, and this device looks pretty promising,” Chidekel said. It also appears “patient friendly,” he noted.
Similar to a Gatorade Patch
The sweat sticker technology is similar to that used in a new Gatorade product, Gx Sweat Patch, which was designed to provide athletes with information about their sweat rate and sodium composition, Rogers said. A company that Rogers cofounded, Epicore Biosystems, developed the product with Gatorade after Rogers and colleagues described the underlying microfluidic technology in 2016.
While Gatorade saw a way to optimize hydration, others saw possible medical applications.
Susanna McColley, MD, a pediatric pulmonologist at Lurie Children’s Hospital and Northwestern Medicine and a coauthor on the new study, reached out about using the technology in cystic fibrosis, Rogers said. With this genetic disorder, the concentration of chloride in sweat is “the most robust biomarker for confirmatory diagnosis,” the researchers note.
The sweat sticker was a natural fit for measuring this biomarker, Rogers said.
“Sweat is piped into a very small circular reservoir where we have preloaded a chemical acid that changes in color by an amount determined by the concentration of the chloride,” Rogers said. “And so then you just take a digital picture of the device.”
Imaging technology quantitatively determines the color, which indicates the chloride concentration.
Rogers has led research programs that focus on the development of electronic biosensors that can integrate with the human body. When their efforts turned to biochemical signatures of health, they focused on sweat.
“The natural instinct would be to try to figure out how to get access to blood or interstitial fluid,” but those approaches require some degree of penetration of the skin, Rogers said. Sweat can be obtained noninvasively and reveal information about glucose, lactate, vitamin C, iron, zinc, calcium, and chloride, for example.
They developed ways to embed tiny channels, valves, and reservoirs in flexible platforms that can adhere to the surface of the skin to capture sweat as it emerges from the surface. “The channel structures and these tiny reservoirs are being produced using the same technologies that are used in the semiconductor manufacturing industry,” he said.
Leave Testing to the Labs?
The device is comparable to the current sweat testing system but might not be a better option, said Robert J. Giusti, MD, founder and director of the Pediatric Cystic Fibrosis Center, which is part of Hassenfeld Children’s Hospital at NYU Langone in New York City.
“Sweat testing is a complex procedure that is best performed at a cystic fibrosis care center” with appropriate quality control, Giusti said. “I am concerned that insurance companies will prefer a sweat collection that is cheap and done in a non-CF care center to save money.”
In addition, the study may overstate the need for ongoing sweat testing of patients with cystic fibrosis, as well as the limitations of current tests, Giusti said. “It is true that young infants can occasionally not produce adequate sweat collection, but this problem is overcome in 1 to 2 weeks as the baby gets older,” he said.
Whether sweat stickers could reduce the frequency of this issue requires further study, he said. “This device will need rigorous verification and validation before such a statement can be made.”
Larger studies are needed, particularly in younger patients with various cystic fibrosis conditions, birth weights, and hydration states, the study authors note. It also is necessary to test the color analysis technology in environments with uneven lighting, which could affect accuracy, they add.
Although further verification and regulatory approval are needed, trends point toward more healthcare happening at home, Rogers said. To that end, future research may evaluate whether a warm bath or shower could induce sufficient sweat and avoid the need for pilocarpine iontophoresis.
“I think that’s where healthcare is going to happen more and more, that is pretty clear,” he said. “It just needs to be done super carefully.”
The study was supported by the Querrey Simpson Institute for Bioelectronics at Northwestern University, the University of Hawaii at Manoa, the Hawaii Community Foundation, Ann & Robert H. Lurie Children’s Hospital, Stanley Manne Research Institute, Northwestern Memorial Hospital, and the National Institutes of Health. 3M provided access to adhesive materials used in the research.
Rogers and first study author Tyler R. Ray, PhD, are inventors on patents and patent applications related to epidermal microfluidics, including applications in cystic fibrosis diagnostics. Rogers and several coauthors are cofounders of Epicore Biosystems, a company that develops epidermal microfluidic devices, including the Gatorade patch. Ray has ties to the company. Chidekel and Giusti have disclosed no relevant financial relationships.
Sci Transl Med. Published online March 31, 2021. Abstract