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A new fluorescent sensor, derived from citric acid molecules, is highly sensitive and highly selective for chloride, the key diagnostic marker in cystic fibrosis.

The device detects salt concentrations in sweat or other bodily fluids. “Salt concentrations can be important for many health-related conditions,” says Jian Yang, professor of biomedical engineering at Penn State. “Our method uses fluorescent molecules based on citrate, a natural molecule that is essential for bone health.”

Compared to other methods used for chloride detection, the new material is much more sensitive to chloride and is able to detect it over a far wider range of concentrations—and is also sensitive to bromide, another salt that can interfere with the results of traditional clinical laboratory tests. Even trace amounts of bromide can throw off test results.

The citrate-based sensor makes it possible to distinguish the difference between chloride and bromide. The group is also working to establish a possible new standard for bromide detection in diagnosis of the disease.

Yang is collaborating with Zhiwen Liu, professor of electrical engineering to build a handheld device that can measure salt concentrations in sweat using his citrate-based molecules and a cell phone. This could be especially useful in developing countries where people have limited access to expensive analytical equipment.

“We are developing a platform material for sensing that is low cost, can be automated, requires no titration by trained staff or expensive instrumentation as in hospitals, and provides fast, almost instantaneous, results,” Liu says.

The findings, published in the journal Chemical Science, show that results using the citrate sensor were similar to those of the gold standard sweat test performed in a clinical laboratory.

“Beyond cystic fibrosis, our platform can also be used for many other diseases, such as metabolic alkalosis, Addison’s disease, and amyotrophic lateral sclerosis,” Yang says. “All of those diseases display abnormal concentrations of chloride in the urine, serum, or cerebral spinal fluid.”

Cystic fibrosis is a common genetic disease within the white population of the United States. The disease occurs in 1 in 2,500 to 3,500 white newborns. Cystic fibrosis is less common in other ethnic groups, affecting about 1 in 17,000 African Americans and 1 in 31,000 Asian Americans.

According to recommendations from the CF Foundation, based in Bethesda, Maryland, “all patients undergoing evaluation for possible diagnosis of CF should have sweat testing performed,” says Robert Vender, a pulmonary specialist who treats cystic fibrosis patients.

“To date, measurements of sweat chloride—in millimoles per liter—are only used for diagnostic purposes. However, given the recent scientific and medical advances in CF patient-directed therapy and the development and FDA approval of therapies specifically designed to modify cystic fibrosis transmembrane conductance regulator protein function, serial measurements of sweat chloride may have potential as a therapeutic surrogate indicator of drug effect and is currently measured in many pharmaceutical-industry sponsored studies as a response to these novel treatments. The link between the surrogate marker of sweat chloride and actual objective clinical outcomes such as improved lung function still remains to be determined.”

“Our citrate-based platform for designing fluorescent sensors provides us with great versatility in tailoring sensors to specific applications,” says lead author Jimin Kim, a graduate student in Yang’s lab. “We hope to produce more sensors with interesting applications in the near future.”

The National Institutes of Health and the National Science Foundation supported this work in part.

Source: Penn State