A new, cost-effective technique for identifying salt concentrations in sweat or various other bodily fluids has been developed by Penn State biomaterials scientists. The fluorescent sensor, obtained from citric acid molecules, is highly sensitive and extremely selective for chloride, which is the chief diagnostic marker in cystic fibrosis.
Naturally fluorescing polymer nanoparticles can be used to detect a key marker of cystic fibrosis. Image: Yang Lab / Penn State
Salt concentrations can be important for many health-related conditions. Our method uses fluorescent molecules based on citrate, a natural molecule that is essential for bone health.
Jian Yang, professor of biomedical engineering
When compared to several other techniques used for detecting chloride, Yang's citrate-based fuorescent material seems to be a lot more sensitive to chloride and is also capable of detecting it even across a much wider range of concentrations. This new material is also sensitive to bromide, which is another variety of salt that can hamper with the results of standard clinical laboratory tests. Yang's group will be able to differentiate between bromide and chloride with the help of the citrate-based sensor. The group is also working towards developing a possible new technique for bromide detection diagnosis of the disease.
Yang is working in partnership with Penn State electrical engineer professor Zhiwen Liu to develop a handheld device capable of measuring salt concentrations in sweat by using a cell phone and his citrate-based molecules. This will be especially ideal for use 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.
In "Citrate-based fluorescent materials for low-cost chloride sensing in the diagnosis of Cystic Fibrosis," which was recently published online in Chemical Science, Yang highlighted a comparison between their citrate sensors and the gold standard sweat test executed in a clinical laboratory. Similar results were obtained.
Beyond cystic fibrosis, our platform can also be used for many other diseases, such as metabolic alkalosis, Addison's disease, and amyotrophic lateral sclerosis. All of those diseases display abnormal concentrations of chloride in the urine, serum or cerebral spinal fluid.
The U.S. National Library of Medicine highlights that cystic fibrosis is considered to be a common genetic disease existing in the white population of the United States. The disease is present in 1 in 2,500 to 3,500 white newborns. The occurrence of cystic fibrosis in other ethnic groups is less, affecting about 1 in 17,000 African Americans and 1 in 31,000 Asian Americans.
According to recommendations from the CF Foundation, Bethesda, MD, all patients undergoing evaluation for possible diagnosis of CF should have sweat testing performed. 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.
Robert Vender, a pulmonary specialist at Penn State Health Milton S. Hershey Medical Center who treats cystic fibrosis patients.
Jimin Kim, lead author and a graduate student in Yang's lab, said,
"Our citrate-based platform for designing fluorescent sensors provides us with great versatility in tailoring sensors to specific applications. We hope to produce more sensors with interesting applications in the near future"
Other contributors of the work include Yang's former postdoctoral fellow Zhiwei Xie and Michael Creer, professor in the Penn State College of Medicine and chief of clinical pathology, Yang's colleague, Chris Pederson, who verified the results in the clinical laboratory.
The National Science Foundation and the National Institutes of Health supported this research in part.