Fluorescent Sensor May Offer Quick But Reliable Way of Diagnosing CF Based on Salt in Sweat

Penn State researchers developed a fluorescent sensor able to easily and accurately detect salt concentrations in the sweat or other bodily fluids. Based on citric acid molecules, the sensor is highly sensitive and selective for chloride, the main diagnostic marker for cystic fibrosis (CF), and may enable rapid and low-cost point-of-care diagnostics that can be translated into clinical settings.

“Salt concentrations can be important for many health-related conditions,” said Jian Yang, a professor of biomedical engineering and the lead study author, in a news release. “Our method uses fluorescent molecules based on citrate, a natural molecule that is essential for bone health.”

The findings were reported in the article, “Citrate-based fluorescent materials for low-cost chloride sensing in the diagnosis of cystic fibrosis,” published in the journal Chemical Science.

Chloride is an essential electrolyte that maintains homeostasis within the body, but is found in abnormal levels in people with diseases such as CF. Current analytical approaches for chloride detection fail to meet the clinical needs of both high performance and low material or labor costs, hindering their use by clinicians.

In contrast, the new citrate-based fluorescent sensor is able to identify chloride in a wide range of concentrations, and  is also sensitive to bromide, another salt that, even in extremely low concentrations, can interfere with laboratory results.

Using the sensor, researchers were able to distinguish differences between chloride and bromide, and are now working to possibly establish a new standard for bromide detection in the diagnosis of CF.

Yang, working alongside Professor Zhiwen Liu, a Penn State electrical engineer, is also trying to build a highly portable, handheld device for measuring salt concentrations in sweat.

“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,” said Yang.

Researchers compared CF diagnosis made using the new fluorescence chloride sensors approach to those made using the traditional sweat test performed in a clinical laboratory, and found that results were similar.

The importance of accurate, quick and easy determinations of sweat chloride levels in patients cannot be underestimated. “According to recommendations from the CF Foundation …  all patients undergoing evaluation for possible diagnosis of CF should have sweat testing performed. To date, measurements of sweat chloride (mmol/L) are only used for diagnostic purposes,” said Robert Vender, MD, a pulmonary specialist at Penn State Milton S. Hershey Medical Center, who treats CF patients. “Given the recent scientific and medical advances in CF patient directed therapy … measurements of sweat chloride may have potential as a therapeutic surrogate indicator of drug effect.”

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