Low-Cost Sensor Developed for Cystic Fibrosis Diagnosis and Monitoring

Biomaterials scientists have developed an inexpensive method for detecting salt concentrations in sweat or other bodily fluids with a fluorescent sensor derived from citric acid molecules. The sensor is highly sensitive and highly selective for chloride, the key diagnostic marker in cystic fibrosis (CF).

"Salt concentrations can be important for many health-related conditions," said team leader Jian Yang, professor at Penn State University (University Park, PA, USA), "Our method uses fluorescent molecules based on citrate, a natural molecule that is essential for bone health." Compared to other chloride detection methods, the citrate-based fluorescent material is much more sensitive to chloride and can detect it over a far wider range of concentrations.

In the new study, the citrate-based sensor was compared in a clinical lab against the gold standard sweat test – the results from both were found to be similar.

The new material is also sensitive to bromide, which even in trace amounts can interfere with the results of traditional clinical laboratory tests. With the citrate-based sensor, Prof. Yang's group can distinguish between chloride and bromide. The group is also working to establish a possible new standard for bromide detection in diagnosis of the disease.

In collaboration with Penn State electrical engineer Prof. Zhiwen Liu, the team is building a handheld device that can measure salt concentrations in sweat using the citrate-based material and a cell phone, which could be especially useful in areas with 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," said Prof. Liu.

"Beyond CF, 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," said Prof. Yang.

"According to recommendations from the CF Foundation (Bethesda, MD; USA) all patients undergoing evaluation for possible diagnosis of CF should have sweat testing performed," said Robert Vender, a pulmonary specialist at Penn State Health Milton S. Hershey Medical Center, "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 CF 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."

Jimin P. Kim, lead author and Yang lab graduate student, 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"

The study, by Kim JP et al, was published online August 30, 2016, in the journal Chemical Science.

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