title: Citrate-based fluorescent materials for low-cost chloride sensing in the diagnosis of Cystic Fibrosis.
abstract: Chloride is an essential electrolyte that maintains homeostasis within the body, where abnormal chloride levels in biological fluids may indicate various diseases such as Cystic Fibrosis. However, current analytical solutions for chloride detection fail to meet the clinical needs of both high performance and low material or labor costs, hindering translation into clinical settings. Here we present a new class of fluorescence chloride sensors derived from a facile citrate -based synthesis platform that utilize dynamic quenching mechanisms. Based on this low-cost platform, we demonstrate for the first time a selective sensing strategy that uses a single fluorophore to detect multiple halides simultaneously, promising both selectivity and automation to improve performance and reduce labor costs. We also demonstrate the clinical utility of citrate-based sensors as a new sweat chloride test method for the diagnosis of Cystic Fibrosis by performing analytical validation with sweat controls and clinical validation with sweat from individuals with or without Cystic Fibrosis. Lastly, molecular modeling studies reveal the structural mechanism behind chloride sensing, serving to expand this class of fluorescence sensors with improved chloride sensitivities. Thus citrate-based fluorescent materials may enable low-cost, automated multi-analysis systems for simpler, yet accurate, point-of-care diagnostics that can be readily translated into clinical settings. More broadly, a wide range of medical, industrial, and environmental applications can be achieved with such a facile synthesis platform, demonstrated in our citrate-based biodegradable polymers with intrinsic fluorescence sensing.
authors.affiliation: Department of Biomedical Engineering, Materials Research Institutes, the Huck Institutes of Life Sciences, The Penn-sylvania State University, University Park, PA 16802.
authors.forename: Jimin P
authors.initials: JP
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Materials Research Institutes, the Huck Institutes of Life Sciences, The Penn-sylvania State University, University Park, PA 16802.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Pathology, College of Medicine, The Pennsylvania State University, Hershey, PA 17033.
authors.forename: Michael
authors.initials: M
authors.lastname: Creer
authors.affiliation: Department of Electrical Engineering, The Pennsylvania State University, University Park, PA 16802.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Biomedical Engineering, Materials Research Institutes, the Huck Institutes of Life Sciences, The Penn-sylvania State University, University Park, PA 16802.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang