title: Paper-based microfluidic system for tear electrolyte analysis.
abstract: The analysis of tear constituents at point-of-care settings has a potential for early diagnosis of ocular disorders such as dry eye disease, low-cost screening, and surveillance of at-risk subjects. However, current minimally-invasive rapid tear analysis systems for point-of-care settings have been limited to assessment of osmolarity or inflammatory markers and cannot differentiate between dry eye subclassifications. Here, we demonstrate a portable microfluidic system that allows quantitative analysis of electrolytes in the tear fluid that is suited for point-of-care settings. The microfluidic system consists of a capillary tube for sample collection, a reservoir for sample dilution, and a paper-based microfluidic device for electrolyte analysis. The sensing regions are functionalized with fluorescent crown ethers, o-acetanisidide, and seminaphtorhodafluor that are sensitive to mono- and divalent electrolytes, and their fluorescence outputs are measured with a smartphone readout device. The measured sensitivity values of Na+, K+, Ca2+ions and pH in artificial tear fluid were matched with the known ion concentrations within the physiological range. The microfluidic system was tested with samples having different ionic concentrations, demonstrating the feasibility for the detection of early-stage dry eye, differential diagnosis of dry eye sub-types, and their severity staging.
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA. akyetisen@gmail.com and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. syun@mgh.harvard.edu.
authors.forename: Ali K
authors.identifier: 0000-0003-0896-267X
authors.initials: AK
authors.lastname: Yetisen
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA. akyetisen@gmail.com and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. syun@mgh.harvard.edu and State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, 122 Luoshi Road, Wuhan, 430070, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA. akyetisen@gmail.com and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. syun@mgh.harvard.edu.
authors.forename: Ali
authors.initials: A
authors.lastname: Tamayol
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA. akyetisen@gmail.com and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. syun@mgh.harvard.edu.
authors.forename: Guillermo U
authors.initials: GU
authors.lastname: Ruiz-Esparza
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA. akyetisen@gmail.com and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. syun@mgh.harvard.edu.
authors.forename: Yu Shrike
authors.identifier: 0000-0002-0045-0808
authors.initials: YS
authors.lastname: Zhang
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA. akyetisen@gmail.com.
authors.forename: Sofía
authors.initials: S
authors.lastname: Medina-Pando
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. syun@mgh.harvard.edu.
authors.forename: Aditi
authors.identifier: 0000-0001-6834-7973
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Ophthalmic Research Group, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
authors.forename: James S
authors.identifier: 0000-0003-4673-8927
authors.initials: JS
authors.lastname: Wolffsohn
authors.affiliation: Nanotechnology Laboratory, School of Engineering, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Haider
authors.initials: H
authors.lastname: Butt
authors.affiliation: Biomaterials Innovation Research Center, Division of Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA. akyetisen@gmail.com and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. syun@mgh.harvard.edu and Department of Physics, King Abdulaziz University, Jeddah, 21589, Saudi Arabia and Department of Bioindustrial Technologies, College of Animal Bioscience and Technology, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. syun@mgh.harvard.edu and Harvard Medical School and Wellman Center for Photomedicine, Massachusetts General Hospital, 65 Landsdowne Street, Cambridge, Massachusetts 02139, USA.
authors.forename: Seok-Hyun
authors.initials: SH
authors.lastname: Yun
mesh_terms: D015352:Dry Eye Syndromes; D004573:Electrolytes / Q000032:analysis*; D004867:Equipment Design; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods*; D010209:Paper; D011188:Potassium / Q000032:analysis; D012964:Sodium / Q000032:analysis; D013666:Tears / Q000737:chemistry*
chemical_list: D004573:Electrolytes; D012964:Sodium; D011188:Potassium