title: A Paper-Based "Pop-up" Electrochemical Device for Analysis of Beta-Hydroxybutyrate.
abstract: This paper describes the design and fabrication of a "pop-up" electrochemical paper-based analytical device (pop-up-EPAD) to measure beta-hydroxybutyrate (BHB)-a biomarker for diabetic ketoacidosis-using a commercial combination BHB/glucometer. Pop-up-EPADs are inspired by pop-up greeting cards and children's books. They are made from a single sheet of paper folded into a three-dimensional (3D) device that changes shape, and fluidic and electrical connectivity, by simply folding and unfolding the structure. The reconfigurable 3D structure makes it possible to change the fluidic path and to control timing; it also provides mechanical support for the folded and unfolded structures that enables good registration and repeatability on folding. A pop-up-EPAD designed to detect BHB shows performance comparable to commercially available plastic test strips over the clinically relevant range of BHB in blood when used with a commercial glucometer that integrates the ability to measure glucose and BHB (combination BHB/glucometer). With simple modifications of the electrode and the design of the fluidic path, the pop-up-EPAD also detects BHB in buffer using a simple glucometer-a device that is more available than the combination BHB/glucometer. Strategies that use a "3D pop-up"-that is, large-scale changes in 3D structure and fluidic paths-by folding/unfolding add functionality to EPADs (e.g., controlled timing, fluidic handling and path programming, control over complex sequences of steps, and alterations in electrical connectivity) and should enable the development of new classes of paper-based diagnostic devices.
authors.affiliation: Department of Chemistry & Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: Chien-Chung
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Department of Chemistry & Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Hennek
authors.affiliation: Department of Chemistry & Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: Alar
authors.initials: A
authors.lastname: Ainla
authors.affiliation: Department of Chemistry & Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: Ashok A
authors.initials: AA
authors.lastname: Kumar
authors.affiliation: Department of Chemistry & Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Lan
authors.affiliation: Department of Chemistry & Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: Judy
authors.initials: J
authors.lastname: Im
authors.affiliation: Department of Chemistry & Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Smith
authors.affiliation: Department of Chemistry & Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: Mengxia
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Chemistry & Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.|Wyss Institute for Biologically Inspired Engineering, Harvard University , 60 Oxford Street, Cambridge, Massachusetts 02138, United States.|Kavli Institute for Bionano Science & Technology, Harvard University , 29 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: George M
authors.initials: GM
authors.lastname: Whitesides
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood* / Q000737:chemistry; D015415:Biomarkers / Q000097:blood; D016883:Diabetic Ketoacidosis / Q000175:diagnosis; D055664:Electrochemical Techniques / Q000295:instrumentation / Q000379:methods*; D004566:Electrodes; D006801:Humans; D057230:Limit of Detection; D009243:NAD / Q000737:chemistry; D010209:Paper; D019095:Point-of-Care Systems
chemical_list: D015415:Biomarkers; D009243:NAD; D020155:3-Hydroxybutyric Acid