A Paper-Based “Pop-up” Electrochemical Device for Analysis of Beta-Hydroxybutyrate

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.