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 key biomarker for diabetic ketoacidosis—using a commercial 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 fluid path design, the pop-up-EPAD also detects BHB using a simple glucometer—a device that is much more available than combination BHB/glucometers. Strategies that use a “3D pop-up”—that is, large-scale changes a 3D structure and fluidic paths—by folding/unfolding add functionality (e.g., controlled timing, fluidic handling and path programming, control over complex sequences of steps, and alterations in electrical connectivity) to EPADs, and should enable the development of new classes of paper-based diagnostic devices.

Electrochemical Microphysiometry Detects Cellular Glutamate Uptake

“…[6][7][8] Electrochemical sensors are also versatile: They can be made on the nanoscale, 1 have been 3D-printed, 9 and can be inexpensive. 10,11 The highly translatable nature of electrochemical techniques has already been demonstrated with the advent of Smart Bands 12 and iSTAT meters (Abbott Point of Care Inc.). 13,14 Detecting glutamate has many advantages: It advances our knowledge of the effects of pesticide exposure, explains some of the erratic behaviors seen after traumatic brain injuries, informs our dietary considerations (MSG), and, perhaps most importantly, functions as a window to understanding human memory and consciousness.…”

Trends in Paper-based Electrochemical Biosensors: From Design to Application

“…21 The main difference (B) A "pop-up" electrochemical paper-based analytical device for analyzing β-hydroxybutyrate. 40 (C) Paper-based multilayer circuits for development of paper-based devices. 46 (D) Quantitative detection of oligonucleotides and proteins via paper electrochemical device.…”

“…78 Figures are reproduced with permission from American Chemical Society. 21,40,46,53,78 between 2D and 3D sensors is how electrodes are displayed. In a 2D sensor, the three electrodes system is fabricated onto a single piece of paper, commonly on a circular or a channel-like hydrophobic test zone.…”

“…1B). 40 The microfluidic channels were defined by wax printing on chromatography paper, followed by stencil-printing of the three electrodes system and circuits using graphite ink. A solution of enzyme and cofactor were added into the reaction zone and dried in the dark.…”

“…1B). 40 This single-use PAD contained a sample port, a reaction zone for storing the enzyme and a detection zone spatially isolated from the first two zones. The device changed from "off" to "on" configuration when the sample port, reaction zone and detection zone were in contact through modest mechanical pressure by folding the device between thumb and forefinger or by placing some weight on top of the device.…”