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.
Anal Chem. 2016 Jun 21;88(12):6326-33. doi: 10.1021/acs.analchem.6b00568. Epub 2016 May 31.
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.
本文描述了一种“弹出式”电化学纸基分析器件（pop-up-EPAD）的设计和制造，该器件用于使用商业组合 BHB/血糖仪测量β-羟丁酸（BHB）——糖尿病酮症酸中毒的生物标志物。pop-up-EPAD 受到弹出式贺卡和儿童书籍的启发。它们由一张纸折叠成三维（3D）器件制成，通过简单地折叠和展开结构，改变形状、流体和电连通性。可重构的 3D 结构使得改变流体路径和控制时间成为可能；它还为折叠和展开结构提供机械支撑，使折叠时具有良好的配准性和可重复性。设计用于检测 BHB 的 pop-up-EPAD 与临床相关范围内的血液中 BHB 时，与集成了测量葡萄糖和 BHB 能力的商业血糖仪（组合 BHB/血糖仪）一起使用时，其性能可与商业塑料测试条相媲美。通过对电极和流体路径设计进行简单修改，pop-up-EPAD 还可以使用简单的血糖仪在缓冲液中检测到 BHB——这种设备比组合 BHB/血糖仪更容易获得。使用“3D 弹出式”（即 3D 结构和流体路径的大规模变化）的策略通过折叠/展开为 EPAD 增加了功能（例如，定时控制、流体处理和路径编程、对复杂步骤序列的控制以及电连通性的改变），并应能够开发新类别的基于纸张的诊断设备。
