Electrochemical microfluidic paper-based analytical devices for cancer biomarker detection: From 2D to 3D sensing systems

Microfluidic paper-based analytical devices (μPADs) offer a unique possibility for a cost-effective portable and rapid detection of a wide range of small molecules and macromolecules and even microorganisms. In this line, electrochemical detection methods are key techniques for the qualitative analysis of different types of ligands. The electrochemical sensing μPADs have been devised for the rapid, accurate, and quantitative detection of oncomarkers through two-/three-dimensional (2D/3D) approaches. The 2D μPADs were first developed and then transformed into 3D systems via folding and/or twisting of paper. The microfluidic channels and connections were created within the layers of paper. Based on the fabrication methods, 3D μPADs can be classified into origami and stacking devices. Various fabrication methods and materials have been used to create hydrophilic channels in μPADs, among which the wax printing technique is the most common method in fabricating μPADs. In this review, we discuss the fabrication and design strategies of μPADs, elaborate on their detection modes, and highlight their applications in affinity-based electrochemical μPADs methods for the detection of oncomarkers.