Microfluidic paper-based biomolecule preconcentrator based on ion concentration polarization

Abstract

Microfluidic paper-based analytical devices (μPADs) for molecular detection have great potential in the field of point-of-care diagnostics. Currently, a critical problem being faced by μPADs is improving their detection sensitivity. Various preconcentration processes have been developed, but they still have complicated structures and fabrication processes to integrate into μPADs. To address this issue, we have developed a novel paper-based preconcentrator utilizing ion concentration polarization (ICP) with minimal addition on lateral-flow paper. The cation selective membrane (i.e., Nafion) is patterned on adhesive tape, and this tape is then attached to paper-based channels. When an electric field is applied across the Nafion, ICP is initiated to preconcentrate the biomolecules in the paper channel. Departing from previous paper-based preconcentrators, we maintain steady lateral fluid flow with the separated Nafion layer; as a result, fluorescent dyes and proteins (FITC-albumin and bovine serum albumin) are continuously delivered to the preconcentration zone, achieving high preconcentration performance up to 1000-fold. In addition, we demonstrate that the Nafion-patterned tape can be integrated with various geometries (multiplexed preconcentrator) and platforms (string and polymer microfluidic channel). This work would facilitate integration of various ICP devices, including preconcentrators, pH/concentration modulators, and micro mixers, with steady lateral flows in paper-based platforms.

Rapid evaporation-driven chemical pre-concentration and separation on paper

“…The most commonly used method is ion concentration polarization (ICP) [20][21][22][23]. This can provide concentration factors of 100-1000 in 2-10 minutes after filling, but require nanoporous membranes, electrodes and relatively high voltages.…”

Paper-based ion concentration polarization device for selective preconcentration of muc1 and lamp-2 genes

“…While the accuracy, performance and reproducibility of paper-based ICP device were lower than conventional ICP device, it was always suffered from the extraction of preconcentrated sample and the instability. Since a paper is easily cut by any methods, the endeavor for the sample extraction for further processes become extremely simple [7][8][9][10]. With the advantage of cost-effective fabrication and easy extraction, paperbased ICP platform would be one of the major field of this ICP research society.…”

Folding-paper-based preconcentrator for low dispersion of preconcentration plug

“…The ion enrichment and depletion zones are generated in the fluidic channel [1]. Employing micro/nanofluidic networks, the ICP phenomena are frequently utilized to preconcentrate charged sample analytes [3,7,8]. Han et al have investigated ICP preconcentration of various biomolecules in fluidic systems [9][10][11].…”

“…Ion concentration polarization (ICP) phenomena, wherein ion concentrations are distributed at the interface between an ion exchange membrane (IEM) and an electrolyte having an electric potential [1], are intensively studied in the field of micro/nanofluidics [2][3][4][5][6]. In general, ICP occurs near an IEM via the permeation of specific charged ions (cation or anion).…”

“…Recently, Kwak and Hong et al proposed a paper-based ICP preconcentrator to facilitate extraction. Hong et al developed a continuous-flow preconcentrator with a bifurcation system to collect and separate the samples [19,20] Recently, we proposed a paper-based preconcentrator, which preconcentrates FITC-albumin with a high preconcentration factor of up to 310-fold for 400 s [3], however, there are limitations in applying the preconcentrator for using external analytical devices because of dispersion of preconcentrated sample plug. In this study, a 3D foldable-paper-based ICP preconcentration system is proposed for obtaining a preconcentration plug with minimal dispersion.…”