Folding-paper-based preconcentrator for low dispersion of preconcentration plug
© The Author(s) 2017
Received: 23 November 2016
Accepted: 24 January 2017
Published: 1 February 2017
Ion concentration polarization (ICP) has been widely studied for collecting target analytes as it is a powerful preconcentrator method employed for charged molecules. Although the method is quite robust, simple, cheap, and yields a high preconcentration factor, a major hurdle to be addressed is extracting the preconcentrated samples without dispersing the plug. This study investigates a 3D folding-paper-based ICP preconcentrator for preconcentrated plug extraction without the dispersion effect. The ICP preconcentrator is printed on a cellulose paper with pre-patterned hydrophobic wax. To extract and isolate the preconcentration plug with minimal dispersion, a 3D pop-up structure is fabricated via water drain, and a preconcentration factor of 300-fold for 10 min is achieved. By optimizing factors such as the electric field, water drain, and sample volume, the technique was enhanced by facilitating sample preconcentration and isolation, thereby providing the possibility for extensive applications in analytical devices such as lateral flow assays and FTAR cards.
KeywordsIon concentration polarization (ICP) Preconcentration Paper FTAR card Separation Extraction
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 , are intensively studied in the field of micro/nanofluidics [2–6]. In general, ICP occurs near an IEM via the permeation of specific charged ions (cation or anion). The ion enrichment and depletion zones are generated in the fluidic channel . 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 [9–11]. Moreover, desalination of seawater using ICP phenomena has been reported [12, 13].
Although many studies investigated analytical systems for both analytical and point-of-care (POC) applications [14–16], detecting biomolecules at concentrations below the limit of detection (LOD) is still a critical issue for analytical devices. To address this problem, an ICP-based preconcentrator has been developed [17, 18] for enhancing the LOD. In many cases, the preconcentration plug, particularly used for the delivery of preconcentrated samples to external equipment and devices, needs to deliver the samples with minimal dispersion; however, the dispersion of the sample plug is a critical issue . When the electric field is removed, the force balance between external hydraulic force/electric field and depletion force cannot be maintained. Hence, the ICP preconcentration plug is drastically dispersed in the fluidic channel, which severely hampers the use of preconcentration devices with external analytical devices (i.e., mass spectrometry and sensors).
To extract and separate the preconcentration plug, Chen et al.  made use of the difference in electrophoretic mobility and a magnetic valve, however, one still needs simple methods without complex additional components. 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 , 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. By employing the 3D pop-up structure, the preconcentration plug was concentrated and isolated up to 300-fold, which is directly applicable for POC test kits and FTAR cards.
Device operation and preconcentration monitoring
Figure 2b shows the sequential process of the operation principle of the 3D folding-paper-based ICP preconcentrator. First, a sample of 10 μL (NaCl buffer of 1 mM) is loaded onto the buffer reservoirs. An electric potential of 100 V/cm using Ag/AgCl electrodes is applied between the buffer reservoirs via a benchtop sourcemeter (Keithley 2410 current–voltage source measurement unit, Keithley Instruments, Inc.). When the electric potential is applied, the sample analytes of volume 10 μL are loaded onto the sample reservoir. They are monitored using an inverted epifluorescence microscope (Olympus, IX-71) and a thermoelectrically cooled charge-coupled device camera (Hamamatsu Co., Japan). After the preconcentration, the outlet reservoir is folded up, and the separated preconcentration plug of the sample reservoir is detached. To monitor the ICP phenomena, fluorescence dyes (Alexa fluor 488, Invitrogen, Carlsbad, CA, USA) and an orange G dye (Sigma-Aldrich, St. Louis, MO) with a buffer solution are utilized. The fluorescence and optical images are analyzed using ImageJ (Wayne Rasband, National Institutes of Health, Bethesda, MD, USA). We carried out all experiments at controlled R.T. and humidity (R.H. = 55 ± 5%) to avoid run-to-run experimental errors.
Results and discussion
ICP phenomena and preconcentration
The total preconcentration volume is one of the essential criteria for the ICP preconcentration. As shown in Fig. 4b, the preconcentration factor was monitored based on the total preconcentration volume. The preconcentration factors of 50-, 90-, and 300-fold are measured for volumes of 10 μL (red line), 15 μL (blue line), and 20 μL (black line), respectively. In general, the preconcentrating volume and factor have been considered as a trade-off. If the preconcentrating volume is increased, the preconcentrating factor generally decreases. In Fig. 4b, a higher preconcentrating factor is observed for a total preconcentration volume of 10 μL.
Isolation and extraction of preconcentration plug with folding structure
In this study, a 3D folding-paper-based ICP preconcentrator was developed for preconcentrating charged biomolecules with a small dispersion. A preconcentration of 300-fold for a sample volume of 10 μL was obtained. By optimizing the electric field, sample volume, and outlet reservoir size, the 3D folding pop-up paper-based preconcentrator was successfully implemented for extracting the ICP preconcentration plug with low dispersion effects. This technique can be used in applications involving bioassay and environment monitoring (i.e., lateral flow assay, FTAR card and mass spectrometry).
ion concentration polarization
ion exchange membrane
KJL helped design, fabricate, and test the device and drafted the manuscript. YKY and SIH reviewed the test methods and results. JL, DL, and CK surveyed the literature on ion concentration polarization. JHL reviewed all the test methods and results and finalized the drafted manuscript. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (MEST) (NRF-2015R1D1A1A01059806) and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant Number: HI16C0272). Kyungjae Lee was also supported by the R&D program of MOTIE/KEIT. [10054570, Highly educated human resources development project on cutting-edge sensor technology for sensor industry acceleration].
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