Microfluidic paper-based biomolecule preconcentrator based on ion concentration polarization.

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.

[1]  Jongyoon Han,et al.  Enhanced Salt Removal by Unipolar Ion Conduction in Ion Concentration Polarization Desalination , 2016, Scientific Reports.

[2]  Wonjung Kim,et al.  Paper-Based Flow Fractionation System Applicable to Preconcentration and Field-Flow Separation. , 2016, Analytical chemistry.

[3]  J. Kang,et al.  Spatiotemporally Defining Biomolecule Preconcentration by Merging Ion Concentration Polarization. , 2016, Analytical chemistry.

[4]  Ruey-Jen Yang,et al.  Ion concentration polarization on paper-based microfluidic devices and its application to preconcentrate dilute sample solutions. , 2015, Biomicrofluidics.

[5]  Jaclyn A. Adkins,et al.  Recent developments in paper-based microfluidic devices. , 2015, Analytical chemistry.

[6]  Mario Cabodi,et al.  Evaporative concentration on a paper-based device to concentrate analytes in a biological fluid. , 2014, Analytical chemistry.

[7]  Tally Rosenfeld,et al.  1000-fold sample focusing on paper-based microfluidic devices. , 2014, Lab on a chip.

[8]  Jonathan D Posner,et al.  Two orders of magnitude improvement in detection limit of lateral flow assays using isotachophoresis. , 2014, Analytical chemistry.

[9]  David Sinton,et al.  Nanoporous membranes enable concentration and transport in fully wet paper-based assays. , 2014, Analytical chemistry.

[10]  Daniel T Kamei,et al.  Simultaneous concentration and detection of biomarkers on paper. , 2014, Lab on a chip.

[11]  Hsueh-Chia Chang,et al.  Microfluidic systems with ion-selective membranes. , 2014, Annual review of analytical chemistry.

[12]  Jonathan D Posner,et al.  Isotachophoretic preconcenetration on paper-based microfluidic devices. , 2014, Analytical chemistry.

[13]  Fei Li,et al.  Advances in paper-based point-of-care diagnostics. , 2014, Biosensors & bioelectronics.

[14]  Lauro T Kubota,et al.  Sensing approaches on paper-based devices: a review , 2013, Analytical and Bioanalytical Chemistry.

[15]  Mariana Medina-Sánchez,et al.  Simple paper architecture modifications lead to enhanced sensitivity in nanoparticle based lateral flow immunoassays. , 2013, Lab on a chip.

[16]  Jongyoon Han,et al.  Microscale electrodialysis: Concentration profiling and vortex visualization , 2013 .

[17]  Sung Jae Kim,et al.  Nanofluidic preconcentration device in a straight microchannel using ion concentration polarization. , 2012, Lab on a chip.

[18]  David Juncker,et al.  Immunochromatographic assay on thread. , 2012, Analytical chemistry.

[19]  Temsiri Songjaroen,et al.  Blood separation on microfluidic paper-based analytical devices. , 2012, Lab on a chip.

[20]  Sung Jae Kim,et al.  Continuous-flow biomolecule and cell concentrator by ion concentration polarization. , 2011, Analytical chemistry.

[21]  Jongyoon Han,et al.  Non-linear and linear enhancement of enzymatic reaction kinetics using a biomolecule concentrator. , 2011, Lab on a chip.

[22]  Sung Jae Kim,et al.  Enhancing protease activity assay in droplet-based microfluidics using a biomolecule concentrator. , 2011, Journal of the American Chemical Society.

[23]  Sung Jae Kim,et al.  Massively parallel concentration device for multiplexed immunoassays. , 2011, Lab on a chip.

[24]  Zhihong Nie,et al.  Programmable diagnostic devices made from paper and tape. , 2010, Lab on a chip.

[25]  Thomas A. Zangle,et al.  Theory and experiments of concentration polarization and ion focusing at microchannel and nanochannel interfaces. , 2010, Chemical Society reviews.

[26]  Sung Jae Kim,et al.  Nanofluidic concentration devices for biomolecules utilizing ion concentration polarization: theory, fabrication, and applications. , 2010, Chemical Society reviews.

[27]  Sung Jae Kim,et al.  Amplified electrokinetic response by concentration polarization near nanofluidic channel. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[28]  G. Whitesides,et al.  Three-dimensional microfluidic devices fabricated in layered paper and tape , 2008, Proceedings of the National Academy of Sciences.

[29]  P. Renaud,et al.  Transport phenomena in nanofluidics , 2008 .

[30]  G. Whitesides,et al.  Simple telemedicine for developing regions: camera phones and paper-based microfluidic devices for real-time, off-site diagnosis. , 2008, Analytical chemistry.

[31]  Jongyoon Han,et al.  Increase of reaction rate and sensitivity of low-abundance enzyme assay using micro/nanofluidic preconcentration chip. , 2008, Analytical chemistry.

[32]  Yong-Ak Song,et al.  Multiplexed proteomic sample preconcentration device using surface-patterned ion-selective membrane. , 2008, Lab on a chip.

[33]  A. L. Stevens,et al.  Million-fold preconcentration of proteins and peptides by nanofluidic filter. , 2005, Analytical chemistry.

[34]  Jongyoon Han,et al.  Two-dimensional protein separation with advanced sample and buffer isolation using microfluidic valves. , 2004, Analytical chemistry.

[35]  Paul Yager,et al.  Transport in two-dimensional paper networks , 2011, Microfluidics and nanofluidics.

[36]  Geertruida A. Posthuma-Trumpie,et al.  Lateral flow (immuno)assay: its strengths, weaknesses, opportunities and threats. A literature survey , 2009, Analytical and bioanalytical chemistry.