Using the Rubik's Cube to directly produce paper analytical devices for quantitative point-of-care aptamer-based assays.

In this article, we describe a facile method named as Rubik's Cube stamping (RCS) for equipment-free fabrication of microfluidic paper-based analytical devices (μPADs). RCS is inspired by the worldwide ubiquitous RC toy and requires no specialized electric equipment other than a classical six-faced RC that is assembled with home-made small iron components. It can pattern various rosin microstructures in paper simply by either using different functional faces of the modified RC or applying its internal pivot mechanism to adjust the components' patterning forms on one functional face. Such a versatile stamping method is quite simple and inexpensive, and thus holds potential for producing rosin-patterned μPADs by untrained users in resource-limited environments such as small laboratories and private clinics, or even at home and in the field. Moreover, a set of one-channel devices are fabricated to design a point-of-care aptamer-based assay with near sample-in-answer-out capability that integrates enzymatic reactions for robust yet efficient signal amplification and a personal glucometer for portable, user-friendly, rapid and quantitative readout. Its utility is well demonstrated with the sensitive and specific detection of adenosine as a model target in buffer samples and undiluted human urine within several minutes. With the advantages of low cost, simplicity, portability, rapidity, and aptamer variety, this general point-of-care assay system reported here may find broad applications including home healthcare, field-based environmental monitoring or food analysis and emergency situations.

[1]  Michael Zuker,et al.  Mfold web server for nucleic acid folding and hybridization prediction , 2003, Nucleic Acids Res..

[2]  Shusheng Zhang,et al.  Electrochemical biosensor for detection of adenosine based on structure-switching aptamer and amplification with reporter probe DNA modified Au nanoparticles. , 2008, Analytical chemistry.

[3]  S. S. Olmsted,et al.  Requirements for high impact diagnostics in the developing world , 2006, Nature.

[4]  Yi Lu,et al.  Abasic site-containing DNAzyme and aptamer for label-free fluorescent detection of Pb(2+) and adenosine with high sensitivity, selectivity, and tunable dynamic range. , 2009, Journal of the American Chemical Society.

[5]  Terence G. Henares,et al.  Paper-based inkjet-printed microfluidic analytical devices. , 2015, Angewandte Chemie.

[6]  Guo-Li Shen,et al.  Reusable electrochemical sensing platform for highly sensitive detection of small molecules based on structure-switching signaling aptamers. , 2007, Analytical chemistry.

[7]  Li-Hsien Lin,et al.  Rubik's cube watermark technology for grayscale images , 2010, Expert Syst. Appl..

[8]  Jiye Shi,et al.  A Bubble‐Mediated Intelligent Microscale Electrochemical Device for Single‐Step Quantitative Bioassays , 2014, Advanced materials.

[9]  Bingling Li,et al.  DNA detection using origami paper analytical devices. , 2013, Analytical chemistry.

[10]  Jilie Kong,et al.  Paper-based fluorescence resonance energy transfer assay for directly detecting nucleic acids and proteins. , 2016, Biosensors & bioelectronics.

[11]  Po-Jung Jimmy Huang,et al.  Flow cytometry-assisted detection of adenosine in serum with an immobilized aptamer sensor. , 2010, Analytical chemistry.

[12]  Yi Lu,et al.  Label-free catalytic and molecular beacon containing an abasic site for sensitive fluorescent detection of small inorganic and organic molecules. , 2012, Analytical chemistry.

[13]  Yun Zhang,et al.  Timing readout in paper device for quantitative point-of-use hemin/G-quadruplex DNAzyme-based bioassays. , 2015, Biosensors & bioelectronics.

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

[15]  Jinghua Yu,et al.  Paper-based electrochemiluminescence origami cyto-device for multiple cancer cells detection using porous AuPd alloy as catalytically promoted nanolabels. , 2015, Biosensors & bioelectronics.

[16]  T. Brown,et al.  New two dimensional liquid-phase colorimetric assay based on old iodine-starch complexation for the naked-eye quantitative detection of analytes. , 2016, Chemical communications.

[17]  Weihong Tan,et al.  Aptamers from cell-based selection for bioanalytical applications. , 2013, Chemical reviews.

[18]  Ali Kemal Yetisen,et al.  Paper-based microfluidic point-of-care diagnostic devices. , 2013, Lab on a chip.

[19]  Snober Ahmed,et al.  Paper-based chemical and biological sensors: Engineering aspects. , 2016, Biosensors & bioelectronics.

[20]  H. Zhou,et al.  Aptamer-based Au nanoparticles-enhanced surface plasmon resonance detection of small molecules. , 2008, Analytical chemistry.

[21]  Yi Lu,et al.  Direct detection of adenosine in undiluted serum using a luminescent aptamer sensor attached to a terbium complex. , 2012, Analytical chemistry.

[22]  Jin Si,et al.  Fabrication techniques for microfluidic paper-based analytical devices and their applications for biological testing: A review. , 2016, Biosensors & bioelectronics.

[23]  Jinghua Yu,et al.  Paper-based biosensor relying on flower-like reduced graphene guided enzymatically deposition of polyaniline for Pb(2+) detection. , 2016, Biosensors & bioelectronics.

[24]  Yun Zhang,et al.  Equipment-free quantitative measurement for microfluidic paper-based analytical devices fabricated using the principles of movable-type printing. , 2014, Analytical chemistry.

[25]  Yi Lu,et al.  Quantum dot encoding of aptamer-linked nanostructures for one-pot simultaneous detection of multiple analytes. , 2007, Analytical chemistry.

[26]  Juewen Liu,et al.  Biomimetic sensing based on chemically induced assembly of a signaling DNA aptamer on a fluid bilayer membrane. , 2012, Chemical communications.

[27]  Dan Du,et al.  Paper‐Based Electrochemical Biosensors: From Test Strips to Paper‐Based Microfluidics , 2014 .

[28]  Zhi Zhu,et al.  Target-responsive "sweet" hydrogel with glucometer readout for portable and quantitative detection of non-glucose targets. , 2013, Journal of the American Chemical Society.

[29]  Jia Li,et al.  Multiplexed lateral flow biosensors: Technological advances for radically improving point-of-care diagnoses. , 2016, Biosensors & bioelectronics.

[30]  J. Eijkel,et al.  Nanofluidics in point of care applications. , 2014, Lab on a chip.

[31]  Yi Lu,et al.  Label-free fluorescent aptamer sensor based on regulation of malachite green fluorescence. , 2010, Analytical chemistry.

[32]  Cloé Desmet,et al.  Paper electrodes for bioelectrochemistry: Biosensors and biofuel cells. , 2016, Biosensors & bioelectronics.

[33]  Yi Lu,et al.  Adenosine-dependent assembly of aptazyme-functionalized gold nanoparticles and its application as a colorimetric biosensor. , 2004, Analytical chemistry.

[34]  Alar Ainla,et al.  A Paper-Based "Pop-up" Electrochemical Device for Analysis of Beta-Hydroxybutyrate. , 2016, Analytical chemistry.

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

[36]  Katherine E. Boehle,et al.  Electrochemistry on Paper‐based Analytical Devices: A Review , 2016 .

[37]  Kemin Wang,et al.  Exciton energy transfer-based fluorescent sensing through aptamer-programmed self-assembly of quantum dots. , 2013, Analytical chemistry.

[38]  F. Rius,et al.  A paper-based potentiometric cell for decentralized monitoring of Li levels in whole blood. , 2014, Lab on a chip.

[39]  Yingfu Li,et al.  DNA aptamer folding on gold nanoparticles: from colloid chemistry to biosensors. , 2008, Journal of the American Chemical Society.

[40]  Zhi Zhu,et al.  Target-responsive DNA hydrogel mediated "stop-flow" microfluidic paper-based analytic device for rapid, portable and visual detection of multiple targets. , 2015, Analytical chemistry.

[41]  Richard M Crooks,et al.  Detection of hepatitis B virus DNA with a paper electrochemical sensor. , 2015, Analytical chemistry.

[42]  Yi Lu,et al.  Aptamer-based origami paper analytical device for electrochemical detection of adenosine. , 2012, Angewandte Chemie.

[43]  Audrey K. Ellerbee,et al.  Quantifying colorimetric assays in paper-based microfluidic devices by measuring the transmission of light through paper. , 2009, Analytical chemistry.

[44]  Jie Xu,et al.  Detection of heavy metal by paper-based microfluidics. , 2016, Biosensors & bioelectronics.

[45]  Yun Zhang,et al.  Naked-eye quantitative aptamer-based assay on paper device. , 2016, Biosensors & bioelectronics.

[46]  Juewen Liu,et al.  A simple and sensitive "dipstick" test in serum based on lateral flow separation of aptamer-linked nanostructures. , 2006, Angewandte Chemie.

[47]  Longhua Guo,et al.  Oriented gold nanoparticle aggregation for colorimetric sensors with surprisingly high analytical figures of merit. , 2013, Journal of the American Chemical Society.

[48]  D. Sechi,et al.  Three-dimensional paper-based microfluidic device for assays of protein and glucose in urine. , 2013, Analytical chemistry.

[49]  Wei Liu,et al.  Plasma treatment of paper for protein immobilization on paper-based chemiluminescence immunodevice. , 2016, Biosensors & bioelectronics.

[50]  Utkan Demirci,et al.  Advances in Plasmonic Technologies for Point of Care Applications , 2014, Chemical reviews.

[51]  Eka Noviana,et al.  Paper-Based Microfluidic Devices: Emerging Themes and Applications. , 2017, Analytical chemistry.

[52]  Jinghua Yu,et al.  Paper-Based Device for Colorimetric and Photoelectrochemical Quantification of the Flux of H2O2 Releasing from MCF-7 Cancer Cells. , 2016, Analytical chemistry.

[53]  N. Zheng,et al.  Embryonic Growth of Face-Center-Cubic Silver Nanoclusters Shaped in Nearly Perfect Half-Cubes and Cubes. , 2017, Journal of the American Chemical Society.