Paper Microfluidics for POC Testing in Low-Resource Settings

Paper microfluidics is a subarea of microfluidics in which porous materials are used to create devices. Advantages of paper microfluidics include fluid transport via capillary forces, so that external pumping equipment is not necessary, and the use of less expensive materials than those commonly used in conventional microfluidic devices. Paper microfluidics enables the development of fully disposable devices that are appropriate for use in even the lowest-resource settings, and the potential for high impact improvement to human health. In this chapter, we first discuss the paper microfluidic device fabrication processes of materials selection, fluidic boundary definition, and reagent patterning. Next, we discuss tools development for manipulating fluids in paper microfluidic devices. Then, we describe specific medical applications with discussion of three promising paper microfluidic devices. Finally, we close with a general discussion of challenges in the translation of paper microfluidic devices from the lab to the field.

[1]  Robert Robinson,et al.  Development of a Whole Blood Paper-Based Device for Phenylalanine Detection in the Context of PKU Therapy Monitoring , 2016, Micromachines.

[2]  Paul Yager,et al.  Highly Sensitive Immunoassay Based on Controlled Rehydration of Patterned Reagents in a 2-Dimensional Paper Network , 2014, Analytical chemistry.

[3]  Seok-woo Hong,et al.  Dynamics of water imbibition through paper channels with wax boundaries , 2015 .

[4]  Elain Fu,et al.  Porous stamp-based reagent patterning for lateral flow immunoassays , 2017 .

[5]  Daniel Citterio,et al.  Toward practical application of paper-based microfluidics for medical diagnostics: state-of-the-art and challenges. , 2017, Lab on a chip.

[6]  Orawon Chailapakul,et al.  Novel, simple and low-cost alternative method for fabrication of paper-based microfluidics by wax dipping. , 2011, Talanta.

[7]  Di Wu,et al.  A paper-based microfluidic Dot-ELISA system with smartphone for the detection of influenza A , 2017 .

[8]  S. Shevkoplyas,et al.  Integrated separation of blood plasma from whole blood for microfluidic paper-based analytical devices. , 2012, Lab on a chip.

[9]  Bingcheng Lin,et al.  Patterned paper as a low-cost, flexible substrate for rapid prototyping of PDMS microdevices via "liquid molding". , 2011, Analytical chemistry.

[10]  P. Yager,et al.  A rapid, instrument-free, sample-to-result nucleic acid amplification test. , 2016, Lab on a chip.

[11]  Charles S Henry,et al.  Simple, distance-based measurement for paper analytical devices. , 2013, Lab on a chip.

[12]  Zhike He,et al.  Determination of glucose and uric acid with bienzyme colorimetry on microfluidic paper-based analysis devices. , 2012, Biosensors & bioelectronics.

[13]  S. S. Sibbett,et al.  Multiplex lateral-flow test strips fabricated by two-dimensional shaping. , 2009, ACS applied materials & interfaces.

[14]  S. T. Phillips,et al.  Metering the capillary-driven flow of fluids in paper-based microfluidic devices. , 2010, Analytical chemistry.

[15]  Qiaohong He,et al.  A simple method for fabrication of microfluidic paper-based analytical devices and on-device fluid control with a portable corona generator , 2016 .

[16]  G. Whitesides,et al.  Understanding wax printing: a simple micropatterning process for paper-based microfluidics. , 2009, Analytical chemistry.

[17]  Orawon Chailapakul,et al.  A facile low-cost enzymatic paper-based assay for the determination of urine creatinine. , 2015, Talanta.

[18]  Paul Yager,et al.  Long-term dry storage of an enzyme-based reagent system for ELISA in point-of-care devices. , 2014, The Analyst.

[19]  C. Bridges,et al.  The annual impact of seasonal influenza in the US: measuring disease burden and costs. , 2007, Vaccine.

[20]  Gonzalo Domingo,et al.  Disposable Autonomous Device for Swab-to-Result Diagnosis of Influenza. , 2017, Analytical chemistry.

[21]  Ramakrishna Prasad,et al.  Low sensitivity of rapid diagnostic test for influenza. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[22]  Paul Yager,et al.  Controlled release of dry reagents in porous media for tunable temporal and spatial distribution upon rehydration. , 2012, Lab on a chip.

[23]  Matthew Darlison,et al.  Global epidemiology of haemoglobin disorders and derived service indicators. , 2008, Bulletin of the World Health Organization.

[24]  P. Yarnold,et al.  Hepatotoxicity Associated with Long-versus Short-Course HIV-Prophylactic Nevirapine Use , 2009, Drug safety.

[25]  Yanfen Peng,et al.  Covalent Binding of Antibodies to Cellulose Paper Discs and Their Applications in Naked-eye Colorimetric Immunoassays. , 2016, Journal of visualized experiments : JoVE.

[26]  Thomas Berthelot,et al.  A one-step and biocompatible cellulose functionalization for covalent antibody immobilization on immunoassay membranes. , 2013, Journal of materials chemistry. B.

[27]  Everson T S G da Silva,et al.  Triboelectric effect as a new strategy for sealing and controlling the flow in paper-based devices. , 2015, Lab on a chip.

[28]  W. Dungchai,et al.  A low-cost, simple, and rapid fabrication method for paper-based microfluidics using wax screen-printing. , 2011, The Analyst.

[29]  P. Yager,et al.  Point-of-care diagnostics for global health. , 2008, Annual review of biomedical engineering.

[30]  Bingcheng Lin,et al.  Rapid prototyping of paper‐based microfluidics with wax for low‐cost, portable bioassay , 2009, Electrophoresis.

[31]  I. Roy,et al.  Effect of trehalose on protein structure , 2008, Protein science : a publication of the Protein Society.

[32]  Bernhard H. Weigl,et al.  Field Evaluation of a Prototype Paper-Based Point-of-Care Fingerstick Transaminase Test , 2013, PloS one.

[33]  Xinyu Liu,et al.  Magnetic timing valves for fluid control in paper-based microfluidics. , 2013, Lab on a chip.

[34]  Paul Yager,et al.  Tunable-delay shunts for paper microfluidic devices. , 2013, Analytical chemistry.

[35]  P. Yager,et al.  Perspective on Diagnostics for Global Health , 2011, IEEE Pulse.

[36]  Charles Henry,et al.  Electrochemical paper‐based microfluidic devices , 2015, Electrophoresis.

[37]  Jinghua Yu,et al.  Paper-Based Analytical Devices Relying on Visible-Light-Enhanced Glucose/Air Biofuel Cells. , 2015, ACS applied materials & interfaces.

[38]  Aart van Amerongen,et al.  Distribution of biomolecules in porous nitrocellulose membrane pads using confocal laser scanning microscopy and high-speed cameras. , 2013, Analytical chemistry.

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

[40]  Xiaoxi Yang,et al.  Validation of a Low-Cost Paper-Based Screening Test for Sickle Cell Anemia , 2016, PloS one.

[41]  Shawn Vasoo,et al.  Rapid Antigen Tests for Diagnosis of Pandemic (Swine) Influenza A/H1N1 , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[42]  Hongmei Lu,et al.  Multiplexed bioactive paper based on GO@SiO2@CeO2 nanosheets for a low-cost diagnostics platform. , 2014, Biosensors & bioelectronics.

[43]  Koji Suzuki,et al.  High-Resolution Microfluidic Paper-Based Analytical Devices for Sub-Microliter Sample Analysis , 2016, Micromachines.

[44]  George M Whitesides,et al.  Integration of paper-based microfluidic devices with commercial electrochemical readers. , 2010, Lab on a chip.

[45]  Orawon Chailapakul,et al.  Use of multiple colorimetric indicators for paper-based microfluidic devices. , 2010, Analytica chimica acta.

[46]  George M Whitesides,et al.  Millimeter-scale contact printing of aqueous solutions using a stamp made out of paper and tape. , 2010, Lab on a chip.

[47]  Orawon Chailapakul,et al.  Electrochemical detection for paper-based microfluidics. , 2009, Analytical chemistry.

[48]  A. Vlessidis,et al.  Programming fluid transport in paper-based microfluidic devices using razor-crafted open channels. , 2014, Analytical chemistry.

[49]  Shenguang Ge,et al.  Paper-based chemiluminescence ELISA: lab-on-paper based on chitosan modified paper device and wax-screen-printing. , 2012, Biosensors & bioelectronics.

[50]  R. Peeling,et al.  Rapid tests for sexually transmitted infections (STIs): the way forward , 2006, Sexually Transmitted Infections.

[51]  George M Whitesides,et al.  FLASH: a rapid method for prototyping paper-based microfluidic devices. , 2008, Lab on a chip.

[52]  Elain Fu,et al.  Progress in the development and integration of fluid flow control tools in paper microfluidics. , 2017, Lab on a chip.

[53]  E. F. Ullman,et al.  Enzyme immunochromatography--a quantitative immunoassay requiring no instrumentation. , 1985, Clinical chemistry.

[54]  S. Shevkoplyas,et al.  A Paper-Based Test for Screening Newborns for Sickle Cell Disease , 2017, Scientific Reports.

[55]  Jennifer L. Osborn,et al.  Enabling a microfluidic immunoassay for the developing world by integration of on-card dry reagent storage. , 2008, Lab on a chip.

[56]  Elain Fu,et al.  Investigation of Reagent Delivery Formats in a Multivalent Malaria Sandwich Immunoassay and Implications for Assay Performance. , 2016, Analytical chemistry.

[57]  Orawon Chailapakul,et al.  Development of automated paper-based devices for sequential multistep sandwich enzyme-linked immunosorbent assays using inkjet printing. , 2013, Lab on a chip.

[58]  Paul Yager,et al.  Dissolvable fluidic time delays for programming multi-step assays in instrument-free paper diagnostics. , 2013, Lab on a chip.

[59]  Mohammad Faghri,et al.  A fluidic diode, valves, and a sequential-loading circuit fabricated on layered paper. , 2012, Lab on a chip.

[60]  David Baker,et al.  Immobilizing affinity proteins to nitrocellulose: a toolbox for paper-based assay developers , 2016, Analytical and Bioanalytical Chemistry.

[61]  S. Paek,et al.  Semiquantitative, bar code version of immunochromatographic assay system for human serum albumin as model analyte. , 2001, Biotechnology and bioengineering.

[62]  Anthony Turner,et al.  Lateral-flow technology: From visual to instrumental , 2016 .

[63]  Paul Yager,et al.  CO2 laser cutting and ablative etching for the fabrication of paper-based devices , 2013 .

[64]  Aart van Amerongen,et al.  Influence of Pluronic F127 on the distribution and functionality of inkjet-printed biomolecules in porous nitrocellulose substrates. , 2015, Talanta.

[65]  Aydogan Ozcan,et al.  A personalized food allergen testing platform on a cellphone. , 2013, Lab on a chip.

[66]  C. K. Koo,et al.  An inkjet-printed electrowetting valve for paper-fluidic sensors. , 2013, The Analyst.

[67]  Yunus Alapan,et al.  Emerging point-of-care technologies for sickle cell disease screening and monitoring , 2016, Expert review of medical devices.

[68]  Paul Yager,et al.  Enhanced sensitivity of lateral flow tests using a two-dimensional paper network format. , 2011, Analytical chemistry.

[69]  Brendan O’Farrell,et al.  Evolution in Lateral Flow–Based Immunoassay Systems , 2008, Lateral Flow Immunoassay.

[70]  D. Noyola,et al.  Effect of rapid diagnosis on management of influenza A infections , 2000, The Pediatric infectious disease journal.

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

[72]  Sergey S Shevkoplyas,et al.  A simple, rapid, low-cost diagnostic test for sickle cell disease. , 2013, Lab on a chip.

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

[74]  Paul Yager,et al.  A versatile valving toolkit for automating fluidic operations in paper microfluidic devices. , 2015, Lab on a chip.

[75]  Reinhard Renneberg,et al.  Development of enzyme-based bar code-style lateral-flow assay for hydrogen peroxide determination. , 2009, Analytica chimica acta.

[76]  D. Beebe,et al.  Physics and applications of microfluidics in biology. , 2002, Annual review of biomedical engineering.

[77]  F. Kirkham,et al.  Mortality in Sickle Cell Anemia in Africa: A Prospective Cohort Study in Tanzania , 2011, PloS one.

[78]  Richard M Crooks,et al.  Hollow-channel paper analytical devices. , 2013, Analytical chemistry.

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

[80]  Yi Zhang,et al.  Imbibition in porous membranes of complex shape: quasi-stationary flow in thin rectangular segments. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[81]  B. Lin,et al.  Fabrication and characterization of paper-based microfluidics prepared in nitrocellulose membrane by wax printing. , 2010, Analytical chemistry.

[82]  Daniel Citterio,et al.  Inkjet-printed paperfluidic immuno-chemical sensing device , 2010, Analytical and bioanalytical chemistry.

[83]  G. Whitesides,et al.  Patterned paper as a platform for inexpensive, low-volume, portable bioassays. , 2007, Angewandte Chemie.

[84]  George M Whitesides,et al.  "Paper Machine" for Molecular Diagnostics. , 2015, Analytical chemistry.

[85]  C. Quinn Sickle cell disease in childhood: from newborn screening through transition to adult medical care. , 2013, Pediatric clinics of North America.

[86]  Paul Yager,et al.  Two-dimensional paper network format that enables simple multistep assays for use in low-resource settings in the context of malaria antigen detection. , 2012, Analytical chemistry.

[87]  Howard A Stone,et al.  Two-ply channels for faster wicking in paper-based microfluidic devices. , 2015, Lab on a chip.

[88]  Jacqueline C Linnes,et al.  Paper-Based RNA Extraction, in Situ Isothermal Amplification, and Lateral Flow Detection for Low-Cost, Rapid Diagnosis of Influenza A (H1N1) from Clinical Specimens. , 2015, Analytical chemistry.

[89]  Elain Fu,et al.  Dissolvable bridges for manipulating fluid volumes in paper networks. , 2013, Analytical chemistry.

[90]  P. Yager,et al.  The evolution of nitrocellulose as a material for bioassays , 2013 .

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

[92]  Mas Angeles Mosso,et al.  Enumeration of Bacillus and Bacillus cereus Spores in Food from Spain. , 1989, Journal of food protection.

[93]  Junfei Tian,et al.  Paper-based microfluidic devices by plasma treatment. , 2008, Analytical chemistry.

[94]  Elain Fu,et al.  Progress in the development of paper-based diagnostics for low-resource point-of-care settings. , 2013, Bioanalysis.

[95]  Elain Fu,et al.  Enabling robust quantitative readout in an equipment-free model of device development. , 2014, The Analyst.

[96]  G. Whitesides,et al.  Diagnostics for the developing world: microfluidic paper-based analytical devices. , 2010, Analytical chemistry.

[97]  Valentin Romanov,et al.  A critical comparison of protein microarray fabrication technologies. , 2014, The Analyst.

[98]  Brendan O’Farrell,et al.  Lateral Flow Immunoassay Systems: Evolution from the Current State of the Art to the Next Generation of Highly Sensitive, Quantitative Rapid Assays , 2013 .

[99]  G. Whitesides,et al.  Low-cost printing of poly(dimethylsiloxane) barriers to define microchannels in paper. , 2008, Analytical chemistry.

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

[101]  Richard M Crooks,et al.  Three-dimensional wax patterning of paper fluidic devices. , 2014, Langmuir : the ACS journal of surfaces and colloids.

[102]  P. Yager,et al.  Controlled reagent transport in disposable 2D paper networks. , 2010, Lab on a chip.

[103]  Paul Yager,et al.  Chemical signal amplification in two-dimensional paper networks. , 2010, Sensors and actuators. B, Chemical.

[104]  Jorgen W. Nelson,et al.  Rapid Diagnostic Assay for Intact Influenza Virus Using a High Affinity Hemagglutinin Binding Protein. , 2017, Analytical chemistry.

[105]  Richard M Crooks,et al.  Paper-based SlipPAD for high-throughput chemical sensing. , 2013, Analytical chemistry.

[106]  Paul Yager,et al.  Programming paper networks for point of care diagnostics , 2013, Photonics West - Micro and Nano Fabricated Electromechanical and Optical Components.

[107]  Robert Pelton,et al.  Creating fast flow channels in paper fluidic devices to control timing of sequential reactions. , 2012, Lab on a chip.

[108]  T. Berthelot,et al.  Photolinker-free photoimmobilization of antibodies onto cellulose for the preparation of immunoassay membranes. , 2015, Journal of materials chemistry. B.

[109]  D. Citterio,et al.  Inkjet-printed microfluidic multianalyte chemical sensing paper. , 2008, Analytical chemistry.

[110]  Lin Zhang,et al.  Multiplex microfluidic paper-based immunoassay for the diagnosis of hepatitis C virus infection. , 2014, Analytical chemistry.

[111]  Kevin Pennings,et al.  Paper-based microfluidics with an erodible polymeric bridge giving controlled release and timed flow shutoff. , 2014, Lab on a chip.

[112]  Gary Milavetz,et al.  MULTICENTRE EVALUATION OF DISPOSABLE VISUAL MEASURING DEVICE TO ASSAY THEOPHYLLINE FROM CAPILLARY BLOOD SAMPLE , 1986, The Lancet.

[113]  R. Miller,et al.  Why diagnose influenza infections in hospitalized pediatric patients? , 1993, The Pediatric infectious disease journal.

[114]  Tomi Erho,et al.  A paper-based lateral flow assay for morphine , 2014, Analytical and Bioanalytical Chemistry.

[115]  E. W. Washburn The Dynamics of Capillary Flow , 1921 .

[116]  George M Whitesides,et al.  Rapid fabrication of pressure-driven open-channel microfluidic devices in omniphobic R(F) paper. , 2013, Lab on a chip.

[117]  George M. Whitesides,et al.  A Paper-Based Multiplexed Transaminase Test for Low-Cost, Point-of-Care Liver Function Testing , 2012, Science Translational Medicine.

[118]  Shenguang Ge,et al.  Electrochemical DNA sensor based on three-dimensional folding paper device for specific and sensitive point-of-care testing , 2012 .

[119]  Jinghua Yu,et al.  Sensitive origami dual-analyte electrochemical immunodevice based on polyaniline/Au-paper electrode and multi-labeled 3D graphene sheets , 2014 .

[120]  Roman Gerbers,et al.  A new paper-based platform technology for point-of-care diagnostics. , 2014, Lab on a chip.

[121]  Elain Fu,et al.  Two-dimensional paper networks: programmable fluidic disconnects for multi-step processes in shaped paper. , 2011, Lab on a chip.

[122]  Li Li,et al.  Multiplex electrochemical origami immunodevice based on cuboid silver-paper electrode and metal ions tagged nanoporous silver-chitosan. , 2014, Biosensors & bioelectronics.

[123]  Wei Shen,et al.  Progress in patterned paper sizing for fabrication of paper-based microfluidic sensors , 2010 .

[124]  Richard Lucas,et al.  Ueber das Zeitgesetz des kapillaren Aufstiegs von Flüssigkeiten , 1918 .

[125]  Gi-Ja Lee,et al.  A stand-alone pressure-driven 3D microfluidic chemical sensing analytic device , 2016 .

[126]  A. Adamson Physical chemistry of surfaces , 1960 .

[127]  Dermot Diamond,et al.  Fast prototyping of paper-based microfluidic devices by contact stamping using indelible ink , 2013 .

[128]  G. Whitesides,et al.  Measuring markers of liver function using a micropatterned paper device designed for blood from a fingerstick. , 2012, Analytical chemistry.

[129]  Babak Ziaie,et al.  Laser-treated hydrophobic paper: an inexpensive microfluidic platform. , 2011, Lab on a chip.

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

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

[132]  Kin Fong Lei,et al.  Paper-based enzyme-free immunoassay for rapid detection and subtyping of influenza A H1N1 and H3N2 viruses. , 2015, Analytica chimica acta.

[133]  Longfei Cai,et al.  Defining microchannels and valves on a hydrophobic paper by low-cost inkjet printing of aqueous or weak organic solutions. , 2015, Biomicrofluidics.

[134]  Elain Fu,et al.  Wax transfer printing to enable robust barrier definition in devices based on non-standard porous materials , 2017 .

[135]  Joong Ho Shin,et al.  Programmed sample delivery on a pressurized paper. , 2014, Biomicrofluidics.

[136]  George M Whitesides,et al.  Folding analytical devices for electrochemical ELISA in hydrophobic R(H) paper. , 2014, Analytical chemistry.

[137]  A. J. van der Ven,et al.  Antituberculosis drug‐induced hepatotoxicity: Concise up‐to‐date review , 2008, Journal of gastroenterology and hepatology.

[138]  Aydogan Ozcan,et al.  Integrated rapid-diagnostic-test reader platform on a cellphone. , 2012, Lab on a chip.

[139]  Chen-Hsun Weng,et al.  Colored wax-printed timers for two-dimensional and three-dimensional assays on paper-based devices. , 2014, Biomicrofluidics.

[140]  Hongying Zhu,et al.  Cost-effective and compact wide-field fluorescent imaging on a cell-phone. , 2011, Lab on a chip.

[141]  Nathaniel W. Martinez,et al.  Paper Microzone Plates as Analytical Tools for Studying Enzyme Stability: A Case Study on the Stabilization of Horseradish Peroxidase Using Trehalose and SU-8 Epoxy Novolac Resin. , 2017, Analytical chemistry.

[142]  Martti Toivakka,et al.  Controlling capillary-driven surface flow on a paper-based microfluidic channel , 2016 .

[143]  Jong-Soon Choi,et al.  Three-dimensional paper-based slip device for one-step point-of-care testing , 2016, Scientific Reports.

[144]  O. Chailapakul,et al.  Novel paper-based cholesterol biosensor using graphene/polyvinylpyrrolidone/polyaniline nanocomposite. , 2014, Biosensors & bioelectronics.

[145]  Jinghua Yu,et al.  3D origami-based multifunction-integrated immunodevice: low-cost and multiplexed sandwich chemiluminescence immunoassay on microfluidic paper-based analytical device. , 2012, Lab on a chip.

[146]  T. Sterling,et al.  American Thoracic Society Documents An Official ATS Statement : Hepatotoxicity of Antituberculosis Therapy , 2006 .