Self-contained microfluidic systems: a review.

Microfluidic systems enable rapid diagnosis, screening and monitoring of diseases and health conditions using small amounts of biological samples and reagents. Despite these remarkable features, conventional microfluidic systems rely on bulky expensive external equipment, which hinders their utility as powerful analysis tools outside of research laboratories. 'Self-contained' microfluidic systems, which contain all necessary components to facilitate a complete assay, have been developed to address this limitation. In this review, we provide an in-depth overview of self-contained microfluidic systems. We categorise these systems based on their operating mechanisms into three major groups: passive, hand-powered and active. Several examples are provided to discuss the structure, capabilities and shortcomings of each group. In particular, we discuss the self-contained microfluidic systems enabled by active mechanisms, due to their unique capability for running multi-step and highly controllable diagnostic assays. Integration of self-contained microfluidic systems with the image acquisition and processing capabilities of smartphones, especially those equipped with accessory optical components, enables highly sensitive and quantitative assays, which are discussed. Finally, the future trends and possible solutions to expand the versatility of self-contained, stand-alone microfluidic platforms are outlined.

[1]  R. Fair,et al.  Droplet-based microfluidic lab-on-a-chip for glucose detection , 2004 .

[2]  Gregory G. Lewis,et al.  Quantitative Fluorescence Assays Using a Self-Powered Paper-Based Microfluidic Device and a Camera-Equipped Cellular Phone. , 2014, RSC advances.

[3]  Nam-Trung Nguyen,et al.  Micromixers?a review , 2005 .

[4]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[5]  Robin H. Liu,et al.  Functional hydrogel structures for autonomous flow control inside microfluidic channels , 2000, Nature.

[6]  Shoji Takeuchi,et al.  A glass fiber sheet-based electroosmotic lateral flow immunoassay for point-of-care testing. , 2012, Lab on a chip.

[7]  L. Gervais,et al.  Toward one-step point-of-care immunodiagnostics using capillary-driven microfluidics and PDMS substrates. , 2009, Lab on a chip.

[8]  S. Quake,et al.  Monolithic microfabricated valves and pumps by multilayer soft lithography. , 2000, Science.

[9]  Jin-Woo Choi,et al.  Point-of-care testing (POCT) diagnostic systems using microfluidic lab-on-a-chip technologies , 2015 .

[10]  David Sinton,et al.  A miniaturized high-voltage integrated power supply for portable microfluidic applications. , 2004, Lab on a chip.

[11]  Kyungsup Han,et al.  Self-powered switch-controlled nucleic acid extraction system. , 2016, Lab on a chip.

[12]  J. Kong,et al.  Loop-mediated isothermal amplification integrated on microfluidic chips for point-of-care quantitative detection of pathogens. , 2010, Analytical chemistry.

[13]  Ann M Gronowski,et al.  Analytical performance evaluation of the i-STAT Total β-human chorionic gonadotropin immunoassay. , 2015, Clinica chimica acta; international journal of clinical chemistry.

[14]  Manjima Dhar,et al.  Research highlights: microfluidic point-of-care diagnostics , 2014 .

[15]  A Roda,et al.  Gravitational field-flow fractionation integrated with chemiluminescence detection for a self-standing point-of-care compact device in bioanalysis. , 2013, The Analyst.

[16]  Samuel K Sia,et al.  Mixing with bubbles: a practical technology for use with portable microfluidic devices. , 2006, Lab on a chip.

[17]  Luke P. Lee,et al.  Self-powered Imbibing Microfluidic Pump by Liquid Encapsulation: SIMPLE. , 2014, Lab on a chip.

[18]  R Zengerle,et al.  Rapid and fully automated bacterial pathogen detection on a centrifugal-microfluidic LabDisk using highly sensitive nested PCR with integrated sample preparation. , 2015, Lab on a chip.

[19]  J. Ducrée,et al.  Rapid, low-cost and instrument-free CD4+ cell counting for HIV diagnostics in resource-poor settings. , 2014, Lab on a chip.

[20]  Cameron Martin,et al.  Hook effect in Abbott i-STAT β-human chorionic gonadotropin (β-hCG) point of care assay. , 2014, Clinical biochemistry.

[21]  Chong H. Ahn,et al.  Institute of Physics Publishing Journal of Micromechanics and Microengineering a Review of Microvalves , 2022 .

[22]  Jijun Xiong,et al.  Passive valves based on hydrophobic microfluidics , 2003 .

[23]  Tasuku Yotoriyama,et al.  Point-of-care testing system enabling 30 min detection of influenza genes. , 2011, Lab on a chip.

[24]  Hua Zhang,et al.  Chemistry pumps: a review of chemically powered micropumps. , 2016, Lab on a chip.

[25]  W. Marsden.  I and J , 2012 .

[26]  David E. Williams,et al.  Point of care diagnostics: status and future. , 2012, Analytical chemistry.

[27]  Y. S. Zhang,et al.  A cost-effective fluorescence mini-microscope for biomedical applications. , 2015, Lab on a chip.

[28]  Andrew G. Glen,et al.  APPL , 2001 .

[29]  P ? ? ? ? ? ? ? % ? ? ? ? , 1991 .

[30]  Jane Ru Choi,et al.  An integrated paper-based sample-to-answer biosensor for nucleic acid testing at the point of care. , 2016, Lab on a chip.

[31]  Heather A Clark,et al.  Fluorescent sensors for the basic metabolic panel enable measurement with a smart phone device over the physiological range. , 2014, The Analyst.

[32]  Arnan Mitchell,et al.  Creation of Liquid Metal 3D Microstructures Using Dielectrophoresis , 2015 .

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

[34]  Luke P. Lee,et al.  Stand-alone self-powered integrated microfluidic blood analysis system (SIMBAS). , 2011, Lab on a chip.

[35]  Zhi Zhu,et al.  Distance-based microfluidic quantitative detection methods for point-of-care testing. , 2016, Lab on a chip.

[36]  Albert Folch,et al.  3D-printed microfluidic automation. , 2015, Lab on a chip.

[37]  Ke Yang,et al.  Novel developments in mobile sensing based on the integration of microfluidic devices and smartphones. , 2016, Lab on a chip.

[38]  Erdogan Gulari,et al.  Gene-Z: a device for point of care genetic testing using a smartphone. , 2012, Lab on a chip.

[39]  Ioannis Kymissis,et al.  An integrated CMOS quantitative-polymerase-chain-reaction lab-on-chip for point-of-care diagnostics. , 2014, Lab on a chip.

[40]  Stefan Lenk,et al.  A prefilled, ready-to-use electrophoresis based lab-on-a-chip device for monitoring lithium in blood. , 2010, Lab on a chip.

[41]  Wei Zhang,et al.  Liquid Metal Actuator for Inducing Chaotic Advection , 2014 .

[42]  Jinghua Yu,et al.  Microfluidic paper-based chemiluminescence biosensor for simultaneous determination of glucose and uric acid. , 2011, Lab on a chip.

[43]  P Ghazal,et al.  Development of a PCR-free electrochemical point of care test for clinical detection of methicillin resistant Staphylococcus aureus (MRSA). , 2013, The Analyst.

[44]  A. Abate,et al.  Syringe-vacuum microfluidics: A portable technique to create monodisperse emulsions. , 2011, Biomicrofluidics.

[45]  George M Whitesides,et al.  Egg beater as centrifuge: isolating human blood plasma from whole blood in resource-poor settings. , 2008, Lab on a chip.

[46]  Bingbing Gao,et al.  An exothermic chip for point-of-care testing using a forehead thermometer as a readout. , 2016, Lab on a chip.

[47]  J. Masson,et al.  Single chip SPR and fluorescent ELISA assay of prostate specific antigen. , 2015, Lab on a chip.

[48]  Baiyang Ren,et al.  Reusable acoustic tweezers for disposable devices. , 2015, Lab on a chip.

[49]  Aaas News,et al.  Book Reviews , 1893, Buffalo Medical and Surgical Journal.

[50]  Aliaa I. Shallan,et al.  Cost-effective three-dimensional printing of visibly transparent microchips within minutes. , 2014, Analytical chemistry.

[51]  Donald Wlodkowic,et al.  Immunology on chip: promises and opportunities. , 2014, Biotechnology advances.

[52]  Yi Zhang,et al.  A stacking flow immunoassay for the detection of dengue-specific immunoglobulins in salivary fluid. , 2015, Lab on a chip.

[53]  Tae-Hyeong Kim,et al.  Lab-on-a-disc for fully integrated multiplex immunoassays. , 2012, Analytical Chemistry.

[54]  M. Bergeron,et al.  From cellular lysis to microarray detection, an integrated thermoplastic elastomer (TPE) point of care Lab on a Disc. , 2015, Lab on a chip.

[55]  Meng Xiao,et al.  An integrated microfluidic device utilizing dielectrophoresis and multiplex array PCR for point-of-care detection of pathogens. , 2014, Lab on a chip.

[56]  R. Stephenson.  A and V , 1962, The British journal of ophthalmology.

[57]  J. Kang,et al.  How the capillary burst microvalve works. , 2007, Journal of colloid and interface science.

[58]  Lidong Qin,et al.  Self-powered microfluidic chips for multiplexed protein assays from whole blood. , 2009, Lab on a chip.

[59]  Ali Khademhosseini,et al.  A mini-microscope for in situ monitoring of cells. , 2012, Lab on a chip.

[60]  Mohammadali Safavieh,et al.  A simple cassette as point-of-care diagnostic device for naked-eye colorimetric bacteria detection. , 2014, The Analyst.

[61]  Arnan Mitchell,et al.  Concurrent shear stress and chemical stimulation of mechano-sensitive cells by discontinuous dielectrophoresis. , 2016, Biomicrofluidics.

[62]  Hui Chen,et al.  A portable and integrated nucleic acid amplification microfluidic chip for identifying bacteria. , 2012, Lab on a chip.

[63]  Y. K. Cheung,et al.  1 Supplementary Information for : Microfluidics-based diagnostics of infectious diseases in the developing world , 2011 .

[64]  Samuel K Sia,et al.  Microfluidics and point-of-care testing. , 2008, Lab on a chip.

[65]  Adam L. Washburn,et al.  Quantitative, label-free detection of five protein biomarkers using multiplexed arrays of silicon photonic microring resonators. , 2010, Analytical chemistry.

[66]  Khashayar Khoshmanesh,et al.  An Integrated Liquid Cooling System Based on Galinstan Liquid Metal Droplets. , 2016, ACS applied materials & interfaces.

[67]  Samuel K Sia,et al.  Actuation of elastomeric microvalves in point-of-care settings using handheld, battery-powered instrumentation. , 2010, Lab on a chip.

[68]  Feng Xu,et al.  Biomarker detection for disease diagnosis using cost-effective microfluidic platforms. , 2015, The Analyst.

[69]  J R Buser,et al.  One-step purification and concentration of DNA in porous membranes for point-of-care applications. , 2015, Lab on a chip.

[70]  H. Bau,et al.  A self-heating cartridge for molecular diagnostics. , 2011, Lab on a chip.

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

[72]  David Erickson,et al.  A smartphone platform for the quantification of vitamin D levels. , 2014, Lab on a chip.

[73]  P. Neužil,et al.  Disposable real-time microPCR device: lab-on-a-chip at a low cost. , 2006, Molecular bioSystems.

[74]  H. Morgan,et al.  Integrated systems for rapid point of care (PoC) blood cell analysis. , 2011, Lab on a chip.

[75]  Mandy L Y Sin,et al.  An AC electrokinetics facilitated biosensor cassette for rapid pathogen identification. , 2013, The Analyst.

[76]  Arnan Mitchell,et al.  Analysing calcium signalling of cells under high shear flows using discontinuous dielectrophoresis , 2015, Scientific Reports.

[77]  Shuichi Takayama,et al.  Multiplexed hydraulic valve actuation using ionic liquid filled soft channels and Braille displays , 2007 .

[78]  Mats Nystrand,et al.  A lateral flow paper microarray for rapid allergy point of care diagnostics. , 2014, The Analyst.

[79]  Ute Drechsler,et al.  Autonomous microfluidic capillary system. , 2002, Analytical chemistry.

[80]  Lin Li,et al.  A smartphone controlled handheld microfluidic liquid handling system. , 2014, Lab on a chip.

[81]  Melanie Kess,et al.  Multi-parameter determination of TNFα, PCT and CRP for point-of-care testing. , 2011, The Analyst.

[82]  Sehwan Lee,et al.  Development of functional lab-on-a-chip on polymer for point-of-care testing of metabolic parameters. , 2008, Lab on a chip.

[83]  Saeid Nahavandi,et al.  Particle trapping using dielectrophoretically patterned carbon nanotubes , 2010, Electrophoresis.

[84]  C. Ahn,et al.  An innovative sample-to-answer polymer lab-on-a-chip with on-chip reservoirs for the POCT of thyroid stimulating hormone (TSH) , 2013, 2013 IEEE 26th International Conference on Micro Electro Mechanical Systems (MEMS).

[85]  A Manz,et al.  Chemical amplification: continuous-flow PCR on a chip. , 1998, Science.

[86]  Jan Roelof van der Meer,et al.  Compact portable biosensor for arsenic detection in aqueous samples with Escherichia coli bioreporter cells. , 2014, The Review of scientific instruments.

[87]  Juan G. Santiago,et al.  A review of micropumps , 2004 .

[88]  W. Qiu,et al.  Integration of cell phone imaging with microchip ELISA to detect ovarian cancer HE4 biomarker in urine at the point-of-care. , 2011, Lab on a chip.

[89]  Donald Wlodkowic,et al.  Fish on chips: Microfluidic living embryo array for accelerated in vivo angiogenesis assays , 2013 .

[90]  Jørgen Jespersen,et al.  Analytical and clinical validation of a new point-of-care testing system for determination of D-Dimer in human blood. , 2010, Thrombosis research.

[91]  A. Woolley,et al.  3D printed microfluidic devices with integrated valves. , 2015, Biomicrofluidics.

[92]  Mohammadali Safavieh,et al.  A flexible and low-cost polypropylene pouch for naked-eye detection of herpes simplex viruses. , 2015, The Analyst.

[93]  Cheng Guo Li,et al.  A self-powered one-touch blood extraction system: a novel polymer-capped hollow microneedle integrated with a pre-vacuum actuator. , 2015, Lab on a chip.

[94]  Samuel K Sia,et al.  Commercialization of microfluidic point-of-care diagnostic devices. , 2012, Lab on a chip.

[95]  Ji Yoon Kang,et al.  A polymer lab-on-a-chip for reverse transcription (RT)-PCR based point-of-care clinical diagnostics. , 2008, Lab on a chip.

[96]  Herman Goossens,et al.  Integrated DNA and RNA extraction and purification on an automated microfluidic cassette from bacterial and viral pathogens causing community-acquired lower respiratory tract infections. , 2014, Lab on a chip.

[97]  Kevin W Plaxco,et al.  Detection of IP-10 protein marker in undiluted blood serum via an electrochemical E-DNA scaffold sensor. , 2013, The Analyst.

[98]  Tae Seok Seo,et al.  An integrated slidable and valveless microdevice with solid phase extraction, polymerase chain reaction, and immunochromatographic strip parts for multiplex colorimetric pathogen detection. , 2015, Lab on a chip.

[99]  David Erickson,et al.  Cholesterol testing on a smartphone. , 2014, Lab on a chip.

[100]  Joseph C Liao,et al.  Advances and challenges in biosensor-based diagnosis of infectious diseases , 2014, Expert review of molecular diagnostics.

[101]  S. Quake,et al.  Microfluidics: Fluid physics at the nanoliter scale , 2005 .

[102]  Andrea Valsesia,et al.  Multiplexed label-free optical biosensor for medical diagnostics , 2014, Journal of biomedical optics.

[103]  Lukas Novak,et al.  Rapid detection of viral RNA by a pocket-size real-time PCR system. , 2010, Lab on a chip.

[104]  Saeid Nahavandi,et al.  Microfluidic platforms for biomarker analysis. , 2014, Lab on a chip.

[105]  David Issadore,et al.  Miniature magnetic resonance system for point-of-care diagnostics. , 2011, Lab on a chip.

[106]  Ehsan Samiei,et al.  A review of digital microfluidics as portable platforms for lab-on a-chip applications. , 2016, Lab on a chip.

[107]  Po Ki Yuen,et al.  Multidimensional modular microfluidic system. , 2009, Lab on a chip.

[108]  David Erickson,et al.  Detection of Kaposi's sarcoma associated herpesvirus nucleic acids using a smartphone accessory. , 2014, Lab on a chip.

[109]  Hongying Zhu,et al.  Cost-effective and rapid blood analysis on a cell-phone. , 2013, Lab on a chip.

[110]  Vijay Srinivasan,et al.  Development of a digital microfluidic platform for point of care testing. , 2008, Lab on a chip.

[111]  Mehmet Toner,et al.  Enhancing the performance of a point-of-care CD4+ T-cell counting microchip through monocyte depletion for HIV/AIDS diagnostics. , 2009, Lab on a chip.

[112]  Wei Jin,et al.  Self-priming compartmentalization digital LAMP for point-of-care. , 2012, Lab on a chip.

[113]  Da Xing,et al.  A handheld flow genetic analysis system (FGAS): towards rapid, sensitive, quantitative and multiplex molecular diagnosis at the point-of-care level. , 2015, Lab on a chip.

[114]  Andreas Manz,et al.  Handheld real-time PCR device. , 2016, Lab on a chip.

[115]  S Elizabeth Hulme,et al.  Incorporation of prefabricated screw, pneumatic, and solenoid valves into microfluidic devices. , 2009, Lab on a chip.

[116]  Uli Lemmer,et al.  Flexible planar microfluidic chip employing a light emitting diode and a PIN-photodiode for portable flow cytometers. , 2012, Lab on a chip.

[117]  Nuno M Reis,et al.  A lab-in-a-briefcase for rapid prostate specific antigen (PSA) screening from whole blood. , 2014, Lab on a chip.

[118]  S. Tang,et al.  Liquid metal enabled pump , 2014, Proceedings of the National Academy of Sciences.

[119]  Kwang W. Oh,et al.  Vacuum-driven power-free microfluidics utilizing the gas solubility or permeability of polydimethylsiloxane (PDMS). , 2015, Lab on a chip.

[120]  Shuichi Takayama,et al.  Handheld recirculation system and customized media for microfluidic cell culture. , 2006, Lab on a chip.

[121]  Roland Zengerle,et al.  Centrifugal microfluidic system for primary amplification and secondary real-time PCR. , 2010, Lab on a chip.

[122]  Chao Ma,et al.  A self-powered, one-step chip for rapid, quantitative and multiplexed detection of proteins from pinpricks of whole blood. , 2010, Lab on a chip.

[123]  Syed A Hashsham,et al.  Miniaturized nucleic acid amplification systems for rapid and point-of-care diagnostics: a review. , 2012, Analytica chimica acta.

[124]  F. Schwemmer,et al.  LabDisk with complete reagent prestorage for sample-to-answer nucleic acid based detection of respiratory pathogens verified with influenza A H3N2 virus. , 2016, Lab on a chip.

[125]  Jinzhao Song,et al.  A high-efficiency superhydrophobic plasma separator. , 2016, Lab on a chip.