Microfluidics for DNA and protein analysis with multiplex microbead-based assays

Early screening and diagnosis of diseases require the development of sensitive, reliable, and inexpensive high-throughput assays. There is a growing need for innovative diagnostic technologies that provide accurate detection of a broad range of diseases and enhance laboratory productivity. Developments in micro- and nanotechnology have advanced the “lab-on-a-chip” concept towards a new generation of point-of-care diagnostic devices that enable parallel detection of multiple analytes in small-volume samples with high sensitivity in a short time. These features fulfill some of the important criteria of bioanalysis used for biochemical studies, environmental analyses, and clinical diagnostics. However, the multiplexing capability of microfluidic-based assay is limited compared to conventional flow cytometric assays, particularly for encoded microbead-based assays, which are capable of simultaneously analyzing multiple analyte. It is possible to incorporate the microbead-based assays into microfluidic devices in order to retain all the advantages of the microdevice and significantly improve multiplexing capability. In this chapter, we summarize the latest development in microbead-based assays and discuss the integration of the microbead technology with microfluidic devices. Applications of the integrated approach in multiplexed protein and DNA analysis are growing rapidly in the areas of biomarker research, cancer screening, and disease diagnosis. The prospects for future development and commercialization of these microbead-based microfluidic devices are also discussed.

[1]  S. Jon,et al.  High-density immobilization of antibodies onto nanobead-coated cyclic olefin copolymer plastic surfaces for application as a sensitive immunoassay chip , 2012, Biomedical Microdevices.

[2]  Frédéric Reymond,et al.  Why the move to microfluidics for protein analysis? , 2004, Current opinion in biotechnology.

[3]  David G Spiller,et al.  Encoded microcarriers for high-throughput multiplexed detection. , 2006, Angewandte Chemie.

[4]  Donald Wlodkowic,et al.  Microfluidic single-cell array cytometry for the analysis of tumor apoptosis. , 2009, Analytical chemistry.

[5]  Daniel I. C. Wang,et al.  Engineering cell shape and function. , 1994, Science.

[6]  Xingyu Jiang,et al.  Nanomaterials for Ultrasensitive Protein Detection , 2013, Advanced materials.

[7]  He Zhang,et al.  Aptamer-based microfluidic beads array sensor for simultaneous detection of multiple analytes employing multienzyme-linked nanoparticle amplification and quantum dots labels. , 2014, Biosensors & bioelectronics.

[8]  D. J. Harrison,et al.  Immunomagnetic T cell capture from blood for PCR analysis using microfluidic systems. , 2004, Lab on a chip.

[9]  K. Sato,et al.  Synergism between particle-based multiplexing and microfluidics technologies may bring diagnostics closer to the patient , 2008, Analytical and bioanalytical chemistry.

[10]  James F Rusling,et al.  Ultrasensitive immunosensor for cancer biomarker proteins using gold nanoparticle film electrodes and multienzyme-particle amplification. , 2009, ACS nano.

[11]  Robert Puers,et al.  Digital microfluidics-enabled single-molecule detection by printing and sealing single magnetic beads in femtoliter droplets. , 2013, Lab on a chip.

[12]  Nicole Pamme,et al.  Mobile magnetic particles as solid-supports for rapid surface-based bioanalysis in continuous flow. , 2009, Lab on a chip.

[13]  Richard A. Flynn,et al.  VCSEL Arrays as Micromanipulators in Chip-Based Biosystems , 2003 .

[14]  C. S. Chen,et al.  Geometric control of cell life and death. , 1997, Science.

[15]  William A. Mcmillan,et al.  Rapid, automated nucleic acid probe assays using silicon microstructures for nucleic acid concentration. , 1999, Journal of biomechanical engineering.

[16]  O. Siiman,et al.  Covalently Bound Antibody on Polystyrene Latex Beads: Formation, Stability, and Use in Analyses of White Blood Cell Populations. , 2001, Journal of colloid and interface science.

[17]  I-Ming Hsing,et al.  A DNA biochip for on-the-spot multiplexed pathogen identification , 2006, Nucleic acids research.

[18]  Hywel Morgan,et al.  Bead-based immunoassays using a micro-chip flow cytometer. , 2007, Lab on a chip.

[19]  Frank Diehl,et al.  Detection and quantification of mutations in the plasma of patients with colorectal tumors. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[20]  K. Dholakia,et al.  Microfluidic sorting in an optical lattice , 2003, Nature.

[21]  Hongyan Sun,et al.  Single layer linear array of microbeads for multiplexed analysis of DNA and proteins. , 2014, Biosensors & bioelectronics.

[22]  Andreas Manz,et al.  Total nucleic acid analysis integrated on microfluidic devices. , 2007, Lab on a chip.

[23]  Peter Enoksson,et al.  Micromachined flow-through filter-chamber for chemical reactions on beads , 2000 .

[24]  Shuming Nie,et al.  Quantum dot-encoded mesoporous beads with high brightness and uniformity: rapid readout using flow cytometry. , 2004, Analytical chemistry.

[25]  Won-Gun Koh,et al.  Fabrication of microfluidic devices incorporating bead-based reaction and microarray-based detection system for enzymatic assay , 2009 .

[26]  Mengsu Yang,et al.  Microfluidics technology for manipulation and analysis of biological cells , 2006 .

[27]  Wanqing Yue,et al.  Nanoparticle-based signal generation and amplification in microfluidic devices for bioanalysis. , 2013, The Analyst.

[28]  Shuichi Takayama,et al.  Multiplexed spectral signature detection for microfluidic color-coded bioparticle flow. , 2010, Analytical chemistry.

[29]  Alan Aderem,et al.  A microfluidic device for multiplexed protein detection in nano-liter volumes. , 2009, Analytical biochemistry.

[30]  Xiaobo Yu,et al.  µFBI: A Microfluidic Bead-Based Immunoassay for Multiplexed Detection of Proteins from a µL Sample Volume , 2010, PloS one.

[31]  Liwei Lin,et al.  A dynamic bead-based microarray for parallel DNA detection , 2011 .

[32]  M. Trau,et al.  Multiplexed microsphere diagnostic tools in gene expression applications: factors and futures , 2006, International journal of nanomedicine.

[33]  Richard A. Flynn,et al.  Optical Manipulation of Objects and Biological Cells in Microfluidic Devices , 2003 .

[34]  S. Dunbar,et al.  Application of the luminex LabMAP in rapid screening for mutations in the cystic fibrosis transmembrane conductance regulator gene: A pilot study , 2000, Clinical chemistry.

[35]  Frank Diehl,et al.  BEAMing: single-molecule PCR on microparticles in water-in-oil emulsions , 2006, Nature Methods.

[36]  S. Nie,et al.  Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules , 2001, Nature Biotechnology.

[37]  C. S. Wong,et al.  Surface Modification of Polystyrene Beads by UV/Ozone Treatment , 2011 .

[38]  Helen Song,et al.  Reactions in droplets in microfluidic channels. , 2006, Angewandte Chemie.

[39]  K. Neuman,et al.  Tethered-bead, immune sandwich assay. , 2015, Biosensors & bioelectronics.

[40]  Fook Siong Chau,et al.  Filter-based microfluidic device as a platform for immunofluorescent assay of microbial cells. , 2004, Lab on a chip.

[41]  Anupam Singhal,et al.  Microfluidic measurement of antibody-antigen binding kinetics from low-abundance samples and single cells. , 2010, Analytical chemistry.

[42]  Jin Chang,et al.  Structural design and preparation of high-performance QD-encoded polymer beads for suspension arrays , 2011 .

[43]  Dieter Stoll,et al.  Miniaturised multiplexed immunoassays. , 2002, Current opinion in chemical biology.

[44]  H. Bau,et al.  Pulsating bead-based assay. , 2011, Analytical chemistry.

[45]  Howon Lee,et al.  Colour-barcoded magnetic microparticles for multiplexed bioassays. , 2010, Nature materials.

[46]  Anthony G. Frutos,et al.  Rare earth-doped glass microbarcodes , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[47]  Mattias Goksör,et al.  Optical tweezers applied to a microfluidic system. , 2004, Lab on a chip.

[48]  Mengsu Yang,et al.  PDMS-based microfluidic device with multi-height structures fabricated by single-step photolithography using printed circuit board as masters. , 2003, The Analyst.

[49]  David R Walt,et al.  Very high density sensing arrays. , 2008, Chemical reviews.

[50]  Ji Liang,et al.  Tailoring the adsorption rate of porous chitosan and chitosan–carbon nanotube core–shell beads , 2014 .

[51]  Mengsu Yang,et al.  Hydrodynamic simulation of cell docking in microfluidic channels with different dam structures. , 2004, Lab on a chip.

[52]  Takaaki Kojima,et al.  PCR amplification from single DNA molecules on magnetic beads in emulsion: application for high-throughput screening of transcription factor targets , 2005, Nucleic acids research.

[53]  David R Walt,et al.  Intelligent medical diagnostics via molecular logic. , 2009, Journal of the American Chemical Society.

[54]  Sebastian J Maerkl,et al.  Integration of plasmonic trapping in a microfluidic environment. , 2009, Optics express.

[55]  Ali Khademhosseini,et al.  Cell docking in double grooves in a microfluidic channel. , 2009, Small.

[56]  C. Batt,et al.  Nucleic acid purification using microfabricated silicon structures. , 2003, Biosensors & bioelectronics.

[57]  Robert Penchovsky,et al.  Programmable and automated bead-based microfluidics for versatile DNA microarrays under isothermal conditions. , 2013, Lab on a chip.

[58]  Qiao Lin,et al.  A MEMS-Based Approach to Single Nucleotide Polymorphism Genotyping. , 2013, Sensors and actuators. A, Physical.

[59]  R. Schasfoort,et al.  TUTORIAL REVIEW , 2001 .

[60]  S. Goodman,et al.  Sensitive digital quantification of DNA methylation in clinical samples , 2009, Nature Biotechnology.

[61]  A. Manz,et al.  Miniaturized total chemical analysis systems: A novel concept for chemical sensing , 1990 .

[62]  T. Joos,et al.  Multiplex microsphere‐based flow cytometric platforms for protein analysis and their application in clinical proteomics – from assays to results , 2009, Electrophoresis.

[63]  David R Walt,et al.  Microsensor Arrays for Saliva Diagnostics , 2007, Annals of the New York Academy of Sciences.

[64]  A. Ashkin,et al.  Optical trapping and manipulation of viruses and bacteria. , 1987, Science.

[65]  Darwin R. Reyes,et al.  Micro total analysis systems. 2. Analytical standard operations and applications. , 2002, Analytical chemistry.

[66]  Samuel K Sia,et al.  Effect of volume- and time-based constraints on capture of analytes in microfluidic heterogeneous immunoassays. , 2008, Lab on a chip.

[67]  Gwo-Bin Lee,et al.  Extraction of genomic DNA and detection of single nucleotide polymorphism genotyping utilizing an integrated magnetic bead-based microfluidic platform , 2009 .

[68]  W. Greenleaf,et al.  Direct observation of base-pair stepping by RNA polymerase , 2005, Nature.

[69]  K. Jensen,et al.  Cells on chips , 2006, Nature.

[70]  B. Séraphin,et al.  The tandem affinity purification (TAP) method: a general procedure of protein complex purification. , 2001, Methods.

[71]  Ming C. Wu,et al.  Massively parallel manipulation of single cells and microparticles using optical images , 2005, Nature.

[72]  A S Rudolph,et al.  Spatially controlled adhesion, spreading, and differentiation of endothelial cells on self-assembled molecular monolayers. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[73]  Catherine Situma,et al.  Merging microfluidics with microarray-based bioassays. , 2006, Biomolecular engineering.

[74]  U. Prabhakar,et al.  Simultaneous quantification of proinflammatory cytokines in human plasma using the LabMAP assay. , 2002, Journal of immunological methods.

[75]  T. Vo‐Dinh,et al.  Biosensors and biochips: advances in biological and medical diagnostics , 2000, Fresenius' journal of analytical chemistry.

[76]  Kenji Yasuda,et al.  On-chip single-cell microcultivation assay for monitoring environmental effects on isolated cells. , 2003, Biochemical and biophysical research communications.

[77]  Zhongze Gu,et al.  Encoded silica colloidal crystal beads as supports for potential multiplex immunoassay. , 2008, Analytical chemistry.

[78]  Pooja Sabhachandani,et al.  Approaching near real-time biosensing: microfluidic microsphere based biosensor for real-time analyte detection. , 2015, Biosensors & bioelectronics.

[79]  J. McDevitt,et al.  Modeling analyte transport and capture in porous bead sensors. , 2012, Analytical chemistry.

[80]  Ali Khademhosseini,et al.  Molded polyethylene glycol microstructures for capturing cells within microfluidic channels. , 2004, Lab on a chip.

[81]  P. Cremer,et al.  Microfluidic tools for studying the specific binding, adsorption, and displacement of proteins at interfaces. , 2005, Annual review of physical chemistry.

[82]  J. Landers,et al.  Evaluation of silica resins for direct and efficient extraction of DNA from complex biological matrices in a miniaturized format. , 2000, Analytical biochemistry.

[83]  D. Peterson,et al.  Solid supports for micro analytical systems. , 2005, Lab on a chip.

[84]  Wenwan Zhong,et al.  Typing of multiple single-nucleotide polymorphisms by a microsphere-based rolling circle amplification assay. , 2007, Analytical chemistry.

[85]  Richard A Mathies,et al.  An integrated microfluidic processor for single nucleotide polymorphism-based DNA computing. , 2005, Lab on a chip.

[86]  Mengsu Yang,et al.  Integrated sieving microstructures on microchannels for biological cell trapping and droplet formation. , 2011, Lab on a chip.

[87]  Elisabeth Verpoorte,et al.  Beads and chips: new recipes for analysis. , 2003, Lab on a chip.

[88]  S. Tokura,et al.  Surface modification of nonporous glass beads with chitosan and their adsorption property for transition metal ions , 2002 .

[89]  D. Walt,et al.  Microsphere-based rolling circle amplification microarray for the detection of DNA and proteins in a single assay. , 2009, Analytical chemistry.

[90]  W. Ford,et al.  Surface modification of colloidal silica , 1990 .

[91]  Laurent Malaquin,et al.  A low cost and high throughput magnetic bead-based immuno-agglutination assay in confined droplets. , 2013, Lab on a chip.

[92]  Luke P. Lee,et al.  Single-cell enzyme concentrations, kinetics, and inhibition analysis using high-density hydrodynamic cell isolation arrays. , 2006, Analytical chemistry.

[93]  D. Dressman,et al.  Transforming single DNA molecules into fluorescent magnetic particles for detection and enumeration of genetic variations , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[94]  Raphael M. Ottenbrite,et al.  Surface modification of inorganic oxide particles with silane coupling agent and organic dyes , 2001 .

[95]  Haim H Bau,et al.  Microfluidic, bead-based assay: Theory and experiments. , 2010, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[96]  Yoon-Kyoung Cho,et al.  One-Step Pathogen Specific DNA Extraction from Whole Blood on a Centrifugal Microfluidic Device , 2007, TRANSDUCERS 2007 - 2007 International Solid-State Sensors, Actuators and Microsystems Conference.

[97]  Martin A M Gijs,et al.  Ultrasensitive protein detection: a case for microfluidic magnetic bead-based assays. , 2013, Lab on a chip.

[98]  Guoqing Hu,et al.  Modeling micropatterned antigen-antibody binding kinetics in a microfluidic chip. , 2007, Biosensors & bioelectronics.

[99]  J. Rusling,et al.  On-line protein capture on magnetic beads for ultrasensitive microfluidic immunoassays of cancer biomarkers. , 2014, Biosensors & bioelectronics.

[100]  R. Lavery,et al.  DNA: An Extensible Molecule , 1996, Science.

[101]  Suhyeon Kim,et al.  Microchip-based one step DNA extraction and real-time PCR in one chamber for rapid pathogen identification. , 2006, Lab on a chip.

[102]  Mengsu Yang,et al.  Multienzyme-nanoparticles amplification for sensitive virus genotyping in microfluidic microbeads array using Au nanoparticle probes and quantum dots as labels. , 2011, Biosensors & bioelectronics.

[103]  H. Ju,et al.  A chemiluminescent immunosensor based on antibody immobilized carboxylic resin beads coupled with micro-bubble accelerated immunoreaction for fast flow-injection immunoassay. , 2008, Biosensors & bioelectronics.

[104]  G. Whitesides,et al.  Fabrication of microfluidic systems in poly(dimethylsiloxane) , 2000, Electrophoresis.

[105]  M. Sheetz,et al.  Transcription by single molecules of RNA polymerase observed by light microscopy , 1991, Nature.

[106]  F. Graziano,et al.  Simultaneous measurement of six cytokines in a single sample of human tears using microparticle-based flow cytometry: allergics vs. non-allergics. , 2001, Journal of immunological methods.

[107]  C. Y. Teo,et al.  Enhanced microfiltration devices configured with hydrodynamic trapping and a rain drop bypass filtering architecture for microbial cells detection. , 2008, Lab on a chip.

[108]  H. Fenniri,et al.  Preparation, physical properties, on-bead binding assay and spectroscopic reliability of 25 barcoded polystyrene-poly(ethylene glycol) graft copolymers. , 2003, Journal of the American Chemical Society.

[109]  David R Walt,et al.  Fiber-optic microsphere-based antibody array for the analysis of inflammatory cytokines in saliva. , 2009, Analytical chemistry.

[110]  Cheuk-Wing Li,et al.  Microfluidics study of intracellular calcium response to mechanical stimulation on single suspension cells. , 2013, Lab on a chip.

[111]  He Zhang,et al.  Microfluidic beads-based immunosensor for sensitive detection of cancer biomarker proteins using multienzyme-nanoparticle amplification and quantum dots labels. , 2013, Biosensors & bioelectronics.

[112]  Frank Diehl,et al.  BEAMing up for detection and quantification of rare sequence variants , 2006, Nature Methods.

[113]  Ju Hun Yeon,et al.  Drug permeability assay using microhole-trapped cells in a microfluidic device. , 2009, Analytical chemistry.

[114]  K E Healy,et al.  Kinetics of bone cell organization and mineralization on materials with patterned surface chemistry. , 1996, Biomaterials.

[115]  Mengsu Yang,et al.  Cell docking and on-chip monitoring of cellular reactions with a controlled concentration gradient on a microfluidic device. , 2002, Analytical chemistry.

[116]  E. Hornes,et al.  Assessment of methods for covalent binding of nucleic acids to magnetic beads, Dynabeads, and the characteristics of the bound nucleic acids in hybridization reactions. , 1988, Nucleic acids research.

[117]  Mengsu Yang,et al.  Dose-dependent cell-based assays in V-shaped microfluidic channels. , 2006, Lab on a chip.

[118]  Hicham Fenniri,et al.  Self-encoded polymer beads for microarray technologies , 2007 .

[119]  Soong Ho Um,et al.  Multifunctional nanoarchitectures from DNA-based ABC monomers , 2009, Nature nanotechnology.

[120]  David R Walt,et al.  Fibre optic microarrays. , 2010, Chemical Society reviews.

[121]  Kevin Braeckmans,et al.  Encoding microcarriers: present and future technologies , 2002, Nature Reviews Drug Discovery.

[122]  G. Cai,et al.  Microfluidic formation of single cell array for parallel analysis of Ca2+ release-activated Ca2+ (CRAC) channel activation and inhibition. , 2010, Analytical biochemistry.

[123]  Patrick S Doyle,et al.  Multiplexed protein quantification with barcoded hydrogel microparticles. , 2010, Analytical chemistry.

[124]  He Zhang,et al.  Microfluidic bead-based enzymatic primer extension for single-nucleotide discrimination using quantum dots as labels. , 2012, Analytical biochemistry.

[125]  A. Manz,et al.  Micro total analysis systems. Recent developments. , 2004, Analytical chemistry.

[126]  G. Whitesides,et al.  Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device , 2002, Nature Biotechnology.

[127]  J. Dougherty,et al.  Rapid hybridization kinetics of DNA attached to submicron latex particles. , 1987, Nucleic acids research.

[128]  Toshinori Munakata,et al.  Flow resistance for microfluidic logic operations , 2004 .

[129]  D. Beebe,et al.  Controlled microfluidic interfaces , 2005, Nature.