Porous Bead-Based Diagnostic Platforms: Bridging the Gaps in Healthcare

Advances in lab-on-a-chip systems have strong potential for multiplexed detection of a wide range of analytes with reduced sample and reagent volume; lower costs and shorter analysis times. The completion of high-fidelity multiplexed and multiclass assays remains a challenge for the medical microdevice field; as it struggles to achieve and expand upon at the point-of-care the quality of results that are achieved now routinely in remote laboratory settings. This review article serves to explore for the first time the key intersection of multiplexed bead-based detection systems with integrated microfluidic structures alongside porous capture elements together with biomarker validation studies. These strategically important elements are evaluated here in the context of platform generation as suitable for near-patient testing. Essential issues related to the scalability of these modular sensor ensembles are explored as are attempts to move such multiplexed and multiclass platforms into large-scale clinical trials. Recent efforts in these bead sensors have shown advantages over planar microarrays in terms of their capacity to generate multiplexed test results with shorter analysis times. Through high surface-to-volume ratios and encoding capabilities; porous bead-based ensembles; when combined with microfluidic elements; allow for high-throughput testing for enzymatic assays; general chemistries; protein; antibody and oligonucleotide applications.

[1]  J. O’Grady,et al.  Development and validation of a rapid real-time PCR based method for the specific detection of Salmonella on fresh meat. , 2009, Meat science.

[2]  M. Weiner,et al.  Flow cytometric platform for high-throughput single nucleotide polymorphism analysis. , 2001, BioTechniques.

[3]  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.

[4]  Axel Warsinke,et al.  Point-of-care testing of proteins , 2009, Analytical and bioanalytical chemistry.

[5]  P. Gustavsson,et al.  Direct measurements of convective fluid velocities in superporous agarose beads. , 1998, Journal of chromatography. A.

[6]  J. McDevitt,et al.  Programmable nano-bio-chip sensors: analytical meets clinical. , 2010, Analytical chemistry.

[7]  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.

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

[9]  G. Kovacs,et al.  Evolving point-of-care diagnostics using up-converting phosphor bioanalytical systems. , 2009, Analytical chemistry.

[10]  John P Nolan,et al.  Suspension array technology: evolution of the flat-array paradigm. , 2002, Trends in biotechnology.

[11]  B. Weimer,et al.  Optimizing the immobilization of single-stranded DNA onto glass beads. , 2001, Journal of biochemical and biophysical methods.

[12]  R. Powers,et al.  Bedside diagnostic testing of body fluids. , 1997, The American journal of emergency medicine.

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

[14]  N. Anderson,et al.  The clinical plasma proteome: a survey of clinical assays for proteins in plasma and serum. , 2010, Clinical chemistry.

[15]  D. Vignali Multiplexed particle-based flow cytometric assays. , 2000, Journal of immunological methods.

[16]  Protein profiling comes of age , 2001, Genome Biology.

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

[18]  Jesse V Jokerst,et al.  Location of biomarkers and reagents within agarose beads of a programmable bio-nano-chip. , 2011, Small.

[19]  Wen-Tso Liu,et al.  A spatially addressable bead-based biosensor for simple and rapid DNA detection. , 2008, Biosensors & bioelectronics.

[20]  Peter B. Luppa,et al.  Point-of-care testing (POCT): Current techniques and future perspectives , 2011, TrAC Trends in Analytical Chemistry.

[21]  S. Shoji Micro Total Analysis Systems , 1999 .

[22]  Shu-Hui Chen,et al.  Functionalized 3D-hydrogel plugs covalently patterned inside hydrophilic poly(dimethylsiloxane) microchannels for flow-through immunoassays. , 2009, Analytical chemistry.

[23]  J. Fell,et al.  Use of a Suspension Array for Rapid Identification of the Varieties and Genotypes of the Cryptococcus neoformans Species Complex , 2005, Journal of Clinical Microbiology.

[24]  C T Lim,et al.  Bead-based microfluidic immunoassays: the next generation. , 2007, Biosensors & bioelectronics.

[25]  R J Fulton,et al.  Advanced multiplexed analysis with the FlowMetrix system. , 1997, Clinical chemistry.

[26]  S. Dunbar,et al.  Quantitative, multiplexed detection of bacterial pathogens: DNA and protein applications of the Luminex LabMAP system. , 2003, Journal of microbiological methods.

[27]  Terry J. Smith,et al.  tmRNA--a novel high-copy-number RNA diagnostic target--its application for Staphylococcus aureus detection using real-time NASBA. , 2009, FEMS microbiology letters.

[28]  Bryan Lincoln,et al.  Integrated microfluidic tmRNA purification and real-time NASBA device for molecular diagnostics. , 2008, Lab on a chip.

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

[30]  Joseph Wang,et al.  Point-of-care biosensor systems for cancer diagnostics/prognostics. , 2006, Biosensors & bioelectronics.

[31]  Chad A Mirkin,et al.  A bio-barcode assay for on-chip attomolar-sensitivity protein detection. , 2006, Lab on a chip.

[32]  J B Shear,et al.  Development of multianalyte sensor arrays composed of chemically derivatized polymeric microspheres localized in micromachined cavities. , 2001, Journal of the American Chemical Society.

[33]  Leigh B. Bangs,et al.  New developments in particle-based immunoassays: Introduction , 1996 .

[34]  P. Bourbeau,et al.  Use of Gen-Probe AccuProbe Group B streptococcus test to detect group B streptococci in broth cultures of vaginal-anorectal specimens from pregnant women: comparison with traditional culture method , 1997, Journal of clinical microbiology.

[35]  F. H. Garner,et al.  Chemical Engineering , 1955, Nature.

[36]  Jesse V Jokerst,et al.  Programmable nano-bio-chips: multifunctional clinical tools for use at the point-of-care. , 2010, Nanomedicine.

[37]  P. Gustavsson,et al.  Superporous agarose beads as a hydrophobic interaction chromatography support. , 1999, Journal of chromatography. A.

[38]  Pei Wang,et al.  The interface between biomarker discovery and clinical validation: The tar pit of the protein biomarker pipeline , 2008, Proteomics. Clinical applications.

[39]  Noritada Kaji,et al.  Immuno-pillar chip: a new platform for rapid and easy-to-use immunoassay. , 2010, Lab on a chip.

[40]  M F Burritt,et al.  Point-of-care testing. , 1995, Mayo Clinic proceedings.

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

[42]  H. Bau,et al.  Porous bead-based microfluidic assay: theory and confocal microscope imaging , 2012 .

[43]  Samuel K Sia,et al.  Lab-on-a-chip devices for global health: past studies and future opportunities. , 2007, Lab on a chip.

[44]  Amy E Herr,et al.  Fully integrated microfluidic platform enabling automated phosphoprofiling of macrophage response. , 2009, Analytical chemistry.

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

[46]  U. Prabhakar,et al.  Multiplexed cytokine sandwich immunoassays: clinical applications. , 2005, Methods in molecular medicine.

[47]  Takehiko Kitamori,et al.  Integration of Chemical and Biochemical Analysis Systems into a Glass Microchip , 2003, Analytical sciences : the international journal of the Japan Society for Analytical Chemistry.

[48]  David R. Walt,et al.  Bead-based Fiber-Optic Arrays , 2000, Science.

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

[50]  John T McDevitt,et al.  A microchip-based assay for interleukin-6. , 2007, Methods in molecular biology.

[51]  V. Gold Compendium of chemical terminology , 1987 .

[52]  Bernhard H Weigl,et al.  Microfluidic technologies in clinical diagnostics. , 2002, Clinica chimica acta; international journal of clinical chemistry.

[53]  Steven A Carr,et al.  Protein biomarker discovery and validation: the long and uncertain path to clinical utility , 2006, Nature Biotechnology.

[54]  R. Boom,et al.  Premix emulsification: A review , 2010 .

[55]  Rajendrani Mukhopadhyay,et al.  Microfluidics: on the slope of enlightenment. , 2009, Analytical chemistry.

[56]  Richard M Crooks,et al.  Efficient mixing and reactions within microfluidic channels using microbead-supported catalysts. , 2002, Journal of the American Chemical Society.

[57]  S. Melanson,et al.  Literature Review on Point-of-Care Testing (August 2009-December 2010) , 2011 .

[58]  Maitreya J. Dunham,et al.  Comparing whole genomes using DNA microarrays , 2008, Nature Reviews Genetics.

[59]  L. Gervais,et al.  Microfluidic Chips for Point‐of‐Care Immunodiagnostics , 2011, Advanced materials.

[60]  E. Gillanders,et al.  Translational Research in Cancer Genetics: The Road Less Traveled , 2009, Public Health Genomics.

[61]  Mehmet Toner,et al.  Detection of mutations in EGFR in circulating lung-cancer cells. , 2008, The New England journal of medicine.

[62]  Jinseok Heo,et al.  Hybridization of DNA to bead-immobilized probes confined within a microfluidic channel. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[63]  P. Luciw,et al.  A comparison of multiplex suspension array large‐panel kits for profiling cytokines and chemokines in rheumatoid arthritis patients , 2009, Cytometry. Part B, Clinical cytometry.

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

[65]  R. Mage,et al.  A comparison of ELISA and flow microsphere-based assays for quantification of immunoglobulins. , 2002, Journal of immunological methods.

[66]  John T McDevitt,et al.  Programmable bio-nanochip technology for the diagnosis of cardiovascular disease at the point-of-care. , 2012, Methodist DeBakey cardiovascular journal.

[67]  Mehmet Toner,et al.  Blood-on-a-chip. , 2005, Annual review of biomedical engineering.

[68]  S. Dunbar,et al.  Rapid screening for 31 mutations and polymorphisms in the cystic fibrosis transmembrane conductance regulator gene by Lminex xMAP suspension array. , 2005, Methods in molecular medicine.

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

[70]  Nigel Beard,et al.  Dealing with real samples: sample pre-treatment in microfluidic systems. , 2003, Lab on a chip.

[71]  Samuel K Sia,et al.  An integrated approach to a portable and low-cost immunoassay for resource-poor settings. , 2004, Angewandte Chemie.

[72]  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.

[73]  T Kitamori,et al.  Integration of an immunosorbent assay system: analysis of secretory human immunoglobulin A on polystyrene beads in a microchip. , 2000, Analytical chemistry.

[74]  Richard M Crooks,et al.  Hydrogel-based microreactors as a functional component of microfluidic systems. , 2002, Analytical chemistry.

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

[76]  S. Quake,et al.  Microfluidic Large-Scale Integration , 2002, Science.

[77]  John Spertus,et al.  Use of saliva-based nano-biochip tests for acute myocardial infarction at the point of care: a feasibility study. , 2009, Clinical chemistry.

[78]  S. Dunbar Applications of Luminex® xMAP™ technology for rapid, high-throughput multiplexed nucleic acid detection , 2005, Clinica Chimica Acta.

[79]  Thomas Gervais,et al.  Mass transport and surface reactions in microfluidic systems , 2006 .

[80]  D R Walt,et al.  Techview: molecular biology. Bead-based fiber-optic arrays. , 2000, Science.

[81]  Dieter Stoll,et al.  Protein microarrays for diagnostic assays , 2009, Analytical and bioanalytical chemistry.

[82]  Kristen L. Helton,et al.  Microfluidic Overview of Global Health Issues Microfluidic Diagnostic Technologies for Global Public Health , 2006 .

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

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

[85]  Thomas Joos,et al.  Protein microarray technology , 2004, Expert review of proteomics.

[86]  Srivatsa Venkatasubbarao,et al.  Microarrays--status and prospects. , 2004, Trends in biotechnology.

[87]  David R. Walt,et al.  Miniature Analytical Methods for Medical Diagnostics , 2005, Science.

[88]  Ali Khademhosseini,et al.  Nano/Microfluidics for diagnosis of infectious diseases in developing countries. , 2010, Advanced drug delivery reviews.

[89]  Bernhard Weigl,et al.  Towards non- and minimally instrumented, microfluidics-based diagnostic devices. , 2008, Lab on a chip.

[90]  D. MacDougall,et al.  Guidelines for data acquisition and data quality evaluation in environmental chemistry , 1980 .

[91]  J. McDevitt,et al.  Nano-Bio-Chip Sensor Platform for Examination of Oral Exfoliative Cytology , 2010, Cancer Prevention Research.

[92]  David R Walt,et al.  Optical‐fiber bundles , 2007, The FEBS journal.

[93]  Nolan,et al.  Flow cytometry: a versatile tool for all phases of drug discovery. , 1999, Drug discovery today.

[94]  John T McDevitt,et al.  Cell-based sensor for analysis of EGFR biomarker expression in oral cancer. , 2007, Lab on a chip.

[95]  Yan Sun,et al.  Fabrication of superporous agarose beads for protein adsorption: effect of CaCO3 granules content. , 2010, Journal of chromatography. A.

[96]  Mounir Maaloum,et al.  Pore size of agarose gels by atomic force microscopy , 1997, Electrophoresis.

[97]  John T McDevitt,et al.  Effects of sample delivery on analyte capture in porous bead sensors. , 2012, Lab on a chip.

[98]  Frank Vitzthum,et al.  Proteomics: from basic research to diagnostic application. A review of requirements & needs. , 2005, Journal of proteome research.

[99]  A. Mirzabekov,et al.  Protein microchips: use for immunoassay and enzymatic reactions. , 2000, Analytical biochemistry.

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

[101]  Xiaomei Yan,et al.  Multiplexed flow cytometric immunoassay for influenza virus detection and differentiation. , 2005, Analytical chemistry.

[102]  Zhongze Gu,et al.  Multiplex detection of tumor markers with photonic suspension array. , 2009, Analytica chimica acta.

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

[104]  John T McDevitt,et al.  Application of microchip assay system for the measurement of C-reactive protein in human saliva. , 2005, Lab on a chip.

[105]  J. Remacle,et al.  Comparison between microwell and bead supports for the detection of human cytomegalovirus amplicons by sandwich hybridization. , 1997, Analytical biochemistry.

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

[107]  S. Hanash,et al.  Mining the plasma proteome for cancer biomarkers , 2008, Nature.

[108]  Roland Zengerle,et al.  Microfluidic platforms for lab-on-a-chip applications. , 2007, Lab on a chip.

[109]  P. Gergely,et al.  One-step indirect migration inhibiton (LIF) assay. , 1982, Journal of immunological methods.

[110]  M. Tortorello,et al.  Comparison of assurance gold salmonella EIA, BAX for screening/Salmonella, and GENE-TRAK Salmonella DLP rapid assays for detection of Salmonella in alfalfa sprouts and sprout irrigation water. , 2002, Journal of AOAC International.

[111]  A. Agadir,et al.  Cytometric bead array: a multiplexed assay platform with applications in various areas of biology. , 2004, Clinical immunology.

[112]  Shannon E. Stitzel,et al.  Artificial noses. , 2011, Annual review of biomedical engineering.

[114]  D. Grainger,et al.  Diagnostic devices as biomaterials: a review of nucleic acid and protein microarray surface performance issues , 2008, Journal of biomaterials science. Polymer edition.

[115]  O. V. Moiseeva,et al.  Comparison of surface and hydrogel-based protein microchips. , 2007, Analytical biochemistry.

[116]  David R Walt Chemistry. Miniature analytical methods for medical diagnostics. , 2005, Science.

[117]  G. Whitesides The origins and the future of microfluidics , 2006, Nature.

[118]  Luke P. Lee,et al.  Innovations in optical microfluidic technologies for point-of-care diagnostics. , 2008, Lab on a chip.

[119]  Xiang‐Yang Liu,et al.  Architecture of fiber network: from understanding to engineering of molecular gels. , 2006, The journal of physical chemistry. B.

[120]  Jason A. Thompson,et al.  Microbead-based biosensing in microfluidic devices , 2011 .

[121]  Marc Madou,et al.  Lab on a CD. , 2006, Annual review of biomedical engineering.

[122]  N. Anderson,et al.  The Human Plasma Proteome , 2002, Molecular & Cellular Proteomics.

[123]  Mary B Meza,et al.  Bead-based HTS applications in drug discovery , 2000 .

[124]  J. D. Winefordner,et al.  Limit of detection. A closer look at the IUPAC definition , 1983 .

[125]  David R Walt,et al.  Bead-based optical fiber arrays for artificial olfaction. , 2010, Current opinion in chemical biology.

[126]  Muin J. Khoury,et al.  Letting the genome out of the bottle--will we get our wish? , 2008, The New England journal of medicine.

[127]  H. Bau,et al.  Single bead-based electrochemical biosensor. , 2009, Biosensors & bioelectronics.

[128]  Kent Lewandrowski,et al.  Point-of-care testing: an overview and a look to the future (circa 2009, United States). , 2009, Clinics in laboratory medicine.

[129]  Craig S. Miller,et al.  Current development of saliva/oral fluid-based diagnostics. , 2010, Texas dental journal.

[130]  Jürgen Durner,et al.  Clinical chemistry: challenges for analytical chemistry and the nanosciences from medicine. , 2009, Angewandte Chemie.

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

[132]  A. Berg,et al.  Micro Total Analysis Systems , 1995 .

[133]  Kanti Pabbaraju,et al.  Comparison of the Luminex xTAG Respiratory Viral Panel with In-House Nucleic Acid Amplification Tests for Diagnosis of Respiratory Virus Infections , 2008, Journal of Clinical Microbiology.

[134]  A V Chudinov,et al.  Hydrogel drop microchips with immobilized DNA: properties and methods for large-scale production. , 2004, Analytical biochemistry.

[135]  Frances S Ligler,et al.  A microarray immunoassay for simultaneous detection of proteins and bacteria. , 2002, Analytical chemistry.

[136]  A. Mirzabekov,et al.  Hydrogel-based protein microchips: manufacturing, properties, and applications. , 2003, BioTechniques.

[137]  John T McDevitt,et al.  A microchip-based multianalyte assay system for the assessment of cardiac risk. , 2002, Analytical chemistry.

[138]  S. Xiao,et al.  Gel-pad microarrays templated by patterned porous silicon for dual-mode detection of proteins. , 2009, Lab on a chip.

[139]  A S Zasedatelev,et al.  Effect of mixing on reaction-diffusion kinetics for protein hydrogel-based microchips. , 2006, Journal of biotechnology.

[140]  F. Ligler,et al.  Multiplexed detection of bacteria and toxins using a microflow cytometer. , 2009, Analytical chemistry.

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

[142]  J P Nolan,et al.  Suspension array technology: new tools for gene and protein analysis. , 2001, Cellular and molecular biology.

[143]  Mauro Ferrari,et al.  Seven challenges for nanomedicine. , 2008, Nature nanotechnology.

[144]  P. Gustavsson,et al.  Improved lectin-mediated immobilization of human red blood cells in superporous agarose beads. , 2003, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[145]  J R Kettman,et al.  Multiplexed analysis of human cytokines by use of the FlowMetrix system. , 1998, Clinical chemistry.

[146]  D. Walt Fiber optic array biosensors. , 2006, BioTechniques.

[147]  H. Kawaguchi,et al.  Functional polymer microspheres , 2000 .

[148]  H. Humphreys,et al.  Multiplex PCR to determine Streptococcus pneumoniae serotypes causing otitis media in the Republic of Ireland with further characterisation of antimicrobial susceptibilities and genotypes , 2011, European Journal of Clinical Microbiology & Infectious Diseases.

[149]  Peter K Sorger,et al.  Microfluidics closes in on point-of-care assays , 2008, Nature Biotechnology.

[150]  I. Brewis The human plasma proteome , 2006 .

[151]  L A Sklar,et al.  High throughput flow cytometry. , 2001, Cytometry.

[152]  N. Lee,et al.  Superporous agarose beads as a solid support for microfluidic immunoassay. , 2008, Ultramicroscopy.

[153]  Robert L White,et al.  Multiplex protein assays based on real-time magnetic nanotag sensing , 2008, Proceedings of the National Academy of Sciences.

[154]  L. Shapiro,et al.  tmRNAs that encode proteolysis-inducing tags are found in all known bacterial genomes: A two-piece tmRNA functions in Caulobacter. , 2000, Proceedings of the National Academy of Sciences of the United States of America.