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Nucleic acid detection based on the use of microbeads: a review

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Abstract

Microbead-based technologies represent elegant and versatile approaches for highly parallelized quantitative multiparameter assays. They also form the basis of various techniques for detection and quantification of nucleic acids and proteins. Nucleic acid-based methods include hybridization assays, solid-phase PCR, sequencing, and trapping assays. Microbead assays have been improved in the past decades and are now important tools in routine and point-of-care diagnostics as well as in life science. Its advances include low costs, low workload, high speed and high-throughput automation. The potential of microbead-based assays therefore is apparent, and commercial applications can be found in the detection and discrimination of single nucleotide polymorphism, of pathogens, and in trapping assays. This review provides an overview on microbead-based platforms for biosensing with a main focus on nucleic acid detection (including amplification strategies and on selected probe systems using fluorescent labeling). Specific sections cover chemical properties of microbeads, the coupling of targets onto solid surfaces, microbead probe systems (mainly oligonucleotide probes), microbead detection schemes (with subsections on suspension arrays, microfluidic devices, and immobilized microbeads), quantification of nucleic acids, PCR in solution and the detection of amplicons, and methods for solid-phase amplification. We discuss selected trends such as microbead-coupled amplification, heterogeneous and homogenous DNA hybridization assays, real-time assays, melting curve analysis, and digital microbead assays. We finally discuss the relevance and trends of the methods in terms of high-level multiplexed analysis and their potential in diagnosis and personalized medicine. Contains 211 references.

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Abbreviations

μTAS:

micro total analysis systems

aPCR:

asymmetric PCR

dPCR:

digital PCR

EDC:

1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide

emPCR:

emulsion PCR

FRET:

Förster resonance energy transfer

ICAN:

isothermal and chimeric primer-initiated amplification of nucleic acids

LAMP:

loop-mediated isothermal amplification

MDHB:

hydrogel bead-array

PCR:

polymerase chain reaction

RCA:

rolling circle amplification

RPA:

recombinase polymerase amplification

SNP:

single-nucleotide polymorphism

Tm :

melting temperature

SNR:

signal-to-noise ratio

References

  1. Filipponi L, Sawant PD, Fulga F, Nicolau DV (2009) Microbeads on microposts: an inverted architecture for bead microarrays. Biosens Bioelectron 24:1850–1857. doi:10.1016/j.bios.2008.09.015

    CAS  Google Scholar 

  2. Chou J, Wong J, Christodoulides N et al (2012) Porous bead-based diagnostic platforms: bridging the gaps in healthcare. Sensors 12:15467–15499. doi:10.3390/s121115467

    Google Scholar 

  3. Hwang K-Y, Kwon SH, Jung S-O et al (2011) Miniaturized bead-beating device to automate full DNA sample preparation processes for gram-positive bacteria. Lab Chip 11:3649–3655. doi:10.1039/c1lc20692c

    CAS  Google Scholar 

  4. Hwang K-Y, Kwon SH, Jung S-O et al (2012) Solid phase DNA extraction with a flexible bead-packed microfluidic device to detect methicillin-resistant Staphylococcus aureus in nasal swabs. Anal Chem 84:7912–7918. doi:10.1021/ac3016533

    CAS  Google Scholar 

  5. Archer MJ, Lin B, Wang Z, Stenger DA (2006) Magnetic bead-based solid phase for selective extraction of genomic DNA. Anal Biochem 355:285–297. doi:10.1016/j.ab.2006.05.005

    CAS  Google Scholar 

  6. Chen Y, Seo TS (2011) PCR-free digital minisatellite tandem repeat genotyping. Electrophoresis 32:1456–1464. doi:10.1002/elps.201100073

    CAS  Google Scholar 

  7. Mahalanabis M, Do J, Almuayad H et al (2010) An integrated disposable device for DNA extraction and helicase dependent amplification. Biomed Microdevices 12:353–359

    CAS  Google Scholar 

  8. Zhang M, Liu Y, Chen L et al (2013) One simple DNA extraction device and its combination with modified visual loop-mediated isothermal amplification for rapid on-field detection of genetically modified organisms. Anal Chem 85:75–82. doi:10.1021/ac301640p

    CAS  Google Scholar 

  9. Frömmel U, Lehmann W, Rödiger S et al (2013) Adhesion of human and animal escherichia coli strains in association with their virulence-associated genes and phylogenetic origins. Appl Environ Microbiol 79:5814–5829. doi:10.1128/AEM.01384-13

    Google Scholar 

  10. Rödiger S, Schierack P, Böhm A et al (2013) A highly versatile microscope imaging technology platform for the multiplex real-time detection of biomolecules and autoimmune antibodies. Adv Biochem Eng Biotechnol 133:35–74. doi:10.1007/10_2011_132

    Google Scholar 

  11. Fulton RJ, McDade RL, Smith PL et al (1997) Advanced multiplexed analysis with the FlowMetrix system. Clin Chem 43:1749–1756

    CAS  Google Scholar 

  12. Chapin SC, Appleyard DC, Pregibon DC, Doyle PS (2011) Rapid microRNA profiling on encoded gel microparticles. Angew Chem Int Ed 50:2289–2293. doi:10.1002/anie.201006523

    CAS  Google Scholar 

  13. Sorensen K (2012) Individualized miRNA assay panels using optically encoded beads. Methods Mol Biol Clifton NJ 822:131–141. doi:10.1007/978-1-61779-427-8_9

    CAS  Google Scholar 

  14. Giovannetti E, van der Velde A, Funel N et al (2012) High-Throughput MicroRNA (miRNAs) Arrays Unravel the Prognostic Role of MiR-211 in Pancreatic Cancer. PLoS ONE 7

  15. Jun B-H, Kim J-E, Rho C et al (2011) Immobilization of aptamer-based molecular beacons onto optically-encoded micro-sized beads. J Nanosci Nanotechnol 11:6249–6252

    CAS  Google Scholar 

  16. Wu J, Wang C, Li X et al (2012) Identification, characterization and application of a G-quadruplex structured DNA aptamer against cancer biomarker protein anterior gradient homolog 2. PloS One 7:e46393. doi:10.1371/journal.pone.0046393

    CAS  Google Scholar 

  17. Nagarkatti R, Bist V, Sun S et al (2012) Development of an aptamer-based concentration method for the detection of Trypanosoma cruzi in blood. PloS One 7:e43533. doi:10.1371/journal.pone.0043533

    CAS  Google Scholar 

  18. Zhao Q, Gao J (2013) Fluorogenic assays for activated protein C using aptamer modified magnetic beads. Microchim Acta 180:813–819. doi:10.1007/s00604-013-1004-9

    CAS  Google Scholar 

  19. Yang L, Tran DK, Wang X (2001) BADGE, Beads Array for the Detection of Gene Expression, a high-throughput diagnostic bioassay. Genome Res 11:1888–1898. doi:10.1101/gr.190901

    CAS  Google Scholar 

  20. Naciff JM, Richardson BD, Oliver KG et al (2005) Design of a microsphere-based high-throughput gene expression assay to determine estrogenic potential. Environ Health Perspect 113:1164–1171

    CAS  Google Scholar 

  21. Dunbar J (2000) Application of the luminex LabMAP in rapid screening for mutations in the cystic fibrosis transmembrane conductance regulator gene: a pilot study. Clin Chem 46:1498–1500

    CAS  Google Scholar 

  22. Chen J, Iannone MA, Li MS et al (2000) A microsphere-based assay for multiplexed single nucleotide polymorphism analysis using single base chain extension. Genome Res 10:549–557

    CAS  Google Scholar 

  23. Taylor JD, Briley D, Nguyen Q et al (2001) Flow cytometric platform for high-throughput single nucleotide polymorphism analysis. BioTechniques 30(661–666):668–669

    Google Scholar 

  24. Ye F, Li MS, Taylor JD et al (2001) Fluorescent microsphere-based readout technology for multiplexed human single nucleotide polymorphism analysis and bacterial identification. Hum Mutat 17:305–316. doi:10.1002/humu.28

    CAS  Google Scholar 

  25. Ali MF, Kirby R, Goodey AP et al (2003) DNA hybridization and discrimination of single-nucleotide mismatches using chip-based microbead arrays. Anal Chem 75:4732–4739

    CAS  Google Scholar 

  26. Armstrong B, Stewart M, Mazumder A (2000) Suspension arrays for high throughput, multiplexed single nucleotide polymorphism genotyping. Cytometry 40:102–108

    CAS  Google Scholar 

  27. Dunbar SA, Vander Zee CA, Oliver KG et al (2003) Quantitative, multiplexed detection of bacterial pathogens: DNA and protein applications of the Luminex LabMAP system. J Microbiol Methods 53:245–252

    CAS  Google Scholar 

  28. Hadd AG, Laosinchai-Wolf W, Novak CR et al (2004) Microsphere bead arrays and sequence validation of 5/7/9T genotypes for multiplex screening of cystic fibrosis polymorphisms. J Mol Diagn JMD 6:348–355. doi:10.1016/S1525-1578(10)60531-4

    CAS  Google Scholar 

  29. Jin S-Q, Ye B-C, Huo H et al (2010) Multiplexed bead-based mesofluidic system for gene diagnosis and genotyping. Anal Chem 82:9925–9931. doi:10.1021/ac1024792

    CAS  Google Scholar 

  30. Jin S-Q, Yin B-C, Ye B-C (2009) Multiplexed bead-based mesofluidic system for detection of food-borne pathogenic bacteria. Appl Environ Microbiol 75:6647–6654. doi:10.1128/AEM.00854-09

    CAS  Google Scholar 

  31. Chernukhin I, Kang SY, Brown S et al (2011) BioVyon Protein A, an alternative solid-phase affinity matrix for chromatin immunoprecipitation. Anal Biochem 412:183–188. doi:10.1016/j.ab.2011.01.036

    CAS  Google Scholar 

  32. Wang Z, Huang H, Zhang H et al (2012) A magnetic bead-integrated chip for the large scale manufacture of normalized esiRNAs. PLoS ONE. doi:10.1371/journal.pone.0039419

    Google Scholar 

  33. Hudson EP, Nikoshkov A, Uhlen M, Rockberg J (2012) Automated solid-phase subcloning based on beads brought into proximity by magnetic force. PloS One 7:e37429. doi:10.1371/journal.pone.0037429

    CAS  Google Scholar 

  34. Wiesmayr A, Fournier P, Jäschke A (2012) An on-bead tailing/ligation approach for sequencing resin-bound RNA libraries. Nucleic Acids Res 40:e68. doi:10.1093/nar/gks004

    CAS  Google Scholar 

  35. Lee D, Chen P-J, Lee G-B (2010) The evolution of real-time PCR machines to real-time PCR chips. Biosens Bioelectron 25:1820–1824. doi:10.1016/j.bios.2009.11.021

    CAS  Google Scholar 

  36. Russom A, Haasl S, Brookes AJ et al (2006) Rapid melting curve analysis on monolayered beads for high-throughput genotyping of single-nucleotide polymorphisms. Anal Chem 78:2220–2225. doi:10.1021/ac051771u

    CAS  Google Scholar 

  37. Derveaux S, Stubbe BG, Braeckmans K et al (2008) Synergism between particle-based multiplexing and microfluidics technologies may bring diagnostics closer to the patient. Anal Bioanal Chem 391:2453–2467. doi:10.1007/s00216-008-2062-4

    CAS  Google Scholar 

  38. Konry T, Bale SS, Bhushan A et al (2012) Particles and microfluidics merged: perspectives of highly sensitive diagnostic detection. Microchim Acta 176:251–269. doi:10.1007/s00604-011-0705-1

    CAS  Google Scholar 

  39. Roos P, Skinner CD (2003) A two bead immunoassay in a micro fluidic device using a flat laser intensity profile for illumination. Analyst 128:527–531

    CAS  Google Scholar 

  40. Herrmann M, Veres T, Tabrizian M (2006) Enzymatically-generated fluorescent detection in micro-channels with internal magnetic mixing for the development of parallel microfluidic ELISA. Lab Chip 6:555–560. doi:10.1039/b516031f

    CAS  Google Scholar 

  41. Thompson JA, Bau HH (2010) Microfluidic, bead-based assay: theory and experiments. J Chromatogr B Analyt Technol Biomed Life Sci 878:228. doi:10.1016/j.jchromb.2009.08.050

    CAS  Google Scholar 

  42. Florescu O, Wang K, Au P et al (2010) On-chip magnetic separation of superparamagnetic beads for integrated molecular analysis. J Appl Phys. doi:10.1063/1.3272779

    Google Scholar 

  43. Park BH, Kim YT, Jung JH, Seo TS Integration of sample pretreatment, μPCR, and detection for a total genetic analysis microsystem. Microchim Acta 1–14. doi:10.1007/s00604-013-1128-y

  44. Casadevall i Solvas X, deMello A (2011) Droplet microfluidics: recent developments and future applications. Chem Commun Camb Engl 47:1936–1942. doi:10.1039/c0cc02474k

    CAS  Google Scholar 

  45. Seong GH, Zhan W, Crooks RM (2002) Fabrication of microchambers defined by photopolymerized hydrogels and weirs within microfluidic systems: application to DNA hybridization. Anal Chem 74:3372–3377

    CAS  Google Scholar 

  46. Hartwell SK, Grudpan K (2010) Flow based immuno/bioassay and trends in micro-immuno/biosensors. Microchim Acta 169:201–220. doi:10.1007/s00604-010-0333-1

    CAS  Google Scholar 

  47. Mazutis L, Araghi AF, Miller OJ et al (2009) Droplet-based microfluidic systems for high-throughput single DNA molecule isothermal amplification and analysis. Anal Chem 81:4813–4821. doi:10.1021/ac900403z

    CAS  Google Scholar 

  48. Chang C-C, Chen C-C, Wei S-C et al (2012) Diagnostic devices for isothermal nucleic acid amplification. Sensors 12:8319–8337. doi:10.3390/s120608319

    CAS  Google Scholar 

  49. Sapsford KE, Tyner KM, Dair BJ et al (2011) Analyzing nanomaterial bioconjugates: a review of current and emerging purification and characterization techniques. Anal Chem 83:4453–4488. doi:10.1021/ac200853a

    CAS  Google Scholar 

  50. Hennig A, Borcherding H, Jaeger C et al (2012) Scope and limitations of surface functional group quantification methods: exploratory study with poly(acrylic acid)-grafted micro- and nanoparticles. J Am Chem Soc 134:8268–8276. doi:10.1021/ja302649g

    CAS  Google Scholar 

  51. Sapsford KE, Algar WR, Berti L et al (2013) Functionalizing nanoparticles with biological molecules: developing chemistries that facilitate nanotechnology. Chem Rev 113:1904–2074. doi:10.1021/cr300143v

    CAS  Google Scholar 

  52. Wilkins Stevens P, Henry MR, Kelso DM (1999) DNA hybridization on microparticles: determining capture-probe density and equilibrium dissociation constants. Nucleic Acids Res 27:1719–1727

    CAS  Google Scholar 

  53. Henry MR, Wilkins Stevens P, Sun J, Kelso DM (1999) Real-time measurements of DNA hybridization on microparticles with fluorescence resonance energy transfer. Anal Biochem 276:204–214. doi:10.1006/abio.1999.4344

    CAS  Google Scholar 

  54. Baker BA, Milam VT (2011) Hybridization kinetics between immobilized double-stranded DNA probes and targets containing embedded recognition segments. Nucleic Acids Res 39:e99. doi:10.1093/nar/gkr293

    CAS  Google Scholar 

  55. Lund V, Schmid R, Rickwood D, Hornes E (1988) Assessment of methods for covalent binding of nucleic acids to magnetic beads, Dynabeads, and the characteristics of the bound nucleic acids in hybridization reactions. Nucleic Acids Res 16:10861–10880

    CAS  Google Scholar 

  56. Kim J, Heo J, Crooks RM (2006) Hybridization of DNA to bead-immobilized probes confined within a microfluidic channel. Langmuir ACS J Surf Colloids 22:10130–10134. doi:10.1021/la0616956

    CAS  Google Scholar 

  57. Dressman D, Yan H, Traverso G et al (2003) Transforming single DNA molecules into fluorescent magnetic particles for detection and enumeration of genetic variations. Proc Natl Acad Sci U S A 100:8817–8822. doi:10.1073/pnas.1133470100

    CAS  Google Scholar 

  58. Nakano M, Komatsu J, Matsuura S et al (2003) Single-molecule PCR using water-in-oil emulsion. J Biotechnol 102:117–124

    CAS  Google Scholar 

  59. Nord O, Uhlén M, Nygren P-A (2003) Microbead display of proteins by cell-free expression of anchored DNA. J Biotechnol 106:1–13

    CAS  Google Scholar 

  60. Kojima T, Takei Y, Ohtsuka M et al (2005) PCR amplification from single DNA molecules on magnetic beads in emulsion: application for high-throughput screening of transcription factor targets. Nucleic Acids Res 33:e150. doi:10.1093/nar/gni143

    Google Scholar 

  61. Meyerhans A, Vartanian JP, Wain-Hobson S (1990) DNA recombination during PCR. Nucleic Acids Res 18:1687–1691

    CAS  Google Scholar 

  62. Zhu Z, Jenkins G, Zhang W et al (2012) Single-molecule emulsion PCR in microfluidic droplets. Anal Bioanal Chem 403:2127–2143. doi:10.1007/s00216-012-5914-x

    CAS  Google Scholar 

  63. Qi Z, Ma Y, Deng L et al (2011) Digital analysis of the expression levels of multiple colorectal cancer-related genes by multiplexed digital-PCR coupled with hydrogel bead-array. Analyst 136:2252–2259. doi:10.1039/c0an00976h

    CAS  Google Scholar 

  64. Huang H, Qi Z, Deng L et al (2009) Highly sensitive mutation detection based on digital amplification coupled with hydrogel bead-array. Chem Commun Camb Engl 4094–4096. doi:10.1039/b902196e

  65. Boulanger J, Muresan L, Tiemann-Boege I (2012) Massively parallel haplotyping on microscopic beads for the high-throughput phase analysis of single molecules. PLoS ONE. doi:10.1371/journal.pone.0036064

    Google Scholar 

  66. Epstein JR, Lee M, Walt DR (2002) High-density fiber-optic genosensor microsphere array capable of zeptomole detection limits. Anal Chem 74:1836–1840

    CAS  Google Scholar 

  67. Gunderson KL, Steemers FJ, Lee G et al (2005) A genome-wide scalable SNP genotyping assay using microarray technology. Nat Genet 37:549–554. doi:10.1038/ng1547

    CAS  Google Scholar 

  68. Wilson R, Cossins AR, Spiller DG (2006) Encoded microcarriers for high-throughput multiplexed detection. Angew Chem Int Ed Engl 45:6104–6117. doi:10.1002/anie.200600288

    CAS  Google Scholar 

  69. Dufva M (2005) Fabrication of high quality microarrays. Biomol Eng 22:173–184. doi:10.1016/j.bioeng.2005.09.003

    CAS  Google Scholar 

  70. Han M, Gao X, Su JZ, Nie S (2001) Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules. Nat Biotechnol 19:631–635. doi:10.1038/90228

    CAS  Google Scholar 

  71. Gao Y, Stanford WL, Chan WCW (2011) Quantum-dot-encoded microbeads for multiplexed genetic detection of non-amplified DNA samples. Small Weinh Bergstr Ger 7:137–146. doi:10.1002/smll.201000909

    CAS  Google Scholar 

  72. Xu H, Sha MY, Wong EY et al (2003) Multiplexed SNP genotyping using the Qbead system: a quantum dot-encoded microsphere-based assay. Nucleic Acids Res 31:e43

    Google Scholar 

  73. Wang X, Wang G, Li W et al (2013) NIR-emitting quantum dot-encoded microbeads through membrane emulsification for multiplexed immunoassays. Small Weinh Bergstr Ger 9:3327–3335. doi:10.1002/smll.201203156

    CAS  Google Scholar 

  74. Cao Y-C, Liu T-C, Hua X-F et al (2006) Quantum dot optical encoded polystyrene beads for DNA detection. J Biomed Opt 11:054025. doi:10.1117/1.2358957

    Google Scholar 

  75. Horejsh D, Martini F, Poccia F et al (2005) A molecular beacon, bead-based assay for the detection of nucleic acids by flow cytometry. Nucleic Acids Res 33:e13. doi:10.1093/nar/gni015

    Google Scholar 

  76. Yuen PK, Despa M, Li C-CJ, Dejneka MJ (2003) Microbarcode sorting device. Lab Chip 3:198–201. doi:10.1039/b305703h

    CAS  Google Scholar 

  77. Bong KW, Chapin SC, Doyle PS (2010) Magnetic barcoded hydrogel microparticles for multiplexed detection. Langmuir ACS J Surf Colloids 26:8008–8014. doi:10.1021/la904903g

    CAS  Google Scholar 

  78. Lee H, Kim J, Kim H et al (2010) Colour-barcoded magnetic microparticles for multiplexed bioassays. Nat Mater 9:745–749. doi:10.1038/nmat2815

    CAS  Google Scholar 

  79. Peters J, Thomas D, Boers E et al (2013) Colour-encoded paramagnetic microbead-based direct inhibition triplex flow cytometric immunoassay for ochratoxin A, fumonisins and zearalenone in cereals and cereal-based feed. Anal Bioanal Chem 405:7783–7794. doi:10.1007/s00216-013-7095-7

    CAS  Google Scholar 

  80. Theilacker N, Roller EE, Barbee KD et al (2011) Multiplexed protein analysis using encoded antibody-conjugated microbeads. J R Soc Interface R Soc 8:1104–1113. doi:10.1098/rsif.2010.0594

    CAS  Google Scholar 

  81. Nolan JP, Mandy F (2006) Multiplexed and microparticle-based analyses: quantitative tools for the large-scale analysis of biological systems. Cytom Part J Int Soc Anal Cytol 69:318–325. doi:10.1002/cyto.a.20266

    Google Scholar 

  82. Resch-Genger U, Hoffmann K, Nietfeld W et al (2005) How to improve quality assurance in fluorometry: fluorescence-inherent sources of error and suited fluorescence standards. J Fluoresc 15:337–362. doi:10.1007/s10895-005-2630-3

    CAS  Google Scholar 

  83. Mistlberger G, Koren K, Scheucher E et al (2010) Multifunctional magnetic optical sensor particles with tunable sizes for monitoring metabolic parameters and as a basis for nanotherapeutics. Adv Funct Mater 20:1842–1851. doi:10.1002/adfm.201000321

    CAS  Google Scholar 

  84. Sheng H, Ye B-C (2009) Different strategies of covalent attachment of oligonucleotide probe onto glass beads and the hybridization properties. Appl Biochem Biotechnol 152:54–65. doi:10.1007/s12010-008-8245-9

    CAS  Google Scholar 

  85. Walsh MK, Wang X, Weimer BC (2001) Optimizing the immobilization of single-stranded DNA onto glass beads. J Biochem Biophys Methods 47:221–231

    CAS  Google Scholar 

  86. Lewis CL, Choi C-H, Lin Y et al (2010) Fabrication of uniform DNA-conjugated hydrogel microparticles via replica molding for facile nucleic acid hybridization assays. Anal Chem 82:5851–5858. doi:10.1021/ac101032r

    CAS  Google Scholar 

  87. Perro A, Reculusa S, Ravaine S et al (2005) Design and synthesis of Janus micro- and nanoparticles. J Mater Chem 15:3745–3760. doi:10.1039/B505099E

    CAS  Google Scholar 

  88. Yuet KP, Hwang DK, Haghgooie R, Doyle PS (2010) Multifunctional superparamagnetic Janus particles. Langmuir 26:4281–4287. doi:10.1021/la903348s

    CAS  Google Scholar 

  89. Rödiger S, Ruhland M, Schmidt C et al (2011) Fluorescence dye adsorption assay to quantify carboxyl groups on the surface of poly(methyl methacrylate) microbeads. Anal Chem 83:3379–3385. doi:10.1021/ac103277s

    Google Scholar 

  90. Hennig A, Hoffmann A, Borcherding H et al (2011) Simple colorimetric method for quantification of surface carboxy groups on polymer particles. Anal Chem 83:4970–4974. doi:10.1021/ac2007619

    CAS  Google Scholar 

  91. Huber A, Behnke T, Würth C et al (2012) Spectroscopic characterization of coumarin-stained beads: quantification of the number of fluorophores per particle with solid-state 19F-NMR and measurement of absolute fluorescence quantum yields. Anal Chem 84:3654–3661. doi:10.1021/ac3000682

    CAS  Google Scholar 

  92. Heise C, Bier FF (2005) Immobilization of DNA on microarrays. In: Wittmann C (ed) Immobil. DNA Chips II. Springer, Berlin Heidelberg, pp 1–25

    Google Scholar 

  93. Penchovsky R, Birch-Hirschfeld E, McCaskill JS (2000) End-specific covalent photo-dependent immobilisation of synthetic DNA to paramagnetic beads. Nucleic Acids Res 28:E98

    CAS  Google Scholar 

  94. Hermanson GT (1996) Bioconjugate Techniques. Academic Press

  95. Alberts B, Johnson A, Lewis J et al (2002) Molecular Biology of the Cell. http://www.ncbi.nlm.nih.gov/books/NBK21054/?depth=2. Accessed 18 Feb 2014

  96. Wolfbeis OS (2007) The click reaction in the luminescent probing of metal ions, and its implications on biolabeling techniques. Angew Chem Int Ed 46:2980–2982. doi:10.1002/anie.200604897

    Google Scholar 

  97. Cull MG, Schatz PJ (2000) Biotinylation of proteins in vivo and in vitro using small peptide tags. Methods Enzymol 326:430–440

    CAS  Google Scholar 

  98. Rödiger S, Böhm A, Schimke I (2013) Surface Melting Curve Analysis with R, http://journal.r-project.org/archive/accepted/roediger-bohm-schimke.pdf. R J. 5

  99. Russom A, Haasl S, Ohlander A et al (2004) Genotyping by dynamic heating of monolayered beads on a microheated surface. Electrophoresis 25:3712–3719. doi:10.1002/elps.200406065

    CAS  Google Scholar 

  100. Strömqvist Meuzelaar L, Hopkins K, Liebana E, Brookes AJ (2007) DNA diagnostics by surface-bound melt-curve reactions. J Mol Diagn JMD 9:30–41. doi:10.2353/jmoldx.2007.060057

    Google Scholar 

  101. Brenner S, Johnson M, Bridgham J et al (2000) Gene expression analysis by massively parallel signature sequencing (MPSS) on microbead arrays. Nat Biotechnol 18:630–634. doi:10.1038/76469

    CAS  Google Scholar 

  102. Syvänen AC (2001) Accessing genetic variation: genotyping single nucleotide polymorphisms. Nat Rev Genet 2:930–42. doi:10.1038/35103535

    Google Scholar 

  103. Piunno PAE, Krull UJ (2005) Trends in the development of nucleic acid biosensors for medical diagnostics. Anal Bioanal Chem 381:1004–1011. doi:10.1007/s00216-004-3024-0

    CAS  Google Scholar 

  104. Mir KU, Southern EM (1999) Determining the influence of structure on hybridization using oligonucleotide arrays. Nat Biotechnol 17:788–792. doi:10.1038/11732

    CAS  Google Scholar 

  105. Shchepinov MS, Case-Green SC, Southern EM (1997) Steric factors influencing hybridisation of nucleic acids to oligonucleotide arrays. Nucleic Acids Res 25:1155–1161

    CAS  Google Scholar 

  106. Palecek E, Fojta M (2007) Magnetic beads as versatile tools for electrochemical DNA and protein biosensing. Talanta 74:276–290. doi:10.1016/j.talanta.2007.08.020

    CAS  Google Scholar 

  107. Ghosh SS, Musso GF (1987) Covalent attachment of oligonucleotides to solid supports. Nucleic Acids Res 15:5353–5372

    CAS  Google Scholar 

  108. Albretsen C, Kalland KH, Haukanes BI et al (1990) Applications of magnetic beads with covalently attached oligonucleotides in hybridization: isolation and detection of specific measles virus mRNA from a crude cell lysate. Anal Biochem 189:40–50

    CAS  Google Scholar 

  109. Liu Y, Rauch CB (2003) DNA probe attachment on plastic surfaces and microfluidic hybridization array channel devices with sample oscillation. Anal Biochem 317:76–84

    CAS  Google Scholar 

  110. Schena M, Shalon D, Davis RW, Brown PO (1995) Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270:467–470

    CAS  Google Scholar 

  111. Klein D (2002) Quantification using real-time PCR technology: applications and limitations. Trends Mol Med 8:257–60

    CAS  Google Scholar 

  112. Nuhiji E, Mulvaney P (2007) Detection of unlabeled oligonucleotide targets using whispering gallery modes in single, fluorescent microspheres. Small 3:1408–1414. doi:10.1002/smll.200600676

    CAS  Google Scholar 

  113. Steemers FJ, Ferguson JA, Walt DR (2000) Screening unlabeled DNA targets with randomly ordered fiber-optic gene arrays. Nat Biotechnol 18:91–94. doi:10.1038/72006

    CAS  Google Scholar 

  114. Wetmur JG, Fresco J (1991) DNA probes: applications of the principles of nucleic acid hybridization. Crit Rev Biochem Mol Biol 26:227–259. doi:10.3109/10409239109114069

    CAS  Google Scholar 

  115. Hoheisel JD (2006) Microarray technology: beyond transcript profiling and genotype analysis. Nat Rev Genet 7:200–10. doi:10.1038/nrg1809

    CAS  Google Scholar 

  116. Zuo X, Yang X, Wang K et al (2007) A novel sandwich assay with molecular beacon as report probe for nucleic acids detection on one-dimensional microfluidic beads array. Anal Chim Acta 587:9–13. doi:10.1016/j.aca.2007.01.032

    CAS  Google Scholar 

  117. Lai R, Liang F, Pearson D et al (2012) PrimRglo: a multiplexable quantitative real-time polymerase chain reaction system for nucleic acid detection. Anal Biochem 422:89–95. doi:10.1016/j.ab.2011.12.038

    CAS  Google Scholar 

  118. Liang F, Lai R, Arora N et al (2013) Multiplex-microsphere-quantitative polymerase chain reaction: nucleic acid amplification and detection on microspheres. Anal Biochem 432:23–30. doi:10.1016/j.ab.2012.09.017

    CAS  Google Scholar 

  119. Bortolin S (2009) Multiplex genotyping for thrombophilia-associated SNPs by universal bead arrays. Methods Mol Biol Clifton NJ 496:59–72. doi:10.1007/978-1-59745-553-4_6

    CAS  Google Scholar 

  120. Sachidanandam R, Weissman D, Schmidt SC et al (2001) A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 409:928–33. doi:10.1038/35057149

    CAS  Google Scholar 

  121. Bruchez MJ, Moronne M, Gin P et al (1998) Semiconductor nanocrystals as fluorescent biological labels. Science 281:2013–2016

    CAS  Google Scholar 

  122. Tyagi S, Bratu DP, Kramer FR (1996) Molecular beacons: probes that fluoresce upon hybridization. Nat Biotechnol 16:49–53

    Google Scholar 

  123. Tyagi S, Kramer FR (1998) Multicolor molecular beacons for allele discrimination. Nat BiotechnolBiotechnol 14

  124. Resch-Genger U, Grabolle M, Cavaliere-Jaricot S et al (2008) Quantum dots versus organic dyes as fluorescent labels. Nat Methods 5:763–775. doi:10.1038/nmeth.1248

    CAS  Google Scholar 

  125. Sapsford KE, Berti L, Medintz IL (2006) Materials for fluorescence resonance energy transfer analysis: beyond traditional donor–acceptor combinations. Angew Chem Int Ed 45:4562–4589. doi:10.1002/anie.200503873

    CAS  Google Scholar 

  126. Vet JAM, Majithia AR, Marras SAE et al (1999) Multiplex detection of four pathogenic retroviruses using molecular beacons. Proc Natl Acad Sci U S A 96:6394–6399

    CAS  Google Scholar 

  127. Du H, Disney MD, Miller BL, Krauss TD (2003) Hybridization-based unquenching of DNA hairpins on au surfaces: prototypical “molecular beacon” biosensors. J Am Chem Soc 125:4012–3. doi:10.1021/ja0290781

    CAS  Google Scholar 

  128. Li J, Tan W, Wang K et al (2001) Ultrasensitive optical DNA biosensor based on surface immobilization of molecular beacon by a bridge structure. Anal Sci Int J Jpn Soc Anal Chem 17:1149–53

    CAS  Google Scholar 

  129. Liu X, Farmerie W, Schuster S, Tan W (2000) Molecular beacons for DNA biosensors with micrometer to submicrometer dimensions. Anal Biochem 283:56–63. doi:10.1006/abio.2000.4656

    CAS  Google Scholar 

  130. Sochol RD, Mahajerin a., Casavant BP et al (2009) Bead-Immobilized Molecular Beacons for High Throughput SNP Genotyping Via a Microfluidic System. 2009 I.E. 22nd Int Conf Micro Electro Mech Syst 304–307. doi:10.1109/MEMSYS.2009.4805379

  131. Nolan JP, Sklar LA (2002) Suspension array technology: evolution of the flat-array paradigm. Trends Biotechnol 20:9–12

    CAS  Google Scholar 

  132. Michael KL, Taylor LC, Schultz SL, Walt DR (1998) Randomly ordered addressable high-density optical sensor arrays. Anal Chem 70:1242–1248

    CAS  Google Scholar 

  133. Gunderson KL, Kruglyak S, Graige MS et al (2004) Decoding randomly ordered DNA arrays. Genome Res 14:870–877. doi:10.1101/gr.2255804

    CAS  Google Scholar 

  134. Oliphant A, Barker DL, Stuelpnagel JR, Chee MS (2002) BeadArray technology: enabling an accurate, cost-effective approach to high-throughput genotyping. BioTechniques Suppl 56–58:60–61

    Google Scholar 

  135. Dendukuri D, Doyle PS (2009) The synthesis and assembly of polymeric microparticles using microfluidics. Adv Mater 21:4071–4086. doi:10.1002/adma.200803386

    CAS  Google Scholar 

  136. Wang L, Li PCH (2011) Microfluidic DNA microarray analysis: a review. Anal Chim Acta 687:12–27. doi:10.1016/j.aca.2010.11.056

    CAS  Google Scholar 

  137. Zammatteo N, Alexandre I, Ernest I et al (1997) Comparison between microwell and bead supports for the detection of human cytomegalovirus amplicons by sandwich hybridization. Anal Biochem 253:180–189. doi:10.1006/abio.1997.2352

    CAS  Google Scholar 

  138. Clausell-Tormos J, Lieber D, Baret J-C et al (2008) Droplet-based microfluidic platforms for the encapsulation and screening of mammalian cells and multicellular organisms. Chem Biol 15:427–437. doi:10.1016/j.chembiol.2008.04.004

    CAS  Google Scholar 

  139. Niu X, deMello AJ (2012) Building droplet-based microfluidic systems for biological analysis. Biochem Soc Trans 40:615–623. doi:10.1042/BST20120005

    CAS  Google Scholar 

  140. Zhang Y, Ozdemir P (2009) Microfluidic DNA amplification–a review. Anal Chim Acta 638:115–125. doi:10.1016/j.aca.2009.02.038

    CAS  Google Scholar 

  141. Godin J, Chen C-H, Cho SH et al (2008) Microfluidics and photonics for Bio-system-on-a-chip: a review of advancements in technology towards a microfluidic flow cytometry chip. J Biophotonics 1:355–376. doi:10.1002/jbio.200810018

    CAS  Google Scholar 

  142. Dressler OJ, Maceiczyk RM, Chang S-I, Demello AJ (2013) Droplet-based microfluidics: enabling impact on drug discovery. J Biomol Screen. doi:10.1177/1087057113510401

    Google Scholar 

  143. Stanley CE, Wootton RCR, deMello AJ (2012) Continuous and segmented flow microfluidics: applications in high-throughput chemistry and biology. Chimia 66:88–98. doi:10.2533/chimia.2012.88

    CAS  Google Scholar 

  144. Casadevall i Solvas X, Niu X, Leeper K et al (2011) Fluorescence detection methods for microfluidic droplet platforms. J Vis Exp JoVE. doi:10.3791/3437

    Google Scholar 

  145. Oleschuk RD, Shultz-Lockyear LL, Ning Y, Harrison DJ (2000) Trapping of bead-based reagents within microfluidic systems: on-chip solid-phase extraction and electrochromatography. Anal Chem 72:585–590. doi:10.1021/ac990751n

    CAS  Google Scholar 

  146. Riegger L, Grumann M, Nann T et al (2006) Read-out concepts for multiplexed bead-based fluorescence immunoassays on centrifugal microfluidic platforms. Sens Actuators Phys 126:455–462. doi:10.1016/j.sna.2005.11.006

    CAS  Google Scholar 

  147. Diercks AH, Ozinsky A, Hansen CL et al (2009) A microfluidic device for multiplexed protein detection in nano-liter volumes. Anal Biochem 386:30–35. doi:10.1016/j.ab.2008.12.012

    CAS  Google Scholar 

  148. Sochol RD, Casavant BP, Dueck ME et al (2011) A dynamic bead-based microarray for parallel DNA detection. J Micromech Microeng 21:054019. doi:10.1088/0960-1317/21/5/054019

    Google Scholar 

  149. Fan ZH, Mangru S, Granzow R et al (1999) Dynamic DNA hybridization on a chip using paramagnetic beads. Anal Chem 71:4851–4859. doi:10.1021/ac9902190

    CAS  Google Scholar 

  150. Noda H, Kohara Y, Okano K, Kambara H (2003) Automated bead alignment apparatus using a single bead capturing technique for fabrication of a miniaturized bead-based DNA probe array. Anal Chem 75:3250–3255

    CAS  Google Scholar 

  151. Kohara Y, Noda H, Okano K, Kambara H (2002) DNA probes on beads arrayed in a capillary, “Bead-array”, exhibited high hybridization performance. Nucleic Acids Res 30:e87

    Google Scholar 

  152. Noda H, Kaise M, Kohara Y et al (2003) A bead-alignment device with a bead-sized microchamber on a rotating cylinder for fabrication of a miniaturized probe array. J Biosci Bioeng 96:86–88

    CAS  Google Scholar 

  153. Kohara Y, Noda H, Okano K, Kambara H (2001) DNA hybridization using “bead-array”: probe-attached beads arrayed in a capillary in a predetermined order. Nucleic Acids Res Suppl 2001 83–84

  154. Wen J, Yang X, Wang K et al (2007) One-dimensional microfluidic beads array for multiple mRNAs expression detection. Biosens Bioelectron 22:2759–2762. doi:10.1016/j.bios.2006.11.029

    CAS  Google Scholar 

  155. Gumpenberger T, Sato T, Narazaki A et al (2006) Fabrication and Characterisation of a Microfluidic Device for Bead-array Analysis by the LIBWE Method. J Laser MicroNanoengineering 201–206

    Google Scholar 

  156. Jokerst JV, McDevitt JT (2010) Programmable nano-bio-chips: multifunctional clinical tools for use at the point-of-care. Nanomed 5:143–155. doi:10.2217/nnm.09.94

    CAS  Google Scholar 

  157. Ng JK, Selamat ES, Liu W-T (2008) A spatially addressable bead-based biosensor for simple and rapid DNA detection. Biosens Bioelectron 23:803–810. doi:10.1016/j.bios.2007.08.026

    CAS  Google Scholar 

  158. Monk DJ, Walt DR (2004) Optical fiber-based biosensors. Anal Bioanal Chem 379:931–945. doi:10.1007/s00216-004-2650-x

    CAS  Google Scholar 

  159. Fan J-B, Gunderson KL, Bibikova M et al (2006) Illumina universal bead arrays. Methods Enzymol 410:57–73. doi:10.1016/S0076-6879(06)10003-8

    CAS  Google Scholar 

  160. Albert KJ, Gill DS, Pearce TC, Walt DR (2002) Automatic decoding of sensor types within randomly ordered, high-density optical sensor arrays. Anal Bioanal Chem 373:792–802. doi:10.1007/s00216-002-1406-8

    CAS  Google Scholar 

  161. Biran I, Walt DR (2002) Optical imaging fiber-based single live cell arrays: a high-density cell assay platform. Anal Chem 74:3046–3054

    CAS  Google Scholar 

  162. Epstein JR, Ferguson JA, Lee K-H, Walt DR (2003) Combinatorial decoding: an approach for universal DNA array fabrication. J Am Chem Soc 125:13753–13759. doi:10.1021/ja0365577

    CAS  Google Scholar 

  163. Munro SB, Kuypers J, Jerome KR (2013) Comparison of a multiplex real-time PCR assay with a multiplex luminex assay for influenza virus detection. J Clin Microbiol 51:1124–1129. doi:10.1128/JCM.03113-12

    CAS  Google Scholar 

  164. Asiello PJ, Baeumner AJ (2011) Miniaturized isothermal nucleic acid amplification, a review. Lab Chip - Miniaturisation Chem Biol 11:1420–1430

    CAS  Google Scholar 

  165. Vincent M, Xu Y, Kong H (2004) Helicase-dependent isothermal DNA amplification. EMBO Rep 5:795–800. doi:10.1038/sj.embor.7400200

    CAS  Google Scholar 

  166. Gill P, Ghaemi A (2008) Nucleic acid isothermal amplification technologies: a review. Nucleosides Nucleotides Nucleic Acids 27:224–243. doi:10.1080/15257770701845204

    CAS  Google Scholar 

  167. Murakami T, Sumaoka J, Komiyama M (2009) Sensitive isothermal detection of nucleic-acid sequence by primer generation-rolling circle amplification. Nucleic Acids Res 37:e19. doi:10.1093/nar/gkn1014

    Google Scholar 

  168. Zhang D, Wu J, Ye F et al (2006) Amplification of circularizable probes for the detection of target nucleic acids and proteins. Clin Chim Acta Int J Clin Chem 363:61–70. doi:10.1016/j.cccn.2005.05.039

    CAS  Google Scholar 

  169. Marciniak J, Kummel A, Esener S et al (2008) Coupled rolling circle amplification loop-mediated amplification for rapid detection of short DNA sequences. BioTechniques 45:275–280. doi:10.2144/000112910

    CAS  Google Scholar 

  170. Huang G, Yang X, Zhu J et al (2008) Detection and application of microfluidic isothermal amplification on chip. J Innov Opt Health Sci 1:257–265

    Google Scholar 

  171. Xu JD, Lv XF, Liu Y et al (2012) Design of integrated control system for microfluidic PCR analysis instrument. Appl Mech Mater 241–244:1491–1495. doi:10.4028/www.scientific.net/AMM.241-244.1491

    Google Scholar 

  172. Zanoli LM, Spoto G (2012) Isothermal amplification methods for the detection of nucleic acids in microfluidic devices. Biosensors 3:18–43. doi:10.3390/bios3010018

    Google Scholar 

  173. Schopf E, Fischer NO, Chen Y, Tok JB-H (2008) Sensitive and selective viral DNA detection assay via microbead-based rolling circle amplification. Bioorg Med Chem Lett 18:5871–5874. doi:10.1016/j.bmcl.2008.07.064

    CAS  Google Scholar 

  174. Sato K, Tachihara A, Renberg B et al (2010) Microbead-based rolling circle amplification in a microchip for sensitive DNA detection. Lab Chip 10:1262–1266. doi:10.1039/b927460j

    CAS  Google Scholar 

  175. Li J, Zhong W (2007) Typing of multiple single-nucleotide polymorphisms by a microsphere-based rolling circle amplification assay. Anal Chem 79:9030–9038. doi:10.1021/ac701702t

    CAS  Google Scholar 

  176. Long Y, Zhou X, Xing D (2011) Sensitive and isothermal electrochemiluminescence gene-sensing of Listeria monocytogenes with hyperbranching rolling circle amplification technology. Biosens Bioelectron 26:2897–2904. doi:10.1016/j.bios.2010.11.034

    CAS  Google Scholar 

  177. Konry T, Hayman RB, Walt DR (2009) Microsphere-based rolling circle amplification microarray for the detection of DNA and proteins in a single assay. Anal Chem 81:5777–5782. doi:10.1021/ac900694y

    CAS  Google Scholar 

  178. Dean FB, Hosono S, Fang L et al (2002) Comprehensive human genome amplification using multiple displacement amplification. Proc Natl Acad Sci U S A 99:5261–5266. doi:10.1073/pnas.082089499

    CAS  Google Scholar 

  179. Butler H, Ragoussis J (2008) BeadArray-based genotyping. Methods Mol Biol Clifton NJ 439:53–74. doi:10.1007/978-1-59745-188-8_4

    CAS  Google Scholar 

  180. Steemers FJ, Gunderson KL (2007) Whole genome genotyping technologies on the BeadArray platform. Biotechnol J 2:41–49. doi:10.1002/biot.200600213

    CAS  Google Scholar 

  181. Steemers FJ, Chang W, Lee G et al (2006) Whole-genome genotyping with the single-base extension assay. Nat Methods 3:31–33. doi:10.1038/nmeth842

    CAS  Google Scholar 

  182. Inami H, Tsuge K, Matsuzawa M et al (2009) Semi-automated bacterial spore detection system with micro-fluidic chips for aerosol collection, spore treatment and ICAN DNA detection. Biosens Bioelectron 24:3299–3305

    CAS  Google Scholar 

  183. Wang C-H, Lien K-Y, Wu J-J, Lee G-B (2011) A magnetic bead-based assay for the rapid detection of methicillin-resistant Staphylococcus aureus by using a microfluidic system with integrated loop-mediated isothermal amplification. Lab Chip 11:1521–1531. doi:10.1039/c0lc00430h

    CAS  Google Scholar 

  184. Parisi C, Markou A, Lianidou ES (2012) Development of a multiplexed PCR-coupled liquid bead array assay for vascular endothelial growth factor (VEGF) splice variants. Clin Biochem 45:475–482. doi:10.1016/j.clinbiochem.2012.01.025

    CAS  Google Scholar 

  185. Dunbar SA (2006) Applications of Luminex xMAP technology for rapid, high-throughput multiplexed nucleic acid detection. Clin Chim Acta Int J Clin Chem 363:71–82. doi:10.1016/j.cccn.2005.06.023

    CAS  Google Scholar 

  186. Taniuchi M, Verweij JJ, Noor Z et al (2011) High throughput multiplex PCR and probe-based detection with Luminex beads for seven intestinal parasites. Am J Trop Med Hyg 84:332–337. doi:10.4269/ajtmh.2011.10-0461

    CAS  Google Scholar 

  187. Schmitt M, Bravo IG, Snijders PJF et al (2006) Bead-based multiplex genotyping of human papillomaviruses. J Clin Microbiol 44:504–512. doi:10.1128/JCM.44.2.504-512.2006

    CAS  Google Scholar 

  188. Lawrie GA, Robinson J, Corrie S et al (2006) Multiplexed microsphere diagnostic tools in gene expression applications: factors and futures. Int J Nanomedicine 1:195–201

    CAS  Google Scholar 

  189. Corrie S, Sova P, Lawrie G et al (2009) Development of a multiplexed bead-based assay for detection of DNA methylation in cancer-related genes. Mol Biosyst 5:262–268. doi:10.1039/b813077a

    CAS  Google Scholar 

  190. Thierry S, Hamidjaja RA, Girault G et al (2013) A multiplex bead-based suspension array assay for interrogation of phylogenetically informative single nucleotide polymorphisms for Bacillus anthracis. J Microbiol Methods 95:357–365. doi:10.1016/j.mimet.2013.10.004

    CAS  Google Scholar 

  191. Song Q, Yang H, Zou B et al (2013) Improvement of LATE-PCR to allow single-cell analysis by pyrosequencing. Analyst 138:4991–4997. doi:10.1039/C3AN00821E

    CAS  Google Scholar 

  192. Sanchez JA, Pierce KE, Rice JE, Wangh LJ (2004) Linear-After-The-Exponential (LATE)–PCR: an advanced method of asymmetric PCR and its uses in quantitative real-time analysis. Proc Natl Acad Sci U S A 101:1933–1938. doi:10.1073/pnas.0305476101

    CAS  Google Scholar 

  193. Pierce KE, Wangh LJ (2011) LATE-PCR and allied technologies: real-time detection strategies for rapid, reliable diagnosis from single cells. Methods Mol Biol Clifton NJ 688:47–66. doi:10.1007/978-1-60761-947-5_5

    CAS  Google Scholar 

  194. Ma Z, Lee RW, Li B et al (2013) Isothermal amplification method for next-generation sequencing. Proc Natl Acad Sci 201311334. doi:10.1073/pnas.1311334110

  195. Khan Z, Poetter K, Park DJ (2008) Enhanced solid phase PCR: mechanisms to increase priming by solid support primers. Anal Biochem 375:391–393. doi:10.1016/j.ab.2008.01.021

    CAS  Google Scholar 

  196. Adessi C, Matton G, Ayala G et al (2000) Solid phase DNA amplification: characterisation of primer attachment and amplification mechanisms. Nucleic Acids Res 28:e87

    CAS  Google Scholar 

  197. Sjöroos M, Ilonen J, Lövgren T (2001) Solid-phase PCR with hybridization and time-resolved fluorometry for detection of HLA-B27. Clin Chem 47:498–504

    Google Scholar 

  198. Carmon A, Vision TJ, Mitchell SE et al (2002) Solid-phase PCR in microwells: effects of linker length and composition on tethering, hybridization, and extension. BioTechniques 32:410, 412, 414–418, 420

    CAS  Google Scholar 

  199. Andreadis JD, Chrisey LA (2000) Use of immobilized PCR primers to generate covalently immobilized DNAs for in vitro transcription/translation reactions. Nucleic Acids Res 28:e5

    CAS  Google Scholar 

  200. Shapero MH, Leuther KK, Nguyen A et al (2001) SNP genotyping by multiplexed solid-phase amplification and fluorescent minisequencing. Genome Res 11:1926–1934. doi:10.1101/gr.205001

    CAS  Google Scholar 

  201. Xu MY, Aragon AD, Mascarenas MR et al (2010) Dual primer emulsion PCR for next- generation DNA sequencing. BioTechniques 48:409–412. doi:10.2144/000113423

    CAS  Google Scholar 

  202. Kiss MM, Ortoleva-Donnelly L, Beer NR et al (2008) High-throughput quantitative polymerase chain reaction in picoliter droplets. Anal Chem 80:8975–8981

    CAS  Google Scholar 

  203. Song L, Shan D, Zhao M et al (2013) Direct detection of bacterial genomic DNA at sub-femtomolar concentrations using single molecule arrays. Anal Chem 85:1932–1939. doi:10.1021/ac303426b

    CAS  Google Scholar 

  204. Nilsen TW, Grayzel J, Prensky W (1997) Dendritic nucleic acid structures. J Theor Biol 187:273–284. doi:10.1006/jtbi.1997.0446

    CAS  Google Scholar 

  205. Lowe M, Spiro A, Zhang Y-Z, Getts R (2004) Multiplexed, particle-based detection of DNA using flow cytometry with 3DNA dendrimers for signal amplification. Cytom Part J Int Soc Anal Cytol 60:135–144. doi:10.1002/cyto.a.20021

    Google Scholar 

  206. Klamp T, Camps M, Nieto B et al (2013) Highly rapid amplification-free and quantitative DNA imaging assay. Sci Rep 3:1852. doi:10.1038/srep01852

    Google Scholar 

  207. Chen Y, Shortreed MR, Olivier M, Smith LM (2005) Parallel single nucleotide polymorphism genotyping by surface invasive cleavage with universal detection. Anal Chem 77:2400–2405. doi:10.1021/ac0483825

    CAS  Google Scholar 

  208. Rao KVN, Stevens PW, Hall JG et al (2003) Genotyping single nucleotide polymorphisms directly from genomic DNA by invasive cleavage reaction on microspheres. Nucleic Acids Res 31:e66

    Google Scholar 

  209. De Ronde H, González Alonso P, van Soolingen D et al (2012) Bead array direct rRNA capture assay (rCapA) for amplification free speciation of Mycobacterium cultures. PloS One 7:e32575. doi:10.1371/journal.pone.0032575

    Google Scholar 

  210. Mirnezami R, Nicholson J, Darzi A (2012) Preparing for precision medicine. N Engl J Med 366:489–491. doi:10.1056/NEJMp1114866

    Google Scholar 

  211. Regierer B, Zazzu V, Sudbrak R et al (2013) Future of Medicine: Models in Predictive Diagnostics and Personalized Medicine. In: Seitz H, Schumacher S (eds) Mol. Diagn. Springer Berlin Heidelberg, pp 15–33

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Acknowledgments

This work was supported by BMBF (Federal Ministry of Education and Research, Germany) projects InnoProfile 03IP611, InnoProfile-Transfer 03IPT611A and InnoProfile-Transfer 03IP611X. We gratefully thank Julius-Tachu Babila and Friedjof Lechart for improving our manuscript. URG gratefully acknowledges financial support from the Federal Ministry of Economics and Technology (MNPQ projects BMWI-22/06 and BMWI-17/07) and from the EU (EMRP grant NanoChOp, NEW03).

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  1. Faculty of Natural Sciences, Brandenburg University of Technology Cottbus - Senftenberg, Großenhainer Str. 57, 01968, Senftenberg, Germany

    Stefan Rödiger, Claudia Liebsch, Carsten Schmidt & Peter Schierack

  2. Attomol GmbH, Schulweg 6, 03205, Bronkow, Germany

    Werner Lehmann

  3. Division Biophotonics, BAM Federal Institute for Materials Research and Testing, Richard-Willstätter-Straße 11, 12489, Berlin, Germany

    Ute Resch-Genger

  4. PolyAn GmbH, Rudolf-Baschant-Straße 2, 13086, Berlin, Germany

    Uwe Schedler

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  1. Stefan Rödiger
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Rödiger, S., Liebsch, C., Schmidt, C. et al. Nucleic acid detection based on the use of microbeads: a review. Microchim Acta 181, 1151–1168 (2014). https://doi.org/10.1007/s00604-014-1243-4

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