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Advanced methods for microRNA biosensing: a problem-solving perspective

Abstract

MicroRNAs (miRNAs) present several features that make them more difficult to analyze than DNA and RNA. For this reason, efforts have been made in recent years to develop innovative platforms for the efficient detection of microRNAs. The aim of this review is to provide an overview of the sensing strategies able to deal with drawbacks and pitfalls related to microRNA detection. With a critical perspective of the field, we identify the main challenges to be overcome in microRNA sensing, and describe the areas where several innovative approaches are likely to come for managing those issues that put limits on improvement to the performances of the current methods. Then, in the following sections, we critically discuss the contribution of the most promising approaches based on the peculiar properties of nanomaterials or nanostructures and other hybrid strategies which are envisaged to support the adoption of these new methods useful for the detection of miRNA as biomarkers of practical clinical utility.

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References

  1. 1.

    Nana-Sinkam SP, Croce CM. Clinical applications for microRNAs in cancer. Clin Pharmacol Ther. 2013;93:98–104.

  2. 2.

    Van Kouwenhove M, Kedde M, Agami R. MicroRNA regulation by RNA-binding proteins and its implications for cancer. Nat Rev Canc. 2011;11:644–56.

  3. 3.

    Kosaka N, Iguchi H, Ochiya T. Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010;101:2087–92.

  4. 4.

    Pritchard CC, Cheng HH, Tewari M. MicroRNA profiling: approaches and considerations. Nat Rev Genet. 2012;13:358–69.

  5. 5.

    Liang Y, Ridzon D, Wong L, Chen C. Characterization of microRNA expression profiles in normal human tissues. BMC Genomics. 2007;8:166.

  6. 6.

    Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, et al. The microRNA spectrum in 12 body fluids. Clin Chem. 2010;56:1733–41.

  7. 7.

    Cheng Y, Dong L, Zhang J, Zhao Y, Li Z. Recent advances in microRNA detection. Analyst. 2018;143:1758–74.

  8. 8.

    Kalogianni DP, Kalligosfy PM, Kyriakou IK, Christopoulos TK. Advances in microRNA analysis. Anal Bioanal Chem. 2018;410:695–713.

  9. 9.

    Kilic T, Erdem A, Ozsoz M, Carrara S. MicroRNA biosensors: opportunities and challenges among conventional and commercially available techniques. Biosens Bioelectron. 2018;99:525–46.

  10. 10.

    Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215–33.

  11. 11.

    Benes V, Castoldi M. Expression profiling of microRNA using real-time quantitative PCR, how to use it and what is available. Methods. 2010;50:244–9.

  12. 12.

    Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, et al. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 2005;33:e179.1–9.

  13. 13.

    Thomson JM, Parker J, Perou CM, Hammond SM. A custom microarray platform for analysis of microRNA gene expression. Nat Methods. 2004;1:47–53.

  14. 14.

    Li W, Ruan K. MicroRNA detection by microarray. Anal Bioanal Chem. 2009;394:1117–24.

  15. 15.

    Qavi AJ, Kindt JT, Bailey RC. Sizing up the future of microRNA analysis. Anal Bioanal Chem. 2010;98:2535–49.

  16. 16.

    Chugh P, Dittmer DP. Potential pitfalls in microRNA profiling. Wiley Interdiscip Rev RNA. 2012;3:601–16.

  17. 17.

    Syedmoradi L, Daneshpour M, Alvandipour M, Gomez FA, Hajghassem H, Omidfar K. Point of care testing: the impact of nanotechnology. Biosens Bioelectron. 2017;87:373–87.

  18. 18.

    Degliangeli F, Pompa PP, Fiammengo R. Nanotechnology-based strategies for the detection and quantification of microRNA. Chem Eur J. 2014;20:9476–92.

  19. 19.

    Jamali AA, Pourhassan-Moghaddam M, Dolatabadi JEN, Omidi Y. Nanomaterials on the road to microRNA detection with optical and electrochemical nanobiosensors. Trend Anal Chem. 2014;55:24–42.

  20. 20.

    Chen YX, Huang KJ, Niu KX. Recent advances in signal amplification strategy based on oligonucleotide and nanomaterials for microRNA detection—a review. Biosens Bioelectron. 2018;99:612–24.

  21. 21.

    Zanoli LM, D’Agata R, Spoto G. Functionalized gold nanoparticles for ultrasensitive DNA detection. Anal Bioanal Chem. 2012;402:1759–71.

  22. 22.

    D’Agata R, Corradini R, Ferretti C, Zanoli L, Gatti M, Marchelli R, et al. Ultrasensitive detection of non-amplified genomic DNA by nanoparticle-enhanced surface plasmon resonance imaging. Biosens Bioelectron. 2010;25:2095–100.

  23. 23.

    D’Agata R, Breveglieri G, Zanoli LM, Borgatti M, Spoto G, Gambari R. Direct detection of point mutations in nonamplified human genomic DNA. Anal Chem. 2011;83:8711–7.

  24. 24.

    Johnson BN, Mutharasan R. Sample preparation-free, real-time detection of microRNA in human serum using piezoelectric cantilever biosensors at attomole level. Anal Chem. 2012;84:10426–36.

  25. 25.

    Seo H, Kim S, Kim JI, Kang H, Jung W, Yeo WS. Ultrasensitive detection of microRNAs using nanoengineered micro gold shells and laser desorption/ionization time-of-flight MS. Anal Biochem. 2013;434:199–201.

  26. 26.

    D’Agata R, Spoto G. Surface plasmon resonance imaging for nucleic acid detection. Anal Bioanal Chem. 2013;405:573–84.

  27. 27.

    Spoto G, Minunni M. Surface plasmon resonance imaging: what next? J Phys Chem Lett. 2013;3:2682–91.

  28. 28.

    Lee HJ, Wark AW, Corn RM. Enhanced bioaffinity sensing using surface plasmons, surface enzyme reactions, nanoparticles and diffraction gratings. Analyst. 2008;133:596–601.

  29. 29.

    Sipova H, Zhang S, Dudley AM, Galas D, Wang K, Homola J. Surface plasmon resonance biosensor for rapid label-free detection of microribonucleic acid at subfemtomole level. Anal Chem. 2010;82:10110–5.

  30. 30.

    Zhang D, Yan Y, Cheng W, Zhang W, Li Y, Ju H, et al. Streptavidin-enhanced surface plasmon resonance biosensor for highly sensitive and specific detection of microRNA. Microchim Acta. 2013;180:397–403.

  31. 31.

    Qian S, Lin M, Ji W, Yuan H, Zhang Y, Jing Z, et al. Boronic acid functionalized Au nanoparticles for selective microRNA signal amplification in fiber-optic surface plasmon resonance sensing system. ACS Sens. 2018;3:929–35.

  32. 32.

    Cialla-May D, Zheng XS, Weber K, Popp J. Recent progress in surface-enhanced Raman spectroscopy for biological and biomedical applications: from cells to clinics. Chem Soc Rev. 2017;46:3945–61.

  33. 33.

    Chen Y, Chen G, Feng S, Pan J, Zheng X, Su Y, et al. Label-free serum ribonucleic acid analysis for colorectal cancer detection by surface-enhanced Raman spectroscopy and multivariate analysis. J Biomed Opt. 2012;17:067003.

  34. 34.

    Chiado A, Novara C, Lamberti A, Geobaldo F, Giorgis F, Rivolo P. Immobilization of oligonucleotides on metal-dielectric nanostructures for miRNA detection. Anal Chem. 2016;88:9554–63.

  35. 35.

    Guo R, Yin F, Sun Y, Mi L, Shi L, Tian Z, et al. Ultrasensitive simultaneous detection of multiplex disease-related nucleic acids using double-enhanced surface-enhanced Raman scattering nanosensors. ACS Appl Mater Interfaces. 2018;10:25770–8.

  36. 36.

    Song CY, Yang YJ, Yang BY, Sun YZ, Zhao YP, Wang LH. An ultrasensitive SERS sensor for simultaneous detection of multiple cancer-related miRNAs. Nanoscale. 2016;8:17365–73.

  37. 37.

    Zhou W, Tian YF, Yin BC, Ye BC. Simultaneous surface-enhanced Raman spectroscopy detection of multiplexed microRNA biomarkers. Anal Chem. 2017;89:6120–8.

  38. 38.

    Su J, Wang D, Nörbel L, Shen J, Zhao Z, Dou Y, et al. Multicolor gold–silver nano-mushrooms as ready-to-use SERS probes for ultrasensitive and multiplex DNA/miRNA detection. Anal Chem. 2017;89:2531–8.

  39. 39.

    Skeete Z, Cheng HW, Crew E, Lin LQ, Zhao W, Joseph P, et al. Design of functional nanoparticles and assemblies for theranostic applications. ACS Appl Mater Interfaces. 2014;6:21752–68.

  40. 40.

    Pang Y, Wang C, Wang J, Sun Z, Xiao R, Wang S. Fe3O4@Ag magnetic nanoparticles for microRNA capture and duplex-specific nuclease signal amplification based SERS detection in cancer cells. Biosens Bioelectron. 2016;79:574–80.

  41. 41.

    Moore TJ, Moody AS, Payne TD, Sarabia GM, Daniel AR, Sharma B. In vitro and in vivo SERS biosensing for disease diagnosis. Biosensors. 2018. https://doi.org/10.3390/bios8020046.

  42. 42.

    Hamidi-Asl E, Palchetti I, Hasheminejad E, Mascini M. A review on the electrochemical biosensors for determination of microRNAs. Talanta. 2013;115:74–83.

  43. 43.

    Wu X, Chai Y, Yuan R, Su H, Han J. A novel label-free electrochemical microRNA biosensor using Pd nanoparticles as enhancer and linker. Analyst. 2013;138:1060–6.

  44. 44.

    Wang J, Yi X, Tang H, Han H, Wu M, Zhou F. Direct quantification of microRNA at low pM level in sera of glioma patients using a competitive hybridization followed by amplified voltammetric detection. Anal Chem. 2012;84:6400–6.

  45. 45.

    Gao ZQ, Yang ZC. Ultrasensitive detection of microRNA using electrocatalytic nanoparticle tags. Anal Chem. 2006;78:1470–7.

  46. 46.

    Fan Y, Chen X, Trigg AD, Tung C, Kong J, Gao Z. Detection of microRNAs using target-guided formation of conducting polymer nanowires in nanogaps. J Am Chem Soc. 2007;129:5437–43.

  47. 47.

    Gao Z, Peng Y. A highly sensitive and specific biosensor for ligation- and PCR-free detection of microRNAs. Biosens Bioelectron. 2011;26:3768–73.

  48. 48.

    Peng Y, Yi G, Gao Z. A highly sensitive microRNA biosensor based on ruthenium oxide nanoparticle-initiated polymerization of aniline. Chem Commun. 2010;46:9131–3.

  49. 49.

    D’Agata R, Corradini R, Grasso G, Marchelli R, Spoto G. Ultrasensitive detection of DNA by PNA and nanoparticle-enhanced surface plasmon resonance imaging. ChemBioChem. 2008;9:2067–70.

  50. 50.

    Gao Z, Deng H, Shen W, Ren Y. A label-free biosensor for electrochemical detection of femtomolar microRNAs. Anal Chem. 2013;85:1624–30.

  51. 51.

    Jolly P, Batistuti MR, Miodek A, Zhurauski P, Mulato M, Lindsay MA, et al. Highly sensitive dual mode electrochemical platform for microRNA detection. Sci Rep. 2016. https://doi.org/10.1038/srep36719.

  52. 52.

    Labib M, Khan N, Ghobadloo SM, Cheng J, Pezacki JP, Berezovski MV. Three-mode electrochemical sensing of ultralow microRNA levels. J Am Chem Soc. 2013;135:3027–38.

  53. 53.

    Gerasimova YV, Kolpashchikov DM. Enzyme-assisted target recycling (EATR) for nucleic acid detection. Chem Soc Rev. 2014;43:6405–38.

  54. 54.

    Castañeda AD, Brenes NJ, Kondajji A, Crooks RM. Detection of microRNA by electrocatalytic amplification: a general approach for single-particle biosensing. J Am Chem Soc. 2017;139:7657–64.

  55. 55.

    Zhang K, Wang K, Zhu X, Xu F, Xie M. Sensitive detection of microRNA in complex biological samples by using two stages DSN-assisted target recycling signal amplification method. Biosens Bioelectron. 2017;87:358–64.

  56. 56.

    Yin BC, Liu YQ, Ye BC. One-step, multiplexed fluorescence detection of microRNAs based on duplex-specific nuclease signal amplification. J Am Chem Soc. 2012;134:5064–7.

  57. 57.

    Ma F, Liu W, Zhang Q, Zhang C. Chem Commun. 2017;53:10596–9.

  58. 58.

    Gillespie P, Ladame S, O’Hare D. Molecular methods in electrochemical microRNA detection. Analyst. 2019;144:114–29.

  59. 59.

    Islam MN, Masud MK, Haque MH, Hossain MSA, Yamauchi Y, Nguyen NT, et al. RNA biomarkers: diagnostic and prognostic potentials and recent developments of electrochemical biosensors. Small Methods. 2017;1:1700131.

  60. 60.

    Almlie CK, Larkey NE, Burrows SM. Fluorescent microRNA biosensors: a comparison of signal generation to quenching. Anal Methods. 2015;7:7296–310.

  61. 61.

    Voccia D, Bettazzi F, Fratini E, Berti D, Palchetti I. Improving impedimetric nucleic acid detection by using enzyme-decorated liposomes and nanostructured screen-printed electrodes. Anal Bioanal Chem. 2016;408:7271–81.

  62. 62.

    Voccia D, Sosnowska M, Bettazzi F, Roscigno G, Fratini E, De Franciscis V, et al. Direct determination of small RNAs using a biotinylated polythiophene impedimetric genosensor. Biosens Bioelectron. 2017;87:1012–9.

  63. 63.

    Miao XM, Cheng ZY, Ma HY, Li ZB, Xue N, Wang P. Label-free platform for microRNA detection based on the fluorescence quenching of positively charged gold nanoparticles to silver nanoclusters. Anal Chem. 2018;90:1098–103.

  64. 64.

    Su S, Fan J, Xue B, Yuwen L, Liu X, Pan D, et al. DNA-conjugated quantum dot nanoprobe for high-sensitivity fluorescent detection of DNA and micro-RNA. ACS Appl Mater Interfaces. 2014;6:1152–7.

  65. 65.

    Wang Y, Howes PD, Kim E, Spicer CD, Thomas MR, Lin Y, et al. Duplex-specific nuclease-amplified detection of microRNA using compact quantum dot-DNA conjugates. ACS Appl Mater Interfaces. 2018;10:28290–300.

  66. 66.

    Tran HV, Piro B, Reisberg S, Tran LD, Duc HT, Pham MC. Label-free and reagentless electrochemical detection of microRNAs using a conducting polymer nanostructured by carbon nanotubes: application to prostate cancer biomarker miR-141. Biosens Bioelectron. 2013;49:164–9.

  67. 67.

    Tran HV, Piro B, Reisberg S, Duc HT, Pham MC. Antibodies directed to RNA/DNA hybrids: an electrochemical immunosensor for microRNAs detection using graphene-composite electrodes. Anal Chem. 2013;85:8469–74.

  68. 68.

    Liao X, Wang Q, Ju H. A peptide nucleic acid-functionalized carbon nitride nanosheet as a probe for in situ monitoring of intracellular microRNA. Analyst. 2015;140:4245–52.

  69. 69.

    Bettazzi F, Palchetti I. Photo electrochemical genosensors for the determination of nucleic acid cancer biomarkers. Cur Op Elect. 2018;12:51–9.

  70. 70.

    Cao H, Liu S, Tu W, Bao J, Da Z. A carbon nanotube/quantum dot based photoelectrochemical biosensing platform for the direct detection of microRNAs. Chem Commun. 2014;50:13315–8.

  71. 71.

    Zou Q, Mao Y, Hu L, Wu Y, Ji Z. miRClassify: an advanced web server for miRNA family classification and annotation. Comput Biol Med. 2014;45:157–60.

  72. 72.

    Muller H, Marzi MJ, Nicassio F. IsomiRage: from functional classification to differential expression of miRNA isoforms. Front Bioeng Biotechnol| J Bioinf Comput Biol. 2014;2:1–6.

  73. 73.

    Kamanu TKK, Radovanovic A, Archer JAC, Bajic VB. Exploration of miRNA families for hypotheses generation. Sci Rep. 2013. https://doi.org/10.1038/srep02940.

  74. 74.

    Lin S, Gregory RI. MicroRNA biogenesis pathways in cancer. Nature Rev Cancer. 2015;15:321–33.

  75. 75.

    Rupaimoole R, Slack FJ. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nature Rev Drug Discov. 2017;16:203–21.

  76. 76.

    Yin JQ, Zhao RC, Morris KV. Profiling microRNA expression with microarrays. Trends Biotechnol. 2008;26:70–6.

  77. 77.

    Nielsen BS. MicroRNA in situ hybridization. Methods Mol Biol. 2012;822:67–84.

  78. 78.

    Yao B, Li Y, Huang H, Sun CH, Wang Z, Fan Y, et al. Quantitative analysis of zeptomole microRNAs based on isothermal ramification amplification. RNA. 2009;15:1787–94.

  79. 79.

    Lin X, Zhang C, Huang Y, Zhu Z, Chen X, Yang CJ. Backbone-modified molecular beacons for highly sensitive and selective detection of microRNAs based on duplex specific nuclease signal amplification. Chem Commun. 2013;49:7243–5.

  80. 80.

    Wang XP, Yin BC, Wang P, Ye BC. Highly sensitive detection of microRNAs based on isothermal exponential amplification-assisted generation of catalytic G-quadruplex DNAzyme. Biosens Bioelectron. 2013;42:131–5.

  81. 81.

    Hartig JS, Grune I, Najafi-Shoushtari SH, Famulok M. Sequence-specific detection of microRNAs by signal-amplifying ribozymes. J Am Chem Soc. 2004;126:722–3.

  82. 82.

    Castoldi M, Schmidt S, Benes V, Hentze MW, Muckenthaler MU. miChip: an array-based method for microRNA expression profiling using locked nucleic acid capture probes. Nat Protoc. 2008;3:321–9.

  83. 83.

    Ma CB, Yeung ES, Qi SD, Han R. Highly sensitive detection of microRNA by chemiluminescence based on enzymatic polymerization. Anal Bioanal Chem. 2012;402:2217–20.

  84. 84.

    Baker MB, Bao G, Searles CD. In vitro quantification of specific microRNA using molecular beacons. Nucleic Acids Res. 2012. https://doi.org/10.1093/nar/gkr1016.

  85. 85.

    Baker MB, Bao G, Searles CD. The use of molecular beacons to detect and quantify microRNA. Methods Mol Biol. 2013;1039:279–87.

  86. 86.

    D’Agata R, Spoto G. Artificial DNA and surface plasmon resonance. Artificial DNA: PNA & XNA. 2012;3:45–52.

  87. 87.

    D’Agata R, Giuffrida MC, Spoto G. Peptide nucleic acid-based biosensors for cancer diagnosis. Molecules. 2017;11:22–33.

  88. 88.

    Goldman JM, Zhang LA, Manna A, Armitage BA, Ly DH, Schneider JW. High affinity γPNA sandwich hybridization assay for rapid detection of short nucleic acid targets with single mismatch discrimination. Biomacromolecules. 2013;14:2253–61.

  89. 89.

    Alhasan AH, Kim DY, Daniel WL, Watson E, Meeks JJ, Thaxton CS, et al. Scanometric microRNA array profiling of prostate cancer markers using spherical nucleic acid-gold nanoparticle conjugates. Anal Chem. 2012;84:4153–60.

  90. 90.

    Liao T, Li X, Tong Q, Zou K, Zhang H, Tang L, et al. Ultrasensitive detection of microRNAs with morpholino-functionalized nanochannel biosensor. Anal Chem. 2017;89:5511–8.

  91. 91.

    Neely LA, Patel S, Garver J, Gallo M, Hackett M, McLaughlin S, et al. A single-molecule method for the quantitation of microRNA gene expression. Nat Methods. 2006;3:41–6.

  92. 92.

    Denys B, El HH, Nollet F, Verhasselt B, Philippe J. A real-time polymerase chain reaction assay for rapid, sensitive, and specific quantification of the JAK2V617F mutation using a locked nucleic acid-modified oligonucleotide. J Mol Diagn. 2010;12:512–9.

  93. 93.

    Nuovo GJ, Elton TS, Nana-Sinkam P, Volinia S, Croce CM, Schmittgen TD. A methodology for the combined in situ analyses of the precursor and mature forms of microRNAs and correlation with their putative targets. Nat Protoc. 2009;4:107–15.

  94. 94.

    De Planell-Saguer M, Rodicio MC. Detection methods for microRNAs in clinic practice. Clin Biochem. 2013;46:869–78.

  95. 95.

    De Planell-Saguer M, Rodicio MC, Mourelatos Z. Rapid in situ codetection of noncoding RNAs and proteins in cells and formalin-fixed paraffin-embedded tissue sections without protease treatment. Nat Protoc. 2010;5:1061–73.

  96. 96.

    Wang Y, Stanzel M, Gumbrecht W, Humenik M, Sprinzl M. Biosens Bioelectron. 2007;22:1798–806.

  97. 97.

    Pohlmann C, Sprinzl M. Electrochemical detection of microRNAs via gap hybridization assay. Anal Chem. 2010;82:4434–40.

  98. 98.

    Zanoli LM, Spoto G. Isothermal amplification methods for the detection of nucleic acids in microfluidic devices. Biosensors. 2012;3:18–43.

  99. 99.

    Giuffrida MC, Zanoli LM, D’Agata R, Finotti A, Gambari R, Spoto G. Isothermal circular-strand-displacement polymerization of DNA and microRNA in digital microfluidic devices. Anal Bioanal Chem. 2015;407:1533–43.

  100. 100.

    Lu Z, Zhang L, Deng Y, Lia S, He N. Graphene oxide for rapid microRNA detection. Nanoscale. 2012;4:5840–2.

  101. 101.

    He SJ, Song B, Li D, Zhu CF, Qi WP, Wen YQ, et al. A graphene nanoprobe for rapid, sensitive, and multicolor fluorescent DNA analysis. Adv Funct Mater. 2010;20:453–9.

  102. 102.

    Tang ZW, Wu H, Cort JR, Buchko GW, Zhang YY, Shao YY, et al. Constraint of DNA on functionalized graphene improves its biostability and specificity. Small. 2010. https://doi.org/10.1002/smll.201000024.

  103. 103.

    Cui L, Lin XY, Lin NH, Song YL, Zhu Z, Chen X, et al. Graphene oxide-protected DNA probes for multiplex microRNA analysis in complex biological samples based on a cyclic enzymatic amplification method. Chem Commun. 2012;48:194–6.

  104. 104.

    Tu Y, Li W, Wu P, Zhang H, Cai C. Fluorescence quenching of graphene oxide integrating with the site-specific cleavage of the endonuclease for sensitive and selective microRNA detection. Anal Chem. 2013;85:2536–42.

  105. 105.

    Guo Q, Bian F, Liu Y, Qu X, Hu X, Sun Q. Hybridization chain reactions on silica coated Qbeads for the colorimetric detection of multiplex microRNAs. Chem Commun. 2017;53:4954–7.

  106. 106.

    Zhu D, Zhang L, Ma W, Lu S, Xing X. Detection of microRNA in clinical tumor samples by isothermal enzyme-free amplification and label-free graphene oxide-based SYBR green I fluorescence platform. Biosens Bioelectron. 2015;65:152–8.

  107. 107.

    Huang RC, Chiu WJ, Li YJ, Huang CC. Detection of microRNA in tumor cells using exonuclease III and graphene oxide-regulated signal amplification. ACS Appl Mater Interfaces. 2014;6:21780–7.

  108. 108.

    Robertson NM, Hizir MS, Balcioglu M, Wang R, Selman MY, Yumak H, et al. Discriminating a single nucleotide difference for enhanced miRNA detection using tunable graphene and oligonucleotide nanodevices. Langmuir. 2015;31:9943–52.

  109. 109.

    Howorka S, Siwy Z. Nanopore analytics: sensing of single molecules. Chem Soc Rev. 2009;38:2360–84.

  110. 110.

    Venkatesan BM, Bashir R. Nanopore sensors for nucleic acid analysis. Nature Nanotech. 2011;6:615–24.

  111. 111.

    Wanunu M, Dadosh T, Ray V, Jin J, McReynolds L, Drndic M. Rapid electronic detection of probe-specific microRNAs using thin nanopore sensors. Nature Nanotech. 2010;5:807–14.

  112. 112.

    Jin J, Cid M, Poole CB, McReynolds LA. Protein mediated miRNA detection and siRNA enrichment using p19. BioTechniques. 2010;48:xvii–xxiii.

  113. 113.

    Zhang X, Wang Y, Fricke BL, Gu LQ. Programming nanopore ion flow for encoded multiplex microRNA detection. ACS Nano. 2014;8:3444–50.

  114. 114.

    Tian K, He Z, Wang Y, Chen SJ, Gu LQ. Designing a polycationic probe for simultaneous enrichment and detection of microRNAs in a nanopore. ACS Nano. 2013;7:3962–9.

  115. 115.

    Wang Y, Zheng D, Tan Q, Wang MX, Gu LQ. Nanopore-based detection of circulating microRNAs in lung cancer patients. Nature Nanotechnol. 2011;6:668–74.

  116. 116.

    Lu M, Zhang Q, Deng M, Miao J, Guo Y, Gao W, et al. An analysis of human microRNA and disease associations. PLoS One. 2008. https://doi.org/10.1371/journal.pone.0003420.

  117. 117.

    Dong HF, Gao WC, Yan F, Ji HX, Ju HX. Fluorescence resonance energy transfer between quantum dots and graphene oxide for sensing biomolecules. Anal Chem. 2010;82:5511–7.

  118. 118.

    Ryoo SR, Lee J, Yeo J, Na HK, Kim YK, Jang H, et al. Quantitative and multiplexed microRNA sensing in living cells based on peptide nucleic acid and nano graphene oxide (PANGO). ACS Nano. 2013;7:5882–91.

  119. 119.

    Zhu X, Zheng HY, Wei XF, Lin ZY, Guo LH, Qiu B, et al. Metal–organic framework (MOF): a novel sensing platform for biomolecules. Chem Commun. 2013;49:1276–8.

  120. 120.

    Wu Y, Han J, Xue P, Xu R, Kang Y. Nano metal–organic framework (NMOF)-based strategies for multiplexed microRNA detection in solution and living cancer cells. Nanoscale. 2015;7:1753–9.

  121. 121.

    Dong H, Zhang J, Ju H, Lu H, Wang S, Jin S, et al. Highly sensitive multiple microRNA detection based on fluorescence quenching of graphene oxide and isothermal strand-displacement polymerase reaction. Anal Chem. 2012;15:4587–93.

  122. 122.

    Zhu W, Su X, Gao X, Dai Z, Zou X. A label-free and PCR-free electrochemical assay for multiplexed microRNA profiles by ligase chain reaction coupling with quantum dots barcodes. Biosens Bioelectron. 2014;53:414–9.

  123. 123.

    Qiu Z, Hildebrandt N. Rapid and multiplexed microRNA diagnostic assay using quantum dot-based Förster resonance energy transfer. ACS Nano. 2015;9:8449–57.

  124. 124.

    Jin Z, Geissler D, Qiu X, Wegner KD, Hildebrandt N. A rapid, amplification-free, and sensitive diagnostic assay for single-step multiplexed fluorescence detection of microRNA. Angew Chem Int Ed. 2015;54:10024–9.

  125. 125.

    Bendall SC, Nolan GP, Roederer M, Chattopadhyay PK. A deep profiler’s guide to cytometry. Trends Immunol. 2012;33:323–32.

  126. 126.

    Liu Z, Li X, Xiao G, Chen B, He M, Hu B. Application of inductively coupled plasma mass spectrometry in the quantitative analysis of biomolecules with exogenous tags: a review. Trends in Anal Chem. 2017;93:78–101.

  127. 127.

    Qiu X, Zhang H, Yu H, Jiang T, Luo Y. Duplex-specific nuclease-mediated bioanalysis. Trends Biotechnol. 2015;3:180–8.

  128. 128.

    Zhang S, Liu R, Xing Z, Zhang S, Zhang X. Multiplex miRNA assay using lanthanide-tagged probes and the duplex-specific nuclease amplification strategy. Chem Commun. 2016;52:14310–3.

  129. 129.

    Qavi AJ, Bailey RC. Multiplexed detection and label-free quantitation of microRNAs using arrays of silicon photonic microring resonators. Angew Chem Int Ed. 2010;49:4608–11.

  130. 130.

    Qavi AJ, Kindt JT, Gleeson MA, Bailey RC. Anti-DNA:RNA antibodies and silicon photonic microring resonator arrays enable the ultrasensitive, multiplexed detection of microRNAs. Anal Chem. 2011;83:5949–56.

  131. 131.

    Hu F, Xu J, Chen Y. Surface plasmon resonance imaging detection of sub-femtomolar microRNA. Anal Chem. 2017;89:10071–7.

  132. 132.

    Sguassero A, Artiga Á, Morasso C, Jimenez RR, Rapún RM, Mancuso R, et al. A simple and universal enzyme-free approach for the detection of multiple microRNAs using a single nanostructured enhancer of surface plasmon resonance imaging. Anal Bioanal Chem. 2018. https://doi.org/10.1007/s00216-018-1331-0.

  133. 133.

    Wegman DW, Krylov SN. Direct quantitative analysis of multiple miRNAs (DQAMmiR). Angew Chem Int Ed. 2011;50:10335–9.

  134. 134.

    Yang TH, Ou DL, Hsu C, Huang SH, Chang PL. Comparative microRNA detection from precursor-microRNA-transfected hepatocellular carcinoma cells by capillary electrophoresis with dual-color laser-induced fluorescence. Electrophoresis. 2012;33:2769–76.

  135. 135.

    Bang E, Chae DK, Song EJ. Simultaneous detection of multiple microRNAs for expression profiles of microRNAs in lung cancer cell lines by capillary electrophoresis with dual laser-induced fluorescence. J Chromatogr A. 2013;1315:195–9.

  136. 136.

    Berezovski MV, Khan N. Quantitative analysis of microRNA in blood serum with protein-facilitated affinity capillary electrophoresis. Methods Mol Biol. 2013;1039:245–59.

  137. 137.

    Na J, Shin GW, Son HG, Lee SJV, Jung GY. Multiplex quantitative analysis of microRNA expression via exponential isothermal amplification and conformation-sensitive DNA separation. Sci Rep. 2017;7:11396.

  138. 138.

    Khan N, Mironov G, Berezovski MV. Direct detection of endogenous MicroRNAs and their post-transcriptional modifications in cancer serum by capillary electrophoresis-mass spectrometry. Anal Bioanal Chem. 2016;408:2891–9.

  139. 139.

    Ghasemi F, Wegman DW, Kanoatov M, Yang BB, Liu SK, Yousef GM, et al. Improvements to direct quantitative analysis of multiple microRNAs facilitating faster analysis. Anal Chem. 2013;85:10062–6.

  140. 140.

    Wegman DW, Cherney LT, Yousef GM, Krylov SN. Universal drag tag for direct quantitative analysis of multiple microRNAs. Anal Chem. 2013;85:6518–23.

  141. 141.

    Dodgson BJ, Mazouchi A, Wegman DW, Gradinaru CC, Krylov SN. Detection of a thousand copies of miRNA without enrichment or modification. Anal Chem. 2012;84:5470–4.

  142. 142.

    Anfossi S, Babayan A, Pantel K, Calin GA. Clinical utility of circulating non-coding RNAs—an update. Nat Rev Clin Oncol. 2018;15:541–63.

  143. 143.

    Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105:10513–8.

  144. 144.

    Farina NH, Wood ME, Perrapato SD, Francklyn CS, Stein GS, Stein JL, et al. Standardizing analysis of circulating microRNA: clinical and biological relevance. J Cell Biochem. 2014;115:805–11.

  145. 145.

    Wen Y, Pei H, Shen Y, Xi J, Lin M, Lu N, et al. DNA nanostructure-based interfacial engineering for PCR-free ultrasensitive electrochemical analysis of microRNA. Sci Rep. 2012;2:867–1513.

  146. 146.

    Ren Y, Deng H, Shen W, Gao Z. A highly sensitive and selective electrochemical biosensor for direct detection of microRNAs in serum. Anal Chem. 2013;85:4784–9.

  147. 147.

    Gau V, Wong D. Oral fluid nanosensor test (OFNASET) with advanced electrochemical-based molecular analysis platform. Ann N Y Acad Sci. 2007;1098:401–10.

  148. 148.

    Goon IY, Lai LMH, Lim M, Amal R, Gooding JJ. ‘Dispersible electrodes’: a solution to slow response times of sensitive sensors. Chem Commun. 2010;46:8821–3.

  149. 149.

    Tavallaie R, McCarroll J, Le Grand M, Ariotti N, Schuhmann W, Bakker E, et al. Nucleic acid hybridization on an electrically reconfigurable network of gold-coated magnetic nanoparticles enables microRNA detection in blood. Nat Nanotechnol. 2018. https://doi.org/10.1038/s41565-018-0232-x.

  150. 150.

    Mariani S, Minunni M. Surface plasmon resonance applications in clinical analysis. Anal Bioanal Chem. 2014;406:2303–23.

  151. 151.

    Fang S, Lee HJ, Wark AW, Corn RM. Attomole microarray detection of microRNAs by nanoparticle-amplified SPR imaging measurements of surface polyadenylation reactions. J Am Chem Soc. 2006;128:14044–6.

  152. 152.

    Breveglieri G, Bianchi N, Finotti A, Gambari R. MicroRNAs: from basic research to therapeutic applications. Minerva Biotecnologica. 2014;26:93–102.

  153. 153.

    Nasheri N, Cheng J, Singaravelu R, Wu P, McDermott MT, Pezack JP. An enzyme-linked assay for the rapid quantification of microRNAs based on the viral suppressor of RNA silencing protein p19. Anal Biochem. 2011;412:165–72.

  154. 154.

    Vaisocherová H, Šípová H, Víšová I, Bocková M, Špringer T, Ermini ML, et al. Rapid and sensitive detection of multiple microRNAs in cell lysate by low-fouling surface plasmon resonance biosensor. Biosens Bioelectron. 2015;70:226–31.

  155. 155.

    Ding X, Yan Y, Li S, Zhang Y, Cheng W, Cheng Q, et al. Surface plasmon resonance biosensor for highly sensitive detection of microRNA based on DNA super-sandwich assemblies and streptavidin signal amplification. Anal Chimica Acta. 2015;874:59–65.

  156. 156.

    Cheng N, Xu Y, Luo Y, Zhu L, Zhang Y, Huang K, et al. Specific and relative detection of urinary microRNA signatures in bladder cancer for point-of-care diagnostics. Chem Commun. 2017;3:4222–5.

  157. 157.

    Jia H, Li Z, Liu C, Cheng Y. Ultrasensitive detection of microRNAs by exponential isothermal amplification. Angew Chem. 2010;49:5498–501.

  158. 158.

    Giuffrida MC, Spoto G. Integration of isothermal amplification methods in microfluidic devices: recent advances. Biosens Bioelectron. 2017;90:174–86.

  159. 159.

    Shang L, Cheng Y, Zhao Y. Emerging droplet microfluidics. Chem Rev. 2017;117:7964–8040.

  160. 160.

    Zhang Y, Noji H. Digital bioassays: theory, applications, and perspectives. Anal Chem. 2017;89:92–101.

  161. 161.

    Wang P, Jing F, Li G, Wu Z, Cheng Z, Zhang J, et al. Absolute quantification of lung cancer related microRNA by droplet digital PCR. Biosens Bioelectron. 2015;74:836–42.

  162. 162.

    Tian H, Sun Y, Liu C, Duan X, Tang W, Li Z. Precise quantitation of microRNA in a single cell with droplet digital PCR based on ligation reaction. Anal Chem. 2016;88:11384–9.

  163. 163.

    Zhao G, Jiang T, Liu Y, Huai G, Lan C, Li G, et al. Droplet digital PCR-based circulating microRNA detection serve as a promising diagnostic method for gastric cancer. BMC Cancer. 2018. https://doi.org/10.1186/s12885-018-4601-5.

  164. 164.

    Gasparello J, Allegretti M, Tremante E, Fabbri E, Amoreo CA, Romania P, et al. Liquid biopsy in mice bearing colorectal carcinoma xenografts: gateways regulating the levels of circulating tumor DNA (ctDNA) and miRNA (ctmiRNA). J Exp Clin Cancer Res. 2018. https://doi.org/10.1186/s13046-018-0788-1.

  165. 165.

    Chin CD, Chin SY, Laksanasopin T, Sia SK. Low-cost microdevices for point-of-care testing. In: Issadore D, Westervelt RM, editors. Point-of-care diagnostics on a chip. Berlin: Springer; 2013. p. 3–21.

  166. 166.

    Ishihara R, Hasegawa K, Hosokawa K, Maeda M. Multiplex microRNA detection on a power-free microfluidic chip with laminar flow-assisted dendritic amplification. Anal Sci. 2015;31:573–6.

  167. 167.

    Tokel O, Inci F, Demirci U. Advances in plasmonic technologies for point of care applications. Chem Rev. 2014;114:5728–52.

  168. 168.

    Mousavi MZ, Chen HY, Lee KL, Lin H, Chen HH, Lin Y, et al. Urinary micro-RNA biomarker detection using capped gold nanoslit SPR in a microfluidic chip. Analyst. 2015;140:4097–104.

  169. 169.

    Zhang K, Kang D, Ali MM, Liu L, Labanieh L, Lu M, et al. Digital quantification of miRNA directly in plasma using integrated comprehensive droplet digital detection. Lab Chip. 2015;15:4217–26.

  170. 170.

    Lee H, Shapiro SJ, Chapin SC, Doyle PS. Encoded hydrogel microparticles for sensitive and multiplex microRNA detection directly from raw cell lysates. Anal Chem. 2016;88:3075–81.

  171. 171.

    Chapin SC, Doyle PS. Ultrasensitive multiplexed microRNA quantification on encoded gel microparticles using rolling circle amplification. Anal Chem. 2011;83:7179–85.

  172. 172.

    McArdle H, Jimenez-Mateos EM, Raoof R, Carthy E, Boyle D, ElNaggar H, et al. “TORNADO”—theranostic one-step RNA detector; microfluidic disc for the direct detection of microRNA-134 in plasma and cerebrospinal fluid. Sci Rep. 2017;7:1750.

  173. 173.

    Ge S, Zhang L, Zhang Y, Lan F, Yan M, Yu J. Nanomaterials-modified cellulose paper as a platform for biosensing applications. J Nanoscale. 2017;9:4366–82.

  174. 174.

    Mahato K, Srivastava A, Chandra P. Paper based diagnostics for personalized health care: emerging technologies and commercial aspects. Biosens Bioelectron. 2017;96:246–59.

  175. 175.

    Yildiz UH, Alagappan P, Liedberg B. Naked eye detection of lung cancer associated miRNA by paper based biosensing platform. Anal Chem. 2013;85:820–4.

  176. 176.

    Nelson PT, Wang WX, Wilfred BR, Tang G. Technical variables in high-throughput miRNA expression profiling: much work remains to be done. Biochim Biophys Acta. 2008;1779:758–65.

  177. 177.

    Meyer SU, Pfaff MW, Ulbrich SE. Normalization strategies for microRNA profiling experiments: a ‘normal’ way to a hidden layer of complexity? Biotechnol Lett. 2010;32:1777–88.

  178. 178.

    Tonge DP, Gant TW. Evidence based housekeeping gene selection for microRNA-sequencing (miRNA-seq) studies. Toxicol Res. 2013;2:328–34.

  179. 179.

    Peltier HJ, Latham GJ. Normalization of microRNA expression levels in quantitative RT-PCR assays: identification of suitable reference RNA targets in normal and cancerous human solid tissues. RNA. 2008;14:844–52.

  180. 180.

    Cheng G. Circulating miRNAs: roles in cancer diagnosis, prognosis and therapy. Adv Drug Deliv Rev. 2015;81:75–93.

  181. 181.

    Yang MC, Ruan QG, Yang JJ, Eckenrode S, Wu S, McIndoe RA, et al. A statistical method for flagging weak spots improves normalization and ratio estimates in microarrays. Physiol Genomics. 2001;7:45–53.

  182. 182.

    Mestdagh P, Van Vlierberghe P, De Weer A, Muth D, Westermann F, Speleman F, et al. A novel and universal method for microRNA RT-qPCR data normalization. Genome Biol. 2009;10:R64.

  183. 183.

    Bissels U, Wild S, Tomiuk S, Holste A, Hafner M, Tuschl T, et al. Absolute quantification of microRNAs by using a universal reference. RNA. 2009;12:2375–84.

  184. 184.

    Kroh EM, Parkin RK, Mitchell PS, Tewari M. Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods. 2010;50:298–301.

  185. 185.

    D'haene B, Mestdagh P, Hellemans J, Vandesompele J. miRNA expression profiling: from reference genes to global mean normalization. Methods Mol Biol. 2012;822:261–72.

  186. 186.

    Bustin SA, Nolan T. Pitfalls of quantitative real-time reverse-transcription polymerase chain reaction. J Biomol Tech. 2004;15:155–66.

  187. 187.

    Shi R, Chiang V. Facile means for quantifying microRNA expression by real-time PCR. BioTechniques. 2005;39:519–25.

  188. 188.

    Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, et al. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 2005;33:e179.1–9.

  189. 189.

    Deng R, Zhang K, Li J. Isothermal amplification for microRNA detection: from the test tube to the cell. Acc Chem Res. 2017;50:1059–68.

  190. 190.

    Zhao Y, Chen F, Li Q, Wang L, Fan C. Isothermal amplification of nucleic acids. Chem Rev. 2015;115:12491–545.

  191. 191.

    Bellassai N, Spoto G. Biosensors for liquid biopsy: circulating nucleic acids to diagnose and treat cancer. Anal Bioanal Chem. 2016;408:7255–64.

  192. 192.

    Alix-Panabieres C, Pantel K. Challenges in circulating tumour cell research. Nat Rev Cancer. 2014;14:623–31.

  193. 193.

    Taylor DD, Gercel-Taylor C. Exosomes/microvesicles: mediators of cancer-associated immunosuppressive microenvironments. Semin Immunopathol. 2011;33:441–54.

  194. 194.

    Spellman PT, Gray JW. Detecting cancer by monitoring circulating tumor DNA. Nat Med. 2014;20:474–5.

  195. 195.

    Luna Coronell JA, Syed P, Sergelen K, Gyurján I, Weinhäusel A. The current status of cancer biomarker research using tumour-associated antigens for minimal invasive and early cancer diagnostics. J Proteome. 2012;76:102–15.

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Correspondence to Roberta D’Agata.

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Published in the topical collection Young Investigators in (Bio-)Analytical Chemistry with guest editors Erin Baker, Kerstin Leopold, Francesco Ricci, and Wei Wang.

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D’Agata, R., Spoto, G. Advanced methods for microRNA biosensing: a problem-solving perspective. Anal Bioanal Chem 411, 4425–4444 (2019). https://doi.org/10.1007/s00216-019-01621-8

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Keywords

  • MicroRNA
  • Biosensing
  • Surface plasmon resonance
  • Electrochemistry
  • Fluorescence
  • Microfluidics