Skip to main content
Log in

Signal differentiation models for multiple microRNA detection: a critical review

  • Critical Review
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

MicroRNAs (miRNAs) are a class of small, single-stranded non-coding RNAs which have critical functions in various biological processes. Increasing evidence suggested that abnormal miRNA expression was closely related to many human diseases, and they are projected to be very promising biomarkers for non-invasive diagnosis. Multiplex detection of aberrant miRNAs has great advantages including improved detection efficiency and enhanced diagnostic precision. Traditional miRNA detection methods do not meet the requirements of high sensitivity or multiplexing. Some new techniques have opened novel paths to solve analytical challenges of multiple miRNA detection. Herein, we give a critical overview of the current multiplex strategies for the simultaneous detection of miRNAs from the perspective of two different signal differentiation models, including label differentiation and space differentiation. Meanwhile, recent advances of signal amplification strategies integrated into multiplex miRNA methods are also discussed. We hope this review provides the reader with future perspectives on multiplex miRNA strategies in biochemical research and clinical diagnostics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Treiber T, Treiber N, Meister G. Regulation of microRNA biogenesis and its crosstalk with other cellular pathways. Nat Rev Mol Cell Biol. 2019;20(1):5–20. https://doi.org/10.1038/s41580-018-0059-1.

    Article  CAS  PubMed  Google Scholar 

  2. Dong H, Lei J, Ding L, Wen Y, Ju H, Zhang X. MicroRNA: function, detection, and bioanalysis. Chem Rev. 2013;113(8):6207–33. https://doi.org/10.1021/cr300362f.

    Article  CAS  PubMed  Google Scholar 

  3. Peng Y, Croce CM. The role of MicroRNAs in human cancer. Signal Transduct Target Ther. 2016;1:15004. https://doi.org/10.1038/sigtrans.2015.4.

    Article  PubMed  PubMed Central  Google Scholar 

  4. van den Berg MMJ, Krauskopf J, Ramaekers JG, Kleinjans JCS, Prickaerts J, Briede JJ. Circulating microRNAs as potential biomarkers for psychiatric and neurodegenerative disorders. Prog Neurobiol. 2020;185:101732. https://doi.org/10.1016/j.pneurobio.2019.101732.

  5. Eliasson L, Esguerra JLS. MicroRNA networks in pancreatic islet cells: normal function and type 2 diabetes. Diabetes. 2020;69(5):804–12. https://doi.org/10.2337/dbi19-0016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Barwari T, Joshi A, Mayr M. MicroRNAs in cardiovascular disease. J Am Coll Cardiol. 2016;68(23):2577–84. https://doi.org/10.1016/j.jacc.2016.09.945.

    Article  CAS  PubMed  Google Scholar 

  7. Alles J, Fehlmann T, Fischer U, Backes C, Galata V, Minet M, Hart M, Abu-Halima M, Grasser FA, Lenhof HP, Keller A, Meese E. An estimate of the total number of true human miRNAs. Nucleic Acids Res. 2019;47(7):3353–64. https://doi.org/10.1093/nar/gkz097.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Li W, Ruan K. MicroRNA detection by microarray. Anal Bioanal Chem. 2009;394:1117–24. https://doi.org/10.1007/s00216-008-2570-2.

    Article  CAS  PubMed  Google Scholar 

  9. Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, Barbisin M, Xu NL, Mahuvakar VR, Andersen MR, Lao KQ, Livak KJ, Guegler KJ. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 2005;33 (20):e179. https://doi.org/10.1093/nar/gni178.

  10. Bang TCd, Husted S. Lanthanide elements as labels for multiplexed and targeted analysis of proteins, DNA and RNA using inductively-coupled plasma mass spectrometry. Trends Anal Chem. 2015;72:45–52. https://doi.org/10.1016/j.trac.2015.03.021.

    Article  CAS  Google Scholar 

  11. Wang C, Song H, Zhao X, Liu R, Lv Y. Multiplex DNA walking machines for lung cancer-associated miRNAs. Anal Chem. 2022;94(3):1787–94. https://doi.org/10.1021/acs.analchem.1c04557.

    Article  CAS  PubMed  Google Scholar 

  12. Bang TCd, Shah P, Cho SK, Yang SW, Husted S. Multiplexed microRNA detection using lanthanide-labeled DNA probes and laser ablation inductively coupled plasma mass spectrometry. Anal Chem. 2014;86(14):6823–6. https://doi.org/10.1021/ac5017166.

    Article  CAS  PubMed  Google Scholar 

  13. 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 (Camb). 2016;52(99):14310–3. https://doi.org/10.1039/c6cc08334j.

    Article  CAS  PubMed  Google Scholar 

  14. Kang Q, He M, Chen B, Xiao G, Hu B. MNAzyme-catalyzed amplification assay with lanthanide tags for the simultaneous detection of multiple microRNAs by inductively coupled plasma-mass spectrometry. Anal Chem. 2021;93(2):737–44. https://doi.org/10.1021/acs.analchem.0c02455.

    Article  CAS  PubMed  Google Scholar 

  15. Shen J, Li T, Wang M, Yao B. Isothermal and enzyme-free MicroRNA assay based on catalytic hairpin assembly and rare earth element labeled probes. Sens Actuators B Chem. 2022;357. https://doi.org/10.1016/j.snb.2022.131364.

  16. Zhang Y, Zhang Q, Weng X, Du Y, Zhou X. NEase-based amplification for detection of miRNA, multiple miRNAs and circRNA. Anal Chim Acta. 2021;1145:52–8. https://doi.org/10.1016/j.aca.2020.12.024.

    Article  CAS  PubMed  Google Scholar 

  17. Wang Z, Zong S, Liu Y, Qian Z, Zhu K, Yang Z, Wang Z, Cui Y. Simultaneous detection of multiple exosomal microRNAs for exosome screening based on rolling circle amplification. Nanotechnology. 2021;32 (8):085504. https://doi.org/10.1088/1361-6528/abc7d4.

  18. Chen J, Fan T, Chen Y, Ye L, Zhang C, Liu F, Qin Y, Tan Y, Jiang Y. Zeptomolar-level one-pot simultaneous detection of multiple colorectal cancer microRNAs by cascade isothermal amplification. Biosens Bioelectron. 2020;169:112631. https://doi.org/10.1016/j.bios.2020.112631.

  19. Khoothiam K, Treerattrakoon K, Iempridee T, Luksirikul P, Dharakul T, Japrung D. Ultrasensitive detection of lung cancer-associated miRNAs by multiple primer-mediated rolling circle amplification coupled with a graphene oxide fluorescence-based (MPRCA-GO) sensor. Analyst. 2019;144(14):4180–7. https://doi.org/10.1039/c9an00517j.

    Article  CAS  PubMed  Google Scholar 

  20. Xiao M, Man T, Zhu C, Pei H, Shi J, Li L, Qu X, Shen X, Li J. MoS2 nanoprobe for microRNA quantification based on duplex-specific nuclease signal amplification. ACS Appl Mater Interfaces. 2018;10(9):7852–8. https://doi.org/10.1021/acsami.7b18984.

    Article  CAS  PubMed  Google Scholar 

  21. Peng S, Liu M, Bie B, Zhang Y, Tang H, Sun Y, Zhou X. Multiplexed microRNA detection using metal-organic framework for signal output. ACS Appl Bio Mater. 2020;3(5):2604–9. https://doi.org/10.1021/acsabm.9b01189.

    Article  CAS  PubMed  Google Scholar 

  22. Zhao H, Wang M, Xiong X, Liu Y, Chen X. Simultaneous fluorescent detection of multiplexed miRNA of liver cancer based on DNA tetrahedron nanotags. Talanta. 2020;210:120677. https://doi.org/10.1016/j.talanta.2019.120677.

  23. Tang Y, He X, Yuan R, Liu X, Zhao Y, Wang T, Chen H, Feng X. Logic-signal-based multiplex detection of MiRNAs with high tension hybridization and multiple signal amplification. Analyst. 2020;145(12):4314–20. https://doi.org/10.1039/d0an00550a.

    Article  CAS  PubMed  Google Scholar 

  24. Xu J, Guo J, Golob-Schwarzl N, Haybaeck J, Qiu X, Hildebrandt N. Single-measurement multiplexed quantification of microRNAs from human tissue using catalytic hairpin assembly and forster resonance energy transfer. ACS Sens. 2020;5(6):1768–76. https://doi.org/10.1021/acssensors.0c00432.

    Article  CAS  PubMed  Google Scholar 

  25. Park Y, Yoon J, Lee J, Lee S, Park HG. Multiplexed miRNA detection based on target-triggered transcription of multicolor fluorogenic RNA aptamers. Biosens Bioelectron. 2022;204:114071. https://doi.org/10.1016/j.bios.2022.114071.

  26. Wang JJ, Liu Y, Ding Z, Zhang L, Han C, Yan C, Amador E, Yuan L, Wu Y, Song C, Liu Y, Chen W. The exploration of quantum dot-molecular beacon based MoS2 fluorescence probing for myeloma-related miRNAs detection. Bioact Mater. 2022;17:360–8. https://doi.org/10.1016/j.bioactmat.2021.12.036.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Li M, Xu X, Cai Q. DNA polymerase/NEase-assisted signal amplification coupled with silver nanoclusters for simultaneous detection of multiple microRNAs and molecular logic operations. Sens Actuators B Chem. 2021;327. https://doi.org/10.1016/j.snb.2020.128915.

  28. Wang JJ, Zheng C, Jiang YZ, Zheng Z, Lin M, Lin Y, Zhang ZL, Wang H, Pang DW. One-step monitoring of multiple enterovirus 71 infection-related microRNAs usingcore-satellite structure of magnetic nanobeads and multicolor quantum dots. Anal Chem. 2020;92(1):830–7. https://doi.org/10.1021/acs.analchem.9b03317.

    Article  CAS  PubMed  Google Scholar 

  29. Xiang L, Zhang F, Feng J, Chen C, Cai C. Single-excited double-emission CdTe@CdS quantum dots for use in a fluorometric hybridization assay for multiple tumor-related microRNAs. Mikrochim Acta. 2020;187(2):134. https://doi.org/10.1007/s00604-020-4117-y.

    Article  CAS  PubMed  Google Scholar 

  30. Xu S, Nie Y, Jiang L, Wang J, Xu G, Wang W, Luo X. Polydopamine nanosphere/gold nanocluster (Au NC)-based nanoplatform for dual color simultaneous detection of multiple tumor-related microRNAs with DNase-I-assisted target recycling amplification. Anal Chem. 2018;90(6):4039–45. https://doi.org/10.1021/acs.analchem.7b05253.

    Article  CAS  PubMed  Google Scholar 

  31. Wu X, Li Y, Yang MY, Mao CB. Simultaneous ultrasensitive detection of two breast cancer microRNA biomarkers by using a dual nanoparticle/nanosheet fluorescence resonance energy transfer sensor. Mater Today Adv. 2021;12. https://doi.org/10.1016/j.mtadv.2021.100163.

  32. Ye S, Wang M, Wang Z, Zhang N, Luo X. A DNA-linker-DNA bifunctional probe for simultaneous SERS detection of miRNAs via symmetric signal amplification. Chem Commun (Camb). 2018;54(56):7786–9. https://doi.org/10.1039/c8cc02910e.

    Article  CAS  PubMed  Google Scholar 

  33. Wu J, Zhou X, Li P, Lin X, Wang J, Hu Z, Zhang P, Chen D, Cai H, Niessner R, Haisch C, Sun P, Zheng Y, Jiang Z, Zhou H. Ultrasensitive and simultaneous SERS detection of multiplex microRNA using fractal gold nanotags for early diagnosis and prognosis of hepatocellular carcinoma. Anal Chem. 2021;93(25):8799–809. https://doi.org/10.1021/acs.analchem.1c00478.

    Article  CAS  PubMed  Google Scholar 

  34. Kim J, Park J, Ki J, Rho HW, Huh YM, Kim E, Son HY, Haam S. Simultaneous dual-targeted monitoring of breast cancer circulating miRNA via surface-enhanced Raman spectroscopy. Biosens Bioelectron. 2022;207:114143. https://doi.org/10.1016/j.bios.2022.114143.

  35. Guo R, Yin F, Sun Y, Mi L, Shi L, Tian Z, Li T. Ultrasensitive simultaneous detection of multiplex disease-related nucleic acids using double-enhanced surface-enhanced Raman scattering nanosensors. ACS Appl Mater Interfaces. 2018;10(30):25770–8. https://doi.org/10.1021/acsami.8b06757.

    Article  CAS  PubMed  Google Scholar 

  36. Chang J, Wang X, Wang J, Li H, Li F. Nucleic acid-functionalized metal-organic framework-based homogeneous electrochemical biosensor for simultaneous detection of multiple tumor biomarkers. Anal Chem. 2019;91(5):3604–10. https://doi.org/10.1021/acs.analchem.8b05599.

    Article  CAS  PubMed  Google Scholar 

  37. Xu S, Chang Y, Wu Z, Li Y, Yuan R, Chai Y. One DNA circle capture probe with multiple target recognition domains for simultaneous electrochemical detection of miRNA-21 and miRNA-155. Biosens Bioelectron. 2020;149:111848. https://doi.org/10.1016/j.bios.2019.111848.

  38. Chang Y, Wu Z, Sun Q, Zhuo Y, Chai Y, Yuan R. Simply constructed and highly efficient classified cargo-discharge DNA robot: a DNA walking nanomachine platform for ultrasensitive multiplexed sensing. Anal Chem. 2019;91(13):8123–8. https://doi.org/10.1021/acs.analchem.9b00363.

    Article  CAS  PubMed  Google Scholar 

  39. Mohammadniaei M, Koyappayil A, Sun Y, Min J, Lee MH. Gold nanoparticle/MXene for multiple and sensitive detection of oncomiRs based on synergetic signal amplification. Biosens Bioelectron. 2020;159:112208. https://doi.org/10.1016/j.bios.2020.112208.

  40. Lin Q, Wu J, Jiang L, Kong D, Xing C, Lu C. Target-driven assembly of DNAzyme probes for simultaneous electrochemical detection of multiplex microRNAs. Analyst. 2022;147(2):262–7. https://doi.org/10.1039/d1an02036f.

    Article  CAS  PubMed  Google Scholar 

  41. Xu E, Feng Y, Yang H, Li P, Kong L, Wei W, Liu S. Ultrasensitive and specific multi-miRNA detection based on dual signal amplification. Sens Actuators B Chem. 2021;337. https://doi.org/10.1016/j.snb.2021.129745.

  42. Pimalai D, Putnin T, Waiwinya W, Chotsuwan C, Aroonyadet N, Japrung D. Development of electrochemical biosensors for simultaneous multiplex detection of microRNA for breast cancer screening. Mikrochim Acta. 2021;188(10):329. https://doi.org/10.1007/s00604-021-04995-8.

    Article  CAS  PubMed  Google Scholar 

  43. Cao Z, Duan F, Huang X, Liu Y, Zhou N, Xia L, Zhang Z, Du M. A multiple aptasensor for ultrasensitive detection of miRNAs by using covalent-organic framework nanowire as platform and shell-encoded gold nanoparticles as signal labels. Anal Chim Acta. 2019;1082:176–85. https://doi.org/10.1016/j.aca.2019.07.062.

    Article  CAS  PubMed  Google Scholar 

  44. Qi T, Song C, He J, Shen W, Kong D, Shi H, Tan L, Pan R, Tang S, Lee HK. Highly sensitive detection of multiple microRNAs by high-performance liquid chromatography coupled with long and short probe-based recycling amplification. Anal Chem. 2020;92(7):5033–40. https://doi.org/10.1021/acs.analchem.9b05301.

    Article  CAS  PubMed  Google Scholar 

  45. Shi CX, Li SX, Chen ZP, Liu Q, Yu RQ. Label-free and multiplexed quantification of microRNAs by Mass spectrometry based on duplex-specific-nuclease-assisted recycling amplification. Anal Chem. 2019;91(3):2120–7. https://doi.org/10.1021/acs.analchem.8b04583.

    Article  CAS  PubMed  Google Scholar 

  46. Kuang Y, Cao J, Xu F, Chen Y. Duplex-specific nuclease-mediated amplification strategy for mass spectrometry quantification of miRNA-200c in breast cancer stem cells. Anal Chem. 2019;91(14):8820–6. https://doi.org/10.1021/acs.analchem.8b04468.

    Article  CAS  PubMed  Google Scholar 

  47. Liu L, Kuang Y, Yang H, Chen Y. An amplification strategy using DNA-peptide dendrimer probe and mass spectrometry for sensitive MicroRNA detection in breast cancer. Anal Chim Acta. 2019;1069:73–81. https://doi.org/10.1016/j.aca.2019.04.009.

    Article  CAS  PubMed  Google Scholar 

  48. Xu F, Zhou W, Cao J, Xu Q, Jiang D, Chen Y. A combination of DNA-peptide probes and liquid chromatography-tandem mass spectrometry (LC-MS/MS): a quasi-targeted proteomics approach for multiplexed microRNA quantification. Theranostics. 2017;7(11):2849–62. https://doi.org/10.7150/thno.19113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Lv W, Ye H, Yuan Z, Liu X, Chen X, Yang W. Recent advances in electrochemiluminescence-based simultaneous detection of multiple targets. Trends Anal Chem. 2020;123:115767. https://doi.org/10.1016/j.trac.2019.115767.

  50. Sun Y, Shi L, Mi L, Guo R, Li T. Recent progress of SERS optical nanosensors for miRNA analysis. J Mater Chem B. 2020;8(24):5178–83. https://doi.org/10.1039/d0tb00280a.

    Article  CAS  PubMed  Google Scholar 

  51. Si Y, Xu L, Wang N, Zheng J, Yang R, Li J. Target microRNA-responsive DNA hydrogel-based surface-enhanced Raman scattering sensor arrays for microRNA-marked cancer screening. Anal Chem. 2020;92(3):2649–55. https://doi.org/10.1021/acs.analchem.9b04606.

    Article  CAS  PubMed  Google Scholar 

  52. Si Y, Xu L, Deng T, Zheng J, Li J. Catalytic hairpin self-assembly-based SERS sensor array for the simultaneous measurement of multiple cancer-associated miRNAs. ACS Sens. 2020;5(12):4009–16. https://doi.org/10.1021/acssensors.0c01876.

    Article  CAS  PubMed  Google Scholar 

  53. Song Y, Xu T, Zhu Q, Zhang X. Integrated individually electrochemical array for simultaneously detecting multiple Alzheimerʼs biomarkers. Biosens Bioelectron. 2020;162:112253. https://doi.org/10.1016/j.bios.2020.112253.

  54. Liu Y, Huang Z, Xu Q, Zhang L, Liu Q, Xu T. Portable electrochemical micro-workstation platform for simultaneous detection of multiple Alzheimerʼs disease biomarkers. Mikrochim Acta. 2022;189(3):91. https://doi.org/10.1007/s00604-022-05199-4.

    Article  CAS  PubMed  Google Scholar 

  55. Zhou M, Fan C, Wang L, Xu T, Zhang X. Enhanced isothermal amplification for ultrafast sensing of SARS-CoV-2 in microdroplets. Anal Chem. 2022;94(10):4135–40. https://doi.org/10.1021/acs.analchem.2c00008.

    Article  CAS  PubMed  Google Scholar 

  56. Luo Y, Fan C, Song Y, Xu T, Zhang X. Ultra-trace enriching biosensing in nanoliter sample. Biosens Bioelectron. 2022;210:114297. https://doi.org/10.1016/j.bios.2022.114297.

  57. Causa F, Aliberti A, Cusano AM, Battista E, Netti PA. Supramolecular spectrally encoded microgels with double strand probes for absolute and direct miRNA fluorescence detection at high sensitivity. J Am Chem Soc. 2015;137(5):1758–61. https://doi.org/10.1021/ja511644b.

    Article  CAS  PubMed  Google Scholar 

  58. Han M, Gao X, Su JZ, Nie S. Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules. Nat Biotechnol. 2001;19:631–5.

    Article  CAS  PubMed  Google Scholar 

  59. Ho Y-P, Kung MC, Yang S, Wang T-H. Multiplexed hybridization detection with multicolor colocalization of quantum dot nanoprobes. Nano Lett. 2005;5(9):1693–7.

    Article  CAS  PubMed  Google Scholar 

  60. Qu X, Jin H, Liu Y, Sun Q. Strand displacement amplificationr reaction on quantum dot-encoded silica bead for visual detection of multiplex microRNAs. Anal Chem. 2018;90(5):3482–9. https://doi.org/10.1021/acs.analchem.7b05235.

    Article  CAS  PubMed  Google Scholar 

  61. Wang Y, Lau C, Lu J. Target-initiated labeling for the dual-amplified detection of multiple microRNAs. Anal Chim Acta. 2017;992:76–84. https://doi.org/10.1016/j.aca.2017.08.029.

    Article  CAS  PubMed  Google Scholar 

  62. Wang J, Sun Y, Lau C, Lu J. Target-fueled catalytic hairpin assembly for sensitive and multiplex microRNA detection. Anal Bioanal Chem. 2020;412:3019–27. https://doi.org/10.1007/s00216-020-02531-w.

    Article  CAS  PubMed  Google Scholar 

  63. Li D, Wang Y, Lau C, Lu J. xMAP array microspheres based stem-loop structured probes as conformational switches for multiplexing detection of miRNAs. Anal Chem. 2014;86(20):10148–56. https://doi.org/10.1021/ac501989b.

    Article  CAS  PubMed  Google Scholar 

  64. Wang Y, Sun Y, Lau C, Lu J. Duplex microRNAs assay based on target-triggered universal reporter hybridization. J Pharm Anal. 2018;8(4):265–70. https://doi.org/10.1016/j.jpha.2018.07.004.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Sun Y, Wang Y, Lau C, Chen G, Lu J. Hybridization-initiated exonuclease resistance strategy for simultaneous detection of multiple microRNAs. Talanta. 2018;190:248–54. https://doi.org/10.1016/j.talanta.2018.07.070.

    Article  CAS  PubMed  Google Scholar 

  66. Tao G, Lai T, Xu X, Ma Y, Wu X, Pei X, Liu F, Li N. Colocalized particle counting platform for zeptomole level multiplexed quantification. Anal Chem. 2020;92(5):3697–706. https://doi.org/10.1021/acs.analchem.9b04823.

    Article  CAS  PubMed  Google Scholar 

  67. Wang N, Song L, Deng T, Li J. Microsphere-based suspension array for simultaneous recognition and quantification of multiple cancer-associated miRNA via DNAzyme-mediated signal amplification. Anal Chim Acta. 2020;1140:69–77. https://doi.org/10.1016/j.aca.2020.10.003.

    Article  CAS  PubMed  Google Scholar 

  68. Al Sulaiman D, Juthani N, Doyle PS. Quantitative and multiplex detection of extracellular vesicle-derived microRNA via rolling circle amplification within encoded hydrogel microparticles. Adv Healthc Mater. 2022;11(10):e2102332. https://doi.org/10.1002/adhm.202102332.

  69. Shin K, Choi J, Kim Y, Lee Y, Kim J, Lee S, Chung H. Feasibility study for combination of field-flow fractionation (FFF)-based separation of size-coded particle probes with amplified surface enhanced Raman scattering (SERS) tagging for simultaneous detection of multiple miRNAs. J Chromatogr A. 2018;1556:97–102. https://doi.org/10.1016/j.chroma.2018.04.057.

    Article  CAS  PubMed  Google Scholar 

  70. Miyagawa A, Harada M, Okada T. Zeptomole detection scheme based on levitation coordinate measurements of a single microparticle in a coupled acoustic-gravitational field. Anal Chem. 2018;90(3):2310–6. https://doi.org/10.1021/acs.analchem.7b04752.

    Article  CAS  PubMed  Google Scholar 

  71. Miyagawa A, Harada M, Okada T. Multiple microRNA quantification based on acoustic levitation of single microspheres after one-pot sandwich interparticle hybridizations. Anal Chem. 2018;90(22):13729–35. https://doi.org/10.1021/acs.analchem.8b04143.

    Article  CAS  PubMed  Google Scholar 

  72. Qiu LY, Zhang YC, Liu CH, Li ZP. A versatile size-coded flow cytometric bead assay for simultaneous detection of multiple microRNAs coupled with a two-step cascading signal amplification. Chem Commun. 2017;53(20):2926–9.

    Article  CAS  Google Scholar 

  73. Xu T, Soto F, Gao W, Dong R, Garcia-Gradilla V, Magana E, Zhang X, Wang J. Reversible swarming and separation of self-propelled chemically powered nanomotors under acoustic fields. J Am Chem Soc. 2015;137(6):2163–6. https://doi.org/10.1021/ja511012v.

    Article  CAS  PubMed  Google Scholar 

  74. Sun Y, Luo Y, Xu T, Cheng G, Cai H, Zhang X. Acoustic aggregation-induced separation for enhanced fluorescence detection of Alzheimerʼs biomarker. Talanta. 2021;233:122517. https://doi.org/10.1016/j.talanta.2021.122517.

  75. Wang X, Yuan W, Xu Y, Yuan H, Li F. Sensitive multiplex detection of microRNAs based on liquid suspension nano-chip. Anal Chim Acta. 2020;1112:24–33. https://doi.org/10.1016/j.aca.2020.03.026.

    Article  CAS  PubMed  Google Scholar 

  76. Liu S, Fang H, Sun C, Wang N, Li J. Highly sensitive and multiplexed miRNA analysis based on digitally encoded silica microparticles coupled with RCA-based cascade amplification. Analyst. 2018;143(21):5137–44. https://doi.org/10.1039/c8an01393d.

    Article  CAS  PubMed  Google Scholar 

  77. Juthani N, Doyle PS. A platform for multiplexed colorimetric microRNA detection using shape-encoded hydrogel particles. Analyst. 2020;145(15):5134–40. https://doi.org/10.1039/d0an00938e.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Xiang Y, Yan H, Zheng B, Faheem A, Hu Y. Microorganism@UiO-66-NH2 composites for the detection of multiple colorectal cancer-related microRNAs with fow cytometry. Anal Chem. 2020;92(18):12338–46. https://doi.org/10.1021/acs.analchem.0c02017.

    Article  CAS  PubMed  Google Scholar 

  79. Wang R, Xu X, Li X, Zhang N, Jiang W. pH-responsive ZnO nanoprobe mediated DNAzyme signal amplification strategy for sensitive detection and live cell imaging of multiple microRNAs. Sens Actuators B Chem. 2019;293:93–9. https://doi.org/10.1016/j.snb.2019.05.002.

    Article  CAS  Google Scholar 

  80. Zhang Y, Shen X, Li W, Long Z, Ouyang J, Na N. Multi-dimensionally extended functionalization innovates to an entropy-driven detection of multi-miRNAs for one-step cancer screening and diagnosis in living cells. Anal Chem. 2020;92(12):8125–32. https://doi.org/10.1021/acs.analchem.0c00045.

    Article  CAS  PubMed  Google Scholar 

  81. Wang S, Zhang L, Kan A, Xu X, Zhang N, Jiang W. MnO(2) nanosheet-mediated target-binding-induced FRET strategy for multiplexed microRNAs detection and imaging in living cells. Talanta. 2021;226:122202. https://doi.org/10.1016/j.talanta.2021.122202.

  82. Dong J, Dong H, Dai W, Meng X, Zhang K, Cao Y, Yang F, Zhang X. Functional DNA hexahedron for real-time detection of multiple microRNAs in living cells. Anal Chim Acta. 2019;1078:176–81. https://doi.org/10.1016/j.aca.2019.06.034.

    Article  CAS  PubMed  Google Scholar 

  83. Yang Q, Yang F, Dai W, Meng X, Wei W, Cheng Y, Dong J, Lu H, Dong H. DNA logic circuits for multiple tumor cells identification using intracellular microRNA molecular bispecific recognition. Adv Healthc Mater. 2021;10(21):e2101130. https://doi.org/10.1002/adhm.202101130.

  84. Lu H, Guo K, Cao Y, Yang F, Wang D, Dou L, Liu Y, Dong H. Cancer cell membrane vesicle for multiplex microRNA imaging in living cells. Anal Chem. 2020;92(2):1850–5. https://doi.org/10.1021/acs.analchem.9b03764.

    Article  CAS  PubMed  Google Scholar 

  85. Zhao D, Yin Q, Chang Y, Liu M. Nucleic acid circuits for cell imaging: from the test tube to the cell. TrAC Trends Anal Chem. 2020;122. https://doi.org/10.1016/j.trac.2019.115706.

  86. Zada S, Lu H, Dai W, Tang S, Khan S, Yang F, Qiao Y, Fu P, Dong H, Zhang X. Multiple amplified microRNAs monitoring in living cells based on fluorescence quenching of Mo2B and hybridization chain reaction. Biosens Bioelectron. 2022;197:113815. https://doi.org/10.1016/j.bios.2021.113815.

  87. Wei W, Dai W, Yang F, Lu H, Zhang K, Xing Y, Meng X, Zhou L, Zhang Y, Yang Q, Cheng Y, Dong H. Spatially resolved, error-robust multiplexed microRNA profiling in single living cells. Angew Chem Int Ed Engl. 2022;61(20):e202116909. https://doi.org/10.1002/anie.202116909.

  88. Li S, Tang Y, Hu L, Qian W, Ma L, Sun X, Ji W, Zhang B, Han S, Chi Y, Zhu D. Autonomously driving multiplexed hierarchical hybridization chain reaction of a DNA cobweb sensor for monitoring intracellular microRNA. Sens Actuators B Chem. 2021;344. https://doi.org/10.1016/j.snb.2021.130205.

  89. Wang YX, Wang DX, Wang J, Liu B, Tang AN, Kong DM. DNA nanolantern-mediated catalytic hairpin assembly nanoamplifiers for simultaneous detection of multiple microRNAs. Talanta. 2022;236:122846. https://doi.org/10.1016/j.talanta.2021.122846.

  90. Meng X, Dai W, Zhang K, Dong H, Zhang X. Imaging multiple microRNAs in living cells using ATP self-powered strand-displacement cascade amplification. Chem Sci. 2018;9(5):1184–90. https://doi.org/10.1039/c7sc04725h.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We acknowledge funding from the Natural Science Foundation of Zhejiang Province (LQ23H300003), National Natural Science Foundation of China (81903576), Shenzhen Key Laboratory for Nano-Biosensing Technology (ZDSYS20210112161400001), and Shenzhen Stability Support Plan (20200806163622001), Shenzhen Overseas Talent Program.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tailin Xu.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Published in the topical collection Young Investigators in (Bio-)Analytical Chemistry 2023 with guest editors Zhi-Yuan Gu, Beatriz Jurado-Sánchez, Thomas H. Linz, Leandro Wang Hantao, Nongnoot Wongkaew, and Peng Wu.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sun, Y., Wang, Y., Fang, L. et al. Signal differentiation models for multiple microRNA detection: a critical review. Anal Bioanal Chem 415, 3967–3981 (2023). https://doi.org/10.1007/s00216-023-04626-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-023-04626-6

Keywords

Navigation