Functional Nucleic Acid Based Platforms for Heavy Metal Ion Detection

  • Yunbo Luo


The detection of heavy metal ions plays a crucial role in the monitoring of environmental pollution. With the discovery of functional nucleic acids, more and more scientists have combined the detection of heavy metals with functional nucleic acids, because functional nucleic acids can convert metal ion signals into nucleic acid signals. With the continuous development of metal ion detection methods, the absolute quantification method of metal ions is gradually expected by people. Therefore, metal ions can be detected by a combination of digital PCR (dPCR) and functional nucleic acid. As the same time, dPCR have many advantages for metal ions detection and many examples was developed. Biological ion channels that exist in living organisms serve a significant function in vital activities, nanopore sensing combining with DNA also providing an opportunity to control or regulate the molecular transport on demand. In this chapter, Digital PCR and Nanopore sensing composed of FNAs for signal recognition and sensing components for signal output are reviewed for diverse categories of metal ions.


Functional nucleic acids Metal ion detection Digital PCR Principle Advantages Application Nanopore 


  1. 1.
    J. Willis, Determination of lead and other heavy metals in urine by atomic absorption spectroscopy. Anal. Chem. 34(6), 614–617 (1962)CrossRefGoogle Scholar
  2. 2.
    F. Shemirani, M. Rajabi, Preconcentration of chromium (III) and speciation of chromium by electrothermal atomic absorption spectrometry using cellulose adsorbent. Fresenius J. Anal. Chem. 371(7), 1037–1040 (2001)CrossRefPubMedGoogle Scholar
  3. 3.
    K. Uysal, Y. Emre, E. Köse, The determination of heavy metal accumulation ratios in muscle, skin and gills of some migratory fish species by inductively coupled plasma-optical emission spectrometry (ICP-OES) in Beymelek Lagoon (Antalya/Turkey). Microchem. J. 90(1), 67–70 (2008)CrossRefGoogle Scholar
  4. 4.
    W. Wolf, M. Taylor, B. Hughes, T. Tiernan, R. Sievers, Determination of chromium and beryllium at the picogram level by gas chromatography-mass spectrometry. Anal. Chem. 44(3), 616–618 (1972)CrossRefPubMedGoogle Scholar
  5. 5.
    W. Zhou, R. Saran, J. Liu, Metal Sensing by DNA. Chem. Rev. 117, 8272–8325 (2017)CrossRefPubMedGoogle Scholar
  6. 6.
    B.C. Ye, B.C. Yin, Highly sensitive detection of mercury (II) ions by fluorescence polarization enhanced by gold nanoparticles. Angew. Chem. Int. Ed. 47(44), 8386–8389 (2008)CrossRefGoogle Scholar
  7. 7.
    J. Liu, Z. Cao, Y. Lu, Functional nucleic acid sensors. Chem. Rev. 109(5), 1948–1998 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    S. Oliveira, O. Corduneanu, A. Oliveira-Brett, In situ evaluation of heavy metal-DNA interactions using an electrochemical DNA biosensor. Bioelectrochemistry 72(1), 53–58 (2008)CrossRefPubMedGoogle Scholar
  9. 9.
    D. Li, A. Wieckowska, I. Willner, Optical analysis of Hg2+ ions by oligonucleotide-gold-nanoparticle hybrids and DNA-based machines. Angew. Chem. 120(21), 3991–3995 (2008)CrossRefGoogle Scholar
  10. 10.
    W. Li, Y. Yang, J. Chen, Q. Zhang, Y. Wang, F. Wang, C. Yu, Detection of lead (II) ions with a DNAzyme and isothermal strand displacement signal amplification. Biosens. Bioelectron. 53, 245–249 (2014)CrossRefPubMedGoogle Scholar
  11. 11.
    J. Huang, X. Gao, J. Jia, J.-K. Kim, Z. Li, Graphene oxide-based amplified fluorescent biosensor for Hg2+ detection through hybridization chain reactions. Anal. Chem. 86(6), 3209–3215 (2014)CrossRefPubMedGoogle Scholar
  12. 12.
    A. Daser, M. Thangavelu, R. Pannell, A. Forster, L. Sparrow, G. Chung, P.H. Dear, T.H. Rabbitts, Interrogation of genomes by molecular copy-number counting (MCC). Nat. Methods. 3(6), 447 (2006)CrossRefPubMedGoogle Scholar
  13. 13.
    P.H. Dear, P.R. Cook, Happy mapping: linkage mapping using a physical analogue of meiosis. Nucleic Acids Res. 21(1), 13–20 (1993)CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    R. Sanders, J.F. Huggett, C.A. Bushell, S. Cowen, D.J. Scott, C.A. Foy, Evaluation of digital PCR for absolute DNA quantification. Anal. Chem. 83(17), 6474–6484 (2011)CrossRefPubMedGoogle Scholar
  15. 15.
    L.B. Pinheiro, V.A. Coleman, C.M. Hindson, J. Herrmann, B.J. Hindson, S. Bhat, K.R. Emslie, Evaluation of a droplet digital polymerase chain reaction format for DNA copy number quantification. Anal. Chem. 84(2), 1003–1011 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    S. Bhat, J. Herrmann, P. Armishaw, P. Corbisier, K.R. Emslie, Single molecule detection in nanofluidic digital array enables accurate measurement of DNA copy number. Anal. Bioanal. Chem. 394(2), 457–467 (2009)CrossRefPubMedGoogle Scholar
  17. 17.
    E.A. Ottesen, J.W. Hong, S.R. Quake, J.R. Leadbetter, Microfluidic digital PCR enables multigene analysis of individual environmental bacteria. Science 314(5804), 1464–1467 (2006)CrossRefPubMedGoogle Scholar
  18. 18.
    L. Warren, D. Bryder, I.L. Weissman, S.R. Quake, Transcription factor profiling in individual hematopoietic progenitors by digital RT-PCR. Proc. Natl. Acad. Sci. 103(47), 17807–17812 (2006)CrossRefPubMedGoogle Scholar
  19. 19.
    H.C. Fan, S.R. Quake, Detection of aneuploidy with digital polymerase chain reaction. Anal. Chem. 79(19), 7576–7579 (2007)CrossRefPubMedGoogle Scholar
  20. 20.
    B.J. Hindson, K.D. Ness, D.A. Masquelier, P. Belgrader, N.J. Heredia, A.J. Makarewicz, I.J. Bright, M.Y. Lucero, A.L. Hiddessen, T.C. Legler, High-throughput droplet digital PCR system for absolute quantitation of DNA copy number. Anal. Chem. 83(22), 8604–8610 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    E. Day, P.H. Dear, F. McCaughan, Digital PCR strategies in the development and analysis of molecular biomarkers for personalized medicine. Methods 59(1), 101–107 (2013)CrossRefPubMedGoogle Scholar
  22. 22.
    M.M. Kiss, L. Ortoleva-Donnelly, N.R. Beer, J. Warner, C.G. Bailey, B.W. Colston, J.M. Rothberg, D.R. Link, J.H. Leamon, High-throughput quantitative polymerase chain reaction in picoliter droplets. Anal. Chem. 80(23), 8975–8981 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    M.D. GP, D. Do, C.M. Litterst, D. Maar, C.M. Hindson, E.R. Steenblock, T.C. Legler, Y. Jouvenot, S.H. Marrs, A. Bemis, Multiplexed target detection using DNA-binding dye chemistry in droplet digital PCR. Anal. Chem. 85(23), 11619–11627 (2013)CrossRefGoogle Scholar
  24. 24.
    S.C. Taylor, J. Carbonneau, D.N. Shelton, G. Boivin, Optimization of droplet digital PCR from RNA and DNA extracts with direct comparison to RT-qPCR: Clinical implications for quantification of oseltamivir-resistant subpopulations. J. Virol. Methods 224, 58–66 (2015)CrossRefPubMedGoogle Scholar
  25. 25.
    M.C. Strain, S.M. Lada, T. Luong, S.E. Rought, S. Gianella, V.H. Terry, C.A. Spina, C.H. Woelk, D.D. Richman, Highly precise measurement of HIV DNA by droplet digital PCR. PLoS One 8(4), e55943 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    T.C. Dingle, R.H. Sedlak, L. Cook, K.R. Jerome, Tolerance of droplet-digital PCR vs real-time quantitative PCR to inhibitory substances. Clin. Chem. 59(11), 1670–1672 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    N. Rački, T. Dreo, I. Gutierrez-Aguirre, A. Blejec, M. Ravnikar, Reverse transcriptase droplet digital PCR shows high resilience to PCR inhibitors from plant, soil and water samples. Plant Methods 10(1), 42 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    M.F. Sanmamed, S. Fernández-Landázuri, C. Rodríguez, R. Zárate, M.D. Lozano, L. Zubiri, J.L. Perez-Gracia, S. Martín-Algarra, A. González, Quantitative cell-free circulating BRAFV600E mutation analysis by use of droplet digital PCR in the follow-up of patients with melanoma being treated with BRAF inhibitors. Clin. Chem. 61(1), 297–304 (2015)CrossRefPubMedGoogle Scholar
  29. 29.
    A.V. Todd, C.J. Fuery, H.L. Impey, T.L. Applegate, M.A. Haughton, DzyNA-PCR: use of DNAzymes to detect and quantify nucleic acid sequences in a real-time fluorescent format. Clin. Chem. 46(5), 625–630 (2000)PubMedGoogle Scholar
  30. 30.
    F. Wang, Z. Wu, Y. Lu, J. Wang, J.H. Jiang, R.Q. Yu, A label-free DNAzyme sensor for lead (II) detection by quantitative polymerase chain reaction. Anal. Biochem. 405(2), 168–173 (2010)CrossRefPubMedGoogle Scholar
  31. 31.
    J. Xu, Y. Sun, Y. Sheng, Y. Fei, J. Zhang, D. Jiang, Engineering a DNA-cleaving DNAzyme and PCR into a simple sensor for zinc ion detection. Anal. Bioanal. Chem. 406(13), 3025–3029 (2014)CrossRefPubMedGoogle Scholar
  32. 32.
    N. Cheng, P. Zhu, Y. Xu, K. Huang, Y. Luo, Z. Yang, W. Xu, High-sensitivity assay for Hg (II) and Ag (I) ion detection: a new class of droplet digital PCR logic gates for an intelligent DNA calculator. Biosens. Bioelectron. 84, 1–6 (2016)CrossRefPubMedGoogle Scholar
  33. 33.
    S. Johannsen, N. Megger, D. Böhme, R.K. Sigel, J. Müller, Solution structure of a DNA double helix with consecutive metal-mediated base pairs. Nat. Chem. 2(3), 229–234 (2010)CrossRefPubMedGoogle Scholar
  34. 34.
    S. Katz, The reversible reaction of Hg (II) and double-stranded polynucleotides a step-function theory and its significance. Biochim. Biophys. Acta (BBA)-Specialized Sect. Nucleic Acids Relat. Subj 68, 240–253 (1963)Google Scholar
  35. 35.
    J. Liu, Y. Lu, A DNAzyme catalytic beacon sensor for paramagnetic Cu2+ ions in aqueous solution with high sensitivity and selectivity. J. Am. Chem. Soc. 129(32), 9838–9839 (2007)CrossRefPubMedGoogle Scholar
  36. 36.
    P. Zhu, Y. Shang, W. Tian, K. Huang, Y. Luo, W. Xu, Ultra-sensitive and absolute quantitative detection of Cu2+ based on DNAzyme and digital PCR in water and drink samples. Food Chem. 221, 1770–1777 (2017)CrossRefPubMedGoogle Scholar
  37. 37.
    P. Zhu, W. Tian, N. Cheng, K. Huang, Y. Luo, W. Xu, Ultra-sensitive “turn-on” detection method for Hg2+ based on mispairing biosensor and emulsion PCR. Talanta 155, 168–174 (2016)CrossRefPubMedGoogle Scholar
  38. 38.
    E. Perozo, D.M. Cortes, P. Sompornpisut, A. Kloda, B. Martinac, Open channel structure of MscL and the gating mechanism of mechanosensitive channels. Nature 418(6901), 942 (2002)CrossRefPubMedGoogle Scholar
  39. 39.
    X. Hou, W. Guo, F. Xia, F.Q. Nie, H. Dong, Y. Tian, L. Wen, L. Wang, L. Cao, Y. Yang, A biomimetic potassium responsive nanochannel: G-quadruplex DNA conformational switching in a synthetic nanopore. J. Am. Chem. Soc. 131(22), 7800–7805 (2009)CrossRefPubMedGoogle Scholar
  40. 40.
    Y. Jiang, N. Liu, W. Guo, F. Xia, L. Jiang, Highly-efficient gating of solid-state nanochannels by DNA supersandwich structure containing ATP aptamers: a nanofluidic IMPLICATION logic device. J. Am. Chem. Soc. 134(37), 15395–15401 (2012)CrossRefPubMedGoogle Scholar
  41. 41.
    W. Guo, L. Cao, J. Xia, F.Q. Nie, W. Ma, J. Xue, Y. Song, D. Zhu, Y. Wang, L. Jiang, Energy harvesting with single-ion-selective nanopores: aconcentration-gradient-driven nanofluidic power source. Adv. Funct. Mater. 20(8), 1339–1344 (2010)CrossRefGoogle Scholar
  42. 42.
    L. Wen, X. Hou, Y. Tian, J. Zhai, L. Jiang, Bio-inspired photoelectric conversion based on smart-gating nanochannels. Adv. Funct. Mater. 20(16), 2636–2642 (2010)CrossRefGoogle Scholar
  43. 43.
    S. Wen, T. Zeng, L. Liu, K. Zhao, Y. Zhao, X. Liu, H.C. Wu, Highly sensitive and selective DNA-based detection of mercury (II) with α-hemolysin nanopore. J. Am. Chem. Soc. 133(45), 18312–18317 (2011)CrossRefPubMedGoogle Scholar
  44. 44.
    Z. Zhang, D. Balogh, F. Wang, I. Willner, Smart mesoporous SiO2 nanoparticles for the DNAzyme-induced multiplexed release of substrates. J. Am. Chem. Soc. 135(5), 1934–1940 (2013)CrossRefPubMedGoogle Scholar
  45. 45.
    Y. Chen, D. Zhou, Z. Meng, J. Zhai, An ion-gating multinanochannel system based on a copper-responsive self-cleaving DNAzyme. Chem. Commun. 52(65), 10020–10023 (2016)CrossRefGoogle Scholar
  46. 46.
    F. Xia, W. Guo, Y. Mao, X. Hou, J. Xue, H. Xia, L. Wang, Y. Song, H. Ji, Q. Ouyang, Gating of single synthetic nanopores by proton-driven DNA molecular motors. J. Am. Chem. Soc. 130(26), 8345–8350 (2008)CrossRefPubMedGoogle Scholar
  47. 47.
    X. Hou, Y. Liu, H. Dong, F. Yang, L. Li, L. Jiang, A pH-gating ionic transport nanodevice: asymmetric chemical modification of single nanochannels. Adv. Mater. 22(22), 2440–2443 (2010)CrossRefPubMedGoogle Scholar
  48. 48.
    E.B. Kalman, O. Sudre, I. Vlassiouk, Z.S. Siwy, Control of ionic transport through gated single conical nanopores. Anal. Bioanal. Chem. 394(2), 413–419 (2009)CrossRefPubMedGoogle Scholar
  49. 49.
    X. Hou, F. Yang, L. Li, Y. Song, L. Jiang, D. Zhu, A biomimetic asymmetric responsive single nanochannel. J. Am. Chem. Soc. 132(33), 11736–11742 (2010)CrossRefPubMedGoogle Scholar
  50. 50.
    Y. Tian, X. Hou, L. Jiang, Biomimetic ionic rectifier systems: asymmetric modification of single nanochannels by ion sputtering technology. J. Electroanal. Chem. 656(1), 231–236 (2011)CrossRefGoogle Scholar
  51. 51.
    M. Liu, H. Zhang, K. Li, L. Heng, S. Wang, Y. Tian, L. Jiang, A bio-inspired potassium and pH responsive double-gated nanochannel. Adv. Funct. Mater. 25(3), 421–426 (2015)CrossRefGoogle Scholar
  52. 52.
    X. Hou, W. Guo, L. Jiang, Biomimetic smart nanopores and nanochannels. Chem. Soc. Rev. 40(5), 2385–2401 (2011)CrossRefPubMedGoogle Scholar
  53. 53.
    R. Wei, T.G. Martin, U. Rant, H. Dietz, DNA origami gatekeepers for solid-state nanopores. Angew. Chem. 124(20), 4948–4951 (2012)CrossRefGoogle Scholar
  54. 54.
    S.Z. Chu, K. Wada, S. Inoue, M. Isogai, A. Yasumori, Fabrication of ideally ordered nanoporousaluminafilms and integrated alumina nanotubulearrays by high-field anodization. Adv. Mater. 17(17), 2115–2119 (2005)CrossRefGoogle Scholar
  55. 55.
    J.J. Kasianowicz, E. Brandin, D. Branton, D.W. Deamer, Characterization of individual polynucleotide molecules using a membrane channel. Proc. Natl. Acad. Sci. 93(24), 13770–13773 (1996)CrossRefPubMedGoogle Scholar
  56. 56.
    G. Wang, B. Zhang, J.R. Wayment, J.M. Harris, H.S. White, Electrostatic-gated transport in chemically modified glass nanopore electrodes. J. Am. Chem. Soc. 128(23), 7679–7686 (2006)CrossRefPubMedGoogle Scholar
  57. 57.
    C.C. Chen, Y. Zhou, L.A. Baker, Scanning ion conductance microscopy. Annu. Rev. Anal. Chem. 5, 207–228 (2012)CrossRefPubMedGoogle Scholar
  58. 58.
    R.M. Souto, Y. González-García, J. Izquierdo, S. González, Examination of organic coatings on metallic substrates by scanning electrochemical microscopy in feedback mode: revealing the early stages of coating breakdown in corrosive environments. Corros. Sci. 52(3), 748–753 (2010)CrossRefGoogle Scholar
  59. 59.
    J. Feng, J. Liu, B. Wu, G. Wang, Impedance characteristics of amine modified single glass nanopores. Anal. Chem. 82(11), 4520–4528 (2010)CrossRefPubMedGoogle Scholar
  60. 60.
    E.A. Manrao, I.M. Derrington, A.H. Laszlo, K.W. Langford, M.K. Hopper, N. Gillgren, M. Pavlenok, M. Niederweis, J.H. Gundlach, Reading DNA at single-nucleotide resolution with a mutant MspAnanopore and phi29 DNA polymerase. Nat. Biotechnol. 30(4), 349–353 (2012)CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Yunbo Luo
    • 1
  1. 1.Food Science &Nutritional EngineeringChina Agricultural UniversityBeijingChina

Personalised recommendations