Skip to main content
SpringerLink
Log in

Nanopore-based sensing and analysis: beyond the resistive-pulse method

  • Review
  • Chemistry
  • Published:
Science Bulletin

Abstract

Solid-state nanopores are generally considered as an indispensable element in the research field of fundamental ion transport and molecular sensing. The improvement in fabrication and chemical modification of the solid-state nanopores remains increasingly updated. During the last decades, numerous works have been reported on the nanopore-based sensing applications. More and more new analytical methods using nanopore-based devices are emerging. In this review, we highlight the recent progress on the analytical methods for the interdisciplinary and fast-growing area of nanopore research. According to the different types of the electrical readout, whether it is steady-state ionic current or transient current fluctuation, the nanopore-based sensing and analysis can be generally divided into two categories. For the first type, the electrical readout shows a stable blockade or reopening of the nanopore conductance in the presence of target analytes, termed steady-state analysis, including the conductance change, electrochemical analysis, and two-dimensional scanning and imaging. The other type is based on the transient fluctuation in the transmembrane ionic current, termed transient-state analysis, including the noise analysis, transient ion transport, and transverse tunneling current. The investigation of solid-state nanopores for chemical sensing is just in its infancy. For further research work, not only new nanopore materials and chemical modifications are needed, but also other non-electric-based sensing techniques should be developed. We will focus our future research in the framework of bio-inspired, smart, multiscale interfacial materials and extend the spirit of binary cooperative complementary nanomaterials.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

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

Similar content being viewed by others

References

  1. Branton D, Deamer DW, Marziali A et al (2008) The potential and challenges of nanopore sequencing. Nat Biotechnol 26:1146–1153

    Article  Google Scholar 

  2. Howorka S, Siwy Z (2009) Nanopore analytics: sensing of single molecules. Chem Soc Rev 38:2360–2384

    Article  Google Scholar 

  3. Venkatesan BM, Bashir R (2011) Nanopore sensors for nucleic acid analysis. Nat Nanotechnol 6:615–624

    Article  Google Scholar 

  4. Huang S (2014) Nanopore-based sensing devices and applications to genome sequencing: a brief history and the missing pieces. Chin Sci Bull 59:4918–4928

    Article  Google Scholar 

  5. Martin CR, Siwy ZS (2007) Learning nature’s way: biosensing with synthetic nanopores. Science 317:331–332

    Article  Google Scholar 

  6. Gao R, Ying YL, Yan BY et al (2014) An integrated current measurement system for nanopore analysis. Chin Sci Bull 59:4968–4973

    Article  Google Scholar 

  7. Guo W, Tian Y, Jiang L (2013) Asymmetric ion transport through ion-channel-mimetic solid-state nanopores. Acc Chem Res 46:2834–2846

    Article  Google Scholar 

  8. Hou X, Guo W, Jiang L (2011) Biomimetic smart nanopores and nanochannels. Chem Soc Rev 40:2385–2401

    Article  Google Scholar 

  9. Zhang H, Tian Y, Jiang L (2013) From symmetric to asymmetric design of bio-inspired smart single nanochannels. Chem Commun 49:10048–10063

    Article  Google Scholar 

  10. Zhang S, Sun T, Wang E et al (2014) Investigation of self-assembled protein dimers through an artificial ion channel for DNA sensing. Chin Sci Bull 59:4946–4952

    Article  Google Scholar 

  11. Jiang Y, Liu N, Guo W et al (2012) Highly-efficient gating of solid-state nanochannels by DNA supersandwich structure containing ATP aptamers: a nanofluidic IMPLICATION logic device. J Am Chem Soc 134:15395–15401

    Article  Google Scholar 

  12. Liu N, Jiang Y, Zhou Y et al (2013) Two-way nanopore sensing of sequence-specific oligonucleotides and small-molecule targets in complex matrices using integrated DNA supersandwich structures. Angew Chem Int Ed 52:2007–2011

    Article  Google Scholar 

  13. Scott ER, White HS, Phipps JB (1991) Scanning electrochemical microscopy of a porous membrane. J Mem Sci 58:71–87

    Article  Google Scholar 

  14. Morris CA, Chen CC, Baker LA (2012) Transport of redox probes through single pores measured by scanning electrochemical–scanning ion conductance microscopy (SECM–SICM). Analyst 137:2933–2938

    Article  Google Scholar 

  15. Smeets R, Keyser UF, Wu MY et al (2006) Nanobubbles in solid-state nanopores. Phys Rev Lett 97:088101

    Article  Google Scholar 

  16. Guo W, Cao L, Xia J et al (2010) Energy harvesting with single-ion-selective nanopores: a concentration-gradient-driven nanofluidic power source. Adv Funct Mater 20:1339–1344

    Article  Google Scholar 

  17. Kasianowicz JJ, Brandin E, Branton D et al (1996) Characterization of individual polynucleotide molecules using a membrane channel. Proc Natl Acad Sci USA 93:13770–13773

    Article  Google Scholar 

  18. Li J, Stein D, McMullan C et al (2001) Ion-beam sculpting at nanometre length scales. Nature 412:166–169

    Article  Google Scholar 

  19. Yusko EC, Johnson JM, Majd S et al (2011) Controlling protein translocation through nanopores with bio-inspired fluid walls. Nat Nanotechnol 6:253–260

    Article  Google Scholar 

  20. Bayley H, Martin CR (2000) Resistive-pulse sensing—from microbes to molecules. Chem Rev 100:2575–2594

    Article  Google Scholar 

  21. Piruska A, Gong M, Sweedler JV et al (2010) Nanofluidics in chemical analysis. Chem Soc Rev 39:1060–1072

    Article  Google Scholar 

  22. Ying YL, Cao C, Long YT (2014) Single molecule analysis by biological nanopore sensors. Analyst 139:3826–3835

    Article  Google Scholar 

  23. Makra I, Gyurcsanyi RE (2014) Electrochemical sensing with nanopores: a mini review. Electrochem Commun 43:55–59

    Article  Google Scholar 

  24. Wang L, Guo W, Xie Y et al (2009) Nanofluidic diode generated by pH gradient inside track-etched conical nanopore. Radiat Meas 44:1119–1122

    Article  Google Scholar 

  25. Xia H, Xia F, Tang Y et al (2011) Tuning surface wettability through supramolecular interactions. Soft Matter 7:1638–1640

    Article  Google Scholar 

  26. Chen Q, Meng L, Li Q et al (2011) Water transport and purification in nanochannels controlled by asymmetric wettability. Small 7:2225–2231

    Article  Google Scholar 

  27. Cao L, Guo W, Wang Y et al (2012) Concentration-gradient-dependent ion current rectification in charged conical nanopores. Langmuir 28:2194–2199

    Article  Google Scholar 

  28. Zhou Y, Guo W, Jiang L (2014) Water wettability in nanoconfined environment. Sci China-Phys Mech Astron 57:836–843

    Article  Google Scholar 

  29. Zhou Y, Guo W, Cheng J et al (2012) High-temperature gating of solid-state nanopores with thermo-responsive macromolecular nanoactuators in ionic liquids. Adv Mater 24:962–967

    Article  Google Scholar 

  30. Zhang M, Hou X, Wang J et al (2012) Light and pH cooperative nanofluidic diode using a spiropyran-functionalized single nanochannel. Adv Mater 24:2424–2428

    Article  Google Scholar 

  31. Tian Y, Zhang Z, Wen L et al (2013) A biomimetic mercury(II)-gated single nanochannel. Chem Commun 49:10679–10681

    Article  Google Scholar 

  32. Guo W, Cheng C, Wu YZ et al (2013) Bio-inspired two-dimensional nanofluidic generators based on a layered graphene hydrogel membrane. Adv Mater 25:6064–6068

    Article  Google Scholar 

  33. Cao L, Guo W, Ma W et al (2011) Towards understanding the nanofluidic reverse electrodialysis system: well matched charge selectivity and ionic composition. Energ Environ Sci 4:2259–2266

    Article  Google Scholar 

  34. Gao J, Cheng C, Wu Y et al (2014) High-performance ionic diode membrane for salinity gradient power generation. J Am Chem Soc 136:12265–12272

    Article  Google Scholar 

  35. Xia F, Guo W, Mao Y et al (2008) Gating of single synthetic nanopores by proton-driven DNA molecular motors. J Am Chem Soc 130:8345–8350

    Article  Google Scholar 

  36. Hou X, Guo W, Xia F et al (2009) A biomimetic potassium responsive nanochannel: G-quadruplex DNA conformational switching in a synthetic nanopore. J Am Chem Soc 131:7800–7805

    Article  Google Scholar 

  37. Wen L, Hou X, Tian Y et al (2010) Bioinspired smart gating of nanochannels toward photoelectric-conversion systems. Adv Mater 22:1021–1024

    Article  Google Scholar 

  38. Ali M, Nasir S, Quoc HN et al (2011) Metal ion affinity-based biomolecular recognition and conjugation inside synthetic polymer nanopores modified with iron-terpyridine complexes. J Am Chem Soc 133:17307–17314

    Article  Google Scholar 

  39. Vlassiouk I, Park CD, Vail SA et al (2006) Control of nanopore wetting by a photochromic spiropyran: a light-controlled valve and electrical switch. Nano Lett 6:1013–1017

    Article  Google Scholar 

  40. Guo W, Xia H, Xia F et al (2010) Current rectification in temperature-responsive single nanopores. ChemPhysChem 11:859–864

    Article  Google Scholar 

  41. Wen L, Hou X, Tian Y et al (2010) Bio-inspired photoelectric conversion based on smart-gating nanochannels. Adv Funct Mater 20:2636–2642

    Article  Google Scholar 

  42. Hou X, Yang F, Li L et al (2010) A biomimetic asymmetric responsive single nanochannel. J Am Chem Soc 132:11736–11742

    Article  Google Scholar 

  43. Guo W, Xia H, Cao L et al (2010) Integrating ionic gate and rectifier within one solid-state nanopore via modification with dual-responsive copolymer brushes. Adv Funct Mater 20:3561–3567

    Article  Google Scholar 

  44. Ali M, Nasir S, Ahmed I et al (2013) Tuning nanopore surface polarity and rectification properties through enzymatic hydrolysis inside nanoconfined geometries. Chem Commun 49:8770–8772

    Article  Google Scholar 

  45. Szczepanski V, Vlassiouk I, Smirnov S (2006) Stability of silane modifiers on alumina nanoporous membranes. J Mem Sci 281:587–591

    Article  Google Scholar 

  46. Guo W, Xue J, Wang L et al (2008) Controllable etching of heavy ion tracks with organic solvent addition in etchant. Nucl Instrum Method B 266:3095–3099

    Article  Google Scholar 

  47. Gao J, Guo W, Geng H et al (2011) Layer-by-layer removal of insulating few-layer mica flakes for asymmetric ultra-thin nanopore fabrication. Nano Res 5:99–108

    Article  Google Scholar 

  48. Jiang Y, Gao J, Guo W et al (2014) Mechanical exfoliation of track-etched two-dimensional layered materials for the fabrication of ultrathin nanopores. Chem Commun 50:14149–14152

    Article  Google Scholar 

  49. Zhang B, Zhang YH, White HS (2004) The nanopore electrode. Anal Chem 76:6229–6238

    Article  Google Scholar 

  50. Wang GL, Zhang B, Wayment JR et al (2006) Electrostatic-gated transport in chemically modified glass nanopore electrodes. J Am Chem Soc 128:7679–7686

    Article  Google Scholar 

  51. Li Q, Xie S, Liang Z et al (2009) Fast ion-transfer processes at nanoscopic liquid/liquid interfaces. Angew Chem Int Ed 48:8010–8013

    Article  Google Scholar 

  52. Lan W, Holden DA, Zhang B et al (2011) Nanoparticle transport in conical-shaped nanopores. Anal Chem 83:3840–3847

    Article  Google Scholar 

  53. German SR, Luo L, White HS et al (2013) Controlling nanoparticle dynamics in conical nanopores. J Phys Chem C 117:703–711

    Article  Google Scholar 

  54. Wang G, Bohaty AK, Zharov I et al (2006) Photon gated transport at the glass nanopore electrode. J Am Chem Soc 128:13553–13558

    Article  Google Scholar 

  55. Morris CA, Friedman AK, Baker LA (2010) Applications of nanopipettes in the analytical sciences. Analyst 135:2190–2202

    Article  Google Scholar 

  56. Zhou Y, Chen CC, Weber AE et al (2014) Potentiometric-scanning ion conductance microscopy. Langmuir 30:5669–5675

    Article  Google Scholar 

  57. Momotenko D, Cortes-Salazar F, Lesch A et al (2011) Microfluidic push-pull probe for scanning electrochemical microscopy. Anal Chem 83:5275–5282

    Article  Google Scholar 

  58. Cortes-Salazar F, Momotenko D, Girault HH et al (2011) Seeing big with scanning electrochemical microscopy. Anal Chem 83:1493–1499

    Article  Google Scholar 

  59. Chen C, Zhou Y, Baker LA (2012) Scanning ion conductance microscopy. Annu Rev Anal Chem 5:207–228

    Article  Google Scholar 

  60. Ervin EN, White HS, Baker LA (2005) Alternating current impedance imaging of membrane pores using scanning electrochemical microscopy. Anal Chem 77:5564–5569

    Article  Google Scholar 

  61. Ervin EN, White HS, Baker LA et al (2006) Alternating current impedance imaging of high-resistance membrane pores using a scanning electrochemical microscope. Application of membrane electrical shunts to increase measurement sensitivity and image contrast. Anal Chem 78:6535–6541

    Article  Google Scholar 

  62. Lee S, Zhang YH, White HS et al (2004) Electrophoretic capture and detection of nanoparticles at the opening of a membrane pore using scanning electrochemical microscopy. Anal Chem 76:6108–6115

    Article  Google Scholar 

  63. Chen C, Derylo MA, Baker LA (2009) Measurement of ion currents through porous membranes with scanning ion conductance microscopy. Anal Chem 81:4742–4751

    Article  Google Scholar 

  64. Chen P, Mitsui T, Farmer DB et al (2004) Atomic layer deposition to fine-tune the surface properties and diameters of fabricated nanopores. Nano Lett 4:1333–1337

    Article  Google Scholar 

  65. Wei R, Pedone D, Zurner A et al (2010) Fabrication of metallized nanopores in silicon nitride membranes for single-molecule sensing. Small 6:1406–1414

    Article  Google Scholar 

  66. Tabard-Cossa V, Trivedi D, Wiggin M et al (2007) Noise analysis and reduction in solid-state nanopores. Nanotechnology 18:305505

    Article  Google Scholar 

  67. Powell MR, Martens C, Siwy ZS (2010) Asymmetric properties of ion current 1/f noise in conically shaped nanopores. Chem Phys 375:529–535

    Article  Google Scholar 

  68. Powell MR, Sa N, Davenport M et al (2011) Noise properties of rectifying nanopores. J Phys Chem C 115:8775–8783

    Article  Google Scholar 

  69. Pedone D, Firnkes M, Rant U et al (2009) Data analysis of translocation events in nanopore experiments. Anal Chem 81:9689–9694

    Article  Google Scholar 

  70. Smeets RM, Keyser UF, Dekker NH et al (2008) Noise in solid-state nanopores. Proc Natl Acad Sci USA 105:417–421

    Article  Google Scholar 

  71. Wang D, Kvetny M, Liu J et al (2012) Transmembrane potential across single conical nanopores and resulting memristive and memcapacitive ion transport. J Am Chem Soc 134:3651–3654

    Article  Google Scholar 

  72. Feng J, Liu J, Wu B et al (2010) Impedance characteristics of amine modified single glass nanopores. Anal Chem 82:4520–4528

    Article  Google Scholar 

  73. Guerrette JP, Zhang B (2010) Scan-rate-dependent current rectification of cone-shaped silica nanopores in quartz nanopipettes. J Am Chem Soc 132:17088–17091

    Article  Google Scholar 

  74. Yokota K, Tsutsui M, Taniguchi M (2014) Electrode-embedded nanopores for label-free single-molecule sequencing by electric currents. RSC Adv 4:15886–15899

    Article  Google Scholar 

  75. Howorka S, Siwy ZS (2012) Nanopores as protein sensors. Nat Biotechnol 30:506–507

    Article  Google Scholar 

  76. Rosen CB, Rodriguez-Larrea D, Bayley H (2014) Single-molecule site-specific detection of protein phosphorylation with a nanopore. Nat Biotechnol 32:179–181

    Article  Google Scholar 

  77. Laszlo AH, Derrington IM, Ross BC et al (2014) Decoding long nanopore sequencing reads of natural DNA. Nat Biotechnol 32:829–833

    Article  Google Scholar 

  78. Manrao EA, Derrington IM, Laszlo AH et al (2012) Reading DNA at single-nucleotide resolution with a mutant MspA nanopore and phi29 DNA polymerase. Nat Biotechnol 30:349–353

    Article  Google Scholar 

  79. Zhao Q, Wang Y, Dong J et al (2012) Nanopore-based DNA analysis via graphene electrodes. J Nanomater 2012:318950

    Google Scholar 

  80. Zwolak M, Di Ventra M (2005) Electronic signature of DNA nucleotides via transverse transport. Nano Lett 5:421–424

    Article  Google Scholar 

  81. Gierhart BC, Flowitt DG, Chen SJ et al (2008) Nanopore with transverse nanoelectrodes for electrical characterization and sequencing of DNA. Sens Actuators B 132:593–600

    Article  Google Scholar 

  82. Tsutsui M, Taniguchi M, Yokota K et al (2010) Identifying single nucleotides by tunnelling current. Nat Nanotechnol 5:286–290

    Article  Google Scholar 

  83. Ivanov AP, Instuli E, McGilvery CM et al (2011) DNA tunneling detector embedded in a nanopore. Nano Lett 11:279–285

    Article  Google Scholar 

  84. Huang S, He J, Chang S et al (2010) Identifying single bases in a DNA oligomer with electron tunnelling. Nat Nanotechnol 5:868–873

    Article  Google Scholar 

  85. Postma HW (2010) Rapid sequencing of individual DNA molecules in graphene nanogaps. Nano Lett 10:420–425

    Article  Google Scholar 

  86. Min SK, Kim WY, Cho Y et al (2011) Fast DNA sequencing with a graphene-based nanochannel device. Nat Nanotechnol 6:162–165

    Article  Google Scholar 

  87. O’Hern SC, Boutilier MSH, Idrobo JC et al (2014) Selective ionic transport through tunable subnanometer pores in single-layer graphene membranes. Nano Lett 14:1234–1241

    Article  Google Scholar 

  88. Garaj S, Hubbard W, Reina A et al (2010) Graphene as a subnanometre trans-electrode membrane. Nature 467:190–193

    Article  Google Scholar 

  89. Merchant CA, Healy K, Wanunu M et al (2010) DNA translocation through graphene nanopores. Nano Lett 10:2915–2921

    Article  Google Scholar 

  90. Schneider GF, Kowalczyk SW, Calado VE et al (2010) DNA translocation through graphene nanopores. Nano Lett 10:3163–3167

    Article  Google Scholar 

  91. Siwy ZS, Davenport M (2010) Making nanopores from nanotubes. Nat Nanotechnol 5:174–175

    Article  Google Scholar 

  92. Liu H, He J, Tang J et al (2009) Translocation of single-stranded DNA through single-walled carbon nanotubes. Science 327:64–67

    Article  Google Scholar 

  93. Liu L, Yang C, Zhao K et al (2013) Ultrashort single-walled carbon nanotubes in a lipid bilayer as a new nanopore sensor. Nat Commun 4:2989

    Google Scholar 

  94. Wei RS, Gatterdam V, Wieneke R et al (2012) Stochastic sensing of proteins with receptor-modified solid-state nanopores. Nat Nanotechnol 7:257–263

    Article  Google Scholar 

  95. Dekker C (2007) Solid-state nanopores. Nat Nanotechnol 2:209–215

    Article  Google Scholar 

  96. Hou X, Dong H, Zhu D et al (2010) Fabrication of stable single nanochannels with controllable ionic rectification. Small 6:361–365

    Article  Google Scholar 

  97. Guo W, Jiang L (2014) Two-dimensional ion channel based soft-matter piezoelectricity. Sci China Mater 57:2–6

    Article  Google Scholar 

  98. Xia F, Jiang L (2008) Bio-inspired, smart, multiscale interfacial materials. Adv Mater 20:2842–2858

    Article  Google Scholar 

  99. Su B, Guo W, Jiang L (2014) Learning from nature: binary cooperative complementary nanomaterials. Small. doi:10.1002/smll.201401307

    Google Scholar 

Download references

Acknowledgments

This work was supported by the National Basic Research Program of China (2011CB935700) and the National Natural Science Foundation of China (21103201, 11290163, 91127025, 21121001). The Chinese Academy of Sciences is gratefully acknowledged under the Key Research Program of the Chinese Academy of Sciences (KJZD-EW-M01). Wei Guo is supported by Beijing Nova Program.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Key Laboratory of Bio-Inspired Smart Interfacial Science and Technology of Ministry of Education, School of Chemistry and Environment, Beihang University, Beijing, 100191, China

    Yanan Jiang

  2. Laboratory of Bio-Inspired Smart Interface Science, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, China

    Wei Guo

Authors
  1. Yanan Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wei Guo.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, Y., Guo, W. Nanopore-based sensing and analysis: beyond the resistive-pulse method. Sci. Bull. 60, 491–502 (2015). https://doi.org/10.1007/s11434-015-0739-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11434-015-0739-6

Keywords

Search

Navigation