Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Rectification of protein translocation in truncated pyramidal nanopores

Nature Nanotechnology volume 14, pages 1056–1062 (2019)Cite this article

Subjects

Abstract

Solid-state nanopore technology presents an emerging single-molecule-based analytical tool for the separation and analysis of nanoparticles. Different approaches have been pursued to attain the anticipated detection performance. Here, we report the rectification behaviour of protein translocation through silicon-based truncated pyramidal nanopores. When the size of translocating proteins is comparable to the smallest physical constriction of the nanopore, the frequency of translocation events observed is lower for proteins that travel from the larger to the small opening of the nanopore than for those that travel in the reverse direction. When the proteins are appreciably smaller than the nanopore, an opposite rectification in the frequency of translocation events is evident. The maximum rectification factor achieved is around ten. Numerical simulations reveal the formation of an electro-osmotic vortex in such asymmetric nanopores. The vortex–protein interaction is found to play a decisive role in rectifying the translocation in terms of polarity and amplitude. The reported phenomenon can be potentially exploitable for the discrimination of various nanoparticles.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Schematic of the nanopore fabrication process and SEM images of the nanopores achieved.
Fig. 2: Electrical characterization of TPPs.
Fig. 3: IgG1 translocation through an 18 nm TPP.
Fig. 4: Mean FTE for streptavidin and IgG1 in TPPs of different a.
Fig. 5

Similar content being viewed by others

Data availability

The data that support the plots within this paper and other findings of this study are available from the corresponding author upon reasonable request.

References

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

    CAS  Google Scholar 

  2. Iqbal, S. M., Akin, D. & Bashir, R. Solid-state nanopore channels with DNA selectivity. Nat. Nanotechnol. 2, 243–248 (2007).

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  4. Muthukumar, M., Plesa, C. & Dekker, C. Single-molecule sensing with nanopores. Phys. Today 68, 40–46 (2015).

    CAS  Google Scholar 

  5. Feng, J. et al. Identification of single nucleotides in MoS2 nanopores. Nat. Nanotechnol. 10, 1070–1076 (2015).

    CAS  Google Scholar 

  6. Yusko, E. C. et al. Controlling protein translocation through nanopores with bio-inspired fluid walls. Nat. Nanotechnol. 6, 253–260 (2011).

    CAS  Google Scholar 

  7. Yusko, E. C. et al. Real-time shape approximation and fingerprinting of single proteins using a nanopore. Nat. Nanotechnol. 12, 360–367 (2017).

    CAS  Google Scholar 

  8. Restrepo-Pérez, L., Joo, C. & Dekker, C. Paving the way to single-molecule protein sequencing. Nat. Nanotechnol. 13, 786–796 (2018).

    Google Scholar 

  9. Montagne, F., Blondiaux, N., Bojko, A. & Pugin, R. Molecular transport through nanoporous silicon nitride membranes produced from self-assembling block copolymers. Nanoscale 4, 5880–5886 (2012).

    CAS  Google Scholar 

  10. Kovarik, M. L. & Jacobson, S. C. Nanofluidics in lab-on-a-chip devices. Anal. Chem. 81, 7133–7140 (2009).

    CAS  Google Scholar 

  11. Walker, M. I. et al. Extrinsic cation selectivity of 2D membranes. ACS Nano 11, 1340–1346 (2017).

    CAS  Google Scholar 

  12. Rollings, R. C., Kuan, A. T. & Golovchenko, J. A. Ion selectivity of graphene nanopores. Nat. Commun. 7, 11408 (2016).

    CAS  Google Scholar 

  13. O’Hern, S. C. et al. Nanofiltration across defect-sealed nanoporous monolayer graphene. Nano Lett. 15, 3254–3260 (2015).

    Google Scholar 

  14. Amadei, C. A., Montessori, A., Kadow, J. P., Succi, S. & Vecitis, C. D. Role of oxygen functionalities in graphene oxide architectural laminate subnanometer spacing and water transport. Environ. Sci. Technol. 51, 4280–4288 (2017).

    CAS  Google Scholar 

  15. Feng, J. et al. Single-layer MoS2 nanopores as nanopower generators. Nature 536, 197–200 (2016).

    CAS  Google Scholar 

  16. Aksu, S. et al. High-throughput nanofabrication of infrared plasmonic nanoantenna arrays for vibrational nanospectroscopy. Nano Lett. 10, 2511–2518 (2010).

    CAS  Google Scholar 

  17. Byun, J., Lee, J. I., Kwon, S., Jeon, G. & Kim, J. K. Highly ordered nanoporous alumina on conducting substrates with adhesion enhanced by surface modification: universal templates for ultrahigh-density arrays of nanorods. Adv. Mater. 22, 2028–2032 (2010).

    CAS  Google Scholar 

  18. Schneider, G. F. & Dekker, C. DNA sequencing with nanopores. Nat. Biotechnol. 30, 326–328 (2012).

    CAS  Google Scholar 

  19. Garaj, S. et al. Graphene as a subnanometre trans-electrode membrane. Nature 467, 190–193 (2010).

    CAS  Google Scholar 

  20. Schneider, G. F. et al. DNA translocation through graphene nanopores. Nano Lett. 10, 3163–3167 (2010).

    CAS  Google Scholar 

  21. Liu, K., Feng, J., Kis, A. & Radenovic, A. Atomically thin molybdenum disulfide nanopores with high sensitivity for DNA translocation. ACS Nano 8, 2504–2511 (2014).

    CAS  Google Scholar 

  22. Zhou, Z. et al. DNA translocation through hydrophilic nanopore in hexagonal boron nitride. Sci. Rep. 3, 3287 (2013).

    Google Scholar 

  23. Wanunu, M. et al. Rapid electronic detection of probe-specific microRNAs using thin nanopore sensors. Nat. Nanotechnol. 5, 807–814 (2010).

    CAS  Google Scholar 

  24. Arjmandi‐Tash, H. et al. Zero-depth interfacial nanopore capillaries. Adv. Mater. 30, 1703602 (2018).

    Google Scholar 

  25. Kong, Z. et al. Charge-tunable absorption behavior of DNA on graphene. J. Mater. Chem. B 3, 4814–4820 (2015).

    CAS  Google Scholar 

  26. Wells, D. B., Belkin, M., Comer, J. & Aksimentiev, A. Assessing graphene nanopores for sequencing DNA. Nano Lett. 12, 4117–4123 (2012).

    CAS  Google Scholar 

  27. Heerema, S. J. et al. 1/f noise in graphene nanopores. Nanotechnology 26, 074001 (2015).

    CAS  Google Scholar 

  28. Kowalczyk, S. W., Wells, D. B., Aksimentiev, A. & Dekker, C. Slowing down DNA translocation through a nanopore in lithium chloride. Nano Lett. 12, 1038–1044 (2012).

    CAS  Google Scholar 

  29. Sha, J. et al. Salt gradient improving signal-to-noise ratio in solid-state nanopore. ACS Sens. 2, 506–512 (2017).

    CAS  Google Scholar 

  30. Fologea, D., Uplinger, J., Thomas, B., McNabb, D. S. & Li, J. Slowing DNA translocation in a solid-state nanopore. Nano Lett. 5, 1734–1737 (2005).

    CAS  Google Scholar 

  31. Di Fiori, N. et al. Optoelectronic control of surface charge and translocation dynamics in solid-state nanopores. Nat. Nanotechnol. 8, 946–951 (2013).

    Google Scholar 

  32. Wei, R., Gatterdam, V., Wieneke, R., Tampé, R. & Rant, U. Stochastic sensing of proteins with receptor-modified solid-state nanopores. Nat. Nanotechnol. 7, 257–263 (2012).

    CAS  Google Scholar 

  33. Emilsson, G. et al. Polymer brushes in solid-state nanopores form an impenetrable entropic barrier for proteins. Nanoscale 10, 4663–4669 (2018).

    CAS  Google Scholar 

  34. Emilsson, G. et al. Gating protein transport in solid state nanopores by single molecule recognition. ACS Cent. Sci. 4, 1007–1014 (2018).

    CAS  Google Scholar 

  35. Storm, A. J., Chen, J. H., Ling, X. S., Zandbergen, H. W. & Dekker, C. Fabrication of solid-state nanopores with single-nanometre precision. Nat. Mater. 2, 537–540 (2003).

    CAS  Google Scholar 

  36. Chen, Q., Wang, Y., Deng, T. & Liu, Z. Fabrication of nanopores and nanoslits with feature sizes down to 5 nm by wet etching method. Nanotechnology 29, 085301 (2018).

    Google Scholar 

  37. Wen, C., Zhang, Z. & Zhang, S.-L. Physical model for rapid and accurate determination of nanopore size via conductance measurement. ACS Sens. 2, 1523–1530 (2017).

    CAS  Google Scholar 

  38. Tagliazucchi, M. & Szleifer, I. Transport mechanisms in nanopores and nanochannels: can we mimic nature? Mater. Today 18, 131–142 (2015).

    CAS  Google Scholar 

  39. Kosmulski, M. The pH-dependent surface charging and the points of zero charge. J. Colloid Interface Sci. 253, 77–87 (2002).

    CAS  Google Scholar 

  40. Smeets, R. M. M. et al. Salt dependence of ion transport and DNA translocation through solid-state nanopores. Nano Lett. 6, 89–95 (2006).

    CAS  Google Scholar 

  41. Ivanov, A. P. et al. DNA tunneling detector embedded in a nanopore. Nano Lett. 11, 279–285 (2011).

    CAS  Google Scholar 

  42. Anderson, B. N., Muthukumar, M. & Meller, A. pH tuning of DNA translocation time through organically functionalized nanopores. ACS Nano 7, 1408–1414 (2013).

    CAS  Google Scholar 

  43. Kox, R. et al. Local solid-state modification of nanopore surface charges. Nanotechnology 21, 335703 (2010).

    Google Scholar 

  44. Luan, B. & Stolovitzky, G. An electro-hydrodynamics-based model for the ionic conductivity of solid-state nanopores during DNA translocation. Nanotechnology 24, 195702 (2013).

    Google Scholar 

  45. Larkin, J., Henley, R. Y., Muthukumar, M., Rosenstein, J. K. & Wanunu, M. High-bandwidth protein analysis using solid-state nanopores. Biophys. J. 106, 696–704 (2014).

    CAS  Google Scholar 

  46. Yamazaki, H., Hu, R., Zhao, Q. & Wanunu, M. Photothermally assisted thinning of silicon nitride membranes for ultrathin asymmetric nanopores. ACS Nano 26, 12472–12481 (2018).

    Google Scholar 

  47. Qiu, Y., Siwy, Z. S. & Wanunu, M. Abnormal ionic–current rectification caused by reversed electroosmotic flow under viscosity gradients across thin nanopores. Anal. Chem. 91, 996–1004 (2019).

    CAS  Google Scholar 

  48. Seidel, H., Csepregi, L., Heuberger, A. & Baumgärtel, H. Anisotropic etching of crystalline silicon in alkaline solutions. I. Orientation dependence and behavior of passivation layers. J. Electrochem. Soc. 137, 3612–3626 (1990).

    CAS  Google Scholar 

  49. Zubel, I. & Barycka, I. Silicon anisotropic etching in alkaline solutions. I. The geometric description of figures developed under etching Si(100) in various solutions. Sens. Actuators A 70, 250–259 (1998).

    CAS  Google Scholar 

Download references

Acknowledgements

The authors thank R. Scheicher, S. Cardoch, U. F. Keyser and S. Li for fruitful discussions. This work was financially supported by the Swedish Research Council (621-2014-6300) and Stiftelsen Olle Engkvist Byggmästare (2016/39).

Author information

Author notes

  1. These authors contributed equally: Shuangshuang Zeng, Chenyu Wen.

Authors and Affiliations

  1. Division of Solid-State Electronics, Department of Engineering Sciences, Uppsala University, Uppsala, Sweden

    Shuangshuang Zeng, Chenyu Wen, Shi-Li Zhang & Zhen Zhang

  2. IBM T.J. Watson Research Center, Yorktown Heights, NY, USA

    Paul Solomon

Authors
  1. Shuangshuang Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chenyu Wen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul Solomon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shi-Li Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhen Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S.Z., C.W., S.-L.Z. and Z.Z. designed the experiments. P.S. and Z.Z. conceived the idea of silicon nanopores. S.Z. fabricated and characterized the nanopore devices under the supervision of Z.Z. C.W. performed the translocation experiments and finite element simulations under the supervision of S.-L.Z. S.Z., C.W., S.-L.Z. and Z.Z. co-wrote the manuscript. All the authors analyzed the data, discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Zhen Zhang.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Additional information

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

Supplementary information

Supplementary information

Supplementary Figs. 1–5, Table 1, Notes 1–2 and refs. 1–8.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zeng, S., Wen, C., Solomon, P. et al. Rectification of protein translocation in truncated pyramidal nanopores. Nat. Nanotechnol. 14, 1056–1062 (2019). https://doi.org/10.1038/s41565-019-0549-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41565-019-0549-0

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing