Nanopipette analysis is a sensitive sensing technology depending on the application of a potential to generate an ionic current at the orifice. Analytes such as DNA, proteins, and vesicles can be driven by the electric field inside the nanopipette, leading to detectable current blockage. However, it remains challenging to translocate negatively charged gold nanoparticles (AuNPs) through a conventional sharp nanopipette filled with symmetric physiological buffer. In this work, we introduce a strategy to drive the AuNPs out of the nanopipette tip conveniently without inner-wall functionalization. We intentionally break the nanopipette tip to change the geometry of orifice. Compared with intact nanopipettes, translocation events of AuNPs are significantly increased and detectable upon using nanopipettes with a broken-tip. This allows us to gain valuable insights into the driving force and translocation behaviour of AuNPs in nanopipettes with short necks and irregular edge at the tip. Our findings demonstrate a simple and effective strategy for AuNPs detection by nanopipettes and highlight the important role of tip geometry in pressure-assisted nanoparticle transport.
- Open Access
- Article
A Broken Tip Allows a Better Trip: Translocation of Gold Nanoparticles Clusters through a Nanopipette
- Qianyi Wu 1,
- Jian Lv 2,*,
- Ruocan Qian 1,3,4,5,*
Author Information
Received: 07 Apr 2026 | Revised: 26 May 2026 | Accepted: 16 Jun 2026 | Published: 25 Jun 2026
Abstract
Keywords
nanopipette | tip geometry modification | pressure-assisted transport | ionic current sensing
References
- 1.
Actis, P.; Mak, A.C.; Pourmand, N. Functionalized Nanopipettes: Toward Label-Free, Single Cell Biosensors. Bioanal. Rev. 2010, 1, 177–185.
- 2.
Albrecht, T. Single-Molecule Analysis with Solid-State Nanopores. Annu. Rev. Anal. Chem. 2019, 12, 371–387.
- 3.
Stanley, J.; Pourmand, N. Nanopipettes—The Past and the Present. APL Mater. 2020, 8, 100902.
- 4.
Yu, R.-J.; Ying, Y.-L.; Gao, R.; et al. Confined Nanopipette Sensing: From Single Molecules, Single Nanoparticles, to Single Cells. Angew. Chem. Int. Ed. 2019, 58, 3706–3714.
- 5.
Denuga, S.; Dutta, P.; Duleba, D.; et al. Tuning Ion Current Rectifying Nanopipettes for Sensitive Detection of Methicillin-Resistant Staphylococcus aureus. Anal. Chem. 2025, 97, 2003–2010.
- 6.
Kuanaeva, R.M.; Vaneev, A.N.; Gorelkin, P.V.; et al. Nanopipettes as a Potential Diagnostic Tool for Selective Nanopore Detection of Biomolecules. Biosensors 2024, 14, 627.
- 7.
Song, J.; Xia, C.-W.; Zhang, X.; et al. A Modular DNA-Assembled Nanopipette (mDNP) Platform for Spatially Confined Single-Cell Nuclear Detection of Methyltransf erase Activity. Anal. Chem. 2025, 97, 21150–21157.
- 8.
Zhang, X.; Wu, Z.-Q.; Zheng, Y.-W.; et al. Bridging Ionic Current Rectification and Resistive-Pulse Sensing for Reliable Wide-Linearity Detection. Anal. Chem. 2024, 96, 6444–6449.
- 9.
Tian, S.-Y.; Gao, R.-X.; Du, Z.-Q.; et al. Dual-Interface Nanopipette Sensor for Electrochemical Interferent Shielding. Angew. Chem. Int. Ed. 2025, 64, e202504520.
- 10.
Fraccari, R.L.; Ciccarella, P.; Bahrami, A.; et al. High-Speed Detection of DNA Translocation in Nanopipettes. Nanoscale 2016, 8, 7604–7611.
- 11.
Demirtas, M. Enhancing the Sensitivity of Nanopipette Biosensors for Protein Analysis. Brain Behav. 2024, 14, e3405.
- 12.
Lv, J.; Wang, X.-Y.; Chang, S.; et al. Amperometric Identification of Single Exosomes and Their Dopamine Contents Secreted by Living Cells. Anal. Chem. 2023, 95, 11273–11279.
- 13.
Yu, R.-J.; Ying, Y.-L.; Hu, Y.-X.; et al. Label-Free Monitoring of Single Molecule Immunoreaction with a Nanopipette. Anal. Chem. 2017, 89, 8203–8206.
- 14.
Zhang, X.; Luo, D.; Zheng, Y.-W.; et al. Translocation of Specific DNA Nanocarrier through an Ultrasmall Nanopipette: Toward Single-Protein-Molecule Detection with Superior Signal-to-Noise Ratio. ACS Nano 2022, 16, 15108–15114.
- 15.
Jain, P.K.; Huang, X.; El-Sayed, I.H.; et al. Noble Metals on the Nanoscale: Optical and Photothermal Properties and Some Applications in Imaging, Sensing, Biology, and Medicine. Acc. Chem. Res. 2008, 41, 1578–1586.
- 16.
Karnwal, A.; Kumar Sachan, R.S.; Devgon, I.; et al. Gold Nanoparticles in Nanobiotechnology: From Synthesis to Biosensing Applications. ACS Omega 2024, 9, 29966–29982.
- 17.
Qian, X.; Peng, X.-H.; Ansari, D.O.; et al. In Vivo Tumor Targeting and Spectroscopic Detection with Surface-Enhanced Raman Nanoparticle Tags. Nat. Biotechnol. 2008, 26, 83–90.
- 18.
Saha, K.; Agasti, S.S.; Kim, C.; et al. Gold Nanoparticles in Chemical and Biological Sensing. Chem. Rev. 2012, 112, 2739–2779.
- 19.
Dykman, L.; Khlebtsov, B.; Khlebtsov, N. Drug Delivery Using Gold Nanoparticles. Adv. Drug Deliv. Rev. 2025, 216, 115481.
- 20.
Ghosh, P.; Han, G.; De, M.; et al. Gold Nanoparticles in Delivery Applications. Adv. Drug Deliv. Rev. 2008, 60, 1307–1315.
- 21.
Lan, W.-J.; Holden, D.A.; Zhang, B.; et al. Nanoparticle Transport in Conical-Shaped Nanopores. Anal. Chem. 2011, 83, 3840–3847.
- 22.
Ramirez, A.B.; Lazenby, R.A. Fabricating Reproducible, Reversible, and High Signal Change Aptasensors with Gold-Modified Nanopipettes. ACS Appl. Mater. Interfaces 2025, 17, 24877–24886.
- 23.
Zhou, Y.; Wang, D.; Li, C.; et al. Resistive-Pulse Sensing and Surface Charge Analysis of a Single Nanoparticle Collision at a Conical Glass Nanopore. Anal. Chem. 2019, 91, 7648–7653.
- 24.
Zheng, X.; Liu, J.; Li, M.; et al. Dual-Nanopipettes for the Detection of Single Nanoparticles and Small Molecules. Anal. Chem. 2022, 94, 17431–17438.
- 25.
Wei, R.; Gatterdam, V.; Wieneke, R.; et al. Stochastic Sensing of Proteins with Receptor-Modified Solid-State Nanopores. Nat. Nanotechnol. 2012, 7, 257–263.
- 26.
Sa, N.; Baker, L.A. Rectification of Nanopores at Surfaces. J. Am. Chem. Soc. 2011, 133, 10398–10401.
- 27.
White, H.S.; Bund, A. Ion Current Rectification at Nanopores in Glass Membranes. Langmuir 2008, 24, 2212–2218.
- 28.
Ma, L.; Li, Z.; Yuan, Z.; et al. Modulation of Ionic Current Rectification in Ultrashort Conical Nanopores. Anal. Chem. 2020, 92, 16188–16196.
- 29.
Zhang, P.; Li, Y.; Wang, D.; et al. High-Yield Production of Uniform Gold Nanoparticles with Sizes from 31 to 577 nm via One-Pot Seeded Growth and Size-Dependent SERS Property. Part. Part. Syst. Charact. 2016, 33, 924–932.
- 30.
Yusko, E.C.; An, R.; Mayer, M. Electroosmotic Flow can Generate Ion Current Rectification in Nano- and Micropores. ACS Nano 2010, 4, 477–487.
- 31.
Venditti, I.; Fontana, L.; Scaramuzzo, F.A.; et al. Nanocomposite Based on Functionalized Gold Nanoparticles and Sulfonated Poly (Ether Ether Ketone) Membranes: Synthesis and Characterization. Materials 2017, 10, 258.
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