Nanopore-based Manipulation and Separation of Single-stranded DNA Molecules through Tuning pH Values

Cheng-Kai Zhou; Sheng-Wen Miao; Li-Zhen Sun

doi:10.1007/s10118-026-3640-7

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Nanopore-based Manipulation and Separation of Single-stranded DNA Molecules through Tuning pH Values

RESEARCH ARTICLE | Updated：2026-04-07

- Nanopore-based Manipulation and Separation of Single-stranded DNA Molecules through Tuning pH Values
- Chinese Journal of Polymer Science Vol. 44, Pages: 1-9(2026)
- Affiliations：
  
  School of Physics, Zhejiang University of Technology, Hangzhou 310023, China
- Author bio：
  
  sunlizhen@zjut.edu.cn
- Funds：
- DOI：10.1007/s10118-026-3640-7
  CLC：
- Received：30 January 2026，
  
  Revised：2026-02-21，
  
  Accepted：01 March 2026，
  
  Online First：07 April 2026，
  
  Published：2026-03
- Accepted：
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Zhou, C. K.; Miao, S. W.; Sun, L. Z. Nanopore-based manipulation and separation of single-stranded DNA molecules through tuning pH values. Chinese J. Polym. Sci. https://doi.org/10.1007/s10118-026-3640-7

Cheng-Kai Zhou, Sheng-Wen Miao, Li-Zhen Sun. Nanopore-based Manipulation and Separation of Single-stranded DNA Molecules through Tuning pH Values[J/OL]. Chinese Journal of Polymer Science, 2026, 441-9.
Zhou, C. K.; Miao, S. W.; Sun, L. Z. Nanopore-based manipulation and separation of single-stranded DNA molecules through tuning pH values. Chinese J. Polym. Sci. https://doi.org/10.1007/s10118-026-3640-7 DOI：

Cheng-Kai Zhou, Sheng-Wen Miao, Li-Zhen Sun. Nanopore-based Manipulation and Separation of Single-stranded DNA Molecules through Tuning pH Values[J/OL]. Chinese Journal of Polymer Science, 2026, 441-9. DOI： 10.1007/s10118-026-3640-7.

摘要

Abstract

The unique regulatory effect of pH on electrostatic interactions offers a powerful approach for manipulating and separating single-stranded DNA (ssDNA) molecules. In this study

we employ Langevin dynamics simulations to investigate the translocation dynamics of two ssDNAs

poly(dA) and poly(dT)

through a silicon nitride nanopore under acidic conditions. The key distinction between the two chains is their different pH-dependent protonation. At low pH

the highly protonated adenine bases experience repulsive interactions from the similarly protonated nanopore surface and the retarding force from the external voltage

whereas neutral thymine bases do not. Consequently

compared to poly(dT)

poly(dA) exhibits a lower capture probability and slower translocation speed under strongly acidic conditions. However

the difference in the translocation behaviors between the two chains gradually diminishes as the pH increases. Based on their distinct pH-dependent behaviors

poly(dA) and poly(dT) of identical length can be successfully separated through the translocation strategy at low pH

even when they are initially mixed on the same side of the nanopore.

关键词

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references

Muthukumar, M.; Plesa, C.; Dekker, C. Single-molecule sensing with nanopores. Phys. Today 2015 , 68 , 40−46..

Deamer, D.; Akeson, M.; Branton, D. Three decades of nanopore sequencing. Nat. Biotechnol . 2016 , 34 , 518−524..

Ying, Y. L.; Hu, Z. L.; Zhang, S.; Qing, Y.; Fragasso, A.; Maglia, G.; Meller, A.; Bayley, H.; Dekker, C.; Long, Y. T. Nanopore-based technologies beyond DNA sequencing. Nat. Nanotechnol. 2022 , 17 , 1136−1146..

Kasianowicz, J. J.; Brandin, E.; Branton, D.; Deamer, D. W. Characterization of individual polynucleotide molecules using a membrane channel. Proc. Natl. Acad. Sci. U.S.A. 1996 , 93 , 13770−13773..

Panja, D.; Barkema, G. T.; Ball, R. C. Anomalous dynamics of unbiased polymer translocation through a narrow pore. J. Phys.: Condens. Matter 2007 , 19 , 432202..

Gauthier, M. G.; Slater, G. W. A Monte Carlo algorithm to study polymer translocation through nanopores. II. Scaling laws. J. Chem. Phys. 2008 , 128 , 205103..

Hu, R; Rodrigues, J. V.; Waduge, P.; Yamazaki, H.; Cressiot, B.; Chishti, Y.; Makowski, L.; Yu, D.; Shakhnovich, E.; Zhao, Q.; Wanunu, M. Differential enzyme flexibility probed using solid-state nanopores. ACS Nano 2018 , 12 , 4494−4502..

Zhang, X.; Xu, X.; Yang, Z.; Burcke, A. J.; Gates, K. S.; Chen, S. J.; Gu, L. Q. Mimicking ribosomal unfolding of RNA pseudoknot in a protein channel. J. Am. Chem. Soc. 2015 , 137 , 15742−15752..

Zhang, X.; Zhang, D.; Zhao, C.; Tian, K.; Shi, R.; Du, X.; Burcke, A. J.; Wang, J.; Chen, S. J.; Gu, L. Q. Nanopore electric snapshots of an RNA tertiary folding pathway. Nat. Commun. 2017 , 8 , 1458..

Waduge, P.; Hu, R.; Bandarkar, P.; Yamazaki, H.; Cressiot, B.; Zhao, Q.; Whitford, P. C.; Wanunu, M. Nanopore-based measurements of protein size, fluctuations, and conformational changes. ACS Nano 2017 , 11 , 5706−5716..

Astier, Y.; Braha, O.; Bayley, H. Toward single molecule DNA sequencing: direct identification of ribonucleoside and deoxyribonucleoside 5’-monophosphates by using an engineered protein nanopore equipped with a molecular adapter. J. Am. Chem. Soc. 2006 , 128 , 1705−1710..

Clarke, J.; Wu, H. C.; Jayasinghe, L.; Patel, A.; Reid, S.; Bayley, H. Continuous base identification for single-molecule nanopore DNA sequencing. Nat. Nanotechnol. 2009 , 4 , 265−270..

Yu, W.; Luo, K. Chaperone-assisted translocation of a polymer through a nanopore. J. Am. Chem. Soc. 2011 , 133 , 13565−13570..

He, Y.; Tsutsui, M.; Scheicher, R. H.; Bai, F.; Taniguchi, M.; Kawai, T. Thermophoretic manipulation of DNA translocation through nanopores. ACS Nano 2013 , 7 , 538−546..

Luo, M. B.; Tsehay, D. A.; Sun, L. Z. Temperature dependence of the translocation time of polymer through repulsive nanopores. J. Chem. Phys. 2017 , 147 , 034901..

Lu, B.; Albertorio, F.; Hoogerheide, D. P.; Golovchenko, J. A. Origins and consequences of velocity fluctuations during DNA passage through a nanopore. Biophys. J. 2011 , 101 , 70−79..

Meller, A.; Nivon, L.; Branton, D. Voltage-driven DNA translocations through a nanopore. Phys. Rev. Lett. 2001 , 86 , 3435−3438..

Liu, Q.; Wu, H.; Wu, L.; Xie, X.; Kong, J.; Ye, X.; Liu, L. Voltage-driven translocation of DNA through a high throughput conical solid-state nanopore. PLoS ONE 2012 , 7 , e46014..

Di Fiori, N.; Squires, A.; Bar, D.; Gilboa, T.; Moustakas, T. D.; Meller, A. Optoelectronic control of surface charge and translocation dynamics in solid-state nanopores. Nat. Nanotechnol. 2013 , 8 , 946−951..

Jou, I.; Muthukumar, M. Effects of nanopore charge decorations on the translocation dynamics of DNA. Biophys. J. 2017 , 113 , 1664−1672..

Mereuta, L.; Asandei, A.; Andricioaei, I.; Park, J.; Park, Y.; Luchian, T. Considerable slowdown of short DNA fragment translocation across a protein nanopore using pH-induced generation of enthalpic traps inside the permeation pathway. Nanoscale 2023 , 15 , 14754−14763..

Luan, B.; Stolovitzky, G.; Martyna, G. Slowing and controlling the translocation of DNA in a solid-state nanopore. Nanoscale 2012 , 4 , 1068−1077..

Lin, X.; Chen, H .; Wu, G.; Zhao, J.; Zhang, Y.; Sha, J.; Si, W. Selective capture and manipulation of DNA through double charged nanopores. J. Phys. Chem. Lett. 2024 , 15 , 5120−5129..

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

Liao, D.; Cao, C.; Ying, Y.; Long, Y. A general strategy of aerolysin nanopore detection for oligonucleotides with the secondary structure. Small 2018 , 14 , 1704520..

Vu, T.; Borgesi, J.; Soyring, J.; D’Alia, M.; Davidson, S. L.; Shim, J. Employing LiCl salt gradient in the wild-typeα-hemolysin nanopore to slow down DNA translocation and detect methylated cytosine. Nanoscale 2019 , 11 , 10536−10545..

Goto, Y.; Matsui, K.; Yanagi, I.; Takeda, K. Silicon nitride nanopore created by dielectric breakdown with a divalent cation: deceleration of translocation speed and identification of single nucleotides. Nanoscale 2019 , 11 , 14426−14433..

Sun, L. Z.; Q ian, J. L.; Cai, P.; Hu, H. X.; Xu, X.; Luo, M. B. Mg 2+ effects on the single-stranded DNA conformations and nanopore translocation dynamics. Polymer 2022 , 250 , 124895..

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

Jeon, B.; Muthukumar, M. Electrostatic control of polymer translocation speed through α-Hemolysin protein pore. Macromolecules 2016 , 49 , 9132−9138..

[Buyukdagli, S.; Ala-Nissila, T. pH-mediated regulation of polymer transport through SiN pores. EPL 2018 , 123 , 38003..

Ghosh, B.; Chaudhury, S. Translocation dynamics of an asymmetrically charged polymer through a pore under the influence of different pH conditions. J. Phys. Chem. B 2019 , 123 , 4318−4323..

Mereuta, L.; Bhatti, H.; Asandei, A.; Cimpanu, A.; Ying, Y. L.; Long, Y. T.; Luchian, T. Controlli ng DNA fragments translocation across nanopores with the synergic use of site-directed mutagenesis, pH-dependent charge tuning, and electroosmotic flow. ACS Appl. Mater. Interfaces 2024 , 16 , 40100−40110..

Sun, L. Z.; Qian, J. L.; Cai, P.; Xu, X. Mutual effects between single-stranded DNA conformation and Na + -Mg 2+ ion competition in mixed salt solutions. Phys. Chem. Chem. Phys. 2022 , 24 , 20867−20881..

Rao, Y. F.; Sun, L. Z.; Luo, M. B. Na + -Mg 2+ ion effects on conformation and translocation dynamics of single-stranded RNA: cooperation and competition. Int. J. Biol. Macromol. 2024 , 267 , 131273..

Hu, Z. L.; Li, M. Y.; Liu, S. C.; Ying, Y. L.; Long, Y. T.A lithium-ion-active aerolysin nanopore for effectively trapping long single-stranded DNA. Chem. Sci. 2019 , 10 , 354−358..

Asandei, A.; Chinappi, M.; Kang, H. K.; Seo, C. H.; Mereuta, L.; Park, Y.; Luchian, T. Acidity-mediated, electrostatic tuning of asymmetrically charged peptides interactions with protein nanopores. ACS Appl. Mater. Interfaces 2015 , 7 , 16706−16714..

Verdolino, V.; Cammi, R.; Munk, B. H.; Schlegel, H. B. Calculation of p K a Values of nucleobases and the guanine oxidation products guanidinohydantoin and spiroiminodihydantoin using density functional theory and a polarizable continuum model. J. Phys. Chem. B 2008 , 112 , 16860−16873..

Goh, G. B.; Knight, J. L.; Brooks, C. L. Toward accurate prediction of the protonation equilibrium of nucleic acids. J. Phys. Chem. Lett. 2013 , 4 , 760−766..

Lin, K.; Li, Z.; Tao, Y.; Li, K.; Yang, H.; Ma, J.; Li, T.; Sha, J.; Chen, Y. Surface charge density inside a silicon nitride nanopore. Langmuir 2021 , 37 , 10521−10528..

Behrens, S. H.; Grier, D. G. The charge of glass and silica surfaces. J. Chem. Phys. 2001 , 115 , 6716−6721..

Čerović, L. S.; Milonjić, S. K.; Bahloul-Hourlier, D.; Doucey, B. Surface properties of silicon nitride powders. Colloids Surf., A 2002 , 197 , 147−156..

[Williams, R. pKa in water compilation, Organic Chemistry Data&Info. [accessed 24-January-2026]. https://organicchemistrydata.org/hansreich/resources/pka/pka_data/pka-compilation-williams.pdf.

[pKa of adenine, WolframAlpha.[accessed 24 January 2026]. https://www.wolframalpha.com.

Chakraborty, D.; Hori, N.; Thirumalai, D. Sequence-dependent three interaction site model for single- and double-stranded DNA. J. Chem. Theory Comput. 2018 , 14 , 3763−3769..

Denesyuk, N. A.; Thirumalai, D. Coarse-grained model for predicting RNA folding thermodynamics. J. Phys. Chem. B 2013 , 117 , 4901−4911..

Manning, G. S. The molecular theory of polyelectrolyte solutions with applications to the electrostatic properties of polynucleotides. Q Rev. Biophys. 1978 , 11 , 179−246..

Sun, L. Z.; Li, H.; Xu, X.; Luo, M. B. Simulation study on the translocation of polyelectrolyte through conical nanopores. J. Phys.: Condens. Matter 2018 , 30 , 495101..

Comer, J.; Aksimentiev, A. DNA sequence-dependent ionic currents in ultra-smallsolid-state nanopores. Nanoscale 2016 , 8 , 9600−9613..

Sakaue, T. Nonequilibrium dynamics of polymer translocation and straightening. Phys. Rev. E 2007 , 76 , 021803..

Ikonen, T.; Bhattacharya, A.; Ala-Nissila, T.; Sung, W. Influence of non-universal effects on dynamical scaling in driven polymer translocation. J. Chem. Phys. 2012 , 137 , 085101..

Lee, P. Y.; Costumbrado, J.; Hsu, C. Y.; Kim, Y. H. Agarose gel electrophoresis for the separation of DNA fragments. JoVE 2012 , 62 , e3923..

Zeng, Y.; Harrison, D. J. Self-assembled colloidal arrays as three-dimensional nanofluidic sieves for separation of biomolecules on microchips. Anal. Chem. 2007 , 79 , 2289−2295..

Fu, J.; Schoch, R. B.; Stevens, A. L.; Tannenbaum, S. R.; Han, J. A patterned anisotropic nanofluidic sieving structure for continuous-flow separation of DNA and proteins. Nat. Nanotechnol. 2007 , 2 , 121−128..

Han, J.; Craighead, H. G. Separation of long DNA molecules in a microfabricated entropic trap array. Science 2000 , 288 , 1026−1029..

Zhang, M.; Ngampeerapong, C.; Redin, D.; Ahmadian, A.; Sychugov, I.; Linnros, J. Thermophoresis-controlled size-dependent DNA translocation through an array of nanopores. ACS Nano 2018 , 12 , 4574−4582..

Zhan, L.; Zhang, Y.; Si, W.; Sha, J.; Chen, Y. Detection and separation of single-stranded DNA fragments using solid-state nanopores. J. Phys. Chem. Lett. 2021 , 12 , 6469−6477..

Bhai, S.; Ganguly, B. Role of pH in the stability of cytosine-cytosine mismatch and canonical AT and GC base pairs mediated with silver ion: a DFT study. Struct. Chem. 2022 , 33 , 35−47..

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