Abstract
Fluid transport at the nanoscale is ubiquitous in nature. However, rigorous study of fluid flow and structure in artificial nanopores only emerged relatively recently. Termed nanofluidics, the field is driven by the rise of nanomaterials and nanofabrication techniques and supported by theoretical progress beyond continuum fluid dynamics. Nanofluidics has a wide range of applications, such as nanopore sensing and membrane technologies for sieving and energy harvesting, leading to growth of the field. In this Primer, an overview of nanofluidic methods is provided, from the fabrication of the first nanopores to advanced functionalities, such as brain-inspired ionic computing. Focus is given to experimental approaches, including device fabrication and scale-up strategies, in addition to a discussion of limitations, margin for improvements and future directions.
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References
Gouaux, E. & MacKinnon, R. Principles of selective ion transport in channels and pumps. Science 310, 1461–1465 (2005).
Agre, P. et al. Aquaporin water channels — from atomic structure to clinical medicine. J. Physiol. 542, 3–16 (2002).
Kitchen, P. et al. Beyond water homeostasis: diverse functional roles of mammalian aquaporins. Biochim. Biophys. Acta Gen. Subj. 1850, 2410–2421 (2015).
Yellen, G. The voltage-gated potassium channels and their relatives. Nature 419, 35–42 (2002).
Li, J. et al. Ion-beam sculpting at nanometre length scales. Nature 412, 166–169 (2001). This paper reports early fabrication of nanoscale holes.
Stein, D., Kruithof, M. & Dekker, C. Surface-charge-governed ion transport in nanofluidic channels. Phys. Rev. Lett. 93, 035901 (2004).
Lee, C. Y., Choi, W., Han, J.-H. & Strano, M. S. Coherence resonance in a single-walled carbon nanotube ion channel. Science 329, 1320–1324 (2010).
Siria, A. et al. Giant osmotic energy conversion measured in a single transmembrane boron nitride nanotube. Nature 494, 455–458 (2013).
Feng, J. et al. Electrochemical reaction in single layer MoS2: nanopores opened atom by atom. Nano Lett. 15, 3431–3438 (2015).
Bhardwaj, A. et al. Fabrication of angstrom-scale two-dimensional channels for mass transport. Nat. Protoc. 19, 240–280 (2024).
Dikin, D. A. et al. Preparation and characterization of graphene oxide paper. Nature 448, 457–460 (2007). This paper reports the first fabrication of graphene oxide membranes.
Engst, C. R. et al. DNA origami nanopores. Nano Lett. 12, 512–517 (2012).
Lu, J. & Wang, H. Emerging porous framework material-based nanofluidic membranes toward ultimate ion separation. Matter 4, 2810–2830 (2021).
Holt, J. K. et al. Fast mass transport through sub-2-nanometer carbon nanotubes. Science 312, 1034–1037 (2006). To our knowledge, this paper shows the first experimental observation of fast water flows in carbon nanotubes.
Secchi, E. et al. Massive radius-dependent flow slippage in carbon nanotubes. Nature 537, 210–213 (2016). This paper reports the observation of giant slippage in single carbon nanotubes.
Garaj, S. et al. Graphene as a subnanometre trans-electrode membrane. Nature 467, 190–193 (2010).
Feng, J. et al. Single-layer MoS2 nanopores as nanopower generators. Nature 536, 197–200 (2016).
Radha, B. et al. Molecular transport through capillaries made with atomic-scale precision. Nature 538, 222–225 (2016). To our knowledge, this is the first paper with 2D slits made by van der Waals assembly.
Emmerich, T. et al. Enhanced nanofluidic transport in activated carbon nanoconduits. Nat. Mater. 21, 696–702 (2022).
Kasianowicz, J. J., Brandin, E., Branton, D. & Deamer, D. W. Characterization of individual polynucleotide molecules using a membrane channel. Proc. Natl Acad. Sci. USA 93, 13770–13773 (1996).
Deamer, D., Akeson, M. & Branton, D. Three decades of nanopore sequencing. Nat. Biotechnol. 34, 518–524 (2016).
Robin, P. et al. Long-term memory and synapse-like dynamics in two-dimensional nanofluidic channels. Science 379, 161–167 (2023).
Marcotte, A., Mouterde, T., Niguès, A., Siria, A. & Bocquet, L. Mechanically activated ionic transport across single-digit carbon nanotubes. Nat. Mater. 19, 1057–1061 (2020).
Davis, S. J. et al. Pressure-induced enlargement and ionic current rectification in symmetric nanopores. Nano Lett. 20, 8089–8095 (2020).
Kavokine, N., Bocquet, M.-L. & Bocquet, L. Fluctuation-induced quantum friction in nanoscale water flows. Nature 602, 84–90 (2022). This paper reports a quantum-based theory explaining the low water–carbon friction.
Yu, X., Principi, A., Tielrooij, K.-J., Bonn, M. & Kavokine, N. Electron cooling in graphene enhanced by plasmon–hydron resonance. Nat. Nanotechnol. 18, 898–904 (2023).
Xiong, T. et al. Neuromorphic functions with a polyelectrolyte-confined fluidic memristor. Science 379, 156–161 (2023).
Emmerich, T. et al. Nanofluidic logic with mechano-ionic memristive switches. Nat. Electron. 7, 271–278 (2024). To our knowledge, this paper reports the first logic circuit with nanofluidic memristors.
Schoch, R. B., Han, J. & Renaud, P. Transport phenomena in nanofluidics. Rev. Mod. Phys. 80, 839–883 (2008).
Bocquet, L. & Charlaix, E. Nanofluidics, from bulk to interfaces. Chem. Soc. Rev. 39, 1073–1095 (2010).
Kavokine, N., Netz, R. R. & Bocquet, L. Fluids at the nanoscale: from continuum to subcontinuum transport. Annu. Rev. Fluid Mech. 53, 377–410 (2021).
Ying, Y.-L. et al. Nanopore-based technologies beyond DNA sequencing. Nat. Nanotechnol. 17, 1136–1146 (2022).
Miles, B. N. et al. Single molecule sensing with solid-state nanopores: novel materials, methods, and applications. Chem. Soc. Rev. 42, 15–28 (2013).
Xue, L. et al. Solid-state nanopore sensors. Nat. Rev. Mater. 5, 931–951 (2020).
Gao, J., Feng, Y., Guo, W. & Jiang, L. Nanofluidics in two-dimensional layered materials: inspirations from nature. Chem. Soc. Rev. 46, 5400–5424 (2017).
Logan, B. E. & Elimelech, M. Membrane-based processes for sustainable power generation using water. Nature 488, 313–319 (2012).
Siria, A., Bocquet, M.-L. & Bocquet, L. New avenues for the large-scale harvesting of blue energy. Nat. Rev. Chem. 1, 0091 (2017).
Macha, M., Marion, S., Nandigana, V. V. R. & Radenovic, A. 2D materials as an emerging platform for nanopore-based power generation. Nat. Rev. Mater. 4, 588–605 (2019).
Zhang, Z., Wen, L. & Jiang, L. Nanofluidics for osmotic energy conversion. Nat. Rev. Mater. 6, 622–639 (2021).
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).
Karnik, R. et al. Electrostatic control of ions and molecules in nanofluidic transistors. Nano Lett. 5, 943–948 (2005).
Karnik, R., Duan, C., Castelino, K., Daiguji, H. & Majumdar, A. Rectification of ionic current in a nanofluidic diode. Nano Lett. 7, 547–551 (2007).
Siwy, Z. & Fuliński, A. Fabrication of a synthetic nanopore ion pump. Phys. Rev. Lett. 89, 198103 (2002).
Guo, W. et al. Energy harvesting with single-ion-selective nanopores: a concentration-gradient-driven nanofluidic power source. Adv. Funct. Mater. 20, 1339–1344 (2010).
Bocquet, L. Nanofluidics coming of age. Nat. Mater. 19, 254–256 (2020).
Celebi, K. et al. Ultimate permeation across atomically thin porous graphene. Science 344, 289–292 (2014).
Tunuguntla, R. H. et al. Enhanced water permeability and tunable ion selectivity in subnanometer carbon nanotube porins. Science 357, 792–796 (2017).
Gopinadhan, K. et al. Complete steric exclusion of ions and proton transport through confined monolayer water. Science 363, 145–148 (2019).
Geim, A. K. & Grigorieva, I. V. van der Waals heterostructures. Nature 499, 419–425 (2013).
Nair, R. R., Wu, H. A., Jayaram, P. N., Grigorieva, I. V. & Geim, A. K. Unimpeded permeation of water through helium-leak–tight graphene-based membranes. Science 335, 442–444 (2012). This paper reports very high water permeation across graphene oxide membranes.
Ji, Y.-L. et al. Superfast water transport zwitterionic polymeric nanofluidic membrane reinforced by metal–organic frameworks. Adv. Mater. 33, 2102292 (2021).
Lu, J. et al. Ultraselective monovalent metal ion conduction in a three-dimensional sub-1 nm nanofluidic device constructed by metal–organic frameworks. ACS Nano 15, 1240–1249 (2021).
Yang, J. et al. Advancing osmotic power generation by covalent organic framework monolayer. Nat. Nanotechnol. 17, 622–628 (2022).
Liu, Q. et al. Unit-cell-thick zeolitic imidazolate framework films for membrane application. Nat. Mater. 22, 1387–1393 (2023).
Park, H. G. & Jung, Y. Carbon nanofluidics of rapid water transport for energy applications. Chem. Soc. Rev. 43, 565–576 (2013).
Mouterde, T. et al. Molecular streaming and its voltage control in ångström-scale channels. Nature 567, 87–90 (2019).
Bui, A. T., Thiemann, F. L., Michaelides, A. & Cox, S. J. Classical quantum friction at water–carbon interfaces. Nano Lett. 23, 580–587 (2023).
Capone, R., Blake, S., Rincon Restrepo, M., Yang, J. & Mayer, M. Designing nanosensors based on charged derivatives of gramicidin A. J. Am. Chem. Soc. 129, 9737–9745 (2007).
Butler, T. Z., Pavlenok, M., Derrington, I. M., Niederweis, M. & Gundlach, J. H. Single-molecule DNA detection with an engineered MspA protein nanopore. Proc. Natl Acad. Sci. USA 105, 20647–20652 (2008).
Hernández-Ainsa, S. & Keyser, U. F. DNA origami nanopores: developments, challenges and perspectives. Nanoscale 6, 14121–14132 (2014).
Mayer, S. F., Cao, C. & Dal Peraro, M. Biological nanopores for single-molecule sensing. iScience 25, 104145 (2022).
Wei, R., Pedone, D., Zürner, A., Döblinger, M. & Rant, U. Fabrication of metallized nanopores in silicon nitride membranes for single-molecule sensing. Small 6, 1406–1414 (2010).
Thangaraj, V. et al. Detection of short ssDNA and dsDNA by current–voltage measurements using conical nanopores coated with Al2O3 by atomic layer deposition. Microchim. Acta 183, 1011–1017 (2016).
Yameen, B. et al. Single conical nanopores displaying pH-tunable rectifying characteristics. Manipulating ionic transport with zwitterionic polymer brushes. J. Am. Chem. Soc. 131, 2070–2071 (2009).
Venkatesan, B. M. et al. Lipid bilayer coated Al2O3 nanopore sensors: towards a hybrid biological solid-state nanopore. Biomed. Microdev. 13, 671–682 (2011).
Galla, L. et al. Hydrodynamic slip on DNA observed by optical tweezers-controlled translocation experiments with solid-state and lipid-coated nanopores. Nano Lett. 14, 4176–4182 (2014).
Yuzvinsky, T. D., Fennimore, A. M., Mickelson, W., Esquivias, C. & Zettl, A. Precision cutting of nanotubes with a low-energy electron beam. Appl. Phys. Lett. 86, 053109 (2005).
Thiele, C. et al. Electron-beam-induced direct etching of graphene. Carbon 64, 84–91 (2013).
Traversi, F. et al. Detecting the translocation of DNA through a nanopore using graphene nanoribbons. Nat. Nanotechnol. 8, 939–945 (2013).
Chen, Y. Nanofabrication by electron beam lithography and its applications: a review. Microelectron. Eng. 135, 57–72 (2015).
Vieu, C. et al. Electron beam lithography: resolution limits and applications. Appl. Surf. Sci. 164, 111–117 (2000).
Jonsson, M. P., Dahlin, A. B., Feuz, L., Petronis, S. & Höök, F. Locally functionalized short-range ordered nanoplasmonic pores for bioanalytical sensing. Anal. Chem. 82, 2087–2094 (2010).
Briggs, K. et al. Kinetics of nanopore fabrication during controlled breakdown of dielectric membranes in solution. Nanotechnology 26, 084004 (2015).
Graf, M. et al. Fabrication and practical applications of molybdenum disulfide nanopores. Nat. Protoc. 14, 1130–1168 (2019).
Gilboa, T., Zvuloni, E., Zrehen, A., Squires, A. H. & Meller, A. Automated, ultra-fast laser-drilling of nanometer scale pores and nanopore arrays in aqueous solutions. Adv. Funct. Mater. 30, 1900642 (2020).
Fried, J. P. et al. In situ solid-state nanopore fabrication. Chem. Soc. Rev. 50, 4974–4992 (2021).
Zvuloni, E., Zrehen, A., Gilboa, T. & Meller, A. Fast and deterministic fabrication of sub-5 nanometer solid-state pores by feedback-controlled laser processing. ACS Nano 15, 12189–12200 (2021).
Huang, S. et al. In situ nucleation-decoupled and site-specific incorporation of Å-scale pores in graphene via epoxidation. Adv. Mater. 34, 2206627 (2022).
Bondaz, L. et al. Selective photonic gasification of strained oxygen clusters on graphene for tuning pore size in the Å regime. JACS Au 3, 2844–2854 (2023).
Gösele, U. & Tong, Q.-Y. Semiconductor wafer bonding. Annu. Rev. Mater. Sci. 28, 215–241 (1998).
Wang, H. Y., Foote, R. S., Jacobson, S. C., Schneibel, J. H. & Ramsey, J. M. Low temperature bonding for microfabrication of chemical analysis devices. Sens. Actuators B Chem. 45, 199–207 (1997).
Novoselov, K. S., Mishchenko, A., Carvalho, A. & Castro Neto, A. H. 2D materials and van der Waals heterostructures. Science 353, aac9439 (2016).
Schranghamer, T. F., Sharma, M., Singh, R. & Das, S. Review and comparison of layer transfer methods for two-dimensional materials for emerging applications. Chem. Soc. Rev. 50, 11032–11054 (2021).
Hirunpinyopas, W. et al. Desalination and nanofiltration through functionalized laminar MoS2 membranes. ACS Nano 11, 11082–11090 (2017).
Ries, L. et al. Enhanced sieving from exfoliated MoS2 membranes via covalent functionalization. Nat. Mater. 18, 1112–1117 (2019).
Chen, L. et al. Ion sieving in graphene oxide membranes via cationic control of interlayer spacing. Nature 550, 380–383 (2017).
Abraham, J. et al. Tunable sieving of ions using graphene oxide membranes. Nat. Nanotechnol. 12, 546–550 (2017).
Burns, J. R., Seifert, A., Fertig, N. & Howorka, S. A biomimetic DNA-based channel for the ligand-controlled transport of charged molecular cargo across a biological membrane. Nat. Nanotechnol. 11, 152–156 (2016).
Xing, Y., Dorey, A., Jayasinghe, L. & Howorka, S. Highly shape- and size-tunable membrane nanopores made with DNA. Nat. Nanotechnol. 17, 708–713 (2022).
You, Y. et al. Angstrofluidics: walking to the limit. Annu. Rev. Mater. Res. 52, 189–218 (2022).
Storm, A. J. et al. Fast DNA translocation through a solid-state nanopore. Nano Lett. 5, 1193–1197 (2005).
Li, J., Gershow, M., Stein, D., Brandin, E. & Golovchenko, J. A. DNA molecules and configurations in a solid-state nanopore microscope. Nat. Mater. 2, 611–615 (2003).
Xiao, K. et al. Enhanced stability and controllability of an ionic diode based on funnel-shaped nanochannels with an extended critical region. Adv. Mater. 28, 3345–3350 (2016).
Zhao, Y., Janot, J.-M., Balanzat, E. & Balme, S. Mimicking pH-gated ionic channels by polyelectrolyte complex confinement inside a single nanopore. Langmuir 33, 3484–3490 (2017).
Déjardin, P., Vasina, E. N., Berezkin, V. V., Sobolev, V. D. & Volkov, V. I. Streaming potential in cylindrical pores of poly(ethylene terephthalate) track-etched membranes: variation of apparent ζ potential with pore radius. Langmuir 21, 4680–4685 (2005).
Ma, T., Janot, J.-M. & Balme, S. Track-etched nanopore/membrane: from fundamental to applications. Small Methods 4, 2000366 (2020).
van der Heyden, F. H. J., Stein, D. & Dekker, C. Streaming currents in a single nanofluidic channel. Phys. Rev. Lett. 95, 116104 (2005).
Kim, D.-K., Duan, C., Chen, Y.-F. & Majumdar, A. Power generation from concentration gradient by reverse electrodialysis in ion-selective nanochannels. Microfluid. Nanofluid. 9, 1215–1224 (2010).
Ohayon, S. et al. Full-length single protein molecules tracking and counting in thin silicon channels. Adv. Mater. 36, 2314319 (2024).
Yuan, Z. et al. Direct chemical vapor deposition synthesis of porous single-layer graphene membranes with high gas permeances and selectivities. Adv. Mater. 33, 2104308 (2021).
Griffin, E. et al. Proton and Li-ion permeation through graphene with eight-atom-ring defects. ACS Nano 14, 7280–7286 (2020).
Jain, T. et al. Heterogeneous sub-continuum ionic transport in statistically isolated graphene nanopores. Nat. Nanotechnol. 10, 1053–1057 (2015).
Kidambi, P. R. et al. Facile fabrication of large-area atomically thin membranes by direct synthesis of graphene with nanoscale porosity. Adv. Mater. 30, 1804977 (2018).
Walker, M. I. et al. Extrinsic cation selectivity of 2D membranes. ACS Nano 11, 1340–1346 (2017).
Levita, G., Restuccia, P. & Righi, M. C. Graphene and MoS2 interacting with water: a comparison by ab initio calculations. Carbon 107, 878–884 (2016).
Cheng, C., Iyengar, S. A. & Karnik, R. Molecular size-dependent subcontinuum solvent permeation and ultrafast nanofiltration across nanoporous graphene membranes. Nat. Nanotechnol. 16, 989–995 (2021).
Secchi, E., Niguès, A., Jubin, L., Siria, A. & Bocquet, L. Scaling behavior for ionic transport and its fluctuations in individual carbon nanotubes. Phys. Rev. Lett. 116, 154501 (2016).
Choi, W., Lee, C. Y., Ham, M.-H., Shimizu, S. & Strano, M. S. Dynamics of simultaneous, single ion transport through two single-walled carbon nanotubes: observation of a three-state system. J. Am. Chem. Soc. 133, 203–205 (2011).
Choi, W. et al. Diameter-dependent ion transport through the interior of isolated single-walled carbon nanotubes. Nat. Commun. 4, 2397 (2013).
Agrawal, K. V., Shimizu, S., Drahushuk, L. W., Kilcoyne, D. & Strano, M. S. Observation of extreme phase transition temperatures of water confined inside isolated carbon nanotubes. Nat. Nanotechnol. 12, 267–273 (2017).
Li, Z. et al. Breakdown of the Nernst–Einstein relation in carbon nanotube porins. Nat. Nanotechnol. 18, 177–183 (2023).
Fornasiero, F. et al. Ion exclusion by sub-2-nm carbon nanotube pores. Proc. Natl Acad. Sci. USA 105, 17250–17255 (2008).
Sakai, N. & Matile, S. Synthetic ion channels. Langmuir 29, 9031–9040 (2013).
Zheng, S.-P., Huang, L.-B., Sun, Z. & Barboiu, M. Self-assembled artificial ion-channels toward natural selection of functions. Angew. Chem. Int. Ed. 60, 566–597 (2021).
Barboiu, M. Artificial water channels. Angew. Chem. Int. Ed. 51, 11674–11676 (2012).
Song, W. & Kumar, M. Artificial water channels: toward and beyond desalination. Curr. Opin. Chem. Eng. 25, 9–17 (2019).
Jubin, L., Poggioli, A., Siria, A. & Bocquet, L. Dramatic pressure-sensitive ion conduction in conical nanopores. Proc. Natl Acad. Sci. USA 115, 4063–4068 (2018).
Nadappuram, B. P. et al. Nanoscale tweezers for single-cell biopsies. Nat. Nanotechnol. 14, 80–88 (2019).
Leitao, S. M. et al. Spatially multiplexed single-molecule translocations through a nanopore at controlled speeds. Nat. Nanotechnol. 18, 1078–1084 (2023).
Fumagalli, L. et al. Anomalously low dielectric constant of confined water. Science 360, 1339–1342 (2018). This paper reports the reduced in-plane dielectric constant of interfacial water.
Lee, C. et al. Osmotic flow through fully permeable nanochannels. Phys. Rev. Lett. 112, 244501 (2014).
Ronceray, N. et al. Liquid-activated quantum emission from pristine hexagonal boron nitride for nanofluidic sensing. Nat. Mater. 22, 1236–1242 (2023).
Esfandiar, A. et al. Size effect in ion transport through ångström-scale slits. Science 358, 511–513 (2017).
Keerthi, A. et al. Ballistic molecular transport through two-dimensional channels. Nature 558, 420–424 (2018).
Goutham, S. et al. Beyond steric selectivity of ions using ångström-scale capillaries. Nat. Nanotechnol. 18, 596–601 (2023).
Liu, C. et al. Controllable van der Waals gaps by water adsorption. Nat. Nanotechnol. 19, 1–7 (2024).
Ramirez, P., Gómez, V., Cervera, J., Mafe, S. & Bisquert, J. Synaptical tunability of multipore nanofluidic memristors. J. Phys. Chem. Lett. 14, 10930–10934 (2023).
Paulo, G. et al. Hydrophobically gated memristive nanopores for neuromorphic applications. Nat. Commun. 14, 8390 (2023).
Sheng, Q., Xie, Y., Li, J., Wang, X. & Xue, J. Transporting an ionic-liquid/water mixture in a conical nanochannel: a nanofluidic memristor. Chem. Commun. 53, 6125–6127 (2017).
Soni, N., Chandra Verma, N., Talor, N. & Meller, A. Over 30-fold enhancement in DNA translocation dynamics through nanoscale pores coated with an anionic surfactant. Nano Lett. 23, 4609–4616 (2023).
Zhou, Z. et al. Electrochemical-repaired porous graphene membranes for precise ion-ion separation. Nat. Commun. 15, 4006 (2024).
Zhao, K. et al. Tuning pore size in graphene in the angstrom regime for highly selective ion–ion separation. ACS Nano 18, 5571–5580 (2024).
Zhong, J. et al. Exploring anomalous fluid behavior at the nanoscale: direct visualization and quantification via nanofluidic devices. Acc. Chem. Res. 53, 347–357 (2020).
Shen, Y. et al. Highly permeable artificial water channels that can self-assemble into two-dimensional arrays. Proc. Natl Acad. Sci. USA 112, 9810–9815 (2015).
Xie, Q. et al. Fast water transport in graphene nanofluidic channels. Nat. Nanotechnol. 13, 238–245 (2018). This paper reports the observation of large slippage in 2D graphitic channels.
Ronceray, N. et al. Elastocapillarity-driven 2D nano-switches enable zeptoliter-scale liquid encapsulation. Nat. Commun. 15, 185 (2024).
Gilboa, T. & Meller, A. Optical sensing and analyte manipulation in solid-state nanopores. Analyst 140, 4733–4747 (2015).
Heron, A. J., Thompson, J. R., Cronin, B., Bayley, H. & Wallace, M. I. Simultaneous measurement of ionic current and fluorescence from single protein pores. J. Am. Chem. Soc. 131, 1652–1653 (2009).
Ivankin, A. et al. Label-free optical detection of biomolecular translocation through nanopore arrays. ACS Nano 8, 10774–10781 (2014).
Laohakunakorn, N. et al. A Landau–Squire nanojet. Nano Lett. 13, 5141–5146 (2013).
Secchi, E., Marbach, S., Niguès, A., Siria, A. & Bocquet, L. The Landau–Squire plume. J. Fluid Mech. 826, R3 (2017).
Sharma, P. et al. A direct sensor to measure minute liquid flow rates. Nano Lett. 18, 5726–5730 (2018).
Koenig, S. P., Wang, L., Pellegrino, J. & Bunch, J. S. Selective molecular sieving through porous graphene. Nat. Nanotechnol. 7, 728–732 (2012).
Wang, L. et al. Molecular valves for controlling gas phase transport made from discrete ångström-sized pores in graphene. Nat. Nanotechnol. 10, 785–790 (2015).
Sun, P. Z. et al. Limits on gas impermeability of graphene. Nature 579, 229–232 (2020).
Zeng, Y. et al. Irreversible synthesis of an ultrastrong two-dimensional polymeric material. Nature 602, 91–95 (2022).
Agrawal, K. V. et al. Fabrication, pressure testing, and nanopore formation of single-layer graphene membranes. J. Phys. Chem. C 121, 14312–14321 (2017).
Deveci, S., Oksuz, Y., Birtane, T. & Oner, M. Application of constant volume–variable pressure (time-lag) method to measure oxygen gas diffusion through polypropylene pipes. Polym. Test. 55, 287–296 (2016).
Sahin, Z. E., Rahimalimamaghani, A., Gazzani, M. & Gallucci, F. Gas permeation through carbon membranes: model development and experimental validation. Int. J. Hydrog. Energy 50, 561–581 (2024).
Marbach, S. & Bocquet, L. Osmosis, from molecular insights to large-scale applications. Chem. Soc. Rev. 48, 3102–3144 (2019).
Gubbiotti, A. et al. Electroosmosis in nanopores: computational methods and technological applications. Adv. Phys. X 7, 2036638 (2022).
Hall, J. E. Access resistance of a small circular pore. J. Gen. Physiol. 66, 531–532 (1975).
Manghi, M. et al. Ionic conductance of carbon nanotubes: confronting literature data with nanofluidic theory. J. Phys. Chem. C 125, 22943–22950 (2021).
Smeets, R. M. M., Keyser, U. F., Wu, M. Y., Dekker, N. H. & Dekker, C. Nanobubbles in solid-state nanopores. Phys. Rev. Lett. 97, 088101 (2006).
Smeets, R. M. M., Keyser, U. F., Dekker, N. H. & Dekker, C. Noise in solid-state nanopores. Proc. Natl Acad. Sci. USA 105, 417–421 (2008).
Gravelle, S., Netz, R. R. & Bocquet, L. Adsorption kinetics in open nanopores as a source of low-frequency noise. Nano Lett. 19, 7265–7272 (2019).
Vlassiouk, I. & Siwy, Z. S. Nanofluidic diode. Nano Lett. 7, 552–556 (2007).
Daiguji, H., Oka, Y. & Shirono, K. Nanofluidic diode and bipolar transistor. Nano Lett. 5, 2274–2280 (2005).
Ali, M., Ramirez, P., Mafé, S., Neumann, R. & Ensinger, W. A pH-tunable nanofluidic diode with a broad range of rectifying properties. ACS Nano 3, 603–608 (2009).
Smirnov, S. N., Vlassiouk, I. V. & Lavrik, N. V. Voltage-gated hydrophobic nanopores. ACS Nano 5, 7453–7461 (2011).
Cantley, L. et al. Voltage gated inter-cation selective ion channels from graphene nanopores. Nanoscale 11, 9856–9861 (2019).
Marion, S., Macha, M., Davis, S. J., Chernev, A. & Radenovic, A. Wetting of nanopores probed with pressure. Phys. Chem. Chem. Phys. 23, 4975–4987 (2021).
Green, Y. Ion transport in nanopores with highly overlapping electric double layers. J. Chem. Phys. 154, 084705 (2021).
Mouterde, T. & Bocquet, L. Interfacial transport with mobile surface charges and consequences for ionic transport in carbon nanotubes. Eur. Phys. J. E 41, 148 (2018).
Daiguji, H., Yang, P. & Majumdar, A. Ion transport in nanofluidic channels. Nano Lett. 4, 137–142 (2004).
Henderson, P. Zur Thermodynamik der Flüssigkeitsketten. Z. für Physikalische Chem. 59U, 118–127 (1907).
Goldman, D. E. Potential, impedance, and rectification in membranes. J. Gen. Physiol. 27, 37–60 (1943).
Sten-Knudsen, O. Biological Membranes: Theory of Transport, Potentials and Electric Impulses (Cambridge Univ. Press, 2002).
Zhan, C. et al. Specific ion effects at graphitic interfaces. Nat. Commun. 10, 4858 (2019).
Gonella, G. et al. Water at charged interfaces. Nat. Rev. Chem. 5, 466–485 (2021).
Kapil, V. et al. The first-principles phase diagram of monolayer nanoconfined water. Nature 609, 512–516 (2022).
Cicero, G., Grossman, J. C., Schwegler, E., Gygi, F. & Galli, G. Water confined in nanotubes and between graphene sheets: a first principle study. J. Am. Chem. Soc. 130, 1871–1878 (2008).
Hummer, G., Rasaiah, J. C. & Noworyta, J. P. Water conduction through the hydrophobic channel of a carbon nanotube. Nature 414, 188–190 (2001).
Corti, H. R. et al. Structure and dynamics of nanoconfined water and aqueous solutions. Eur. Phys. J. E 44, 136 (2021).
Motevaselian, M. H. & Aluru, N. R. Universal reduction in dielectric response of confined fluids. ACS Nano 14, 12761–12770 (2020).
Wang, R. et al. In-plane dielectric constant and conductivity of confined water. Preprint at https://doi.org/10.48550/arXiv.2407.21538 (2024).
Yang, H. et al. Suppressed terahertz dynamics of water confined in nanometer gaps. Sci. Adv. 10, eadm7315 (2024).
Wang, Y. et al. Interfaces govern structure of angstrom-scale confined water. Preprint at http://arxiv.org/abs/2310.10354 (2023).
Montenegro, A. et al. Asymmetric response of interfacial water to applied electric fields. Nature 594, 62–65 (2021).
Wang, Y. et al. Chemistry governs water organization at a graphene electrode. Nature 615, E1–E2 (2023).
Branton, D. et al. The potential and challenges of nanopore sequencing. Nat. Biotechnol. 26, 1146–1153 (2008).
Marx, V. Method of the year: long-read sequencing. Nat. Methods 20, 6–11 (2023).
Jain, M., Abu-Shumays, R., Olsen, H. E. & Akeson, M. Advances in nanopore direct RNA sequencing. Nat. Methods 19, 1160–1164 (2022).
Restrepo-Pérez, L., Joo, C. & Dekker, C. Paving the way to single-molecule protein sequencing. Nat. Nanotechnol. 13, 786–796 (2018).
Varongchayakul, N., Song, J., Meller, A. & Grinstaff, M. W. Single-molecule protein sensing in a nanopore: a tutorial. Chem. Soc. Rev. 47, 8512–8524 (2018).
Nguyen, D. N. et al. Polymer-stabilized Cas9 nanoparticles and modified repair templates increase genome editing efficiency. Nat. Biotechnol. 38, 44–49 (2020).
Chavis, A. E. et al. Single molecule nanopore spectrometry for peptide detection. ACS Sens. 2, 1319–1328 (2017).
Restrepo-Pérez, L. et al. Resolving chemical modifications to a single amino acid within a peptide using a biological nanopore. ACS Nano 13, 13668–13676 (2019).
Yusko, E. C. et al. Real-time shape approximation and fingerprinting of single proteins using a nanopore. Nat. Nanotechnol. 12, 360–367 (2017).
Thakur, A. K. & Movileanu, L. Real-time measurement of protein–protein interactions at single-molecule resolution using a biological nanopore. Nat. Biotechnol. 37, 96–101 (2019).
Bejerano, T., Etzion, S., Elyagon, S., Etzion, Y. & Cohen, S. Nanoparticle delivery of miRNA-21 mimic to cardiac macrophages improves myocardial remodeling after myocardial infarction. Nano Lett. 18, 5885–5891 (2018).
Graf, M., Lihter, M., Altus, D., Marion, S. & Radenovic, A. Transverse detection of DNA using a MoS2 nanopore. Nano Lett. 19, 9075–9083 (2019).
Heerema, S. J. & Dekker, C. Graphene nanodevices for DNA sequencing. Nat. Nanotechnol. 11, 127–136 (2016).
Feng, J. et al. Identification of single nucleotides in MoS2 nanopores. Nat. Nanotechnol. 10, 1070–1076 (2015).
Yang, W. et al. Translocation of DNA through ultrathin nanoslits. Adv. Mater. 33, 2007682 (2021).
Fried, J. P., Wu, Y., Tilley, R. D. & Gooding, J. J. Optical nanopore sensors for quantitative analysis. Nano Lett. 22, 869–880 (2022).
Schmidt, T., Zhang, M., Sychugov, I., Roxhed, N. & Linnros, J. Nanopore arrays in a silicon membrane for parallel single-molecule detection: fabrication. Nanotechnology 26, 314001 (2015).
Zhang, M. et al. Nanopore arrays in a silicon membrane for parallel single-molecule detection: DNA translocation. Nanotechnology 26, 314002 (2015).
Huh, D. et al. Tuneable elastomeric nanochannels for nanofluidic manipulation. Nat. Mater. 6, 424–428 (2007).
Zrehen, A., Ohayon, S., Huttner, D. & Meller, A. On-chip protein separation with single-molecule resolution. Sci. Rep. 10, 15313 (2020).
Gao, M., Tsai, P.-C., Su, Y.-S., Peng, P.-H. & Yeh, L.-H. Single mesopores with high surface charges as ultrahigh performance osmotic power generators. Small 16, 2006013 (2020).
Ajdari, A. & Bocquet, L. Giant amplification of interfacially driven transport by hydrodynamic slip: diffusio-osmosis and beyond. Phys. Rev. Lett. 96, 186102 (2006).
Zhang, H. et al. Bioinspired artificial single ion pump. J. Am. Chem. Soc. 135, 16102–16110 (2013).
Xu, Y., Yazbeck, R. & Duan, C. Anomalous mechanosensitive ion transport in nanoparticle-blocked nanopores. J. Chem. Phys. 154, 224702 (2021).
Armstrong, C. M. & Hille, B. Voltage-gated ion channels and electrical excitability. Neuron 20, 371–380 (1998).
Pérez-Mitta, G., Albesa, A. G., Trautmann, C., Toimil-Molares, M. E. & Azzaroni, O. Bioinspired integrated nanosystems based on solid-state nanopores: ‘iontronic’ transduction of biological, chemical and physical stimuli. Chem. Sci. 8, 890–913 (2017).
Bocquet, L. Concluding remarks: iontronics, from fundamentals to ion-controlled devices — random access memories. Faraday Discuss. 246, 618–622 (2023).
Ali, M., Mafe, S., Ramirez, P., Neumann, R. & Ensinger, W. Logic gates using nanofluidic diodes based on conical nanopores functionalized with polyprotic acid chains. Langmuir 25, 11993–11997 (2009).
Liu, W. et al. Bioinspired carbon nanotube-based nanofluidic ionic transistor with ultrahigh switching capabilities for logic circuits. Sci. Adv. 10, eadj7867 (2024).
Li, T. et al. A nanofluidic ion regulation membrane with aligned cellulose nanofibers. Sci. Adv. 5, eaau4238 (2019).
Cheng, C., Jiang, G., Simon, G. P., Liu, J. Z. & Li, D. Low-voltage electrostatic modulation of ion diffusion through layered graphene-based nanoporous membranes. Nat. Nanotechnol. 13, 685–690 (2018).
Wang, Y. et al. Voltage-gated ion transport in two-dimensional sub-1 nm nanofluidic channels. ACS Nano 13, 11793–11799 (2019).
Mei, T. et al. Bio-inspired two-dimensional nanofluidic ionic transistor for neuromorphic signal processing. Angew. Chem. Int. Ed. 63, e202401477 (2024).
Di Fiori, N. et al. Optoelectronic control of surface charge and translocation dynamics in solid-state nanopores. Nat. Nanotechnol. 8, 946–951 (2013).
Graf, M. et al. Light-enhanced blue energy generation using MoS2 nanopores. Joule 3, 1549–1564 (2019).
Xie, B. et al. Perspective on nanofluidic memristors: from mechanism to application. Chem. Asian J. 17, e202200682 (2022).
Yu, L. et al. Bioinspired nanofluidic iontronics for brain-like computing. Nano Res. 17, 503–514 (2023).
Noy, A. & Darling, S. B. Nanofluidic computing makes a splash. Science 379, 143–144 (2023).
Robin, P. & Bocquet, L. Nanofluidics at the crossroads. J. Chem. Phys. 158, 160901 (2023).
Sheridan, P., Ma, W. & Lu, W. Pattern recognition with memristor networks. In 2014 IEEE International Symp. Circuits and Systems (ISCAS) 1078–1081 (2014).
Li, C. et al. Analogue signal and image processing with large memristor crossbars. Nat. Electron. 1, 52–59 (2018).
Wang, D. et al. Transmembrane potential across single conical nanopores and resulting memristive and memcapacitive ion transport. J. Am. Chem. Soc. 134, 3651–3654 (2012).
Najem, J. S. et al. Memristive ion channel-doped biomembranes as synaptic mimics. ACS Nano 12, 4702–4711 (2018).
Bu, Y., Ahmed, Z. & Yobas, L. A nanofluidic memristor based on ion concentration polarization. Analyst 144, 7168–7172 (2019).
Zhang, P. et al. Nanochannel-based transport in an interfacial memristor can emulate the analog weight modulation of synapses. Nano Lett. 19, 4279–4286 (2019).
Kumar, M. & Stone, H. A. Membrane science emerging as a convergent scientific field with molecular origins and understanding, and global impact. Proc. Natl Acad. Sci. USA 118, e2106494118 (2021).
Pendse, A. et al. Highly efficient osmotic energy harvesting in charged boron-nitride-nanopore membranes. Adv. Funct. Mater. 31, 2009586 (2021).
Gao, J. et al. Understanding the giant gap between single-pore- and membrane-based nanofluidic osmotic power generators. Small 15, 1804279 (2019).
Di Vincenzo, M. et al. Tunable membranes incorporating artificial water channels for high-performance brackish/low-salinity water reverse osmosis desalination. Proc. Natl Acad. Sci. USA 118, e2022200118 (2021).
Wen, Q. et al. Electric-field-induced ionic sieving at planar graphene oxide heterojunctions for miniaturized water desalination. Adv. Mater. 32, 1903954 (2020).
Huang, S. et al. Millisecond lattice gasification for high-density CO2- and O2-sieving nanopores in single-layer graphene. Sci. Adv. 7, eabf0116 (2021).
Yang, Y. et al. Large-area graphene-nanomesh/carbon-nanotube hybrid membranes for ionic and molecular nanofiltration. Science 364, 1057–1062 (2019).
Huang, S. et al. Single-layer graphene membranes by crack-free transfer for gas mixture separation. Nat. Commun. 9, 2632 (2018).
Kumar, M., Habel, J. E. O., Shen, Y., Meier, W. P. & Walz, T. High-density reconstitution of functional water channels into vesicular and planar block copolymer membranes. J. Am. Chem. Soc. 134, 18631–18637 (2012).
Tu, Y.-M. et al. Rapid fabrication of precise high-throughput filters from membrane protein nanosheets. Nat. Mater. 19, 347–354 (2020).
Shen, Y. et al. Achieving high permeability and enhanced selectivity for Angstrom-scale separations using artificial water channel membranes. Nat. Commun. 9, 2294 (2018).
Zhang, Z. et al. Vertically transported graphene oxide for high-performance osmotic energy conversion. Adv. Sci. 7, 2000286 (2020).
Ghanbari, H. & Esfandiar, A. Ion transport through graphene oxide fibers as promising candidate for blue energy harvesting. Carbon 165, 267–274 (2020).
Yang, F. et al. Vertical iontronic energy storage based on osmotic effects and electrode redox reactions. Nat. Energy 9, 263–271 (2024).
Wang, L., Wang, Z., Patel, S. K., Lin, S. & Elimelech, M. Nanopore-based power generation from salinity gradient: why it is not viable. ACS Nano 15, 4093–4107 (2021).
Loessberg-Zahl, J. et al. Exploring voltage mediated delamination of suspended 2D materials as a cause of commonly observed breakdown. J. Phys. Chem. C 124, 430–435 (2020).
Macha, M., Thakur, M., Radenovic, A. & Marion, S. Stress induced delamination of suspended MoS2 in aqueous environments. Phys. Chem. Chem. Phys. 24, 19948–19955 (2022).
Heerema, S. J. et al. Probing DNA translocations with inplane current signals in a graphene nanoribbon with a nanopore. ACS Nano 12, 2623–2633 (2018).
Zhao, Y. et al. Plasmonic bowl-shaped nanopore for Raman detection of single DNA molecules in flow-through. Nano Lett. 23, 4830–4836 (2023).
Chou, I.-H. et al. Nanofluidic biosensing for β-amyloid detection using surface enhanced Raman spectroscopy. Nano Lett. 8, 1729–1735 (2008).
Wu, Z. F. et al. Proton and molecular permeation through the basal plane of monolayer graphene oxide. Nat. Commun. 14, 7756 (2023).
Prakash, M. & Gershenfeld, N. Microfluidic bubble logic. Science 315, 832–835 (2007).
Zhou, X. et al. Nanofluidic memristor by elastic deformation of nanopores with nanoparticles adsorption. Natl Sci. Rev. 11, nwad216 (2023).
McCutcheon, J. R. & Mauter, M. S. Fixing the desalination membrane pipeline. Science 380, 242–244 (2023).
Wang, L. et al. Water transport in reverse osmosis membranes is governed by pore flow, not a solution-diffusion mechanism. Sci. Adv. 9, eadf8488 (2023).
Villalobos, L. F., Babu, D. J., Hsu, K.-J., Van Goethem, C. & Agrawal, K. V. Gas separation membranes with atom-thick nanopores: the potential of nanoporous single-layer graphene. Acc. Mater. Res. 3, 1073–1087 (2022).
Wang, Y., Zhao, Y., Bollas, A., Wang, Y. & Au, K. F. Nanopore sequencing technology, bioinformatics and applications. Nat. Biotechnol. 39, 1348–1365 (2021).
Manrao, E. A. et al. Reading DNA at single-nucleotide resolution with a mutant MspA nanopore and phi29 DNA polymerase. Nat. Biotechnol. 30, 349–353 (2012).
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Contributions
Introduction (T.E., N.R., K.V.A., S.G., M.K., A.N. and A.R.); Experimentation (T.E., N.R., K.V.A., S.G., M.K., A.N. and A.R.); Results (T.E., N.R., K.V.A., S.G., M.K., A.N. and A.R.); Applications (T.E., N.R., K.V.A., S.G., M.K., A.N. and A.R.); Reproducibility and data deposition (T.E., N.R., K.V.A., S.G., M.K., A.N. and A.R.); Limitations and optimizations (T.E., N.R., K.V.A., S.G., M.K., A.N. and A.R.); Outlook (T.E., N.R., K.V.A., S.G., M.K., A.N. and A.R.); Overview of the Primer (all authors).
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Nature Reviews Methods Primers thanks Nikita Kavokine and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Aquaporin-based biomimetic membranes: http://www.aquatechtrade.com/news/water-treatment/aquaporin-turns-to-pou-and-public-listing
DNA sequencing: https://nanoporetech.com/about-us/news/oxford-nanopore-announces-breakthrough-performance-simplex-single-molecule-accuracy
Ion channel library: https://www.ionchannellibrary.com/ion-channel-software/
Glossary
- Ångström-scale pores
-
Pores with dimensions on the order of ångström (10−10 m) achieved through atomically precise fabrication methods.
- Confinement
-
Restriction of fluid motion and behaviour within small-scale channels or pores, leading to unique phenomena and effects owing to the proximity of surfaces.
- Electro-osmotic flow
-
Liquid motion driven by an applied electric field, occurring at charged solid–liquid walls.
- Landau–Squire jet
-
A submerged jet coming from a point source into an infinite volume of fluid of the same kind.
- Osmotic flow
-
Liquid motion driven by a solute concentration gradient.
- Osmotic ion current
-
Ion current driven by a concentration gradient.
- Reactive ion etching
-
A process used to pattern surfaces at the nanoscale by bombarding them with energetic ions in a reactive gas environment, commonly used in nanofluidic device fabrication to create precise structures.
- Slip length
-
Imaginary extent of the liquid flow velocity profile extrapolation within the solid wall. A positive slip length means that the liquid velocity at the wall surface is non-zero.
- Streaming ion current
-
Ion current driven by a pressure gradient, which drives counter-ions in the Debye layer.
- van der Waals assembly
-
Stacking of 2D materials by deterministic or stochastic transfer processes. The resulting multilayer heterostructures are held together by van der Waals interactions.
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Emmerich, T., Ronceray, N., Agrawal, K.V. et al. Nanofluidics. Nat Rev Methods Primers 4, 69 (2024). https://doi.org/10.1038/s43586-024-00344-0
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DOI: https://doi.org/10.1038/s43586-024-00344-0
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