Nanopores and Nanochannels: From Gene Sequencing to Genome Mapping

DNA strands can be analyzed at the single-molecule level by isolating them inside nanoscale holes. The strategy is used for the label-free and portable sequencing with nanopores. Nanochannels can also be applied to map genomes with high resolution, as shown by Jeffet et al. in this issue of ACS Nano. Here, we compare the two strategies in terms of biophysical similarities and differences and describe that both are complementary and can improve the DNA analysis for genomic research and diagnostics

Rectification in synthetic conical nanopores: a one-dimensional Poisson-Nernst-Planck modeling

Ion transport in biological and synthetic nanochannels is characterized by phenomena such as ion current fluctuations and rectification. Recently, it has been demonstrated that nanofabricated synthetic pores can mimic transport properties of biological ion channels [P. Yu. Apel, {\it et al.}, Nucl. Instr. Meth. B {\bf 184}, 337 (2001); Z. Siwy, {\it et al.}, Europhys. Lett. {\bf 60}, 349 (2002)]. Here, the ion current rectification is studied within a reduced 1D Poisson-Nernst-Planck (PNP) model of synthetic nanopores. A conical channel of a few $\mathrm{nm}$ to a few hundred of nm in diameter, and of few $\mu$m long is considered in the limit where the channel length considerably exceeds the Debye screening length. The rigid channel wall is assumed to be weakly charged. A one-dimensional reduction of the three-dimensional problem in terms of corresponding entropic effects is put forward. The ion transport is described by the non-equilibrium steady-state solution of the 1D Poisson-Nernst-Planck system within a singular perturbation treatment. An analytic formula for the approximate rectification current in the lowest order perturbation theory is derived. A detailed comparison between numerical results and the singular perturbation theory is presented. The crucial importance of the asymmetry in the potential jumps at the pore ends on the rectification effect is demonstrated. This so constructed 1D theory is shown to describe well the experimental data in the regime of small-to-moderate electric currents.Comment: 27 pages, 7 figure

Correlation studies of open and closed states fluctuations in an ion channel: Analysis of ion current through a large conductance locust potassium channel

Ion current fluctuations occurring within open and closed states of large conductance locust potassium channel (BK channel) were investigated for the existence of correlation. Both time series, extracted from the ion current signal, were studied by the autocorrelation function (AFA) and the detrended fluctuation analysis (DFA) methods. The persistent character of the short- and middle-range correlations of time series is shown by the slow decay of the autocorrelation function. The DFA exponent $\alpha$ is significantly larger than 0.5. The existence of strongly-persistent long-range correlations was detected only for closed-states fluctuations, with $\alpha=0.98\pm0.02$. The long-range correlation of the BK channel action is therefore determined by the character of closed states. The main outcome of this study is that the memory effect is present not only between successive conducting states of the channel but also independently within the open and closed states themselves. As the ion current fluctuations give information about the dynamics of the channel protein, our results point to the correlated character of the protein movement regardless whether the channel is in its open or closed state.Comment: 12 pages, 5 figures; to be published in Phys. Rev.

Voltage-controlled current loops with nanofluidic diodes electrically coupled to solid state capacitors

[EN] We describe experimentally and theoretically voltage-controlled current loops obtained with nanofluidic diodes immersed in aqueous salt solutions. The coupling of these soft matter diodes with conventional electronic elements such as capacitors permits simple equivalent circuits which show electrical properties reminiscent of a resistor with memory. Different conductance levels can be reproducibly achieved under a wide range of experimental conditions (input voltage amplitudes and frequencies, load capacitances, electrolyte concentrations, and single pore and multipore membranes) by electrically coupling two types of passive components: the nanopores (ionics) and the capacitors (electronics). Remarkably, these electrical characteristics do not result from slow ionic redistributions within the nanopores, which should be difficult to control and would give only small conductance changes, but arise from the robust collective response of equivalent circuits. Coupling nanoscale diodes with conventional electronic elements allows interconverting ionic and electronic currents, which should be useful for electrochemical signal processing and energy conversion based on charge transport.Support from the Ministry of Economic Affairs and Competitiveness and FEDER (project MAT2015-65011-P), the Generalitat Valenciana (project Prometeo/GV/0069 for Groups of Excellence). M. A, S. N. and W. E acknowledge the funding from the Hessen State Ministry of Higher Education, Research and the Arts, Germany, in the frame of LOEWE project iNAPO. Z. S. acknowledges the funding from the National Science Foundation (CHE 1306058).Ramirez Hoyos, P.; Gómez Lozano, V.; Cervera, J.; Nasir, S.; Ali, M.; Ensinger, W.; Siwy, Z.... (2016). Voltage-controlled current loops with nanofluidic diodes electrically coupled to solid state capacitors. RSC Advances. 6(60):54742-54746. https://doi.org/10.1039/c6ra08277gS5474254746660Fologea, D., Krueger, E., Mazur, Y. 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Fundamental studies and practical applications of bio-inspired smart solid-state nanopores and nanochannels. Nano Today, 11(1), 61-81. doi:10.1016/j.nantod.2015.11.001Chun, H., & Chung, T. D. (2015). Iontronics. Annual Review of Analytical Chemistry, 8(1), 441-462. doi:10.1146/annurev-anchem-071114-040202Tagliazucchi, M., & Szleifer, I. (2015). Transport mechanisms in nanopores and nanochannels: can we mimic nature? Materials Today, 18(3), 131-142. doi:10.1016/j.mattod.2014.10.020Misra, N., Martinez, J. A., Huang, S.-C. J., Wang, Y., Stroeve, P., Grigoropoulos, C. P., & Noy, A. (2009). Bioelectronic silicon nanowire devices using functional membrane proteins. Proceedings of the National Academy of Sciences, 106(33), 13780-13784. doi:10.1073/pnas.0904850106Senapati, S., Basuray, S., Slouka, Z., Cheng, L.-J., & Chang, H.-C. (2011). A Nanomembrane-Based Nucleic Acid Sensing Platform for Portable Diagnostics. Topics in Current Chemistry, 153-169. doi:10.1007/128_2011_142Haywood, D. G., Saha-Shah, A., Baker, L. A., & Jacobson, S. C. (2014). Fundamental Studies of Nanofluidics: Nanopores, Nanochannels, and Nanopipets. Analytical Chemistry, 87(1), 172-187. doi:10.1021/ac504180hPérez-Mitta, G., Tuninetti, J. S., Knoll, W., Trautmann, C., Toimil-Molares, M. E., & Azzaroni, O. (2015). Polydopamine Meets Solid-State Nanopores: A Bioinspired Integrative Surface Chemistry Approach To Tailor the Functional Properties of Nanofluidic Diodes. Journal of the American Chemical Society, 137(18), 6011-6017. doi:10.1021/jacs.5b01638Ali, M., Nasir, S., Ramirez, P., Ahmed, I., Nguyen, Q. H., Fruk, L., … Ensinger, W. (2011). Optical Gating of Photosensitive Synthetic Ion Channels. Advanced Functional Materials, 22(2), 390-396. doi:10.1002/adfm.201102146Ali, M., Nasir, S., Ramirez, P., Cervera, J., Mafe, S., & Ensinger, W. (2013). Carbohydrate-Mediated Biomolecular Recognition and Gating of Synthetic Ion Channels. The Journal of Physical Chemistry C, 117(35), 18234-18242. doi:10.1021/jp4054555Ali, M., Ahmed, I., Nasir, S., Ramirez, P., Niemeyer, C. M., Mafe, S., & Ensinger, W. (2015). Ionic Transport through Chemically Functionalized Hydrogen Peroxide-Sensitive Asymmetric Nanopores. ACS Applied Materials & Interfaces, 7(35), 19541-19545. doi:10.1021/acsami.5b06015Albrecht, T. (2011). How to Understand and Interpret Current Flow in Nanopore/Electrode Devices. ACS Nano, 5(8), 6714-6725. doi:10.1021/nn202253zLemay, S. G. (2009). Nanopore-Based Biosensors: The Interface between Ionics and Electronics. ACS Nano, 3(4), 775-779. doi:10.1021/nn900336jGomez, V., Ramirez, P., Cervera, J., Nasir, S., Ali, M., Ensinger, W., & Mafe, S. (2015). Charging a Capacitor from an External Fluctuating Potential using a Single Conical Nanopore. Scientific Reports, 5(1). doi:10.1038/srep09501Ramirez, P., Gomez, V., Cervera, J., Nasir, S., Ali, M., Ensinger, W., & Mafe, S. (2015). Energy conversion from external fluctuating signals based on asymmetric nanopores. Nano Energy, 16, 375-382. doi:10.1016/j.nanoen.2015.07.013Tybrandt, K., Forchheimer, R., & Berggren, M. (2012). Logic gates based on ion transistors. Nature Communications, 3(1). doi:10.1038/ncomms1869Apel, P. (2001). Track etching technique in membrane technology. Radiation Measurements, 34(1-6), 559-566. doi:10.1016/s1350-4487(01)00228-1Cervera, J., Schiedt, B., Neumann, R., Mafé, S., & Ramírez, P. (2006). Ionic conduction, rectification, and selectivity in single conical nanopores. The Journal of Chemical Physics, 124(10), 104706. doi:10.1063/1.2179797Ali, M., Ramirez, P., Mafé, S., Neumann, R., & Ensinger, W. (2009). A pH-Tunable Nanofluidic Diode with a Broad Range of Rectifying Properties. ACS Nano, 3(3), 603-608. doi:10.1021/nn900039fRamirez, P., Gomez, V., Verdia-Baguena, C., Nasir, S., Ali, M., Ensinger, W., & Mafe, S. (2016). Designing voltage multipliers with nanofluidic diodes immersed in aqueous salt solutions. Physical Chemistry Chemical Physics, 18(5), 3995-3999. doi:10.1039/c5cp07203dWang, D., Kvetny, M., Liu, J., Brown, W., Li, Y., & Wang, G. (2012). Transmembrane Potential across Single Conical Nanopores and Resulting Memristive and Memcapacitive Ion Transport. Journal of the American Chemical Society, 134(8), 3651-3654. doi:10.1021/ja211142eMomotenko, D., & Girault, H. H. (2011). Scan-Rate-Dependent Ion Current Rectification and Rectification Inversion in Charged Conical Nanopores. Journal of the American Chemical Society, 133(37), 14496-14499. doi:10.1021/ja2048368Zhang, A., & Lieber, C. M. (2015). Nano-Bioelectronics. Chemical Reviews, 116(1), 215-257. doi:10.1021/acs.chemrev.5b0060

Local solid-state modification of nanopore surface charges

The last decade, nanopores have emerged as a new and interesting tool for the study of biological macromolecules like proteins and DNA. While biological pores, especially alpha-hemolysin, have been promising for the detection of DNA, their poor chemical stability limits their use. For this reason, researchers are trying to mimic their behaviour using more stable, solid-state nanopores. The most successful tools to fabricate such nanopores use high energy electron or ions beams to drill or reshape holes in very thin membranes. While the resolution of these methods can be very good, they require tools that are not commonly available and tend to damage and charge the nanopore surface. In this work, we show nanopores that have been fabricated using standard micromachning techniques together with EBID, and present a simple model that is used to estimate the surface charge. The results show that EBID with a silicon oxide precursor can be used to tune the nanopore surface and that the surface charge is stable over a wide range of concentrations.Comment: 10 pages, 6 figure

Exact formula for currents in strongly pumped diffusive systems

We analyze a generic model of mesoscopic machines driven by the nonadiabatic variation of external parameters. We derive a formula for the probability current; as a consequence we obtain a no-pumping theorem for cyclic processes satisfying detailed balance and demonstrate that the rectification of current requires broken spatial symmetry.Comment: 10 pages, accepted for publication in the Journal of Statistical Physic

Charging a Capacitor from an External Fluctuating Potential using a Single Conical Nanopore

We explore the electrical rectification of large amplitude fluctuating signals by an asymmetric nanostructure operating in aqueous solution. We show experimentally and theoretically that a load capacitor can be charged to voltages close to 1 V within a few minutes by converting zero time-average potentials of amplitudes in the range 0.5–3 V into average net currents using a single conical nanopore. This process suggests that significant energy conversion and storage from an electrically fluctuating environment is feasible with a nanoscale pore immersed in a liquid electrolyte solution, a system characteristic of bioelectronics interfaces, electrochemical cells, and nanoporous membranes.We acknowledge the support from the Ministry of Economic Affairs and Competitiveness and FEDER (project MAT2012-32084) and the Generalitat Valenciana (project Prometeo/GV/0069).Gómez Lozano, V.; Ramirez Hoyos, P.; Cervera Montesinos, J.; Nasir, S.; Ali, M.; Ensinger, W.; Mafé, S. (2015). Charging a Capacitor from an External Fluctuating Potential using a Single Conical Nanopore. Scientific Reports. 5(9501):1-5. https://doi.org/10.1038/srep09501S1559501Astumian, R. D. Stochastic conformational pumping: A mechanism for free-energy transduction by molecules. Annu. Rev. Biophys. 40, 289–313 (2011).Qian, H. Cooperativity in cellular biochemical processes: Noise-enhanced sensitivity, fluctuating enzyme, bistability with nonlinear feedback and other mechanisms for sigmoidal responses. Annu. Rev. Biophys. 41, 179–204 (2012).Hille, B. Ionic Channels of Excitable Membranes (Sinauer Associates Inc., Sunderland, MA, 1992).Levin, M. Molecular bioelectricity in developmental biology: new tools and recent discoveries: control of cell behavior and pattern formation by transmembrane potential gradients. Bioessays 34, 205–217 (2012).Queralt-Martín, M. et al. Electrical pumping of potassium ions against an external concentration gradient in a biological ion channel. Appl. Phys. Lett. 103, 043707 (2013).Hudspeth, A. J., Choe, Y., Mehta, A. D. & Martin, P. Putting ion channels to work: Mechanoelectrical transduction, adaptation and amplification by hair cells. Proc. Nat. Acad. Sci. U.S.A. 97, 11765–11772 (2000).Siwy, Z. & Fuliński, A. Fabrication of a Synthetic Nanopore Ion Pump. Phys. Rev. Lett. 89, 198103 (2002).Siwy, Z. & Fuliński, A. A nanodevice for rectification and pumping ions. Am. J. Phys. 72, 567–574 (2004).Ramirez, P., Gomez, V., Ali, M., Ensinger, W. & Mafe, S. Net currents obtained from zero-average potentials in single amphoteric nanopores. Electrochem. Commun. 31, 137–140 (2013).Ali, M. et al. Current rectification by nanoparticle blocking in single cylindrical nanopores. Appl. Phys. Lett. 104, 043703 (2014).Misra, N. et al. Bioelectronic silicon nanowire devices using functional membrane proteins. Proc. Natl. Acad. Sci. U.S.A. 106, 13780–13784 (2009).Ramirez, P., Ali, M., Ensinger, W. & Mafe, S. Information processing with a single multifunctional nanofluidic diode. Appl. Phys. Lett. 101, 133108 (2012).Hou, Y., Vidu, R. & Stroeve, P. Solar energy storage methods. Ind. Eng. Chem. Res. 50, 8954–8964 (2011).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).Cervera, J., Ramirez, P., Mafe, S. & Stroeve, P. Asymmetric nanopore rectification for ion pumping, electrical power generation and information processing applications. Electrochim. Acta, 56, 4504–4511 (2011).Tybrandt, K., Forchheimer, R. & Berggren, M. Logic gates based on ion transistors. Nat. Commun., 3, 871 (2012)Apel, P. Track etching technique in membrane technology. Radiat. Meas. 34, 559–566 (2001).Ali, M., Ramirez, P., Mafe, S., Neumann, R. & Ensinger, W. A pH-tunable nanofluidic diode with a broad range of rectifying properties. ACS Nano 3, 603–608 (2009).Albrecht, T. How to Understand and Interpret Current Flow in Nanopore/Electrode Devices. ACS Nano 5, 6714–6725 (2011).Ali, M. et al. Carbohydrate-Mediated Biomolecular Recognition and Gating of Synthetic Ion Channels. J. Phys. Chem. C 117, 18234–18242 (2013)

Noise Properties of Rectifying Nanopores

Ion currents through three types of rectifying nanoporous structures are studied and compared for the first time: conically shaped polymer nanopores, glass nanopipettes, and silicon nitride nanopores. Time signals of ion currents are analyzed by power spectrum. We focus on the low-frequency range where the power spectrum magnitude scales with frequency, f, as 1/f. Glass nanopipettes and polymer nanopores exhibit non-equilibrium 1/f noise, thus the normalized power spectrum depends on the voltage polarity and magnitude. In contrast, 1/f noise in rectifying silicon nitride nanopores is of equilibrium character. Various mechanisms underlying the voltage-dependent 1/f noise are explored and discussed, including intrinsic pore wall dynamics, and formation of vortices and non-linear flow patterns in the pore. Experimental data are supported by modeling of ion currents based on the coupled Poisson-Nernst-Planck and Navier Stokes equations. We conclude that the voltage-dependent 1/f noise observed in polymer and glass asymmetric nanopores might result from high and asymmetric electric fields inducing secondary effects in the pore such as enhanced water dissociation

Dynamic Control of Nanoprecipitation in a Nanopipette

Studying the earliest stages of precipitation at the nanoscale is technically challenging but quite valuable as such phenomena reflect important processes such as crystallization and biomineralization. Using a quartz nanopipette as a nanoreactor, we induced precipitation of an insoluble salt to generate oscillating current blockades. The reversible process can be used to measure both kinetics of precipitation and relative size of the resulting nanoparticles. Counter ions for the highly water-insoluble salt zinc phosphate were separated by the pore of a nanopipette and a potential applied to cause ion migration to the interface. By analyzing the kinetics of pore blockage, two distinct mechanisms were identified: a slower process due to precipitation from solution, and a faster process attributed to voltage-driven migration of a trapped precipitate. We discuss the potential of these techniques in studying precipitation dynamics, trapping particles within a nanoreactor, and electrical sensors based on nanoprecipitation

Pores with Longitudinal Irregularities Distinguish Objects by Shape

The resistive-pulse technique has been used to detect and size objects which pass through a single pore. The amplitude of the ion current change observed when a particle is in the pore is correlated with the particle volume. Up to date, however, the resistive-pulse approach has not been able to distinguish between objects of similar volume but different shapes. In this manuscript, we propose using pores with longitudinal irregularities as a sensitive tool capable of distinguishing spherical and rod-shaped particles with different lengths. The ion current modulations within resulting resistive pulses carry information on the length of passing objects. The performed experiments also indicate the rods rotate while translocating, and displace an effective volume that is larger than their geometrical volume, and which also depends on the pore diameter