Label-free histamine detection with nanofluidic diodes through metal ion displacement mechanism

[EN] We design and characterize a nanofluidic device for the label-free specific detection of histamine neurotransmitter based on a metal ion displacement mechanism. The sensor consists of an asymmetric polymer nanopore fabricated via ion track-etching technique. The nanopore sensor surface having metal-nitrilotriacetic (NTA-Ni2+) chelates is obtained by covalent coupling of native carboxylic acid groups with N-alpha,N-alpha-bis(carboxymethyl)-L-lysine (BCML), followed by exposure to Ni2+ ion solution. The BCML immobilization and subsequent Ni2+ ion complexation with NTA moieties change the surface charge concentration, which has a significant impact on the current-voltage (I-V) curve after chemical modification of the nanopore. The sensing mechanism is based on the displacement of the metal ion from the NTA-Ni2+ chelates. When the modified pore is exposed to histamine solution, the Ni2+ ion in NTA-Ni2+ chelate recognizes histamine through a metal ion coordination displacement process and formation of stable Ni-histamine complexes, leading to the regeneration of metal-free NTA groups on the pore surface, as shown in the current-voltage characteristics. Nanomolar concentrations of the histamine in the working electrolyte can be detected. On the contrary, other neurotransmitters such as glycine, serotonin, gamma-aminobutyric acid, and dopamine do not provoke significant changes in the nanopore electronic signal due to their inability to displace the metal ion and form a stable complex with Ni2+ ion. The nanofluidic sensor exhibits high sensitivity, specificity and reusability towards histamine detection and can then be used to monitor the concentration of biological important neurotransmitters.M.A., I.D., S.N. and W.E. acknowledge the funding from the Hessen State Ministry of Higher Education, Research and the Arts, Germany, under the LOEWE project iNAPO. P. R. and S. M. acknowledge financial support by the Spanish Ministry of Economic Affairs and Competitiveness (MAT2015-65011-P) and FEDER. The authors are also thankful to Prof. C. Trautmann, Department of Materials Research from GSI, for support with irradiation experiments.Ali, M.; Ramirez Hoyos, P.; Duznovic, I.; Nasir, S.; Mafe, S.; Ensinger, W. (2017). Label-free histamine detection with nanofluidic diodes through metal ion displacement mechanism. Colloids and Surfaces B Biointerfaces. 150:201-208. https://doi.org/10.1016/j.colsurfb.2016.11.038S20120815

Tetraalkylammonium Cations Conduction through a Single Nanofluidic Diode: Experimental and Theoretical Studies

[EN] We describe experimentally and theoretically the concentration-dependent conduction of tetraalkylammonium (TAA+) cations through a nanofluidic diode fabricated in a polymer membrane via asymmetric track-etching techniques. This single-pore membrane exhibits current rectification characteristics because of the ionized carboxylate groups on the pore surface. We use aqueous solutions of potassium (K+ ), ammonium (A+ ), tetramethylammonium (TMA+ ), tetraethylammonium (TEA+ ), and tetrabutylammonium (TBA+ ) ions with concentrations ranging from 50 to 500 mM under acidic (pH 3.5) and physiological (pH 6.5) conditions. Compared with the K+ and A+ ions, the TMA+ , TEA+ , and TBA+ ions show relatively low rectified ion currents because the cation hydrophobicity increases with the alkyl chain. At low concentrations and acidic conditions, an inversion in the current rectification characteristics is observed, which is attributed to the adsorption of the organic cations on the pore surfaces. The experimental results can be analyzed in terms of the Poisson-Nernst-Planck equations and the geometrical and electrical single pore characteristics for the different ions, pH values, and salt concentrations employed. This theoretical approach is qualitative and could be extended further to include a self-consistent theoretical treatment of the ionic adsorption and surface charge equilibriaM. A., S. N., and W. E. acknowledge the funding from the Hessen State Ministry of Higher Education, Research and the Arts, Germany, under the LOEWE project iNAPO. P. R., J. C., and S. M. acknowledge financial support by the Spanish Ministry of Economic Affairs and Competitiveness (MAT2015-65011-P) and FEDER. The authors are also thankful to Prof. C. Trautmann, Department of Materials Research from GSI, for support with irradiation experiments.Ali, M.; Ramirez Hoyos, P.; Nasir, S.; Cervera Montesinos, J.; Mafe, S.; Ensinger, W. (2017). Tetraalkylammonium Cations Conduction through a Single Nanofluidic Diode: Experimental and Theoretical Studies. ELECTROCHIMICA ACTA. 250:302-308. https://doi.org/10.1016/j.electacta.2017.08.078S30230825

Electrical network of nanofluidic diodes in electrolyte solutions: Connectivity and coupling to electronic elements

[EN] We consider a nanopore network with simple connectivity, demonstrating a two-dimensional circuit (full-wave rectifier) with ensembles of conical pores acting as nanofluidic diodes. When the bridge nanopore network is fed with an input potential signal of fluctuating polarity, a fixed output polarity is obtained. The full-wave rectification characteristics are demonstrated with square, sinusoidal, and white noise input waveforms. The charging of a load capacitor located between the two legs of the bridge demonstrates that the nanofluidic network is effectively coupled to this electronic element. These results can be relevant for energy transduction and storage procedures with nanopores immersed in electrolyte solutions. Because the individual nanofluidic resistances can be modulated by chemical, electrical, and optical signals, the balanced bridge circuit can also be useful to miniaturize nanopore-based sensing devices. (c) 2015 Elsevier B.V. All rights reserved.We acknowledge the support from the Ministry of Economic Affairs and Competitiveness and FEDER (project MAT2015-65011-P) and 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, under the frame of LOEWE project iNAPO.Gómez Lozano, V.; Cervera, J.; Nasir, S.; Ali, M.; Ensinger, W.; Mafe, S.; Ramirez Hoyos, P. (2016). Electrical network of nanofluidic diodes in electrolyte solutions: Connectivity and coupling to electronic elements. Electrochemistry Communications. 62:29-33. https://doi.org/10.1016/j.elecom.2015.10.022S29336

Ionic transport through chemically functionalized hydrogen peroxide-sensitive asymmetric nanopores

We describe the fabrication of a chemical-sensitive nanofluidic device based on asymmetric nanopores whose transport characteristics can be modulated upon exposure to hydrogen peroxide (H2O2). We show experimentally and theoretically that the current-voltage curves provide a suitable method to monitor the H2O2-mediated change in pore surface characteristics from the electronic readouts. We demonstrate also that the single pore characteristics can be scaled to the case of a multipore membrane whose electric outputs can be readily controlled. Because H2O2 is an agent significant for medical diagnostics, the results should be useful for sensing nanofluidic devices.MA, S.N. and W.E. acknowledge the funding from the Hessen State Ministry of Higher Education, Research and the Arts, Germany, under the LOEWE project iNAPO. P.R and S.M. acknowledge the support from the Ministry of Economic Affairs and Competitiveness and FEDER (project MAT2012-32084) and the Generalitat Valenciana (project Prometeo/GV/0069 for Groups of Excellence). I.A. and C.M.N. acknowledge financial support through the Helmholtz programme Bio-Interfaces in Technology and Medicine. The authors are thankful to Prof. C. Trautmann, Department of Materials Research from GSI, for support with irradiation experiments.Ali, M.; Ahmed, I.; Nasir, S.; Ramirez Hoyos, P.; Niemeyer, CM.; Mafe, S.; Ensinger, W. (2015). Ionic transport through chemically functionalized hydrogen peroxide-sensitive asymmetric nanopores. ACS Applied Materials and Interfaces. 7(35):19541-19545. https://doi.org/10.1021/acsami.5b06015S195411954573

A redox-sensitive nanofluidic diode based on nicotinamide-modified asymmetric nanopores

[EN] We demonstrate a redox-sensitive nanofluidic diode whose ion rectification is modulated by the oxidation and reduction of chemical moieties incorporated on its surface. To achieve this goal, we have first synthesized the chemical compounds 1-(4-aminobutyl)-3-carbamoylpyridin-1-ium (Nic-BuNH2) and 3-carbamoyl-1-(2,4-dinitrophenyl)pyridinium (Nic-DNP). Then, the surface of track-etched single asymmetric nanopores is decorated with the redox-sensitive Nic-BuNH2 and Nic-DNP molecules using carbodiimide coupling chemistry and Zincke reaction, respectively. The success of the modification reactions is monitored through the changes in the current¿voltage (I¿V) curves prior to and after pore functionalization. Upon exposing the modified pore to solutions of hydrogen peroxide (oxidizing agent) and sodium dithionite (reducing agent) the surface charge is reversibly modulated from positive to neutral, leading to measurable changes in the electronic readout of ion current passing through the nanopore. On oxidation, the quaternary nicotinamide units impart positive charge to the pore surface, resulting in the ion current rectification (anion-selective pore). On the contrary, the complementary reduced dihydronicotinamide moieties resulted in the loss of surface charge and ohmic behaviour (non-selective pore). The experimental results are further theoretically described by using Poisson-Nernst-PlanckM.A., S.N. and W.E. acknowledge the funding from the Hessen State Ministry of Higher Education, Research and the Arts, Germany, under the LOEWE project iNAPO. P. R. and S. M. acknowledge financial support by the Generalitat Valenciana (Program of Excellence Prometeo/GV/0069), the Spanish Ministry of Economic Affairs and Competitiveness (MAT2015-65011-P), and FEDER. I.A. and C.M.N. acknowledge financial support through the Helmholtz programme BioInterfaces in Technology and Medicine. The authors are also thankful to Prof. C. Trautmann, Department of Materials Research from GSI, for support with irradiation experiments.Ali, M.; Ahmed, I.; Ramirez Hoyos, P.; Nasir, S.; Mafe, S.; Niemeyer, CM.; Ensinger, W. (2017). A redox-sensitive nanofluidic diode based on nicotinamide-modified asymmetric nanopores. Sensors and Actuators B Chemical. 240:895-902. https://doi.org/10.1016/j.snb.2016.09.061S89590224

Hybrid Circuits with Nanofluidic Diodes and Load Capacitors

[EN] The chemical and physical input signals characteristic of micro- and nanofluidic devices operating in ionic solutions should eventually be translated into output electric currents and potentials that are monitored with solid-state components. This crucial step requires the design of hybrid circuits showing robust electrical coupling between ionic solutions and electronic elements. We study experimentally and theoretically the connectivity of the nanofluidic diodes in single-pore and multipore membranes with conventional capacitor systems for the cases of constant, periodic, and white-noise input potentials. The experiments demonstrate the reliable operation of these hybrid circuits over a wide range of membrane resistances, electrical capacitances, and solution pH values. The model simulations are based on empirical equations that have a solid physical basis and provide a convenient description of the electrical circuit operation. The results should contribute to advance signal transduction and processing using nanoporebased biosensors and bioelectronic interfaces.We acknowledge the support from the Ministry of Economic Affairs and Competitiveness and FEDER (Project No. MAT2015-65011-P). M. A., S. N., and W. E. acknowledge the funding from the Hessen State Ministry of Higher Education, Research and the Arts, Germany, under the LOEWE project iNAPO.Ramirez Hoyos, P.; García-Morales, V.; Gómez Lozano, V.; Ali, M.; Nasir, S.; Ensinger, W.; Mafe, S. (2017). Hybrid Circuits with Nanofluidic Diodes and Load Capacitors. Physical Review Applied. 7(6):064035-1-064035-8. https://doi.org/10.1103/PhysRevApplied.7.064035S064035-1064035-876Tagliazucchi, 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.2014.10.020Liu, Q., Wen, L., Xiao, K., Lu, H., Zhang, Z., Xie, G., … Jiang, L. (2016). A Biomimetic Voltage-Gated Chloride Nanochannel. Advanced Materials, 28(16), 3181-3186. doi:10.1002/adma.201505250Ramirez, P., Cervera, J., Ali, M., Ensinger, W., & Mafe, S. (2014). Logic Functions with Stimuli-Responsive Single Nanopores. ChemElectroChem, 1(4), 698-705. doi:10.1002/celc.201300255Pérez-Mitta, G., Albesa, A. G., Trautmann, C., Toimil-Molares, M. E., & Azzaroni, O. (2017). Bioinspired integrated nanosystems based on solid-state nanopores: «iontronic» transduction of biological, chemical and physical stimuli. Chemical Science, 8(2), 890-913. doi:10.1039/c6sc04255dMisra, 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.0904850106Hou, Y., Vidu, R., & Stroeve, P. (2011). Solar Energy Storage Methods. Industrial & Engineering Chemistry Research, 50(15), 8954-8964. doi:10.1021/ie2003413Ramirez, P., Ali, M., Ensinger, W., & Mafe, S. (2012). Information processing with a single multifunctional nanofluidic diode. Applied Physics Letters, 101(13), 133108. doi:10.1063/1.4754845Gomez, 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/srep09501Verdia-Baguena, C., Gomez, V., Cervera, J., Ramirez, P., & Mafe, S. (2017). Energy transduction and signal averaging of fluctuating electric fields by a single protein ion channel. Physical Chemistry Chemical Physics, 19(1), 292-296. doi:10.1039/c6cp06035hYehezkeli, O., Tel-Vered, R., Wasserman, J., Trifonov, A., Michaeli, D., Nechushtai, R., & Willner, I. (2012). Integrated photosystem II-based photo-bioelectrochemical cells. Nature Communications, 3(1). doi:10.1038/ncomms1741Apel, P. (2001). Track etching technique in membrane technology. Radiation Measurements, 34(1-6), 559-566. doi:10.1016/s1350-4487(01)00228-1Ali, 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/nn900039fCervera, J., Ramirez, P., Gomez, V., Nasir, S., Ali, M., Ensinger, W., … Mafe, S. (2016). Multipore membranes with nanofluidic diodes allowing multifunctional rectification and logical responses. Applied Physics Letters, 108(25), 253701. doi:10.1063/1.4954764Gomez, V., Ramirez, P., Cervera, J., Nasir, S., Ali, M., Ensinger, W., & Mafe, S. (2015). Converting external potential fluctuations into nonzero time-average electric currents using a single nanopore. Applied Physics Letters, 106(7), 073701. doi:10.1063/1.4909532Kalman, E., Healy, K., & Siwy, Z. S. (2007). Tuning ion current rectification in asymmetric nanopores by signal mixing. Europhysics Letters (EPL), 78(2), 28002. doi:10.1209/0295-5075/78/28002Siwy, Z., Kosińska, I. D., Fuliński, A., & Martin, C. R. (2005). Asymmetric Diffusion through Synthetic Nanopores. Physical Review Letters, 94(4). doi:10.1103/physrevlett.94.048102Siwy, Z. S., & Howorka, S. (2010). Engineered voltage-responsive nanopores. Chem. Soc. Rev., 39(3), 1115-1132. doi:10.1039/b909105

Multipore membranes with nanofluidic diodes allowing multifunctional rectification and logical responses

[EN] We have arranged two multipore membranes with conical nanopores in a three-compartment electrochemical cell. The membranes act as tunable nanofluidic diodes whose functionality is entirely based on the pH-reversed ion current rectification and does not require specific surface functionalizations. This electrochemical arrangement can display different electrical behaviors (quasi-linear ohmic response and inward/outward rectifications) as a function of the electrolyte concentration in the external solutions and the applied voltage at the pore tips. The multifunctional response permits to implement different logical responses including NOR and INHIBIT functions.Support from the Ministry of Economic Affairs and Competitiveness and FEDER (Project No. MAT2015-65011-P) and the Generalitat Valenciana (Project Prometeo/GV/0069 for Groups of Excellence) is gratefully acknowledged. 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.Cervera, J.; Ramirez Hoyos, P.; Gómez Lozano, V.; Nasir, S.; Ali, M.; Ensinger, W.; Stroeve, P.... (2016). Multipore membranes with nanofluidic diodes allowing multifunctional rectification and logical responses. Applied Physics Letters. 108:253701-1-253701-5. https://doi.org/10.1063/1.4954764S253701-1253701-510

Nernst-Planck model of photo-triggered, pH-tunable ionic transport through nanopores functionalized with "caged" lysine chains

We describe the fabrication of asymmetric nanopores sensitive to ultraviolet (UV) light, and give a detailed account of the divalent ionic transport through these pores using a theoretical model based on the Nernst-Planck equations. The pore surface is decorated with lysine chains having pH-sensitive (amine and carboxylic acid) moieties that are caged with photo-labile 4,5-dimethoxy- 2-nitrobenzyl (NVOC) groups. The uncharged hydrophobic NVOC groups are removed using UV irradiation, leading to the generation of hydrophilic “uncaged” amphoteric groups on the pore surface. We demonstrate experimentally that polymer membranes containing single pore and arrays of asymmetric nanopores can be employed for the pH-controlled transport of ionic and molecular analytes. Comparison between theory and experiment allows for understanding the individual properties of the phototriggered nanopores, and provides also useful clues for the design and fabrication of multipore membranes to be used in practical applications. © 2013 American Institute of Physics.The authors would like to thank Miguel Ferrandez and Juan Pablo Arranz for assistance in the preparation of the artwork. P. R. and S. M. acknowledge financial support from the Ministerio de Economia y Competitividad (Projects Nos. MAT2009-07747 and MAT2012-32084), the Generalitat Valenciana (Project No. PROMETEO/GV/0069), and FEDER. S.N., M. A., and W. E. gratefully acknowledge financial support by the Beilstein-Institut, Frankfurt/Main, Germany, within the research collaboration NanoBiC, and L. F. and I. A. DFG-CFN Excellence Initiative Project A5.7. The authors thank Dr. Christina Trautmann from GSI (Materials research group) for support with the heavy ion irradiation experiments, and Dr. M. N. Tahir (Mainz University) for fruitful discussions and help in performing the UV light irradiation experiments.Nasir, S.; Ramirez Hoyos, P.; Ali, M.; Ahmed, I.; Fruk, L.; Mafé, S.; Ensinger, W. (2013). Nernst-Planck model of photo-triggered, pH-tunable ionic transport through nanopores functionalized with "caged" lysine chains. Journal of Chemical Physics. 138(3):034709-1-034709-11. doi:10.1063/1.4775811S034709-1034709-111383Healy, K. (2007). Nanopore-based single-molecule DNA analysis. Nanomedicine, 2(4), 459-481. doi:10.2217/17435889.2.4.459Griffiths, J. (2008). The Realm of the Nanopore. Analytical Chemistry, 80(1), 23-27. doi:10.1021/ac085995zJovanovic-Talisman, T., Tetenbaum-Novatt, J., McKenney, A. S., Zilman, A., Peters, R., Rout, M. P., & Chait, B. T. (2008). Artificial nanopores that mimic the transport selectivity of the nuclear pore complex. Nature, 457(7232), 1023-1027. doi:10.1038/nature07600Schoch, R. B., Han, J., & Renaud, P. (2008). Transport phenomena in nanofluidics. Reviews of Modern Physics, 80(3), 839-883. doi:10.1103/revmodphys.80.839Nam, S.-W., Rooks, M. J., Kim, K.-B., & Rossnagel, S. M. (2009). Ionic Field Effect Transistors with Sub-10 nm Multiple Nanopores. Nano Letters, 9(5), 2044-2048. doi:10.1021/nl900309sPerry, J. M., Zhou, K., Harms, Z. D., & Jacobson, S. C. (2010). Ion Transport in Nanofluidic Funnels. ACS Nano, 4(7), 3897-3902. doi:10.1021/nn100692zGuan, W., Fan, R., & Reed, M. A. (2011). Field-effect reconfigurable nanofluidic ionic diodes. Nature Communications, 2(1). doi:10.1038/ncomms1514Striemer, C. C., Gaborski, T. R., McGrath, J. L., & Fauchet, P. M. (2007). Charge- and size-based separation of macromolecules using ultrathin silicon membranes. Nature, 445(7129), 749-753. doi:10.1038/nature05532Van den Berg, A., & Wessling, M. (2007). Silicon for the perfect membrane. Nature, 445(7129), 726-726. doi:10.1038/445726aDekker, C. (2007). Solid-state nanopores. Nature Nanotechnology, 2(4), 209-215. doi:10.1038/nnano.2007.27Mager, M. D., & Melosh, N. A. (2008). Nanopore-Spanning Lipid Bilayers for Controlled Chemical Release. Advanced Materials, 20(23), 4423-4427. doi:10.1002/adma.200800969Apel, P. Y., Korchev, Y. ., Siwy, Z., Spohr, R., & Yoshida, M. (2001). Diode-like single-ion track membrane prepared by electro-stopping. Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 184(3), 337-346. doi:10.1016/s0168-583x(01)00722-4Siwy, Z., & Fuliński, A. (2002). Fabrication of a Synthetic Nanopore Ion Pump. Physical Review Letters, 89(19). doi:10.1103/physrevlett.89.198103Ramírez, P., Mafé, S., Aguilella, V. M., & Alcaraz, A. (2003). Synthetic nanopores with fixed charges: An electrodiffusion model for ionic transport. Physical Review E, 68(1). doi:10.1103/physreve.68.011910Siwy, Z., & Fuliński, A. (2004). A nanodevice for rectification and pumping ions. American Journal of Physics, 72(5), 567-574. doi:10.1119/1.1648328Siwy, Z., Kosińska, I. D., Fuliński, A., & Martin, C. R. (2005). Asymmetric Diffusion through Synthetic Nanopores. Physical Review Letters, 94(4). doi:10.1103/physrevlett.94.048102Powell, M. R., Sullivan, M., Vlassiouk, I., Constantin, D., Sudre, O., Martens, C. C., … Siwy, Z. S. (2007). Nanoprecipitation-assisted ion current oscillations. Nature Nanotechnology, 3(1), 51-57. doi:10.1038/nnano.2007.420García-Giménez, E., Alcaraz, A., Aguilella, V. M., & Ramírez, P. (2009). Directional ion selectivity in a biological nanopore with bipolar structure. Journal of Membrane Science, 331(1-2), 137-142. doi:10.1016/j.memsci.2009.01.026Hou, X., Zhang, H., & Jiang, L. (2012). Building Bio-Inspired Artificial Functional Nanochannels: From Symmetric to Asymmetric Modification. Angewandte Chemie International Edition, 51(22), 5296-5307. doi:10.1002/anie.201104904Harrell, C. C., Siwy, Z. S., & Martin, C. R. (2006). Conical Nanopore Membranes: Controlling the Nanopore Shape. Small, 2(2), 194-198. doi:10.1002/smll.200500196Apel, P. Y., Blonskaya, I. V., Dmitriev, S. N., Orelovitch, O. L., Presz, A., & Sartowska, B. A. (2007). Fabrication of nanopores in polymer foils with surfactant-controlled longitudinal profiles. Nanotechnology, 18(30), 305302. doi:10.1088/0957-4484/18/30/305302Apel, P. Y., Blonskaya, I. V., Orelovitch, O. L., Ramirez, P., & Sartowska, B. A. (2011). Effect of nanopore geometry on ion current rectification. Nanotechnology, 22(17), 175302. doi:10.1088/0957-4484/22/17/175302Ali, M., Ramirez, P., Nguyen, H. Q., Nasir, S., Cervera, J., Mafe, S., & Ensinger, W. (2012). Single Cigar-Shaped Nanopores Functionalized with Amphoteric Amino Acid Chains: Experimental and Theoretical Characterization. ACS Nano, 6(4), 3631-3640. doi:10.1021/nn3010119Kalman, E. B., Sudre, O., Vlassiouk, I., & Siwy, Z. S. (2008). Control of ionic transport through gated single conical nanopores. Analytical and Bioanalytical Chemistry, 394(2), 413-419. doi:10.1007/s00216-008-2545-3Mafe, S., Manzanares, J. A., & Ramirez, P. (2010). Gating of Nanopores: Modeling and Implementation of Logic Gates. The Journal of Physical Chemistry C, 114(49), 21287-21290. doi:10.1021/jp1087114Nasir, S., Ali, M., & Ensinger, W. (2012). Thermally controlled permeation of ionic molecules through synthetic nanopores functionalized with amine-terminated polymer brushes. Nanotechnology, 23(22), 225502. doi:10.1088/0957-4484/23/22/225502Guo, W., Xia, H., Cao, L., Xia, F., Wang, S., Zhang, G., … Zhu, D. (2010). Integrating Ionic Gate and Rectifier Within One Solid-State Nanopore via Modification with Dual-Responsive Copolymer Brushes. Advanced Functional Materials, 20(20), 3561-3567. doi:10.1002/adfm.201000989Ali, 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/nn900039fAli, M., Mafe, S., Ramirez, P., Neumann, R., & Ensinger, W. (2009). Logic Gates Using Nanofluidic Diodes Based on Conical Nanopores Functionalized with Polyprotic Acid Chains. Langmuir, 25(20), 11993-11997. doi:10.1021/la902792fHou, X., Liu, Y., Dong, H., Yang, F., Li, L., & Jiang, L. (2010). A pH-Gating Ionic Transport Nanodevice: Asymmetric Chemical Modification of Single Nanochannels. Advanced Materials, 22(22), 2440-2443. doi:10.1002/adma.200904268Hou, X., Guo, W., Xia, F., Nie, F.-Q., Dong, H., Tian, Y., … Jiang, L. (2009). A Biomimetic Potassium Responsive Nanochannel: G-Quadruplex DNA Conformational Switching in a Synthetic Nanopore. Journal of the American Chemical Society, 131(22), 7800-7805. doi:10.1021/ja901574cHe, Y., Gillespie, D., Boda, D., Vlassiouk, I., Eisenberg, R. S., & Siwy, Z. S. (2009). Tuning Transport Properties of Nanofluidic Devices with Local Charge Inversion. Journal of the American Chemical Society, 131(14), 5194-5202. doi:10.1021/ja808717uAli, M., Neumann, R., & Ensinger, W. (2010). Sequence-Specific Recognition of DNA Oligomer Using Peptide Nucleic Acid (PNA)-Modified Synthetic Ion Channels: PNA/DNA Hybridization in Nanoconfined Environment. ACS Nano, 4(12), 7267-7274. doi:10.1021/nn102119qAli, M., Tahir, M. N., Siwy, Z., Neumann, R., Tremel, W., & Ensinger, W. (2011). Hydrogen Peroxide Sensing with Horseradish Peroxidase-Modified Polymer Single Conical Nanochannels. Analytical Chemistry, 83(5), 1673-1680. doi:10.1021/ac102795aVlassiouk, I., & Siwy, Z. S. (2007). Nanofluidic Diode. Nano Letters, 7(3), 552-556. doi:10.1021/nl062924bKalman, E. B., Vlassiouk, I., & Siwy, Z. S. (2008). Nanofluidic Bipolar Transistors. Advanced Materials, 20(2), 293-297. doi:10.1002/adma.200701867Ali, M., Ramirez, P., Tahir, M. N., Mafe, S., Siwy, Z., Neumann, R., … Ensinger, W. (2011). Biomolecular conjugation inside synthetic polymer nanopores via glycoprotein–lectin interactions. Nanoscale, 3(4), 1894. doi:10.1039/c1nr00003aHou, X., Yang, F., Li, L., Song, Y., Jiang, L., & Zhu, D. (2010). A Biomimetic Asymmetric Responsive Single Nanochannel. Journal of the American Chemical Society, 132(33), 11736-11742. doi:10.1021/ja1045082Healy, K., Schiedt, B., & Morrison, A. P. (2007). Solid-state nanopore technologies for nanopore-based DNA analysis. Nanomedicine, 2(6), 875-897. doi:10.2217/17435889.2.6.875Martin, C. R., & Siwy, Z. S. (2007). CHEMISTRY: Learning Nature’s Way: Biosensing with Synthetic Nanopores. Science, 317(5836), 331-332. doi:10.1126/science.1146126Guo, W., Cao, L., Xia, J., Nie, F.-Q., Ma, W., Xue, J., … Jiang, L. (2010). Energy Harvesting with Single-Ion-Selective Nanopores: A Concentration-Gradient-Driven Nanofluidic Power Source. Advanced Functional Materials, 20(8), 1339-1344. doi:10.1002/adfm.200902312Cervera, J., Ramirez, P., Mafe, S., & Stroeve, P. (2011). Asymmetric nanopore rectification for ion pumping, electrical power generation, and information processing applications. Electrochimica Acta, 56(12), 4504-4511. doi:10.1016/j.electacta.2011.02.056Ramirez, P., Ali, M., Ensinger, W., & Mafe, S. (2012). Information processing with a single multifunctional nanofluidic diode. Applied Physics Letters, 101(13), 133108. doi:10.1063/1.4754845Jiang, Y., Liu, N., Guo, W., Xia, F., & Jiang, L. (2012). Highly-Efficient Gating of Solid-State Nanochannels by DNA Supersandwich Structure Containing ATP Aptamers: A Nanofluidic IMPLICATION Logic Device. Journal of the American Chemical Society, 134(37), 15395-15401. doi:10.1021/ja3053333Ali, 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.201102146Zhang, M., Hou, X., Wang, J., Tian, Y., Fan, X., Zhai, J., & Jiang, L. (2012). Light and pH Cooperative Nanofluidic Diode Using a Spiropyran-Functionalized Single Nanochannel. Advanced Materials, 24(18), 2424-2428. doi:10.1002/adma.201104536Ramírez, P., Apel, P. Y., Cervera, J., & Mafé, S. (2008). Pore structure and function of synthetic nanopores with fixed charges: tip shape and rectification properties. Nanotechnology, 19(31), 315707. doi:10.1088/0957-4484/19/31/315707Ali, M., Yameen, B., Cervera, J., Ramírez, P., Neumann, R., Ensinger, W., … Azzaroni, O. (2010). Layer-by-Layer Assembly of Polyelectrolytes into Ionic Current Rectifying Solid-State Nanopores: Insights from Theory and Experiment. Journal of the American Chemical Society, 132(24), 8338-8348. doi:10.1021/ja101014yYu Apel, P., Blonskaya, I. V., Orelovitch, O. L., Sartowska, B. A., & Spohr, R. (2012). Asymmetric ion track nanopores for sensor technology. Reconstruction of pore profile from conductometric measurements. Nanotechnology, 23(22), 225503. doi:10.1088/0957-4484/23/22/225503Li, N., Yu, S., Harrell, C. C., & Martin, C. R. (2004). Conical Nanopore Membranes. Preparation and Transport Properties. Analytical Chemistry, 76(7), 2025-2030. doi:10.1021/ac035402eHarrell, C. C., Kohli, P., Siwy, Z., & Martin, C. R. (2004). DNA−Nanotube Artificial Ion Channels. Journal of the American Chemical Society, 126(48), 15646-15647. doi:10.1021/ja044948vManzanares, J. A., Mafé, S., & Pellicer, J. (1992). Current efficiency enhancement in membranes with macroscopic inhomogeneities in the fixed charge distribution. J. Chem. Soc., Faraday Trans., 88(16), 2355-2364. doi:10.1039/ft9928802355MacGillivray, A. D. (1968). Nernst‐Planck Equations and the Electroneutrality and Donnan Equilibrium Assumptions. The Journal of Chemical Physics, 48(7), 2903-2907. doi:10.1063/1.1669549Rubinstein, I. (1990). Electro-Diffusion of Ions. doi:10.1137/1.9781611970814Kontturi, K., Murtomäki, L., & Manzanares, J. A. (2008). Ionic Transport Processes. doi:10.1093/acprof:oso/9780199533817.001.0001Burger, M. (2011). Inverse problems in ion channel modelling. Inverse Problems, 27(8), 083001. doi:10.1088/0266-5611/27/8/083001Burger, M., Eisenberg, R. S., & Engl, H. W. (2007). Inverse Problems Related to Ion Channel Selectivity. SIAM Journal on Applied Mathematics, 67(4), 960-989. doi:10.1137/060664689Cervera, J., Schiedt, B., & Ramírez, P. (2005). A Poisson/Nernst-Planck model for ionic transport through synthetic conical nanopores. Europhysics Letters (EPL), 71(1), 35-41. doi:10.1209/epl/i2005-10054-xCervera, 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:10.1063/1.2179797Cervera, J., Alcaraz, A., Schiedt, B., Neumann, R., & Ramírez, P. (2007). Asymmetric Selectivity of Synthetic Conical Nanopores Probed by Reversal Potential Measurements. The Journal of Physical Chemistry C, 111(33), 12265-12273. doi:10.1021/jp071884cLee, S. B., & Martin, C. R. (2001). pH-Switchable, Ion-Permselective Gold Nanotubule Membrane Based on Chemisorbed Cysteine. Analytical Chemistry, 73(4), 768-775. doi:10.1021/ac0008901Pellicer, J., Mafé, S., & Aguilella, V. M. (1986). Ionic Transport Across Porous Charged Membranes and the Goldman Constant Field Assumption. Berichte der Bunsengesellschaft für physikalische Chemie, 90(10), 867-872. doi:10.1002/bbpc.19860901008LAKSHMINARAYANAIAH, N. (1984). ELECTRICAL POTENTIALS ACROSS MEMBRANES. Equations of Membrane Biophysics, 129-164. doi:10.1016/b978-0-12-434260-6.50007-2Cervera, J., Ramírez, P., Manzanares, J. A., & Mafé, S. (2009). Incorporating ionic size in the transport equations for charged nanopores. Microfluidics and Nanofluidics, 9(1), 41-53. doi:10.1007/s10404-009-0518-2Wang, G., Bohaty, A. K., Zharov, I., & White, H. S. (2006). Photon Gated Transport at the Glass Nanopore Electrode. Journal of the American Chemical Society, 128(41), 13553-13558. doi:10.1021/ja064274jEisenberg, R. S. (1996). Computing the Field in Proteins and Channels. Journal of Membrane Biology, 150(1), 1-25. doi:10.1007/s00232990002

Size‐Based Cationic Molecular Sieving through Solid‐State Nanochannels

The molecular sieving behavior of soft‐etched polyimide membranes having negatively charged nanochannels is described experimentally and theoretically using alkali metal–crown ether cationic complexes and alkylammonium cations. To this end, the electrical conduction and current rectification obtained with different alkali electrolyte solutions (LiCl, NaCl, and KCl) and crown ether molecules (12‐crown‐4, 15‐crown‐5, and 18‐crown‐6) are studied. The results suggest that only the [Li(12C4)]⁺ complex can readily permeate through the nanochannels because significant current decreases are obtained in the cases of the [Na(15C5)]⁺ and [K(18C6)]⁺ complexes. In solutions of organic cations ranging from ammonium (NH₄⁺) to alkylammonium (R₄N⁺) with increasing molecular size, only the smaller ions can conduct high electric currents, suggesting again that the membrane channels are in the nanometer range. Taken together, the observed current decreases and rectification phenomena demonstrate that the functionalized membranes allow a versatile combination of molecular and electrostatic sieving

Protein diffusion through charged nanopores with different radii at low ionic strength

[EN] The diffusion of two similar molecular weight proteins, bovine serum albumin (BSA) and bovine haemoglobin (BHb), through nanoporous charged membranes with a wide range of pore radii is studied at low ionic strength. The effects of the solution pH and the membrane pore diameter on the pore permeability allow quantifying the electrostatic interaction between the chargedpore and the protein. Because of the large screening Debye length, both surface and bulk diffusion occur simultaneously. By increasing the pore diameter, the permeability tends to the bulk self-diffusion coefficient for each protein. By decreasing the pore diameter, the charges on the pore surface electrostatically hinder the transport even at the isoelectric point of the protein. Surprisingly, even at pore sizes 100 times larger than the protein, the electrostatic hindrance still plays a major role in the transport. The experimental data are qualitatively explained using a two-region model for the membrane pore and approximated equations for the pH dependence of the protein and pore charges. The experimental and theoretical results should be useful for designing protein separation processes based on nanoporous charged membranes.This work was supported by a grant from the University of California Office of the President UCOP Lab Fee Program. P.R. and S.M. acknowledge the financial support from the Ministry of Economy and Competitiveness of Spain and FEDER (project PROMAT2012-32084) and the Generalitat Valenciana (project PROMETEO/GV/0069). We thank Mr Victor Awad and Mr Linh Doan for laboratory assistance. We also thank an anonymous referee for valuable comments.Stroeve, P.; Rahman, M.; Naidu, LD.; Chu, G.; Mahmoudi, M.; Ramirez Hoyos, P.; Mafé, S. (2014). Protein diffusion through charged nanopores with different radii at low ionic strength. Physical Chemistry Chemical Physics. 16(39):21570-21576. https://doi.org/10.1039/c4cp03198aS21570215761639Pujar, N. S., & Zydney, A. L. (1998). Electrostatic effects on protein partitioning in size-exclusion chromatography and membrane ultrafiltration. Journal of Chromatography A, 796(2), 229-238. doi:10.1016/s0021-9673(97)01003-0Chun, K.-Y., Mafé, S., Ramírez, P., & Stroeve, P. (2006). Protein transport through gold-coated, charged nanopores: Effects of applied voltage. Chemical Physics Letters, 418(4-6), 561-564. doi:10.1016/j.cplett.2005.11.029Ileri, N., Faller, R., Palazoglu, A., Létant, S. E., Tringe, J. W., & Stroeve, P. (2013). Molecular transport of proteins through nanoporous membranes fabricated by interferometric lithography. Phys. Chem. Chem. Phys., 15(3), 965-971. doi:10.1039/c2cp43400hBurns, D. B., & Zydney, A. L. (2001). Contributions to electrostatic interactions on protein transport in membrane systems. AIChE Journal, 47(5), 1101-1114. doi:10.1002/aic.690470517Chun, K.-Y., & Stroeve, P. (2002). Protein Transport in Nanoporous Membranes Modified with Self-Assembled Monolayers of Functionalized Thiols. Langmuir, 18(12), 4653-4658. doi:10.1021/la011250bOsmanbeyoglu, H. U., Hur, T. B., & Kim, H. K. (2009). Thin alumina nanoporous membranes for similar size biomolecule separation. Journal of Membrane Science, 343(1-2), 1-6. doi:10.1016/j.memsci.2009.07.027Tanford, C., & Buzzell, J. G. (1956). The Viscosity of Aqueous Solutions of Bovine Serum Albumin between pH 4.3 and 10.5. The Journal of Physical Chemistry, 60(2), 225-231. doi:10.1021/j150536a020Stroeve, P., & Ileri, N. (2011). Biotechnical and other applications of nanoporous membranes. Trends in Biotechnology, 29(6), 259-266. doi:10.1016/j.tibtech.2011.02.002Ho, C.-C., & Zydney, A. L. (2001). Protein Fouling of Asymmetric and Composite Microfiltration Membranes. Industrial & Engineering Chemistry Research, 40(5), 1412-1421. doi:10.1021/ie000810jKu, J.-R., & Stroeve, P. (2004). Protein Diffusion in Charged Nanotubes:  «On−Off» Behavior of Molecular Transport. Langmuir, 20(5), 2030-2032. doi:10.1021/la0357662Yu, S., Lee, S. B., Kang, M., & Martin, C. R. (2001). Size-Based Protein Separations in Poly(ethylene glycol)-Derivatized Gold Nanotubule Membranes. Nano Letters, 1(9), 495-498. doi:10.1021/nl010044lYu, S., Lee, S. B., & Martin, C. R. (2003). Electrophoretic Protein Transport in Gold Nanotube Membranes. Analytical Chemistry, 75(6), 1239-1244. doi:10.1021/ac020711aHou, Z., Abbott, N. L., & Stroeve, P. (2000). Self-Assembled Monolayers on Electroless Gold Impart pH-Responsive Transport of Ions in Porous Membranes. Langmuir, 16(5), 2401-2404. doi:10.1021/la991045kBöhme, U., & Scheler, U. (2007). Effective charge of bovine serum albumin determined by electrophoresis NMR. Chemical Physics Letters, 435(4-6), 342-345. doi:10.1016/j.cplett.2006.12.068Beretta, S., Chirico, G., Arosio, D., & Baldini, G. (1997). Role of Ionic Strength on Hemoglobin Interparticle Interactions and Subunit Dissociation from Light Scattering. Macromolecules, 30(25), 7849-7855. doi:10.1021/ma971137lGaigalas, A. K., Hubbard, J. B., McCurley, M., & Woo, S. (1992). Diffusion of bovine serum albumin in aqueous solutions. The Journal of Physical Chemistry, 96(5), 2355-2359. doi:10.1021/j100184a063LaGattuta, K. J., Sharma, V. S., Nicoli, D. F., & Kothari, B. K. (1981). Diffusion coefficients of hemoglobin by intensity fluctuation spectroscopy: effects of varying pH and ionic strength. Biophysical Journal, 33(1), 63-79. doi:10.1016/s0006-3495(81)84872-2Mafé, S., Manzanares, J. A., & Ramirez, P. (2003). Modeling of surface vs. bulk ionic conductivity in fixed charge membranes. Phys. Chem. Chem. Phys., 5(2), 376-383. doi:10.1039/b209438jBiesheuvel, P. M., Stroeve, P., & Barneveld, P. A. (2004). Effect of Protein Adsorption and Ionic Strength on the Equilibrium Partition Coefficient of Ionizable Macromolecules in Charged Nanopores. The Journal of Physical Chemistry B, 108(45), 17660-17665. doi:10.1021/jp047913qBiesheuvel, P. M., & Wittemann, A. (2005). A Modified Box Model Including Charge Regulation for Protein Adsorption in a Spherical Polyelectrolyte Brush. The Journal of Physical Chemistry B, 109(9), 4209-4214. doi:10.1021/jp0452812Keesom, W. ., Zelenka, R. ., & Radke, C. . (1988). A zeta-potential model for ionic surfactant adsorption on an ionogenic hydrophobic surface. Journal of Colloid and Interface Science, 125(2), 575-585. doi:10.1016/0021-9797(88)90024-0G. B. Benedek and F. M. H.Villars , Physics with illustrative examples from Medicine and Biology (Statistical Physics) , Springer-Verlag , Heidelberg , 2000Arosio, D., Kwansa, H. E., Gering, H., Piszczek, G., & Bucci, E. (2001). Static and dynamic light scattering approach to the hydration of hemoglobin and its supertetramers in the presence of osmolites. Biopolymers, 63(1), 1-11. doi:10.1002/bip.1057Axelsson, I. (1978). Characterization of proteins and other macromolecules by agarose gel chromatography. Journal of Chromatography A, 152(1), 21-32. doi:10.1016/s0021-9673(00)85330-3Beck, R. E., & Schultz, J. S. (1970). Hindered Diffusion in Microporous Membranes with Known Pore Geometry. Science, 170(3964), 1302-1305. doi:10.1126/science.170.3964.1302Burns, D. B., & Zydney, A. L. (1999). Effect of solution pH on protein transport through ultrafiltration membranes. Biotechnology and Bioengineering, 64(1), 27-37. doi:10.1002/(sici)1097-0290(19990705)64:13.0.co;2-eSchoch, R. B., Bertsch, A., & Renaud, P. (2006). pH-Controlled Diffusion of Proteins with Different pI Values Across a Nanochannel on a Chip. Nano Letters, 6(3), 543-547. doi:10.1021/nl052372hDurand, N. F. Y., Dellagiacoma, C., Goetschmann, R., Bertsch, A., Märki, I., Lasser, T., & Renaud, P. (2009). Direct Observation of Transitions between Surface-Dominated and Bulk Diffusion Regimes in Nanochannels. Analytical Chemistry, 81(13), 5407-5412. doi:10.1021/ac900617bRohani, M. M., & Zydney, A. L. (2010). Role of electrostatic interactions during protein ultrafiltration. Advances in Colloid and Interface Science, 160(1-2), 40-48. doi:10.1016/j.cis.2010.07.002Rohani, M. M., & Zydney, A. L. (2009). Effect of surface charge distribution on protein transport through semipermeable ultrafiltration membranes. Journal of Membrane Science, 337(1-2), 324-331. doi:10.1016/j.memsci.2009.04.007Mafé, S., Manzanares, J. A., & Pellicer, J. (1990). On the introduction of the pore wall charge in the space-charge model for microporous membranes. Journal of Membrane Science, 51(1-2), 161-168. doi:10.1016/s0376-7388(00)80899-6Bosma, J. C., & Wesselingh, J. A. (1998). pH dependence of ion-exchange equilibrium of proteins. AIChE Journal, 44(11), 2399-2409. doi:10.1002/aic.690441108Shi, Q., Zhou, Y., & Sun, Y. (2008). Influence of pH and Ionic Strength on the Steric Mass-Action Model Parameters around the Isoelectric Point of Protein. Biotechnology Progress, 21(2), 516-523. doi:10.1021/bp049735oJönsson, B., & Ståhlberg, J. (1999). The electrostatic interaction between a charged sphere and an oppositely charged planar surface and its application to protein adsorption. Colloids and Surfaces B: Biointerfaces, 14(1-4), 67-75. doi:10.1016/s0927-7765(99)00025-9Brenner, H., & Gaydos, L. J. (1977). The constrained brownian movement of spherical particles in cylindrical pores of comparable radius. Journal of Colloid and Interface Science, 58(2), 312-356. doi:10.1016/0021-9797(77)90147-3Cannell, D. S., & Rondelez, F. (1980). Diffusion of Polystyrenes through Microporous Membranes. Macromolecules, 13(6), 1599-1602. doi:10.1021/ma60078a046Kuo, T.-C., Sloan, L. A., Sweedler, J. V., & Bohn, P. W. (2001). Manipulating Molecular Transport through Nanoporous Membranes by Control of Electrokinetic Flow:  Effect of Surface Charge Density and Debye Length. Langmuir, 17(20), 6298-6303. doi:10.1021/la010429jAPEL, P., BLONSKAYA, I., DMITRIEV, S., ORELOVITCH, O., & SARTOWSKA, B. (2006). Structure of polycarbonate track-etch membranes: Origin of the «paradoxical» pore shape. Journal of Membrane Science, 282(1-2), 393-400. doi:10.1016/j.memsci.2006.05.04