Voltage-Driven DNA Translocations through a Nanopore

Meller, A.; Nivón, Lucas G.; Branton, Daniel

doi:10.1103/physrevlett.86.3435

Cited by 860 publications

(1,042 citation statements)

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“…They also found that the rate of entry is higher when the DNA enters the channel through the protein's larger vestibule rather than through the other end. Meller and co-workers [7] also studied this particular system in the presence of a voltage difference along the channel. They found that the translocation speed of long ssDNA strands, i.e., longer than the channel, is independent of the polymer length.…”

Section: Nanopore Technologiesmentioning

confidence: 99%

Theory of DNA electrophoresis (∼ 1999 –2002 ½)

et al. 2002

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Over the last two decades, the introduction of new methods such as pulsed-field gel electrophoresis and capillary array electrophoresis has made it possible to map and sequence entire genomes, including our own. The development of these experimental methods has been helped by the progress of theoretical and computational sciences, and the interactions between these three modi operandi of modern science are still pushing the limits of our technologies. We now see a clear trend towards proteomics and microfluidic (even nanofluidic!) devices. In this review, we take a look at the progress of the field over the last 3 years using the glasses of the theoretical scientist and focusing mostly on new ideas and concepts. About a dozen different subfields are discussed and reviewed. We conclude by giving a commented list of some of the best review articles published over the last 2-3 years.

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Section: Nanopore Technologiesmentioning

confidence: 99%

Theory of DNA electrophoresis (∼ 1999 –2002 ½)

et al. 2002

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“…Detailed insight has been gained from studies on pores of known molecular structure and the electrophoretically-driven movement of individual DNA and RNA strands. 3,11,21,23,[28][29][30] Several biophysical parameters have been determined such as threading frequency, [31][32][33][34] orientation of strands, [35][36][37][38][39] velocity of DNA transport, 40 influence of pore geometry, 41 and interactions with the pore wall. 39 In addition to nucleic acids, translocation has also been investigated for peptides, [42][43][44][45] proteins, [46][47][48] and peptide-oligonucleotide conjugates, 49 which, unlike nucleic acid strands, frequently feature inhomogeneous charge distributions and vary considerably in diameter along the polymer sequence.…”

Section: Introductionmentioning

confidence: 99%

Disentangling Steric and Electrostatic Factors in Nanoscale Transport Through Confined Space

et al. 2013

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The voltage-driven passage of biological polymers through nanoscale pores is an analytically, technologically, and biologically relevant process. Despite various studies on homopolymer translocation there are still several open questions on the fundamental aspects of the pore transport. One of the most important unresolved issues revolves around the passage of biopolymers which vary in charge and volume along their sequence. Here we exploit an experimentally tunable system to disentangle and quantify electrostatic and steric factors. This new, fundamental framework facilitates the understanding of how complex biopolymers are transported through confined space and indicates how biopolymer translocation can be slowed down to enable future sensing methods.SYNOPSIS: The voltage-driven translocation of complex biopolymers through a protein nanopore is biophysically modeled to disentangle and quantify electrostatic and steric factors which can oppose electrophoretic movement.

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“…[1][2] Subsequently, the pioneering studies of the use of R-hemolysin protein pore within a lipid bilayer for the translocation of single strands of DNA molecules using a voltage bias across the membranes sparked tremendous interest in such single molecule sensors. [3][4][5][6][7][8] The normal ionic current through the protein pore in a lipid bilayer would detectably reduce as a polyanionic chain of ssDNA molecules traversed through the pore, even allowing the distinction between polycytosine and polyadenine molecules, thus demonstrating the potential of single base discrimination in these sensors. 4,5 Despite these advantages, robust integration of these biological sensors within practical devices is quite problematic, and a mechanical pore 9,10 provides numerous advantages over biological pores.…”

mentioning

confidence: 99%

“…Recent reports of the use of ion milling 7 and transmission electron beam imaging 15,16 with real time feedback to form controlled pore size have paved the way to begin the exploration of single DNA molecule translocations and conformational studies using artificial pores. The electronic signature of dsDNA moving through these nanopores can be quite complex and the conformational changes in the molecule cannot be ignored, as shown recently by Li et al 9 One possibility to suppress signatures due to conformational changes is to increase the entropic energy barrier for molecules to enter the nanopore by the use of "channels" with nanoscale diameters.…”

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confidence: 99%

DNA-Mediated Fluctuations in Ionic Current through Silicon Oxide Nanopore Channels

et al. 2004

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Single molecule sensors in which nanoscale pores within biological or artificial membranes act as mechanical gating elements are very promising devices for the rapid characterization and sequencing of nucleic acid molecules. The two terminal electrical measurements of translocation of polymers through single ion channels and that of ssDNA molecules through protein channels have been demonstrated, and have sparked tremendous interest in such single molecule sensors. The prevailing view regarding the nanopore sensors is that there exists no electrical interaction between the nanopore and the translocating molecule, and that all nanopore sensors reported to-date, whether biological or artificial, operate as a coulter-counter, i.e., the ionic current measured across the pore decreases (is mechanically blocked) when the DNA molecule transverses through the pore. We have fabricated nanopore "channel" sensors with a silicon oxide inner surface, and our results challenge the prevailing view of exclusive mechanical interaction during the translocation of dsDNA molecules through these channels. We demonstrate that the ionic current can actually increase due to electrical gating of surface current in the channel due to the charge on the DNA itself.As a first step toward the ultimate goal of single-molecule DNA sequencing using nanopore sensors, one must first identify the key mechanical and electrical variables that control the translocation of the molecules through the nanopores. First, a nanopore used for characterization and sequencing of a single molecule must have a diameter of less than the persistence length (∼50 nm for dsDNA) to avoid any signal averaging from thermally induced conformational changes. Second, the pores must be chemically stable and mechanically robust under a wide variety of conditions of use. Third, and finally, the mechanical and electrical interaction between the nanopores and the single molecules must be well characterized. Toward this end, the electrical detection of translocation of polymers through single ion channels has been demonstrated. 1-2 Subsequently, the pioneering studies of the use of R-hemolysin protein pore within a lipid bilayer for the translocation of single strands of DNA molecules using a voltage bias across the membranes sparked tremendous interest in such single molecule sensors. [3][4][5][6][7][8] The normal ionic current through the protein pore in a lipid bilayer would detectably reduce as a polyanionic chain of ssDNA molecules traversed through the pore, even allowing the distinction between polycytosine and polyadenine molecules, thus demonstrating the potential of single base discrimination in these sensors. 4,5 Despite these advantages, robust integration of these biological sensors within practical devices is quite problematic, and a mechanical pore 9,10 provides numerous advantages over biological pores. Besides the obvious advantages of being able to drastically change ambient conditions such as pH, electric field, and temperature without distorting the s...

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Voltage-Driven DNA Translocations through a Nanopore

Cited by 860 publications

References 14 publications

Theory of DNA electrophoresis (∼ 1999 –2002 ½)

Theory of DNA electrophoresis (∼ 1999 –2002 ½)

Disentangling Steric and Electrostatic Factors in Nanoscale Transport Through Confined Space

DNA-Mediated Fluctuations in Ionic Current through Silicon Oxide Nanopore Channels

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