Nanopore sensors for nucleic acid analysis

Nakane, Jonathan; Akeson, Mark; Marziali, Andre

doi:10.1088/0953-8984/15/32/203

Cited by 113 publications

(95 citation statements)

References 103 publications

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“…Currents as a function of time for a poly(dC) 15 translocating through a nanopore. Blue (red) curve indicates the current, for a bias of 1 V, between the right and left (front and back) electrodes represented in gray in the snapshots (the fourth electrode is located behind the field of view and is hence not visible in the snapshots).…”

Section: Figmentioning

confidence: 99%

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Fast DNA Sequencing via Transverse Electronic Transport

2006

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A rapid and low-cost method to sequence DNA would usher in a revolution in medicine. We propose and theoretically show the feasibility of a protocol for sequencing based on the distributions of transverse electrical currents of single-stranded DNA while it translocates through a nanopore. Our estimates, based on the statistics of these distributions, reveal that sequencing of an entire human genome could be done with very high accuracy in a matter of hours without parallelization, e.g., orders of magnitude faster than present techniques. The practical implementation of our approach would represent a substantial advancement in our ability to study, predict and cure diseases from the perspective of the genetic makeup of each individual.Recent innovations in manufacturing processes have made it possible to fabricate devices with pores at the nanometer scale [1][2][3][4][5], i.e., the scale of individual nucleotides. This opens up fascinating new venues for sequencing DNA. For instance, one suggested method is to measure the so called blockade current [6][7][8][9][10][11][12][13][14][15][16][17][18][19]. In this method, a longitudinal electric field is applied to pull DNA through a pore. As the DNA goes through, a significant fraction of ions is blocked from simultaneously entering the pore. By continuously measuring the ionic current, single molecules of DNA can be detected. Other methods using different detection schemes, ranging from optical [20] to capacitive [21], have also been suggested. Despite much effort, however, single nucleotide resolution has not yet been achieved [22].In this Letter, we explore an alternative idea which would allow single-base resolution by measuring the electrical current perpendicular to the DNA backbone while a single strand immersed in a solution translocates through a pore. To do this, we envision embedding electrodes in the walls of a nanopore as schematically shown in the inset of Figure 1. The realization of such a configuration, while difficult to achieve in practice, is within reach of present experimental capabilities [1][2][3][4][5]. The DNA is sequenced by using the measured current as an electronic signature of the bases as they pass through the pore. We couple molecular dynamics simulations and quantum mechanical current calculations to examine the feasibility of this approach. We find that if some control is exerted over the DNA dynamics, the distributions of current values for each nucleotide will be sufficiently different to allow for rapid sequencing. We show that a transverse field of the same magnitude as that driving the current provides sufficient control.We first discuss an idealized case of DNA dynamics which sets the foundations for the approach we describe. Second, we look at the distributions of transverse currents through the nucleotides in a realistic setting using a combination of quantum-mechanical calculations of current and molecular dynamics simulations of DNA translocation through the pore. We use a Green's function method to calculate the c...

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Section: Figmentioning

confidence: 99%

“…This opens up fascinating new venues for sequencing DNA. For instance, one suggested method is to measure the so called blockade current [6][7][8][9][10][11][12][13][14][15][16][17][18][19]. In this method, a longitudinal electric field is applied to pull DNA through a pore.…”

Section: Introductionmentioning

confidence: 99%

Fast DNA Sequencing via Transverse Electronic Transport

2006

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“…This will hybridize to the DNA sticking out of the nanopore and prevent the DNA from leaving. This nice trick can be used to prolong the presence of molecules in the nanopores and notably allows even the massive parallelization of nanopore sensing as was demonstrated by Marziali et al [44][45][46]. In a very similar way, the dumbbell approach was used by the Ghadiri group to detect the incorporation of single bases into DNA by a polymerase [47,48].…”

Section: Modification Of the Translocating Moleculementioning

confidence: 99%

Controlling molecular transport through nanopores

Keyser

2011

J. R. Soc. Interface.

173

191

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Nanopores are emerging as powerful tools for the detection and identification of macromolecules in aqueous solution. In this review, we discuss the recent development of active and passive controls over molecular transport through nanopores with emphasis on biosensing applications. We give an overview of the solutions developed to enhance the sensitivity and specificity of the resistive-pulse technique based on biological and solid-state nanopores.

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“…Proteins translocation through endoplasmic reticulum or organelles like mitochondria are also some other important instances Alberts et al (2002); Muthukumar (2007); Rapoport (2007). Drug delivery, gene therapy and fast cheap sequencing are some of its significant applications in biotechnology Marzio and Kasianowicz (2003); Nakane et al (2003); Branton et al (2008); Cohen et al (2012); Fanzio et al (2012); Carson and Wanunu (2015); Liang and Zhang (2015). After the study of Bezrukov et al on counting polyethylene oxide molecules using an alamethicin ion channel Bezrukov et al (1994) and seminal experimental work of Kasianowicz et al Kasianowicz et al (1996) on ssRNA translocation through an α-hemolysin channel embedded in a bilayer, there has been flurry of theoretical works, experiments and simulations in the field Meller (2003); Panja et al (2013); Sun and Luo (2014); Palyulin et al (2014).…”

Section: Introductionmentioning

confidence: 99%

Chaperone-driven polymer translocation through nanopore: Spatial distribution and binding energy

Abdolvahab

2017

Eur. Phys. J. E

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Chaperones are binding proteins which work as a driving force to bias the biopolymer translocation by binding to it near the pore and preventing its backsliding. Chaperones may have different spatial distribution. Recently we show the importance of their spatial distribution in translocation and how it effects on sequence dependency of the translocation time. Here we focus on homopolymers and exponential distribution. As a result of the exponential distribution of chaperones, energy dependency of the translocation time will changed and one see a minimum in translocation time versus effective energy curve. The same trend can be seen in scaling exponent of time versus polymer length, β (T ∼ β). Interestingly in some special cases e.g. chaperones of size λ = 6 and with exponential distribution rate of α = 5, the minimum reaches even to amount of less than 1 (β < 1). We explain the possibility of this rare result and base on a theoretical discussion we show that by taking into account the velocity dependency of the translocation on polymer length, one could truly predict the amount of this minimum.

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Nanopore sensors for nucleic acid analysis

Cited by 113 publications

References 103 publications

Fast DNA Sequencing via Transverse Electronic Transport

Fast DNA Sequencing via Transverse Electronic Transport

Controlling molecular transport through nanopores

Chaperone-driven polymer translocation through nanopore: Spatial distribution and binding energy

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