Rapid nanopore discrimination between single polynucleotide molecules.

By Amit Meller, L. Nivón, E. Brandin, J. Golovchenko, D. Branton. Proceedings of the National Academy of Sciences of the United States of America, 2000

867 citations recorded by the source corpus.

A variety of different DNA polymers were electrophoretically driven through the nanopore of an alpha-hemolysin channel in a lipid bilayer. Single-channel recording of the translocation duration and current flow during traversal of individual polynucleotides yielded a unique pattern of events for each of the several polymers tested. Statistical data derived from this pattern of events demonstrate that in several cases a nanopore can distinguish between polynucleotides of similar length and composition that differ only in sequence. Studies of temperature effects on the translocation process show that translocation duration scales as approximately T(-2). A strong correlation exists between the temperature dependence of the event characteristics and the tendency of some polymers to form secondary structure. Because nanopores can rapidly discriminate and characterize unlabeled DNA molecules at low copy number, refinements of the experimental approach demonstrated here could eventually provide a low-cost high-throughput method of analyzing DNA polynucleotides.

Subfields: Biomedical Engineering, Computational Mechanics

View Paper: https://www.semanticscholar.org/paper/f04bbdccd4736b92bdc91cf1fe99f4a08a408239

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Citations in the corpus

Nanopore sequencing technology, bioinformatics and applications (2021, background): “1,9 ), was the first nanopore shown to detect recognizable ionic current blockades by both RNA and DNA homopolymers 10–12 .”
Solid-state nanopores. (2007, background): “Translocation appears to be a thermally activated process as indicated by an exponential temperature dependence of the translocation tim”
Nanopore-based Fourth-generation DNA Sequencing Technology (2015, neutral): “The optimization of experimental physical conditions is also useful to control the DNA translocation rate, including reducing the voltage [3], decreasing the solution temperature [75], increasing the viscosity [75,95], and increasing the salt concentration [64].”
Characteristics of solid-state nanometre pores fabricated using a transmission electron microscope (2007, methodology): “…single-stranded DNA and RNA molecules can be electrophoretically threaded through the pore, and that the ion current flowing through the pore contains information on the biopolymer sequence, its type, length and secondary structure (Kasianowicz et al 1996, Akeson et al 1999, Meller et al 2000).”
Three decades of nanopore sequencing (2016, background): “This accounted for the earlier puzzling observation that samples containing only one type of polynucleotide consistently produced two types of blockades 6,8 .”
Sequence-specific detection of individual DNA strands using engineered nanopores (2001, background): “The accompanying change in the ionic current flowing through the pore has allowed discrimination between homo or block polymers with different base composition”