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Review
. 2011 Jun 15;83(12):4327-41.
doi: 10.1021/ac2010857. Epub 2011 May 25.

Landscape of next-generation sequencing technologies

Thomas P Niedringhaus  1 , Denitsa Milanova, Matthew B Kerby, Michael P Snyder, Annelise E Barron
Affiliations
Review

Landscape of next-generation sequencing technologies

Thomas P Niedringhaus et al. Anal Chem. .
No abstract available

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Figures

Figure 1
Figure 1
Estimated cost required to sequence a complete human genome based on data generated from NHGRI-funded large-scale DNA sequencing centers.
Figure 2
Figure 2
Schematic of PacBio’s real-time single molecule sequencing. (A) The side view of a single ZMW nanostructure containing a single DNA polymerase (Φ29) bound to the bottom glass surface. The ZMW and the confocal imaging system allow fluorescence detection only at the bottom surface of each ZMW. (B) Representation of fluorescently labeled nucleotide substrate incorporation on to a sequencing template. The corresponding temporal fluorescence detection with respect to each of the five incorporation steps is shown below. Reprinted with permission from ref . Copyright 2009 American Association for the Advancement of Science.
Figure 3
Figure 3
Schematic of Complete Genomics’ DNB array generation and cPAL technology. (A) Design of sequencing fragments, subsequent DNB synthesis, and dimensions of the patterned nanoarray used to localize DNBs illustrate the DNB array formation. (B) Illustration of sequencing with a set of common probes corresponding to 5 bases from the distinct adapter site. Both standard and extended anchor schemes are shown. Reprinted with permission from ref . Copyright XXXX American Association for the Advancement of Science.
Figure 4
Figure 4
Layout of Ion Torrent’s semiconductor sequencing chip technology. (A) A layer-by-layer view of the chip revealing the structural design. The top layer contains the individual DNA polymerization reaction wells, and the bottom two layers comprise the FET ion sensor. Each well has a corresponding FET detector that identifies a change in pH. (B) A side view of an individual reaction well depicting DNA polymerase incorporation of a repeat of two TTP nucleotides on a sequencing fragment. The hydrogen ions released during this process are detected by the FET below. Reprinted with permission from Ion Torrent (Wes Conrad).
Figure 5
Figure 5
Nanopore DNA sequencing using electronic measurements and optical readout as detection methods. (A) In electronic nanopore schemes, signal is obtained through ionic current, tunneling current, and voltage difference measurements. Each method must produce a characteristic signal to differentiate the four DNA bases. Reprinted with permission from ref . Copyright 2008 Annual Reviews. (B) In the optical readout nanopore design, each nucleotide is converted to a preset oligonucleotide sequence and hybridized with labeled markers that are detected during translocation of the DNA fragment through the nanopore. Reprinted from ref . Copyright 2010 American Chemical Society.
Figure 6
Figure 6
Biological nanopore scheme employed by Oxford Nanopore. (A) Schematic of αHL protein nanopore mutant depicting the positions of the cyclodextrin (at residue 135) and glutamines (at residue 139). (B) A detailed view of the β barrel of the mutant nanopore shows the locations of the arginines (at residue 113) and the cysteines. (C) Exonuclease sequencing: A processive enzyme is attached to the top of the nanopore to cleave single nucleotides from the target DNA strand and pass them through the nanopore. (D) A residual current-vs-time signal trace from an αHL protein nanopore that shows a clear discrimination between single bases (dGMP, dTMP, dAMP, and dCMP). (E) Strand sequencing: ssDNA is threaded through a protein nanopore and individual bases are identified, as the strand remains intact. Panels A, B, and D reprinted with permission from ref . Copyright 2009 Nature Publishing Group. Panels C and E reprinted with permission from Oxford Nanopore Technologies (Zoe McDougall).
Figure 7
Figure 7
Several synthetic nanopore sequencing device designs. (A) The device consists of 1–5 nm thick graphene membrane which is suspended in a Si chip coated with 5 µm SiO2 layer. It is placed in a PDMS cell with microfluidic channels on both sides of the chip. Reprinted from ref . Copyright 2010 American Chemical Society. (B) A nanopore (shown in the inset to the figure) is drilled through a graphene membrane, which is suspended in SiNx across a Si frame. The graphene membrane separates two ionic solutions and is in contact with Ag/AgCl electrodes. Reprinted with permission from ref . Copyright 2010 Nature Publishing Group. (C) IBM DNA transistor setup. A nanometer sized pore is fabricated using an electron beam. Electric field is created between the gated regions allowing for charge trapping. The substrate is composed of metal and dielectric regions, labeled with “M” and “D”, respectively. Reprinted with permission from IBM (Gustavo Stolovitzky). (D) HANS method adopted by NABsys for electronic readout of DNA fragments through solid-state nanopores. 6-mer oligonucleotide probes are hybridized to ssDNA fragments, and current-verses-time trace is detected. Reprinted with permission from NABsys (John Oliver).
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