DNA Sequencer

I just read this paper and found that this DNA sequencing technology has been so advance.

GENOMICS: Cheap third-generation sequencing, Nicole Rusk, Nature Methods 6, 244 (2009).
By covalently attaching cyclodextrin to a hemolysin nanopore, researchers show single-molecule, label-free sequencing at very high accuracy.

1st generation sequencers: What's this? Applied Biosystems' (ABI) 370s (such as Prism3700)?
This article "Genome Sequencer Industry Evolution" has talked about it.

2nd generation sequencers:
Illumina/Solexa's Genome Analyzer (Illumina, Inc., San Diego, CA, USA)

Roche's 454 sequencer (454 Life Sciences, Branford, CT, USA) (ps. All text and images below are cited from 454 Life Sciences' Sequencing Chemistry)
454 Sequencing, based on sequencing-by-synthesis (Figure 1), is the power behind the performance of the Genome Sequencer FLX System.

Figure 1: Sequencing reaction of the Genome Sequencer System. Millions of copies of a single clonal fragment are contained on each DNA Capture Bead.

Each 10 hour sequencing run on the GS FLX Titanium series will typically produce over one million flowgrams, one flowgram per read. (Figure 2)

Figure 2: GS FLX System Image processing overview.

Applied Biosystems's SOLiD (Applied Biosystems Inc., Foster City, CA, USA) (ps. below images are cited from Overview of SOLiD™ Sequencing Chemistry)






3rd generation sequencers:
Helicos's Single Molecule Sequencer (Helicos BioSciences Corporation, Cambridge, MA, USA)

Pacific Biosciences's Single Molecule Real Time (SMRT) technology (Pacific Biosciences, Menlo Park, CA, USA) (ps. below texts and images are cited from Pacific Biosciences' SMRT™ TECHNOLOGY)

Figure 1. Problem of background interference. For proper functioning, DNA polymerase requires a high concentration of labeled nucleotides, which creates a fluorescent background thousands of times brighter than the signal of a single incorporation event.

Figure 6. ZMW with DNA polymerase and phospholink nucleotides. Phospholink nucleotides are added into the ZMW at the high concentrations required by the enzyme.

Figure 12. Continuous and simultaneous excitation and detection. Both excitation and detection occur without interruption through the transparent glass bottom of the SMRT™ chip.

Figure 14. Generation of sequence data. Enzymatic incorporation of the labeled nucleotide creates a flash of light, which is converted into a base call using optimized algorithms

Oxford Nanopore's nanopore sequencing:
Continuous base identification for single-molecule nanopore DNA sequencing, James Clarke, Hai-Chen Wu, Lakmal Jayasinghe, Alpesh Patel, Stuart Reid & Hagan Bayley, Nature Nanotechnology (Published online: 22 February 2009 | doi:10.1038/nnano.2009.12).