Ion torrent sequencing: Bringing sensitivity to the next level

April 8, 2011

“Simplicity” is a keyword when it comes to Life Technologies latest DNA sequencing technology called “Ion torrent”. As the company announced on its homepage only “simplest sequencing chemistry” is used during the process of DNA sequencing. In nature when a new nucleotide is incorporated into the DNA a hydrogen ion is released in order to form a phosphodiester bond between the two new neighbours within the DNA macromolecular structure (Figure 1). On the other hand it should not be forgotten that “simplicity” is not the only keyword in this process. “Technology” is at least the second essential term describing ion torrent sequencing, since extremely small changes in the hydrogen ion concentration have to be detected.

Figure 1: Nucleotide incorporation by a polymerase. Every nucleotide incorporation releases an ion which in turn can be detected as a pH change associated with one of the nucleotides (A, T, G or C) that are supplied in consecutive order. This leads to sequence information of the leading and lagging strand (1).

A little number of hydrogen ions causes only small pH change per incorporated nucleotide, so the detecting technology must be quite refined and a little bit less trivial than the idea behind the original project (even though sequencing is performed in a massively parallel way so signals become stronger).  One of the smallest ever-constructed solid-state pH meters detects the ion caused pH change and converts the chemical into digital information. This centerpiece of the machine is in essence a semiconductor chip which holds 1.5 million sensors which are connected to one well each. Within those wells the single-stranded sample DNA strands are contained, one strand per well. Subsequent steps lead now to the synthesis of the complementary strand by adding one nucleotide type at a time in repeating cycles. Information about the changing hydrogen ion concentration (pH) is now connected with information when which nucleotide was inserted. Complete sequence information is thus available.

I am not an expert, but personally I think that this innovation will bring DNA sequencing to a next level by making this technology available to a wide array of professions and research fields. This seems probable since an Ion Torrent sequencer is priced at $50,000 which is only one tenth of the price of a conventional sequencer. The price per sequenced base, however, has to be considered also since the chip has to be disposed after usage (2). The people at Life Technologies expect that the prices for the chips will drop eventually with each machine that is sold. The future is thus becoming more defined for the fields of DNA based diagnostics and personal medicine.

Sources:

(1) http://www.iontorrent.com/the-simplest-sequencing-chemistry/ (23-02-2011, 10:30h)

(2) http://www.technologyreview.com/biomedicine/26850/?a=f  (08-04-2011, 10:30h)   

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