Ion Torrent

Ion Torrent is a DNA sequencing technology that reads a strand by detecting hydrogen ions on a semiconductor chip, and the name of the company founded in 2007 to build it. When a polymerase adds a nucleotide to a growing DNA strand it releases one hydrogen ion, and a transistor under the well that holds the reaction senses the change in acidity. The method needs no light, no camera and no chemically labeled nucleotides. Life Technologies bought the company in 2010, and since 2014 it has belonged to Thermo Fisher Scientific.^[1]

The chip is made by the CMOS process used for ordinary integrated circuits. It holds an array of wells, 1.2 million of them in the version its authors described in 2011, and each has an ion-sensitive field-effect transistor in "perfect register" beneath it. Template DNA and polymerase sit in the wells. The instrument floods the chip with one unmodified nucleotide, A, C, G or T, at a time and washes it out before the next. A nucleotide that matches the next base of the template is incorporated, a hydrogen ion is released, the pH in the well shifts and the transistor registers a voltage.^[1]

The authors named the need for imaging technology as one of the limits on cheaper and more compact sequencers, and they argued that the CMOS process would let the chips scale to higher densities. They reported chips with up to ten times as many sensors as the 1.2 million-well version.^[1]

The transistor is older than the sequencer. The ion-sensitive field-effect transistor was described in 1970 by Piet Bergveld, who built it for neurophysiological measurements.^[2] In 2006 a group at Stanford reported electrical detection of DNA synthesis with a gold electrode that sensed a charge change when a nucleotide was incorporated.^[3]

Rothberg had earlier founded 454 Life Sciences, whose 2005 sequencer read DNA in picoliter reactors by light.^[4] He founded Ion Torrent in 2007, in Guilford, Connecticut, and led it until 2010, to remove the optics.^[5] In August 2010 Life Technologies agreed to buy it for $375 million in cash and stock, with up to $350 million more tied to milestones, and the purchase closed on October 1, 2010.^[6] The first machine, the Personal Genome Machine, was priced at $49,500.^[7] Thermo Fisher completed its purchase of Life Technologies for about $13.6 billion on February 3, 2014.^[8]

The paper of July 21, 2011, reported the genomes of three bacteria and of one person, Gordon Moore, the Intel co-founder whose observation about the growth of transistor counts is known as Moore's law. A press report of the same day said that the machine decoded a bacterial genome in about two hours.^[1][7]

In 2012 a comparison of three benchtop sequencers, which sequenced an Escherichia coli isolate from the German outbreak of 2011, found that run in 100-base mode the Ion Torrent machine had the highest throughput, 80 to 100 megabases an hour. Illumina's MiSeq had the lowest error rates and the highest yield per run, 1.6 gigabases. The Ion Torrent and the 454 GS Junior both made errors at homopolymers, runs of the same base. A run of eight identical bases releases eight ions at once, and the signal has to be converted back into a count; the Ion Torrent machine made 1.5 insertion or deletion errors per 100 bases of that kind.^[9]

No company source discusses Ion Torrent. Like it, the MR1 Nanopore Reader reads electrically: it is meant to hold a voltage across a nanopore and record the current 100,000 times a second, with no optics. The reader's status line, "Designed. Simulated. Built and measured: not yet.", dates from its release in October 2026.^[10] Rothberg's later company, Quantum-Si, is one of 38 flagship entries in the company's atlas of molecular-sensing groups, The Hole World, where its caption is "Protein sequencing chip".^[11]

• Illumina
• Pacific Biosciences
• Nanopore sequencing
• Human Genome Project