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Life Tech Developing Ion Torrent as a Platform for Proteomics Research

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Life Technologies said this week that it plans to accelerate development of its Ion Torrent technology for proteomic applications.

The company noted that it had passed certain internal R&D milestones linked to applying the technology to proteomics, and that it anticipated initial applications in transplant diagnostics, microbiology, and food safety testing.

"Our internal efforts are accelerating the research and development to build products which use Ion Torrent to detect signals inherent in the binding complexes with proteins, antigens, and antibodies," Alan Sachs, chief scientific officer of Life Technologies, said in a statement.

The Ion Torrent system is based on ion sensitive field effect transistors, a technology that can detect biomolecules and binding events by monitoring changes in ion concentration.

In the case of DNA sequencing – the company's primary use of the technology to date – the system detects the presence of hydrogen ions that are released as a byproduct when a nucleotide is incorporated into a strand of DNA. Protein binding can similarly cause changes in an ionic environment, making the principle applicable to protein detection, as well.

The current Ion Torrent machines perform sequencing in high-density micro-well arrays, with each well containing a different DNA template. In theory, these micro-wells could be functionalized with antibodies to the target proteins. Binding of a target protein to the capture antibody would cause a change in the ionic environment of the well, enabling the system to detect the presence of the protein.

Life Tech declined to comment further on its plans for applying the technology to proteomics and did not offer information on precisely how it might be adapted for protein measurement, but the company did provide in its announcement a general outline of the principles underlying the effort that suggest an approach similar to its DNA sequencing efforts.

"Antibody/antigen complexes and proteins can be combined with bead-based sample-preparation technologies used on Ion Torrent's semiconductor sequencing technologies," the company said. "The sensitive signal detection available on the Ion Torrent's semiconductor chip works by recognizing electrical and ionic changes through a sensor, and the currently available products are being used with nucleic acids."

ISFETs were invented in 1970 by researcher Piet Bergveld, and since then a number of scientists have explored use of the technology for protein measurement, with some studies achieving femtomolar levels of detection.

The technology is a variety of field-effect transistor, a class of device consisting of a channel through which charge flows, with the channel's conductivity regulated by a gate. In biosensing applications, the target molecules serve the function of the gate, which allows the presence of the molecules to be detected by changes in the device's electrical properties.

Because of their small size, high sensitivity, and relatively low cost of production, FETs have drawn interest for applications including genomics and label-free protein detection, with facilities including the University of Copenhagen's Nano-Science Center and the University of California, Santa Barbara's Nanoelectronics Research Lab exploring use of the technology for proteomics applications.

The UCSB effort, led by researcher Kaustav Banerjee, is exploring an advanced FET called a tunnel-FET that, Banerjee said, offers significant improvements in speed and sensitivity over conventional FETs and could potentially detect proteins at attomolar levels (PM 4/27/2012).

In addition to researchers investigating other FET-based proteomic approaches, some of Life Tech's sequencing competitors are pursuing other protein detection techniques.

Oxford Nanopore, for instance, is researching nanopore-based platforms for protein measurement. The company has yet to releas any commercial protein detection devices, but in January founder Hagan Bayley and other researchers from the company published a study in the Journal of the American Chemical Society on using nanopores linked to aptamers for protein detection.

Proteomics researchers and firms have also been investigating the use of sequencing platforms as read-out systems for proteins detected via affinity agents like aptamers or DNA-linked antibodies (PM 5/6/2011). For instance, Uppsala University researcher Ulf Landegren has been investigating the use of next-generation sequencing for reading proteins detected via proximity ligation assays, a technique he invented that uses pairs of antibodies attached to unique DNA sequences to capture proteins of interest.

Currently, PLA's approach uses real-time PCR to quantify the DNA amplicons formed when target proteins are captured, but NGS offers potential advantages in terms of precision and multiplexing, Landegren told ProteoMonitor in an interview last year.

Landegren is a founder and board member of Olink Bioscience, which sells the PLA technology under the name DuoLink. Life Tech has licensed the PLA technology from Olink and offers it as part of Applied Biosystems' TaqMan product line. In February 2011, as part of its European Ion Torrent Personal Genome Machine Sequencer Grants Program, Life Tech awarded Landegren an Ion Torrent sequencer to support his PLA work.

Life Tech's competitor in the sequencing space, Illumina, has also shown some interest in proteomics work. In 2010, the company purchased for an undisclosed amount antibody firm Affomix, which had similarly been exploring the use of NGS to read proteins, in this case after detecting them using antibodies with attached oliginucleotide backbones (PM 06/04/2010).

In Life Tech's announcement, Ronnie Andrews, the company's president of medical sciences, suggested that the desire to analyze protein and genetic data on the same systems was an important driver of the firm's foray into proteomics.

"In disease areas like transplant diagnostics and cancer, having the ability to analyze proteins and genes on the same system, in the same lab, brings better convenience, better turnaround time, and allows for democratization of critical information for better patient management," he said.

Koen Kas, then-CEO of protein diagnostics firm Pronota, said much the same thing in an interview last year with ProteoMonitor on that company's use of NGS in its proteomics research.

"Not everything you want to measure… can be measured at the DNA level," he said. "It might be handy to measure something at the protein level. So I see [protein biomarker measurements] in the clinic combined with DNA and RNA-based measurements to give a comprehensive analysis in one single device."

A move into proteomics could down the road also provide sequencing firms like Life Tech with a more routine application for their platforms, Larry Gold, CEO of protein diagnostics firm SomaLogic, suggested to ProteoMonitor in an interview last year.

Sequencing vendors "at some point have to turn their machines into a workhorse for something that’s done all the time, not just once when you sequence your individual genome," he said. "Proteomics [testing] is something that people will do in their lives 100 times, and genomics is something they'll probably do once, unless they get cancer, and then they'll probably do some cancer genomics."

"So there's an enormous reason the deep sequencing guys want to move towards [proteomic] assays," he added. "It's the difference between an annuity and winning the lottery."

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