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With IBI Buy, Thermo Aims to Expand In-House Diagnostics Offerings, Position Mass Spec for the Clinic

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By Adam Bonislawski

With its purchase this month of Intrinsic Bioprobes, Thermo Fisher Scientific is aiming not only to expand its reagent offerings for clinical proteomics customers, but also accelerate its own in-house assay development program.

According to James LaDine, global director of research and development for Thermo Fisher's Lab Consumables Division, the company has a "substantial" list of clinically-relevant analytes it has identified for assay development and is "working down the list" using IBI's mass spectrometric immunoassay, or MSIA, technology.

LaDine declined to say what analyte the company will focus on first or when it hopes to bring a test to market, but he told ProteoMonitor "that we know what [the analyte] is and we understand its performance pretty well." He added that the list of analytes has been prioritized "on the basis of analytes that play to our strength relative to other competing methods" like ELISAs or bead-based immunocapture platforms.

Thermo Fisher's BRIMS Center is the "most publicly visible" portion of the firm taking part in the work, LaDine said, but several other parts of the company are also involved, and clinical validation for the developed assays will be done in partnership with outside research centers, he added.

MSIA uses a patented pipette immunoenrichment technology that features a high-throughput, high-binding-capacity microcolumn activated with antibodies to isolate low-abundance proteins in complex samples. The isolated proteins are then passed on for mass spec analysis.

The platform is particularly useful for quantifying levels of different protein isoforms, which has become an area of growing interest in proteomics as evidence has grown that an understanding of such forms is key to basic biological and clinical research.

"There are three axes of variation," LaDine said. "There's [protein] truncation – that's one axis. Another axis is splice variants. The third axis is post-translational modification – things like phosphorylation. There are many, many phosphorylation sites in many proteins of clinical interest, and they can be singly, doubly, or triply phosphorylated, and they can move around. So assigning one number to all of that [in a biomarker assay] and calling that a quantity is, I believe, something that in the long term we're going to stop doing. We're going to start assigning numbers to specific forms within these three axes of variations."

He cited as an example work on parathyroid hormone that Thermo Fisher and IBI collaborated on before the acquisition (PM 07/16/2010). In the case of PTH, IBI and Thermo Scientific BRIMS Center researchers resolved 17 variants of the molecule present in human plasma.

Since then, IBI has launched an in vitro diagnostic for kidney disease and renal failure comprising assays for beta-2-microglobulin, cystatin C, and retinol binding protein. Prior to the acquisition the assay was available through the CLIA-certified laboratory at the University of Medicine and Dentistry of New Jersey's Institute of Genomics Medicine. Ladine declined to officially comment on whether those assays would continue to be available, but said that he had no reason to think they would not be.

Thermo Fisher's plan to develop clinical proteomics assays using the MSIA platform follows other recent moves to expand its diagnostics portfolio – most notably the $3.5 billion purchase in May of allergy and autoimmunity diagnostic firm Phadia (GWDN 5/19/2011).

Beyond using the IBI acquisition to add to its own clinical biomarker portfolio, Thermo Fisher will market the MSIA technology as a tool for scientists doing proteomics research, biomarker discovery and validation, and drug development as well, LaDine said

"We see proteomics maturing into clinical applications and clinical diagnostics, and we see mass spectrometers maturing into those applications as well," he said. "We are interested in maturing our business approach to the proteomic market by way of providing fully integrated workflow solutions – instruments, reagents, consumables, validated protocols, pre-programmed software analysis tools, etc. – that are easy to deploy and scalable and get you all the way from a sample of blood to a clinical answer."

"It isn't just a matter of the incremental sales of the new MSIA tip," he added. "It's that this tip opens up more market space for our mass spectrometers, for our HPLC systems and columns, our manual and automated liquid handling systems, our antibody and peptide reagents portfolio, software tools, and more - everything needed from sample prep to analysis."

In this sense, the purchase recalls another collaboration between a large mass spec vendor and a small proteomics firm – the ongoing work between Agilent and SISCAPA Assay Technologies CEO Leigh Anderson. The partners have been collaborating for several years on an automated workflow for Anderson's stable isotope standards and capture by anti-peptide antibodies, or SISCAPA, assay.

Like MSIA, that technique is an immunoaffinity-based mass spec assay that combines antibody-based peptide enrichment with mass spec to increase the sensitivity of mass spec instruments, which by themselves are often not sensitive enough to detect low-abundance proteins in complex samples.

By automating the technique, Anderson hopes to make it high-throughput and reproducible enough for use in clinical validation of protein biomarkers as well as a platform for proteomics-based diagnostics. At the Association for Mass Spectrometry's Applications to the Clinical Lab meeting in February, he present an automated SISCAPA workflow using an Agilent Bravo liquid handling system for sample prep attached to an Agilent 1200 series LC system and an Agilent 6490 triple quadrupole instrument (PM 02/11/2011).

At the American Society for Mass Spectrometry annual meeting in June, Gustavo Salem, vice president and general manager of Agilent's Biological Systems division, noted Agilent's interest in the SISCAPA workflow, telling ProteoMonitor that the company was "actively in discussion about ways to bring the technology both to a set of pharma clients and as well as to the clinical vision [Anderson] has always talked about where this becomes a set of reagents for clinical diagnostics."

Agilent's March purchase of separations firm Biocius Life Sciences also suggested clinical ambitions. While Biocius' RapidFire separations technology has traditionally been used for ADME assays in drug screening work, Salem observed at the time that "one of the key opportunities" the company saw for the platform was applying it "to the clinical proteomics space" (PM 03/04/2011).

In particular, he said, it could be useful "as a tool for measuring intact protein modifications" and as part of workflows like SISCAPA.


Have topics you'd like to see covered in ProteoMonitor? Contact the editor at abonislawski [at] genomeweb [.] com.

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