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PTH at picograms
October 2011
by Lloyd Dunlap  |  Email the author


ROCHESTER, N.Y.—Thermo Fisher Scientific Inc. has enhanced its workflow for biomarker research and diagnostics by acquiring Intrinsic Bioprobes Inc. (IBI), a manufacturer of immuno-enrichment, sample-preparation tools used in quantitative mass spectrometry.
Adding IBI's consumable sample-preparation technologies to Thermo Fisher's automated sample processing and quantitative mass spectrometry instruments and software creates a complete, integrated workflow for the quantitative detection of protein biomarkers, enabling Thermo Fisher to offer its worldwide life science research and clinical diagnostics customers an enhanced solution for quantitative protein biomarker detection, according to a Thermo Fisher media release.  
"We began our collaboration about a year ago," says Dr. James Ladine, global director of R&D with Thermo Fisher's lab consumables division.  

The collaboration recently resulted in a paper published in the Journal of Clinical Chemistry that detailed the workflow and assay results for parathyroid hormone (PTH) in blood.
"We showed 17 different PTH hormone variations," Ladine notes, most resulting from ends having been truncated. "Other techniques just show a big, dumb number," he says, and lump together forms of the hormone that may not be active. Sensitivity is 8 picograms per milliliter, which compares favorably with other assays, he says.  
The IBI portfolio includes its novel Mass Spectrometric Immunoassay (MSIA), featuring a patented sample preparation technique. This technology allows enrichment of low-abundance proteins in biological samples. The specificity of immuno-enrichment, coupled with the sensitivity and quantitative capability of mass spectrometry, gives researchers a complete, higher-resolution view of the proteome. Furthermore, the MSIA technology provides greater sensitivity and higher throughput than conventional ELISA and bead-based immunoassay formats, according to Thermo Fisher.
Ladine notes that there are two trends in biomarker assays like that for PTH—greater complexity and lower abundance. In terms of complexity, he cites PSA as an example of a "traditional marker" that is being seen as more complex than previously thought.
"Complexity can involve truncation," as with PTH, "splicing variances and different sites or extent of phosphorylation," he says.  
IBI's proprietary immunoenrichment technology involves 10 steps, Ladine notes, nine of which are now made by Thermo Fisher (only the serum or plasma isn't) and is based on a patented pipette tip that integrates a high-throughput, high-binding-capacity microcolumn activated with antibodies. This technology addresses one of the key challenges of biomarker discovery and validation—the isolation and analysis of very low-abundance proteins such as PTH in complex biological matrices. Conventional approaches involving depletion of interfering high-abundance proteins are time consuming and introduce analytical variability. Compared to other immunoenrichment approaches, IBI's approach promises more effective capture of low-abundance proteins. A key challenge in proteomics research is the ability to differentiate between, and accurately quantitate, intact proteins and their variants. Traditional enzyme-linked immunosorbent assays (ELISA) are limited by the inability of the antibodies to discriminate between all variants and quantify their abundance, Thermo Fisher states.  
"The Intrinsic Bioprobes portfolio will enhance Thermo Fisher's position in the rapidly emerging field of clinical proteomics," says Chuck Kummeth, president of Thermo Fisher's laboratory consumables business. "It is a simple, yet powerful approach to uncovering the proteomic basis of disease, and it better positions us to support our customers in their efforts to realize the promise of personalized medicine."   
IBI was founded in 1996 by Randall W. Nelson, who has served as its president since then. He will continue to be involved with the business as a consultant.
Thermo Fisher declined to comment on the possible integration of IBI's staff or facilities or provide information on the dollar value of the acquisition.  
Thermo Fisher was created in 2006 by the merger of Thermo Electron and Fisher Scientific, resulting in formation of Thermo Scientific (analytical instruments, laboratory equipment, software, services, consumables and reagents) and Fisher Scientific (laboratory equipment, chemicals, supplies and services). The company employs about 37,000 and has annual revenues of almost $11 billion.
Code: E101104



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