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Nov 15, 2013 (Vol. 33, No. 20)

Honing in on Cancer Biomarkers

  • NMR Technology

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    LipoScience researchers using NMR technology to look for cancer biomarkers expect that panels of metabolites covering a range biochemical processes will need to be analyzed. They produced these 1H NMR spectra of unprocessed serum focusing on (A) macromolecular signals and (B) the small molecule metabolome.

    LipoScience is also developing new ways to search for biomarkers. Specifically, to find biomarkers of clinical value, they are using NMR technology. “We take advantage of two of the key features of the NMR platform,” explained Thomas O’Connell, Ph.D., senior director of research and development. “These are the lack of required sample preparation for routine biofluids and the inherently quantitative signals.” This means that they can profile large sample sets very quickly.

    LipoScience researchers are now using NMR to look for cancer biomarkers. “Given the heterogeneity of most cancers, it is not likely that a single biomarker will provide the necessary clinical performance,” said Dr. O’Connell, “so we are examining panels of metabolites that cover a range of biochemical processes, including lipid and lipoprotein metabolism, energy perturbations, inflammatory processes, and others.”

    They plan to use NMR and metabolomic profiling to develop clinical assays that help to choose patient-specific therapies. “We are hopeful that one day in the near future, panels of biomarkers could provide clinicians with much more objective, quantifiable, and personalized information regarding the diagnosis and management of their patients,” added Dr. O’Connell.

  • Single Molecule Arrays

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    The Simoa (for single molecule array) instrument from Quanterix uses a digital ELISA technique, trapping fluorescent reaction product in indiv-idual wells, to speed blood testing for HIV.

    Researchers at Quanterix have developed a method of testing for a different type of biomarker—one that indicates the early and acute (and most contagious) stage of HIV infection. Their method is faster, cheaper, and more sensitive than previous tests.

    Previously, the gold standard HIV test with the highest sensitivity was nucleic acid testing, which detects viral genetic material. The new test from Quanterix, called Simoa for “single molecule arrays,” is a digital ELISA technique. Simoa works by preventing the sensitivity loss that can occur in conventional ELISAs because of the dilution of reaction product into the reaction volume. Simoa essentially miniaturizes the ELISA principle, trapping fluorescent reaction product in individual wells to prevent dilution.

    “The technology basically supercharges a standard ELISA to give 1,000-times greater sensitivity,” said David Wilson, Ph.D., vp of product development. “Due to this extreme sensitivity of Simoa to enzyme label, label molecules can be reduced, which lowers nonspecific interactions and improves signal background. This drives the sensitivity of Simoa digital immunoassays down to the level of nucleic acid testing.”

    Simoa assays are easily amenable to high-throughput fluidics instrumentation and automation. So Dr. Wilson hopes Simoa will be applied to HIV screening in blood banks, as well as other blood-borne viruses to which Quanterix is developing new Simoa assays. “A key need in many blood banking centers is high throughput,” Dr. Wilson said. “Blood units are screened for a number of pathogens, so effective throughput is measured in number of units processed in a given period of time.”

    Simoa immunoassays can be multiplexed to test for up to 10 different target proteins simultaneously, which may benefit blood banks. However, blood banking is highly regulated, so introducing Simoa assays may take time. “As with any new test used to ensure a blood unit is pathogen-free,” explained Dr. Wilson, “a substantial amount of data is needed to prove to regulatory bodies that the test exhibits the claimed performance, and that the manufacturing processes are fully validated and controlled.”

    Perhaps one day, it will be possible to detect biomarkers of viral infection, cancer, and other diseases for many people very quickly. Then, armed with the relevant information, healthcare providers will be able to fight disease more effectively.

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