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Beefing Up Biomarkers

Beefing Up Biomarkers
Protein kinase C in HeLa cells moves to the plasma membrane after treatment with phorbol myristate acetate.
Images courtesy of Perkinelmer.

Biomarkers represent essentially anything that can be used to measure a biological state. In terms of health, researchers look for biomarkers that provide some information about a person’s condition, healthy or otherwise. These biomarkers range from weight and blood pressure to cholesterol levels and gene expression. As health research advances, screening for relevant biomarkers is becoming more and more important, resulting in an increase in molecular markers.

“Since we have sequenced the human genome and have reliable single nucleotide polymorphism analysis, certain genetic variants can be linked to disease states,” says Martina Bielefeld-Sevigny, vice president and general manager of research reagent solutions at PerkinElmer in Waltham, Mass. “That’s the first step that will lead us into personalized medicine.” Bielefeld-Sevigny points out that biomarkers could indicate for whom a drug will be beneficial and patients who will not respond. She adds, “We will be able to increase drug safety by determining toxic side effects occurring only in individuals with a specific genetic make-up.”

To improve the biomarkers used in healthcare, researchers need the right tools. According to Bielefeld-Sevigny, the key features required in such tools are sensitivity and throughput. “Biomarkers can be present in very minute amounts,” she says, “so more sensitive tools are more likely to detect a low-abundance biomarker, which may be missed otherwise.” The desire for high throughput comes from the need to screen a large number of samples. For instance, Bielefeld-Sevigny describes one customer seeking to discover cancer biomarkers linked to kinase activity. “He has access to freezers full of tissue samples from cancer patients, collected over many years,” she says. “He aims to profile them against more than 200 kinases. Evidently, this researcher needs throughput.” Once a biomarker is identified, validating it as, say, a diagnostic tool to accompany a drug requires statistics on the biomarker, which means an even higher need for throughput. “A single validation study can easily exceed 100,000 samples,” she explains.

To increase throughput and enhance sensitivity, Bielefeld-Sevigny and her colleagues developed the AlphaLISA platform. AlphaLISA replaces the traditional ELISA test, being more sensitive and eliminating wash steps, making it faster to both develop and run the tests. “AlphaLISA is a bead-based technology where the signal is largely amplified while the background remains low.” Consequently, this technology can work with biomarkers at concentrations in the femtomolar range.

Although many discussions on molecular biomarkers focus on cancer research, other diseases are also being studied with the same tools. PerkinElmer’s AlphaLISA technology can also be used with any antibodies or proteins related to inflammation, neurodegenerative diseases and other illnesses.

According to some experts, pharmaceutical companies are just beginning to discover the possibilities the use of biomarkers provide for drug discovery and development. As Bielefeld-Sevigny says, “There is an enormous potential for the pharma industry to expand biomarker testing for the development of safe and efficient medication, making medicine more personalized.”

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