ESA Metabolomics system eases biomarker discovery
discovery and reduce the overwhelming amounts of data often
associated with these studies.
The system integrates standard liquid chromatography (LC) mass spectrometry (MS) systems with coulombic electrochemical (EC) techniques to provide researchers with a powerful tool to identify and monitor small molecule cellular biomarkers of disease and disease treatment while reducing the amount of superfluous data collected.
Metabolomics is the study of an organism's metabolites such as amino acids, peptides, lipids and carbohydrates. By detecting and understanding the metabolic differences between normal and diseased states, researchers can find biomarkers that provide earlier and more precise diagnosis as well as aiding prevention and following disease or treatment progression.
"For decades people have been working on drugs and therapies as single causable factors, but more and more often people are finding disease pathways," Dr Darwin Asa, ESA's drug discovery business development manager, told DrugResearcher.com.
"Metabolomics represents the ultimate outcome of those pathways: find the outcome of the pathways and in turn you find the biomarkers."
The samples studied are frequently biological samples such as urine or blood, which can lead to very complex chromatographic profiles when using nuclear magnetic resonance (NMR) or LC/MS approaches to metabolomics research.
The results are often complicated by the complexity and quantity of data generated as thousands of different molecules can be in the sample. It is often a laborious job to sift through the vast quantities of data collected to find those peaks that correspond to meaningful biomarkers.
Dr Asa continued: "The Metabolomics System allows researchers to focus in quickly and clearly on potential biomarker molecules that are changing from sample to sample."
"It allows researchers to sort through the thousands of potential biomarkers so that we can filter out the noise from the sample, allowing us to save the mass spectrometer for identifying the particular components that have changed - providing a way to break the data log jam in metabolomics research."
ESA's CoulArray, used in parallel with LC/MS allows the targeted analysis of compounds that can be either reduced or oxidised (redox). These redox active compounds are often highly relevant to metabolic changes associated with drug pharmacology, toxicity and disease. The technique allows simple differentiation of these relevant compounds from those compounds that are generally chemically and electrochemically inert such as urea.
The systems cost between $50,000 (€38,000) and $100,000 and include the electrochemical detctor, instrument control software and pattern recognition software.
EC provides a way of detecting molecules at very low detection limits that other techniques might miss using routine settings. The EC array consists of a series of 16 coulometric electrochemical cells set to different redox potentials, which oxidise and detect compounds as they pass through the cells.
MS systems can run out of detection sensitivity to low-level metabolites when running complex mixtures as the signals can be swamped by higher concentration species. The parallel use of an EC array allows for more specific settings to be utilised, which improve the specificity and sensitivity of the bioanalytical system.
"We've got a nice orthogonal technique to use with LC/MS or NMR studies giving us the ability to rapidly locate potential biomarkers," said Dr Asa.
"The system is a good solution to identifying what is important in a sample allowing researchers to use their mass spectrometer or NMR machine much more efficiently and will help propel metabolomics to the next level."
The use of EC array detection in metabolomics has been demonstrated in numerous studies. One such study by Kristal et al in Archives of Biochemistry and Biophysics showed that the use of EC array systems allowed the identification and monitoring of a series of biomarkers that could be used to measure mitochondrial changes due to different diets of Type I diabetics.
The system can also be coupled to ESA Biosciences' Corona Charged Aerosol Detection (CAD) detection system that can reliably detect and quantify virtually any non-volatile or semi-volatile compound, including proteins, peptides and small molecules.
According to Dr Asa, CAD system adds a way to quantify the amount of a biomarker or molecule in the sample and "keeps you out of the quantification problem often associated with MS or UV detection."
The new Metabolomics system is a result of a 'Roadmap Initiative' grant from the National Institutes of Health (NIH) awarded to ESA in March 2005 to accelerate ESA's metabolomics research programmes.
