A major concern in the analysis of complex samples such as blood by mass spectrometry is the signal suppression due to overlapping components eluting at the same time which results in lower sensitivity and higher precision and accuracy. With the advent of multi-dimensional liquid chromatography combined with MS there is a need to investigate the advantage of using this high resolution chromatographic system on the front end of MS to improve the analytical figures of merit such as sensitivity, precision and accuracy. Some preliminary experiments were carried out in my lab in 2011 to show that two-dimensional LC/MS improved the precision of signal measurement for the analysis of peptides in antibody digests. We would like to expand on that work for the analysis of blood and publish the results.
In addition, the analysis of biomarkers in blood is very dependent on the above analytical figures of merit to accurately predict if there is change over time (fold change). By improving the sensitivity, precision, and accuracy of the measurement of individual biomarkers we would be better able to predict a change in an individuals blood profile and improve predictions in preventative medicine. Thus, the next logical step for future research would be to develop a platform technology of two-dimensional LC/MS/MS to investigate the improvement in biomarker analysis in blood of hundreds of biomarkers simultaneously.
During the stay at the University of Messina, a seminar on the “Development of multidimensional liquid chromatography” will be organized for PhD and post doc students working in the analytical chemistry field.
Measure accuracy, precision, and sensitivity of a several molecule at low medium and high concentration levels in blood over 6 replicates for LC/MS or LC/MS/MS analysis.
Develop 2DLC/MS method and repeat above measurement and compare results.