Understanding biology at the systems level is difficult, especially when studying complex specimens like tissue slices or communities of organisms in a biofilm. Scientists must be able to identify, quantify and locate the molecules present in the samples.

At Georgia Tech, researchers from the Colleges of Sciences and Engineering have joined forces to create the Center for Bio-Imaging Mass Spectrometry (BIMS), which aims to tackle these types of the challenges.

Mass spectrometry imaging is a powerful analytical technique with the potential to unravel the molecular complexities of biological systems. It allows researchers to visualize the spatial arrangement and relative abundance of specific molecules – from simple metabolites to peptides and proteins – in biological samples.

The technique also takes advantage of the ability of biological molecules to be converted into ions that can then be separated and analyzed by a mass spectrometer.

Today, a popular method for studying biological samples is matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). In this technique, sample preparation plays a very important role in image quality because it requires that a matrix compound be uniformly deposited over the surface of a histological tissue slice mounted on a special plate.

In the April 15 issue of the journal Analytical Chemistry, a research team including Merrill, Cameron Sullards, director of Georgia Tech’s Bioanalytical Mass Spectrometry Facility, and Yanfeng Chen, a research scientist in the School of Chemistry and Biochemistry, showed that the homogeneity of the matrix could be improved. With this development, broader categories of compounds, such as lipids, could be analyzed.

The researchers used an oscillating capillary nebulizer to spray small droplets of matrix aerosol onto the sample surface Using histological samples provided by Timothy Cox, a professor of medicine at the University of Cambridge, the researchers could profile and localize many different lipid species in the samples.

While MALDI samples must be analyzed in a vacuum, recent advances allow samples to be studied under ambient conditions. Facundo Fernandez, an assistant professor in the School of Chemistry and Biochemistry, has been using a technique called desorption electrospray ionization (DESI).

With DESI, a high-speed, charged spray containing alcohol and water is directed at a sample a few millimeters away. The solvent droplets pick up portions of the sample through interaction with the surface and then form highly charged ions that can be analyzed.

Fernandez and his research team recently used DESI to analyze nearly 400 drug samples provided by public health authorities to identify counterfeit anti-malarial drugs.

“We have done a lot of work using DESI to analyze pharmaceutical formulations, but we are moving into new avenues of research including looking at algae samples, as well as ovarian cancer tissue samples provided by the Ovarian Cancer Institute, which is housed at Georgia Tech and headed by School of Biology chair John McDonald,” noted Fernandez.

“We’ve focused on researching computational methods that can clean up, visualize and look for interesting patterns in thousands of mass spectrometry tissue images that you wouldn’t necessarily be able to find or have time to find with the naked eye,” explained May Dongmei Wang, an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering and a Georgia Cancer Coalition Distinguished Cancer Scholar.

As a cell biologist, Merrill sees potential in the ability of mass spectrometry imaging to detect all of the important molecules that control cell behavior instead of just a few. Another advantage to mass spectrometry is the ability to test whether all of the cells are being affected in the same ways.

The BIMS center at Georgia Tech includes researchers like Merrill who propose biological and clinical problems that may be solved by mass spectrometry imaging. It also brings together researchers who are improving current mass spectrometry imaging technologies and developing innovative techniques, and researchers who are analyzing the large sets of complicated data collected by mass spectrometry systems.

With the advances in software and hardware, the use of mass spectrometry in the life sciences promises to become even more prevalent and diversified for systems biology research.

Source: Georgia Institute of Technology