This may especially benefit cancer research and treatment thanks to MALDI’s ability to provide pathologists with a view of the whole-tissue micro-environment
Though it may be years before Matrix-Assisted Laser Desorption Ionization (MALDI) mass spectrometry finds use in clinical applications, recent developments show medical laboratories and anatomic pathologists how one type of technology is being rapidly adapted for use in diagnosing cancers.
Richard Drake, PhD, Director of the Medical University of South Carolina (MUSC) Proteomics Center, notes the importance of MALDI to cancer research. “In the clinic, there has to be something that will facilitate looking at all this data—tools that will let the pathologists look at it as well as the mass spec person,” Drake told GenomeWeb.
“It has been known for decades that glycosylation changes on the cell surface promotes cancer progression and the way the immune system sees a tumor or doesn’t see a tumor,” he explained. “That’s the advantage of MALDI imaging. You’re looking at the whole tissue micro-environment, and particularly for cancer it turns out to be important.”
Imaging Mass Spectrometry Applications for Anatomic Pathology
MALDI uses mass spectrometry imaging technology to enable high-molecular identification and an overall view of tissue. It differs from liquid chromatography-mass spectrometry (LC-MS), which is a chemical analysis technique.
An article by News-Medical describes in detail how MALDI technology works:
“MALDI imaging works through the utilization of a matrix, an acidic aromatic molecule that absorbs energy of the same wavelength produced by the irradiating laser. The matrix transfers the substance being examined to the gas state, thereby producing ionization in a three-step process:
1. “Thin sample sections on a metal slide are first covered with the matrix and the procedure for extracting molecules of interest from the tissue into the matrix begins. The matrix can be applied both manually and automatically.
2. “The laser irradiates the sample only in the matrix layer, meaning the underlying tissue remains intact.
3. “The released molecules are transferred to the gas state as the matrix absorbs the laser energy. Ions are formed due to the addition or removal of protons when in the gas state.
“The irons are required for further analysis via the mass spectrometer. The metal slide is placed into a MALDI mass spectrometer where the spatial distribution of the biological molecules is mapped. Within the mass spectrometer, the tissue specimen is raster scanned forming a mass spectrum for each spot measured. Image processing software is then required to import the data from the mass spectrometer to allow visualization of the image produced.”
The above schematic illustrates “the identification of bacteria and yeast by MALDI-TOF MS using the intact-cell method. Bacterial or fungal growth is isolated from plated culture media (or can be concentrated from broth culture by centrifugation in specific cases) and applied directly onto the MALDI test plate. Samples are then overlaid with matrix and dried. The plate is subsequently loaded into the MALDI-TOF MS instrument and analyzed by software associated with the respective system, allowing rapid identification of the organism.” (Caption and image copyright: Clinical Microbiology Reviews/American Society for Microbiology.)
MALDI in Clinical Laboratories
MALDI experts at MUSC worked with researchers at Bruker Corporation, a developer of scientific instruments and analytical diagnostic solutions for cell biology, preclinical imaging, clinical phenomics and proteomics research, clinical microbiology, and for molecular pathology research. Bruker is reportedly working with labs in Europe on MALDI-based assays for clinical use.
Developing MALDI applications for use in clinical laboratories and anatomic pathology groups could result in major improvements. Imaging mass spectrometry could:
- make more molecular information available;
- reduce pathology’s subjectivity and intra-observer nature;
- enable more accuracy and ability to duplicate current pathology assays; and,
- pave the way for new assays to be made.
“MALDI-IMS [imaging mass spectrometry] identifies the distributions of proteins, peptides, small molecules, lipids, and drugs and their metabolites in tissues, with high spatial resolution. This unique capacity to directly analyze tissue samples without the need for lengthy sample preparation reduces technical variability and renders MALDI-IMS ideal for the identification of potential diagnostic and prognostic biomarkers and disease gradation,” noted authors of a MALDI study published in the July 2017 edition of Biochimica et Biophysica Acta Proteins and Proteomics.
“You can take a slide of tissue and essentially do metabolomics on it so that you can look at the intricate nature of what metabolism is happening within a tissue,” James MacRae, PhD, Head of Metabolomics at the Francis Crick Institute in London, told Technology Networks, which described development of new mass spectrometry imaging technologies as “potentially game-changing.”
Mass Spectrometry in Clinical Laboratories
This is just the latest in a string of scientific developments involving mass spectrometry over the past decade that are potential boons to clinical laboratories. In “Is Mass Spectrometry Ready to Challenge ELISA for Medical Laboratory Testing Applications?” Dark Daily reported on the development of a new technique from the Department of Energy’s Pacific Northwest National Laboratory that uses mass spectrometry to identify protein biomarkers associated with cancer and other diseases. Researchers dubbed the technique PRISM, which stands for Proteomics Research Information System and Management.
And in “Swiss Researchers Use New Mass Spectrometry Technique to Obtain Protein Data, Create Strategy That Could Lead to Clinical Laboratory Advances in Personalized Medicine,” Dark Daily reported on researchers at the Swiss Federal Institute of Technology in Lausanne and ETH Zurich who developed a new way to use mass spectrometry to explain why patients respond differently to specific therapies. The method potentially could become a useful tool for clinical laboratories that want to support the practice of precision medicine.
As mass spectrometry’s role in clinical laboratories continues to expand, MALDI technology development and research could eventually lead to tools and applications that enhance how anatomic pathologist view tissue specimens in the medical laboratory. Though the research is ongoing, the technology seems particularly suited to cancer research and treatment.
—Donna Marie Pocius
Related Information:
Technical Advances Position MALDI Imaging as Plausible Tool for Clinical Pathology
The Proteomics of Prostate Cancer Exosomes
Metabolomics and Health – On the Cusp of a Revolution
Is Mass Spectrometry Ready to Challenge ELISA for Medical Laboratory Testing Applications?
