Mass spectrometry brings speed, accuracy, specificity to labs

2020 01 31 19 24 1068 Lab Maldi Tof Pipette 400

For years, mass spectrometry found extensive use as a valuable analytical tool in industries ranging from chemical processing to drug discovery and development. Now the technology has transitioned into the clinical lab, with the commercialization of mass spectrometry platforms for microbial identification.

In the clinical setting, mass spectrometry has gained attention as a more specific alternative to immunoassays for determining the presence of sex steroids and for use in testing for illicit or abused drug use.

Mass spectrometry can reliably measure and analyze a number of analytes, including small molecules and biomolecules. After the technology gained exposure for microbial identification, it was harnessed for many clinical applications, such as for laboratory tests quantifying analytes, for diagnostic applications in infectious disease, and for detecting inborn errors of metabolism.

The market in clinical labs reached $859 million in 2018, accounting for 17% of the overall total for mass spectrometry, according to a recent report from Strategic Directions International (SDi), a sister company of

"The market has expanded robustly in a very short time, and there is plenty of room for continued innovation and growth in multiple areas over the next decade," SDi analysts noted.

More manageable instrumentation

Traditionally, labs were performing laboratory-developed tests on mass spectrometry as opposed to tests approved by regulatory authorities and sold by diagnostics manufacturers, but this is changing with the introduction of integrated systems and platforms, according to the SDi report.

As the clinical uses for mass spectrometers increased, the instrumentation shrank in size and has become more manageable. Gone are the huge instruments with cumbersome electronics that consumed a lot of power. Many systems now have smaller footprints and are portable analytical tools that yield rapid results. This is good news for labs that have limited space for deploying equipment.

"The main advantages of mass spectrometry include speed, accuracy, and specificity," explained Dr. David Herold, a professor of pathology at the University of California, San Diego (UCSD) School of Medicine, in an interview.

Herold believes that mass spectrometry for the clinical lab will become more widely accepted as more systems for clinical labs are commercialized. Companies that offer mass spectrometry products for labs include Sciex, BioMérieux, Bruker, and Thermo Fisher Scientific.

Currently, Thermo Fisher Scientific is marketing its Cascadion SM clinical analyzer with high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS), which is intended to meet the needs of routine clinical laboratories. At Roche, a fully integrated mass spectrometry analyzer is being developed and is expected to include a diverse test menu.

Herold indicated that clinical lab applications for mass spectrometry initially got a boost with the drugs-of-abuse problems that the military experienced in the 1970s. The technology has now advanced to the point that performing mass spectrometry on a urine specimen enables clinicians to detect adrenal cortical carcinoma about six to 12 months before imaging tests could, he explained.

Due to its ability to analyze certain small molecules in biofluids, mass spectrometry also is finding use in diagnosing inborn errors of metabolism, Herold noted. These are unusual inherited disorders in which the body cannot properly metabolize foods, leading to the buildup of toxic compounds in the body.

Other applications that have drawn mass spectrometry to the clinical lab include electrospray ionization combined with LC-MS/MS, which helped speed sample analysis. LC-MS/MS is finding use in analyzing steroids too. The technique is well-accepted in part because it is more sensitive and specific than immunoassays.

Moreover, matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry has evolved into an effective clinical microbiology technique for quickly and accurately identifying cultured bacteria and fungi. Following on this model, rapid turnaround tests are also being developed for the clinical chemistry laboratory, Herold said.

Expanding test menus

While mass spectrometry in the clinical lab for the most part has been limited to single tests, eventually labs will be able to perform panels of tests, Herold said, including those involving metabolomics and proteomics.

"It may be possible in the future to use mass spectrometry to examine someone's metabolome and determine certain items that someone should not eat, or supplements someone should take, to help them lead healthier lives," he theorized.

Additionally, tissue imaging by mass spectrometry is making inroads into surgical pathology, he noted. But there are challenges. A certain amount of technical knowledge is needed to support clinical testing, he explained.

"One of the drawbacks to using mass spectrometry involves the need for trained personnel," Herold said. "Labs need personnel involved in clinical chemistry who know the right tests needed to make an accurate diagnosis."

Identifying molds

Investigators have found that MALDI-TOF mass spectrometry can optimize the diagnosis of infections caused by filamentous fungi. Molecular techniques, such as DNA sequencing, have been the gold standard for quite some time for identifying species of fungi. These methodologies yield accurate results; however, they are expensive, require specialized equipment or trained staff to run, and are not the domain of many clinical laboratories.

In research published in the Journal of Clinical Microbiology, scientists at the Università Cattolica del Sacro Cuore in Rome indicated that MALDI-TOF mass spectrometry has application as an accurate, rapid tool for identifying common species or usual strains of filamentous fungi, including Aspergillus, Fusarium, and dermatophytes (Sanguinetti et al, February 2017, Vol. 55:2, pp. 369-379).

In this use, MALDI-TOF mass spectrometry would compete against conventional phenotypic methods which are relatively inexpensive. However, the time needed for fungal growth is very long with phenotyping, creating a turnaround time of several days. As a result, early antifungal therapy of an infection may be somewhat speculative, and the proper therapy may be delayed.

MALDI-TOF mass spectrometry has reduced the length of turnaround time for clinical labs, although these instruments continue to rely on fungal cultures. However, in some instances, MALDI-TOF mass spectrometry is being used to analyze patient specimens directly, which avoids fungal growth requirements, according to the researchers.

The scientists proposed that MALDI-TOF-based identification techniques should be adopted into common antifungal diagnostic regimens. Utilizing the technology would be a benefit because rapidly and precisely detecting fungal pathogens can improve patient treatment and outcomes.

Such efforts show how mass spectrometry is becoming more essential in the clinical lab and will continue to find greater use as analytical and expertise issues are overcome. Toward this end, an educational nonprofit, the Association for Mass Spectrometry: Applications to the Clinical Lab (MSACL), is committed to advancing the use of mass spectrometry in the clinical laboratory through education and training. The group's 12th annual conference will be held in Palm Springs, CA, from March 29 to April 3.

Page 1 of 9
Next Page