MALDI-TOF MS Breaking Through

MALDI-TOF MS provides for rapid identification of an organism to a species level within minutes, utilizing the proteomic fingerprint of the organism tested. MALDI-TOF MS stands for Matrix-Assisted Laser Desorption Ionization-Time-of-Flight Mass Spectrometry. This technology has been explored in different labs as they seek to assess its potential impact for routine clinical use in the near future.

The technology’s speed is what drives the interest among labs; MALDI-TOF MS is able to return pathogen identification results in minutes, compared to standard biochemical techniques that can take from six to 48 hours. The potential of this regained time can mean that targeted therapy is implemented earlier, or that therapy can be modified as much as 24 hours earlier than the norm because MALDI-TOF MS also allows for expedited antimicrobial susceptibility testing. In terms of patient outcomes, faster identification promises more targeted therapy resulting in more effective treatment and faster recovery. All of this equates to lower cost per patient. Faster identification will also be critical as the healthcare system seeks to address the problem of antimicrobial-resistant pathogens, as it will hasten the ability of clinicians to change treatment and avoid the overuse of antibiotics with no effect on the responsible pathogen.

MALDI-TOF technology also allows the consolidation of testing of bacteria (Gram positive and Gram negative), Fungi and mycobacterium onto a single platform, cutting the turnaround time considerably for identification.

MALDI-TOF is expected to offer significant cost savings, as it minimizes the need for reagents for sample preparation. The integration of MALDI-TOF identification to antibiotic susceptibility testing is required to ensure that the antibiotic profiles generated match the organism, which in turn allows for the determination of the organism phenotype. The software in automated systems utilizes the organism phenotype to apply any therapeutic correction or changes in interpretation, which is essential for antibiotic therapy.

The process begins when the sample is added to a metal target slide. A matrix solution is then applied to the sample; this causes crystals to form in the solution. A laser pulse then ionizes the sample, the matrix crystals absorb the energy and the proteins present are accelerated before vaporizing.

The velocity of the proteins is inversely proportional to their size and charge. As the proteins separate based on size and charge, the proteins rise to reach the MALDI-TOF’s detector in order of size, going from smallest to largest, based on time of flight. This creates a series of peaks called the spectra. The rapid separation and identification of proteins allows the MALDI-TOF MS to quickly identify large volumes of samples economically.

The fingerprint generated from the organism tested is compared against a large database that serves as an archive of all known organisms. The databases were developed using different algorithms, where traditional methods employ matching the spectra pattern generated to an archive of known patterns in the database while calculating a deviation from the typical spectra. A second more efficient and informed approach works through defining the presence or absence of species-specific proteins (commonly referred to as the species biomarkers), which provides a higher specificity and prevents misidentification.

MALDI-TOF technology represents a breakthrough in microbiology by using a single platform that provides organism identification within minutes, reduces setup time, consolidates testing, reduces cost and improves detection of difficult organisms. The benefits to the lab include improved workflow, improved time-to-results and a more active role in guiding targeted patient therapies.

Dr. Safwat is Senior U.S. Clinical Marketing Manager, bioM‚rieux Inc., Durham, NC.

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