Mass Spectrometry in the Clinic
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A widely used analytical technique in fields ranging from environmental analysis to forensics, mass spectrometry is increasingly finding its way into the clinic. The advantages the technique can offer over currently established methods such as immunoassays include the generation of faster, more sensitive data, with increased specificity and reduced costs.
Despite these advantages, the adoption of mass spectrometry (MS) in the clinic has been a slow process. Historically spectrometers have been large, expensive and complex pieces of equipment, requiring specialist technicians. Added to this, software interfaces that were not particularly user friendly, a lack of standardised reference materials, and questionable reliability have added to the challenges of making mass spectrometry more common in the clinic.
With the development of more compact, affordable and reliable systems, the use of MS in the clinical laboratory has steadily evolved over the past 30 years, to include an ever-wider range of applications. Early roles included drug testing, with MS becoming a part of the mandatory guidelines for federal drug testing in 1988. This was followed by the introduction of tandem mass spectrometry for newborn screening in 1990, enabling the detection of an increased number of metabolic disorders from heel-prick dried blood-spot samples.1 Other now common applications were subsequently introduced, such as therapeutic drug monitoring, steroid analysis, and Vitamin D monitoring.
In 2013, the first FDA approval for a MALDI-TOF-based system for the clinical identification of microbes in the U.S. was granted, highlighting the potential of the technology to significantly reduce the time of microbiology diagnosis and improve patient care. A comparative study found that identification of bacteria responsible for infectious diarrhoea could be completed within 30 minutes using MALDI-TOF MS, shortening test time by around 2-3 days when compared to using routine phenotypic methods. Rapid identification of pathogens in other clinical sample types such as blood, urine, and cerebrospinal fluid is also possible with MALDI-TOF MS.2 This speed of identification enables clinicians to rapidly commence appropriate treatment, increasing the chances of patient recovery, whilst reducing the potential overuse of inappropriate antibiotics.
In addition to improving test times, MALDI-TOF has the added advantages of being a relatively simple and economical process, with no need for prior sample separation. The costs of reagents for MS-based identification are estimated to not exceed US$0.50, compared to US$10 per isolate for phenotypic identification methods, which equates to substantial savings for hospitals. MALDI-TOF MS is revolutionising clinical microbiology, and is becoming widely used in the detection of bacterial, fungal and viral diseases, as well as the determination of antibiotic resistance.
As well as playing a role in clinical microbiology, MS is also weaving its way into cancer diagnosis.
2013 saw the creation of the iKnife, an electrosurgical knife connected to a mass spectrometer, which can help surgeons identify cancerous tissue in real-time. Developed by Dr Zoltan Takats at Imperial College, and acquired by Waters, the iKnife creates vapour by heating the tissue as it cuts. Molecules in this vapour can then be analysed by Rapid Evaporative Ionisation Mass Spectrometry (REIMS) to identify cancerous and healthy tissue. Speaking in 2013, Dr. Takats described how “It provides a result almost instantly, allowing surgeons to carry out procedures with a level of accuracy that hasn't been possible before.” It is hoped that the adoption of technology such as this could help to improve cancer surgery, reduce tumour recurrence rates and increase patient survival.
To match the growing trend of providing point-of-care diagnostics, miniaturisation is a growing area of research in the MS field. Handheld, portable devices could democratise MS based diagnosis, opening up the use of the technology in resource limited regions. Since the Cooks lab at Purdue University developed the first miniature ion trap mass spectrometer in 1991, a growing number of research groups are focusing their efforts on this area. One example is the Ramsey group at the University of North Carolina, where high pressure systems are being developed to create a portable mass spectrometer suitable for a range of applications.
As well as the move towards miniaturised systems, the future of clinical MS is likely to see growth in the use of automation. This should help increase the ease of use and lead to greater adoption by smaller laboratories. Other areas of interest may include tissue imaging, where MS may begin to replace traditional histology techniques, to provide a wealth of new information to pathologists and clinicians. MS looks set to play a key role in the future of diagnostics, with continued improvements making the technology more accessible, cost-effective and informative to a range of clinical applications.
1 Jannetto, P. J., & Fitzgerald, R. L. (2015). Effective Use of Mass Spectrometry in the Clinical Laboratory. Clinical Chemistry, 62(1), 92-98. doi:10.1373/clinchem.2015.248146
2 Singhal, N., Kumar, M., Kanaujia, P. K., & Virdi, J. S. (2015). MALDI-TOF mass spectrometry: an emerging technology for microbial identification and diagnosis. Frontiers in Microbiology, 6. doi:10.3389/fmicb.2015.00791