The sheer power and accuracy of mass spectrometry is undeniable. Put simply, mass spectrometry is designed to identify, and often quantify, the chemical makeup of a sample by measuring the mass-to-charge ratio of the ions that constitute that sample. A growing number of hospital laboratories are starting to consider the value it can bring to them not in the distant future, but now. By offering the benefits of time savings, cost savings, and improved patient care, mass spectrometry could be one of the clinical laboratory's most important improvements in decades. This technique holds the key advantage of being extraordinarily more sensitive than other methods that are so often used in laboratory medicine. Clinical laboratories are becoming increasingly dependent on mass spectrometry data within the areas of toxicology, immunology, cancer genetics, and proteomic analysis.

While the trend toward the clinical adoption of mass spectrometry is gaining momentum, only few mass spectrometry instruments are actually used in the clinical lab today. The rest are in research settings, academic institutions, or reference labs. The clinical laboratory then presents a leadership opportunity for people in the in vitro diagnostics industry who can apply real innovation to current practices.

Global Market

The global mass spectrometry market is expected to reach USD 7279 million by 2020 from USD 4920 million in 2015 at a CAGR of 8.1 percent during the forecast period, 2015-2020. Over the years, the mass spectrometry market has witnessed various technological advancements. These advancements have led to growth in the number of mass spectrometry applications including drug discovery and development, metabolomics, and diagnostics. The global mass spectrometry market is moving away from traditional to high-resolution-based technologies such as the Quadrupole-Time of Flight (Q-TOF) mass spectrometry. The matrix-assisted laser desorption/ionization (MALDI)-TOF segment is expected to grow at a faster rate due to its increasing adoption in clinical diagnostics applications as it offers improved resolution, accuracy, and sensitivity.

Refurbished mass spectrometer is also a growing segment within this market. Buyers consider top players as the most suitable choice to procure these technologies due to a greater post-sales service provided. Being a mature market, there are several mass spectrometry suppliers, yet top players find the largest buyers due to competitive post-sales services and maintenance services. The expensive nature of these devices has resulted in manufacturers opting to provide several discounts and extensive negotiations in terms of supplying accessories and reagents used in mass spectrometry experiments. Greater automation and conjoint software applications for greater data processing capability are also expected. Major future trends to look out for include bacterial identification, tissue imaging, and functional assays. These are also the major areas for investment for companies.

North America dominates the global mass spectrometry market. This is due to increased government investments in biotechnology and biomedical areas. In addition, increased research in the field of proteomics is also supporting the growth of mass spectrometry in the region. The U.S. represents the largest market for mass spectrometry techniques followed by Canada in North America. In Europe, France, Germany, Italy, Spain, and the U.K. hold major share of mass spectrometry market.

However, Asia is expected to show high growth rates in the next 5 years in global mass spectrometry market. This is due to many companies constructing their manufacturing and research facilities in the region.

In addition, increasing number of conferences and exhibitions by manufacturing companies to promote mass spectrometry technology is also contributing in the growth of mass spectrometry market in the region. Japan, China, and India are expected to be the fastest-growing mass spectrometry markets in Asia.

Technology Trends

The need for rapid, sensitive, and effective identification and quantitation of drugs and metabolites to accelerate drug discovery and development has given mass spectrometry its central position in drug metabolism and pharmacokinetic research.

New mass spectrometry technologies, representing upgrades both in performance and versatility, now challenge the traditional workhorse mass spectrometer of proteomics, the linear ion trap (LIT). Competing for share in the high-resolution mass spectrometry market segment, hybrid time-of-flight (TOF) and Orbitrap instruments have become fixtures in proteomics research. The strength of these instrument types is in the production and conversion of richly complex discovery proteomics data into high-throughput targeted analyses needed to advance new drug targets and biomarkers. TOF mass spectrometry technology is integral to modern proteomics research with a long-held advantage in mass resolution over ion trap and triple quadrupole instruments, high-mass range, and amenability to soft MALDI ionization.

Q-TOF mass spectrometry. An added quadrupole to a TOF analyzer allows for more diverse ionization and dissociation or fragmentation options; pure TOF is generally limited pulsed ionization such as MALDI. Resultant quadrupole-TOF (Q-TOF) instruments provide more controllable fragmentation for peptide sequencing and have acquisition speeds that unlock data-independent acquisition (DIA) methods. The fortunes of Q-TOF technology have risen with the development of DIA and labs' need for a versatile workhorse instrument able to participate in proteomics workflows from global discovery to targeted analysis and quantitation. Data-independent acquisition provides thorough, highly complex, post hoc searchable peptide maps; the method also allows researchers to perform targeted searches later at a workstation for peptides of interest and initial relative quantitation.

MALDI-TOF mass spectrometry. Recent years have seen a phenomenal increase in the use of MALDI-TOF mass spectrometry. The introduction of this technology to microbiology has been a major success and MALDI-TOF mass spectrometry is now used for routine diagnostic or diagnostic-like purposes in clinics, veterinary, pharma, and food microbiology laboratories. It has also evolved into a powerful tool for the analysis of organisms in the environment and for research into microbial communities. The throughput capabilities, accuracy, and low running costs of the system enable analyses at a scale which was not possible until recently. MALDI-TOF can rapidly and accurately identify organisms with a high degree of specificity and sensitivity. This technology is gaining popularity and is being adopted in clinical laboratories around the world for organism identification.

GC mass spectrometry. Gas chromatography mass spectrometry innovations in mass spectrometry instrumentation have driven the traditional 2D hyphenated technology, and recently 3D and 4D hyphenated technologies in the case of a second GC and/or a mass spectrometry-equivalent being added, to become one of the dominated platforms for use in a wide assortment of analytical and bio-analytical techniques. The advancement in GC-mass spectrometry instrumentation was initially and still is driven by the need for a more comprehensive analytical and bio-analytical technique that can accurately and precisely discriminate targeted and untargeted analytes from higher-complexity sample mixtures in a sensitive and selective way.

IMS mass spectrometry. Ion mobility spectrometry (IMS) coupled to mass spectrometry has seen spectacular growth over the last two decades. Increasing IMS sensitivity and capacity with improvements in mass spectrometry instrumentation have driven this growth. As a result, a diverse new set of techniques for separating ions by their mobility has arisen, each with characteristics that make them favorable for some experiments and some mass spectrometers.

Growth Drivers

Advancements in mass spectrometry technologies, continuous new product launches by major participants, growing government support in funding for research activities, and rising uptake in the life science and clinical analysis sector are the key factors driving the demand for mass spectrometers. Globally, the market has undergone a number of mergers and acquisitions (M&As) and also seen an increase in co-marketing and partnership agreements among companies with an objective to capture the market share at an early stage by launching advanced solutions for the clinical arena. In addition, technological advancement in mass spectrometry also attracts end users to adopt the technology.

Challenges

Mass spectrometry is an adaptable technique, but it has disadvantages that the industry is constantly attempting to address, especially as the method is increasingly becoming an integral part of clinical diagnostic medicine. A major concern in the adoption of clinical mass spectrometry is the added sample preparation and liquid handling required with bio-specimen processing. Traditionally, sample preparation, liquid/specimen handling, and liquid chromatography (LC)-mass spectrometryacquisition have all been performed on disparate platforms that require different software. Interestingly, technical issues with mass spectrometry devices are not the only growing pains that companies face as they shuttle this technology into clinical laboratories. Mass spectrometry machines have been notoriously complex to operate, and there are too few technicians who are qualified to run the equipment, as well as interpret the results.

Mass spectrometry today remains an expert method, and with little training offered for mass spectrometry in medical technologist programs, most clinical labs are on their own to cultivate the appropriate expertise that will allow them to develop and run the methods they need. This currently limits the technology to laboratories that have the ability to train and dedicate their staff to this technology, not to mention the amount of time that it takes to develop and validate a homebrewed assay within the laboratory.

Additionally, the massive glut of data that is generated by mass spectrometry analysis - similar to what has been a growing problem for users of next-generation sequencing - is beginning to cause frustration among clinical researchers and is a problem that has caught the eye of some mass spectrometer manufacturers.

While great advances have been made in liquid handling and LC/mass spectrometry acquisition, data review by technicians or lab directors remains a cumbersome bottleneck.

The Road Ahead

While mass spectrometry is utilized in all corners of modern biology, there have been several areas where clinical mass spectrometry use has gained traction. Clinical laboratories often use mass spectrometry technology for disease screening and diagnosis, toxicity studies, and in the identification of new biomarkers. However, in recent years, alternatives to standard immunoassay-driven methods have been on the rise as mass spectrometry platforms often make screens much more accurate due to the limitations of nonspecific binding by standard methods.

Dr Aslam Khan, Assistant Vice President, Reliance Life Sciences, Navi Mumbai

Quantification of mAbs in biological matrices utilizes enzyme-linked immune sorbent assay (ELISA), the most-widely applied technique. ELISA generates a result based on antibody binding properties, and does not reveal changes in the structure of mAbs. However, LC/MS exhibits better specificity, and generates a better protein-specific charge envelope.

LC-MS-based approaches have become a focal point of analytical research interest owing to an amalgam of factors including high sensitivity, throughput, and robust nature of these assays with additional advantages of multiplexing capabilities and also alleviate the need to raise antibodies against target analytes, additionally complementing LBA.

Bioanalytical laboratory in Reliance was among the first labs in the country to have developed, validated, and applied LC/MS-based analytical methods for quantitative estimation of large molecules including mAbs. Methods for Trastuzumab and Cetuximab are successfully applied for performing sample analyses of pharmacokinetic studies conducted by Reliance.

Dr Aslam Khan
Assistant Vice President,
Reliance Life Sciences, Navi Mumbai

Moreover, the extreme sensitivity of mass spectrometry is being exploited for the detection and quantitative measurement of cancer tissue biomarkers. Mass spectrometry methods for the diagnosis of specific disease states like cancer have clear advantages over traditional immunohistochemistry assays. Not only is mass spectrometry faster and more sensitive, but it also has the capacity to employ multiplexing conditions - monitoring multiple analytes at once - and in the case for cancer, screening for dozens of protein and nucleic acid biomarkers simultaneously.

Multiplexing is an advantage not only from the ability to test many analytes quickly and accurately but because it is performed with a single sample preparation; additional interrogations of the same sample can be performed at minimal additional cost. In the next few years, one will see more highly multiplexed mass spectrometry platforms with much greater ease of use and integrated sample/reagent liquid handling.

Yet, clinical mass spectrometer manufacturers are not being hindered by some of the concerns coming from the end users. To their credit, companies are not only trying to tackle as many current issues as possible, they are simultaneously pushing the frontiers of laboratory medicine forward by addressing what they believe will be future needs of their clients. The next few years will be critical to continue to improve the database coverage and accuracy. There is also an opportunity to develop the database to identify highly complex organisms.

With emerging technologies and increased use, one can expect to see even broader applications of clinical mass spectrometry. In the burgeoning era of precision medicine, mass spectrometry seems well positioned to provide the heavy lifting for new clinical applications and even replace some of the current routine diagnostic tools.


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