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Mass Spectrometers

Improving Capability and Affordability of Mass Spectrometers

Basic MS technologies used for proteomics have drastically matured improving the potential for sensitivity, resolution, and scan speed that synergistically merge with the chromatographic technology and integrated databases.

Since the turn of the century, mass spectrometer (MS) technologies have continued to improve dramatically, and advanced strategies that were impossible a decade ago are increasingly becoming available. The basic characteristics behind these advancements are MS resolution, quantitative accuracy, and information science for appropriate data processing. In the early 1990s MS was introduced in hospitals or clinical laboratories for new-born screening of inborn errors of metabolism. Since then, the clinical applications of MS have expanded to the infectious disease field, drug toxicology testing, endocrinological testing, and therapeutic drug monitoring.

MS is now capable of measurements with high levels of reproducibility, precision, and accuracy, and has received recent interest in clinical research for its potential to extend current capabilities in biomarker discovery, development, and validation. Workflow enhancements are one of the main reasons for increasing adoption of MSs in the clinical lab. The advances include pre-analytic improvements in sample preparation, more high-performing chromatography options coupled to the MS instrument, and at the back end, better software that allows transfer of data to a hospital’s information system.

Recently, mass spectrometry is also supporting proteomic approaches, and it would be extremely difficult to obtain an overall picture of the proteome without MS. Moreover, the basic MS technologies used for proteomics, in the past two decades, have drastically matured improving the basic potential for sensitivity, resolution, and scan speed that synergistically merge with the chromatographic technology and integrated databases/software. This improvement has enabled high-throughput protein analysis and identification with wide dynamic distribution from complexed biological samples. Current advanced MS is also providing costs savings in cases where it is being used to replace radio isotope-based assays.

Advances in mass spectroscopy technology are continuing to increase both speed and resolution at an incredible rate. However, technological advances are not without pitfalls, barriers do still remain. Most commonly referenced are the high cost of instrumentation and the expertise required to use the technology. Delicate balancing of cost-to-benefit and cross-site reproducibility is required to justify more widespread implementation.

Indian Market Dynamics
The Indian mass spectrometers market in 2017 is estimated at Rs. 268 crores. Sciex has been present in India since the longest time. Waters has aggressive presence, and dominates the HRMS segment. Other brands with considerable presence are Agilent and Shimadzu. Thermo is perhaps the only one offering ion trap models now as its counterpart Bruker offering MALDI-TOF.

Biopharma relies heavily on mass spectrometers and finds that the same analysis can now be performed more speedily with mass spectrometry while using micrograms of product rather than milligrams. Proteomics research continues to dominate in this area and finds mass spectrometry an indispensable tool.  Triple quads find popularity with CROs, and with new ones being set up every year, triple quads shall continue to do well. Food safety shall continue to be an important buyer segment. Environmental clinical is yet to gain significance in India. Specifically in 2017 some of the large customers were National Centre for Biological Sciences (NCBS); Postgraduate Institute of Medical Education and Research (PGIMER); All India Institutes of Medical Sciences (AIIMS); Lupin Limited; Cipla Limited; Syngene International; Defence Research Laboratory (DRL); Hetero Drugs; and ICAR-National Research Centre for Grapes

International testing laboratories continue to generate demand. European Union is looking at India. The technique is becoming popular with MNCs who have reference labs for inspection, and marine among others. Export driven demand is a key factor as is government buying for its research and inspection functions.

Global Market
The global MS market is expected to exhibit a promising 8.1 percent CAGR over the period between 2017 and 2024, rising from a valuation of USD 5.78 billion in 2017 to USD 9.99 billion by 2024, projects Transparency Market Research. The growth of the pharmaceutical and biotechnology industry and technological advancements in mass spectrometry are driving the growth of the global market. The growing use of mass spectrometry in emerging markets and the rising potential for its application in healthcare are the key areas of opportunity in this market.

The vast funds required to undertake research and development activities in this field are however limiting development efforts in the market to a certain extent. The high costs have not only restricted the entry of new and small companies in the market but have also deterred leading players from undertaking large-scale R&D activities. High product costs also limit the growth of the market to mostly developed economies; price-conscious consumers in regions with significant growth opportunities, such as Asia-Pacific, prefer to buy refurbished instruments.

Among the key product varieties, the segment of MALDI-TOF dominates the market and is expected to retain its dominance in the next few years as well. The higher preference to MALDI-TOF spectrometers over other varieties can be attributed to the faster rate of analysis and simple nature of sample preparation achieved with them. Based on technology, in 2017, the hybrid mass spectrometry segment is expected to account for the largest share of the market. The extensive applications of hybrid MSs coupled with the technological advancements in mass spectrometry are driving the growth of this segment.

From a geographical perspective, the market for MS in North America is expected to account for a dominant share in the global market, chiefly owing to the thriving biotechnology industry. The European market closely follows, acquiring a significant share of the global market owing to the established pharmaceutical industry and a flourishing biotechnology industry. In the near future, the Asia-Pacific market is expected to emerge as a promising market for MSs owing to the rising demand for high-quality analysis tools.

The vendor landscape is intensely competitive and has few players, most of them holding large shares in the overall market. These factors have restricted the entry of new players in the market to a large extent and the situation is projected to remain the same in the near future as well. From a competitive perspective, the rise in the number of mergers, acquisitions, and collaborations in the market in the past few years has also benefitted the market by allowing a significant rise in the rate of development of innovative and advanced technologies.

Technological Advances
The demands of life-science applications have led to the improvement of MS technologies and rapid growth of new types of instruments that feature powerful analytical capabilities – sensitivity, selectivity, resolution, throughput, mass range, and mass accuracy. There have not been many MS instrument innovations in the past 10 years. Rather, innovations have been in the peripheral areas of MSs to enhance key requirements for a clinical lab such as accuracy, speed, reproducibility, and multiplexing. Automation is playing a central role in adoption of MS in the clinical arena. Other peripheral advances include multichannel sample preparation; the ability to add more sophisticated HPLC units to handle more samples at once; more automation in middle steps for accuracy and speed; and more intuitive software at the backend. Software advances that enable easier use and integration with other systems are key improvements.

Hybrid instruments. One of the most powerful developments in the evolution of MS technology is the commercialization of hybrid instruments, made by combining two different types of mass analyzers together in tandem; one can choose almost any combination of quadrupole, time-of-flight, or ion-trap hybrids. These hybrid instruments combine the best features from the different components and allow tandem mass spectrometry experiments and unique scanning modes that are not possible on a single instrument.

Software advances. Dedicated data analysis software has been developed for biopharma applications and the workflow-specific design of this software has streamlined the process. In addition, walk-up software has been developed to enable novice MS users, such as biologists, to have access to high-end MS instruments. Special consideration has also been given to provide total workflow solutions to address steps from sample preparation all the way to reporting. High-resolution, top-down, or bottom-up systems combined with novel fragmentation techniques and improved analysis software will be available in a year or two which will overcome the isobaric amino acid issue for de-novo protein sequencing by MS.

Parallel accumulation–serial fragmentation. Proteomics researchers always want improvements in speed, sensitivity, and quantitative capabilities, while maintaining the advantages of high-resolution, accurate mass, and isotopic pattern fidelity so they can go deeper into the proteome. With PASEF, scientists now do not have to trade off resolution for scan speed and sensitivity – they get the triple benefit of high-sensitivity, high-scan speed, and unrivalled specificity. This new technology has the potential to revolutionize several areas in proteomics where speed and robustness are key for running large sample cohorts and applications requiring increased sensitivity.

Advances in biopharmaceuticals. In essence, major development efforts can be divided into two disciplines. From a physics perspective, significant advances in instrument design are very close to release that will greatly improve not just the capability to analyze large biomolecules, but also the reproducibility of such analyses. On the biology front, advancements in data analysis software that can make clear biological sense of the rich data collected by mass spectrometry are critical for multiple applications. Combining these efforts with the latest capabilities in automated sample preparation and separation techniques allows for a big step forward in the total confidence in using mass spectrometry for biopharmaceuticals.

Although MS technology has improved in sensitivity and dynamic range, the hardware capability is ultimately limited by the complexity of samples. In the biopharmaceutical industry, challenges with sample preparation and data processing remain. Biologics manufacturers and analytical laboratories are working closely with instrument suppliers to address these issues. Improvements are continually introduced, and as a result the potential for additional use of this analytical technology for biologic drug development and manufacturing is significant.

Vendors Update
High initial costs for instrument purchase and the facilities required to house and operate the instruments places an enormous financial burden on any hospital or healthcare system that wishes to implement MS into its clinical assessments. Although costs remain high, more affordable MSs have been introduced into the commercial market, albeit often providing reduced functionality to their more expensive counterparts. Many of the modern MS available exhibit a reduced footprint and can be combined with purpose-built benches that contain the necessary background instrument within a sound-insulated base. Although this arrangement is not preferred, it allows MS use in laboratories, which may not have otherwise suitable facilities.

The most recent trend in the arena is a new kind of almost anyone can use MSs. Within the past year, two regulatory agency-cleared, more user-friendly MS kits have become available in the US and Europe. The first mass spec kit approved for use was in Europe and developed by Waters for measuring the presence of an immunosuppressant, tacrolimus, in samples from kidney and liver transplant patients. The second mass spec kit within the past year was by Sciex for vitamin D assays. It was cleared by the FDA in May 2017 via the de novo regulatory pathway.

  • PerkinElmer has launched its NexION 2000 inductively coupled plasma MS (ICP-MS) and QSight triple quadrupole LC/MS/MS instrument for customers in India. The official launch announcement is being conducted in Hyderabad and will be subsequently launched in Mumbai, Ahmedabad, and Delhi. The NexION 2000 ICP-MS system is specifically designed to handle any sample matrix, address any interference, and detect any particle size across a variety of applications. The QSight instrument offers patented flow-based mass spectrometry that enables laboratories to test highly complex samples and experience increased throughput
  • Bruker has introduced the timsTOF Pro system for PASEF mass spectrometry, using proprietary trapped ion mobility spectrometry (TIMS) technology for higher-speed, higher-sensitivity, and robust shotgun proteomics with outstanding single-shot peptide and protein identification performance. The novel timsTOF Pro is particularly advantageous for quantitative proteomics workflows also, as this innovative TIMS-powered QTOF-MS is supported by MaxQuant/Perseus and PEAKS Studio proteome analysis software
  • Thermo Fisher Scientific has strengthened its leadership in mass spectrometry by launching new technologies to advance cutting-edge research and improve results in applied markets. The new Q Exactive HF-X Quadrupole Orbitrap MS is designed for exceptional sensitivity and reproducibility in the analysis of complex biological samples. The Orbitrap Fusion Lumos MS can expand instrument power, performance, and versatility. The new, ready-to-use InsuQuant Mass Spectrometric Kit is designed to simplify sample preparation during insulin bioanalysis
  • Agilent Technologies has expanded its portfolio of scientific instruments with a new LC/MS system that provides even greater sensitivity and accuracy for applications such as peptide quantitation, food safety, clinical research, and forensic toxicology. The new Agilent 6495B triple quadrupole LC/MS system combines HPLC and triple quadrupole MS in an integrated system that delivers outstanding operational efficiencies. The 6495B provides improved mass range, scan speed, and polarity switching – all of which enable scientists to better analyze molecules from a wide array of sample matrices
  • Sciex announced their latest solution in the X-Series QTOF-MS platform. The newest X-series model, the X500B QTOF system, brings simplicity, high-performance, and robustness for bio-therapeutic analyses to one of the most compact MS system footprints on the market. The new user-friendly Sciex OS software interface and powerful BioPharmaView 2.0 processing software comprise an unmatched integrated LC-MS solution for MS experts, or novices, performing standard bio-therapeutic characterization

Outlook
Despite the advances in MS technology achieved to date, the industry expects further notable improvements in the long term. While current MS technology has been primarily limited to the analysis of in-vitro proteins, proteoforms, and multi-protein complexes, the future drive in mass spectrometry is to study the same entities in vivo to determine native biological structures and their dynamics within biological processes. As MS becomes gradually more commonplace in the clinical laboratory, the true benefits of its use will become rapidly apparent.

It is not that MS will replace current low-cost and reliable clinical tests, but as biomarker testing evolves MS has the ability to broaden the inventory of disease-specific molecules and place itself within a clear niche in which to excel. Although improvements in data processing software for throughout enhancement are still needed, MS technology has advanced dramatically in the past 25 years. It is exciting to think about how its capabilities will be expanded over the next 25 years.

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