MS – Poised to scale new heights

The breadth of applications for mass spectrometry surpasses that of any other analytical technique. Combined with innovations, improved sensitivity, and enhanced data analysis capabilities, MS has limitless potential.

Mass spectrometry, despite its long history dating back to the first mass spectrometry (MS) instrument, the parabola spectrograph in 1907, is far from stagnant. Over the years, both mass analyzers and ionization and fragmentation techniques have undergone significant development, paving the way for widespread applications in various fields.

Originally employed primarily in physics, particularly for determining atomic weights and discovering stable isotopes, mass spectrometry has now evolved into a cornerstone technology in chemistry and bioscience too. Its role today chiefly involves identifying and quantifying compounds in samples, as well as elucidating molecular structures. The sensitivity, robustness, and reproducibility of mass spectrometry have made it indispensable in driving advancements in chemistry, biochemistry, molecular biology, and associated fields over the past two to three decades.

The ever-increasing complexity of new therapeutics and the shrinking discovery timelines have spurred the need for innovative analytical techniques. Mass spectrometry stands out as one of the most versatile analytical methods extensively utilized across the entire drug discovery pipeline. To keep pace with the evolving landscape of modern drug development, new mass spectrometers and sampling methods are continuously introduced, catering to the diverse chemistries, therapeutic types, and screening practices employed by contemporary drug researchers.

The breadth of applications for mass spectrometry surpasses that of any other analytical technique. From determining molecular mass in organic chemistry to forensic, environmental, and omics sciences, and even extending to extra-terrestrial exploration, its utility knows no bounds. Mass spectrometry, often coupled with chromatographic techniques, finds wide-ranging applications in the pharmaceutical industry, forensic laboratories, as well as in sanitary and environmental inspection facilities.

In the next decade, the mass spectrometer industry is poised to scale new heights, driven by ongoing technological advancements and expanding applications across diverse sectors. As demand grows for faster, more sensitive, and versatile analytical tools, mass spectrometry is expected to play a pivotal role in shaping the future of scientific research and industrial development.

Indian market dynamics
The Indian mass spectrometers market gained huge traction in 2023. Estimated at ₹935 crore (USD 110 million), it saw a 31.6-percent increase over 2022 by value. The increase in the number of spectrometry service providers have significantly contributed to market growth.

Triple quadrupoles at ₹445 crore and HRMS (including Q TOF and Orbitrap) at ₹153 crore continue to dominate the sector and have a combined 64-percent share. Q trap with single vendor Sciex has its niche customers.

Sciex and Waters dominate the Indian mass spectrometers market. Agilent and Thermo Fisher Scientific are neck-to-neck and very close behind. Shimadzu is also aggressive.

In the last decades, mass spectrometry has been increasingly used in pharmaceutical analysis, both for research aims and routine quality controls. Among different instrumental setups, ultra-high-resolution mass spectrometry with Fourier transform instruments, i.e., Fourier transform ion cyclotron resonance (FTICR) and Orbitrap, give access to valuable molecular information for pharmaceutical analysis. They are increasingly used for the possibility of measuring accurate mass-to-charge ratios, which can often enable a direct interpretation of the studied system without acquiring additional information, as in the case of low-resolution mass spectrometers. In addition to accurate measurement, high-resolution mass spectrometry can produce compositional and structural information on small molecules, biomolecules, and complexes.

The state government agencies and PSUs have invited 33 high-resolution mass spectrometer system tenders so far this year. Because of the possibilities for advancement in developing markets due to the greenfield initiatives being installed in numerous end-user industries in those international locations, India significantly demands single mass spectrometers and hybrid spectrometry devices.

A central facility for mass spectrometry-based proteomics, metabolomics, and lipidomics platforms was inaugurated in May 2023 at the Rajiv Gandhi Centre for Biotechnology (RGCB) in Thiruvananthapuram by Dr Vinod Kumar Paul, Member NITI Aayog.

Mass spectrometers are commonly used for PFAS (per- and polyfluoroalkyl substances) testing. Mass spectrometry is a powerful analytical technique that can detect and quantify various compounds, including PFAS, with high sensitivity and specificity. It is often employed in environmental, food safety, and forensic laboratories for the analysis of PFAS in various matrices, such as water, soil, air, and biological samples. Mass spectrometry techniques, such as liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS), are commonly used for PFAS testing due to their ability to separate and identify individual PFAS compounds in complex mixtures.

In India, the awareness on the PFAS is limited, and currently no regulations are in place in any of the products. The Indian industries need to be prepared for the challenges of PFAS as their products may face scrutiny in the global market, particularly EU, Japan, and the USA. The government is expected to implement PFAS testing regulations soon, and this will provide impetus to the market.

Mass spectrometry is a powerful tool for analyzing the proteome in cancer research. This technique can be combined with machine learning algorithms to identify proteomic signatures that act as potential biomarkers to predict survival outcomes in patients with cancer treated with immunotherapy. MS allows for a top-down approach, enabling global analysis of intact protein from blood samples. Unlike antibody-based approaches (which have the potential to introduce biases based on the specific proteins being targeted), MS looks at the proteome globally, making it an unbiased assay. Many types of MS exist, each with their own advantages for use. One type, matrix-assisted laser desorption/ionization time-of-flight (MALDI-ToF) MS uses laser energy to convert analytes into gaseous ions with minimal protein fragmentation. An ionization matrix is used to absorb the laser energy and assist in the ionization of the analytes and the conversion into the gaseous phase. Subsequently, the time required for a given analyte to pass through an electric field and be captured by a detector is measured using the ToF mass spectrometer. The mass-to-charge ratio of each detected ion is recorded and yields a spectrum representative of the specific composition and abundance of analytes.

One of the newborn screening methods to detect inherited metabolic disorders caused by congenital enzyme defects uses tandem mass spectrometry. Mass spectrometers ionize a target substance, identify the specific substances, then determine the amounts of such substances in the extremely small samples like dried blood filter paper. This has yet to gain popularity in India.

Global market dynamics
The global mass spectrometry market in terms of revenue is estimated to be worth USD 6.9 billion in 2022, poised to reach USD 14.6 billion by 2032, growing at a CAGR of 7.7 percent from 2023 to 2033. It exhibits high-growth prospects driven by factors, such as increasing applications across various industries, including pharmaceuticals, biotechnology, environmental testing, and food and beverage analysis, development of high-resolution mass spectrometers and portable mass spectrometry devices, rising investments in R&D activities, coupled with the growing demand for personalized medicine and diagnostics.

MS is gaining traction in clinical laboratories for its multiplexing capacity, sensitivity, and potential for real-time analysis. It offers unmatched capabilities in biomolecule identification and quantification across various clinical fields. This adoption aligns with evolving screening programs and treatment modalities, promising significant advancements in diagnostics and personalized medicine.

The market faces challenges during economic downturns, including increased manufacturing and operating costs and fluctuations in shipping costs. Lack of imaging capabilities and the capital expenditure required for device installation and upkeep further constrain market growth. Small diagnostic labs and clinics, particularly in underdeveloped countries, often lack access to mass spectroscopy equipment.

Other challenges include high costs, skilled personnel requirements, lack of automation, and regulatory hurdles. There is also a gap in identifying early-stage biomarkers. Overcoming these challenges necessitates technological innovations, software development, and the integration of machine learning algorithms. Despite obstacles, the continued advancement of mass spectrometry holds potential to revolutionize healthcare delivery and patient outcomes.

Additionally, the labor-intensive nature of mass spectrometry and the need for trained personnel to operate the equipment hinder expansion. High product prices and a shortage of qualified individuals to operate these devices also limit growth.

Product insights. The instruments segment dominated the market in 2023, and the trend is expected to continue over the next five years. This segment includes various types of MS instruments used for analytical purposes. It encompasses different configurations, such as quadrupole mass spectrometers, time-of-flight (TOF) mass spectrometers, ion trap mass spectrometers, magnetic sector mass spectrometers, and hybrid mass spectrometers.

Continuous advancements in mass spectrometry technology have led to improved instrument performance, enhanced sensitivity, higher resolution, faster data acquisition, and more sophisticated data analysis capabilities. The demand for instruments arises from the desire to leverage these technological advancements and gain access to state-of-the-art instrumentation.

The consumables and services segment is expected to witness a noticeable growth too. The segment comprises accessories and consumables required for operating MS instruments. It includes ionization sources (e.g., electrospray ionization, matrix-assisted laser desorption/ionization), sample introduction systems (e.g., autosamplers), chromatography columns (e.g., liquid chromatography columns), calibration standards, sample preparation kits, and other consumables necessary for sample analysis.

The rising focus on cost-effective yet efficient MS procedures in the laboratory promotes the growth of the consumables segment. Consumables offer a cost-effective and convenient solution for MS laboratories. Instead of investing in expensive equipment, laboratories can purchase consumables as needed. Consumables also save time by simplifying sample preparation and instrument maintenance processes.

Application insights. The pharmaceutical segment held the highest market share in 2022, accounting for one-fourths of the mass spectrometry market revenue, owing to use of mass spectrometry in the drug analysis and quality control processes. However, the biotechnology segment is expected to witness the fastest CAGR of 9.0 percent from 2023 to 2032, owing to increase in use of mass spectrometry in the proteomics research.

The proteomics segment has the largest share of the market in 2023. MS-based proteomics has contributed significantly to biomarker discovery, which is crucial for early disease detection, diagnosis, and monitoring. By comparing protein expression profiles between healthy and diseased individuals, mass spectrometry can identify potential biomarkers associated with specific diseases.

A significant rise in research and development activities has also contributed to the segment’s growth in recent years. MS-based proteomics allows researchers to explore the complete proteome of an organism, tissue, or cell and provides insights into protein expression patterns, post-translational modifications, and protein-protein interactions.

The metabolomics segment will witness noticeable growth over the next five years. Metabolomics allows for the profiling and identification of a broad range of metabolites present in biological samples, including endogenous metabolites, drug metabolites, and environmental metabolites. The rising biomarker discovery and research activities promote the growth of the metabolomics segment.

By end-use, the pharmaceutical and biotechnology segment led the market in 2023. The segment will continue to grow at a noticeable pace owing to the increasing rate of discovery, research, and development-based MS activities in the industries. The improving infrastructure at biotechnology and pharmaceutical companies, along with the significant technological advancements, plays a crucial role in the segment’s development.

On the other hand, the government and academic institutions segment is experiencing significant growth with the rising investment in research and development activities by governments. Moreover, the rising focus on research and testing activities, especially focused on therapeutics discovery, will promote the segment’s growth.

Region insights. North America held the highest market share in terms of revenue in 2022, accounting for more than two-fifths of the global MS market revenue, owing to high research activities in this region, availability of advanced mass spectrometers, and strong presence of market key players. However, the Asia-Pacific region is expected to witness the fastest CAGR of 8.6 percent from 2023 to 2032, owing to development of biopharmaceutical industry, and high adoption of new technology equipment.

Major players. The major players in the global MS market are Thermo Fisher Scientific, SCIEX, Agilent Technologies, Waters Corporation, Kore Technologies, Ltd., PerkinElmer, Shimadzu Corporation, Bruker Corp., Analytik Jena, JEOL Ltd., DANI Instruments, LECO, and Hiden Analytical. These players have adopted strategies, such as product launch, acquisition, collaboration, and agreement to increase their market share and maintain dominant shares in different regions.

By technology, the quadrupole liquid chromatography-mass spectrometry segment dominated the market in 2023, and the segment will continue to witness a significant growth over the next five years. The multiple advantages offered by the technology have boosted its application in the market. Quadrupole liquid chromatography-mass spectrometry offers fast analysis times, making it suitable for high-throughput applications. The technique allows for rapid separation of compounds by liquid chromatography, combined with fast scanning and data acquisition by the mass spectrometer.

Quadrupole liquid chromatography-mass spectrometry is a versatile analytical technique that can be applied to a broad range of applications in various industries.

Recent advancements in mass spectrometry include the development of high-throughput techniques, enhanced data analysis software, and improved instrumentation for greater sensitivity and accuracy in compound identification and quantification.

UHPLC. Recent advancements in mass spectrometry have facilitated the widespread use of isotope dilution ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC–MS/MS) for trace analysis of polyfluoroalkyl and perfluoroalkyl substances (PFAS). This technology allows for precise quantification of PFAS in difficult matrices, such as human blood.

A recent development in PFAS analysis involves commercial non-targeted analysis, claiming cost-effective relative concentration measurements comparable to absolute quantification using UHPLC–MS/MS. This emerging approach has sparked interest but requires validation on a larger scale.

This evaluated the performance of targeted absolute quantification via isotope dilution LC–MS/MS against commercial non-targeted relative quantification assays for major PFAS in human blood from a large cohort. Strong correlations were found between the two methods for each PFAS, suggesting the potential of the commercial non-targeted approach.

MSI in n-glycosylation. Glycosylation, a prevalent post-translational modification, has been implicated in various diseases, with N-glycans serving as potential biomarkers due to their evolving patterns. However, their diverse morphologies pose challenges for conventional identification methods. Mass spectrometry imaging techniques offer spatial mapping of glycan distributions, providing insights into their structure and function.

By leveraging developments in MS equipment, data acquisition, and sample handling, glycan MSI holds promise for understanding the role of glycosylation in disease pathology and identifying potential diagnostic and therapeutic targets.

Biotherapeutic drug development. Mass spectrometry (MS) has emerged as a pivotal technology in the development of biotherapeutic drugs, offering unparalleled insights into the structural intricacies of therapeutic proteins. Its evolution from an early-stage tool to a critical component throughout the drug development process underscores its importance in addressing key challenges faced by the biopharmaceutical industry.

uHT–MS in ADME screening. Ultra-high-throughput mass spectrometry holds immense potential in revolutionizing in vitro absorption, distribution, metabolism, and excretion (ADME) screening within the pharmaceutical industry. With the capability to acquire mass spectra of samples within seconds, uHT–MS offers a remarkable enhancement in sample throughput, enabling rapid analysis of compound properties crucial for drug discovery and development. This technology, encompassing methods like matrix-assisted laser desorption/ionization (MALDI) and desorption electrospray ionization (DESI), has garnered significant interest due to its potential applications in high-throughput screening (HTS) and experimentation.

Emerging technologies
Some of the emerging technologies and their potential applications that have a significant impact on mass spectrometry include:

Multipurpose Software – MetAbolomics ReSearch (MARS), a vendor-agnostic software designed for untargeted metabolomics analysis using liquid chromatography-mass spectrometry (LC-MS). MARS encompasses all steps of metabolomics analysis, from data conversion and processing to statistical analysis, annotation/identification, quantification, and preliminary biological interpretation.

Key features of MARS include support for ion mobility data, flexibility in building reference databases, innovative tools for metabolite annotation, such as MS/MS validation and adduct detection, and integration with metabolic maps for biological interpretation. The software prioritizes user-friendliness with a graphical user interface (GUI) suitable for both non-expert and expert users, complemented by a manual and tutorials.

Additionally, MARS ensures compatibility with other software like Lipostar for seamless integration of metabolomics and lipidomics data. Overall, MARS are expected to enhance the application of untargeted metabolomics workflows.

Deep learning-enhanced mass spectrometry, an emerging technology in the field of neuroscience and spatial omics. The use of spatial omics technologies, such as mass spectrometry imaging and single-cell metabolomics, to study the molecular intricacies of the brain at different scales is a rapidly evolving area of research.

A team of researchers from the Beckman Institute for Advanced Science and Technology, led by professors Jonathan Sweedler and Fan Lam, has published groundbreaking research in Nature Methods.

The researchers used a biochemical imaging framework integrated with deep learning to create 3D molecular maps with cell specificity to better understand how the brain functions in health and disease. Their research is supported by a USD 3-million grant from the National Institute on Aging of the National Institutes of Health. They employed a combination of biochemical imaging and deep learning to generate 3D molecular maps with cell specificity, shedding light on how the brain functions in both health and disease.

Machine learning in IMS. Imaging mass spectrometry (IMS) has emerged as a potent tool utilized across diverse fields, such as biology, chemistry, and materials science. This technique offers a qualitative analysis of composition coupled with spatial mapping, delivering high chemical specificity and yielding datasets of varying dimensions, often hyperspectral in nature.

The fast-paced development of AI and machine learning (ML) tools has received significant attention in recent years. These tools, in principle, can enable the unification of data collection and analysis into a single pipeline to make sampling and analysis decisions on the go.

There are various ML approaches that have been applied to IMS data over the last decade, including both unsupervised and supervised methods. In recent years, these methods have gained prominence in extracting valuable insights from the intricate structures and relationships inherent in complex hyperspectral data.

As MS techniques witness increased adoption across various domains, alongside advancements in instrument capabilities, the size and dimensionality of MS data are anticipated to rise. Consequently, the need for advanced analytical methods, particularly ML techniques, becomes imperative. Efforts to consolidate data collection and analysis through edge computing and smart microscopes further underscore the significance of AI/ML in making real-time sampling and analysis decisions.

Recent research
Portable mass spectrometers. A team of researchers from the Massachusetts Institute of Technology (MIT) has developed a breakthrough in MS technology by leveraging additive manufacturing techniques. Mass spectrometers are essential tools for identifying chemical substances and are widely used in various applications, such as crime scene analysis and environmental monitoring. However, traditional mass spectrometers are bulky, expensive, and prone to damage, limiting their deployment in certain settings.

Using additive manufacturing, MIT researchers produced a mass filter, which is the core component of a mass spectrometer that is far lighter and cheaper than the same type of filter made with traditional techniques and materials.

Their miniaturized filter, known as a quadrupole, can be completely fabricated in a matter of hours for a few dollars. The 3D-printed device is as precise as some commercial-grade mass filters that can cost more than USD 100,000 and take weeks to manufacture.

The researchers fabricated the quadrupole from a durable and heat-resistant glass-ceramic resin using vat photopolymerization, a 3D printing process that allows for precise object creation.

Tests conducted with the 3D-printed quadrupoles showed higher resolutions compared to other miniature filters, and further experiments suggested that their performance is on par with large-scale commercial filters. Moving forward, the researchers aim to improve the quadrupole’s performance by increasing its length and exploring different ceramic materials for better heat transfer.

This groundbreaking development opens up new possibilities for mass spectrometry applications, such as portable analysis in remote locations and space exploration. The researchers envision a future where all key components of a mass spectrometer can be 3D printed, resulting in lighter, more cost-effective devices without sacrificing performance.

Outlook
The mass spectrometry industry is undergoing a transformative journey, propelled by continuous innovation and expanding applications across diverse sectors. From revolutionizing scientific research to driving advancements in drug development and diagnostics, mass spectrometry has emerged as a cornerstone technology with limitless potential.

As we look to the future, the trajectory of mass spectrometry appears boundless. With ongoing advancements in technology, such as ultra-high-throughput mass spectrometry and deep-learning-enhanced techniques, the capabilities of mass spectrometry are set to soar to unprecedented heights. These innovations promise to revolutionize not only how we analyze compounds and biomolecules but also how we understand complex biological systems and tackle pressing challenges in healthcare, environmental science, and beyond.

In the coming years, mass spectrometry will continue to be at the forefront of scientific exploration, empowering researchers and industries to push the boundaries of knowledge and innovation.