Triple quadrupoles drive the Indian mass spectrometers market

MS is getting bigger and better and is poised to continue to evolve, both in terms of instrumentation and in the range of applications.

In clinical laboratories all throughout the globe, mass spectrometry has become a standard approach for identifying bacterial isolates. Its high specificity, user-friendliness, and cost-effectiveness, as well as its capacity to produce reliable findings in under 5 minutes, have aided its introduction and growth. In recent years, the number of microbial species that can be consistently identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) has risen, and it is now able to reliably identify non-tuberculous mycobacteria or closely similar species of Nocardia spp. Yeasts, both belonging to Candida and non-Candida genera can also be identified by MALDI-TOF, as well as filamentous fungi. In the latter case, both sample-preparation methods and the available databases have been important factors in achieving accurate identifications at the species level.

The expertise acquired over time has allowed researchers to identify microorganisms directly from clinical samples, facilitating improved management of infected patients. This expertise has also been applied to the development of a MALDI-TOF-based methodology for the detection of different antimicrobial-resistance mechanisms. Therefore, future applications, such as bacterial strain typing, or the detection of virulence markers seems feasible to perform with this technology. Furthermore, other emerging mass spectrometry and spectroscopy technologies may assist MALDI-TOF in the near future to carry out important tasks that nowadays are performed by time-consuming and labor-intensive methods.

The Indian mass spectrometers market is estimated at ₹385 crore in 2021 with 268 units. Single- and triple-quadrupoles dominate the Indian market with a combined share of 74.6 percent by quantity and 63 percent by value.

Within the segment, triple quadrupoles are by far the preferred systems. A triple quadrupole instrument differs from an instrument with a single quadrupole analyzer in that it is a tandem system, with two quadrupole mass analyzers, with a third quadrupole positioned in between to act as a collision cell. Basically, the quadrupoles act as filters so at the end of the process, users only have the element of interest reaching the detector. The main difference between single-quadrupole and triple-quadrupole is that the latter enables more specific analyses in complex matrices by improved interference removal. The vendors are working toward reducing manual sample-preparation time and method-development time as this contributes to standardization, which saves time and increases productivity.

Food-safety laboratories are large customers for triple-quadrupole systems. They measure nutritional, toxic, and essential elements in food samples, and are utilized to trace concentrations of elements, as contaminations, adulterations, and toxic elements in food. Mass spectrometry is being widely used to analyze molecules in pharmaceutical drugs, biosimilars, phytoproducts and regenerative medicines. Moreover, increasing emphasis on environmental testing for pollution control is also augmenting market growth.

Orbitraps are increasingly being utilized more widely for applications in forensic toxicology, food safety, drug-monitoring research, pharmacokinetics, environmental analysis, as well as various qualitative analyses in pharma and academia. A huge range of products is now available, and is heavily discounted with prices declining steadily. The popularity of performing quantitative, qualitative, and screening analyses using Orbitrap mass analyzer technology over the Maldi-TOF is growing rapidly. The coupling of a MALDI-type ion source to a linear ion trap and an Orbitrap mass analyzer offers high-accuracy mass measurements compared to common MALDI-TOF/TOF instruments. Contrary to MALDI-TOF/TOF, the fragmentation of peptides in the new hybrid mass spectrometer is less efficient due to the generation of predominantly singly charged ions by the MALDI process. Therefore, data from two MALDI instruments, TOF/TOF and Orbitrap, are often combined into a single data set in order to obtain accurate precursor masses as well as superior MS/MS spectra.

Increasingly, in USA, tandem mass spectrometry (MS/MS) is being used for new-born screening because this laboratory-testing technology substantially increases the number of metabolic disorders that can be detected from dried blood-spot specimens, routinely collected from new-born. However, mandatorily using MS/MS in new-born screening programs is new, and scientific data are limited regarding incorporating this technology into new-born screening and maternal and child-health programs.

MS/MS technology enables improvements in and consolidation of metabolic screening methods to detect amino acid disorders (e.g., PKU, maple syrup urine disease, and homocystinuria) among new-born, and does so with a low false-positive rate. MS/MS technology expands the metabolic disorder screening panel by incorporating an acylcarni­tine profile, which enables detection of fatty acid oxidation disorders and other organic acid disorders. MS/MS can reliably analyze approximately 20 metabolites in one short-duration run (i.e., ~2 minutes) and provide a comprehensive assessment from a single blood-spot specimen.

Screening for multiple disorders in a single analytical run by using MS/MS requires that program administrators and laboratorians choose which types of conditions are to be screened. For example, laboratory A uses MS/MS to detect amino acids only; laboratory B uses MS/MS to detect acylcarnitines only; and laboratory C screens for both. In addition, other technical concerns must be addressed before MS/MS technology can be integrated effectively into a new-born screening program, including deciding which analytes to use in characterizing each disorder. The Indian industry is pushing for this to be made mandatory in India too. A regulatory authority, independent of the ministry of health and family welfare, may need to be in place to take decisions as these.

The HRMS segment is estimated at ₹57.75 crore, with 35 units. Orbitrap constitutes 60 percent of the market, and quadrupole time-of-flight (QTOF) technology, the balance 40 percent, by units. In India, Thermo Fisher is the leader in this segment.

The global mass spectrometry market size is expected to grow from an estimated USD 4.3 billion in 2021 to USD 5.6 billion by 2025, at a CAGR of 6.5 percent, estimates MarketsandMarkets. The MALDI-TOF MS is a major contributor to the high growth of the MS segment, owing to the introduction of new accessories for MALDI-TOF MS, which expands the application range of this technology. Pharmaceutical analysis occupied a major portion of the revenue generated by the application segment as spectrometer is commonly used in the quality assurance and quality control departments of pharmaceutical companies.

Currently, the tandem mass spectrometry devices are among the most in-demand. Liquid chromatography-mass spectrometry (LC-MS/MS)-based approaches are considered reagent-free. The high sensitivity and specificity of mass spectrometry can overcome many limitations associated with immunoassays, such as cross-reactivity and non-specific antibody binding. There is a higher demand for triple quadrupole mass spectrometer because it is considered one of the highest-end instruments and, moreover, many labs across the world are adopting this instrument.

There has been a trend in mass spectrometry-based characterization of antibody-drug conjugates (ADCs) toward the use of high-resolving mass spectrometry for many of these analyses. Quadrupole mass spectrometers represent a viable alternative for the characterization of ADCs in early-stage drug development.

The hybrid MS segment held a major share of the mass spectrometry market in 2021 and is expected to continue the trend in coming years. This is attributed to their application and level of performance compared to other types of spectrometers. Hybrid MS combines numerous mass-analyzer components to achieve maximum performance in a single test. Increased performance of mass spectrometer can be measured in terms of higher sensitivity and resolving power; rapid data production and abundance of data-sets are additional benefits offered by hybrid mass spectrometers.

A driver of growth is the increasing demand for automation in diagnostic techniques and the need for a cost-effective platform for sample analysis. This has motivated manufacturers to focus on product development and innovations.

In addition, increasing funding in the pharmaceutical and biotechnology industry is expected to drive the growth of the mass spectrometry market. Mass spectrometry plays a key role in the pharmaceutical industry, from the early stages of drug discovery to late-stage development and clinical trials. Moreover, technological breakthroughs in mass spectrometers are expected to drive market trends. Advanced technologies, such as ion mobility spectrometry and capillary electrophoresis, are used to separate complex biological mixtures, such as derived peptide products. Additionally, miniaturization is expected to propel the growth of this market.

The discovery of new tools has the potential to stimulate the usage of mass spectroscopy across drug development, pharmaceuticals, food safety testing, proteomics, and other fields. The demand for life sciences applications has led to the improvement of mass spectrometry technologies. The mass spectrometry MALDI-ToF is used as a clinical diagnostic platform utilizing a highly advanced method of protein pattern recognition to diagnose diseases. Hence, with the increasing technological advancements, the market is expected to grow over the next 5 years.

Bhaumik H Trivedi
Sr Marketing Executive – Clinical Diagnostics,
Shimadzu Analytical (India) Pvt. Ltd.

Newborn screening (NBS) is a public health program, provided by most countries around the world, aimed at screening newborns for a list of serious genetic and metabolic disorders. Early diagnosis of these conditions can help prevent their further development, which if untreated often result in brain damage, organ damage, and even death. A routine neonatal screening procedure requires that a health professional takes a few drops of blood from the baby’s heel, applies them onto a special filter paper, and sends such a prepared sample to a laboratory for several analytical
tests.

LCMS (liquid chromatography-mass spectrometry) offers an approach to high-throughput NBS (new-born screening) by having the ability to screen multiple metabolic disorders in a single analysis, and one run, multiple metabolites can be quantified. This capacity of LCMS reduces the turnaround time of the NBS laboratory. Dried blood spots (DBS) are used for doing NBS. A small disc of a DBS was punched and deposited in a microwell plate.

The sample was extracted by dispensing an extraction solution consisting of a mixture of methanol and aqueous solution. Internal standards, stable heavy isotope analogs of several amino acids, carnitine, acylcarnitine, succinylacetone, adenosine, and deoxyadenosine, were also present in the extract solution.

As a high-risk screening platform/confirmatory screen, urinary GCMS gas chromatography/mass spectrometry-based analysis is used. GCMS with one-step metabolomics enables quick detection, accurate identification, and precise quantification of a wide range of urinary markers that may not be discovered using existing LCMS. The technique is effective as a second-tier test to other established screening technologies, as well as a one-step primary screening tool for a wide spectrum of IEM (inborn errors of metabolism). LCMS and GCMS together become a total solution for NBS as both the techniques have their roles to be played. Due to the high-throughput capabilities of LCMS population screening becomes faster and easy. With the help of GCMS, a close inspection can be done for suspected samples.

Varied types of samples analyses using MS have increased its implication in NBS. The goal of these techniques (LCMS and GCMS) is to capture information of various metabolites using a targeted approach. New horizons and trends indicate a bright future for MS.

Premium product pricing. Spectrometry instruments are equipped with advanced features and functionalities and are thus priced at a premium. Apart from the system’s cost, the cost of compliance of the system to industry standards is also very high. Owing to technological advancements and increased operational efficiencies, the demand for mass spectrometers has grown over the years. However, technological developments have increased system prices. The price of a spectrometer influences the purchase decision of end users. Pharmaceutical companies require many such systems and hence, the capital cost increases significantly. Furthermore, academic research laboratories find it difficult to afford such systems, as they have controlled budgets. These are the major factors limiting the adoption of mass spectrometry systems among end users.

Skilled personnel with relevant experience and knowledge are required for the efficient use of spectrometry equipment. Errors, such as misplacing a sample in GC-MS or LC-MS, or issues, such as fingerprints or bubbles in the solution, can impact the quality of the final result. Moreover, in mass spectrometry, sample preparation (including aliquoting, dilution, and extraction) is a key step in isolating the analyte of interest. It eliminates interferences that could affect the precision of the result.

The lack of knowledge regarding the right choice of technology also affects results and may incur direct and indirect expenses for end users. There is currently a dearth of skilled personnel for method development, validation, operation, and troubleshooting activities, which is expected to restrain the growth of the mass spectrometry market to a certain extent in the coming years.

North America is estimated to be the largest market for mass spectrometry in 2021. The mass spectrometry market in North America is driven primarily by factors, such as the growing funding for research and government initiatives in the US, widespread usage of mass spectrometry in the metabolomics and petroleum sector, and CFI funding toward mass spectrometry projects in Canada. In addition, regulatory agencies in the US, such as the Food and Drug Administration (FDA), are encouraging the use of analytical techniques to ensure that the pharmaceutical products released in the market adhere to quality requirements. Lately, the US has seen a significant increase in the shale gas and crude oil production with increasing oil fields, and this has resulted in subsequent increase in the employment of analytical tools, such as mass spectrometers.

Developing countries like China and India present various opportunities for the growth of the mass spectrometry market. Together, China and India generate a huge demand for single mass spectrometers and hybrid spectrometry instruments due to the Greenfield projects being set up in various end-user industries in these countries. The biopharmaceutical industry in these countries is robust and is expected to contribute largely to the growth of the spectrometry and chromatography markets. Key industry players are establishing new facilities, R&D centers, and innovation centers to capitalize on this opportunity and engaging in collaborations with players in the Asian market.

Prominent players in the mass spectrometry market are Agilent Technologies, Inc., Danaher, Waters Corporation, Bruker, Thermo Fisher Scientific, Perkinelmer, Inc., Shimadzu Corporation, Kore Technologies, Ltd., Dani Instruments S.P.A., Leco Corporation, JEOL Ltd., Eurofins Scientific, Ion Science, FLIR Systems, Inc., Ametek Inc., Hitachi Ltd. and High Technologies Solutions, Thermo Fisher Scientific, SCIEX, Analytik Jena GmbH, Rigaku Corporation, LECO, Hiden Analytical, Kore Technology, Extrel CMS, LLC, MassTech, MKS Instruments, Advion, and FLIR Systems, among other domestic and global players.

There is much to anticipate as the world begins another cycle around the sun. Science has reached significant milestones in the development and dispersal of Covid-19 vaccines. New opportunities for disease research and medicine are emerging. And evolving developments in mass spectrometry promise to enable new approaches to research and medicine. Here are a few exciting applications positioned to affect the future of mass spectrometry, as well as recent major breakthroughs.

Many recent advancements in mass spectrometry have centered on the study of proteomics. One such example comes from the Max Planck Institute of Biochemistry, where research group leader Jürgen Cox and his team released a new version of the pioneering and widely used MaxQuant software platform for analyzing and interpreting data produced from MS-based proteomics research. MaxQuant 2.0. includes an improved computational workflow for data-independent acquisition (DIA) proteomics, called MaxDIA.

The MaxDIA software enables researchers to apply algorithms to DDA (data-dependent acquisition) and DIA data in the same way. The software accomplishes this by combining the use of spectral libraries with machine learning algorithms. By predicting peptide fragmentation and spectral intensities, more precise spectral libraries are created in silico, which can then be applied to the data. Spectral libraries are one of the limiting factors in the application of MS to proteomics, so this innovation is helping to expand the scale and scope of how MS can continue to contribute.

Use of this technology will enable researchers to compare data from DDA and DIA more easily, and harness the power of both techniques to measure and analyze thousands of proteins with greater breadth than before. The Max Planck team is already working on further enhancements for the new software. A paper on MaxDIA was published in July 2021 in Nature Biotechnology.

Another technology gaining significant momentum, primarily in industry but also in academic circles, is MS-based multiple attribute monitoring (MAM). The MAM concept was born from the need to monitor protein production and purification, and limit the inherent heterogeneity of biologics, such as therapeutic antibodies, and their impact on quality control.

Although MAM is not a new concept, advancements in MS instrumentation and data analysis solutions have made MS-based MAM the preferred platform in biologics drug quality control. Immediate applications include biopharmaceutical discovery and development, although the technique is gaining popularity in research groups studying post-translational modifications and other potential modifications of proteins.

MS instrument providers, such as Thermo Fisher Scientific, SCIEX, Waters, and others now offer complete MAM workflows that are built around their MS technology platforms. The solutions are intended to provide comprehensive characterization of proteins and therapeutics by matching reagents and protocols with instrument output and software analysis.

Another new area for MS development centers on the concept of trapped ion mobility MS. The ion mobility mass spectrometry (IM-MS) method combines the separation of ionized molecules based on their mobility in a carrier buffer gas, with the high-accuracy resolving power of mass spectrometry. This enables separation of both mass and size/shape, which provides even greater specificity for analyzing and understanding the complex suite of proteins present in living cells. When combined with chromatography and powerful analytical software, the IM-MS technique offers a multi-dimensional approach toward resolving complex samples, such as those in proteomics studies.

Trapped ion mobility spectrometry is a modification that essentially traps the ions during ion mobility separation, which allows for sequential fragmentation over a series of timed millisecond scans. Combining trapped ion mobility with a method termed parallel accumulation-serial fragmentation (PASEF), these trapped ions can accumulate in parallel, and be released sequentially. Rather than a quadrupole selecting a single precursor ion for fragmentation, such as that of a typical MS/MS experiment, sub-millisecond switching enables the selection and fragmentation of multiple precursors in a single 50-ms run.

Such performance can result in thousands of protein identifications over a short run time, using nanogram amounts of material. These technological developments have led to significant gains in sequencing speed without a decrease in sensitivity, ideally suited for complex, high-throughput proteomics.

Significant advancements have been made recently in trapped ion mobility MS. For instance, at the beginning of June 2021, Bruker Daltonics launched new MS technology that combines time-of-flight and trapped ion mobility MS (TIMSTOF) with liquid chromatography and improved automation software. That combination will allow for big steps forward in the efficiency of epiproteomic and proteomic analyses in labs – along with enabling the rapidly growing field of single-cell proteomics.

An additional advancement impacting both the proteomics and metabolomics spaces is spatially resolved MS. Development of multimodal imaging mass spectrometry is helping researchers reveal more about the workings of biological systems. Yet another area of growth is high-throughput planar solid-phase extraction coupled to high-resolution mass spectrometry, which is helping streamline screening for antibiotics in foods, among other applications.

Researchers have recently been applying established mass spectrometry techniques in many interesting ways. In a study published in the journal Antiquity in August 2021, researchers used accelerator mass spectrometry to analyze 26 human tooth and bone samples from Machu Picchu, Peru, determining that the site is at least two decades older than what textual sources indicate, demonstrating the ability of MS innovations to impact a very wide range of important studies.

In another recent development, MS will have an impact a little farther from Earth in the Southwest Research Institute’s (SwRI’s) Environmental Analysis of the Bounded Lunar Exosphere (ENABLE) project, a three-year USD 2.18-million program, funded by NASA, that was announced in July 2021. The program aims to bring mass spectrometry back to the moon, adapting a commercially available mass spectrometer to identify the composition of the lunar surface.

MS has also been an important tool in studies of SARS-CoV-2, the virus responsible for the current Covid-19 pandemic.

Recently, in three studies explored in a Science research article in August 2021, MS helped reveal how the B.1.427/B.1.429 variant of concern evades the human immune system. Another study published in Sustainability in July 2021 shows how MS could be combined with machine learning to provide surveillance of airborne pathogens during the current Covid-19 pandemic and future ones. Widespread deployment of such an MS-based contagion surveillance could help identify hot zones, create containment perimeters around them, and assist in preventing the endemic-to-pandemic progression of contagious diseases.

While these studies used more established MS techniques, there are a number of new technologies emerging around MS-based SARS-CoV-2 and virus testing. As reported in December 2020, there are two MS-based SARS-CoV-2 diagnostic tests that have received emergency use authorization from the US Food and Drug Administration.

The MassARRAY SARS-CoV-2 Panel commercialized by Agena Bioscience and the SARS-CoV-2 MALDI-TOF Assay from Ethos Laboratories pair RT-PCR with MALDI-TOF MS to detect the Covid-19-causing virus in samples collected at home or at a point-of-care location. Many other MS techniques for virus testing are being developed and used at the research level – certain to be an area of increasing value moving forward.

Mass spectrometry imaging, single-cell proteomics, and remote monitoring are three broad areas in MS that are still undergoing rapid and significant research and hold promise for the future. Progress in these areas will continue to provide academics with new insights and technology that will benefit the general public. With that in mind, expect to see more of the most cutting-edge technologies affecting the MS sector in the future.