Unleashing The Clinical Potential Of Mass Spectrometers

MS-based technologies have the potential to replace current analytical technologies in clinical laboratories, and existing expertise and instruments will undergo rapid evolution in the future.

Mass spectrometers (MS) are sensitive, specific, and versatile analytical instruments in the clinical laboratory that have recently undergone rapid development. From initial use in metabolic profiling, it has matured into applications including clinical toxicology assays, target hormone and metabolite quantitation, and more recently, rapid microbial identification and antimicrobial resistance detection. Technology developments in MS have given rise to several applications of structural biology, both at the single protein and protein complex level.

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 an 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 offers 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 sector is yet to gain significance in India. Specifically, in 2017, some of the large customers for MS 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 will continue to generate demand. European Union is looking at Indian market. 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.

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.

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.

Outlook
While it is beyond doubt that the importance of MS-based techniques in clinical laboratories will continue to grow, one cannot predict its growth trajectory with certainty. Will MS-based techniques merge with the next-generation DNA sequencing techniques to give rise to efficient and economical sequencing solutions applicable to the service laboratory? Will MS-based techniques attain an adequate level of automation and ease-of-operation to replace majority of the chemical and immunological analyzers in the clinical laboratory? Will MS-based techniques see breakthroughs in miniaturization which allow them to move, literally, from bench to bedside, to serve as point-of-care testing devices? Change-embracing yet analytical minds are required to unleash the full potential of this rapid-dominating platform and at the same time establish quality assurance measures to insure accuracy of laboratory results and patient safety.