Breakthrough improvements in the instrumentation of mass spectrometers and introduction of cutting-edge technologies have broadened the horizons for the applicability of mass spectrometers.
With the advent of mass spectrometers nearly a century ago, mass spectrometers have revolutionized a multitude of disciplines within the biomedical, chemical, and pharmaceutical fields as a means for identifying compound structure, quantifying metabolites, and measuring molecules in mixtures of varying complexities. The demands of life science applications have led to the improvement of mass spectrometers and rapid introduction of new instruments that feature powerful analytical capabilities in terms of sensitivity, selectivity, resolution, throughput, mass range, and mass accuracy. While mass spectrometry has been widely used for decades in biomolecules analyses, the story of mass spectrometric characterization of nanoparticles is still short. Mass spectrometry (MS) has recently received much attention in the nanoparticle world due to its powerful usefulness especially in elucidating the chemical structures of the smaller-sized nanoparticles.
The breakthrough improvements in the instrumentation and introduction of cutting-edge technologies have broadened the horizons for the applicability of mass spectrometers. With greater resolving power, analytical speed, and accuracy, new mass spectrometry technology and techniques are infiltrating the biopharmaceuticals workflow, from applications in biomarker identification for new drug target discovery, to validation of molecular activity, and downstream in manufacturing and quality control. The rapidly growing biosimilars industry is also leveraging the analytical capabilities and increasingly automated and easy to use MS systems designed for biopharma applications.The race to develop biosimilars drugs has captured the attention of biopharma companies in countries worldwide and is catalyzing growing interest in mass spectrometers.
With origins in basic research, the use of mass spectrometers in the clinical laboratory has steadily evolved over the past 30 years, to include an ever-wider range of applications. Since then, the technique has evolved, and with the advent of tandem mass spectrometry (MS/MS) to support targeted experimental testing, combined with separation technologies such as gas chromatography (GC), liquid chromatography (LC), and ion mobility spectrometry (IMS), smaller concentrations and metabolites can be targeted. The adoption of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for small molecule targeting and translational clinical applications was driven by a need for higher immunoassay accuracy, a lack of availability in approved immunoassays, and the desire for cost reduction. While sample preparation can be more labor-intensive than immunoassays and an ever-increasing demand for automation integration, in-house mass spectrometry-based assays can be cost-effective, even for smaller labs. To match the growing trend of providing point-of-care diagnostics, miniaturization is a growing area of research in the mass spectrometer industry. Handheld, portable devices could democratize mass spectrometer-based diagnosis, opening up the use of the technology in resource limited regions.
Advances in mass spectroscopy technology continue to increase both speed and resolution at an incredible rate with the addition of new tools and software driving the growth of potential application areas. These factors are stimulating the increased usage of mass spectroscopy across drug development, proteomics, pharmaceuticals, food safety testing and many other fields. High cost of instrumentation and the expertise required to use the technology are the grey areas that still need focus in the years to come.
Mass spectrometry imaging and metabolomics. Mass spectrometric imaging, with the capabilities to combine qualitative and quantitative molecular information with spatial information, has opened a new era of applications for mass spectrometers to explore the metabolome. The spatial resolution obtained by MSI continues to improve and allows mass spectrometers to be used as molecular microscopes, enabling the exploration of the cellular and subcellular metabolome.
New developments in ionization techniques and mass analyzers will further improve the capabilities of MSI, especially when aided by new computational tools and community driven spectral databases.
Dry ion localization and locomotion (DRILL). Developed by researchers at the Georgia Institute of Technology with support from North Carolina State University, DRILL adds a new approach for manipulating the trajectory of charged droplets, which, when combined with hydrodynamic drag forces and electric field forces, provides a rich range of possible operational modes. Adding the equivalent of a miniature tornado to the interface between electrospray ionization (ESI) and a mass spectrometer (MS) has allowed researchers to improve the sensitivity and detection capability of the widely-used ESI-MS analytical technique. Among the scientific fields that could benefit from the new technique are proteomics, metabolomics, and lipidomics, which serve biomedical and health applications ranging from biomarker detection and diagnostics to drug discovery and molecular medicine.
The new device creates a swirling flow that can separate electrospray droplets depending on their size. The smaller droplets are directed to enter themass spectrometer, while the larger ones, which still contain solvent, remain in the vortex flow until the solvent evaporates. Removing the solvent allows analysis of additional ions that may be lost in current techniques and reduces the chemical noise that inhibits selectivity of the mass spectrometer. The researchers plan additional improvements that will allow DRILL to further enhance the ESI-MS process and to continue evolving it as more labs start to use the device.
Software driving growth. The launch of data-analysis software by leading market players is catalyzing the next wave of innovation to make sense of all the data generated. These platforms enable a range of new functions, including monitoring of instrument performance, integration of multi-omics data, and development of routine workflows incorporating online content and allowing users to track, interrogate, and mine data across multiple instruments and labs.
The Road Ahead
With the growing reliance on personalized medicine, mass spectrometers have an innate ability to improve clinical decision making through the measurements of biomarkers that may not be detectable by alternative methods. Mass spectrometers looks set to play a key role in the future of diagnostics, with continued improvements making the technology more accessible, cost-effective, and informative to a range of clinical applications.
Miniature mass spectrometers are emerging as a powerful adjunct in research. The ability to be used outside the laboratory by untrained professionals across many different subsets of science broadens the use of these miniaturized systems. The drive for developing miniaturized forms of mass spectrometers is multifactorial, offering portability, rapid data retrieval, and analysis. The ability to use mass spectrometers without having to learn a complicated analytical method makes miniature mass spectrometers an attractive option for the clinical environment.
The future of clinical MS is likely to see growth in the use of automation, increasing the ease of use and greater adoption by smaller laboratories. The pace at which the technology is evolving, mass spectrometers may soon begin to replace traditional histology techniques, to provide a wealth of new information to pathologists and clinicians. As manufacturers come forward with increasingly automated, user-friendly systems with software to manage and interpret the large volumes of data produced, the spotlight focused on MS for analyzing complex biopharmaceuticals shines brightly. The future of MS cannot be predicted, however, their rate of utilization growth has shown that its evolution and advancement is certain. It cannot be said that MS will replace current low-cost and reliable clinical tests, but as biomarker testing evolves, MS have the ability to broaden the inventory of disease-specific molecules and place it within a clear niche in which to excel.