June 1, 2005 (Vol. 25, No. 11)
Discovering the Range of Technological Capabilities and Applications
Though originally employed in academic exercises during the early part of the last century to characterize the masses and determine the stabilities of nuclear isotopes, the practicality of mass spectrometry (MS) was quickly realized.
During the 1940s, the use of MS spread to nuclear isotope enrichment and the analysis of the components of petroleum. As the number of its industrial uses grew, mass spectrometers became commonplace not only in the field of physics, but also geology, chemistry, and physiology.
Beginning in the 1980s and continuing full steam into the 1990s, technological innovations in ionization techniques allowed for multiple biological entities, including formerly intractable high molecular weight molecules, to be analyzed by MS. The diversity of its biological applications has resulted in MS becoming one of the few quintessential analytical research techniques available today in all of biology.
“Mass Spectrometry: Opportunities in the Life Science Market,” a report released in April by market research firm BioInformatics (Arlington, VA), finds that protein identification and characterization are the top applications for mass spectrometry.
However, there is a broad second tier of applications, including: peptide sequencing, the identification of post-translation modifications, the characterization of multi-protein complexes, small molecule analysis, the analysis of protein digests, biomarker discovery/validation, and quantitative proteomics.
For the report, 850 scientists were surveyed who currently use, or plan to use, mass spectrometry in their research to investigate experimental design, instrument specifications and future purchasing plans, as well as to assess opportunities for suppliers to expand their reach into markets characterized by key parameters such as application, instrumentation type, sample complexity, and throughput.
The survey results indicate that within the life science market, Applied Biosystems/MDS Sciex (www.appliedbiosystems.com) is the leading mass spectrometer brand in all regions and market segments, followed by Agilent Technologies (www.agilent.com) and Thermo Finnigan (www.thermofinnigan.com).
There appears to be a correlation between the brand most recently purchased and the reason for the purchase, which indicates that life scientists associate different brands with specific qualities.
Analysis of the survey data suggests that MS systems were purchased from Applied Biosystems/MDS Sciex and Thermo Finnigan to achieve greater sensitivity, from Agilent Technologies to perform more applications, from Waters (www.waters.com) to create a new platform or capability for the lab, and from either Waters or Bruker Daltonics (www.bdal.com) to provide increased reliability.
These distinctions reflect the market’s perception of the different positions occupied by the leading suppliers of MS instruments.
Scientists have a variety of different types of MS instruments from which to choose. These increased offerings are due in part to technical advances in ionization and separation technology.
Despite impressive variety of platforms available, liquid chromatography mass spectrometry (LC/MS) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) are the instrument configurations most commonly used by the scientists surveyed.
Recently, leading mass spec suppliers have recognized this demand and introduced new MALDI-TOF or LC/MS platforms that offer scientists enhanced sensitivity, greater throughput and more cost-effectiveness.
Additionally, some suppliers are offering a bench-top MALDI-TOF mass spectrometer for analysis of large molecules as well as for applications in clinical proteomics.
Despite the relatively long life of these instruments (5+ years), scientists want to keep up with these new developments. Nineteen percent of current mass spectrometer users plan to purchase a new instrumentthe majority of whom will do so within the next year.
Scientists are most likely to seek new mass spectrometers that have greater mass accuracy, the ability to perform more applications, and greater sensitivity, and most respondents anticipate acquiring them from Applied Biosystems/ MDS Sciex and Thermo Finnigan.
Since “higher mass accuracy” can be achieved by increasing an instrument’s resolution, suppliers are working on obtaining both a cleaner separation of standards and samples from background noise and the formation of sharper and more evenly shaped peaks.
This emphasis on improving resolution is the result of scientists’ more vocal desire to achieve the “gold standard” for MS applications that demand precise, quantitative measurements.
Given the growing attention devoted to quantitative proteomics, scientists were also asked to describe their challenges with, and expectations of, this newer application of MS. Quantitative proteomics involves the identification of proteins from complex mixtures and direct measurement of their relative or absolute abundance in different tissues or under various physiological conditions.
This technique has important implications in several areas of research, including protein biomarker discovery and target validation and screening. Numerous suppliers are already developing productsfrom labeling chemis-tries to sophisticated softwareto meet the needs of this emerging area of research.
The survey revealed that the number of scientists utilizing quantitative proteomics techniques is expected to increase among both current and future users of MS. Of the respondents who currently use MS, 15% perform quantitative proteomics and an additional 17% indicated that they plan to do so.
Of those respondents who anticipate employing MS in their research, 22% claimed that quantitative proteomics would be one of their future applications.
The difficulties associated with experimental design, interpretation of the results and reagent/ instrumentation cost remain significant barriers to widespread adoption. New approaches to labeling as well as novel software for data analysis and interpretation have been developed by suppliers to address these issues.
However, given the nascent state of the market and the relatively small number of actual practitioners, methods for quantitative proteomics are still in flux.
Overall, as more and more life scientists are educated about the capabilities and applications of mass spectrometry and the intimidation factor often associated with the technology is reduced, the use of MS by research labs can be expected to grow.
As one surveyed scientist noted, “Understanding the capabilities, and limitations, of the mass spec is likely to increase its use by biochemists and scientists in general. Pre-conceived ideas about sensitivities and experimental design may prevent a scientist from considering mass spec when, in reality, it would perfectly suit their needs.”