'Drastic' Improvement Seen In Mass Spectrometers

Recent technological advances have vastly improved the mass range and resolution capabilities of mass spectrometers, while making these instruments more versatile and easier to use. “We can work with smaller and smaller amounts of material because the instrumentation sensitivities have improved so drastically over the last few years,” says J. Carter Cook, director of VG Instruments’ laboratory in Savannah, Georgia. Other improvements include advances in computerization that permit more rapid processing of spectrometer information and improvements in ionization techniques, which give samples of the electric charge needed for detection and analysis. New ionization techniques have also allowed a greater variety of chemicals to be analyzed. The instruments use ions for their primary function: the identification and analysis of mass’ spectra, which are used to identify chemicals and deduce the structure of unknown compounds. Part of mass spectrometry’s appeal is its versatility. The instruments can be modified to fit specific applications. For example, secondary ionization mass spectrometers can be used to analyze surface coatings; thermal ionization systems are used for geological analysis, and glow discharge spectrometers have applications for bulk analysis of superconductor materials. Practical applications of mass spectrometry to organic materials are also diverse. The instruments have proven useful in urinalysis to detect drug use, in quality control of pharmaceuticals, and in research into disorders of the endocrine system. While many improvements in mass spectrometry are recent, other methods developed years ago—such as time-of-flight mass spectroscopy—have been rejuvenated. One spectacular example of improvement is fast atom bombardment (FAR), an ionization technique introduced in the early 1980s. FAR enables researchers to ionize nonvolatile samples—such as peptides, carbohydrates, and other intractable compounds— that could not be ionized by means of previous techniques without extensive derivitization. “Classical methods took about two to three months to determine the exact sequence of amino acids (in a decapeptide); with FAR, we can do it in less than a day,” Cook says. These capabilities have recently won FAR a large following in the scientific community. About half of the researchers that go to the University of Illinois for mass spectroscopy sample analysis request the FAB technique, according to Kenneth Rinehart, a professor of chemistry at the university. “FAR has won the hearts of all who use mass spectrometers,” he says. An accessory that may make FAR even more popular was recently developed by Richard Caprioli, a professor of biochemistry at the University of Texas Medical School in Houston. Caprioli’s tool, called a dynamic FAB probe, continually pumps liquid sample into the ion source— most systems provide only a fixed amount of sample—thus sustaining for analysis aqueous solutions that normally evaporate instantly in a spectrometer. This allows scientists to analyze a number of biochemicals that previously could not be analyzed. Kratos Analytical Inc. of Ramsey, N.J., worked with Caprioli to produce the probe. Tandem mass spectrometry is also gaining popularity. These instruments are available in three types—triple quadrupole set-ups, hybrid magnetic sector-quadrupole systems, and four-sector mass spectrometers. In an example of tandem mass spectrometry, a FAR system sends an ion through two mass spectrometers, permitting re searchers to observe an apparent ion in the first spectrometer and its daughter fragments in the second. This approach provides much more structural information on the sample than using a single spectrometer and it also clarifies the structure of complex spectra. Mass spectrometers can be interfaced with gas chromatographs and liquid chromatographs because a mass spectrometer is a nonspecific detector. One new accessory on the market is an interface that will link a mass spectrometer with a supercritical fluid chromatograph. A scientist in the market for a mass spectrometer should carefully consider three basic specifications resolution, sensitivity, and mass range. Resolution: Measured in units of resolving power, resolution is defined as the instrument’s ability to discriminate between two ions of very close mass. Quadrupole mass spectrometers usually have resolving powers of 1 to 2,000 (low resolution) resolving powers; double-focusing magnetic sector instruments can have resolving powers in excess of 100,000 (high resolution), and thus can identify samples much more accurately. Organic applications often require high resolution, which is costly. Sensitivity: A mass spectrometer’s sensitivity is defined as the signal-to-noise ratio produced when a specified amount of a particular compound is analyzed in the spectrometer. Sensitivity is inversely proportional to resolution, and the critical question is “How much resolution do you need?” It is a trade-off: Low resolution can give a simple mass spectroscopy analysis, but for accurate mass measurements less than 10 ppm, one needs high resolution and will have to live with lower sensitivity. Mass Range: The mass range of the instrument is the maximum atomic mass unit to which the instrument can be tuned (minimum is usually mass 1). A scientist working with medium-sized compounds doesn’t need to buy an extremely expensive spectrometer with a fantastic mass range. Similarly, someone working with very large molecules needs to spend a bit extra to buy an instrument with an acceptable range. While some spectrometers analyze inorganic materials, others are intended for analyzing organic materials. The systems are classified in terms of the type of mass analysis performed. Quadrupoles, often used for process control in automated manufacturing and routine measurements, measure easily detected molecules requiring low-resolution analysis and cost from $80,000 to $250,000; magnetic-sector systems, used, for example, to find environmental contaminants and in biotechnology research, can run from $475,000 to $750,000; and tandem mass spectrometers, used in peptide sequencing, cost $1.5 million and more. Basically, all three types perform the same function at different levels. Each spectrometer is composed of an ion source, an analyzer and a detector. But like a new car, a spectrometer’s price depends on the options and specifications requested by the buyer. Miles Weiss and Greg Freiherr are writers with GFI, a Washington, D.C., consulting firm. Technical advice on the article was offered by John Dykins, director of the mass spectrometry lab for the University of Pennsylvania, Philadelphia, Pa.

'Drastic' Improvement Seen In Mass Spectrometers

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