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Encyclopedia of Physical Science and Technology EN009N-406 July 18, 2001 23:32

146 Mass Spectrometry

remain intact, and the supporting instrumentation contin- that “new capabilities catalyze new demands,” and the in-
ues its steady and innovative evolution. But applications in tertwined relationship of modern mass spectrometry, its
biological mass spectrometry have expanded at an extraor- instrumentation, and its market is aptly described.
dinary rate, and fundamental new approaches to the cre-
ation and interpretation of mass spectrometric informa-
A. Sample Introduction Systems
tion are being developed to address new questions. It has
been estimated that a billion mass spectra are recorded The mass analysis and ion detection functions of a mass
daily (Busch, 2000a). The growth and demand for high- spectrometer are completed in a vacuum, usually of 10 −5
throughput mass spectrometry suggests that even that ex- to 10 −6 torr (a slightly higher pressure prevails in the
traordinary number is an underestimate, if not now, then operation of an ion trap mass spectrometer). The pro-
certainly within the next few years. Classically, mass spec- cesses of electron ionization, chemical ionization, and
tra were interpreted to provide details of molecular struc- matrix assisted laser desorption ionization (MALDI) also
ture revealed through the unimolecular dissociations of operate under vacuum, while the electrospray ionization
the molecular ion. Increasingly, however, mass spectral (ESI) source operates at atmospheric pressure, and ESI-
data in other forms are being recorded and manipulated. generated ions then pass through a set of differential pres-
Mass spectrometry is now used to study interactions be- sure apertures into the mass spectrometer. Mass spectrom-
tween complex molecules in the gas phase to provide eters must operate under vacuum so that the ions move
clues in combinatorial investigations. Mass spectrometric through the instrument in a controlled manner rather than
data is transparently summarized in databases that support being scattered by collisions with residual gas molecules.
repetitive high-throughput proteomics analysis. Multidi- The mean free path of the ion should be larger than the
mensional MS/MS data is stored in arrays examined with dimensions of the mass spectrometer itself. The issues of
chemometric-based routines that mine the data in search vacuum in mass spectrometry are more thoroughly dealt
of answers for complex questions of pattern and structure with elsewhere (Busch, 2000b); the many orders of mag-
that have just now begun to be formulated. nitude difference between instrument operating pressure
This overview covers relevant issues in instrumentation and the atmospheric pressure of the laboratory, or the pres-
for modern mass spectrometry, an overview of techniques sure regime of a column-based separations method, is a
used in both classical and newer areas of mass spectromet- basic design parameter of the sample introduction system.
ric investigation and a preview of growth areas in mass Mass spectrometry is unique among many modern an-
spectrometry research and application. Current applica- alytical methods in that sample molecules are physically
tions are best reviewed by examination of the manuscripts and irretrievably introduced into the instrument. The sam-
published in the current journals of mass spectrometry, ple handling devices must be transport devices that accom-
and review of the papers presented at the annual profes- modate a wide dynamic range of sample quantities, effi-
sional meetings, especially meetings dealing with biolog- ciently transporting all sample molecules from the outside
ical chemistry, and the annual meetings of the American world into the ionization source of the mass spectrometer.
Society for Mass Spectrometry. Given the diversity of sample types, there is a concurrent
diversity of sample introduction systems.

I. INSTRUMENTATION
1. Direct Insertion Probe
Francis W. Aston won the Nobel Prize in Chemistry in The direct insertion probe (or direct probe) is a device to
1923 for his prolific work in the discovery of isotopes introduce small amounts of solid or liquid samples into the
using mass spectrometers that he had constructed in the ionization source of the mass spectrometer without chro-
Cavendish Laboratory. Aston was experienced and skilled matographic separation. The direct probe is appropriate
in the construction and maintenance and operation of in- for use when the sample is known to be pure or of lim-
struments. But, in his 1942 book “Mass Spectra and Iso- ited complexity, or when a chromatographic separation
topes” Aston described his mass spectrometer as an in- is impossible because of sample volatility, or when such
strument that “behaves at times in the most capricious and a separation would be too time-consuming. About 10 −5
unaccountable manner.” Where would the field of mass to 10 −4 torr of sample pressure is sufficient to record a
spectrometry be today if this were still the case, if, for ex- mass spectrum in an electron ionization or chemical ion-
ample, there had been fewer instrumental developments ization source. This sample pressure can be achieved by
of reliable and capable ionization sources, mass analyz- evaporation of the sample into the vacuum at room (in-
ers, and ion detectors? A well-known adage states that strument ambient) temperature, or by increasing the tem-
“newinstrumentationbegetsnewchemistry”;addacodicil perature of the direct insertion probe, which can be heated