Time-of-flight/ion trap mass spectrometer, a method, and a...

Details Time-of-flight/ion trap mass spectrometer, a method, and a... Time-of-flight/ion trap mass spectrometer, a method, and a...

2001-04-10

2004-08-17

Lee, John R. (Department: 2881)

Radiant energy

Ionic separation or analysis

Ion beam pulsing means with detector synchronizing means

C250S281000, C250S282000, C250S288000, C250S292000, C250S298000

Reexamination Certificate

active

06777671

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a time-of-flight/ion trap mass spectrometer, a method of operating the time-of-flight/ion trap mass spectrometer, and a computer program and a computer-program-product such as for example a hard drive or floppy disk or other medium containing computer code for operation of the time-of-flight/ion trap mass spectrometer.
2. Description of the Background
A mass spectrometer (MS) is used to determine the identity and quantity of constituent materials in a gaseous, liquid or solid specimen.
In a normal mode of operation, specimens are analyzed in mass spectrometers by ionizing the molecules of the specimen in an ion source, separating ions according to their mass-to-charge ratio (m/z) in a mass analyzer, and bombarding the separated ions in an ion detector to obtain a mass spectrum. Typically, the ion mass m is expressed in atomic mass units or Daltons (Da) and the ion charge z is the charge on the ion in terms of the number of elementary charges e.
In a tandem mode of operation, the mass spectrometer includes a device that produces fragmentation of ions into smaller structure-specific ions for further mass analysis. A spectrum referred to as a tandem mass spectrum corresponding to the fragmented ions can be obtained. By repeating the isolation and fragmentation stages a multiple number of times, one can obtain a tandem mass spectrum in this tandem mode of operation in which the ions have been repeatedly fragmented through a number of MS stages, e.g., a MS
n
spectra is obtained (where n≧2) which thereafter are also referred to as tandem mass spectra. In mass analysis of large biological molecules, tandem mass spectral measurements provide structural and sequential information about peptides and other biopolymers.
A time-of-flight (TOF) mass spectrometer (MS) is a known instrument for mass analysis in a normal mode. In TOF-MS, ions formed from sample molecules in an ion source are accelerated to the same energy and allowed to drift along a defined path before detection. Because ions of different mass have different velocity, after acceleration, they are separated in space during flight and in time during detection. Thus, the time of arrival to the detector is measure of the mass or the mass-to-charge ratio m/z, if ions are not singly-charged.
This picture can be complicated by the presence of non-ideal factors, which include: (a) different time of formation or acceleration of ions; (b) different initial location of ions in space; and (c) different initial velocity of ions before acceleration. A number of methods, such as for example time focusing, dual-stage extraction, and time-lag focusing, can be used to correct these factors. Time focusing can be achieved by using pulsed drawout fields with sharp rise times or short laser pulses in the case of laser desorption (LD) or matrix-assisted laser desorption/ionization (MALDI). Alternatively, a dual-stage extraction method can be used to correct the initial spatial distribution of ions in an ion source. Initial velocity (or energy) distribution can be corrected by a time-lag focusing technique (e.g. a pulsed or delayed or time-delayed extraction method) or an ion mirror method (e.g., a method utilizing a reflectron). In addition, orthogonal ion extraction which interfaces with continuous ionization sources such as electrospray ionization (ESI), as described in U.S. Pat. No. 4,531,056, the entire contents of which are incorporated herein by reference, can be used to reduce the impact of the non-ideal factors.
Conventional TOF-MS schemes are shown in
FIGS. 1A-1D
which are discussed below. Details on a TOF-MS are given in: R. J. Cotter,
Time
-
of
-
Flight Mass Spectrometry: Instrumentation and Applications in Biological Research
, ACS Professional Reference Books, Washington, D.C., 1997, pp. 1-327; W. C. Wiley, I. H. McLaren,
Rev. Sci. Instr.,
1955, vol. 26, pp. 1150-1157; A. F. Dodonov, I. V. Chernushevich, V. V. Laiko, in
Time
-
of
-
Flight Mass Spectrometry
, Ed. R. J. Cotter, American Chemical Society, Washington, D.C., 1994, pp. 108-123, the entire contents of each reference are incorporated herein by reference.
Time-of-flight (TOF) mass spectroscopy has several advantages over other types of mass spectroscopy. A TOF mass spectrometer is conservative of the sample since every ion formed in the bunch is detected. Open flight tube designs in TOF mass spectrometers result in high ion transmittance due to a wide aperture to the source. There is no fundamental limit (other than detectability) on the range of analyzed m/z values. Due to the pulsed nature of the TOF technique, the TOF mass spectrometer can be interfaced to pulsed ion sources; importantly, it can be interfaced, as shown in
FIGS. 1A-1C
, to vacuum MALDI ion sources which are widely utilized for the ionization of large biological molecules as described in M. Karas, F. Hillenkamp,
Anal. Chem.
1988, vol. 60, pp. 2299-2301, the entire contents of which are incorporated herein by reference, and the afore-mentioned electrospray ionization sources.
FIG. 1A
shows a linear TOF-MS in which a laser
100
desorbs an ionized species from a sample contained in a matrix-assisted laser desorption/ionization stage
102
. The stage
102
exists at a high voltage potential adjacent to an extraction device
104
. Ionized species are extracted from the region near the stage
102
and directed to an ion detector
106
.
FIG. 1B
shows a reflection TOF-MS similar to the TOF-MS in
FIG. 1A
, but where ions are directed by reflectron
108
to the ion detector
106
through a curved path. The reflection
108
includes a series of rings with each ring set progressively to higher potentials.
FIG. 1C
shows a TOF-MS in which a pulsed voltage signal is applied to the stage
102
after the laser
100
produces the desorbed, ionized species. The pulse voltage signal time-focuses the desorbed ionized species to ensure that ions of a particular m/z value arrive at the ion detector simultaneously. Most commercial MALDI instruments use a TOF-MS as a mass analyzer.
Further, U.S. Pat. No. 5,965,884, the entire contents of which are incorporated herein by reference, describes an atmospheric pressure MALDI technique in which ions are formed outside the vacuum of a mass spectrometer at atmospheric conditions.
FIG. 1D
shows an orthogonal acceleration TOF-MS interfaced with an atmospheric ion source. Ions from the atmospheric ion source
110
pass through a heated capillary
112
and a skimmer
114
to produce a collimated ion beam. Once inside the vacuum of the orthogonal acceleration TOF-MS, electrostatic optics
116
focus the ion beam into a quadrupole
118
which homogenizes the ion beam such that ions exiting the quadrupole
118
have only an axial velocity component and almost no radial velocity. Deflection optics
120
deflect the exiting ions toward the reflectron
108
which in turn reflects the ions to the ion detector
106
.
However, a drawback of TOF-MS technology is that TOF-MS does not easily provide for a tandem mode of operation. Yet, tandem experiments, by analysis of fragmentation patterns from complex molecules, can play a role in structural elucidation of biological molecules. This role of TOF-MS for MALDI analysis of biological molecules has led to the search for mechanisms to provide a tandem mode of operation in TOF-MS instruments.
In the tandem mode, the isolated ions (i.e., precursor ions) undergo an activation process to produce fragmented ions. Activation energy of the precursor ions can come from collisions with buffer gas or surfaces or photoexcitation. One approach, as shown in FIG.
2
A and as described in U.S. Pat. No. 5,202,563, the entire contents of which are incorporated herein by reference, utilizes a tandem reflectron TOF instrument (reTOF/reTOF) with a collision chamber for providing activation and fragmentation.
FIG. 2A
shows a tandem reflectron mass spectrometer in which ions transit through two reflectrons
220
and
222
and a collision chamber
202
before arriving at the

Affiliated with

Also associated with

Rating

Time-of-flight/ion trap mass spectrometer, a method, and a... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Time-of-flight/ion trap mass spectrometer, a method, and a..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Time-of-flight/ion trap mass spectrometer, a method, and a... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3347705