Radiant energy – Ionic separation or analysis – With sample supply means
Reexamination Certificate
2001-03-01
2004-10-19
Lee, John R. (Department: 2881)
Radiant energy
Ionic separation or analysis
With sample supply means
C250S281000, C250S282000, C250S284000, C250S286000, C250S287000, C250S42300F
Reexamination Certificate
active
06806468
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a device, system, and method for delivery of ions from ion sources to a mass spectrometer to perform mass spectroscopy.
2. Discussion of the Background
Ion sources represent an important component of a mass spectrometer (MS). Atmospheric Pressure (AP) ion sources are used in modem analytical mass spectrometry. AP ion sources produce ions under ambient atmospheric conditions outside the vacuum of a mass spectrometer instrument. Atmospheric pressure chemical ionization APCI sources, as described by Bruins, in Mass Spectrom. Rev. 1991, vol. 10, beginning at p. 53, the entire contents of which are incorporated herein by reference, produce ions of volatile analytes with molecular masses 1-150 atomic mass units or Daltons (DA). Electrospray ionization (ESI) sources, as described in Yamashita, et al., J. Chem. Phys. 1984, vol. 88, pp. 4451 and Fenn, et al., Science 1989, vol. 246, p. 64-71, the entire contents of each reference are incorporated herein by reference, are used in analytical biochemistry to transfer heavy molecular ions (with masses up to several hundred thousand Da) intact from a liquid analyte solution to the gas phase for subsequent mass analysis. Further, an atmospheric pressure matrix assisted laser desorption ionization source (AP MALDI), as described in U.S. Pat. No. 5,965,884, the entire contents of which are incorporated herein by reference, produces ions of heavy biomolecules under normal atmospheric pressure conditions by laser irradiation, desorption, and ionization of analyte/matrix solid microcrystals.
AP ion sources are more accessible than “internal” vacuum ion sources. In an AP ion source, sample ionization takes place outside the MS instrument itself The gas/liquid/solid sample delivery (or loading) takes place under normal laboratory atmospheric pressure condition. Ions produced under atmospheric pressure by an AP ion source are introduced into the vacuum chamber of mass spectrometer through an atmospheric pressure interface (API). Typically, the API consists of several stages of differential pumping separated by gas apertures.
In one approach as described in Horning et. al., Anal. Chem. 1973, vol. 455, pp. 936-943, the entire contents of which are incorporated herein by reference, a pinhole orifice in a thin membrane-type flange separates an atmospheric pressure region from an initial vacuum stage of the MS instrument (typically at a pressure of 0.1-5 mTorr). Ions leak through the pinhole into the mass spectrometer.
In another approach, as described in Whitehouse et al., Anal. Chem. 1985, vol. 57, pp. 675-679, the entire contents of which are incorporated herein by reference, an intermediate pumping chamber typically at a pressure of (0.1-5 mTorr) is connected via a capillary tube, typically having an inner diameter of 0.1-1.0 mm. The capillary tube is frequently heated to a temperature of 80-250° C. for ion desolvation. The heated capillary tube delivers atmospheric pressure ions to the vacuum of the mass spectrometer, as described in U.S. Pat. Nos. 4,977,320 and 5,245,186, the entire contents of which are incorporated herein by reference.
A capillary tube can be used in modern commercial and scientific MS instruments. Ions produced at atmospheric pressure can be effectively transported through metal or insulating capillaries as long as 15 meters. Ion diffusion toward the walls of the capillary tube during transport through the tube represents an ion loss factor. However, the transport of heavy ions in capillary tubes is effective because heavy ions, having lower diffusion coefficients than light ions, do not diffuse as rapidly to the walls of the capillary.
Ion losses in a capillary tube depend mainly on the ion residence time inside the capillary. If a gas flow through a capillary is fixed, the loss of ions to the walls of the capillary tube will depend mainly on the capillary length, and not on the capillary diameter. Both metallic and insulating (e.g., glass) capillaries show similar ion transport properties. The process of ion transport by viscous gas flow through capillaries is described in B. Lin and J. Sunner, J. Am. Soc. Mass Spectrom. 1994, vol. 5, pp. 873-885, the entire contents of which are incorporated herein by reference.
FIGS. 1 and 2
represent schematically two APIs for introducing ions from an atmospheric pressure ion source into a mass spectrometer. As shown in these figures, the API can be include either an inlet capillary tube
2
(as shown in
FIG. 1
) or a pinhole orifice
3
(as shown in FIG.
2
). The inlet capillary tube
2
as shown in
FIG. 1
is located on a MS inlet flange
4
a
. The pinhole orifice
3
as shown in
FIG. 2
is located on a MS inlet flange
4
b.
In
FIG. 1
, an electrospray ion (ESI) source
5
is placed into an atmospheric pressure region
6
close to an inlet orifice
7
of the inlet capillary tube
2
. The capillary tube
2
is attached to the inlet flange
4
a
of the mass spectrometer. The pressure in vacuum chamber behind the inlet capillary tube
2
is typically 1-5 Torr.
In
FIG. 2
, the ESI source
5
is placed into the atmospheric pressure region
6
close to the pinhole orifice
3
. The pinhole orifice
3
is attached to the inlet flange
4
b
and separates the atmospheric pressure region
6
from a first pumped region
8
behind the inlet flange
4
b
. A skimmer
9
separates the first pumped region
8
from a second pumped region
10
. In the second pumped region
10
, the pressure is several orders of magnitude lower than in the first pumped region
8
. Typically, a gas curtain is used to prevent large droplets from the ESI source from blocking the inlet orifice
3
. The gas curtain includes a gas curtain electrode
11
. A gas counterflow flows as shown by the arrow in
FIG. 2
between the gas curtain electrode
11
and the inlet flange
4
b
restricts large droplets from reaching the pinhole orifice
3
. In
FIGS. 1 and 2
, the ESI source
5
is placed as close as possible to the respective inlet orifices
3
or
7
in order to enhance mass spectrometer ion collection.
Because an atmospheric pressure ion source is an external part of a mass spectrometer, in theory a MS instrument can work with a number of the existing ion sources. However, commercial MS instruments are designed to accommodate only one or two particular ion sources. Usually, commercial MS instruments will accommodate only an ESI or an APCI source. Other atmospheric pressure ion sources such as the AP MALDI source previously noted are not readily accommodated.
As shown in
FIG. 3
, the AP MALDI source includes a target plate
11
, a laser beam
12
which irradiates the target plate
11
via mirror
13
which reflects the irradiated laser beam onto a position of the target plate where desorption and ionization of adsorbed species occurs. A detailed description of an AP MALDI source can be found in U.S. Pat. No. 5,965,884, the entire contents of which has been previously incorporated herein by reference. In
FIG. 3
, the physical size and geometric arrangement of the laser optics and the size of the target plate
11
do not permit the placement of an AP MALDI source in close proximity to the inlet orifice
7
of the inlet capillary tube
2
. U.S. Pat. No. 5,965,884 describes a modification to the API which enables an AP MALDI ion source to interface to a mass spectrometer. In this modification, a flange with an inlet orifice is attached to a mass spectrometer and becomes an integral part of the mass spectrometer instrument. As such, the interchangeability to other atmospheric pressure sources such as ESI and APCI sources is complex and time-consuming. To change the flange requires, venting the mass spectrometer, installing another flange, and evacuating the mass spectrometer back to a low operating pressure.
SUMMARY OF THE INVENTION
In conventional approaches, variations in the pressure and temperature conditions in front of the inlet capillary tube
2
or the pinhole orifice
3
change the transport characteristics into the mass spectrome
Doroshenko Vladimir
Laiko Victor
Lee John R.
Science & Engineering Services Inc.
Vanore David A.
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