The present invention relates to ion traps for mass spectrometry, and in particular, to a linear ion trap device for efficient storage of ions providing high sensitivity, rapid, high efficiency mass spectrometry.
Ion trap mass spectrometers have conventionally operated with a three-dimensional (3D) quadrupole field formed, for example, using a ring electrode and two end caps. In this configuration, the minimum of the potential energy well created by the radio-frequency (RF) field distribution is positioned in the center of the ring. Because the kinetic energy of ions injected into an ion trap decreases in collisions with buffer gas molecules, usually helium, the injected ions naturally localize at the minimum of the potential well. As has been shown using laser tomography imaging, the ions in these conventionally constructed ion traps congregate in a substantially spherical distribution, which is typically smaller than about 1 millimeter in diameter. The result is a degradation of performance of the device due to space charge effects, especially when attempting to trap large numbers of ions.
As one possible solution to this problem, quadrupole mass spectrometers having a two-dimensional quadrupole electric field were introduced in order to expand the ion storage area from a small sphere into a beam. An example of this type of spectrometer is provided in U.S. Pat. No. 5,420,425 to Bier, et al. The Bier, et al. patent discloses a substantially quadrupole ion trap mass spectrometer with an enlarged or elongated ion occupied volume. The ion trap has a space charge limit that is proportional to the length of the device. After collision relaxation, ions occupy an extended region coinciding with the axis of the device. The Bier, et al. patent discloses a two-dimensional ion trap, which can be straight, or of a circular or curved shape, and also an ellipsoidal three-dimensional ion trap with increased ion trapping capacity. Ions are mass-selectively ejected from the ion trap through an elongated aperture corresponding to the elongated storage area.
Though increased ion storage volume is provided by the ion trap geometry of the Bier, et al. patent, the efficiency and versatility of the mass spectrometer suffer, for example, due to the elongated slit and subsequent focusing of the ions required after ejection. In addition, the storage volume is limited by practical considerations, since the length of the spectrometer must be increased in order to increase the ion storage volume.
There is a need, therefore, unmet by the prior art, to provide an efficient and compact ion trap, particularly for use in a mass spectrometer, which provides both good ion storage volume and efficient ejection of selected ions.
The present invention provides an efficient and compact ion trap and a method for manipulating ions in an ion trap. The ion trap and method provide both good ion storage volume and efficient ejection of selected ions. A high resolution, high sensitivity mass spectrometer that includes the ion trap is also provided.
In particular, the present invention provides a method for manipulating ions in an ion trap, which includes storing ions in the ion trap; spatially compressing the ions in a mass-to-charge ratio dependent manner; and ejecting the spatially compressed ions in a defined range of mass-to-charge ratios.
The method may include ejecting the ions orthogonally to an axis of the ion trap. Alternatively, the ions may be ejected axially, i.e., parallel to the injection path.
An ion trap of the present invention includes an injection port for introducing ions into the ion trap, an arm having a first end and a second end for confining and spatially compressing the ions, and an ejection port for ejecting the spatially compressed ions from the second end of the arm of the ion trap. The arm includes two pairs of opposing electrodes between the first end and the second end. Each electrode includes an interior surface suitably shaped for providing a quadrupole electric field potential at any cross-section of the ion trap. In addition, the distance between each opposing electrode increases from the first end to the second end. Ions selected for ejection are spatially compressed into a region at the second end.
The present invention also provides an ion trap including two pairs of opposing electrodes, where each pair is separated by a distance equal to twice an effective radius R of an electric field potential U(x,y,z), and a length L, which is measured along the z-axis. The two pairs of opposing electrodes are shaped to create an electric field potential described by an equation (1) as follows:
and the effective radius R varies as a function of a variable length z according to
where k, C, r0 and U0 are constants dimensioned to satisfy the equation (1) of the electric field potential for the chosen boundary condition.
The present invention additionally provides an ion trap including an injection port for introducing ions into the ion trap, a length L along which injected ions are stored, which is measured along a z-axis, and an arm including two pairs of opposing electrodes extending the length L and suitably shaped to confine the injected ions. Each pair of opposing electrodes is separated by a distance 2R, wherein R varies as a function of the variable z. The two pairs of opposing electrodes include a larger or wider end, and a smaller (narrower) end. Ions selected for ejection are compressed toward the larger end. The ion trap also includes an ejection port for ejecting the selected ions from the larger end.
The electrodes of the ion trap of the present invention may include a hyperbolic cross-sectional shape, with a cross-sectional area that increases from the narrower to the wider end.
Alternatively, the electrodes may include tapered rods, which have a circular cross-sectional shape. Preferably, these tapered rods have a circular cross-section of diameter D at each value 2R along the length, which satisfies the equation:
D=1.148×2R (4).
As a result, the present invention provides an efficient and compact ion trap and a method for manipulating ions in an ion trap, which provide both increased ion storage volume and efficient ejection of selected ions. The ion trap may be adapted for use in a high resolution, high sensitivity mass spectrometer.
Other objects and features of the present invention will become apparent from the following detailed description considered in conjunction with the accompanying drawings. It is to be understood, however, that the drawings are designed as an illustration only and not as a definition of the limits of the invention.
Referring to
The ion trap 10 of the present invention provides ion storage of high capacity. The ion trap 10 also allows all stored ions to be sequentially ejected by compressing them according to their mass-to-charge value, also called the m/z value. Therefore, in one ejection scan, a mass spectrometer including the ion trap 10 (see
The ion trap 10 of the present invention includes a set of two pairs of opposing electrodes 14 (one pair is shown in
The four-electrode structure allows a radio frequency (RF) quadrupole field to be established, which traps the ions in the radial dimension. The RF field is generated according to methods well-known to those skilled in the art, including the application of static direct-current (DC) potentials applied to the ends of the electrodes 14.
The z-axis 18 is also referred to as the axis of the ion trap 10, and refers to the axis along which ions are stored. The length of the ion trap is measured along the axis or z-axis 18.
Ions are injected into the ion trap 10 via an injection port 20. The two pairs of opposing electrodes 14 together form an arm 22 of the ion trap 10 for confining the injected ions between the electrodes 14. The arm 22 preferably includes a first end 24 and a second end 26. As shown in
The ion trap 10 also preferably includes stopping plates 29 at each end, to which small DC stopping potentials are applied in order to prevent ions from escaping along the z-axis 18.
In a preferred embodiment shown in
An ion trap mass spectrometer 40 formed according to the present invention includes the ion trap 10. As shown in
Preferably, the spectrometer 40 further includes a buffer gas, such as Helium, which fills the interior 48 of the spectrometer 40 for cooling of the ions by collisions with molecules or atoms of the buffer gas 48 before and after injection into the ion trap 10.
Referring to
The electrodes in each arm of the ion trap 10 of the present invention are preferably tapered and suitably shaped to provide a quadrupole electric field potential at any cross-section of the ion trap 10. In particular, the geometry of the ion trap and shape and placement of the pair of opposing electrodes in each arm preferably provide a three-dimensional electric field potential U(x, y, z), which can be described by the equation:
The parameter R represents an effective radius of the field potential, and corresponds to half of the distance separating a pair of opposing electrodes in an arm at any cross-section of the ion trap 10. R varies as a function of a variable length z along the z-axis 18, measured from the first end 24, according to the following:
The variables x and y in equation (1) correspond to coordinates on the x-axis 38 and y-axis 50 respectively, where the z-axis 18 of the coordinate system coincides with the centered axis 12 of the trap 10. The origin of the coordinate system is centered, therefore, on the axis of symmetry 12 between opposing electrodes at the narrowest end of the arm, e.g., at the first end 24. L corresponds to the length of the arm from the first end 24 to the second end 26, for example. The parameters k, U0 and C in equations (1) and (2), represent constants, which are determined according to chosen boundary conditions for a given value of r0. Looking at the left arm 22 of the ion trap 10 in
One skilled in the art will recognize that the angle 16 of the electrodes with respect to the z-axis 18 is related to the parameter k. It can be seen, for example, that the tangent of the angle 16 equals
where RMAX is the value of R in equation (2) evaluated at z=L. In addition, by substitution into equation (2),
for z=L. In general, however, the value of k will be determined by the chosen shape of the rods, which also contributes to a proper choice of angular deviation 16, and the length L of the arm.
The angular deviation 16 is non-zero and preferably, substantially large enough given the geometry of the electrodes and length of the ion trap to spatially compress ions into a region in the widest end, e.g., a second end 26, of the ion trap 10.
In one embodiment, the angular deviation 16 is greater than 0 degrees.
In another embodiment, the angular deviation 16 is greater than 0 degrees and less than 90 degrees.
In yet another embodiment, the angular deviation 16 is greater than 10 degrees.
In still another embodiment, the angular deviation 16 is less than 45 degrees.
The effect of the trapping potential 52 described by equation (1) can be described as follows. Ions entering the ion trap 10, preferably filled with collision gas (such as, for example He or N2), will have a tendency to accumulate along the z-axis 18 of the device 10. As ions collide with molecules of a neutral buffer gas they lose their kinetic energy. At the same time, ions are efficiently confined inside of the device 10 by the RF field created by the quadrupole rods 14 and by the small repelling DC field created by end plates to which a stopping potential is applied. Ions which do not align along the z-axis 18 (ions with excess of kinetic energy) will be influenced by a force arising due to an effective potential which pushes ions towards the wider end of a quadrupole. Eventually, after ions lose enough kinetic energy in collisions with the buffer gas, they will distribute themselves along the z-axis 18 of the entire ion trap. The force along the z-coordinate is negligibly small at small distances from the z-axis.
Ejection of stored ions from the ion trap 10 of the present invention is then preferably achieved by applying an additional small excitation RF signal between opposing pairs of electrodes, and simultaneously ramping up the amplitude of the applied excitation RF voltage. Due to the shape of the electric field potential described by equations (1) and (2) and depicted in
The m/z-dependent compressing of ions essentially decouples the processes of ion storage and ion ejection. While ions are being stored, ions may occupy the entire cylindrical volume of the ion trap 10 along its axis 12. During ejection, ions are selectively compressed according to their m/z ratio into the region 54 at the widest part of ion trap 10, which corresponds to the second ends 26 and 36 of the ion trap 10 of
Controlled ion ejection then occurs from the ejection port 28, when the amplitude of the RF oscillations becomes comparable with the distance between opposing electrodes, resulting in the ions reaching a so-called ejection energy threshold, as is known to those skilled in the art.
Referring again to
As those skilled in the art will recognize, the ion source chamber 43 is typically maintained at a pressure between about 10 and 1000 millitorr and the detector chamber 55 pressure is typically maintained within a range of about 10−7 to 10−4 torr. The ion trap chamber 37 is preferably maintained at about 0.3 to 200 millitorr, and an additional chamber 53 positioned between the ion trap 10 and the detector chamber 55 is preferably maintained at about 10−7 to 10−4 torr.
In the preferred embodiment of the ion trap 10 of
In one embodiment, the central insert 56 includes a small conventional linear quadrupole having a four parallel-rod configuration. FIG. 2A of U.S. Pat. No. 5,420,425 to Bier, et al., provides an example of a quadrupole that may be used as the central insert 56.
In another embodiment of the central insert 56, the ejection port 28 is provided by omitting one of the electrodes (top electrode 58 in
In a further embodiment best shown in
Referring to
The ion guide 62 may include, for example, a set of two opposing pairs of substantially parallel electrodes forming a conventional quadrupole, to which a DC potential is applied in operation as is well-known to those skilled in the art.
In one embodiment, the spectrometer 40 includes the ion guide 62 including a quadrupole, which is used as a collision cell, and an additional four-electrode structure 64, which is used as a mass filter between the collision cell and the detector 60. In this embodiment, the efficiency of a selected ion monitoring scan or a neutral loss scan experiment will be greatly increased over conventional mass spectrometers.
In a further embodiment, the mass spectrometer 40 includes the ion guide 62 including a quadrupole followed by an orthogonal injection time-of-flight mass spectrometer. This embodiment of the spectrometer of the present invention is theoretically capable of performing full-range tandem mass spectrometry without loss of signal, referred to as “MS/MS,” on every ion in the single-stage mass spectrum in order to generate complete structural information for the compound ions of interest.
The present invention, therefore, provides an ion trap which, when used in a spectrometer, enables multiplexing of an MS/MS experiment by sequentially carrying out MS/MS on each ion species ejected from the ion trap in the whole M/Z range of interest without losses. Theoretically, the gain in sensitivity approaches (ΔM/Z)/(Δm/z). ΔM/Z refers to the observable m/z range of the mass spectrometer and is typically on the order of about 4000. Δm/z refers to a resolution of the mass spectrometer and is typically in a range of about 14-40. Therefore, theoretical gains from 100 to 1000 times may be achieved with a mass spectrometer that includes the ion trap of the present invention. As a result of this sensitivity increase, a significant gain in speed of the measurements is also provided.
In one embodiment, ΔM/Z for a spectrometer formed in accordance with the present invention is at least 100.
In another embodiment, ΔM/Z for a spectrometer formed in accordance with the present invention is about 100,000 or less.
In one embodiment, Δm/z for a spectrometer formed in accordance with the present invention is at least 1.
In another embodiment, Δm/z for a spectrometer formed in accordance with the present invention is about 100 or less.
The increased improvement in performance of an ion trap 10 and spectrometer formed in accordance to the present invention is a result of the novel geometry of the electrodes in each arm, which provides a unique electric field potential that selectively and sequentially compresses ions according to their m/z ratios into a region near the ejection port.
As best described by equation (1), the ion trap 10 of the present invention is essentially a three-dimensional ion trap. Equation (1) was derived from the following equation:
where U0, r0, L, k, and C are some constants as described above, and x, y, z are coordinates.
The concrete values for the constants are preferably set from a particular boundary condition, as well-known to those skilled in the art, for which x and y coordinates are set to correspond to r0, i.e., for x2+y2=r02, and z is set to the particular length of a device L.
The potential U(x,y,z) described by equations (1) and (3) satisfy a Laplace (ΔU=0) equation. The first term in the brackets of equation (3) resembles the potential of a two-dimensional quadrupole, which is in turn multiplied by another term that introduces the dependence of the entire potential on the z-coordinate. This similarity to the two-dimensional quadrupole potential is emphasized by rewriting equation (3) in the form of equation (1):
and by defining the variable R according to equation (2) as:
In this form, equation (1) resembles even more an equation for a linear quadrupole, and emphasizes an essential difference. The distance between opposite electrodes, corresponding to 2R, changes as a function of the z-coordinate.
As an example, the graph 70 in
As a result of the tilting angle 16 of the electrodes in the present invention, the shape of the electrode cross-section and the taper, and, consequently, the cross-sectional area of each electrode as a function of z are important. In addition, the optimum taper and shape will depend on the tilting angle 16.
Essentially, the electrodes of the present invention include any shape and arrangement thereof, which can provide a substantially quadrupole potential at any cross-section of the ion trap and thus substantially satisfy equations (1) and (2).
In one embodiment, an electrode 80 for use in the ion trap 10, as shown in
Referring to
In addition, the acuteness or slope of the curve (also referred to herein as eccentricity) at a mid-point of the hyperbolic profile of each electrode 80 preferably decreases from the first end 24 to the second end 26 of the arm 22, in order to maintain the hyperbolic profile and substantially quadrupole potential at each cross-section as the distance between opposing electrodes is increased. The electrodes 80 are thus oriented and shaped to substantially maintain the electric trapping potential described by equation (1).
As shown in
A representation of the shape of the effective potential 90 formed according to
Simulations of ion motion in the trap 10 constructed from two arms 22 and 32 connected by the central insert 56 as shown in
A typical ion trajectory 94 is shown for such a device in
Simulations were performed with ions with different m/z values. All simulations showed similar ion behavior in the trap 10. At first, ions have a tendency to spread along the entire length of the device. However, when the amplitude of the excitation RF voltage begins to ramp up and a small excitation voltage is applied between the two pairs of rods in each arm, the ions compress towards the center of the trap. Eventually ions having the same m/z values bunch in a region 100 at the central widest part of the trap for a few moments before being ejected.
Similar simulations were performed with ions of different m/z values. All simulations indicated stable behavior of the ion trap 10 formed in accordance with the present invention.
In another embodiment of the present invention, the electrodes in each arm of the ion trap include cylindrical rods of circular cross-section. Referring to
Referring to
D=1.148×d0 (4),
where d0 also equals 2R, and where R is defined by equation (2).
The ion trap 10 of
As described above, the electrodes of the present invention include any shape and arrangement of electrodes, which can provide a substantially quadrupole potential at any cross-section of the ion trap to substantially satisfy equations (1) and (2).
In another embodiment, the electrodes include a cross-section of at least a fraction of a circle, arranged so that the interior surface of each opposing electrode within the trap forms at least an arc of the circle. The circle is centered at a point external to the interior of the trap. The taper of the electrode and distance between opposing electrodes is chosen to optimally satisfy equations (1) and (2).
In yet another embodiment, a cross-section of each electrode defines a parabola. The interior surface of each opposing electrode includes an inwardly curved profile. Further, an acuteness of the parabola increases from the second end 26 toward the first end 24, for example in arm 22 of the ion trap 10 of
Referring again to
In another embodiment, however, the injection port 20 and ejection port 36 may be parallel. In yet another embodiment, the injection port 20 and ejection port 28 coincide.
Referring to
A simulation of the ion trajectories 134 after injection is provided in
In one embodiment, the insert 126 includes a small linear conventional quadrupole, such as the Bier, et al. quadrupole of FIG. 2A.
The ion trap 160 of
The ion trap of the present invention is advantageously compact. Preferably, each arm of any of the embodiments of the ion trap has a length of 1 millimeter or more.
In another embodiment, each arm has a length of 50 millimeters or more.
In one embodiment, at least one arm of the ion trap is 1000 millimeters or less.
In another embodiment, at least one arm of the ion trap is 500 millimeters or less.
In another embodiment, the central insert or insert or section of linear conventional quadrupole including the ejection port is at least 1 millimeter long.
In yet another embodiment, the central insert or insert or section of linear conventional quadrupole including the ejection port is at least 50 millimeters long.
In another embodiment, the central insert or insert or section of linear conventional quadrupole including the ejection port is 1000 millimeters or less.
In yet another embodiment, the central insert or insert or section of linear conventional quadrupole including the ejection port is 500 millimeters or less.
An additional embodiment 190 of the ion trap of the present invention is provided in
In addition to its usefulness in a mass spectrometer, the ion trap of the present invention may also be used for building ion-ion and ion-cation reactors.
In another embodiment, the ion trap of the present invention may be used to isolate ions for a given M/Z for other purposes such as optical spectroscopy or for use in preparative purification of compounds.
While there have been described what are presently believed to be the preferred embodiments of the invention, those skilled in the art will realize that changes and modifications may be made thereto without departing from the spirit of the invention, and is intended to claim all such changes and modifications as fall within the true scope of the invention.
The research leading to the present invention was supported, at least in part, by NIH Grant No. RR 00862. Accordingly, the United States Government has certain rights in the invention.