Mass spectrometers often employ multipole ion guides to focus and confine ions as they are transported along a path from the ionization source to the mass analyzer. Ion guides generally include a plurality of elongated electrodes (sometimes referred to as rod electrodes) to which oscillatory voltages are applied to establish a radially confining field. In addition to the ion transport function, ion guides may be employed for the radial confinement of ions in a collision cell, in which the internal volume of the ion guide is pressurized with collision gas, and ions entering the ion guide undergo fragmentation via the collision-induced dissociation mechanism.
When ion guides are located in relatively high-pressure regions of the mass spectrometer, such as in chambers adjacent the ionization source or within a collision cell, the initial axial velocities of the incoming ions are sharply reduced due to collisions between the ions and background/collision gas. This reduction in ion axial velocity results in a higher residence time within the interior of the ion guide, which may adversely affect instrument performance. More specifically, prolonged ion residence times within the ion guide may reduce sample throughput, decrease sensitivity, and impose limits on various aspects of operation. In the example of triple quadrupole mass spectrometers operated in multiple reaction monitoring (MRM) mode, slowing of ions within the collision cell or upstream ion guides will lengthen the required dwell time at each precursor-product ion transition, thereby constraining the number of different transitions that may be monitored per unit time.
In order to increase the rate at which ions are axially transported through ion guides, it is known to establish a static axial field along part or all of the ion guide length to urge ions in the direction of the ion guide exit. Various structures and methods have been disclosed in the prior art for producing an axial field of this type (see, e.g. U.S. Pat. Nos. 5,847,386; 6,111,250; 6,713,757; 7,067,802; and 7,675,031, which are hereby fully incorporated by reference herein). However, these structures and methods tend to cause distortion of the radially-confining oscillatory (e.g., radio-frequency (RF)) field, which may result in defocusing of the ion beam and consequent reduction in transmission efficiency. Applicant believes that there is a need in the mass spectrometry art for an ion guide having structures for establishing an axial field that avoids the radial-field distortion effects present in prior art devices.
An ion guide may include a plurality of electrodes, a plurality of resistive inserts, a RF voltage supply, and a DC voltage supply. The plurality of electrodes may be arranged about a device centerline to form an internal volume. At least two of the electrodes may include a longitudinally extending gap. The electrodes include an inward surface facing the device centerline to form a periphery of the internal volume. The plurality of resistive inserts may be configured to be proximate to at least two of the gaps and radially aligned with respect to the device centerline. The resistive inserts may include an innermost surface that faces the device centerline where the innermost surface is a first distance from the periphery of the internal volume. The RF voltage supply may be configured to apply a RF voltage to the plurality of electrodes that establishes a RF field to radially confine ions. In an embodiment, the RF voltage supply may also be configured to apply the RF voltage to the plurality of resistive inserts. The DC voltage supply may be configured to apply a first DC voltage to a first location of the resistive insert and a second DC voltage to a second location of the resistive insert that establishes an axial electric field gradient along at least a portion of the device centerline. The second DC voltage is different than the first DC voltage and the second location is longitudinally spaced apart from the first location.
A mass spectrometer may include an ionization source, an ion guide, a mass analyzer, and a detector. The ionization source may be configured to ionize molecules. The ion guide may include a plurality of electrodes arranged about a device centerline to form an internal volume. At least two of the electrodes may include a longitudinally extending gap. The electrodes include an inward surface facing the device centerline to form a periphery of the internal volume. A plurality of resistive inserts may be configured to be proximate to at least two of the gaps and radially aligned with respect to the device centerline. The resistive inserts may include an innermost surface that faces the device centerline where the innermost surface is a first distance from the periphery of the internal volume. A RF voltage supply may be configured to apply a RF voltage to the plurality of electrodes that establishes a RF field to radially confine ions. In an embodiment, the RF voltage supply may also be configured to apply the RF voltage to the plurality of resistive inserts. A DC voltage supply may be configured to apply a first DC voltage to a first location of the resistive insert and a second DC voltage to a second location of the resistive insert that establishes an axial electric field gradient along at least a portion of the device centerline. The second DC voltage is different than the first DC voltage and the second location is longitudinally spaced apart from the first location. The mass analyzer may be configured to receive the ionized molecules from the ion guide and filter the ionized molecules so that a subset of ionized molecules having a particular mass to charge ratio passes through. The detector may be configured to receive and measure the ionized molecules from the mass analyzer.
In another embodiment of an ion guide, it includes a plurality of electrodes, a plurality of conductive inserts, a RF voltage supply, and a DC voltage supply. The plurality of electrodes may be arranged about a device centerline to form an internal volume. The internal volume can include a front end configured to allow ions to enter and a back end configured to allow ions to exit. At least two of the electrodes may include a longitudinally extending gap. The electrodes may include an inward surface facing the device centerline to form a periphery of the internal volume. The plurality of conductive inserts may be configured to be proximate to at least two of the gaps and radially aligned with respect to the device centerline. The conductive inserts may include an innermost surface that faces the device centerline. The innermost surface may include a second distance from the periphery of the internal volume at the front end of the ion guide. In addition, the innermost surface may also include a third distance from the periphery of the internal volume at the back end. The second distance at the front end being greater than the third distance at the back end. The RF voltage supply may be configured to apply a RF voltage to the plurality of electrodes that establishes a RF field to radially confine ions. In an embodiment, the RF voltage supply may also be configured to apply the RF voltage to the plurality of conductive inserts. The DC voltage supply may be configured to apply a third DC voltage to the conductive inserts that establishes an axial electric field gradient along at least a portion of the device centerline.
A method of guiding ions in a mass spectrometer may include injecting ions into an ion guide. The ion guide may include a plurality of electrodes and a plurality of inserts. The plurality of electrodes may be arranged about a device centerline to form an internal volume. The internal volume may include a front end configured to allow ions to enter and a back end configured to allow ions to exit. At least two of the electrodes may include a longitudinally extending gap. The plurality of inserts may be configured to be proximate to at least two of the gaps. The inserts may include an innermost surface that faces the device centerline where the innermost surface includes a first distance from a periphery of the internal volume. A RF voltage may be applied to the plurality of electrodes to establish a RF field to radially confine ions. In an embodiment, the RF voltage may also be applied to the plurality of inserts. At least one DC voltage may be applied to the plurality of inserts to establish an axial electric field gradient along at least a portion of the device centerline.
The accompanying drawings, which are incorporated herein and constitute part of this specification, illustrate presently preferred embodiments of the invention, and, together with the general description given above and the detailed description given below, serve to explain features of the invention (wherein like numerals represent like elements). A detailed understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:
The following detailed description should be read with reference to the drawings, in which like elements in different drawings are identically numbered. The drawings, which are not necessarily to scale, depict selected embodiments and are not intended to limit the scope of the invention. The detailed description illustrates by way of example, not by way of limitation, the principles of the invention. This description will clearly enable one skilled in the art to make and use the invention, and describes several embodiments, adaptations, variations, alternatives and uses of the invention, including what is presently believed to be the best mode of carrying out the invention. As used herein, the terms “about” or “approximately” for any numerical values or ranges indicate a suitable dimensional tolerance that allows the part or collection of components to function for its intended purpose as described herein.
As discussed in the background section, it may be advantageous to establish an axial DC field within the interior of an ion guide to assist in the movement of ions therethrough and avoid the problems associated with prolonged ion retention. The prior art includes a variety of structures developed for this purpose, but many of these structures produce significant distortion in the symmetry of the radially-confining RF field.
Applicant will describe a multipole ion guide with axial electric fields that move ions through the ion guide, and has reduced distortion of RF fields. As an example, such multipole ion guides may be implemented on mass spectrometer 600 for ion guides 604 and/or 608.
While the foregoing paragraph describes the implementation of ion guide 100 within a triple quadrupole mass spectrometer 600, it should be understood that this description is provided by way of example only, and does not limit the invention to operation in any particular environment. Those skilled in the art will recognize that embodiments of the invention may be beneficially incorporated into any number of mass spectrometer types and architectures.
It should be noted that although ion guide 100 is depicted as having four longitudinally extending gaps 120, an alternative embodiment may include only two gaps so long as they are in an opposing relation with respect to the device centerline. Additionally, where the alternative embodiment has four electrodes, the two remaining electrodes will not have a longitudinally extending gap and will be in an opposing relation with respect to the device centerline.
Referring back to
The inward electrode surface 124 in
The plurality of resistive inserts (110, 112, 114, and 116) are configured to be proximate to each of the gaps 120, as illustrated in
Referring back to
An insert proximate to the gap may represent that a location of the insert is next to, very close in space to, neighboring, or adjacent to the gap. In another embodiment, the resistive insert may be proximate and, in addition to, be partially disposed within the gap. The proximate location of the resistive with respect to the gap can be configured so that a sufficiently strong electric field gradient is generated for moving along ions along the device centerline in order to meet instrument performance targets. In an embodiment, the proximate inserts need to be sufficiently close to the gap so that a sufficiently strong axial electric field can be created to move ions along the device centerline. The magnitude of the first distance D1 range may be influenced by other factors such as DC voltage, electrode thickness, and gap distance.
In an embodiment, first distance D1 can be approximately uniform for the entire length of the resistive insert, as illustrated in
The resistive insert may be a normal semiconductor, resistive material coated insulator, or a composite material such as resin impregnated with electrically conductive particles (carbon filled PEEK for instance). In an embodiment, the plastic may be an ESd (electrostatic dissipative) material such as, for example, the commercially available Semitron 480 (reinforced polyetheretherketone (PEEK)). The resistive insert may have a surface resistivity ranging from about 102 to about 1010 ohms per square, and preferably range from about 106 to about 1010 ohms per square. In an alternative embodiment, the resistive insert may be in the form of a resistive material disposed on a surface of a printed circuit board (PCB). It should be noted that the resistive insert has a simple configuration; it is one continuous part and does not have multiple segmentations with numerous electrical connections (i.e., >2 per insert) to a DC voltage supply.
The resistive insert may have a relatively uniform resistivity along its length so that a gradient field has relatively low distortion. In an embodiment, the resistivity may have a relative variation (about one standard deviation) ranging from about 5% to about 30%, and preferably be less than about 10% for a typical insert having a length of about 10 centimeters.
DC voltage supply 130 may be electrically connected to the plurality of resistive inserts via wires. In an embodiment, a hole may be drilled into the resistive insert and a conductive epoxy, or any other conductive adhesive may be used to secure the wire directly into the resistive insert. In another embodiment, a clip can be used to secure the wire into the hole in the resistive insert or to the body of the resistive insert.
Referring back to
In an embodiment, the RF voltage supply 128 can also be configured to apply a RF voltage to the plurality of electrodes (102, 104, 106, and 108) and the plurality of resistive inserts (110, 112, 114, and 116). A RF voltage having a first RF potential RF(+) can be applied to electrodes 102a, 102b, 104a, and 104b, and resistive inserts 110 and 112, as shown in
It should be noted that the resistive inserts in ion guide 100 are placed in an approximately zero gradient RF region. This is a result of the resistive inserts being placed proximate to the gap of corresponding electrode portions where the same RF potential is applied to the electrode portions and the resistive insert. By placing the inserts in an approximately zero gradient RF region, there is little change in observed capacitance and RF frequencies in the ion guide with and without the application of an axial electric field gradient. It should be noted that the resistive inserts can be made with relatively high dissipative materials for generating drag fields in ion guides when the resistive inserts are disposed in an approximately zero gradient RF region.
Under circumstances where an insert is placed between two RF electrodes that have different RF potentials, a strong RF gradient can exist and cause power to dissipate into the insert. For example, locating a resistive insert in between electrode portions 102b and 106a would cause the resistive insert to be in a relatively high RF gradient field. This configuration can cause a RF power dissipation in the resistive plastic. During frequency tuning, this can appear as degradation in the measured signal in the form of significant tune curve peak broadening and higher RF current consumption. A possible result of this power dissipation can be heat buildup and destruction of the insert. For the situation where the inserts are exposed to strong RF gradients or fringing RF fields, applicants believe that the inserts need to be constructed with materials having relatively low dissipation loss factors. In turn, applicants believe that there are a limited number of materials that can be used for resistive inserts that have the appropriate resistivity, dissipative loss factor, and uniform resistivity simultaneously. However, for the embodiments where inserts are disposed proximate to the gap in an approximately zero gradient RF region, applicants believe that many other materials could be used as an insert because materials with higher dissipation loss factors could be used. In the embodiment where the resistive inserts are disposed proximate to the gap, the dissipation loss factor of the resistive insert may be greater than about 0.01, and be about 0.266 at 1 MHz for Semitron 480 in the embodiment.
DC voltage supply 130 is configured to apply a DC voltage difference along each one of the plurality of resistive inserts (110, 112, 114, and 116). More particularly, DC voltage supply can apply a first DC voltage DC1 to a first location for each of the resistive inserts (110, 112, 114, and 116) and a second DC voltage DC2 to a second location for each of the resistive inserts, as shown in
It should be noted that the arrangement of resistive inserts in ion guide 100 with the DC voltage difference provides a low distortion in RF field, with the distortion appearing in the dodecapolar non-linear term. In contrast, the tilted and tapered electrode configurations described in U.S. Pat. Nos. 5,847,386 and 6,111,250 provide a higher distortion in RF field where the distortion appears in the octupolar term. Electrode geometries that have rotational symmetry along a device centerline will have less RF distortion as compared to electrodes geometries that do not have rotational symmetry such as, for example, the tilted and tapered electrode configurations. As a result, ion guide 100 and others described herein, that have rotational symmetry with respect to the device centerline, provide RF fields with relatively lower distortion caused by the octupolar field component. Reduced contribution of this component to the RF field will diminish negative effects of non-linear resonances on mass dependency in ion transmission.
Now that the situation has been described where the insert and electrode have about the same length, the following will describe embodiments where the resistive insert length L1 is less than the electrode length L2. More particularly, a back end of the resistive insert can be recessed inward, as illustrated in
Referring back to
Referring back to
Referring back to
Under certain circumstances where there is a need for a simple design, an electrode may have uniform thickness where thickness is a distance between an outward surface and inward surface. However, in
Under certain circumstances, adjacent devices such as, for example, ion lenses or other quadrupoles can introduce fringing RF fields to a front or back end of an ion guide. To reduce such an effect, a front and back plate may be used for each of the electrodes to screen fringing RF fields.
Note that the configuration of ion guide 1000 will have a more open RF gradient field compared to ion guides 100 and 900. For example, RF field gradient between electrodes 1002b and 1006a will propagate further into the location of resistive insert 110 because the open geometry of electrode 1002b does not completely shield resistive insert 110. However, ion guide 1000 can still be a viable device so long as the resistive insert has as a sufficiently low dissipation loss factor.
Referring to back to
Now that various ion guides with resistive inserts have been described, the following will describe an ion guide 1100 constructed in accordance with a different embodiment of the invention that includes conductive inserts. In general, ion guide 1100 is similar to ion guide 100 in regards to the electrode shape, structure, and orientation. In contrast to ion guide 100, ion guide 1100 includes inserts that are more conductive than resistive inserts and have a tilted arrangement, as illustrated in
Referring back to
A plurality of conductive inserts (1156, 1158, 1160, and 1162) can be configured to be proximate to the longitudinally extending gaps 120, as illustrated in
As illustrated in
The innermost surface 1140 is an approximately flat portion of the conductive insert that is closest to and facing the device centerline 118. In an embodiment, the innermost surface of the conductive insert may represent the portion closest to the periphery of the internal volume. The innermost surface does not have to be flat and may be a different shape such as, for example, a curved surface from a cylinder and a hyperbolic surface. In an embodiment, the conductive insert may be elongated rods where the rods can be cylinders, squares, rectangles, or other shape suitable for generating an axial field gradient that can guide ions.
In an embodiment, second distance D2 may range from about 1 millimeter to about 2 millimeters and third distance D3 may be about 0.5 millimeters for a conductive insert having a length of about 10 centimeters. The orientation slope of the conductive insert may range from about 0.005 milliradians to about 0.015 milliradians. Conductive insert may be made of material similar to those used for the electrodes and with a similar resistivity range. It should be noted that conductive insert may also be referred to as a metal insert.
Similar to ion guide 100, the RF voltage supply can be configured to apply a RF voltage to the plurality of electrodes (102, 104, 106, and 108) in ion guide 1100. The application of the RF voltage will establish a RF field to radially confine ions along device centerline 118. In an embodiment, a RF voltage having a first RF potential RF(+) can be applied to electrodes 102a, 102b, 104a, and 104b, and a RF voltage having a second RF potential RF(−) can be applied to electrodes 106a, 106b, 108a, and 108b, as shown in
In an embodiment, the RF voltage supply 128 can also be configured to apply a RF voltage to the plurality of electrodes (102, 104, 106, and 108) and the plurality of conductive inserts (1156, 1158, 1160, and 1162). A RF voltage having a first RF potential RF(+) can be applied to electrodes 102a, 102b, 104a and 104b, and conductive inserts 1156 and 1158. In addition, a RF voltage having a second RF potential RF(−) can be applied to electrodes 106a, 106b, 108a, and 108b, and conductive inserts 1160 and 1162. It should be noted that the conductive inserts in ion guide 1100 are placed in an approximately zero gradient RF region. By placing the inserts in an approximately zero gradient RF region, there is little change in observed capacitance and RF frequencies in the ion guide with and without the application of an axial electric field gradient.
DC voltage supply 130 can be configured to apply a static voltage to the plurality of conductive inserts (1156, 1158, 1160, and 1162). The application of the DC voltage can establish an axial electric field gradient along at least a portion of the device centerline. The static voltage may be referred to as a third DC voltage DC3. Where the second distance D2 is greater than third distance D3, the third DC voltage DC3 may range from about −50 to about −5 volts. For the situation where the third DC voltage DC3 is a negative value, a “push” mechanism occurs to move ions along the ion guide.
DC voltage supply 130 may be electrically connected to the plurality of conductive inserts via wires. In an embodiment, a hole may be drilled into the conductive insert and a conductive epoxy, conductive adhesive, or solder may be used to secure the wire to the conductive insert. In another embodiment, a clip can be used to secure the wire into a hole in the conductive insert.
It should be noted that the configuration of ion guide 1100 with conductive inserts does not significantly change tank circuit parameters such as capacitance and RF frequency. Thus, only a relatively small amount of fine tuning is required for a smooth transition between implementing embodiment designs with and without a drag field.
In an embodiment, a method of guiding ions in a mass spectrometer includes injecting ions into an ion guide. A RF voltage can be applied to a plurality of electrodes to establish a RF field to radially confine ions. The RF voltage can also be applied to the plurality of inserts so that they are in an approximately net zero RF field. At least one DC voltage can be applied to the plurality of inserts to establish an axial electric field gradient along at least a portion of the device centerline. The axial field gradient moves the ions along device centerline so that the ions can be ejected. Next, the ejected ions can be measured as a detection current at a detector so that the detection current achieves a steady-state value ranging from about 0.3 to about 1 milliseconds or less.
In an alternative embodiment, an ion guide having conductive inserts may be configured to use a “pull” mechanism for moving ions along. Such an ion guide will have the conductive inserts tapered in an opposite manner than that of ion guide 1100 such that the second distance D2 is less than third distance D3. Thus, in the alternative embodiment where the second distance D2 is less than third distance D3, the third DC voltage DC3 may be a positive value ranging from about +5 to about +50 volts.
While preferred embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. While the invention has been described in terms of particular variations and illustrative figures, those of ordinary skill in the art will recognize that the invention is not limited to the variations or figures described. In addition, where methods and steps described above indicate certain events occurring in certain order, those of ordinary skill in the art will recognize that the ordering of certain steps may be modified and that such modifications are in accordance with the variations of the invention. Additionally, certain of the steps may be performed concurrently in a parallel process when possible, as well as performed sequentially as described above. Therefore, to the extent there are variations of the invention, which are within the spirit of the disclosure or equivalent to the inventions found in the claims, it is the intent that this patent will cover those variations as well.
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