Patent Grant
9236232
Generally, mass spectrometers measure mass-to-charge ratios of ions obtained from analyte samples, enabling identification of the molecular contents of the samples. Mass spectrometers include an ion source for ionizing the samples for subsequent fragmentation, analysis and detection. Different types of inlet devices provide the samples to the ion source for ionization. For example, in a liquid chromatograph mass spectrometer (LCMS), the inlet device is a liquid chromatograph device which provides molecular samples in liquid form, and in a gas chromatograph mass spectrometer (GCMS), the inlet device is a gas chromatograph device which provides molecular samples in gaseous form. Both types of mass spectrometers provide samples at atmospheric pressure. Mass spectrometers require these samples at vacuum pressures via a pressure reduction means.
To accomplish this task, one type of LCMS includes a capillary that is about 18 cm in length and has a central capillary bore of about 0.6 mm in diameter. In an LCMS, for example, the capillary receives ions from a vaporized sample of an effluent stream (e.g., analyte ion vapor) from an ion source, such as an electrospray ionization (ESI) ion source, and transports the received ions through the single capillary bore to an LCMS inlet region. However, the flow rate of ions through the single capillary bore is restricted, in part, by the physical dimensions of the capillary bore.
For example, a capillary bore having small diameter would typically have a lower ion flow rate than a capillary bore having a larger diameter. However, simply increasing the diameter of the capillary bore does not always result in a higher ion flow rate. For example, with respect to a capillary about 18 cm in length, it has been determined that the extraction of ions formed in a sample plume from a liquid chromatograph device is limited by the onset of turbulence and attendant ion losses in the capillary bore when the internal diameter of the capillary bore is increased beyond 0.9 mm, resulting in an actual reduction in the ion flow rate.
Attempts to improve ion flow include providing multiple metal capillaries (e.g., stainless steel), as described, for example, in U.S. Pat. No. 6,803,565 (Smith et al.), issued Oct. 12, 2004. However, metal capillary tubes are electrically conductive. Therefore, the metal capillary tubes are limited with respect to various techniques for attracting ions having different charges, and especially for transporting ions through potential differences in the capillary tubes, such as applying a potential difference across opposite ends of the capillary tubes.
The illustrative embodiments are best understood from the following detailed description when read with the accompanying drawing figures. It is emphasized that the various features are not necessarily drawn to scale. In fact, the dimensions may be arbitrarily increased or decreased for clarity of discussion. Wherever applicable and practical, like reference numerals refer to like elements.
In the following detailed description, for purposes of explanation and not limitation, illustrative embodiments disclosing specific details are set forth in order to provide a thorough understanding of embodiments according to the present teachings. However, it will be apparent to one having had the benefit of the present disclosure that other embodiments according to the present teachings that depart from the specific details disclosed herein remain within the scope of the appended claims. Moreover, descriptions of well-known devices and methods may be omitted so as not to obscure the description of the example embodiments. Such methods and devices are within the scope of the present teachings.
Generally, increased sensitivity of a mass spectrometer improves the limit of detection of analytes of interest. Such increased sensitivity relies, in part, on increasing ion extraction and delivery from the ion source to the mass analyzer of the mass spectrometer. A generally linear relationship exists between ion flow and gas flow through the capillary that transports ions from the ion source. However, as stated above, this relationship of the extraction of ions formed in a sample plume of the ion source is limited, for example, by the onset of turbulence and attendant ion losses in the a capillary bore when the internal diameter of the capillary bore is increased beyond about 0.9 mm (e.g., for an 18 cm capillary). The various embodiments discussed herein enable increased ion flow through the capillary, while keeping internal diameters of the multiple capillary bores small enough to avoid such turbulence and attendant ion losses.
In addition, the capillary body through which the multiple capillary bores are formed is a non-metallic material, such as insulating glass or resistive glass, for example. Accordingly, a difference in electrical potential may be applied to opposite ends of the capillary, e.g., via metalized end portions or bands, on the respective input and output ends of the capillary. The difference in electrical potential provides a change of potential energy of ions when they exit from the multiple capillary bores.
According to various embodiments, a capillary that delivers ions from an ion source to a mass analyzer of a mass spectrometer has multiple bores for transporting higher ion flows without turbulence losses, as well as serving to decluster the ion vapor. The capillary may also be heated to aid the desolvation and declustering action. The multi-bore capillary may be produced and installed using similar processes as a conventional single bore capillary, and therefore can be an efficient and cost-effective upgrade to existing mass spectrometers. For example, a mass spectrometer incorporating embodiments of the multi-bore capillary disclosed herein may use the same high-voltage equipment and software typically is used in conventional mass spectrometers. The pattern of the multiple capillary bores, including the number, layout, sizes and shapes of the bores, can be varied to optimize ion flow based on characteristics of the ion source, such as plume distribution and characteristics of the available vacuum pumping system. The multi-bore capillary may be adjusted in length over a range of a few millimeters to about 20 cm or more, for example, depending on the needs for the attendant high voltage gradient applied to the metalized end portions and consideration of voltage and pressure induced plasma breakdown internally in the bores. Often, a length of about 18 cm is used in a commercial instrument.
Referring to
Accordingly, ions generated by the ion source 110 are drawn into the multiple capillary bores at an input end of the capillary 120, and pass through the multiple capillary bores to the ion focusing optics 130. By having multiple capillary bores, the flow of ions through the capillary 120 may be increased, since the total area available to ion flow increases, without having to increase the size of any one capillary bore above the threshold that causes turbulence losses of ions to the bore walls of the capillary 120 (e.g., about 0.9 mm for an 18 cm capillary), as discussed above.
In various embodiments, the capillary 120 has a generally elongated shape, having an input end adjacent the ion source 110, an output end adjacent the ion focusing optics 130, and a center longitudinal axis. The capillary 120 may also include first and second conductive (e.g., metal) end portions 121 and 122 on the input and output ends, respectively, for receiving electrical voltages. The first and second conductive end portions 121 and 122 may be formed from nickel-chrome (Nichrome), for example, although other materials may be used in various embodiments. The capillary 120 may be formed of glass, a high temperature polymer, or other compatible non-metal material, that does not conduct electricity (insulating material) or conducts very little electricity (resistive material), such that a difference in electrical potential can be applied across the input and output ends of the capillary 120 via the conductive end portions 121 and 122. The conductive end portions 121 and 122 may be formed on the input and output ends of the capillary 120 by physical vapor deposition, for example, or other compatible technique.
For example, in order to enhance flow of positively charged ions, the input end of the capillary 120 may be negatively charged (e.g., about −4000V) and the output end may be positively charged (e.g., about +200V) to create a negative-to-positive voltage differential, drawing in the positively charged ions. In other words, for positively charged ions, negative and positive voltages are respectively applied to the conductive end portions 121 and 122 to create an electrical polarity including a negative pole at the input end and a positive pole, relative to the input end, at the output end. The received positively charged ions thus have a change in potential energy while being transported through the multiple bores of the capillary 120. Polarities are reversed for negative ions.
When the capillary 120 is formed from glass, it may be insulting glass, such as silicate glass, borosilicate glass (e.g., Pyrex®) or the like, or resistive glass, such as lead silicate material supplied by Photonis, Inc, for example. In various embodiments, when resistive glass is used, the polarity of the input and output ends of the capillary 120 may be rapidly switched, enabling rapid voltage reversal, by applying opposite polarity electrical charges to the metal end portions 121 and 122, respectively. For example, the polarity of the input and output ends of the capillary 120 may be switched at a rate of about 5 to 10 times per second, although other rapid switching rates may be incorporated to provide unique benefits for any particular situation or to meet application specific design requirements of various implementations, as would be apparent to one skilled in the art. The rapid voltage reversal across the capillary 120 enables a positive-ion/negative-ion alternating data collection scheme. Thus, the capillary 120 is able to transport ions over a significant reverse voltage gradient by means of the gas (vapor) flow.
The ion focusing optics 130 focus the beam of ions from the capillary 120 on a nozzle or orifice 141 of the skimmer 140 to further improve transfer efficiency of the ions. The orifice 141 of the skimmer 140 passes or selects a center core of ions to the RF multipole 150, after which the ions pass through orifice 143 of partition 142 to the mass analyzer 160 for detection. The RF multipole 150 may include four, six or eight rods (quadrapole, hexapole or octopole), for example, and the mass analyzer may be of the quadrupole or time-of-flight types.
In an embodiment, a vacuum chamber 170 of the mass spectrometer 100 contains the output end of the capillary 120, the ion focusing optics 130, the RF multipole 150 and the mass analyzer 160. More particularly, the output end of the capillary 120 and the ion focusing optics 130 are located in a first vacuum region 171, the RF multipole 150 is located in a second vacuum region 172 separated from the first vacuum region 171 by the skimmer 140, and the mass analyzer 160 is located in a third vacuum region 173, separated from the second vacuum region 172 by the partition 142.
The skimmer 140 includes the orifice 141 formed in a hollow conical frustum mounted on a conductive wall, which is aligned with the focal point of the ion focusing optics 130. The skimmer 140 serves as a barrier between the first vacuum region 171 and the second vacuum region 172, which are respectively pumped through first port 175 and second port 176 by representative high vacuum pump 178, such as a vane pump, turbomolecular pump or diffusion pump. Similarly, the partition 142 serves as a barrier between the second vacuum region 172 and the third vacuum region 173, which is pumped through third port 177 by the high vacuum pump 178. In an embodiment, the pressure in the second vacuum chamber 172 (e.g., about 10e-3 Torr) is lower than the pressure in the first vacuum chamber 171 (e.g., about 1 Torr) to enhance flow of the ions through the orifice 141 of the skimmer 140 to the RF multipole 150. Likewise, the pressure in the third vacuum chamber 173 (e.g., about 10e-5 Torr) is lower than the pressure in the second vacuum chamber 172 to enhance flow of the ions through the orifice 143 of the partition 142 and to provide appropriate high vacuum for mass analyzer 160. Thus, the capillary 120 is able to transport ions using consecutively applied drops in pressure into and through the vacuum chamber 170, as well as using a significant reverse voltage gradient, discussed above.
An example of a mass spectrometer incorporating a skimmer (such as skimmer 140) is described in U.S. Pat. No. 4,542,293 (Fenn et al.), issued Sep. 17, 1985, the subject matter of which is hereby incorporated by reference. However, the multi-bore capillary according to various embodiments may be included in other types and configurations of mass spectrometers, including mass spectrometers having ion funnels (discussed below with reference to
In an embodiment, the mass spectrometer 100 may be an LCMS and the ion source 110 may be an electrospray ionization (ESI) source, for example, which generates a vapor plume of ions from samples input by a liquid chromatograph device (not shown). That is, the ion source 110 produces an electrically charged jet of vapor from a solution containing the sample and outputs charged droplets (vapor plume) containing the sample ions, as the solution evaporates. The vapor plume is directed past the input end of the capillary 120, typically along a path orthogonal to the direction of flow through the multiple capillary bores. Ions of the vapor plume are drawn through the capillary 120, e.g., based on pressure differential and difference in electrical potential between the conductive end portions 121 and 122 of the input and output ends of the capillary 120.
As discussed above, the capillary 120 has multiple bores traversing its length. According to various embodiments, the capillary 120 is formed of glass or other compatible non-metal material, such as a high temperature polymer, and may have a substantially tubular shape with a center longitudinal axis. In various embodiments, the multiple bores traversing the capillary 120 may likewise have substantially tubular shapes, each of which having a corresponding longitudinal axis that is substantially parallel to the longitudinal axis of the capillary 120 and/or the longitudinal axes of the other bores.
For example,
Notably, the pattern of the bores 221-227, which includes the number, sizes, shapes and arrangement of the bores 221-227, may vary to provide unique benefits for any particular situation or to meet application specific design requirements of various implementations, as would be apparent to one skilled in the art. For example, the pattern of the bores 221-227 may be altered to match a particular vapor plume distribution output by the ion source 110, further discussed below with reference to
Numerous variations are possible within the scope of the present teachings. For example, in various embodiments, the bores 221-227 may not be parallel to one another, but rather may diverge from one another or converge toward one another as the bores 221-227 extend through the capillary 220 from the front face 211 to the back face 212. Likewise, the bores 221-227 may have cross-sectional shapes other than circles, such as ovals, squares, rectangles or trapezoidal shapes, for example. Also, the bores 221-227 may have different sizes of cross-sections. For example, in various embodiments, the center bore 221 may have a larger cross-section than each of the peripheral bores 222-227, or the center bore 221 may have a smaller cross-section than each of the peripheral bores 222-227. Similarly, the bores 221-227 may have different shaped cross-sections. For example, in various embodiments, the center bore 221 may have a square cross-section, while each of the peripheral bores 222-227 has circular cross-section.
As stated above with reference to capillary 120, representative capillary 220 may be formed of glass, for example, and the bores 221-227 may be formed through the glass body of the capillary 220 using any technique for fabricating glass, as would be apparent to one skilled in the art, without departing from the scope of the present teachings. For example, the bores may be formed by drawing (pulling) molten glass through a pre-form pattern corresponding to the desired bore pattern. Or, the bores may be formed by drawing a softened perform bundle of larger glass tubes, in proportionate sizes, such that all of the tubes are reduced in diameter and increased in length to reach the final desired dimensions.
As discussed above, when the capillary 120/220 is formed from glass, it may be insulting glass or resistive glass. When resistive glass is used, the polarity of the input and output ends of the capillary 120/220 may be rapidly switched by applying opposite electrical charges to the input and output ends, respectively, via conductive end portions, e.g., conductive end portions 121 and 122 of
As stated above, the cross-sectional configuration of the capillary bores, including the representative cross-sectional configurations shown in
It is understood that relational terms used herein, such as “vertical,” “horizontal,” “top,” “bottom,” “row,” “column,” “above” and “below,” are intended to describe conveniently the various elements in relation to one another, and are not limiting. In other words, the description addresses positional relationships among the various elements, which are applicable regardless of changes in orientation. For example, if the capillary cross-section depicted in
Referring to
The mass spectrometer 400 includes the ion funnel 430 and the conductance 440 in place of the ion focusing optics 130 and the skimmer 140 of the mass spectrometer 100, discussed above. The other components are substantially the same as the corresponding components of the mass spectrometer 100, and therefore the respective descriptions will not be repeated.
The ion funnel 430 represents one or more ion funnels, in tandem, positioned between an output end of the multi-bore capillary 120 and the conductance 440. Generally, the ion funnel 430 is able to accommodate larger ion flows than the skimmer 140. The ion funnel 430 includes a stack of electrically driven plates, as described, for example, in U.S. Pat. No. 6,107,628 (Smith et al.), issued Aug. 22, 2000, the subject matter of which is hereby incorporated by reference. The ion funnel 430 directs or transports the beam of ions from the capillary 120 to the orifice 441 of the conductance 440 to further improve transfer efficiency of the ions. The orifice 441 of the conductance 440 passes a center core of ions to the RF multipole 150, after which the ions pass through orifice 143 of partition 142 to the mass analyzer 160 for detection.
The conductance 440 serves as a barrier between the first vacuum region 171 and the second vacuum region 172, which are respectively pumped through first port 175 and second port 176 by representative high vacuum pump 178, keeping the pressure in the second vacuum chamber 172 lower than the pressure in the first vacuum chamber 171, as discussed above. The conductance 440 is formed from a thin metal plate, and includes the orifice 441, which is typically about 2 mm in diameter, for example.
Accordingly, in the depicted embodiment, the mass spectrometer 400 may be an LCMS and the ion source 110 may be an ESI source, for example, which generates a vapor plume of ions from samples input by a liquid chromatograph device (not shown). The vapor plume is directed past the input end of the multi-bore capillary 120, typically along a path orthogonal to the direction of the flow through the multiple capillary bores. Ions of the vapor plume are drawn through the capillary 120, based on pressure differential. The ion flow to the RF multipole 150 and the mass analyzer 160 is further enhanced by the ion funnel 430, the conductance 440 and the partition 142.
More particularly,
While specific embodiments are disclosed herein, many variations are possible, which remain within the concept and scope of the invention. Such variations would become clear after inspection of the specification, drawings and claims herein. The invention therefore is not to be restricted except within the scope of the appended claims.
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|---|---|---|---|
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| 4808820 | Blau | Feb 1989 | A |
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| 6107628 | Smith et al. | Aug 2000 | A |
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| Number | Date | Country | |
|---|---|---|---|
| 20110127422 A1 | Jun 2011 | US |
