Patent Grant
8058611
1. Field of the Invention
The present invention relates to the field of mass spectrometry, and more particularly to system that includes a novel internal volume (e.g., a continuous flow guide) configuration that provides for an optimal flow path within a mass spectrometer ion source housing.
2. Discussion of the Related Art
In LC-MS mass spectrometry analyte, ions are generated by nebulizing the ion-containing liquid at pressures around atmospheric in a chamber called the ion source housing. Some of this vapor enters the mass spectrometer's vacuum chamber for analysis. The remainder of the vapor, as well as the gases aiding the nebulizing and desolvation processes (sheath and auxiliary) need to exit the source housing through a different opening called a drain. To prevent contamination of surfaces in the source housing which can cause interference with the analysis of subsequent samples, so called carry-over, it is important that the vapor-laden gases are removed swiftly.
A process that often occurs in conventional housings is back streaming/back drafting, wherein a counter flow of gases out of the drain region are caused by the flow of the high velocity nebulizing and desolvation gases directed towards the drain. This counter flow contains undesired contaminants and can cause stagnation of the vapor-laden gases which can lead to condensation of droplets on source surfaces and therefore contamination of such surfaces, which can lead to carryover. In particular, analyte circulating within an ion source housing creates a memory effect wherein the intensity of the analyte as read by a configured mass analyzer can be seen to decay over a period of time after introduction of the analyte/solvent mixture into the housing has ceased. Accordingly, if a second analyte is introduced too soon after the first analyte, the first analyte can still appear in a subsequent reading. This negatively impacts the performance of the mass spectrometer as expressed in the number of samples that can be analyzed per hour. Moreover, the carryover of analytes can sometimes lead to their re-entry into the chamber atmosphere and contribute to a background that reduces the signal-to-noise ratio of desired mass spectral runs.
Background information on a system and method that attempts to address the aforementioned problems through the use of an inner exhaust tube is described and claimed in U.S. Pat. No. 6,759,650, entitled, METHOD OF AND APPARATUS FOR IONIZING AN ANALYTE AND ION SOURCE PROBE FOR USE THEREIN,” issued Jul. 6, 2004, to Covey et al, including the following, “Ions for analysis are formed from a liquid sample comprising an analyte in a solvent liquid by directing the liquid sample through a capillary tube having a free end so as to form a first flow comprising a spray of droplets of the liquid sample, to promote vaporization of the solvent liquid. An orifice member is spaced from the free-end of the capillary tube and has an orifice therein. An electric field is generated between the free-end of the capillary and the orifice member, thereby causing the droplets to be charged, and the first flow is directed in a first direction along the axis of the capillary tube. Two gas sources, or an arc jet of gas, provide second and third flows, of a gas, and include heaters for heating the second and third flows. The second and third flows intersect with the first flow at a selected mixing region, to promote turbulent mixing of the first, second and third flows, the first, second and third directions being different from one another, and each of the second and third directions being selected to provide each of the second and third flows with a velocity component in the first direction and a velocity component towards the axis of the capillary tube, thereby to promote entrainment of the heated gas in the spray, with the heated gas acting to assist the evaporation of the droplets to release ions therefrom. At least some of the ions produced from the droplets are drawn through the orifice for analysis.”
Background information on a corresponding system and method that attempts to address the aforementioned problems also through the use of an inner exhaust tube is described and claimed in PCT Application No. WO 2008/124264 A2, entitled, DEVICE, APPARATUS AND METHODS FOR MASS SPECTROMETRY,” published Oct. 16, 2008, to Tomany et al, including the following, “The invention comprises apparatus for use with atmospheric pressure ionization sources in which an aerosol is formed from a solution of a sample. The aerosol is received in a hollow member and discharged outside the chamber of the ionization source in order to reduce contamination of the ionization source itself by involatile material in the solution and by previously analysed samples. The hollow member is easily removable from the ionization source to facilitate cleaning and replacement. Ionization sources, mass spectrometers, and ion mobility spectrometers comprising the apparatus are also described.”
Background information on a system and method that minimizes recirculation problems is described and claimed in U.S. Pat. No. 7,145,138, B1 entitled, EXHAUST PORT DESIGN FOR API SOURCES,” issued Dec. 5, 2006, to Rohan A. Thakur, including the following, “The present invention provides Atmospheric Pressure Ionization (API) sources that minimize recirculation of droplets, solvent, and background gas. The APIs of the present invention comprise a chamber for ionizing samples for mass spectroscopy and similar analytical equipment. A spray probe on one side of the chamber directs a spray of a solvent and a sample as a cone of droplets that pass proximate to an ion exit orifice. Ions from the spray cone are extracted through the ion exit orifice. An exhaust port is disposed opposite the spray probe and aligned therewith to collect the spray cone. The design of the exhaust port, as described below, minimizes recirculation within the chamber to reduce the memory effect and to preserve the signal to noise ratio.”
Therefore, a need exists for an improved source housing in which a novel internal volume (e.g., a continuous flow guide) has been designed to have an optimal flow path so as to enable a user to easily clean the entire ion source housing/internal volume apparatus and minimize undesired carryover. The present invention is directed to such a need.
Accordingly, the present invention provides for a system that prevents backflow in an ion source. Such a system includes: a housing chamber; a continuous flow guide configured within the housing chamber, wherein the continuous flow guide comprises a converging first volume and a diverging second volume coupled at a minimal cross-sectional area; a spray probe disposed within the continuous flow guide and configured to provide a spray plume along a desired axis within the continuous flow guide; one or more auxiliary gas inlets configured to provide an inert gas so as to combine with the spray plume and fill the converging first volume; an exhaust drain port operably coupled to the diverging second volume of the continuous flow guide; and a means to provide for a desired pressure differential within the converging first and the diverging second volume to induce a unidirectional flow past a sampling orifice of a mass spectrometer inlet, the unidirectional flow being further directed out of the exhaust drain port so as to prevent recirculation and thus minimize carryover, chemical noise, and source turbulence.
In accordance with another aspect of the present invention, a method for preventing backflow in an ion source as part of a mass spectrometer system is introduced. The method includes: providing a continuous flow guide configured within a housing chamber, wherein the continuous flow guide comprises a converging first volume and a diverging second volume coupled at a minimal cross-sectional area; providing a spray probe disposed within the continuous flow guide, the spray probe configured to direct a spray plume that further comprises ionized charged particles of one or more analytes along a desired axis within the continuous flow guide; providing one or more auxiliary gas inlets configured to provide an inert gas so as to combine with the spray plume and fill the converging first volume; and providing a desired pressure differential within the converging first and the diverging second volume to induce a unidirectional flow past a sampling orifice of a mass spectrometer inlet, wherein the unidirectional flow is thereafter directed out of an exhaust drain port so as to prevent recirculation of thus minimize carryover, chemical noise, and source turbulence.
Accordingly, the present invention provides for a system having an improved source housing/ion source design that includes a substantially reduced internal volume (e.g., a continuous flow guide) with respect to conventional designs. Such an arrangement, as disclosed herein, enables an optimal flow path that results in (1) ease of expansion of the introduced non-turbulent gas towards the exit, (2) prevention of back flows from the exit, and (3) reduced areas of stagnation.
In the description of the invention herein, it is understood that a word appearing in the singular encompasses its plural counterpart, and a word appearing in the plural encompasses its singular counterpart, unless implicitly or explicitly understood or stated otherwise. Furthermore, it is understood that for any given component or embodiment described herein, any of the possible candidates or alternatives listed for that component may generally be used individually or in combination with one another, unless implicitly or explicitly understood or stated otherwise. Moreover, it is to be appreciated that the figures, as shown herein, are not necessarily drawn to scale, wherein some of the elements may be drawn merely for clarity of the invention. Also, reference numerals may be repeated among the various figures to show corresponding or analogous elements. Additionally, it will be understood that any list of such candidates or alternatives is merely illustrative, not limiting, unless implicitly or explicitly understood or stated otherwise.
In addition, unless otherwise indicated, numbers expressing quantities of ingredients, constituents, reaction conditions and so forth used in the specification and claims are to be understood as being modified by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the subject matter presented herein. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the subject matter presented herein are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical values, however, inherently contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
Ion-laden aerosol, after being sampled by an inlet to a mass spectrometer's vacuum system needs to be promptly flowed out of the ion source into a drain system. In non optimal source designs, this mixture is recirculated and is sampled (at progressively lower volume concentrations) over a long time span (tens of seconds to minutes). This causes so-called peak tailing, during which the mass spectrometer's response slowly returns back to the baseline level. During this time the peak area of a subsequent sample injection cannot be accurately determined as it sits on an elevated baseline of an earlier sample injection. This effect is generally called carryover. Other processes associated with a non ideal gas flow pattern towards a drain system include when the sample containing vapor-laden gases can “rain out”, i.e. a condensate is formed on an interior surface of the ion source. This condensate can slowly be re-evaporated and cause a general baseline level increase which results in a coupled mass spectrometer instrument to operate in a non ideal fashion.
Moreover, non optimal gas flow circulation patterns in atmospheric pressure ion sources, e.g. caused by sharp surfaces/corners, “dead” volumes, high velocity gas jets, undersized drain channels, gas streams at non optimal relative angles, etc., can also cause so-called back streaming/back drafting of gas from the drain system, which may contain sample containing solvent vapors, plasticizers (such as phtalates), etc. This back drafting flow, when sampled by the mass spectrometer, can cause chemical noise, carry over effects, non optimal use of the limited ion capacity of an ion trap, and other spurious effects.
Accordingly, the present invention is directed to address the above described problems by providing methods and source arrangements (e.g., atmospheric pressure ionization (API) source arrangements) in a system that minimizes among other effects, carryover, chemical noise, and source turbulence via a configured continuous flow guide/ion sampling position, which is part of the ion source housing. As an example design according to the present invention, the continuous flow guide of the ion source housing, which operates as an airfoil, can be configured with a double conic-type shape, wherein the probe (e.g., a nebulizer probe) is mounted in a portion of decreasing diameter followed by a portion of increasing diameter towards the exit of the source, which collectively allows the gas to expand but does not allow for backflow. Alternative airfoil embodiments of the present invention include a design wherein the continuous flow guide of the source housing converges in the middle and then diverges subsequently in a manner that forms a Laval nozzle. As part of the benefits of such an airfoil design of the present invention, sharp surfaces/corners are minimized and thus the trapping of contaminants are also minimized so as to enable the ease of cleaning of the system during periods of routine maintenance.
In particular, to address the above described issues, the present invention provides for a novel continuous flow guide design (i.e., a nozzle conduit to control fluid flow), within an ion source housing such that a probe disposed within the continuous flow guide is along a desired axis wherein, in the spray direction, the cross sectional area that defines the first portion of the continuous flow guide initially decreases in a convergent-like manner and thereafter increases in a divergent-like manner towards the exit opening of the source housing. In an example embodiment, such a desired axis in the spray direction is often configured so as to be coincident with an axis that runs down the centerline of the converging and diverging axis. While such an arrangement is beneficial, it is to also be appreciated that the axis that includes the direction of the spray centerline axis does not necessarily have to be parallel to or coincident with the axis that includes the centerline of the converging and diverging axis.
Moreover, the ion probe sprayer tip, which is often beneficially positioned about where the divergent gas flows emanate, is capable of being moveably arranged before, at, or just after the minimal cross sectional area of the novel continuous flow guide configured within the housing chamber of the present invention. The opening of the mass spectrometer's vacuum chamber, as disclosed herein, is thus configured to intersect with such a novel continuous flow guide design via a sampling orifice configured in a sampling position within the continuous flow guide. Thus, as the unidirectional flow of material is directed past the configured sampling orifice, analytes of interest can be interrogated as provided by the design parameters of the present invention.
Turning now to the drawings,
As shown in
In a beneficial source arrangement, the probe of
As a novel aspect of the present invention, a unidirectional flow path 8 (shown as dashed directional arrows) of the analyte material is urged along a direction to an exit opening 18 as collectively determined by, for example: gas inlet(s) (not shown) positioned to introduce an inert non-turbulent gas flow (e.g., nitrogen, air), a nebulizer gas flow (i.e., a sheath gas), and importantly, the converging/diverging design of the continuous flow guide 3 configured with a desired minimal cross-section region 12 that enables a desired unidirectional flow path 8.
Correspondingly, during the directed flow 8, ionized analytes are drawn out of the continuous flow guide 3 and source housing 2 through a sampling orifice (not shown), as received in an opening 6, that is operatively coupled to a mass spectrometer analyzer (not shown). It is to be noted that the arrangement of the opening 6 so as to receive the sampling orifice of a mass spectrometer inlet, is merely illustrative as to the positioning of a coupled mass spectrometer (not shown), but such a depiction is not meant to be limited to solely above the minimal cross-sectional area of continuous flow guide 3. For example, positions before, at or below the desired minimal cross-section region 12 but in a close proximity to the resultant neck of the two intersecting portions are equally applicable to the configurations of the present invention.
In the generalized example embodiment of
Moreover, it is also to be appreciated, as discussed briefly above, that the central axes for both of the volumes that make up and run along the continuous flow guide 3 do not necessarily require them to be parallel or coincident. In addition, the directional axis flow out of probe 1 can be on axis with one or both of the axes that make up continuous flow guide 3 but, as another arrangement, can be angled (e.g., of less than 90 degrees) in a slight manner so as to not be coincident with either axis of continuous flow guide 3.
In an example method of operation, solvent/analyte material along with a nebulizing sheath gas is introduced as part of the mass spectrometry method that includes appropriate ionization mechanisms, such as, for example, electrospray ionization. In particular, solvent/analyte material is introduced as a charged spray plume via a configured tip 7 of probe 1 mounted in desired position (e.g., moveably positioned) before, substantially at, or after the minimal cross-sectional region 12 within the channel 4 that is formed within continuous flow guide 3. Simultaneously, an inert auxiliary non-turbulent gas (e.g., nitrogen, air) having a desired flow is introduced by one or more inlet channels (not shown) so as to direct a desired flow of the spray cone (i.e., analyte/solvent material/residual nebulizer gas) along a path, as shown by the dashed directional arrows 8.
As part of the novel design of the present invention, as the liquid solvent/analyte emerges from the opening of the probe tip, the auxiliary flow coming from an inlet(s) (not shown) meets the resultant charged spray cone in a non-turbulent fashion within the channel 4 in a manner that provides a pressure differential between the converging first portion 5 and the second diverging portion 5′ of the continuous flow guide 3 design, as shown in
Thus, turning back to
As similarly discussed above with respect to the embodiment of
It is to be understood that any means as understood by those skilled in the art to provide pressure differentials between the converging and diverging portions of the continuous flow guide 33 can be utilized to induce such a continuous desired flow. For example, the auxiliary gas introduced into chamber 23/upper portion 25 of continuous flow guide 33 can be filled (e.g. at greater than an atmosphere) to provide a pressure differential with respect to lower portion 25′ of continuous flow guide 33 so as to initiate the continuous flow mechanism out to a coupled exhaust drain port 38. As another arrangement, a pump (not shown), e.g., a roughing pump, a roots blower pump, a flow meter, a pressure controller and/or a Venturi pump, alone or in operative conjunction with the desired introduced gas fill pressure (at about atmosphere or greater) can be designed to operate at a pumping speed when coupled to the exhaust drain port 38 to also assist in desired pressure differentials within the continuous flow guide 33. In any chosen arrangement, the means initiates and provide for the resultant overall unidirectional flow within the continuous flow guide 33. When using a pumping means, an operator can optimize the flow rate out to the exhaust drain port 38 so as to throttle the pumping rate speed of configured pump(s) and induce desired pressure differentials, auxiliary gas heating, etc., so as to uniformly direct the Laval-nozzle flow 28 at the desired operating pressure.
As similarly stated above with respect to the embodiment of
In contradistinction to the embodiment of
As before, in a method of operation, analyte/solvent material often with an accompanying nebulizing sheath gas, is introduced as part of the mass spectrometry method of electrospray ionization. In particular, analyte/solvent material is introduced via a configured tip 27 of probe 21 mounted (e.g., moveably positioned) in a desired position before, substantially at, or after the minimal cross-sectional region 32 within the channel 34 that is formed within continuous flow guide 33. Simultaneously, an inert auxiliary gas (e.g., nitrogen, air) having a predetermined non-turbulent flow rate is introduced by one or more inlet channels 24 so as to aid in directing the overall collective flow of material along a path 28 (denoted as flow streams), as shown by the directional arrows within channel 34.
Thus, as the liquid solvent/analyte spray cone emerges from the opening of tip 27 of probe 21, the inert auxiliary gas flow coming from inlets 24, as shown by example as being perpendicular to probe tip 27 in
As part of the unique design of the present invention, as shown in
Such Laval configurations coupled with desired means to induce pressure differentials (e.g., known in the art pumping means, desired fill gas pressures within first portion 25) result in a gas flow velocity that increases at sub-sonic flow rates provided by the pressure differential continuously from the area of the initial introduced analyte/solvent spray cone/auxiliary gas until it reaches the narrowest cross-section of region 32 that forms the Laval nozzle-like throat. Thereafter, the resultant pressure drop at the minimal cross-sectional area 32 causes the inert gas(s) and any residual analyte/solvent to be directed through the minimal cross-sectional area 32 and out to the expanding divergent second portion 25′ so as to accelerate up to supersonic velocities that result in a unidirectional flow throughout the length of the divergent second portion 25′. Accordingly, the overall configuration and operating parameters beneficially produces an ion source system configuration 200 that substantially eliminates any backflow of material via recirculation so as to minimize carryover, chemical noise, and source turbulence.
As generally shown in
As part of the operation of the apparatus shown in
In an example method of operation, solvent/analyte material along with a nebulizing sheath gas is introduced as part of a mass spectrometry method known and understood by those skilled in the art. In the present configuration, solvent/analyte material is introduced as a charged spray plume via probe 41 having a configured tip 47 mounted (e.g., moveably positioned) in desired position before, substantially at, or after the minimal cross-sectional region 46 within the channel that is formed within continuous flow guide 43. Before and/or simultaneously with the introduced material from probe tip 47, and in structural contrast to the example design of
Thereafter, similar to the workings of the example embodiment of
It is to be understood that features described with regard to the various embodiments herein may be mixed and matched in any combination without departing from the spirit and scope of the invention. Although different selected embodiments have been illustrated and described in detail, it is to be appreciated that they are exemplary, and that a variety of substitutions and alterations are possible without departing from the spirit and scope of the present invention.
| Number | Name | Date | Kind |
|---|---|---|---|
| 5412208 | Covey et al. | May 1995 | A |
| 6759650 | Covey et al. | Jul 2004 | B2 |
| 7145138 | Thakur | Dec 2006 | B1 |
| 7199364 | Thakur | Apr 2007 | B2 |
| 7339521 | Scheidemann et al. | Mar 2008 | B2 |
| 7465940 | Franzen | Dec 2008 | B2 |
| 20090194687 | Jolliffe et al. | Aug 2009 | A1 |
| 20090212210 | Finlay et al. | Aug 2009 | A1 |
| 20100163719 | Loucks et al. | Jul 2010 | A1 |
| Number | Date | Country |
|---|---|---|
| WO 2008124264 | Oct 2008 | WO |
| WO 2008129039 | Oct 2008 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 20110068263 A1 | Mar 2011 | US |
