Patent Description:
In the process of analyzing a sample by mass spectrometry (MS), the MS system first ionizes the sample to create analyte ions. The MS system then transfers the ions into a mass analyzer, and the mass analyzer resolves the ions on the basis of the ions' differing mass-to-charge (m/z) ratios. An ion detector measures the abundance of the ions at each mlz ratio detected. The MS system then processes signals outputted by the ion detector to generate mass (m/z) spectra that provide quantitative and qualitative information regarding the components of the sample (e.g., compounds, isomers, elements, etc.).

The mass analyzer operates in a controlled high-vacuum environment, for example at <NUM>-<NUM> to <NUM>-<NUM> Torr. In some MS systems, the ion source (where ionization of the sample is performed) also operates at a vacuum pressure. In other MS systems, such as when coupled to a liquid chromatography (LC) instrument (an LC-MS system), the ion source operates at or around atmospheric pressure. An MS system utilizing an atmospheric pressure ionization (API) source requires an interface between the API source and the evacuated regions of the MS system in which the mass analyzer and other devices are located. The interface needs to effectively isolate the atmospheric-pressure region where the ions are created from the evacuated regions where the ions are processed, while at the same time provide a way to efficiently transport the ions into the evacuated regions after they are created.

A capillary tube is often utilized to transfer the ions from the API source into the first vacuum region of the MS system. The capillary tube has a small inside bore, the inside diameter of which may range from a fraction of a millimeter (mm) to a few millimeters. The capillary tube extends through the boundary between the API source and the first vacuum region, whereby the tube's entrance is exposed to the ionization region of the API source and the tube's exit is exposed to the first vacuum region. Ions and gas in the API source are drawn into the tube's entrance, transported through the tube's bore, and emitted from the tube's exit into the first vacuum region. Ion optics guide the ions further into the MS system and ultimately to the mass analyzer. The capillary tube may be metal. Alternatively, the capillary tube may be glass with an electrically resistive property (coating or bulk resistance) to allow the tube's entrance to be placed at a relatively high voltage level while the tube's exit is maintained at a relatively low voltage level. In this case, the ions are effectively transported through the tube's bore because the gas drag forces on the ions in the capillary tube greatly exceed the ion mobility (electric) forces on the ions in the presence of the internal electric field in the capillary tube.

However, the capillary tube has a tendency to become contaminated after extended use, such as may be due to ion diffusion and space-charge repulsion, and thus periodically requires cleaning or even replacement. It has also been found that the majority of the contamination is within the first <NUM>-<NUM> of the length of the capillary tube, i.e., at its entrance end. Cleaning or replacement requires access to the capillary tube, which often requires breaking the vacuum maintained by the MS system. Hence, cleaning or replacing a contaminated capillary tube can require significant down-time in the operation of the MS system.

<CIT> discloses a method for analyzing a sample comprising the steps of generating ions from the sample within an ionization chamber at substantially atmospheric pressure, entraining the ions in a background gas, transferring the background gas and entrained ions to an evacuated chamber of a mass spectrometer system using an ion transfer tube and analyzing the ions using a mass analyzer of the mass spectrometer system. The ion transfer tube has an inlet end and an outlet end, wherein a portion of the ion transfer tube adjacent to the outlet end comprises an inner diameter that is greater than an inner diameter of an adjoining portion of the ion transfer tube.

<CIT> discloses an ion source including an ion transfer tube having two segments for transporting a sample fluid containing ions between a first chamber and a second chamber maintained at a reduced pressure relative to the first chamber. A first segment may include a plurality of channels and heat conductive walls forming the plurality of channels. The plurality of channels and walls forming the channels promote efficient convective heat transfer to the sample fluid, thereby enabling operation at relatively high sample fluid flow rates, resulting in an increase in the number of ions that may be delivered to a mass analyzer. A second segment forms a single common channel that receives a plurality of sample streams and enables them to combine into a single ion stream that may be introduced as a single gas stream expansion into the second chamber.

<CIT> relates to methods and instruments for ionizing analyte molecules. Liquids are nebulized at atmospheric pressure by electrospraying. Highly charged microdroplets enter the vacuum of a mass spectrometer through an inlet capillary having a portion of reduced cross-section.

<CIT> discloses a concentric atmospheric-pressure chemical ionization, APCI, surface ionization probe, supersonic sampling tube and method for use thereof. The concentric APCI surface ionization probe includes an outer tube, an inner capillary, and a voltage source coupled to the outer tube and the inner capillary. The inner capillary is housed within and concentric with the outer tube such that ionized gas (e.g., air) travels out of the outer tube, reacts with a sample, and the resulting analyte ions are sucked into the inner capillary. A supersonic sampling tube can include a tube coupled to a mass spectrometer and/or concentric APCI surface ionization probe, where the tube includes at least one de Laval nozzle.

Therefore, there is a need for capillary-based ion transfer devices that more effectively address the problem of contamination. There is also a need for capillary-based ion transfer devices that provide improved evaporation of droplets and desolvation of the ions from the droplets. There is also a need for capillary-based ion transfer devices that allow careful control over the supersonic expansion occurring at the vacuum interface to reduce the associated cooling of the gas jet and potential for ion clustering. Reducing the exit velocity into the vacuum may also assist in creating a more stable gas flow in the vacuum chamber and more stable signal levels. There is also a need for capillary-based ion transfer devices having capillary entrance geometries at the higher-pressure side of the interface that are modified so as to change the gas flow near the capillary entrance and/or change the electric field shape at that location in a manner that improves ion capture and transmission and reduce contamination.

To address the foregoing problems, in whole or in part, and/or other problems that may have been observed by persons skilled in the art, the present disclosure provides methods, processes, systems, apparatus, instruments, and/or devices, as described by way of example in implementations set forth below.

According to one embodiment, the invention provides a method for transferring ions according to claim <NUM>. Further developments of the invention are defined in the dependent claims.

Other features and advantages of the invention will be or will become apparent to one with skill in the art upon examination of the following figures and detailed description.

The invention can be better understood by referring to the following figures. In the figures, like reference numerals designate corresponding parts throughout the different views.

As used herein, the term "atmospheric pressure" is not limited to exactly <NUM> Torr, or one atmosphere (<NUM> atm), but instead generally encompasses a range around <NUM> Torr (e.g., <NUM> to <NUM> Torr).

As used herein, the term "vacuum" or "vacuum pressure" generally refers to a pressure that is at least an order of magnitude less than atmospheric pressure. For example, vacuum pressure may encompass sub-atmospheric pressures down to <NUM>-<NUM> Torr or lower.

As appreciated by persons skilled in the art, different types of vacuum pumps may be utilized to bring an enclosed space, or vacuum chamber, down to different ranges of pressure. For example, a "roughing" pump (or "backing" pump) may be utilized to pump a vacuum chamber down to a "rough" vacuum level of, for example, down to about <NUM>-<NUM> Torr. Roughing pumps typically have a predominantly mechanical design, examples of which include, but are not limited to, scroll pumps, rotary vane pumps, diaphragm pumps, Roots blower (positive displacement lobe) pumps, etc. High-vacuum pumps are utilized to achieve higher levels of vacuum (lower pressures), for example down to <NUM>-<NUM> Torr or lower. Examples of high-vacuum pumps include, but are not limited to, turbomolecular pumps and sputter-ion pumps. A roughing pump may be utilized in conjunction with a high-vacuum pump as a first stage of vacuum pump-down and/or to isolate a high-vacuum pump from rough-vacuum or higher-pressure environments.

<FIG> is a schematic view of an example of a mass spectrometry (MS) system <NUM> in which an ion transfer device <NUM> as presently disclosed herein may be provided. An MS system is but one non-exclusive example of an operating environment for the ion transfer device <NUM>. More generally, the ion transfer device <NUM> may be utilized in any system in which ions are transferred from a region held at a relatively high pressure (e.g., atmospheric pressure) to another region held at a relatively lower pressure (e.g., vacuum pressure). Different types of MS systems, their operating principles, and their components are generally known to persons skilled in the art. Therefore, the example of the MS system <NUM> illustrated in <FIG> is described herein only briefly to provide a context for the presently disclosed ion transfer device <NUM>.

In the illustrated example, the MS system <NUM> includes an atmospheric-pressure ionization (API) source <NUM> interfaced with a vacuum housing <NUM> in which a mass analyzer <NUM> and other ion processing components are located. Accordingly, the API source <NUM> is configured to ionize a sample <NUM> generally at atmospheric pressure, whereas the mass analyzer <NUM> is required to operate at high vacuum (very low pressure) in the usual manner. The ion transfer device <NUM> provides a path for ions <NUM> and neutral gas molecules (or atoms) to pass from the API source <NUM> into the vacuum housing <NUM>, as described further below.

The API source <NUM> includes a first chamber <NUM>, which is an ionization chamber in which ions <NUM> are produced from a sample <NUM>. The API source <NUM> also includes an API ionization device <NUM>, which may be any device capable of ionizing a sample <NUM> at atmospheric pressure. Examples of API ionization devices include, but are not limited to, spray-type devices (electrospray ionization (ESI) devices, thermospray ionization devices, etc.), atmospheric-pressure chemical ionization (APCI) devices, atmospheric-pressure photoionization (APPI) devices, atmospheric-pressure laser desorption ionization (AP-LDI) devices, atmospheric-pressure matrix-assisted laser desorption ionization (AP-MALDI) devices, etc. Thus, the ions <NUM> schematically depicted in <FIG> may be representative of an effluent from the API ionization device <NUM> that includes, in addition to the ions <NUM>, droplets containing analytes and non-analytical matrix materials that can be evaporated to produce more ions, and gas molecules or atoms utilized to nebulize the sample <NUM> and/or carry the sample <NUM> to the API ionization device <NUM>. Depending on the type of API ionization device <NUM> utilized, the sample <NUM> may be initially provided in the form of a fluid or a solid. For example, the sample <NUM> may be flowed to or into the API ionization device <NUM> from a sample source. The sample source may be the output of a liquid chromatography (LC) instrument or other type of analytical separation instrument. As another example, the sample <NUM> may be provided on a solid target surface and desorbed from the surface by the API ionization device <NUM>. The API source <NUM> may further include an exhaust port <NUM> through which gases and vapors may be removed from the first chamber <NUM> during the ionization process.

The vacuum housing <NUM> includes one or more vacuum chambers as necessary for pumping the MS system <NUM> down to the very low pressure (high vacuum) required for operating the mass analyzer <NUM>, and for containing intermediate devices utilized for performing operations on the ions <NUM> prior to final mass analysis by the mass analyzer <NUM>. In the illustrated example, the vacuum housing <NUM> includes a second chamber <NUM>, a third chamber <NUM>, and a fourth chamber <NUM>, with the understanding that less or more vacuum chambers may be provided. The chambers <NUM>, <NUM>, and <NUM> include respective ports <NUM>, <NUM>, and <NUM> communicating with a vacuum system (schematically represented by downward arrows), which is configured for maintaining a specific level of vacuum in each of the chambers <NUM>, <NUM>, and <NUM>. Typically, the chambers <NUM>, <NUM>, and <NUM> are held (maintained by the vacuum system) at successively lower pressures, with the final (third) chamber <NUM> enclosing the mass analyzer <NUM> being held at the lowest pressure (highest vacuum) obtained by the MS system <NUM>.

In the illustrated example an ion guide <NUM> is disposed in the third chamber <NUM>, and the mass analyzer <NUM> and an ion detector <NUM> are disposed in the fourth chamber <NUM>. The ion guide <NUM> may be of any type such as, for example, a linear multipole ion guide (as schematically illustrated), an ion funnel, a collision cell, a mass filter or other type of mass analyzer, etc. The mass analyzer <NUM> may be of any type such as, for example, a quadrupole mass analyzer, a time-of-flight (TOF) analyzer, an ion cyclotron resonance (ICR) cell, a magnetic sector, an electric sector, an electrostatic ion trap, etc. The ion detector <NUM> may be of any type such as, for example, an electron multiplier, a photomultiplier, a Faraday cup, etc. Many other types of ion optics may be included in the chambers <NUM>, <NUM>, <NUM>, and <NUM>, as needed for the intended use and operation of the MS system <NUM>, as appreciated by persons skilled in the art.

Adjacent chambers <NUM>, <NUM>, <NUM>, and <NUM> are separated by respective walls <NUM>, <NUM>, and <NUM>. The ion transfer device <NUM> extends into or through an opening <NUM> formed through the thickness of the wall <NUM>, such that an inlet <NUM> of the ion transfer device <NUM> communicates with the first chamber <NUM> and an outlet <NUM> of the ion transfer device <NUM> communicates with the second chamber <NUM>. The ion transfer device <NUM> is mounted to the wall <NUM> in a fluid-tight manner, whereby the interior passage of the ion transfer device <NUM> provides the sole path for ions to travel from the API source <NUM> into the vacuum housing <NUM>. The ion transfer device <NUM> is configured to serve as a gas conductance barrier that limits the flow of gas through the ion transfer device <NUM> and effectively maintains a pressure differential between the atmospheric-pressure first chamber <NUM> and the sub-atmospheric-pressure second chamber <NUM>. Other walls (e.g., walls <NUM> and <NUM>) separating adjacent chambers include openings (e.g., openings <NUM> and <NUM>) that may function as gas conductance barriers, skimmer cones, ion optics, etc..

Ions and gas flow through the ion transfer device <NUM> under the influence of the pressure differential between the first chamber <NUM> and the second chamber <NUM>. The ion transfer device <NUM> may include electrodes (e.g., electrically conductive or electrically resistive elements) at its inlet end and outlet end. A voltage imparted between these electrodes generates an electric field that urges the ions through the ion transfer device <NUM>. The ion transfer device <NUM> may include a heating device <NUM> to promote evaporation of droplets and desolvation of ions while the ions and droplets travel through the ion transfer device <NUM>.

More detailed examples of the ion transfer device <NUM> are described below with reference to <FIG>. These examples may improve ion transmission from a relatively high-pressure environment (e.g. an atmospheric-pressure environment, such as the API source <NUM> described above and illustrated in <FIG>) into a lower-pressure (reduced-pressure) environment (e.g. a vacuum environment, such as the vacuum housing <NUM> described above and illustrated in <FIG>), with reduced contamination. In some implementations, such as those illustrated in <FIG>, an inlet end portion of the ion transfer device <NUM> is removable. The removable inlet end portion, also referred to an ion inlet section or structure, has a length along which most or all of the contamination is expected to occur. Therefore, removing contamination from ion transfer device <NUM> requires only removing the inlet end portion for cleaning or replacement, while the remaining portion of the ion transfer device <NUM> can remain installed. Moreover, the ion transfer device <NUM> may be configured such that removal of the inlet end portion does not require shutting down or changing the operating parameters of the vacuum system of the instrument in which the ion transfer device <NUM> is installed (e.g., an MS system <NUM> as generally described above and illustrated in <FIG>). Thus, such ion transfer devices may minimize the reduction in instrument sample throughput caused by the process of removing contamination in the ion transfer device <NUM>.

In the following sections the term "embodiment" should not be construed as an embodiment of the invention. When referring to the ion transfer devices of <FIG> and <FIG> the term "embodiment" should be construed as a background example not according to the invention. When referring to the ion transfer devices of <FIG> (being implemented such that the inner diameter of the capillary bore increases along its length), <NUM> - <NUM> the term "embodiment" should be construed as an example that is not part of the invention per se, but which may be used in the invention.

<FIG> is a cross-sectional schematic perspective view of an example of an ion transfer device <NUM> according to an embodiment. Generally, the ion transfer device <NUM> has a length along a longitudinal axis L, and includes an inlet end <NUM> and an axially opposite outlet end <NUM>. When installed in an associated instrument (e.g., the MS system <NUM> illustrated in <FIG>), the inlet end <NUM> is disposed in or faces a first chamber (e.g., the first chamber <NUM> illustrated in <FIG>) and the outlet end <NUM> is disposed in or faces a second chamber (e.g., the second chamber <NUM> illustrated in <FIG>), which is separated from the first chamber by a wall <NUM>. In a typical use of the ion transfer device <NUM>, the second chamber is maintained at a pressure lower than the first chamber. For example, the first chamber may be at (or around) atmospheric pressure while the second chamber is at vacuum pressure, as described above.

The ion transfer device <NUM> includes an ion inlet section (or inlet end portion) <NUM> at the inlet end <NUM> and a main capillary section <NUM> extending along the longitudinal axis L from the ion inlet section <NUM> to the outlet end <NUM>. One or both of the ion inlet section <NUM> and the main capillary section <NUM> may extend into an opening <NUM> extending through the thickness of the wall <NUM>, or one of the ion inlet section <NUM> and the main capillary section <NUM> (as in the illustrated embodiment) may extend completely through the opening <NUM>. The ion inlet section <NUM> includes a lumen <NUM> (or first lumen, or first bore) formed through the solid portion (body) of the ion inlet section <NUM>. The lumen <NUM> extends along the longitudinal axis L from a lumen inlet <NUM> to a lumen outlet <NUM>. The main capillary section <NUM> includes a capillary bore <NUM> (or second bore, or second lumen) formed through the solid portion (body) of the main capillary section <NUM>. The capillary bore <NUM> extends along the longitudinal axis L from a bore inlet <NUM> to a bore outlet <NUM>. The ion inlet section <NUM> and the main capillary section <NUM> are positioned adjacent to each other such that the lumen outlet <NUM> communicates with the bore inlet <NUM>, and the lumen outlet <NUM> and the bore inlet <NUM> face each other in alignment along the longitudinal axis L.

In some embodiments, the ion inlet section <NUM> is removable from the main capillary section <NUM>, as described further below. In other embodiments, the ion inlet section <NUM> is integrally formed with the main capillary section <NUM> as a single-piece construction, or is otherwise integrally adjoined to the main capillary section <NUM> in a non-removable manner such as by adhesion, bonding, fusing, welding, etc. In either case, the ion inlet section <NUM> and the main capillary section <NUM> define an ion transfer path running from the lumen inlet <NUM> to the bore outlet <NUM>. The lumen inlet <NUM> defines the inlet or entrance of the ion transfer device <NUM>, the bore outlet <NUM> defines the outlet or exit of the ion transfer device <NUM>, and the lumen <NUM> and capillary bore <NUM> cooperatively define the overall internal passage of the ion transfer device <NUM>. When installed in an associated instrument, ions and gas in the first chamber are drawn into the lumen inlet <NUM>, travel through the lumen <NUM> and the capillary bore <NUM>, and are emitted from the bore outlet <NUM> into the second chamber. In some embodiments, the overall geometry of the ion transfer device <NUM> may be considered as being that of a capillary tube, with the ion inlet section <NUM> being either removable from the main capillary section <NUM> or integral to the main capillary section <NUM>, as described further below.

As illustrated, the inside diameter of the lumen <NUM> is less than the inside diameter of the capillary bore <NUM>. By this configuration, the inside diameter of the internal passage increases at (at least) one point along the longitudinal axis L. In the present embodiment, the inside diameter increases at the interface of the ion inlet section <NUM> (lumen outlet <NUM>) and the main capillary section <NUM> (bore inlet <NUM>). This configuration allows the gas to accelerate as high as the speed of sound at the location where the inside diameter increases. The gas flow speed at the lumen inlet <NUM> is also increased significantly. This increased gas flow speed serves to entrain ions from a larger region in front of the ion transfer device <NUM> in the first chamber. Moreover, due to the increased gas flow speed, the charge density of the ions inside the ion transfer device <NUM> is reduced and the residence time of the ions inside the ion transfer device <NUM> is also reduced. As a result of this configuration and the flow behavior enabled thereby, contamination by ions and neutral particles in the ion transfer device <NUM> (in both the ion inlet section <NUM> and the main capillary section <NUM>) may be reduced.

The inside diameter of the lumen <NUM> may be constant along its length, or it may vary gradually or in one or more steps along its length. According to the invention the inside diameter of the capillary bore <NUM> may vary gradually or in one or more steps along its length. The average value of the inside diameter of the lumen <NUM> along its length is less than the average value of the inside diameter of the capillary bore <NUM> along its length.

In typical implementations of the ion transfer device <NUM> (e.g., typical fluid flow rates and pressures), the inside diameters of the lumen <NUM> and the capillary bore <NUM> are in a range from a fraction of a millimeter to a few millimeters. As one non-limiting example, the inside diameter of the lumen <NUM> may be in a range from <NUM> to <NUM>, and the inside diameter of the capillary bore <NUM> may be in a range from <NUM> to <NUM>. Generally, the overall axial length of the ion transfer device <NUM> from the lumen inlet <NUM> to the bore outlet <NUM> is set to be sufficient for providing an ion transfer path through the wall <NUM>, and to allow a sufficient amount of ion desolvation and droplet evaporation to occur. Also, the axial length may be adjusted so that, in conjunction with the inside diameter(s), the conductance of the ion transfer device <NUM> matches the available pumping speed provided for the first vacuum chamber. Typically, the length of the ion transfer device <NUM> is on the order of tens to a few hundreds of millimeters, for example <NUM> or <NUM>.

The inlet end or face of the ion inlet section <NUM> that surrounds the lumen inlet <NUM> may have a blunt geometry, as illustrated. Alternatively, the inlet end or face of the ion inlet section <NUM> may have a sharper or more pointed shape in which an outside diameter of the ion inlet section <NUM> increases in the direction toward the main capillary section <NUM>. A more pointed geometry may assist in directing the gas flow near the lumen inlet <NUM> in a way that will increase ion transmission and reduce contamination. Moreover, a more pointed geometry may create a higher (inward) radial electric field that helps to direct ions toward the entrance of the ion transfer device <NUM> (lumen inlet <NUM>). In addition, if the interface provides a counter-flow of drying gas in this part of the system, the pointed shape may also increase the (inward) radial component of gas velocity in the same location. The combination of the two effects may increase ion transmission from the region in front of the lumen inlet <NUM> into the lumen <NUM>. By directing more ions into the lumen <NUM>, fewer ions (and droplets) are deposited on the front surface of the ion inlet section <NUM>, reducing the contamination effects there.

In some embodiments and as illustrated, the ion inlet section <NUM> and the main capillary section <NUM> are physically separate components. This enables the ion inlet section <NUM> to be removable from the operating site without having to also remove the main capillary section <NUM>. Thus the ion inlet section <NUM>, as a separate component, may be easily cleaned or replaced without having to also clean or replace the main capillary section <NUM>. As noted above, in many applications most of the contamination occurs within the inlet end region (e.g., the first <NUM>-<NUM> of axial length) of an ion transfer device. Accordingly, removing only the ion inlet section <NUM> may be all that is needed to remove most or all of the contamination from the internal passage of the ion transfer device <NUM>. Hence, the axial length of the ion inlet section <NUM> may be less than the axial length of the main capillary section <NUM>, and may be sufficient to span the length over which most or all of the contamination is expected to occur. As a non-limiting example, the axial length of the ion inlet section <NUM> may be in a range from <NUM>-<NUM>. With the length of the ion inlet section <NUM> being a small portion of the full length of the internal passage of the ion inlet section <NUM>, the main capillary section <NUM> can be designed to have a gas conductance that remains sufficiently low to maintain a pressure differential between the first chamber and the reduced-pressure second chamber. Consequently, in the absence of the ion inlet section <NUM>, any resulting increase in the gas conductance of the ion transfer device <NUM> is limited enough that the ion inlet section <NUM> may be removed without needing to shut down the vacuum system, which is advantageous as noted above.

In some embodiments and as illustrated, the ion inlet section <NUM> when configured as a separate component may be configured so as to be removably engaged with the main capillary section <NUM>. In the illustrated embodiment, the ion inlet section <NUM> is configured as an end cap. In such configuration, the lumen <NUM> transitions to a larger-diameter recess or socket <NUM>. The recess <NUM> is large enough to receive the inlet end of the main capillary section <NUM>. In the embodiment specifically illustrated in <FIG>, the ion inlet section <NUM> is adjacent to the higher-pressure side of the wall <NUM>, and the main capillary section <NUM> extends through the opening <NUM> of the wall <NUM> and into the recess <NUM> of the ion inlet section <NUM>. The end-cap geometry of the ion inlet section <NUM> may be characterized as including a lumen section through which the lumen <NUM> extends, and an adjoining sleeve section through which the recess <NUM> extends and into which the main capillary section <NUM> is inserted.

The ion inlet section <NUM> and the main capillary section <NUM> may be fixed in position relative to each other and to the wall <NUM> by any suitable means. The ion inlet section <NUM> and the main capillary section <NUM> may be attached to each other, and/or one or both of the ion inlet section <NUM> and the main capillary section <NUM> may be attached to the wall <NUM>, by utilizing appropriate mounting components (not shown). The ion transfer device <NUM> may be positioned in the opening <NUM> of the wall <NUM>, and the ion inlet section <NUM> and the main capillary section <NUM> may be positioned adjacent to each other such that the lumen outlet <NUM> communicates with the bore inlet <NUM>, in a fluid-sealed or substantially fluid-sealed manner by providing one or more sealing interfaces. In the illustrated embodiment, for example, sealing elements (e.g., O-rings) <NUM> may be positioned in an annular gap in the opening <NUM> between the main capillary section <NUM> and the wall <NUM>, and in the axial gap between the ion inlet section <NUM> and the wall <NUM>.

Generally, the ion inlet section <NUM> and the main capillary section <NUM> may be composed of electrically conductive materials (e.g., metals, metal alloys, conductive plastics, etc.) or electrically insulating materials (e.g., glass, fused silica, other ceramics, metal oxides, metal nitrides, polymers, etc.). As noted above, it may be desirable to generate an axial electrical field across the length of the ion transfer device <NUM> by coupling voltage sources to the ion inlet section <NUM> at or near the inlet end and the outlet end. For this purpose, the ion inlet section <NUM> and the main capillary section <NUM> if composed of insulating materials may include outer conductive coatings or electrically resistive coatings serving as electrodes (conductive or resistive elements) on the outer surfaces of the ion inlet section <NUM> and the main capillary section <NUM>. A resistive coating may be formed, for example, from a resistive ink such as a carbon ink, cermet ink, metallic ink, conductive plastic ink, or polymer ink, as further described in <CIT>. Alternatively, the insulating material utilized may have a bulk resistance that enables generation of an electric field in response to application of voltages.

In some embodiments, one of the ion inlet section <NUM> and the main capillary section <NUM> may be composed of an electrically conductive material while the other is composed of an electrically insulating material. For example, the ion inlet section <NUM> may be composed of a metallic material (metal or metal alloy) and the main capillary section <NUM> may be composed of a glass. Utilizing a metallic material may facilitate the fabrication of the features of the ion inlet section <NUM>. When composed of a glass or other insulating material, the main capillary section <NUM> may include a first conductive or resistive element proximate to the bore inlet <NUM> and a second resistive element proximate to the bore outlet <NUM>, such that the first resistive element and the second resistive element are independently addressable by respective voltage sources. The first resistive element may be electrically interconnected to the ion inlet section <NUM>.

The main capillary section <NUM> may be a monolithic structure as illustrated. Alternatively, the main capillary section <NUM> may be axially divided along its length so as to include a plurality of tube segments serially positioned adjacent to each other in a fluid-sealed or substantially fluid-sealed manner, such as by providing a surrounding sleeve and sealing elements as necessary. Providing the main capillary section <NUM> in segmented form may be based on manufacturing considerations, such as the tube material, aspect ratio (length to diameter), bore geometry, etc. Tube segments are independently addressable by respective voltage sources, which enables the application of a highly controlled axial voltage gradient if desired.

In the embodiment illustrated in <FIG>, the inside diameters of the lumen <NUM> and the capillary bore <NUM> are constant along their axial lengths, i.e., the lumen <NUM> and the capillary bore <NUM> are shaped as straight cylinders. In this case, the inside diameter of the overall internal passage of the ion transfer device <NUM> is increased (e.g., stepped up) just one once, namely at the transition from the lumen <NUM> to the capillary bore <NUM>. As noted above, the gas may accelerate to the speed of sound at this transition. In the embodiment specifically illustrated in <FIG>, the inside diameter of the lumen <NUM> is only slightly smaller than that of the capillary bore <NUM>. With this configuration, there may be only one supersonic expansion at the bore outlet <NUM>. The capillary bore <NUM> may be sized to limit gas conductance and flow to a safe operating range that allows the ion inlet section <NUM> to be removed without needing to shut down the vacuum system.

<FIG> is a cross-sectional schematic perspective view of an example of an ion transfer device <NUM> according to another embodiment. Like the ion transfer device <NUM> of <FIG>, the ion transfer device <NUM> includes an ion inlet section <NUM> having a lumen <NUM> positioned adjacent to a main capillary section <NUM> having a capillary bore <NUM> communicating with the lumen <NUM>, with the capillary bore <NUM> having a larger inside diameter than that of the lumen <NUM>. The ion transfer device <NUM> differs in that its capillary bore <NUM> is much larger than the capillary bore <NUM> of the ion transfer device <NUM> of <FIG>. Additionally, the difference between the inside diameters of the capillary bore <NUM> and the lumen <NUM> of the ion transfer device <NUM> is much larger than the difference between the inside diameters of the lumen <NUM> and the capillary bore <NUM> of the ion transfer device <NUM> of <FIG>. The respective inside diameters of the lumen <NUM> in the embodiment of <FIG> and the lumen <NUM> in the embodiment of <FIG> may be the same, substantially the same, or different (with the lumen in either embodiment being larger or smaller than the other). With the configuration of the ion transfer device <NUM> of <FIG>, most of the pressure drop and expansion of the gas may occur in the lumen <NUM>. In this case, the gas flow may become fully supersonic downstream from the transition from the lumen <NUM> to the capillary bore <NUM>, and may or may not be supersonic upon exiting the ion transfer device <NUM> into the main vacuum environment (e.g., second chamber). In some embodiments, the inside diameter of the capillary bore <NUM> may be so large as to not provide any significant conductance limit for the gas flow after removing the ion inlet section <NUM>. In such case, however, the main capillary section <NUM> with the comparatively larger capillary bore <NUM> may function as an effective transfer tube that allows ions sufficient time to be fully desolvated by the time of exiting into the main vacuum environment. Moreover, as in other embodiments, the main capillary section <NUM> optionally may be heated to promote evaporation of droplets. The ion transfer device <NUM> in other aspects may be configured the same as or similar to the ion transfer device <NUM> of <FIG>.

<FIG> is a cross-sectional schematic perspective view of an example of an ion transfer device <NUM> according to another embodiment. As in other embodiments, the ion transfer device <NUM> includes an ion inlet section <NUM> having a lumen <NUM> positioned adjacent to a main capillary section <NUM> having a capillary bore <NUM> communicating with the lumen <NUM>, with the capillary bore <NUM> having a larger inside diameter than that of the lumen <NUM>. In the present embodiment, the main capillary section <NUM> includes a plurality of distinct capillary tube sections or segments arranged in series along its axial length. The inside diameter of the capillary bore <NUM> successively increases from one capillary tube segment to another in the direction of the outlet end of the ion transfer device <NUM>. For example, in the illustrated embodiment the main capillary section <NUM> includes a first capillary tube segment 418A having a first bore section 430A, a second capillary tube segment 418B having a second bore section 430B, a third capillary tube segment 418C having a third bore section 430C, and a fourth capillary tube segment 418D having a fourth bore section 430D. The inside diameter of the first bore section 430A is greater than that of the lumen <NUM>, the inside diameter of the second bore section 430B is greater than that of the first bore section 430A, the inside diameter of the third bore section 430C is greater than that of the second bore section 430B, and the inside diameter of the fourth bore section 430D is greater than that of the third bore section 430C. In the present embodiment, the inside diameter of the capillary bore <NUM> is varied (increased) in a step-wise manner. Each step up in inside diameter may be considered as demarcating the interface between adjacent capillary tube segments 418A-418D.

The illustrated embodiment provides four capillary tube segments 418A-418D as one example. However, the number of capillary tube segments may be more or less than four in other embodiments. The number of capillary tube segments 418A-418D, the respective axial lengths of the capillary tube segments 418A-418D, and the respective inside diameters of the bore sections 430A-430D may be set as needed to achieve desired pressure drops, temperature, and flow rates along the length and at the exit of the main capillary section <NUM>. The segmented configuration of the main capillary section <NUM> may enable finer control over such conditions. Specifically, the respective diameters and lengths of the capillary tube segments 418A-418D may be adjusted in a way that achieves control of gas velocity, pressure, and temperature in a desired way. The pressure is gradually reduced down the length of the multi-segment lumen so that the final exit into the vacuum system no longer results in a supersonic expansion at that location. This may have the benefit of reducing the tendency to form ionic clusters and may reduce turbulence in the first vacuum chamber.

The main capillary section <NUM> may be a monolithic structure in which each capillary tube segment (or section) 418A-418D transitions to an adjacent capillary tube segment (or section) 418A-418D in a continuous manner. In other embodiments, the main capillary section <NUM> may have a multi-segment configuration in which the capillary tube segments 418A-418D are positioned adjacent to each other but are physically separate segments. Adjacent capillary tube segments 418A-418D may directly abut each other. A fluid-sealed environment may be maintained by providing suitable sealing elements between the outer surfaces of the capillary tube segments 418A-418D and surrounding structures (e.g., the ion inlet section <NUM>, the wall <NUM>, a surrounding sleeve added to the assembly if needed, etc.). The multi-segment configuration may be desirable for practical considerations, such as to facilitate the realization of the varying inside diameter along the length of the main capillary section <NUM>. In addition, separate capillary tube sections (segments) 418A-418D are able to be independently addressable by respective voltage sources. This may be desirable to enable finer control over the electric field render control over the electric field more independent from the flow conditions in the main capillary section <NUM>.

In some embodiments, the ion inlet section <NUM> may be considered as being the first capillary tube segment or, stated differently, the first capillary tube segment in the series of tube segments provided by the ion transfer device <NUM> may serve as the ion inlet structure. The ion inlet section <NUM> (or the first capillary tube segment) may or may not have an end-cap configuration, and may or may not be removable.

In some embodiments, the lumen <NUM> of the ion inlet section <NUM> may include one or more transitions at which the inside diameter of the lumen <NUM> increases (e.g., steps up).

<FIG> is a cross-sectional schematic perspective view of an example of an ion transfer device <NUM> according to another embodiment. As in other embodiments, the ion transfer device <NUM> includes an ion inlet section <NUM> having a lumen <NUM> positioned adjacent to a main capillary section <NUM> having a capillary bore <NUM> communicating with the lumen <NUM>, with the capillary bore <NUM> having a larger inside diameter than that of the lumen <NUM>. Like the ion transfer device <NUM> of <FIG>, in the present embodiment the inside diameter of the capillary bore <NUM> diverges (increases) in the axial direction toward the outlet end, such that the inside diameter of the capillary bore <NUM> is greater at the bore inlet than at the bore outlet. The ion transfer device <NUM> differs in that the capillary bore <NUM> diverges in a gradual (or smooth, or continuous) manner instead of in a step-wise manner. With this geometry, the pressure drop and gas flow rate may vary gradually along the axial length of the capillary bore <NUM> to achieve desired flow conditions at the outlet end. The gas flow becomes supersonic in the capillary bore <NUM> and transition to subsonic flow upon exiting the ion transfer device <NUM>. The divergence (or expansion) of the inside diameter may be based on a curve function such as, for example, a quadratic function.

In some embodiments and as illustrated, the lumen <NUM> of the ion inlet section <NUM> may also diverge in a gradual manner in the axial direction toward the capillary bore <NUM>, such that inside diameter of the lumen <NUM> is greater at the lumen inlet than at the lumen outlet. Alternatively, the inside diameter of the lumen <NUM> may be constant as in other embodiments. In either case, the ion inlet section <NUM> achieves the initial pressure drop and conductance limit of the ion transfer device <NUM>, and the diverging geometry of the capillary bore <NUM> smoothly adjusts the flow conditions to achieve desired exit conditions (e.g., Mach number, pressure, temperature, flow rate, etc.). In either case, the transition from the lumen outlet to the bore inlet may be in effect continuous, i.e. the diameter of the lumen outlet may be equal or substantially equal to the diameter of the lumen outlet, or the transition may be somewhat abrupt (similar to the embodiments of <FIG> and <FIG>).

In some embodiments and as illustrated, the lumen <NUM> may include a converging section that begins at the lumen inlet and which, after a short axial distance, transitions to a diverging section in a direction toward the lumen outlet. In this case, the lumen inside diameter has a minimum value at a point between the lumen inlet and the lumen outlet, which point is typically closer to the lumen inlet than to the lumen outlet. The initial converging section may be useful for increasing the amount of ions drawn into the lumen inlet.

As in the embodiment of <FIG>, the main capillary section <NUM> may be a monolithic structure or may have a multi-segment configuration. Likewise, when segmented the ion inlet section <NUM> may be provided by the first capillary tube segment. Moreover, the ion inlet section <NUM> (or the first capillary tube segment) may or may not have an end-cap configuration, and may or may not be removable.

<FIG> is a cross-sectional schematic elevation view of an example of an ion transfer device <NUM> according to another embodiment. As in other embodiments, the ion transfer device <NUM> includes an ion inlet section <NUM> having a lumen <NUM> positioned adjacent to a main capillary section <NUM> having a capillary bore <NUM> communicating with the lumen <NUM>, with the capillary bore <NUM> having a larger inside diameter than that of the lumen <NUM>. In the present embodiment, the main capillary section <NUM> has a multi-segment configuration in which a plurality of physically distinct capillary tube segments 618A-618D are arranged in series along the axial length of the main capillary section <NUM>. Adjacent capillary tube segments 618A-618D may directly abut each other. As in the embodiment of <FIG>, the inside diameter of the capillary bore <NUM> successively increases in steps along the axial length in the direction of the outlet end of the ion transfer device <NUM>, which in the present embodiment is implemented on a segment-by-segment basis. Thus as illustrated, the main capillary section <NUM> includes a first capillary tube segment 618A having a first bore section 630A, a second capillary tube segment 618B having a second bore section 630B, a third capillary tube segment 618C having a third bore section 630C, and a fourth capillary tube segment 618D having a fourth bore section 630D. The inside diameter of the first bore section 630A is greater than that of the lumen <NUM>, the inside diameter of the second bore section 630B is greater than that of the first bore section 630A, the inside diameter of the third bore section 630C is greater than that of the second bore section 630B, and the inside diameter of the fourth bore section 630D is greater than that of the third bore section 630C.

In other embodiments, the inside diameter of the capillary bore <NUM> (or the inside diameters of both the capillary bore <NUM> and the lumen <NUM>) may increase gradually, as in the embodiment of <FIG>.

As also illustrated in <FIG>, the main capillary section <NUM> (or both the main capillary section <NUM> and the ion inlet section <NUM>) may be surrounded by a sleeve or other surrounding structure <NUM>. The surrounding structure <NUM> may be configured to provide a fluid-tight sealing interface, with sealing elements positioned in gaps between adjacent structures as described above in conjunction with <FIG>. Additionally or alternatively, all of part of the schematically illustrated surrounding structure <NUM> may be a heating device in thermal contact with the main capillary section <NUM> (or both the main capillary section <NUM> and the ion inlet section <NUM>), as also described above. The heating device may include one or more heating elements (e.g., electrically resistive heating elements) powered by a suitable electrical power source <NUM>, as appreciated by persons skilled in the art. In the present context, the term "thermal contact" means that the heating device (or some part thereof) is positioned appropriately so as to be able to transfer heat to the main capillary section <NUM> in an amount and rate effective for maintaining the fluid temperature at a desired level (typically under control of circuitry operatively associated with the power source <NUM>).

<FIG> is a cross-sectional schematic elevation view of an example of an ion transfer device <NUM> according to another embodiment. As in other embodiments, the ion transfer device <NUM> includes an ion inlet section <NUM> having a lumen <NUM> positioned adjacent to a main capillary section <NUM> having a capillary bore <NUM> communicating with the lumen <NUM>, with the capillary bore <NUM> having a larger inside diameter than that of the lumen <NUM>. In the present embodiment, a first conductive or resistive element <NUM> is disposed in or on the main capillary section <NUM> at or proximate to the inlet end of the main capillary section <NUM>, and a second conductive or resistive element <NUM> at or proximate to the outlet end. The first conductive or resistive element <NUM> may be placed in electrical communication with a first voltage source <NUM>, and the second conductive or resistive element <NUM> may be placed in electrical communication with a second voltage source <NUM>. A relatively high voltage potential may be applied to the first conductive or resistive element <NUM>, and a relatively low voltage level may be applied to the second conductive or resistive element <NUM> to generate a potential difference across the length of the main capillary section <NUM> and thereby aid in the transport of ions through the ion transfer device <NUM>. The first conductive or resistive element <NUM> may be electrically interconnected with the ion inlet section <NUM>. The potential on the ion inlet section <NUM> may be utilized to attract ions to the inlet of the ion transfer device <NUM>.

<FIG> is a cross-sectional schematic elevation view of an example of an ion transfer device <NUM> according to another embodiment. As in other embodiments, the ion transfer device <NUM> includes an ion inlet section <NUM> having a lumen <NUM> positioned adjacent to a main capillary section <NUM> having a capillary bore <NUM> communicating with the lumen <NUM>, with the capillary bore <NUM> having a larger inside diameter than that of the lumen <NUM>. The lumen <NUM> extends from a lumen inlet <NUM> serving as the entrance of the ion transfer device <NUM>, and an internal lumen outlet <NUM>. The capillary bore <NUM> extends from an internal bore inlet <NUM> communicating with the lumen outlet <NUM>, and a bore outlet <NUM> serving as the exit of the ion transfer device <NUM>. In the present embodiment, the ion inlet section <NUM> has a tapered geometry. That is, the ion inlet section <NUM> has a pointed shape in which an outside diameter of the ion inlet section <NUM> (i.e., the outside diameter of an outer surface <NUM> of the ion inlet section <NUM>) increases in a direction toward the main capillary section <NUM>. This tapered or pointed geometry may provide advantages, as described above. In the embodiment specifically illustrated in <FIG>, the ion inlet section <NUM> (whether removable from or integral with the main capillary section <NUM>) is configured such that the tapered portion is integral to the rest of the body constituting the ion inlet section <NUM>. In another embodiment, however, the tapered portion may be a separate part that fits onto or around the (smaller) the ion inlet section <NUM>.

<FIG> is a cross-sectional schematic elevation view of an example of an ion transfer device <NUM> according to another embodiment. As in other embodiments, the ion transfer device <NUM> includes an ion inlet section <NUM> having a lumen <NUM> positioned adjacent to a main capillary section <NUM> having a capillary bore <NUM> communicating with the lumen <NUM>, with the capillary bore <NUM> having a larger inside diameter than that of the lumen <NUM>. The lumen <NUM> extends from a lumen inlet <NUM> serving as the entrance of the ion transfer device <NUM>, and an internal lumen outlet <NUM>. The capillary bore <NUM> extends from an internal bore inlet <NUM> communicating with the lumen outlet <NUM>, and a bore outlet <NUM> serving as the exit of the ion transfer device <NUM>. In the present embodiment, the ion transfer device <NUM> has a single-piece or monolithic configuration in which the ion inlet section <NUM> is integral or contiguous with the main capillary section <NUM> as described earlier in this disclosure. That is, the ion inlet section <NUM> and the main capillary section <NUM> are not physically separate components. In some embodiments and as illustrated, the interface or transition between the ion inlet section <NUM> and the main capillary section <NUM> (and thus also the lumen outlet <NUM> and the bore inlet <NUM>) may be distinct, such as by being demarcated by a distinct change in inside diameter (e.g., the smaller inside diameter of the lumen <NUM> is stepped up to the larger inside diameter of the capillary bore <NUM>). In other embodiments, the inside diameters of the lumen <NUM> and the capillary bore <NUM> may vary gradually such as shown in <FIG>, and the change in inside diameter at the transition from the lumen <NUM> to the capillary bore <NUM> may be less abrupt than what is shown in <FIG>. In this latter case, the ion inlet section <NUM> may be considered as being the inlet end portion or region of the single-piece ion transfer device <NUM>. As in other embodiments, the axial lengths of the ion inlet section <NUM> and the main capillary section <NUM> and the geometries of the lumen <NUM> and the capillary bore <NUM> are configured to reduce contamination and optimize flow behavior through the ion transfer device <NUM>.

The present disclosure also relates to an ion transfer system that includes an ion transfer device as disclosed herein. The ion transfer system may include a first chamber, a second chamber configured to be evacuated down to a pressure lower than a pressure of the first chamber, and a wall separating the first chamber and the second chamber. The wall includes an opening extending through its thickness. The ion transfer device is positioned at the wall in a fluid-sealed manner, with the ion inlet section and/or the main capillary section of the ion transfer device extending into or through the opening. The lumen inlet of the ion transfer device communicates with the first chamber, and the bore outlet of the ion transfer device communicates with the second chamber. <FIG> illustrates an example of an ion transfer system that includes a first chamber <NUM>, a second chamber <NUM>, and an ion transfer device <NUM> with an inlet <NUM> disposed in or facing the first chamber <NUM> and an outlet <NUM> disposed in or facing the second chamber <NUM>.

The present disclosure further relates to an analytical instrument, particularly a mass spectrometry (MS) system, which includes an ion transfer system as disclosed herein. The MS system may include an atmospheric-pressure ionization device configured for producing ions in the first chamber, a vacuum housing enclosing the second chamber, and a mass analyzer disposed in the vacuum housing. <FIG> illustrates an example of an MS system <NUM>, which is described in detail above.

It will be understood that terms such as "communicate" and "in. communication with" (for example, a first component "communicates with" or "is in communication with" a second component) are used herein to indicate a structural, functional, mechanical, electrical, signal, optical, magnetic, electromagnetic, ionic or fluidic relationship between two or more components or elements. As such, the fact that one component is said to communicate with a second component is not intended to exclude the possibility that additional components may be present between, and/or operatively associated or engaged with, the first and second components.

Claim 1:
A method for transferring ions, the method comprising:
creating a pressure differential between a first chamber (<NUM>) and a second chamber (<NUM>) such that the second chamber has a pressure less than a pressure of the first chamber, wherein:
the first chamber and the second chamber are separated by a wall (<NUM>); and
an ion transfer device (<NUM>, <NUM>, <NUM>, <NUM>) extends through the wall and comprises an ion inlet section (<NUM>, <NUM>, <NUM>) and a main capillary section (<NUM>, <NUM>, <NUM>);
the ion inlet section (<NUM>, <NUM>, <NUM>) comprises an inlet (<NUM>) leading to a lumen (<NUM>, <NUM>, <NUM>);
the main capillary section (<NUM>, <NUM>, <NUM>) comprises a bore (<NUM>, <NUM>, <NUM>) communicating with the lumen and leading to an outlet (<NUM>); and
the lumen has a lumen inside diameter and the bore has a bore inside diameter greater than the lumen inside diameter;
producing ions in the first chamber;
drawing the ions into the inlet;
transporting the ions from the inlet through the lumen and into the bore, and through the bore to the outlet; and
emitting the ions from the outlet into the second chamber,
wherein ion inlet section and the main capillary section are configured such that the lumen inside diameter has an average value that is less than an average value of the bore inside diameter, a difference between the average value of the lumen inside diameter and the average value of the bore inside diameter is large enough to cause the gas flow to become fully supersonic downstream from the transition from the lumen to the capillary bore, and the gas flow is not supersonic upon exiting the main capillary section, and
wherein the main capillary section (<NUM>, <NUM>, <NUM>) comprises a plurality of capillary tube segments serially positioned adjacent to each other, the inside diameters of the bores of the capillary tube segments successively increasing from one capillary tube segment to another in a direction toward the bore outlet, or wherein the bore inside diameter of the main capillary section gradually increases from a bore inlet of the bore up to the bore outlet.