Systems and methods for analyzing samples

Abstract

Systems and methods for analyzing a sample are provided. In some embodiments, a mass spectrometer may include a source configured to output a plurality of particles, a tube having a central axis, and a skimmer. In some embodiments, the skimmer may include an opening disposed to receive one or more charged particles deflected by a deflector, and a contact surface including an intersection point that intersects with the central axis of the tube. The intersection point may be spaced from the opening by a distance of at least 5 mm.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application is a PCT international application claiming the benefit of U.S. Patent Application No. 18 / 048,049, filed October 20, 2022, which is incorporated herein by reference in its entirety. U.S. Patent Application No. 18 / 048,049 is a continuation-in-part of U.S. Patent Application No. 17 / 816,734, filed August 2, 2022, which is incorporated herein by reference in its entirety.

[0003] FIELD OF THE DISCLOSURE The present disclosure relates to systems and methods for analyzing samples. More particularly, the present disclosure relates to improved mass spectrometry devices, components thereof, and methods of using same. [Background technology]

[0004] Mass spectrometry is an analytical technique that can be used to analyze samples. Among other applications, mass spectrometry can be used to analyze the composition of a sample. A mass spectrometer may operate by applying energy to a sample, causing the sample to emit ions. The ions move through an electric field, and collisions with a detector may be measured. The location at which the particle is detected, or the time required for the ion to reach the detector, may vary depending on the mass of the ion. Therefore, by measuring these parameters, the mass of the ion can be determined and the composition of the sample can be inferred.

[0005] Time-of-flight mass spectrometers operate by measuring the time required for ions to travel to a detector. Time-of-flight mass spectrometers may include a particle guide that directs ions to the detector. A particular particle guide, called a quadrupole, may include four electrode segments collectively arranged around a central channel through which ions can pass. Mass spectrometers typically have multiple chambers at different pressures, traditionally requiring multiple particle guides. Particle guides are complex electrical devices, and requiring multiple particle guides can significantly increase cost and manufacturing difficulty. There is also a risk that multiple quadrupoles may not be properly aligned or synchronized, which can result in poor performance.

[0006] Furthermore, as ions are directed into the particle guide, droplets and other particles can deposit around the entrance of the particle guide, which poses a risk of contamination and can adversely affect the accuracy of future measurements.

[0007] Therefore, there is a need for a system and method for accurately analyzing sample composition with high reliability and low cost. Additionally, there is a need for a mass spectrometer with an improved skimmer arrangement that reduces the risk of contamination and improves measurement accuracy. Summary of the Invention

[0008] The following presents a simplified summary to provide a basic understanding of some aspects described herein. This summary is not an extensive overview of the claimed subject matter. It is not intended to identify key or critical elements of the claimed subject matter, nor is it intended to limit its scope.

[0009] In some embodiments, a mass spectrometer may be provided. In some embodiments, the mass spectrometer may include a source configured to output one or more ions, a plurality of chambers having different pressures, a detector configured to detect the one or more ions, and a particle guide. The plurality of chambers may include at least a first chamber having a first pressure lower than atmospheric pressure and a second chamber having a second pressure lower than the first pressure. In some embodiments, the particle guide may include a conduit through which the one or more ions may travel along the entire length of the particle guide. The conduit may be disposed within at least the first chamber and the second chamber. The particle guide may further include a housing surrounding the conduit. In some embodiments, the housing may include a first open section having a first vent port, the first vent port defining a passageway between the first chamber and the conduit, a second open section having a second vent port, the second vent port defining a passageway between the second chamber and the conduit, and a closed section disposed between the first and second open sections, at least a portion of the closed section disposed at a junction between the first and second chambers. One or more ions may be configured to travel from the source through at least the first chamber, the second chamber, and the particle guide to the detector.

[0010] In some embodiments, the conduit can include a quadrupole. In some embodiments, the quadrupole can include multiple quadrupole segments, each configured to generate an electric field that can be controlled independently of the other quadrupole segments. The multiple quadrupole segments can be collectively configured to reduce the kinetic energy of one or more ions as they traverse the length of the particle guide.

[0011] In some embodiments, the quadrupole may include at least four linear components axially arranged along the length of the conduit. A central passage may extend between the four linear components and may be open to allow one or more ions to traverse the length of the conduit by traveling through the central passage. A passage defined by a first vent may extend between two of the four linear components to the central passage.

[0012] In some embodiments, the particle guide may have a fluid conductance defined by the open cross-sectional area of ​​the conduit and the length of the closed section, the fluid conductance being less than 1 liter per second.

[0013] In some embodiments, a sealing ring may be disposed between the closed section of the housing and the junction between the first chamber and the second chamber. In some embodiments, the third chamber may have a third pressure that is lower than the second pressure of the second chamber. In some embodiments, the particle guide may terminate in a lens gate disposed at the junction between the second chamber and the third chamber, and the lens gate may be configured to selectively allow one or more ions to enter the third chamber.

[0014] In some embodiments, a particle guide configured to be disposed within a mass spectrometer may be provided. The particle guide may be configured to be disposed within a mass spectrometer including multiple chambers having different pressures, including at least a first chamber having a first pressure lower than atmospheric pressure and a second chamber having a second pressure lower than the first pressure. In some embodiments, the particle guide may include a conduit through which one or more ions may travel along the entire length of the particle guide. The conduit may be configured to be disposed within at least the first and second chambers. The particle guide may further include a housing surrounding the conduit. In some embodiments, the housing may include a first open section including a first vent configured to define a passage between the first chamber and the conduit when the first open section is disposed within the first chamber. The housing may further include a second open section including a second vent configured to define a passage between the second chamber and the conduit when the second open section is disposed within the second chamber. The housing may further include a closed section disposed between the first open section and the second open section, at least a portion of the closed section configured to be disposed at a junction between the first chamber and the second chamber.

[0015] In some embodiments, the particle guide can include a quadrupole. The quadrupole can include multiple quadrupole segments, each configured to generate an electric field that can be controlled independently of the other quadrupole segments. The multiple quadrupole segments can be collectively configured to reduce the kinetic energy of one or more ions as they traverse the length of the particle guide.

[0016] In some embodiments, the quadrupole may include four linear components arranged axially along the length of the particle guide. A central passage may extend between the four linear components, the central passage being open to allow one or more ions to traverse the length of the particle guide by traveling through the central passage. A passage defined by a first vent may extend between two of the four linear components to the central passage. In some embodiments, the closed section may have a fluid conductance defined by the open cross-sectional area of ​​the central passage and the length of the closed section, the fluid conductance being less than 1 liter per second.

[0017] In some embodiments, a sealing ring may be disposed between the closed section of the housing and the junction between the first chamber and the second chamber.

[0018] In some embodiments, the particle guide can terminate in a lens gate configured to be disposed at a junction between a second chamber and a third chamber of the mass analyzer. The third chamber can have a third pressure lower than the second pressure of the second chamber. The lens gate can be configured to selectively allow one or more ions to enter the third chamber.

[0019] In some embodiments, a method for analyzing a sample may be provided. In some embodiments, the method may be performed using a mass spectrometer including multiple chambers having different pressures, including at least a first chamber having a first pressure lower than atmospheric pressure and a second chamber having a second pressure lower than the first pressure. In some embodiments, the method may include applying energy to the sample to generate one or more ions, passing the one or more ions through a particle guide at least partially disposed within the first and second chambers of the mass spectrometer, and detecting the arrival of the one or more ions at a detector. In some embodiments, the particle guide may include a conduit through which the one or more ions may travel along the entire length of the particle guide and a housing surrounding the conduit. In some embodiments, the housing may include a first open section including a first vent configured to define a passage between the first chamber and the conduit. The housing may further include a second open section including a second vent configured to define a passageway between the second chamber and the conduit. The housing may further include a closed section disposed between the first open section and the second open section, at least a portion of the closed section disposed at a junction between the first chamber and the second chamber.

[0020] In some embodiments, a mass spectrometer may be provided. The mass spectrometer may include a source configured to output a plurality of particles, which may include one or more charged particles and one or more uncharged particles. The mass spectrometer may further include a tube having a central axis, a deflector configured to be charged to deflect the one or more charged particles, and a skimmer. The skimmer may include an opening disposed to receive the one or more charged particles deflected by the deflector, and a contact surface including an intersection point that intersects with the central axis of the tube, the intersection point being at least 5 mm away from the opening. The mass spectrometer may further include a particle guide configured to pass the one or more charged particles along a length of the particle guide, and a detector configured to detect the one or more charged particles. In some embodiments, the one or more charged particles may be configured to (i) travel through the tube toward the skimmer, (ii) be deflected toward the opening by the deflector, (iii) travel through the opening into the particle guide, (iv) traverse the length of the particle guide, and (v) be detected by the detector. At least a portion of the one or more uncharged particles can be configured to (i) travel through the tube toward the skimmer and (ii) deposit on the contact surface.

[0021] Further variations encompassed by the systems and methods are described below in the detailed description of the invention. [Brief explanation of the drawings]

[0022] [Figure 1] 1 shows a schematic diagram of an exemplary mass spectrometer. [Figure 2] 1 shows a perspective view of certain components of a mass spectrometer. [Figure 3] 1 illustrates an exemplary particle guide. [Figure 4A] 4 shows an additional view of the particle guide shown in FIG. 3. [Figure 4B] 4 shows an additional view of the particle guide shown in FIG. 3. [Figure 5] 4 shows a longitudinal cross section of the particle guide shown in FIG. 3. [Figure 6A]1 illustrates an exemplary skimmer arrangement for receiving ions. [Figure 6B] 1 illustrates an exemplary skimmer arrangement for receiving ions. [Figure 6C] 1 illustrates an exemplary skimmer arrangement for receiving ions. [Figure 7] 1 shows a perspective view of an exemplary skimmer. [Figure 8] 1 illustrates an exemplary method for analyzing a sample. DETAILED DESCRIPTION OF THE INVENTION

[0023] While aspects of the presently disclosed subject matter may be embodied in a variety of forms, the following description and accompanying drawings are intended to disclose only some of these forms as illustrative examples of the subject matter, and therefore, the presently disclosed subject matter is not intended to be limited to the forms or embodiments so described and illustrated.

[0024] FIG. 1 shows a schematic diagram of an exemplary mass spectrometer 100. In some embodiments, mass spectrometer 100 may include multiple chambers 110a, 110b, 110c, and 110d, each of which may have a different pressure. For example, chamber 110a may have a pressure below atmospheric pressure, and chambers 110b, 110c, and 110d may each have a successively lower pressure, such that chamber 110d has a sufficiently low pressure that air molecules do not affect (or have a minimal effect on) the flow of ions through chamber 110d to detector 118. In an exemplary embodiment, chamber 110a may have a pressure of 0.1 to 10 Torr, or preferably about 1 Torr. Chamber 110b may have a pressure of 0.001 to 0.1 Torr, or preferably about 0.01 Torr. Chamber 110c may have a pressure of 10 Torr. -5 ~10 -3 Torr, or preferably about 10 -4 The chamber 110d may have a pressure of 10 Torr. -8 ~10 -5 Torr, or preferably about 10 -7In some embodiments, a greater or lesser number of chambers may optionally be provided, and the pressure within each chamber may optionally vary from the values ​​described herein.

[0025] In some embodiments, the mass spectrometer 100 may include a source 102 configured to output one or more ions. In some embodiments, the source 102 may include a chamber in which a sample can be received. The source 102 may further include a device for applying energy to molecules in the sample to ionize them. In some embodiments, the source may use capillary electrophoresis and / or electrospray ionization. In some embodiments, ions may flow from the source 102 into a tube 104. The ions may flow from the tube 104 toward a deflector 106 and then into a skimmer 108. The skimmer 108 may direct ions on an intended path into a particle guide 120. Ions that deviate from the intended path may be blocked by the skimmer and prevented from entering the particle guide 120. Exemplary skimmer arrangements are described in more detail below with reference to FIGS. 6A-6C.

[0026] In some embodiments, particle guide 120 may include a quadrupole, as described in more detail below with respect to FIGS. 3-5. The particle guide may include multiple segments 122 to which an electric field may be applied to direct and manipulate the flow of ions through the length of the particle guide. FIG. 1 shows an exemplary particle guide with 13 quadrupole segments. The particle guide may optionally have a greater or lesser number of segments than shown in this embodiment. The particle guide may terminate with a lens gate 112 that may selectively allow ions to pass into chamber 110d. In some embodiments, lens gate 112 may be attached to or integral with particle guide 120. In other embodiments, lens gate 112 may be adjacent to particle guide 120. Lens gate 112 may have a first state that is open to the passage of ions from particle guide 120 to chamber 110d and a second state that blocks the flow of ions from particle guide 120 to chamber 110d. The lens gate 112 may be configured to selectively switch between a first state and a second state based on a signal provided by a controller.

[0027] In some embodiments, the mass spectrometer 100 may include a pusher 114, a reflectron 116, and a detector 118. The pusher 114 may include multiple conductive elements (e.g., stacked plates electrically insulated from one another) that can be selectively charged with different voltages. Ions may be configured to travel from the lens gate 112 to a channel within the pusher 114, which may generate an electric gradient that accelerates ions through the pusher channel toward the reflectron 116. The reflectron 116 may include multiple conductive rings or other elements that can be selectively charged with different voltages, thereby generating an electric gradient configured to reflect ions toward the detector 118. The detector 118 may be configured to detect the arrival of each ion that contacts the detector 118 and record the precise time of each arrival. In some embodiments, the detector 118 may be a microchannel plate that may be configured to detect individual ions.

[0028] In use, a sample is placed in the source 102 and energized to generate ions. The ions may flow from the source 102 through the tube 104, the deflector 106, and through the skimmer 108 to the particle guide 120. The ions may then travel through the particle guide 120, which confines the ion's movement and, in some embodiments, may reduce the ion's kinetic energy. The ions may then travel through the lens gate 112 to the pusher 114. The pusher accelerates the ions toward the reflectron 116 and then reflects them toward the detector 118, where their arrival time may be recorded.

[0029] The flight time of ions from the pusher 114 to the detector 118 can vary based on the mass and charge of the ions. For example, ions with larger masses may accelerate more slowly through the pusher 114 and reflectron 116, resulting in a longer flight time to the detector 118. Conversely, larger charges may result in higher acceleration, resulting in a shorter flight time to the detector 118. By accurately measuring the time between when the pusher 114 begins accelerating ions and when the ions reach the detector 118, the mass and charge of the ions can be inferred and the composition of the sample in the source 102 can be analyzed.

[0030] Figure 2 shows a perspective view of certain components of a mass spectrometer, including particle guide 120, lens gate 112, pusher 114, reflectron 116, and detector 118, as described above in the schematic diagram shown in Figure 1.

[0031] FIG. 3 illustrates an exemplary particle guide 120. The particle guide 120 may include a housing 123 that can house electrical components and provide a rigid support for mounting the particle guide 120 within a mass spectrometer. Multiple quadrupole segments 122 may be disposed within the housing 123. As shown in more detail in FIGS. 4A and 4B , each quadrupole segment 122 may include four conductive members 128 that may be disposed around a central channel 130. The conductive members 128 may be selectively charged such that the conductive members of a quadrupole segment, in conjunction with other quadrupole segments of the particle guide, can direct and manipulate the flow of ions through the central channel 130 of the particle guide. The central channel 130 may extend along the entire length of the particle guide.

[0032] In some embodiments, a deflector 106 and a skimmer 108 may be attached to the particle guide. The deflector 106 and the skimmer 108 may be configured to perform the functions described above with reference to Figure 1 and below with reference to Figures 6A-6C.

[0033] Particle guide 120 may include sections 111a, 111b, and 111c. In some embodiments, section 111a may be an open section that includes a vent 124a that provides a passageway from the exterior of section 111a to central channel 130. For example, the passageway defined by vent 124a may extend between two of the four conductors 128 of one or more quadrupole segments 122 in section 111a.

[0034] Section 111c may also be an open section. Section 111c may include a vent 124b that provides a passageway from the exterior of section 111c to central channel 130. For example, the passageway defined by vent 124b may extend between two of the four conductors 128 of one or more quadrupole segments 122 within section 111c. Section 111b may preferably be a closed section that does not include a vent. Optionally, additional open or closed sections may be provided.

[0035] Particle guide 120 including sections 111a, 111b, and 111c can be disposed in a mass spectrometer having multiple chambers at different pressures. Section 111a can be disposed, for example, in a first chamber (such as chamber 110b in FIG. 1) having a first pressure, and section 111c can be disposed, for example, in a second chamber (such as chamber 110c in FIG. 1). Vent 124a can provide a passage from the first chamber to the central channel, and vent 124b can provide a passage from the second chamber to the central channel. Thus, the portion of the central channel near vent 124a can be at or nearly at the pressure in the first chamber, and the portion of the central channel near vent 124b can be at or nearly at the pressure in the second chamber.

[0036] A pressure difference may exist along the portion of the central channel spanning from the first vent 124a to the second vent 124b. The flow of air molecules may be limited by the fluid conductance of the closed section 111b. For example, the fluid conductance of the closed section 111b may be determined by the cross-sectional area of ​​the opening of the channel 130 and the length of the closed section. By making the fluid conductance low enough (e.g., because the cross-sectional area is small enough and the length of the closed section is large enough), the flow of air from the high-pressure chamber to the low-pressure chamber may be reduced to a level that can be offset using a vacuum pump or other device, thereby maintaining the pressure difference at a desired state. In some embodiments, the length of the closed segment may be at least 1 cm, at least 40 cm, or more preferably at least 4 cm. In some embodiments, the open cross-sectional area of ​​the channel 130 may be less than 0.05 cm. 2 Less than 5cm 2 Less than, or more preferably, 0.3 cm 2 In some embodiments, the fluid conductance of the closed section may be less than 0.01 liters per second, less than 10 liters per second, or more preferably less than 1 liter per second. As shown in FIG. 1 , one or more vacuum pumps 113a, 113b, 113c, and 113d may be positioned to remove air molecules from chambers 110a, 110b, 110c, and 110d, respectively. The one or more vacuum pumps may be attached directly to the housing of mass spectrometer 100 or coupled to the chambers via hoses. In some embodiments, the vacuum pumps may be roughing pumps, such as rotary vane or scroll pumps, or turbomolecular pumps. In some embodiments, higher-power pumps may be used for chambers 110b, 110c, and / or 110d than for chamber 110a. For example, a rotary vane pump may be connected to chamber 110a, and a three-stage turbo pump may be connected to chambers 110b, 110c, and 110d. Other pumping arrangements may also be used.

[0037] When placed in a mass spectrometer such as that shown in FIG. 1, open section 111a may be located within chamber 110b, open section 111c may be located within chamber 110c, and closed section 111b may be located across the junction between chambers 110a and 110b. In this manner, a single particle guide may be placed across multiple chambers at different pressures without creating unacceptable levels of gas flow across the chambers. This may advantageously reduce the number of separate particle guides that need to be provided and installed in a mass spectrometer, thereby reducing the cost of the mass spectrometer and improving the consistency and reliability of the device's performance.

[0038] Particle guide 120 may include one or more circumferential rings 121 a, 121 b, which may be configured to receive electrical contacts for controlling the electric field within the particle guide. In some embodiments, rings 121 a, 121 b may alternatively or additionally be used to provide mechanical support to which particle guide 120 may be attached within a mass spectrometer. In some embodiments, rings 121 a, 121 b may be replaced with mechanical supports having different shapes. For example, the supports may be protrusions that extend less than the entire circumference of the housing, or may have flat outer surfaces (e.g., triangular, rectangular, pentagonal, or hexagonal protrusions).

[0039] In some embodiments, particle guide 120 may also include one or more sealing rings 126a, 126b. Sealing rings 126a, 126b may be made from a deformable material, such as rubber or an elastomeric polymer, so that a sealing connection can be formed when the sealing rings contact a surface. In some embodiments, when particle guide 120 is installed in a mass spectrometer, sealing rings 126a, 126b may align with and contact the wall between adjacent chambers. For example, with reference to FIG. 1 , sealing ring 126a may be positioned to contact the inner surface of an opening in the wall between chambers 110b and 110c. Sealing ring 126b may be positioned to contact the inner surface of an opening in the wall between chambers 110c and 110d.

[0040] Figures 4A and 4B show cross-sectional views of the particle guide 120 shown in Figure 3. In these figures, the housing 123 has been omitted to more clearly show the internal components of the particle guide 120.

[0041] FIG. 4A shows the open section 111a of the particle guide 120. The particle guide 120 may include one or more quadrupole segments 122, each of which may include four conductive members 128 to which a voltage may be applied. Four quadrupole segments are visible in the cross section of the particle guide shown in FIG. 4A. The quadrupole segments 122 may be arranged around a central channel 130, which may define a path through which ions may flow through the length of the particle guide. The vent 124a may form a passage from the exterior of the particle guide to the interior of the particle guide 120, and more particularly, to the central channel 130.

[0042] Figure 4B shows the closed section 111b of the particle guide 120. The open cross-sectional area of ​​the central channel 130 can be seen in Figure 4B. By increasing or decreasing this cross-sectional area, the fluid conductance of the closed section can be altered.

[0043] FIG. 5 shows a longitudinal cross-sectional view of particle guide 120 installed in the mass spectrometer shown in FIG. 1. As shown in FIG. 5, mounting piece 132 can be attached to the wall disposed between chambers 110b and 110c via bolts or other fasteners. Mounting piece 132 can be press-fit or otherwise coupled to housing 123 of the particle guide. Sealing ring 126 can be disposed between mounting piece 132 and housing 123 to provide an airtight seal between these components. Similar or similar structures can also be provided in other sections where particle guide 120 is attached to the mass spectrometer. For example, similar or similar structures can be provided at the distal end of particle guide 120 (e.g., around sealing ring 126b) where particle guide 120 may be attached to the wall between chambers 110c and 110d.

[0044] 6A-6C illustrate exemplary skimmer arrangements for receiving ions. As shown in FIG. 6A, the skimmer arrangement may include one or more surfaces that may be geometrically arranged to reduce the risk of contamination around the opening 146. In the exemplary embodiment of FIG. 6A, the first surface 141 may be arranged at a non-zero angle relative to the second surface 143, and the third surface 143 may be arranged at a non-zero angle relative to the second surface 143. In some embodiments, the first surface 141 and the third surface 143 may be parallel to each other or within 5 degrees of parallel to each other. The second surface 142 may be arranged at an angle parallel to the central axis of the tube 104. Alternatively, the second surface may be arranged at an angle closer to parallel to the central axis of the tube 104 than either surface 141 or surface 143.

[0045] As described above with respect to FIG. 1 , particles may generally flow from a source through a tube 104. As used herein, the term “particles” broadly encompasses any collection of materials that may collectively pass through a mass spectrometer or portion thereof, including both individual molecules and larger groups of materials, such as droplets, and may further include ions, heavy charged molecules or groups of materials, and neutral species. In some embodiments, the tube 104 may be a capillary 104. Various particles with different charge-to-mass ratios enter the flow path and may be deflected by the voltage of the deflector 106. As used herein, the term “deflector” broadly encompasses any element intended to or having the effect of redirecting the flow of charged particles, regardless of the element's shape, and may include both planar and curved electrodes and other structures, such as tubular lenses. Furthermore, variations in particle trajectories may be observed.

[0046] Two exemplary simplified flow paths are shown in dotted lines in Figure 6A. In the first particle path, the particle may be repelled by deflector 106 and directed to particle guide 120 through an opening in surface 141 of skimmer 108 or through an opening between surfaces 141 and 142. In the second particle path, the particle may not be redirected by the deflector or may be minimally redirected (e.g., due to a low charge-to-mass ratio or misalignment) and may pass by the opening and contact surface 143 located a certain distance away from the opening. Surface 143 may include point 147 that intersects with central axis 149 of tube 104. The geometry of skimmer 108 may be such that point 147 is a certain distance away from opening 146, and central axis 149 has a well-defined path to point 147 (i.e., the central axis does not intersect with another part of skimmer 108 before reaching point 147). In some embodiments, the clear path may be such that a cylinder of radius 1, 2, 3, or 5 mm surrounding central axis 149 does not intersect any part of the skimmer until it reaches point 147. In some embodiments, the distance between opening 1416 and point 147 may be at least 500 microns, at least 1 mm, at least 3 mm, at least 5 mm, at least 10 mm, at least 20 mm, at least 50 mm, or at least 100 mm.

[0047] 6B and 6C show further exemplary skimmer shapes. As shown in FIG. 6B, surface 142 may be part of a cone extending toward or including opening 146. As shown in FIG. 6C, opening 146 may be located on an extension 148 or other surface spaced apart from surface 143. Optionally, the extension or spaced apart surface may include a cone or other portion having a surface substantially parallel to the central axis of tube 104. In other embodiments, this may be omitted, and the shape of the extension or spaced apart surface may be used to ensure that uncharged particles that pose a contamination risk primarily travel a consistent distance from opening 146. Similar to FIG. 6A, the shape of the skimmer embodiment shown in FIGS. 6B and 6C may be such that point 147 is a consistent distance from opening 146 and that central axis 149 has a clear path to point 147. The distance between opening 1416 and point 147 can be at least 500 microns, at least 1 mm, at least 3 mm, at least 5 mm, at least 10 mm, at least 20 mm, at least 50 mm, or at least 100 mm.

[0048] By angling surface 142, as shown in Figures 6A and 6B, particles that are not redirected or minimally redirected by the deflector tend to move a distance away from the opening before contacting the skimmer. Alternatively, by using protrusions or other spaced-apart surfaces, as shown in Figure 6C, particles that are not redirected or minimally redirected by the deflector also tend to move a distance away from the opening before contacting the skimmer. In some embodiments, at least 50%, at least 75%, at least 85%, at least 90%, at least 95%, at least 97%, at least 99%, or at least 99.5% of the uncharged particles that pass through the tube and deposit on the skimmer can be deposited at least a distance away from the opening. In some embodiments, the distance can be at least 500 microns, at least 1 mm, at least 3 mm, at least 5 mm, at least 10 mm, at least 20 mm, at least 50 mm, or at least 100 mm. This advantageously reduces the rate at which dislodged particles contact and deposit on or around the aperture, which could potentially dislodge and enter the particle guide during future measurements. In particular, contamination problems are most often caused by liquid droplets and heavy charged or neutral particles, which are not redirected or minimally redirected by deflector 106. Therefore, these particles can reliably move away from the aperture and toward surface 143, with little risk of contaminating future measurements. Therefore, the skimmer arrangement shown in Figures 6A-6C can reduce the risk of deposited particles contaminating future measurements, thereby improving the accuracy and reliability of the mass spectrometer. Neutral gas molecules traveling through the tube can be primarily pumped out of the mass spectrometer by the vacuum pump rather than depositing on surfaces. In theory, some heavy molecules could become airborne and pass through the mass spectrometer, depositing on surfaces within the mass spectrometer; however, the contamination caused by this phenomenon has been found to be minimal.

[0049] Figure 7 shows a perspective view of an exemplary skimmer 108. As shown in Figure 7, particles may approach skimmer 108 by passing through a capillary disposed within recess 105. A voltage may be applied to deflector 106 such that deflector 106 deflects charged particles exiting the capillary. The charged particles are redirected by deflector 106 to opening 146 in surface 141, from which the particles may travel through a particle guide, such as the particle guides described above.

[0050] In some embodiments, surface 142 may be substantially parallel to the central axis of tube 104. For example, surface 142 may be within 30° of parallel to the central axis of tube 104, within 20° of parallel to the central axis of tube 104, within 15° of parallel to the central axis of tube 104, within 10° of parallel to the central axis of tube 104, within 8° of parallel to the central axis of tube 104, within 6° of parallel to the central axis of tube 104, within 4° of parallel to the central axis of tube 104, within 2° of parallel to the central axis of tube 104, or within 1° of parallel to the central axis of tube 104. In some embodiments, the distance between opening 146 and the portion of surface 142 closest to opening 146 may be less than 10 mm, less than 5 mm, less than 1 mm, less than 500 microns, less than 100 microns, less than 50 microns, or less than 10 microns.

[0051] Uncharged particles and particles with a large mass-to-charge ratio may continue to travel along a path substantially parallel to the length of the capillary and may come into contact with the surface 143. Thus, these particles (and their constituents) may be deposited at a distance away from the opening 146 and may pose little risk of contaminating future measurements.

[0052] FIG. 8 illustrates an exemplary method 800 for analyzing a sample. Method 800 may be performed using a mass spectrometer having a particle guide as generally described above with respect to FIGS. 1-5. For example, method 800 may be performed using a mass spectrometer having multiple chambers with different pressures, including at least a first chamber having a first pressure below atmospheric pressure and a second chamber having a second pressure below the first pressure. The mass spectrometer may include a particle guide including a conduit through which one or more ions may travel along the length of the particle guide and a housing surrounding the conduit. The housing may define a first open section with a first vent configured to define a passage between the first chamber and the conduit, a second open section with a second vent configured to define a passage between the second chamber and the conduit, and a closed section disposed between the first and second open sections.

[0053] In step 802, energy may be applied to the sample to generate one or more ions. For example, ions may be generated using capillary electrophoresis and / or electrospray ionization. The ions may then flow from the sample toward a particle guide, optionally via one or more of a capillary, a deflector, and / or a skimmer. In step 804, the ions may pass through the length of the particle guide. The particle guide may span multiple chambers of a mass analyzer at different pressures. In some embodiments, the particle guide may have a first vent defining a passage to a first chamber of the mass analyzer and a second vent defining a passage to a second chamber of the mass analyzer. To reduce the flow of air molecules along the pressure difference between the chambers, the vents may be spaced apart by closed sections whose cross-sectional area and length are selected to provide a sufficiently low fluid conductance. To maintain the desired pressure conditions, the mass analyzer chambers may further be continuously or intermittently evacuated using a vacuum pump.

[0054] In step 806, a detector may detect the arrival of ions at the detector. In some embodiments, the detector may be configured to detect the arrival of each ion that contacts the detector and record the exact time of each arrival. In some embodiments, the detector may be a microchannel plate. In some embodiments, the time between when the pusher begins accelerating the ions and when those ions reach the detector may be analyzed to determine the composition of the sample. Numbered Embodiments

[0055] Exemplary embodiments of the systems and methods disclosed herein are described in the following numbered paragraphs. Embodiment 1. A mass spectrometer comprising: a source configured to output a plurality of particles, the plurality of particles including one or more charged particles and one or more uncharged particles; a tube having a central axis; a deflector configured to be charged to deflect one or more charged particles; an opening positioned to receive the one or more charged particles deflected by the deflector; a contact surface including an intersection point that intersects with the central axis of the tube, the intersection point being at least 5 mm away from the opening; a skimmer comprising: a particle guide configured to pass one or more charged particles along a length of the particle guide; a detector configured to detect one or more charged particles; Equipped with one or more charged particles are configured to (i) travel through the tube toward the skimmer, (ii) be deflected toward the opening by the deflector, (iii) travel through the opening into the particle guide, (iv) traverse the length of the particle guide, and (v) be detected by the detector; at least a portion of the one or more uncharged particles are configured to (i) travel through the tube toward the skimmer and (ii) deposit on the contact surface; Mass spectrometer. Embodiment 2. A mass spectrometer as recited in embodiment 1, wherein the skimmer comprises a tube alignment surface that extends in a direction within 20 degrees of parallel to the central axis of the tube. Embodiment 3. A mass spectrometer as recited in embodiment 2, wherein the contact surface is disposed at a non-zero angle relative to the tube alignment plane. Embodiment 4 The mass spectrometer according to any one of embodiments 2 and 3, wherein the tube alignment surface is within 5 degrees of being parallel to the central axis of the tube. Embodiment 5: The mass spectrometer according to any one of embodiments 2 and 3, wherein the tube alignment surface is within 2 degrees of being parallel to the central axis of the tube. Embodiment 6. A mass spectrometer as described in any one of embodiments 1 to 5, wherein the skimmer is positioned such that at least 75% of the uncharged particles output by the source and deposited on the skimmer during a given period of use are deposited at a location at least 3 mm away from the opening. Embodiment 7. A mass spectrometer as described in any one of embodiments 1 to 6, wherein the skimmer is positioned such that at least 90% of the uncharged particles output by the source and deposited on the skimmer during a given period of use are deposited at a location at least 3 mm away from the opening. Embodiment 8. A mass spectrometer as described in any one of embodiments 1 to 7, wherein the skimmer is positioned such that at least 75% of the uncharged particles output by the source and deposited on the skimmer during a given period of use are deposited at a location at least 5 mm away from the opening. Embodiment 9. A mass spectrometer as described in any one of embodiments 1 to 8, wherein the skimmer is positioned such that at least 90% of the uncharged particles output by the source and deposited on the skimmer during a given period of use are deposited at a location at least 5 mm away from the opening. Embodiment 10 A mass spectrometer according to any one of embodiments 1 to 9, wherein the intersection point is the portion of the skimmer closest to the tube that intersects with the central axis.

[0022] Embodiment 11. A skimmer configured for use in a mass spectrometer, comprising: an opening positioned to receive the one or more charged particles deflected by the deflector; a contact surface including an intersection point that intersects with the central axis of the tube, the intersection point being spaced from the opening by a distance of at least 5 mm; The skimmer is configured to be placed in a mass spectrometer comprising a deflector, a tube, a particle guide, and a detector, whereby: a plurality of particles can travel through the tube toward the skimmer, the plurality of particles including one or more charged particles and one or more uncharged particles; one or more charged particles are configured to (i) travel through the tube toward the skimmer, (ii) be deflected toward the opening by the deflector, (iii) travel through the opening into the particle guide, (iv) traverse the length of the particle guide, and (v) be detected by the detector; at least a portion of the one or more uncharged particles are configured to (i) travel through the tube toward the skimmer and (ii) deposit on the contact surface; Skimmer. Embodiment 12. A skimmer as described in embodiment 11, wherein the skimmer comprises a tube alignment surface extending in a direction within 20 degrees of parallel to the central axis of the tube. Embodiment 13. A skimmer as described in embodiment 12, wherein the contact surface is disposed at a non-zero angle relative to the tube alignment surface. Embodiment 14 The skimmer according to any one of embodiments 12 to 13, wherein the tube alignment surface is within 5 degrees of parallel to the central axis of the tube. Embodiment 15 The skimmer of any one of embodiments 12 to 14, wherein the tube alignment plane is within 2 degrees of parallel to the central axis of the tube. Embodiment 16 A skimmer described in any one of embodiments 11 to 15, wherein the skimmer is positioned so that at least 75% of the uncharged particles output by the source and deposited on the skimmer during a given period of use are deposited at a position at least 3 mm away from the opening. Embodiment 17 A skimmer described in any one of embodiments 11 to 16, wherein the skimmer is positioned so that at least 90% of the uncharged particles output by the source and deposited on the skimmer during a given period of use are deposited at a position at least 3 mm away from the opening. Embodiment 18 A skimmer described in any one of embodiments 11 to 17, wherein the skimmer is positioned so that at least 75% of the uncharged particles output by the source and deposited on the skimmer during a given period of use are deposited at a position at least 5 mm away from the opening. Embodiment 19 A skimmer described in any one of embodiments 11 to 18, wherein the skimmer is positioned so that at least 90% of the uncharged particles output by the source and deposited on the skimmer during a given period of use are deposited at a position at least 5 mm away from the opening. Embodiment 20 A skimmer according to any one of embodiments 11 to 19, wherein the intersection point is the portion of the skimmer closest to the tube that intersects with the central axis.

[0056] While the subject matter of the present disclosure has been described and illustrated in considerable detail with reference to specific exemplary embodiments incorporating various combinations and subcombinations of features, those skilled in the art will readily recognize other embodiments and variations and modifications thereof as encompassed within the scope of the present disclosure. Moreover, the description of such embodiments, combinations, and subcombinations is not intended to convey that the claimed subject matter requires any features or combinations of features other than those expressly recited in the claims. Accordingly, the scope of the present disclosure is intended to include all modifications and variations encompassed within the spirit and scope of the following appended claims.

Claims

1. 1. A mass spectrometer comprising: a source configured to output a plurality of particles, the plurality of particles including one or more charged particles and one or more uncharged particles; a tube having a central axis; a deflector configured to be charged to deflect the one or more charged particles; an opening positioned to receive the one or more charged particles deflected by the deflector; a contact surface including an intersection point that intersects with the central axis of the tube, the intersection point being at least 5 mm away from the opening; a skimmer comprising: a particle guide configured to pass the one or more charged particles along a length of the particle guide; a detector configured to detect the one or more charged particles; Equipped with the one or more charged particles are configured to (i) travel through the tube towards the skimmer, (ii) be deflected by the deflector towards the opening, (iii) travel through the opening into the particle guide, (iv) traverse the length of the particle guide, and (v) be detected by the detector; at least a portion of the one or more uncharged particles are configured to (i) travel through the tube toward the skimmer and (ii) deposit on the contact surface; Mass spectrometer.

2. 10. The mass spectrometer of claim 1, wherein the skimmer comprises a tube alignment surface that extends in a direction within 20 degrees of parallel to the central axis of the tube.

3. The mass spectrometer of claim 2 , wherein the contact surface is disposed at a non-zero angle relative to the tube alignment surface.

4. 3. The mass spectrometer of claim 2, wherein the tube alignment plane is within 5 degrees of parallel to the central axis of the tube.

5. 3. The mass spectrometer of claim 2, wherein the tube alignment plane is within 2 degrees of parallel to the central axis of the tube.

6. 2. The mass spectrometer of claim 1, wherein the skimmer is positioned such that at least 75% of the uncharged particles output by the source and deposited on the skimmer during a given period of use are deposited at a location at least 3 mm from the opening.

7. 2. The mass spectrometer of claim 1, wherein the skimmer is positioned such that at least 90% of the uncharged particles output by the source and deposited on the skimmer during a given period of use are deposited at a location at least 3 mm from the opening.

8. 2. The mass spectrometer of claim 1, wherein the skimmer is positioned such that at least 75% of the uncharged particles output by the source and deposited on the skimmer during a given period of use are deposited at a location at least 5 mm away from the opening.

9. 2. The mass spectrometer of claim 1, wherein the skimmer is positioned such that at least 90% of the uncharged particles output by the source and deposited on the skimmer during a given period of use are deposited at a location at least 5 mm away from the opening.

10. 2. The mass spectrometer of claim 1, wherein the intersection point is the portion of the skimmer nearest the tube that intersects the central axis.

11. 1. A skimmer configured for use in a mass spectrometer, the skimmer comprising: an opening positioned to receive the one or more charged particles deflected by the deflector; a contact surface including an intersection point that intersects with the central axis of the tube, the intersection point being spaced from the opening by a distance of at least 5 mm; The skimmer is configured to be disposed in a mass spectrometer comprising the deflector, the tube, a particle guide, and a detector, whereby: the plurality of particles are capable of traveling through the tube toward the skimmer, the plurality of particles including the one or more charged particles and one or more uncharged particles; the one or more charged particles are configured to (i) travel through the tube towards the skimmer, (ii) be deflected by the deflector towards the opening, (iii) travel through the opening into the particle guide, (iv) traverse a length of the particle guide, and (v) be detected by the detector; at least a portion of the one or more uncharged particles are configured to (i) travel through the tube toward the skimmer and (ii) deposit on the contact surface; Skimmer.

12. 12. The skimmer of claim 11, wherein the skimmer comprises a tube alignment surface that extends in a direction within 20 degrees of parallel to the central axis of the tube.

13. The skimmer of claim 12 , wherein the contact surface is disposed at a non-zero angle relative to the tube alignment surface.

14. 13. The skimmer of claim 12, wherein the tube alignment plane is within 5 degrees of parallel to the central axis of the tube.

15. 13. The skimmer of claim 12, wherein the tube alignment plane is within 2 degrees of parallel to the central axis of the tube.

16. 12. The skimmer of claim 11, wherein the skimmer is positioned such that at least 75% of the uncharged particles output by the source and deposited on the skimmer during a given period of use are deposited at a location at least 3 mm from the opening.

17. 12. The skimmer of claim 11, wherein the skimmer is positioned such that at least 90% of the uncharged particles output by the source and deposited on the skimmer during a given period of use are deposited at a location at least 3 mm from the opening.

18. 12. The skimmer of claim 11, wherein the skimmer is positioned such that at least 75% of the uncharged particles output by the source and deposited on the skimmer during a given period of use are deposited at a location at least 5 mm from the opening.

19. 12. The skimmer of claim 11, wherein the skimmer is positioned such that at least 90% of the uncharged particles output by the source and deposited on the skimmer during a given period of use are deposited at a location at least 5 mm away from the opening.

20. 12. The skimmer of claim 11, wherein the intersection point is the portion of the skimmer nearest the tube that intersects the central axis.

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