Patent Application
20250037985
Mass spectrometry can be used to perform detailed analyses on samples. Furthermore, mass spectrometry can provide both qualitative (is compound X present in the sample) and quantitative (how much of compound X is present in the sample) data for a large number of compounds in a sample. These capabilities have been used for a wide variety of analyses, such as to test for drug use, determine pesticide residues in food, monitor water quality, and the like.
Sensitivity of a mass spectrometer can be limited by the efficiency of the ion source, ion losses in the mass spectrometer and in the mass analyzer, and the sensitivity of the detector. Increasing the efficiency of the ion source (e.g., the number of ions produced per unit sample or per unit time) can significantly improve the detection limits of the mass spectrometer, enabling the detection of lower concentrations of compounds or the use of smaller amounts of sample. Additionally, increasing the stability of the ion source and the number of ions produced as a function of time can improve quantitative comparisons between runs and samples.
It is to be understood that the figures are not necessarily drawn to scale, nor are the objects in the figures necessarily drawn to scale in relationship to one another. The figures are depictions that are intended to bring clarity and understanding to various embodiments of apparatuses, systems, and methods disclosed herein. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts. Moreover, it should be appreciated that the drawings are not intended to limit the scope of the present teachings in any way.
To easily identify the discussion of any particular element or act, the most significant digit or digits in a reference number refer to the figure number in which that element is first introduced.
Embodiments of systems and methods for ion sources having improved performance and robustness are described herein and in the accompanying exhibits.
The section headings used herein are for organizational purposes only and are not to be construed as limiting the described subject matter in any way.
In this detailed description of the various embodiments, for purposes of explanation, numerous specific details are set forth to provide a thorough understanding of the embodiments disclosed. One skilled in the art will appreciate, however, that these various embodiments may be practiced with or without these specific details. In other instances, structures and devices are shown in block diagram form. Furthermore, one skilled in the art can readily appreciate that the specific sequences in which methods are presented and performed are illustrative and it is contemplated that the sequences can be varied (unless explicitly noted otherwise) and still remain within the spirit and scope of the various embodiments disclosed herein.
All literature and similar materials cited in this application, including but not limited to, patents, patent applications, articles, books, treatises, and internet web pages are expressly incorporated by reference in their entirety for any purpose. Unless described otherwise, all technical and scientific terms used herein have a meaning as is commonly understood by one of ordinary skill in the art to which the various embodiments described herein belongs.
It will be appreciated that there is an implied “about” prior to specific temperatures, concentrations, times, pressures, flow rates, cross-sectional areas, etc. discussed in the present teachings, such that slight and insubstantial deviations are within the scope of the present teachings. In this application, the use of the singular includes the plural unless specifically stated otherwise. Also, the use of “comprise”, “comprises”, “comprising”, “contain”, “contains”, “containing”, “include”, “includes”, and “including” are not intended to be limiting. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the present teachings.
As used herein, “a” or “an” also may refer to “at least one” or “one or more.” Also, the use of “or” is inclusive, such that the phrase “A or B” is true when “A” is true, “B” is true, or both “A” and “B” are true. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.
A “system” sets forth a set of components, real or abstract, comprising a whole where each component interacts with or is related to at least one other component within the whole.
In some embodiments, systems and methods taught herein use strategic placement of ferromagnetic elements to generate non-monotonic changes in the magnetic field within the ionization volume of the ionization chamber to improve robustness in chemical ionization processes, particularly negative chemical ionization (CI) processes. In practice, negative CI can have poor robustness due to the challenge of setting up the electrostatic potentials in the ion source to allow analyte anions to pass through the ion source to the analyzer in the presence of electrons. Because anions and electrons have the same polarity, source optics that are attractive or repulsive to anions will also be so for electrons. In the case of an axial source operating in negative CI mode, a beam of electrons may be confined along the center axis of the source. This confined electron beam can create a space charge field. This space charge field affects anion transmission through apertures of the source by repelling anions radially away from the center axis and thus further away from the ion exit aperture through which the ions are intended to pass to exit the source and generate signal at the detector. By employing a non-uniform magnetic field within the ionization volume as taught herein, electrons and anions can be spatially separated such that anions primarily pass through an ion exit aperture in the ionization chamber while electrons are directed to strike side walls or end walls of the ionization chamber away from the ion exit aperture.
Some embodiments of systems and methods taught herein address issues caused by accumulation of electron strikes on surfaces near the ion exit aperture. In particular, systems and methods taught herein improve ion throughput and increase the longevity of instrumentation by avoiding damage that can be caused by electrons striking surfaces around apertures. Electrons with sufficient kinetic energy can interact with species on surfaces of the ion source to form a dielectric layer (sometimes referred to by those skilled in the art as “burn” or “stitch”). Electrons can then impact and reside at the dielectric or burn layer to cause charging that can subsequently repel anions and lead to reductions in transmission of analyte anions through the source. As additional electrons strike this dielectric layer, the surface charges up to the initial potential of the electrons which is typically −70 V. This surface charge repels anions. Another issue caused by burn is that the burned surfaces require periodic cleaning. By using a ferromagnetic element to modify the magnetic field to generate a locally non-monotonic magnetic field within the ionization volume, the disclosed systems and methods reduce burning, which reduces maintenance costs, and reduces the resultant electron accumulation near the ion exit aperture. Moreover, the use of ferromagnetic materials strategically placed in the proximity of the ionization volume can improve negative CI or negative EI processes by reducing burning or stitching of electrons in the vicinity of an ion exit aperture. In conventional ion sources using only paramagnetic materials, electrons strike the end wall around the ion exit aperture resulting in burn. In negative CI or negative EI modes, the accumulated electron charge at the burn repels negative ions thus reducing ion transmission. Embodiments described herein can prevent electrons from burning onto the area around the ion exit aperture to improve ion transmission.
In some embodiments, systems and methods taught herein improve robustness in electron ionization (EI) processes and CI processes by improving injection of electrons into the ionization chamber through an entrance aperture. By introducing a locally increased magnetic field density in the region of the entrance aperture, the electron beam from the filament can be tightened closer to the center axis at the entrance aperture. Consequently, the amount of burning and charging at the entrance aperture is reduced and the flux of electrons through the entrance aperture is increased. Thus, EI and CI processes are enhanced by the presence of a higher number of electrons in the ionization chamber. A reduction in burning also increases longevity of the instrumentation and reduces cleaning or repair requirements.
In some embodiments, systems and methods taught herein can mitigate electron strikes on an exit face of the ion exit aperture by reflected electrons that have exited the ion exit aperture but are turned back by subsequent lens elements. In EI or positive CI processes, a final tube lens in the ion source can be set to repel electrons. Some of the repelled electrons are thereby reflected back towards the source, and a high number of electrons collide with the ion exit aperture on the exit face (i.e., the side facing the exit opposite a side facing the ionization volume) in conventional sources. By employing a non-uniform magnetic field, the reflected electrons can be focused towards the center axis to pass back into the ionization volume through the ion exit aperture and thus avoid striking the exit face of the ion exit aperture. Focusing the electrons to the center axis also increases electron reflection efficiency and increases system robustness by reducing burn intensity at the ion exit aperture.
Various embodiments of mass spectrometry platform 100 can include components as displayed in the block diagram of
In various embodiments, the ion source 102 generates a plurality of ions from a sample. The ion source 102 can include, but is not limited to, an electron ionization (EI) source, a chemical ionization (CI) source, or both an EI and CI source in combination.
In various embodiments, the mass analyzer 104 can separate ions based on a mass to charge ratio of the ions. For example, the mass analyzer 104 can include a quadrupole mass filter analyzer, a quadrupole ion trap analyzer, a time-of-flight (TOF) analyzer, an electrostatic trap (e.g., ORBITRAP) mass analyzer, Fourier transform ion cyclotron resonance (FT-ICR) mass analyzer, and the like. In various embodiments, the mass analyzer 104 can also be configured to fragment the ions using collision induced dissociation (CID), electron transfer dissociation (ETD), electron capture dissociation (ECD), photo induced dissociation (PID), surface induced dissociation (SID), and the like, and further separate the fragmented ions based on the mass-to-charge ratio.
In various embodiments, the ion detector 106 can detect ions. For example, the ion detector 106 can include an electron multiplier, a photomultiplier, an avalanche diode, a silicon photomultiplier, a Faraday cup, and the like. Ions leaving the mass analyzer can be detected by the ion detector. In various embodiments, the ion detector can be quantitative, such that an accurate count of the ions can be determined. In various embodiments, such as when using an electrostatic mass analyzer, the functions of mass analyzer 104 and ion detector 106 can be performed by the same component.
In various embodiments, the controller 108 can communicate with the ion source 102, the mass analyzer 104, and the ion detector 106. For example, the controller 108 can configure the ion source or enable/disable the ion source. Additionally, the controller 108 can configure the mass analyzer 104 to select a particular mass range to detect. Further, the controller 108 can adjust the sensitivity of the ion detector 106, such as by adjusting the gain. Additionally, the controller 108 can adjust the polarity of the ion detector 106 based on the polarity of the ions being detected. For example, the ion detector 106 can be configured to detect positive ions or be configured to detected negative ions.
Electron source 202 can include a thermionic emitter 226 for the generation of electrons. In various embodiments, electron source 202 can include more additional thermionic emitters for redundancy or increased electron production. In alternative embodiments, electron source 202 can include a thermionic filament, a field emitter, electron multiplier, photoelectric effect emitter, or other source of electrons. The electrons can travel axially along ion source 200 through an entrance aperture 246 of an electron lens 204 and into ionization chamber 206 to ionize gas molecules. The electron lens 204 can serve to prevent the ions from traveling back towards the electron source.
Ionization chamber 206 can include gas inlet 228 for directing a gas sample (for example, neutral molecules) into an ionization volume 230 defined by the ionization chamber 206. Gas molecules within the ionization volume 230 can be ionized by the electrons from the thermionic emitter 226. The efficiency of this interaction between neutral molecules and electrons increases as the density of electrons increases, and high electron densities are preferred to ensure sufficient levels of interaction to produce a robust output signal. High densities of electrons can be achieved by confining electrons to the center axis 244 in the paramagnetic section 248. In this context, “confinement” of the electrons means that the magnetic field generated by the magnetic field generator 240 has sufficient strength to restrict motion of electrons away from the center axis 244 of the ionization volume to achieve a target electron density. The confinement of electrons close to the center axis 244 in the paramagnetic section 248 can create a high-density electron region 254 wherein electrons interact with neutral molecules from the gas sample to form ions (e.g., analyte ions in electron ionization or reagent ions in chemical ionization) at a high rate due to the concentration of electrons. In the ferromagnetic section 250, the magnetic field is reduced, and electrons are not well confined to the vicinity of the center axis 248. In other words, the electrons diverge away from the center axis 248 (due, in part, to Coulomb repulsion along with the lower magnetic field) within the ferromagnetic section 250.
Lenses 208 and 210 can define a lens volume 232. Lens volume 232 can include regions of the lenses where some electrons may be present. In various embodiments, it may also include areas outside of the ionization volume and the lenses. End wall 234 can restrict the flow of gas from ionization volume 230 to the lens volume 232, creating a substantial pressure difference between the ionization volume 230 and lens volume 232. In some embodiments, the ferromagnetic element 242 can include the end wall 234. Ion exit aperture 236 can provide a path through end wall 234 for ions to exit the ionization chamber 206.
In various embodiments, the ionization chamber 206 and lens element 208 can be joined to create an extended ionization element defining the ionization volume 230 and at least a portion of the lens volume 232. In such embodiments, lens element 208 can be electrically coupled to ionization chamber 206. In other embodiments, the joined ionization chamber 206 and lens element 208 can be electrically isolated, such that different voltage potentials can be applied to the ionization chamber 206 and the lens element 208.
Lens 210 and 212 and RF ion guide 214 can assist in the axial movement of ions from the ionization volume 230 to additional ion optical elements and mass analyzer 104 of mass spectrometry platform 100. In various embodiments, ion guide assembly 238 can include lens 212 and RF ion guide 214. Ion guide assembly 238 can include additional insulating portions to electrically isolate lens 212 from RF ion guide 214. Additionally, the insulating portions can include standoffs to prevent electrical contact between lens 210 and lens 212.
When assembled into body 216, insulator 218 can prevent electrical contact between lens element 208 and lens element 210. Spacer 220 can prevent electrical contact between electron lens 204 and ionization chamber 206. Spacer 222 can be indexed to prevent rotation of the electron source 202, and retaining clip 224 can hold the other components within body 216.
The ferromagnetic elements 242 can adjust (i.e., increase or decrease) a magnetic field created by the magnetic field generator 240 at localized positions within or near the ionization chamber 206 to control motion of the electrons. The magnetic field generator 240 can include one or more magnetic-field generating sources such as electromagnets and permanent magnetic field generators. While the magnetic field generator 240 is illustrated as being positioned exterior to and at an end of the ion source, one or more magnetic field generators 240 can also be positioned at other locations with respect to the ion source including, for example, outside or inside walls of the ionization chamber 206. For example, magnets located at opposite sides of the ion source can generate a magnetic field that slowly decreases and then starts increasing again across the length of the ionization region. The resulting field produced by one or more magnets is modified by ferromagnetic elements as described in embodiments herein to generate localized and sharp changes in the magnetic field to influence motion of electrons or ions. In some embodiments, the magnetic field generator 240 can be positioned generally at a single radial distance from the center axis 244 and extend along the center axis 244. In the presence of a magnetic field, electrons emitted from thermionic emitter 226 (for example, a heated filament) undergo helical motion perpendicular to the magnetic field lines as the electrons are accelerated and decelerated through the electrostatic field potentials of the source optics (e.g., electron lens 204, lens element 208 lens element 210, lens element 212). By introducing ferromagnetic elements 242 adjacent to one or more lens elements or as part of one or more lens elements, the magnetic permeability becomes dynamic through the source and leads to changes in magnetic flux at different longitudinal locations along the center axis 244.
Ferromagnetic elements 242 can enable reductions in electron collisions with the end wall 234 of ionization chamber 206 and enable reductions in electron outflow through the ion exit aperture 236. With electrostatic potentials set to transmit analyte anions during negative CI analysis, most of the electrons either pass through the source or collide near the ion exit aperture 236 of the ion source 200 (e.g., on the end wall 234). A high density of electron collisions at the end wall 234 near the ion exit aperture 236 increases the rate at which a dielectric layer (i.e., “burning”) is produced, causing charging and repulsion of analyte anions that are intended transmit out through the ion exit aperture 236 to the detector. Similarly, electrons that exit the ionization chamber 206 can collide with other surfaces (and eventually cause charging) that are not as easily cleaned or that are not designed to be cleaned regularly. Both issues can contribute to lack of robustness in negative CI analysis.
The positioning of ferromagnetic elements 242 within, around, or outside the ion source adjusts the magnetic field generated by the magnetic field generator 240. The trajectories of electrons, having low relative mass to analyte ions, will be more affected by changes in the magnetic field, or lack thereof. Because of this, adjusting the magnetic field becomes an additional tool, along with the electrostatic fields within a source, to focus, disperse, or steer electron trajectories, while minimally affecting analyte ions. In particular, the ferromagnetic element can cause spatial separation to occur between a group of ions, which will be less affected by changes in the magnetic field and will tend to stay clustered near the center axis, and a group of electrons, which will be more affected by changes in the magnetic field and will tend to separate away from the center axis.
The ferromagnetic element 242 can be positioned within the ionization chamber. In an example embodiment, the ferromagnetic element 242 can include a cylinder positioned axisymmetrically about the center axis 244. In some embodiments, the ferromagnetic element 242 is permanently or removably affixed or attached to an outer wall of the ionization chamber using fasteners or adhesives. In some embodiments, the ferromagnetic element 242 is retained within the outer wall of the ionization chamber using a friction fit. While the ferromagnetic element is illustrated in
In other embodiments, the ferromagnetic element 242 can be disposed entirely external to (i.e., outside) the ionization chamber or ionization volume. In some embodiments, the ferromagnetic section 250 can be considered as the volume surrounded by the ferromagnetic element 242, particularly for cylindrical ferromagnetic elements that have an inner bore. In some embodiments, the ferromagnetic element 242 can be configured to move to allow adjustment of the position of the non-uniform magnetic field within or adjacent to the ionization chamber. For example, the ferromagnetic element can include or can be connected to translation aides such as tracks, motors, slides, or other structural features. The translation aide can be manually operated or motorized. In some embodiments, motion of the ferromagnetic element can be controlled by a controller, for example, the controller 108 in
Conventionally, paramagnetic materials are used to construct structural elements of the ion source. Paramagnetic materials may include 300 series stainless steels, aluminum and aluminum alloys, certain superalloys such as Inconel (R) (Special Metals Corporation, New Hartford, NY) or Hastelloy (R) (Haynes International, Inc., Kokomo, IN), nichrome (nickel-chromium alloy), titanium, or any other suitable material with a relative magnetic permeability near 1. For purposes of the present disclosure, paramagnetic materials can also include materials considered nonmagnetic such as polymers.
The ferromagnetic element can include ferromagnetic materials. Ferromagnetic materials may include iron, steel, cobalt, nickel, alloys of those metals, Permalloy, mu metal, 400 series stainless steels, or any other materials with a relative magnetic permeability greater than 1.1. It will be understood by one skilled in the art that the ferromagnetic element can include multiple separated or joined ferromagnetic elements or materials and that such a configuration including multiple elements can be referred to as a ferromagnetic section. An additional paramagnetic section may follow the ferromagnetic element of the source. In some embodiments, a surface of the ferromagnetic element 242 can be coated with a different material (e.g., coating) to reduce the chemical reactivity of the surface or make the surface easier to clean. For example, the coating could be applied as an additional layer or by modifying the existing surface layer using chemical vapor deposition, thermal deposition, thermal or electron beam evaporation, or a sputtering process. In some embodiments, a paramagnetic element (such as a form of stainless steel) can be inserted into or around the surface of the ferromagnetic element to block chemical interactions between the constituents of the ionization chamber and the ferromagnetic element. For example, the paramagnetic element can be a foil or thin cylinder insert that lies between the ferromagnetic element 242 and the center axis 244. In some embodiments, the paramagnetic insert can be removable or replaceable when it is dirty thus facilitating permanent mounting of the ferromagnetic element while still keeping the ferromagnetic element surface clean.
In ion source 200, electrons can be on center axis 244 with the ion beam. This can have the advantage of using the negative space charge from the electron beam to focus positive ions to the center axis 244. Additionally, a negatively charged ion exit aperture can help extract positive ions. These features can also be beneficial when used for positive CI.
Electrons striking the area around end wall 234 can result in the accumulation of an insulating layer around the ion exit aperture, changing the potential to close to that of the electrons, −70 V. In various embodiments, neutral molecules from the analyte of matrix can temporarily land on the surfaces of the ionization chamber 206. The molecules will generally leave the surface. However, if electrons strike the neutral molecules while on the surface, they can become attached to the surface in the form of inorganic carbon, silicon dioxide, or other insulating material depending on the composition of the molecule. This can form an insulating layer on the surface of the metal. As charged particles, such as electrons, strike the insulating layer, their charge cannot be quickly dissipated by the underlying metal and instead a charge can accumulate on the insulating layer. Once that occurs, the ion exit aperture can become a barrier to the electrons and the negative ions. This reduces the number of negative ions which leave the ionization volume 230 and travel to the ion detector 106 to be detected.
Curve 404 represents the system as taught herein including a ferromagnetic element. Due to the presence of the ferromagnetic element, the magnetic flux density shown in curve 404 along a length of the ionization volume (e.g., as a function of distance from magnetic field generator 240) is non-monotonic due to sharp fluctuations in density at localized positions along the center axis 244. In the system corresponding to curve 404, an initial section (e.g., paramagnetic section 248) of the ionization chamber is composed of paramagnetic materials, allowing the magnetic field passing through that section of the source, generated by the external magnetic field generator 240 (such as permanent magnetic field generators), to be unaffected. Following the paramagnetic section is the ferromagnetic element that creates a ferromagnetic section 250 and causes the magnetic flux density (B) to sharply and locally increase just before the ferromagnetic element 242 (due to field lines being drawn towards the center axis to preferentially pass through the more permeable ferromagnetic material as opposed to air/vacuum or paramagnetic materials). The magnetic flux density then falls in the center of the ferromagnetic section 250. In this embodiment, following the sharp decrease in magnetic flux density within the ferromagnetic section, the magnetic flux density again increases sharply and locally beyond the ferromagnetic element (again due to field lines having been drawn into the magnetically permeable material). A higher magnetic flux density is achieved upon exiting the material than occurs at the same position absent the ferromagnetic element. For example, this increased magnetic flux density can occur when a second paramagnetic section is disposed after the ferromagnetic section 250 along the center axis 244.
A dashed curve 402 in
The trajectories of electrons, which have low mass relative to analyte ions, are affected to a greater degree than ion trajectories by changes in the magnetic field (or lack thereof). Because of this, adjusting the magnetic field becomes an additional tool, along with the electrostatic fields within a source, to focus, disperse, or steer electron trajectories, while minimally affecting analyte ions.
The intense, localized burn 702 seen in
In embodiments described above, the introduction of ferromagnetic elements 242 enabled a reduction in the number of electrons that pass through or near the ion exit aperture 236 and reduced fouling of the end wall 234. Ferromagnetic elements as described herein can also be employed to achieve other advantages. In some embodiments, an electron lens including an entrance aperture separates the electron source from the ionization chamber. As described below in relation to
In other embodiments, the ferromagnetic element 242 can be placed in the vicinity or proximity of the source filament such as the thermionic emitter 226 at the distance 1208 anterior to the electron lens 204. This configuration differs from the configuration described above and shown in
In some embodiments, ion sources including ferromagnetic elements as taught in embodiments described herein can also reduce the number of reflected electrons that return from outside the ionization chamber and strike the end wall. Such an embodiment is particularly useful for ion sources that are used in particular electron ionization (EI) mode configurations wherein the electron reflections are utilized to increase the chance of ionization events in the ionization volume. In this mode, the final tube lens beyond the ion exit aperture and external to the ionization chamber has voltages set to repel electrons to cause at least some of the electrons to reflect back into the ionization chamber where they have further opportunities to interact with the analyte species. In a conventional ion source operating in EI mode, a high population of reflected electrons can collide with an exit face (i.e., the face opposite the thermionic emitter). Conversely, in embodiments of ion sources taught herein, the ferromagnetic element can be placed at a distance from the end wall (e.g., as a final tube lens) to increase the magnetic field density at the ion exit aperture of the end wall. As a result, fewer electrons collide with the end wall and electron reflection efficiency (i.e., percentage of back-traveling electrons that re-enter the ionization chamber through the ion exit aperture) is increased.
While the present teachings are described in conjunction with various embodiments, it is not intended that the present teachings be limited to such embodiments. On the contrary, the present teachings encompass various alternatives, modifications, and equivalents, as will be appreciated by those of skill in the art.
Further, in describing various embodiments, the specification may have presented a method and/or process as a particular sequence of steps. However, to the extent that the method or process does not rely on the particular order of steps set forth herein, the method or process should not be limited to the particular sequence of steps described. As one of ordinary skill in the art would appreciate, other sequences of steps may be possible. Therefore, the particular order of the steps set forth in the specification should not be construed as a limitation on the claims. In addition, claims directed to a method and/or process should not be limited to the performance of their steps in the order written, and one skilled in the art can readily appreciate that the sequences may be varied and still remain within the spirit and scope of the various embodiments.
The embodiments described herein can be practiced with other computer system configurations including hand-held devices, microprocessor systems, microprocessor-based or programmable consumer electronics, minicomputers, mainframe computers and the like. The embodiments can also be practiced in distributing computing environments where tasks are performed by remote processing devices that are linked through a network.
It should also be understood that the embodiments described herein can employ various computer-implemented operations involving data stored in computer systems. These operations are those requiring physical manipulation of physical quantities. Usually, though not necessarily, these quantities take the form of electrical or magnetic signals capable of being stored, transferred, combined, compared, and otherwise manipulated. Further, the manipulations performed are often referred to in terms such as producing, identifying, determining, or comparing.
Certain embodiments can also be embodied as computer readable code on a computer readable medium. The computer readable medium is any data storage device that can store data, which can thereafter be read by a computer system. Examples of the computer readable medium include hard drives, network attached storage (NAS), read-only memory, random-access memory, CD-ROMs, CD-Rs, CD-RWs, magnetic tapes, and other optical and non-optical data storage devices. The computer readable medium can also be distributed over a network coupled computer systems so that the computer readable code is stored and executed in a distributed fashion.
