The present invention generally relates to mass spectrometry and particularly to a collision cell in mass spectrometer.
Mass spectrometers are used for elemental and molecular analysis. They are versatile and accurate devices for detecting and studying atoms and molecules by means of their mass-to-charge ratio. One type of this technology is called tandem mass spectrometer which has become the preferred method of choice for many applications. Tandem mass spectrometry allows selection and isolation of specific compounds of interest and their subsequent identification. Its extra selectivity enables this technology to be used for quantification of target compounds even in the presence of complex matrices. A typical tandem mass spectrometer comprises of two mass analyzers or filters arranged in series with a collision cell arranged in between them. The first mass analyzer transmits parent ions from the ionization source that have a particular mass to charge ratio. These ions then enter the collision cell with appropriate energy to fragment the parent ions transmitted by the first mass analyzer. Then the second mass analyzer receives and filters the fragmented ions by the collision cell. Eventually, only the ions of interest reach the detector.
There are a variety of collision cells that use different techniques to fragment molecules. The most commonly used type is the gas-based collision cell, in which the cell is filled with a suitable gas and sustained at a few mTorr of pressure. The parent ions, selected by the first mass analyzer, enter the collision cell and undergo energetic collisions with gas molecules. The energy absorbed by these collisions dissipates into the internal structure of the incoming molecules. If this energy is enough to break any bonds, the ions will go through fragmentation. This process is called collision-induced-dissociation (CID). The second mass analyzer is arranged to analyze the products of the fragmentation process. The processes of mass selection, fragmentation, and product ion mass analysis take place sequentially.
Another type of collision cell is surface induced dissociation (SID). In this case the molecules are accelerated towards a hard, impenetrable surface and collide with it for fragmentation. In this case, in contrast to CID which uses gas molecules for the purpose of fragmenting molecules, collision with the hard surface induces fragmentation. This process is not very efficient as it causes the incident fragmented ions to scatter and only a limited number of ions can be detected.
There are several limitations associated with gas-based CID. The first issue is that the cell needs to be pressurized with a collision gas. In tandem mass spectrometry, the collision cell is placed inside the high vacuum section of the mass spectrometer where the pressure needs to be kept in the microTorr levels for the mass analyzers to be able to perform effectively. Pressurizing the collision cell with gas would require larger turbomolecular pumps and roughing pumps to keep the pressure in the microTorr region. This contributes to the size and unit price of the mass spectrometer.
On the other hand, for the fragmentation process to take place effectively, the parent ions need to experience a minimum number of collisions within the collision cell. Therefore, gas-based collision cells have to be long enough to allow for enough collisions to happen. In addition, to prevent loss of fragmented molecules, flow focusing elements are needed, which add to length and complexity of the system. Therefore, current mass spectrometers are relatively long, and it is difficult to build a compact mass spectrometer without addressing the limitations imposed by the collision cell.
Another issue with the gas-based fragmentation is that they cannot fragment large molecules such as proteins and peptides. It is difficult to transfer enough energy from such collisions to large molecules. The efficiency of fragmentation in such collisions is very low. In addition, large molecules have several degrees of freedom, and the energy transferred during the collision is distributed among all different degrees of freedom reducing the effective energy transfer to each bond.
The objective of the present invention is to eliminate these issues and to make a small and compact mass spectrometer.
A completely new collision cell, called Solid Target Collision Cell (STCC), is disclosed here which comprises of a support which is coated or mounted with one to several atomic layers of a suitable target material. An ion beam moving towards the support is accelerated towards the support, for example, by an applied potential connected to the support. Ions collide with the first few layers of the target material placed on the support and undergo fragmentation. The ions lose their radial and axial energy by subsequent collisions while passing through the target material, and finally emerge from the other side of the support with very low energy. The fragmented ions are then extracted and focused by the aid of an aperture lens, an RF multi-pole ion guide, a stack of lenses, or any other means of extraction and focusing methods. The target material can be made from carbon, silicon, a type or combination of these materials, or any other suitable elements, compounds, or alloys which may have an atomic or molecular structure. This solid-target collision cell allows for tandem mass spectrometers to be made significantly smaller, much more cost-effective, and also portable. Since the need for a collision gas is removed (as in gas-based collision cell), the size of the vacuum pumps can also be drastically reduced which again leads to a more compact, portable mass spectrometer.
Embodiments herein will hereinafter be described in conjunction with the appended drawings provided to illustrate and not to limit the scope of the claims, wherein like designations denote like elements, and in which:
In a conventional gas-based collision cell 200, as in
As shown in
Ions may gain energy as a result of the collisions with molecules or atoms of the collision gas. This energy distributes in the entire structure of the molecule. If the deposited energy exceeds the energy of a certain bond, it will break that bond and hence the molecule will undergo the fragmentation process, generating fragmented ions 205. This process is known as Collision Induced Dissociation (CID).
In addition, in most cases, elaborate and costly components and electrical circuit design are also implemented in the mass spectrometer to form an axial field 210 inside the collision cell to be able to move the ions faster through the collision cell (see
As shown in
Some of the major drawbacks of the gas-based CID technique are as follows. By design, a certain number of collisions are required to happen inside the gas-based collision cell to fragment the ions. In addition, further collisions are required for the collisional focusing to take place effectively. Therefore, gas-based collision cells are typically designed to be around 15-20 cm long. Reducing the length of the collision cell below these values, will compromise the performance of the cell. Needless to say, the design of the collision cell and the required electronic circuits are complicated and costly. For example, a complicated RF power supply is required to drive the RF-only ion guides within the collision cell.
In addition, since the cell is pressurized with a gas, using large vacuum pumps is necessary to remove the collision gas and sustain the pressure in the microTorr levels within the vacuum chamber of the mass spectrometer. This is necessary for the functionality of the mass analyzers. Plus, complicated flow controlling systems are required to accurately control the flow of collision gas into the collision cell. Naturally a gas supply is also required to be connected to the mass spectrometer for this purpose. These are the main impediments against reducing the cost and size of tandem mass spectrometers as well as making them portable.
The gas-based collision cell is also incapable of fragmenting large molecules such as proteins and peptides. Smaller diatomic and triatomic molecules also do not fragment easily because of their low collision cross-section or longer mean free path which prevent them from experiencing enough collisions to fragment and subsequent collisional focusing.
An alternative technique to gas-based CID that currently exists is Surface Induced Dissociation (SID) 300, as schematically shown in
Herein, we introduce a novel method for ion fragmentation, which addresses the limitations mentioned above.
The mesh may be made of various materials such as copper, gold, silver, steel, nickel, stainless steel, titanium, molybdenum, aluminum or any other metal, alloy, or a combination of them. The mesh size may be in the range of 10 to 15000 with various thicknesses, for example in the range of 10 nm to a 10 millimeters. The mesh or grid may have openings of any size or shape, for example circular, hexagonal, rectangular, slot-shaped, triple-slot, various apertures, or any other form or geometry. The size of the openings may be in the range of 6000 microns to less than 2 nanometers. The porous support may be made from layers of graphene, carbon, silicon dioxide, silicon nitride or a combination or amalgamation of these materials. The silicon nitride support may be of the holey type. The carbon support may be of the holey or lacey type.
The collision cell further comprises of a number of layers of a target material 420 of a suitable material deposited, mounted, coated, or fixed on top of the mentioned support. The number of layers can be in the range of 1 to 100 atomic layers. The choice of the target material is important and may depend on the molecular or atomic ions of interest. The target material can for example be one or a few layers of graphene fixed on top of each other and on top of the support.
Some examples are chemical vapor deposition, physical vapor deposition, sputtering, aerosol deposition, hybrid physical-chemical vapor deposition, ion plating, thin film deposition, ion beam-assisted deposition, chemical deposition, spraying, thermal spray, or a combination of these methods or any other suitable methods.
In any case, the openings or porosity of the target material should be chosen properly to make sure the incoming ions experience a minimum number of collisions with its atoms or molecules, while allowing the fragmented ions to pass through at the same time. Also, the openings of the support should be large enough to allow the fragmented ions to pass through and not impede the flow of the ion beam.
As shown in
The target material can be made from graphene, carbon, silicon, a type or combination of these materials, or any other suitable elements, compounds, or alloys which may have an atomic or molecular structure. In the case of carbon, the target material may be of the holey or lacey type. In the case of graphene, the target may be comprised of a single layer of graphene, 2 to 10 layers, or multiple layers, based on the nature of the analyte ions and the application.
The ionization source for the tandem mass spectrometer may be for example an electrospray ionization source, an electron impact source, an inductively coupled plasma source, an atmospheric pressure chemical ionization source, an atmospheric pressure photo-ionization source, a plasma source, or any other type of combination of ionization sources based on the application.
The size of the proposed collision cell is significantly reduced compared with a gas-based collision cell.
The physical dimensions of the solid target C.C. can be slightly larger than the cross-sectional area of the ion beam. In most tandem mass spectrometers, the beam cross-section is about 1.0-10.0 mm in diameter. The thickness of the solid target C.C. can therefore be in the order of a few millimeters. This is a significant reduction in the size of collision cell compared with gas-based collision cells which are complicated, expensive devices and are normally designed to be around 15-20 cm long.
The support and the target material mounted on it are configured in a way to prevent them from being sputtered as a result of the incoming ion beam. Therefore, the target material may not be removed from the support.
The presently disclosed solid target collision cell, STCC, allows for the fragmentation of large molecules, such as proteins, lipids and peptides. Small molecules, such as diatomic and triatomic molecules, can also be readily fragmented. The tandem MS of the present disclosure requires much smaller pumping capacity for obtaining vacuum; it can be designed to be smaller and more cost-effective; it is simple, easy-to-build, cost-effective, and requires no elaborate design; it fits all types of tandem MS devices, and it provides more capability compared to gas-based or surface induced dissociation (SID) techniques. In addition, it requires no additional gas and flow controllers for maintaining the CC pressure, and therefore simplifies the MS device design.
The features, geometry, and properties of the support as well as the thickness, properties, and nature of the target material may be optimized for fragmentation of different types of ions and molecules.
In another case, the incoming ions may be atomic rather than molecular. In such a case, the solid target collision cell can be only used to reduce the energy of the incoming atomic ions. The ions can then go through ion/molecular reaction with the reaction gas to deal with isobaric interferences. The target material for the collision cell may also be used in a way to react with the incoming molecular or atomic ions. RF-only ion guide can then be provided to extract the fragmented ions or the new ion species as well confining them. Electrostatics lenses are also feasible for extraction and confinement of the ions.
Filing Document | Filing Date | Country | Kind |
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PCT/CA2023/050118 | 1/27/2023 | WO |
Number | Date | Country | |
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63307786 | Feb 2022 | US |