Apparatus and method

Abstract

A collision / reaction cell (CRC) 53 for a mass spectrometer, the CRC 53 comprising a first multipole RF ion guide 531, a second multipole RF ion guide 532 and a third multipole RF ion guide 533 dispo

Description

Field 5 The present invention relates to collision / reaction cells, CRCs, for mass spectrometers. Background to the invention Generally, collision I reaction cells, CRCs, are used to induce fragmentation of ions by collision 10 induced dissociation (CID, also known as collisionally-activated dissociation, CAD) to thermalize ions of interest and / or to remove interfering ions through ion / neutral reactions before mass spectrometry of the ions of interest. Typically, a CRC comprises an enclosure having a multipole RF ion guide enclosed radially therein and a set of gas inlets, including a first gas inlet, therethrough. Collisional gases such as He, N2 and / or Ar and / or reactive gases such as H2, NH4, 15 CH4 and / or O2 are introduced into the enclosure via the set of gas inlets. Ions are guided axially through the multipole RF ion guide and collide and / or react with the introduced gases. Collisional gases are primarily used to induce fragmentation of ions by CID, for example in tandem quadrupole mass spectrometry, or to attenuate and normalize the axial kinetic energies of the ions (also known as thermalizing, collisional energy damping and / or collisional focusing) but may 20 also secondarily react with some of the ions. Reactive gases are primarily used to remove isobaric interferences through ion / neutral reactions, for example by changing mass-to-charge ratios of the interfering ions away from mass-to-charge ratios of ions of interest. Hence, CRCs may generally be used as collision cells, reaction cells and / or collision / reaction cells, depending on the gases introduced therein and thus are named according to primary use, for example. 25 CRCs are included in organic mass spectrometers such tandem quadrupole (TQ, also known as triple quadrupole, QqQ) mass spectrometers, quadrupole time of flight (QTof) mass spectrometers and hybrid ion trap Fourier transform mass spectrometer (FTMS). CRCs are also included in inorganic mass spectrometers such as commercial inductively coupled plasma mass spectrometers (ICP-MS), such as the Micromass (RTM) hexapole collision cell, the Perkin Elmer 30 (RTM) Dynamic Reaction Cell (RTM), the Agilent (RTM) Octopole Reaction System (ORS) and the Thermo Fisher Scientific (RTM) Collision Cell Technology. Other CRCs are known. Figure 1 schematically depicts a conventional triple quadrupole mass spectrometer 1. Typically, precursor ions (also known as parent ions) are created in an ion source 11, such as an 35 electrospray (ESI) ion source or an atmospheric pressure chemical ionization (APCI) ion source. Other ion sources are known. The precursor ions are accelerated away from the ion source 11, typically through an ion optical system immediately downstream from the ion source 11, and pass through a first analytical quadrupole Q1 12, where the precursor ions are filtered by their respective m / z values, allowing only selected precursor ions in a narrow m / z range to travel 24 04 25 therethrough. Next, the selected precursor ions go through a CRC q2 13, where the selected precursor ions undergo chemical reactions (fragmentations) via collisions with gas therein, generating product ions (also known as fragment ions or daughter ions). This method of fragmentation of precursor ions is called collision induced dissociation (CID). Typically, the CRC 5 q2 13 is kept under relatively increased gas pressure (around 0.01 mbar), and the selected precursor ions enter it accelerated (typical voltage for acceleration is in the range 20 to 100 V). A second analytical quadrupole Q3 14 typically filters the product ions that come out of the CRC. A detector 15 detects the product ions coming out of the second analytical quadrupole Q3 14. 10 The tandem quadrupole arrangement of a TQ mass spectrometer allows for four different scan types to be performed: a precursor ion scan, neutral loss scan, product ion scan, and selected reaction monitoring. In a precursor ion scan, a certain product ion is selected in Q3, and the precursor masses are scanned in Q1. This method is selective for ions having a particular functional group (e.g., a phenyl group) released by the fragmentation in q2. In a neutral loss 15 scan, both Q1 and Q3 are scanned together, but with a constant m / z offset. This allows the selective recognition of all ions which, by fragmentation in q2, lead to the loss of a given neutral fragment (e.g., H2O, NH3). Similar to the precursor ion scan, this method is useful in the selective identification of closely related compounds in a mixture. In a product ion scan, the first quadrupole Q1 is set to select a precursor ion of a known m / z, which is fragmented in q2. The 20 third quadrupole Q3 is then set to scan the entire m / z range, giving ion fragmentation information on the product ions generated. The structure of the original precursor ion can be deduced from the ion fragmentation information. This method is commonly performed to identify transitions used for quantification by tandem MS. In selected reaction monitoring (SRM, also known as multiple reaction monitoring, MRM), both Q1 and Q3 are set at respective specific m / z, allowing 25 only a distinct product ion from a certain precursor ion to be detected. This method results in increased sensitivity. If Q1 and / or Q3 is set to more than a single mass, this configuration is called multiple reaction monitoring. Generally, TQ mass spectrometers have high requirements to the speed of analysis, throughput, 30 size, and cost. Generally, CRCs have an important role in meeting the requirements of TQ mass spectrometers. Curved CRCs are known. Curved CRCs may reduce a stream of neutral particles, for example from the ion source, from entering Q3. When having a curvature of 180 degrees, such CRCs 35 may also allow reduction of a footprint (i.e. size, dimensions, volume) of the mass spectrometer, which is beneficial from environmental and / or economic perspectives, as a relatively smaller vacuum chamber requires a relatively lower pumping rate pump, relatively less energy for heating the chamber and / or relatively shorter pump down waiting times after maintenance. 24 04 25 Figure 2 schematically depicts a conventional triple quadrupole mass spectrometer 2, including a curved CRC 23 having a curvature of 180 degrees. The footprint of this triple quadrupole mass spectrometer 2 is about half the length of the footprint of the triple quadrupole mass spectrometer 1 of Figure 1. 5 While the footprint of this triple quadrupole mass spectrometer 2 is relatively shorter than the footprint of the triple quadrupole mass spectrometer 1 of Figure 1, the ion path in the curved CRC 23 is typically relatively longer than in a linear (also known as a straight) CRC, such as the CRC 13 of the triple quadrupole mass spectrometer 1 of Figure 1. This is due, at least in part, 10 to the need to spatially separate the analytical quadrupoles Q1 22 and Q3 24 within the chamber. This relatively longer ion path in the curved CRC increases a chance that the ions slow down or even come to a complete stop (i.e. rest) inside the CRC 23. As a result of the slowing or stopping ions, the analytical performance of the triple quadrupole mass spectrometer 2, including the 15 curved CRC 23, and / or the speed of analysis drops. The yield of ions coming through a curved CRC may be improved by using an axially-propelling electric field inside the curved CRC, for example using axial drag, that accelerates the ions around the curved CRC and thereby reduces the time the ions spend inside the curved CRC. 20 However, this is relatively complex and / or costly. A relatively less costly way to reduce the time the ions spend inside the curved CRC is to reduce the collision gas pressure. In this way, the number of collisions between the ions and the neutral gas molecules of the collision gas inside the CRC is reduced and the chance of the ions stopping 25 is lowered. While the cost of the CRC is relatively lower compared with using an axially-propelling electric field inside the curved CRC, the efficiency of collisions is lowered. That is, while there is a decreased chance that the ions slow down or even come to a complete stop the ions inside the CRC, the ions may not have enough collisions to undergo fragmentation (i.e. CID) by the time they reach the next stage of mass filtering in Q3. Therefore, the sensitivity of 30 analysis drops. In order for ions to undergo dissociation / fragmentation by CID, the ions need to be accelerated. The acceleration normally happens via a potential drop between the exit end of the analytical quadrupole Q1 and the entrance end of the CRC q2. Accelerated this way, ions divert from the 35 optical axis of the curved CRC. This increases the chance for the ions to pass through the radial pseudo potential barrier of the curved CRC and be lost for further analysis. Figure 3 shows results of a simulation for trajectories of ions accelerated into a curved CRC. This loss of ions adversely affects the sensitivity of the analysis. 24 04 25 Figure 4 schematically depicts a conventional triple quadrupole mass spectrometer 4, including a CRC 43 including a curved section having a curvature of 180 degrees. The CRC 43 also includes a linear section in front of the curved section. 5 Hence, there is a need to improve CRCs, for example to enable a reduction in footprint of TQ mass spectrometers while reducing complexity and / or cost and / or while increasing sensitivity, compared with conventional CRCs. Summary of the Invention 10 It is one aim of the present invention, amongst others, to provide a collision I reaction cell, CRC, for a mass spectrometer which at least partially obviates or mitigates at least some of the disadvantages of the prior art, whether identified herein or elsewhere. For instance, it is an aim of embodiments of the invention to provide a collision / reaction cell, CRC, for a mass 15 spectrometer enabling a reduction in footprint of the mass spectrometer. A first aspect provides a collision / reaction cell, CRC, for a mass spectrometer, comprising: a set of multipole RF ion guides, including a first multipole RF ion guide, a second multipole RF ion guide and a third multipole RF ion guide, disposed serially; 20 wherein the first multipole RF ion guide comprises and / or is a curved multipole RF ion guide, for transferring the ions downstream towards the second multipole RF ion guide, wherein a first central angle of the first multipole RF ion guide is in a range from 45° to 135°, wherein the first multipole RF ion guide is enclosed radially by a first enclosure; wherein the second multipole RF ion guide is enclosed radially by a second enclosure having a 25 set of gas inlets, including a first gas inlet, therethrough, for collision-induced dissociation, CID, of ions therein using a gas introduced therein via the set of gas inlets; wherein the second multipole RF ion guide comprises and / or is a linear multipole RF ion guide configured to accelerate the ions and / or the CID ions axially therealong from the first multipole RF ion guide towards the third multipole RF ion guide; and 30 wherein the third multipole RF ion guide comprises and / or is a curved multipole RF ion guide, for transferring the CID ions downstream away from the second multipole RF ion guide, wherein a third central angle of the third multipole RF ion guide is in a range from 45° to 135°, wherein the third multipole RF ion guide is enclosed radially by a third enclosure; wherein the first multipole RF ion guide and the second multipole RF ion guide are 35 mutually adjacent; and wherein the second multipole RF ion guide and the third multipole RF ion guide are mutually adjacent. 24 04 25 A second aspect provides a mass spectrometer, preferably a tandem quadrupole mass spectrometer, comprising a CRC according to the first aspect, for example wherein the CRC is disposed between quadrupole mass analysers of the tandem quadrupole mass spectrometer. 5 A third aspect provides a method of collision-induced dissociation, CID, of ions comprising: transferring the ions downstream along a first curved path of a first multipole RF ion guide included in a set of multipole RF ion guides, disposed serially, wherein the first multipole RF ion guide comprises and / or is a curved multipole RF ion guide, towards a second multipole RF ion guide included in the set of multipole RF ion guides, wherein a first central angle of the first 10 multipole RF ion guide is in a range from 45° to 135°, wherein the first multipole RF ion guide is enclosed radially by a first enclosure; inducing CID of the ions transferred to the second multipole RF ion guide from the first multipole RF ion guide using a gas introduced therein, wherein the second multipole RF ion guide comprises and / or is a linear multipole RF ion guide and wherein the second multipole RF ion 15 guide is enclosed radially by a second enclosure, and accelerating the ions and / or the CID ions axially along a second linear path from the first multipole RF ion guide towards a third multipole RF ion guide included in the set of multipole RF ion guides; and transferring the accelerated ions and / or the accelerated CID ions downstream along a third curved path of the third multipole RF ion guide, wherein the third multipole RF ion guide 20 comprises and / or is a curved multipole RF ion guide, away from the second multipole RF ion guide, wherein a third central angle of the third multipole RF ion guide is in a range from 45° to 135°, wherein the third multipole RF ion guide is enclosed radially by a third enclosure; wherein the first multipole RF ion guide and the second multipole RF ion guide are mutually adjacent; and 25 wherein the second multipole RF ion guide and the third multipole RF ion guide are mutually adjacent. Detailed Description of the Invention 30 According to the present invention there is provided a collision / reaction cell, CRC, for a mass spectrometer, as set forth in the appended claims. Also provided is a mass spectrometer comprising such a collision I reaction cell, CRC, and a method of collision-induced dissociation, CID, of ions. Other features of the invention will be apparent from the dependent claims, and the description that follows. 35 Collision / reaction cell The first aspect provides a collision / reaction cell, CRC, for a mass spectrometer, comprising: 24 04 25 a set of multipole RF ion guides, including a first multipole RF ion guide (referred to herein also as an entrance section), a second multipole RF ion guide (referred to herein also as a central section) and a third multipole RF ion guide (referred to also herein as an exit section), disposed serially; 5 wherein the first multipole RF ion guide comprises and / or is a curved multipole RF ion guide, for transferring the ions downstream towards the second multipole RF ion guide, wherein a first central angle of the first multipole RF ion guide is in a range from 45° to 135°, wherein the first multipole RF ion guide is enclosed radially by a first enclosure; wherein the second multipole RF ion guide is enclosed radially by a second enclosure having a 10 set of gas inlets, including a first gas inlet, therethrough, for collision-induced dissociation, CID, of ions therein using a gas introduced therein via the set of gas inlets; wherein the second multipole RF ion guide comprises and / or is a linear multipole RF ion guide configured to accelerate the ions and / or the CID ions axially therealong from the first multipole RF ion guide towards the third multipole RF ion guide; and 15 wherein the third multipole RF ion guide comprises and / or is a curved multipole RF ion guide, for transferring the CID ions downstream away from the second multipole RF ion guide, wherein a third central angle of the third multipole RF ion guide is in a range from 45° to 135°, wherein the third multipole RF ion guide is enclosed radially by a third enclosure; wherein the first multipole RF ion guide and the second multipole RF ion guide are 20 mutually adjacent; and wherein the second multipole RF ion guide and the third multipole RF ion guide are mutually adjacent. In this way, a reduction in footprint of a mass spectrometer is enabled since the first multipole 25 RF ion guide and the third multipole RF ion guide respectively comprise and / or are curved multipole RF ion guides, for example having a total curvature of 180 degrees such as similarly to the conventional triple quadrupole mass spectrometer 2, including a curved CRC 23 having a curvature of 180 degrees, schematically depicted in Figure 2. However, the CRC according to the first aspect comprises the second multipole RF ion guide disposes serially between the first 30 multipole RF ion guide and the third multipole RF ion guide. Since the second multipole RF ion guide comprises and / or is a linear multipole RF ion guide configured to accelerate the ions and / or the CID ions axially therealong from the first multipole RF ion guide towards the third multipole RF ion guide, ion losses during axial acceleration for the CID through the second multipole RF ion guide are relatively reduced, compared with a curved multipole RF ion guide. 35 In this way, sensitivity is relatively increased, compared with conventional curved CRCs while complexity and / or cost may be relatively reduced, for example compared with using an axially-propelling electric field inside a conventional curved CRC. 24 04 25 Firstly, the gas pressure in the CID region of a CRC may be controlled to optimise the number of collisions between the precursor ionsand the neutral gas molecules for CID. The gas pressure is typically about 1E-2 mbar (1E-3 kPa). The working pressure in the vacuum chamber of a conventional tandem quadrupole mass spectrometer is typically less than 1E-4 mbar (1E-5 kPa), 5 i.e. at least a factor of 1E2 times lower. If the CID region of the CRC were instead disposed adjacent to an analytical quadrupole, such as Q1 or Q2, the number of neutral gas molecules coming from the CID region into the analytical quadrupole would negatively affect the throughput and / or resolution of the analytical quadrupole, for example due to the relatively increased gas pressure therein compared with the working pressure. In order to attenuate this increase in gas 10 pressure, a diaphragm (also known as an orifice plate or an aperture plate), having a sufficiently small orifice diameter, could be arranged between the CRC and the analytical quadrupole. While such an arrangement would attenuate this increase in gas pressure, scattering of the ions in the fringe field between the analytical quadrupole and the diaphragm would nevertheless reduce the throughput of the ions. Hence, disposing the CID region of the CRC adjacent to an analytical 15 quadrupole is not preferred. In contrast, the CID region of the CRC according to the first aspect would not be disposed adjacent to an analytical quadrupole. Rather, the first multipole RF ion guide and / or the third multipole RF ion guide are instead arranged to be disposed adjacent to an analytical quadrupole. In this way, an increase the gas pressure in an analytical quadrupole is attenuated, for example minimised, while throughput of the ions is not reduced. 20 Secondly, the entrance and exit sections of the CRC serve as gas reducing pipes, for the central section that is at a relatively higher gas pressure. For example, calculation of the gas pressure for an exemplary embodiment of the CRC, as schematically depicted in Figure 5, shows that pressure drop by a factor of at least 1E2 may be achieved between the central section and the 25 vicinities outside the distal ends of the entrance and exit sections of the CRC, for typical pumping rates of the pump (>120 l / s). In one example, the reduced gas conductance of the curved sections substitutes a use of gas-limiting diaphragms. Thirdly, the length of the central section of the CRC may be varied within a relatively large range. 30 If the CID region of the CRC were instead disposed adjacent to an analytical quadrupole, such as Q1 or Q2, increasing the length thereof (e.g. to accommodate the lower pressure in the CID region), a benefit of a relatively small footprint of the instrument diminishes. In contrast, for the CRC according to the first aspect, the length of the straight section is unlikely to increase significantly due to the fact that the pressure inside this central section can be sufficiently high 35 providing the lowering of it within the curved end sections so that there is no resulting increase of the gas pressure in the chamber. Additionally and / or alternatively, a benefit of keeping the central section relatively short is a better control of the DC axial field, that allows fast removal of the ions from the most gas pressurised 24 04 25 region and prevents disadvantageous space charge effects. Moreover, challenging requirements of the market for dwell times of tandem quadrupole mass spectrometers as short as 0.5 ms require the time that the ions spend in the CRC is limited to a range of 0.1 to 0.2 ms. Note, however, that the typical CID reaction times are in the range 0.1 to 1 ms which means that 5 a fast-working CRC may result in poorer CID yield. The CRC according to the first aspect benefits from a relatively short central section while also benefiting from the curved exit section. Once the ions have undergone collisions in the central section, they proceed into the curved exit section, where they have time to cool down (i.e. thermalise) and complete dissociation. 10 The control of the gas conductance within the curved end sections of the CRC can be achieved by adjusting the cross section of the electrodes of the curved sections, e.g., like in Figure 6. Also, a plastic or ceramic inserts could be placed between the electrodes to reduce the cross section available fortravel of the gas particles, e.g., like in Figure 7. Care should be taken not to put any insulating parts close to the ion beam to prevent the contamination and charging. 15 Contemporary simulation means give high level of confidence in calculations of the gas conductance of the pipes of any cross section, curvature, and length. It is also relatively easy to calculate the electric field within the type of collision cell described in this disclosure. Therefore, optimisation of length and cross section of the disclosed CRC would be a well-defined task for 20 a person skilled in the art. Preferably, no diaphragms would be involved at the end sections. However, if it would be found that the gas conductance of the curved sections is not sufficiently low, it would be possible to aid the gas limiting effect with a diaphragm. In this case, the detrimental effect of the fringe field 25 of the diaphragm should preferably be balanced out by other benefits of the invention, e.g., by speeding up the ions’ travel time through the CRC. More generally, the first aspect provides a collision I reaction cell, CRC, for a mass spectrometer, comprising: 30 a set of multipole RF ion guides, including a first multipole RF ion guide, a second multipole RF ion guide and a third multipole RF ion guide, disposed serially; wherein the first multipole RF ion guide comprises and / or is a curved multipole RF ion guide, for transferring the ions downstream towards the second multipole RF ion guide, wherein a first central angle of the first multipole RF ion guide is in a range from 45° to 135°, wherein the first 35 multipole RF ion guide is enclosed radially by a first enclosure; wherein the second multipole RF ion guide is enclosed radially by a second enclosure having a set of gas inlets, including a first gas inlet, therethrough, for example for processing (such as fragmentation, thermalizing and / or reaction) of ions therein using a gas introduced therein via the set of gas inlets; 24 04 25 wherein the second multipole RF ion guide comprises and / or is a linear multipole RF ion guide configured to accelerate the ions and / or the processed ions axially therealong from the first multipole RF ion guide towards the third multipole RF ion guide; and wherein the third multipole RF ion guide comprises and / or is a curved multipole RF ion guide, 5 for transferring the processed ions downstream away from the second multipole RF ion guide, wherein a third central angle of the third multipole RF ion guide is in a range from 45° to 135°, wherein the third multipole RF ion guide is enclosed radially by a third enclosure; wherein the first multipole RF ion guide and the second multipole RF ion guide are mutually adjacent; and 10 wherein the second multipole RF ion guide and the third multipole RF ion guide are mutually adjacent. That is, the CRC according to the first aspect is not limited to CID, for example, but may be used for ion processing including fragmentation, thermalizing and / or reaction, for example, inter alia 15 depending on the gas. Mass spectrometer The collision / reaction cell, CRC, is for a mass spectrometer, for example as described with 20 respect to the second aspect. Set of multipole RF ion guides The CRC comprises the set of multipole RF ion guides, including the first multipole RF ion guide, 25 the second multipole RF ion guide and the third multipole RF ion guide. In one example, the set of multipole RF ion guides includes N multipole RF ion guides, including the first multipole RF ion guide, the second multipole RF ion guide and the third multipole RF ion guide, wherein N is a natural number greater than or equal to 3, for example 3, 4, 5, 6, 7, 8, 9, 10 or more. In one example, the set of multipole RF ion guides includes exactly 3 multipole RF ion guides, including 30 the first multipole RF ion guide, the second multipole RF ion guide and the third multipole RF ion guide. The set of multipole RF ion guides, including the first multipole RF ion guide, the second multipole RF ion guide and the third multipole RF ion guide, is disposed serially (i.e. in series, 35 successively, in tandem). That is, ions move through the CRC via the first multipole RF ion guide, the second multipole RF ion guide and the third multipole RF ion guide, in turn. In other words, the second multipole RF ion guide is downstream of the first multipole RF ion guide and the third multipole RF ion guide is downstream of the second multipole RF ion guide. It should be understood that the first multipole RF ion guide and the second multipole RF ion guide are 24 04 25 mutually adjacent (i.e. the exit end of the first multipole RF ion guide and the entrance end of the second multipole RF ion guide are mutually adjacent), for example directly mutually adjacent such as mutually confronting, spaced apart by a gap and / or without any electrode or aperture therebetween. It should be understood that the second multipole RF ion guide and the third 5 multipole RF ion guide are mutually adjacent (i.e. the exit end of the second multipole RF ion guide and the entrance end of the third multipole RF ion guide are mutually adjacent), for example directly mutually adjacent such as mutually confronting, spaced apart by a gap and / or without any electrode or aperture therebetween. 10 First multipole RF ion guide The first multipole RF ion guide comprises and / or is a curved multipole RF ion guide, for transferring the ions downstream, for example from a first analytical quadrupole, towards the second multipole RF ion guide. Curved multipole RF ion guides are known. In one example, a 15 radius of curvature of the curved multipole RF ion guide of the first multipole RF ion guide is constant (i.e. the first multipole RF ion guide comprises and / or is a curved multipole RF ion guide having a constant radius of curvature i.e. arcuate, a circular arc. A constant radius of curvature may be preferred, to improve transmission of ions and / or to reduce manufacturing complexity. 20 In one example, the first multipole RF ion guide is configured, for example using an enclosure, due to the inscribed radius and / or using an aperture plate, to attenuate conductance of the gas upstream of the second multipole RF ion guide. In this way, flow of gas from the second enclosure via the first multipole RF ion guide, for example towards an analytical quadrupole such as Q1, is reduced, thereby improving performance of the analytical quadrupole such as Q1. 25 In one example, the first multipole RF ion guide is enclosed radially by a first enclosure configured to attenuate conductance of the gas upstream of the second multipole RF ion guide. In one example, the first multipole RF ion guide is enclosed radially by a first enclosure, for example provided at least in part by spacers (also known as inserts) disposed between rods 30 thereof and / or provided by a tube or pipe surrounding the rods thereof. In one example, a first inscribed radius of the first multipole RF ion guide is less than a second inscribed radius of the second multipole RF ion guide. That is, the second inscribed radius of the second multipole RF ion guide is greater than the first inscribed radius of the first multipole 35 RF ion guide. In this way, conductance of gas from the second enclosure via the first multipole RF ion guide is reduced while processing of ions in the second multipole RF ion guide is improved. In one example, a third inscribed radius of the third multipole RF ion guide is less than the second inscribed radius of the second multipole RF ion guide. In this way, conductance of 24 04 25 gas from the second enclosure via the third multipole RF ion guide is reduced while processing of ions in the second multipole RF ion guide is improved. The inscribed radii are typically defined by the size of the instrument, for example a mass 5 spectrometer, as well as by the how much the gas conductance is to be limited. Gas conductance of a pipe in molecular regime is defined by dA3 / L, where d is the diameter of the pipe, and L is its length. For a typical pump of 125 - 260 l / s pumping speed, an 8 mm inscribed diameter 50 mm long pipe would give a >100 times pressure drop between the second multipole RF ion guide and the exit / entrance of the CRCforthe air. In one example, the inscribed diameter 10 (i.e. twice the inscribed radius) of the first multipole RF ion guide and / or the third multipole RF ion guide is in a range from 6 mm to 12 mm or in a range from 0.25 inches to 0.5 inches, preferably in a range from 8 mm to 10 mm or in a range from 0.3 inches to 0.4 inches. In one example, the CRC excludes a first diaphragm disposed proximal an entrance end of the 15 first multipole RF ion guide. In one example, the CRC excludes a third diaphragm disposed proximal an exit end of the third multipole RF ion guide. In other words, in one example, the CRC does not include a diaphragm disposed proximal an entrance end of the first multipole RF ion guide and / or diaphragm disposed proximal an exit end of the third multipole RF ion guide. In this way, scattering of the ions in the fringe field between an analytical quadrupole and the 20 diaphragm(s) is reduced, thereby improving the throughput of the ions. In one example, the first multipole RF ion guide is configured to collisionally cool the ions using the gas conducted therein from the second multipole RF ion guide. In this way, a speed of the ions is reduced before the ions enter the second multipole RF ion guide whereby processing, for 25 example fragmentation, thermalizing and / or reaction, of the ions is improved since the ions will undergo more collisions with the gas introduced into the second multipole RF ion guide. In one example, a first pressure of the gas proximal an entrance end of the first multipole RF ion guide is a factor in a range from 10 to 1,000, preferably in a range from 25 to 750, more 30 preferably in a range from 50 to 500, most preferably in a range from 75 to 250 lower than a second pressure of the gas in the second multipole RF ion guide. In this way, flow of gas from the second enclosure via the first multipole RF ion guide, for example towards an analytical quadrupole such as Q1, is reduced, thereby improving performance of the analytical quadrupole such as Q1. 35 In one example, a first central angle of the first multipole RF ion guide is in a range from 45° to 135°, preferably in a range from 60° to 120°, more preferably in a range from 75° to 105°, most preferably in a range from 82.5° to 97.5°, for example 90°. That is, the first multipole RF ion guide preferably is in the form of a minor arc (i.e. less than 180°). In one example, a first central 24 04 25 angle of the curved multipole RF ion guide of the first multipole RF ion guide is in a range from 45° to 135°, preferably in a range from 60° to 120°, more preferably in a range from 75° to 105°, most preferably in a range from 82.5° to 97.5°, for example 90°. That is, the curved multipole RF ion guide of the first multipole RF ion guide preferably is in the form of a minor arc (i.e. less than 5 180°). In this way, a footprint of the mass spectrometer may be reduced compared with a conventional linear CRC, for example. In one example, a first ratio of a first arc length of the first multipole RF ion guide to a first radius of the first multipole RF ion guide is in a range from 2 : 1 to 1 : 2, preferably in a range from 3 : 10 2 to 2 : 3, for example about 1 :1 or 1 :1. That is, the length and radius of the first multipole RF ion guide are about equal (in a range from 2 : 1 to 1 : 2). In one example, a first ratio of a first arc length of the curved multipole RF ion guide of the first multipole RF ion guide to a first radius of the curved multipole RF ion guide of the first multipole RF ion guide is in a range from 2 :1 to 1 : 2, preferably in a range from 3 : 2 to 2 : 3, for example about 1 :1 or 1 : 1. That is, the length 15 and radius of the curved multipole RF ion guide of the first multipole RF ion guide are about equal (in a range from 2 : 1 to 1 : 2). In one example, the first multipole RF ion guide comprises and / or is a quadrupole, a hexapole, an octapole, a decapole or a dodecapole, preferably a quadrupole. In one example, the first 20 multipole RF ion guide comprises round rods, hyperbolic rods or planar rods, for example rectangular rods or square rods. In one example, the curved multipole RF ion guide of the first multipole RF ion guide comprises and / or is a quadrupole, a hexapole, an octapole, a decapole or a dodecapole, preferably a quadrupole. In one example, the curved multipole RF ion guide of the first multipole RF ion guide comprises round rods, hyperbolic rods or planar rods, for example 25 rectangular rods or square rods. In one example, the planar rods are chamfered (also known as bevelled, for example at an angle of 45°) (i.e. the first inscribed radius of the first multipole RF ion guide is defined by the chamfers of the planar rods). In this way, the electrical field in the first multipole RF ion guide is relatively more uniform compared with a square edge). In one example, outer edges of the planar rods are radiused. In this way, local external electrical fields are 30 attenuated. In one example, the first multipole RF ion guide comprises one or more electrodes for accelerating or decelerating the ions axially therethrough, for example as described herein. 35 Third multipole RF ion guide The third multipole RF ion guide may be as described with respect to the first multipole RF ion guide mutatis mutandis. 24 04 25 The third multipole RF ion guide comprises and / or is a curved multipole RF ion guide, for transferring the CID ions downstream away from the second multipole RF ion guide, for example to a second analytical quadruple or a time of flight mass analyser. Curved multipole RF ion guides are known. In one example, a radius of curvature of the curved multipole RF ion guide of 5 the second multipole RF ion guide is constant (i.e. the second multipole RF ion guide comprises and / or is a curved multipole RF ion guide having a constant radius of curvature i.e. arcuate, a circular arc, for example as described with respect to the first multipole RF ion guide mutatis mutandis. 10 In one example, the first multipole RF ion guide and the third multipole RF ion guide are similar (for example, structurally and / or functionally), interchangeable and / or identical. In one example, the third multipole RF ion guide is configured to attenuate conductance of the gas downstream of the second multipole RF ion guide, for example as described with respect to 15 the first multipole RF ion guide mutatis mutandis. In one example, the third multipole RF ion guide is enclosed radially by a third enclosure, for example provided at least in part by spacers disposed between rods thereof, for example as described with respect to the first multipole RF ion guide mutatis mutandis. 20 In one example, the third multipole RF ion guide is configured to collisionally cool the CID ions using the gas conducted therein from second multipole RF ion guide, for example as described with respect to the first multipole RF ion guide mutatis mutandis. 25 In one example, a third pressure of the gas proximal an exit end of the third multipole RF ion guide is a factor in a range from 10 to 1,000 lower than the second pressure of the gas in the second multipole RF ion guide, for example as described with respect to the first multipole RF ion guide mutatis mutandis. 30 In one example, a third central angle of the third multipole RF ion guide is in a range from 45° to 135°, preferably in a range from 60° to 120°, more preferably in a range from 75° to 105°, most preferably in a range from 82.5° to 97.5°, for example 90°, for example as described with respect to the first multipole RF ion guide mutatis mutandis. 35 In one example, a third ratio of a third arc length of the third multipole RF ion guide to a third radius of the third multipole RF ion guide is in a range from 2 :1 to 1 : 2, preferably in a range from 3 : 2 to 2 : 3, for example about 1 :1 or 1 :1, for example as described with respect to the first multipole RF ion guide mutatis mutandis. 24 04 25 In one example, the third multipole RF ion guide comprises and / or is a quadrupole, a hexapole, an octapole, a decapole or a dodecapole, preferably a quadrupole, wherein the third multipole RF ion guide comprises round rods, hyperbolic rods or planar rods, for example rectangular rods or square rods, for example as described with respect to the first multipole RF ion guide mutatis 5 mutandis. In one example, the third multipole RF ion guide comprises one or more electrodes for accelerating or decelerating the ions axially therethrough, for example as described with respect to the first multipole RF ion guide mutatis mutandis. 10 Second multipole RF ion guide The second multipole RF ion guide is enclosed radially by the second enclosure having the set of gas inlets, including the first gas inlet, therethrough, for collision-induced dissociation, CID, of 15 ions therein using the gas introduced therein via the set of gas inlets. That is, the second enclosure (for example, a tube or a pipe) contains the gas radially therewithin, notwithstanding flow of gas via the entrance and exit ends of the second multipole RF ion guide, for example. In one example, the gas comprises and / or is a collisional gas such as He, N2 and / or Ar and / or a reactive gas such as H2, NH4, CH4 and / or O2 and / or a mixture thereof. In one example, the set 20 of gas inlets includes M gas inlets, including the first gas inlet, wherein M is a natural number greater than or equal to 1, for example 1,2, 3, 4, 5, 6, 7, 8, 9,10 or more. In this way, different gases may be introduced individually and / or as a mixture thereof via the respect gas inlets of the set thereof. In this way, processing (such as fragmentation, thermalizing and / or reaction) of the ions may be selectively performed using different gases. 25 It should be understood that the second enclosure radially surrounds the second multipole RF ion guide. For example, the second enclosure may comprise or be a pipe or cylinder having open ends or respective apertures in ends thereof, providing an entrance and an exit for the ions. It should be understood that the CRC is arranged in a vacuum chamber of a mass 30 spectrometer, maintained at a sufficiently low pressure by a vacuum pump, for example a turbomolecular pump. Since the vacuum chamber is pumped continuously by the vacuum pump and since the second enclosure has open ends or apertures, gas is typically introduced into the enclosure via the set of gas inlets continuously during mass spectrometry at a flow rate sufficient to provide a sufficiently high pressure of the gas in the second enclosure for collision and / or 35 reaction with the ions while the gas is continuously pumped out of the enclosure via the open ends or apertures by the vacuum pump. The set of gas inlets may include a plurality of gas inlets, optionally together with respective mass flow controllers, thereby providing selection of different gases and / or gas mixtures in the enclosure. By mutually spacing apart the first gas inlet and a second gas inlet, for example relatively more proximal the entrance and the exit 24 04 25 respectively of the second enclosure, different gases may be introduced relatively more proximal the entrance and the exit respectively, for example to thermalise the ions and then react with the thermalised ions respectively or vice versa. 5 The second multipole RF ion guide comprises and / or is a linear multipole RF ion guide configured to accelerate the ions and / or the CID ions axially therealong from the first multipole RF ion guide towards the third multipole RF ion guide. Linear multipole RF ion guides are known. In one example, a second ratio of a second length of the second multipole RF ion guide to a first 10 arc length of the first multipole RF ion guide is in a range from 1 : 5 to 1 :1, preferably in a range from 1 : 4 to 2 : 3, for example about 1 :2 or 1 :2. That is, the central section is relatively shorter than the entrance section. In this way, processing of the ions in the central section is improved while conductance of gas from the central section via the entrance section is reduced. In one example, the second ratio of the second length of the second multipole RF ion guide to a third 15 arc length of the third multipole RF ion guide is in a range from 1 : 5 to 1 : 1, preferably in a range from 1 : 4 to 2 : 3, for example about 1 : 2 or 1 : 2. That is, the central section is relatively shorter than the exit section. In this way, processing of the ions in the central section is improved while conductance of gas from the central section via the exit section is reduced. In one example, a second ratio of a second length of the linear multipole RF ion guide of the second multipole RF 20 ion guide to a first arc length of the curved multipole RF ion guide of the first multipole RF ion guide is in a range from 1 : 5 to 1 :1, preferably in a range from 1 : 4 to 2 : 3, for example about 1 : 2 or 1 : 2. That is, the central section is relatively shorter than the entrance section. In this way, processing of the ions in the central section is improved while conductance of gas from the central section via the entrance section is reduced. In one example, the second ratio of the 25 second length of the linear multipole RF ion guide of the second multipole RF ion guide to a third arc length of the linear multipole RF ion guide of the third multipole RF ion guide is in a range from 1 : 5 to 1 :1, preferably in a range from 1 : 4 to 2 : 3, for example about 1 : 2 or 1 : 2. That is, the central section is relatively shorter than the exit section. In this way, processing of the ions in the central section is improved while conductance of gas from the central section via the 30 exit section is reduced. In one example, a second length of the second multipole RF ion guide is in a range from 5 mm to 100 mm, preferably in a range from 10 mm to 75 mm, more preferably in a range from 20 mm to 50 mm. In this way, processing of the ions in the central section is improved, optimising 35 sensitivity and speed. In one example, a second length of the linear multipole RF ion guide of the second multipole RF ion guide is in a range from 5 mm to 100 mm, preferably in a range from 10 mm to 75 mm, more preferably in a range from 20 mm to 50 mm. 24 04 25 In one example, a first arc length (i.e. an arc length along the ion optical axis) of the first multipole RF ion guide is in a range from 25 mm to 500 mm, preferably in a range from 50 mm to 375 mm, more preferably in a range from 100 mm to 250 mm. In this way, conductance of gas from the central section via the entrance section is reduced. In one example, a first arc length of the 5 curved multipole RF ion guide of the first multipole RF ion guide is in a range from 25 mm to 500 mm, preferably in a range from 50 mm to 75 mm, more preferably in a range from 100 mm to 250 mm. In one example, a third arc length of the third multipole RF ion guide is in a range from 25 mm 10 to 500 mm, preferably in a range from 50 mm to 375 mm, more preferably in a range from 100 mm to 250 mm. In this way, conductance of gas from the central section via the entrance section is reduced. In one example, a third arc length of the curved multipole RF ion guide of the third multipole RF ion guide is in a range from 25 mm to 500 mm, preferably in a range from 50 mm to 75 mm, more preferably in a range from 100 mm to 250 mm. 15 In one example, the second multipole RF ion guide comprises and / or is a quadrupole, a hexapole, an octapole, a decapole or a dodecapole (i.e. a multipole of order 2, 3, 4, 5 or 6 respectively), preferably a quadrupole. In one example, the linear RF multipole of the second multipole RF ion guide comprises and / or is a quadrupole, a hexapole, an octapole, a decapole 20 or a dodecapole (i.e. a multipole of order 2, 3, 4, 5 or 6 respectively), preferably a quadrupole. In one example, the linear RF multipole of the second multipole RF ion guide comprises round rods or hyperbolic rods. In one example, the second multipole RF ion guide comprises one or more electrodes for accelerating or decelerating the ions axially therethrough. 25 Mass spectrometer A second aspect provides a mass spectrometer, preferably a tandem quadrupole mass spectrometer, comprising a CRC according to the first aspect, for example wherein the CRC is disposed between quadrupole mass analysers of the tandem quadrupole mass spectrometer. 30 Method The third aspect provides a method of collision-induced dissociation, CID, of ions comprising: transferring the ions downstream along a first curved path of a first multipole RF ion guide 35 included in a set of multipole RF ion guides, disposed serially, wherein the first multipole RF ion guide comprises and / or is a curved multipole RF ion guide, towards a second multipole RF ion guide included in the set of multipole RF ion guides, wherein a first central angle of the first multipole RF ion guide is in a range from 45° to 135°, wherein the first multipole RF ion guide is enclosed radially by a first enclosure; 24 04 25 inducing CID of the ions transferred to the second multipole RF ion guide from the first multipole RF ion guide using a gas introduced therein, wherein the second multipole RF ion guide comprises and / or is a linear multipole RF ion guide and wherein the second multipole RF ion guide is enclosed radially by a second enclosure, and accelerating the ions and / or the CID ions 5 axially along a second linear path from the first multipole RF ion guide towards a third multipole RF ion guide included in the set of multipole RF ion guides; and transferring the accelerated ions and / or the accelerated CID ions downstream along a third curved path of the third multipole RF ion guide, wherein the third multipole RF ion guide comprises and / or is a curved multipole RF ion guide, away from the second multipole RF ion 10 guide, wherein a third central angle of the third multipole RF ion guide is in a range from 45° to 135°, wherein the third multipole RF ion guide is enclosed radially by a third enclosure; wherein the first multipole RF ion guide and the second multipole RF ion guide are mutually adjacent; and wherein the second multipole RF ion guide and the third multipole RF ion guide are mutually 15 adjacent. Definitions Throughout this specification, the term “comprising” or “comprises” means including the 20 components) specified but not to the exclusion of the presence of other components. The term “consisting essentially of’ or “consists essentially of’ means including the components specified but excluding other components except for materials present as impurities, unavoidable materials present as a result of processes used to provide the components, and components added for a purpose other than achieving the technical effect of the invention, such as 25 colourants, and the like. The term “consisting of’ or “consists of’ means including the components specified but excluding other components. 30 Whenever appropriate, depending upon the context, the use of the term “comprises” or “comprising” may also be taken to include the meaning “consists essentially of’ or “consisting essentially of’, and also may also be taken to include the meaning “consists of’ or “consisting of’. 35 The optional features set out herein may be used either individually or in combination with each other where appropriate and particularly in the combinations as set out in the accompanying claims. The optional features for each aspect or exemplary embodiment of the invention, as set out herein are also applicable to all other aspects or exemplary embodiments of the invention, where appropriate. In other words, the skilled person reading this specification should consider 24 04 25 the optional features for each aspect or exemplary embodiment of the invention as interchangeable and combinable between different aspects and exemplary embodiments. Brief description of the drawings 5 For a better understanding of the invention, and to show how exemplary embodiments of the same may be brought into effect, reference will be made, by way of example only, to the accompanying diagrammatic Figures, in which: 10 Figure 1 schematically depicts a conventional triple quadrupole mass spectrometer; Figure 2 schematically depicts a conventional triple quadrupole mass spectrometer; Figure 3 shows results of a simulation for trajectories of ions accelerated into a curved CRC; 15 Figure 4 schematically depicts a conventional triple quadrupole mass spectrometer; Figure 5 schematically depicts gas pressure in a CRC according to an exemplary embodiment; 20 Figure 6 schematically depicts cross sectional shapes of electrodes for a CRC according to an exemplary embodiment; Figure 7 schematically depicts inserts between electrodes for a CRC according to an exemplary embodiment; 25 Figure 8 schematically depicts a CRC according to an exemplary embodiment; Figure 9 schematically depicts a CRC according to an exemplary embodiment; and 30 Figure 10 schematically depicts a method according to an exemplary embodiment. Detailed Description of the Drawings Generally, like reference signs indicate like features. 35 Figure 5 schematically depicts gas pressure in a CRC 53 according to an exemplary embodiment. The collision / reaction cell, CRC, 53 is for a mass spectrometer, the CRC 53 comprising: 24 04 25 a set of multipole RF ion guides, including a first multipole RF ion guide 531 (referred to herein also as an entrance section), a second multipole RF ion guide 532 (referred to herein also as a central section) and a third multipole RF ion guide 533 (referred to also herein as an exit section), disposed serially; 5 wherein the first multipole RF ion guide 531 comprises and / or is a curved multipole RF ion guide, for transferring the ions downstream towards the second multipole RF ion guide 532; wherein the second multipole RF ion guide 532 is enclosed radially by a second enclosure (not shown for clarity) having a set of gas inlets (not shown), including a first gas inlet (not shown), therethrough, for collision-induced dissociation, CID, of ions therein using a gas introduced 10 therein via the set of gas inlets; wherein the second multipole RF ion guide 532 comprises and / or is a linear multipole RF ion guide configured to accelerate the ions and / or the CID ions axially therealong from the first multipole RF ion guide 531 towards the third multipole RF ion guide 533; and wherein the third multipole RF ion guide 533 comprises and / or is a curved multipole RF ion 15 guide, for transferring the CID ions downstream away from the second multipole RF ion guide 532. In this way, a reduction in footprint of a mass spectrometer is enabled since the first multipole RF ion guide 531 and the third multipole RF ion guide 533 respectively comprise and / or are 20 curved multipole RF ion guides, for example having a total curvature of 180 degrees such as similarly to the conventional triple quadrupole mass spectrometer 2, including a curved CRC 53 23 having a curvature of 180 degrees, schematically depicted in Figure 2. However, the CRC 53 according to the first aspect comprises the second multipole RF ion guide 532 disposes serially between the first multipole RF ion guide 531 and the third multipole RF ion guide 533. 25 Since the second multipole RF ion guide 532 comprises and / or is a linear multipole RF ion guide configured to accelerate the ions and / or the CID ions axially therealong from the first multipole RF ion guide 531 towards the third multipole RF ion guide 533, ion losses during axial acceleration for the CID through the second multipole RF ion guide 532 are relatively reduced, compared with a curved multipole RF ion guide. In this way, sensitivity is relatively increased, 30 compared with conventional curved CRC 53s while complexity and / or cost may be relatively reduced, for example compared with using an axially-propelling electric field inside a conventional curved CRC 53. Firstly, the gas pressure in the CID region of a CRC 53 may be controlled to optimise the number 35 of collisions between the precursor ionsand the neutral gas molecules for CID. The gas pressure is typically about 1E-2 mbar (1E-3 kPa). The working pressure in the vacuum chamber of a conventional tandem quadrupole mass spectrometer is typically less than 1E-4 mbar (1E-5 kPa), i.e. at least a factor of 1E2 times lower. If the CID region of the CRC 53 were instead disposed adjacent to an analytical quadrupole, such as Q1 or Q2, the number of neutral gas molecules 24 04 25 coming from the CID region into the analytical quadrupole would negatively affect the throughput and / or resolution of the analytical quadrupole, for example due to the relatively increased gas pressure therein compared with the working pressure. In order to attenuate this increase in gas pressure, a diaphragm (also known as an orifice plate or an aperture plate), having a sufficiently 5 small orifice diameter, could be arranged between the CRC 53 and the analytical quadrupole. While such an arrangement would attenuate this increase in gas pressure, scattering of the ions in the fringe field between the analytical quadrupole and the diaphragm would nevertheless reduce the throughput of the ions. Hence, disposing the CID region of the CRC 53 adjacent to an analytical quadrupole is not preferred. In contrast, the CID region of the CRC 53 according 10 to the first aspect would not be disposed adjacent to an analytical quadrupole. Rather, the first multipole RF ion guide 531 and / or the third multipole RF ion guide 533 are instead arranged to be disposed adjacent to an analytical quadrupole. In this way, an increase the gas pressure in an analytical quadrupole is attenuated, for example minimised, while throughput of the ions is not reduced. 15 Secondly, the entrance and exit sections of the CRC 53 serve as gas reducing pipes, for the central section that is at a relatively higher gas pressure. For example, calculation of the gas pressure for an exemplary embodiment of the CRC 53, as schematically depicted in Figure 5, shows that pressure drop by a factor of at least 1E2 may be achieved between the central section 20 and the vicinities outside the distal ends of the entrance and exit sections of the CRC 53, for typical pumping rates of the pump (>120 l / s). In one example, the reduced gas conductance of the curved sections substitutes a use of gas-limiting diaphragms. Thirdly, the length of the central section of the CRC 53 may be varied within a relatively large 25 range. If the CID region of the CRC 53 were instead disposed adjacent to an analytical quadrupole, such as Q1 or Q2, increasing the length thereof (e.g. to accommodate the lower pressure in the CID region), a benefit of a relatively small footprint of the instrument diminishes. In contrast, for the CRC 53 according to the first aspect, the length of the straight section is unlikely to increase significantly due to the fact that the pressure inside this central section can 30 be sufficiently high providing the lowering of it within the curved end sections so that there is no resulting increase of the gas pressure in the chamber. Additionally and / or alternatively, a benefit of keeping the central section relatively short is a better control of the DC axial field, that allows fast removal of the ions from the most gas pressurised 35 region and prevents disadvantageous space charge effects. Moreover, challenging requirements of the market for dwell times of tandem quadrupole mass spectrometers as short as 0.5 ms require the time that the ions spend in the CRC 53 is limited to a range of 0.1 to 0.2 ms. Note, however, that the typical CID reaction times are in the range 0.1 to 1 ms which means that a fast-working CRC 53 may result in poorer CID yield. The CRC 53 according to the first 24 04 25 aspect benefits from a relatively short central section while also benefiting from the curved exit section. Once the ions have undergone collisions in the central section, they proceed into the curved exit section, where they have time to cool down (i.e. thermalise) and complete dissociation. 5 The control of the gas conductance within the curved end sections of the CRC 53 can be achieved by adjusting the cross section of the electrodes of the curved sections, e.g., like in Figure 6. Also, a plastic or ceramic inserts could be placed between the electrodes to reduce the cross section available fortravel of the gas particles, e.g., like in Figure 7. Care should be 10 taken not to put any insulating parts close to the ion beam to prevent the contamination and charging. Contemporary simulation means give high level of confidence in calculations of the gas conductance of the pipes of any cross section, curvature, and length. It is also relatively easy to 15 calculate the electric field within the type of collision cell described in this disclosure. Therefore, optimisation of length and cross section of the disclosed CRC 53 would be a well-defined task for a person skilled in the art. Preferably, no diaphragms would be involved at the end sections. However, if it would be found 20 that the gas conductance of the curved sections is not sufficiently low, it would be possible to aid the gas limiting effect with a diaphragm. In this case, the detrimental effect of the fringe field of the diaphragm should preferably be balanced out by other benefits of the invention, e.g., by speeding up the ions’ travel time through the CRC 53. 25 Figure 8 schematically depicts a CRC 83 according to an exemplary embodiment. The CRC 83 is generally as described with respect to the CRC 53, description of which is not repeated for brevity. 30 The collision / reaction cell, CRC, 83 is for a mass spectrometer, the CRC 83 comprising: a set of multipole RF ion guides, including a first multipole RF ion guide 831 (referred to herein also as an entrance section), a second multipole RF ion guide 832 (referred to herein also as a central section) and a third multipole RF ion guide 833 (referred to also herein as an exit section), disposed serially; 35 wherein the first multipole RF ion guide 831 comprises and / or is a curved multipole RF ion guide, for transferring the ions downstream towards the second multipole RF ion guide 832; wherein the second multipole RF ion guide 832 is enclosed radially by a second enclosure (not shown for clarity) having a set of gas inlets (not shown), including a first gas inlet (not shown), 24 04 25 therethrough, for collision-induced dissociation, CID, of ions therein using a gas introduced therein via the set of gas inlets; wherein the second multipole RF ion guide 832 comprises and / or is a linear multipole RF ion guide configured to accelerate the ions and / or the CID ions axially therealong from the first 5 multipole RF ion guide 831 towards the third multipole RF ion guide 833; and wherein the third multipole RF ion guide 833 comprises and / or is a curved multipole RF ion guide, for transferring the CID ions downstream away from the second multipole RF ion guide 832. 10 The collision / reaction cell, CRC 83, is for a mass spectrometer, for example as described with respect to the second aspect. In this example, the set of multipole RF ion guides includes exactly 3 multipole RF ion guides, including the first multipole RF ion guide 831, the second multipole RF ion guide 832 and the 15 third multipole RF ion guide 833. In this example, a radius of curvature of the curved multipole RF ion guide of the first multipole RF ion guide 831 is constant (i.e. the first multipole RF ion guide 831 comprises and / or is a curved multipole RF ion guide having a constant radius of curvature i.e. arcuate, a circular arc. 20 In this example, the first multipole RF ion guide 831 is configured, for example using an enclosure, due to the inscribed radius and / or using an aperture plate, to attenuate conductance of the gas upstream of the second multipole RF ion guide 832. 25 In this example, the first multipole RF ion guide 831 is enclosed radially by a first enclosure configured to attenuate conductance of the gas upstream of the second multipole RF ion guide 832. In this example, the first multipole RF ion guide 831 is enclosed radially by a first enclosure, for example provided at least in part by spacers disposed between rods thereof and / or provided by a tube or pipe surrounding the rods thereof. 30 In this example, a first inscribed radius of the first multipole RF ion guide 831 is less than a second inscribed radius of the second multipole RF ion guide 832. In this example, a third inscribed radius of the third multipole RF ion guide 833 is less than the second inscribed radius of the second multipole RF ion guide 832. 35 In this example, the inscribed diameter (i.e. twice the inscribed radius) of the first multipole RF ion guide 831 and / or the third multipole RF ion guide 833 is in a range from 6 mm to 12 mm or in a range from 0.25 inches to 0.5 inches, preferably in a range from 8 mm to 10 mm or in a range from 0.3 inches to 0.4 inches. 24 04 25 In this example, the CRC 83 excludes a first diaphragm disposed proximal an entrance end of the first multipole RF ion guide 831. In this example, the CRC 83 excludes a third diaphragm disposed proximal an exit end of the third multipole RF ion guide 833. 5 In this example, the first multipole RF ion guide 831 is configured to collisionally cool the ions using the gas conducted therein from the second multipole RF ion guide 832. In this example, a first pressure of the gas proximal an entrance end of the first multipole RF ion 10 guide 831 is a factor in a range from 10 to 1,000, preferably in a range from 25 to 750, more preferably in a range from 50 to 500, most preferably in a range from 75 to 250 lower than a second pressure of the gas in the second multipole RF ion guide 832. In this example, a first central angle of the first multipole RF ion guide 831 is 90°. 15 In this example, a first ratio of a first arc length of the first multipole RF ion guide 831 to a first radius of the first multipole RF ion guide 831 is in a range from 2 :1 to 1 : 2, preferably in a range from 3 : 2 to 2 : 3, for example about 1 :1 or 1 :1. In this example, a first ratio of a first arc length of the curved multipole RF ion guide of the first multipole RF ion guide 831 to a first radius of the 20 curved multipole RF ion guide of the first multipole RF ion guide 831 is in a range from 2 :1 to 1 : 2, preferably in a range from 3 : 2 to 2 : 3, for example about 1 :1 or 1 : 1. In this example, the first multipole RF ion guide 831 is a quadrupole. In this example, the first multipole RF ion guide 831 comprises rectangular rods. 25 In this example, the first multipole RF ion guide 831 comprises one or more electrodes for accelerating or decelerating the ions axially therethrough, for example as described herein. The third multipole RF ion guide 833 is as described with respect to the first multipole RF ion 30 guide 831 mutatis mutandis. In this example, a radius of curvature of the curved multipole RF ion guide of the second multipole RF ion guide 832 is constant (i.e. the second multipole RF ion guide 832 comprises and / or is a curved multipole RF ion guide having a constant radius of curvature i.e. arcuate, a 35 circular arc, for example as described with respect to the first multipole RF ion guide 831 mutatis mutandis. In this example, the first multipole RF ion guide 831 and the third multipole RF ion guide 833 are similar (for example, structurally and / or functionally), interchangeable and / or identical. 24 04 25 In this example, the third multipole RF ion guide 833 is configured to attenuate conductance of the gas downstream of the second multipole RF ion guide 832, for example as described with respect to the first multipole RF ion guide 831 mutatis mutandis. 5 In this example, the third multipole RF ion guide 833 is enclosed radially by a third enclosure, for example provided at least in part by spacers disposed between rods thereof, for example as described with respect to the first multipole RF ion guide 831 mutatis mutandis. 10 In this example, the third multipole RF ion guide 833 is configured to collisionally cool the CID ions using the gas conducted therein from second multipole RF ion guide 832, for example as described with respect to the first multipole RF ion guide 831 mutatis mutandis. In this example, a third pressure of the gas proximal an exit end of the third multipole RF ion 15 guide 833 is a factor in a range from 10 to 1,000 lower than the second pressure of the gas in the second multipole RF ion guide 832, for example as described with respect to the first multipole RF ion guide 831 mutatis mutandis. In this example, a third central angle of the third multipole RF ion guide 833 is 90°, for example 20 as described with respect to the first multipole RF ion guide 831 mutatis mutandis. In this example, a third ratio of a third arc length of the third multipole RF ion guide 833 to a third radius of the third multipole RF ion guide 833 is in a range from 2 : 1 to 1 : 2, preferably in a range from 3 : 2 to 2 : 3, for example about 1 :1 or 1 :1, for example as described with respect 25 to the first multipole RF ion guide 831 mutatis mutandis. In this example, the third multipole RF ion guide 833 is a quadrupole, wherein the third multipole RF ion guide 833 comprises rectangular rods, for example as described with respect to the first multipole RF ion guide 831 mutatis mutandis. 30 In this example, the third multipole RF ion guide 833 comprises one or more electrodes for accelerating or decelerating the ions axially therethrough, for example as described with respect to the first multipole RF ion guide 831 mutatis mutandis. 35 The second multipole RF ion guide 832 is enclosed radially by the second enclosure having the set of gas inlets, including the first gas inlet, therethrough, for collision-induced dissociation, CID, of ions therein using the gas introduced therein via the set of gas inlets. In this example, the gas comprises and / or is a collisional gas such as He, N2 and / or Ar and / or a reactive gas such as H2, NH4, CH4 and / or O2 and / or a mixture thereof. 24 04 25 In this example, a second ratio of a second length of the second multipole RF ion guide 832 to a first arc length of the first multipole RF ion guide 831 is in a range from 1 : 5 to 1 :1, preferably in a range from 1 : 4 to 2 : 3, for example about 1 : 2 or 1 : 2. In this example, the second ratio 5 of the second length of the second multipole RF ion guide 832 to a third arc length of the third multipole RF ion guide 833 is in a range from 1 : 5 to 1 :1, preferably in a range from 1 : 4 to 2 : 3, for example about 1 : 2 or 1 : 2. In this example, a second ratio of a second length of the linear multipole RF ion guide of the second multipole RF ion guide 832 to a first arc length of the curved multipole RF ion guide of the first multipole RF ion guide 831 is in a range from 1 : 5 to 1 10 :1, preferably in a range from 1 : 4 to 2 : 3, for example about 1 : 2 or 1 : 2. In this example, the second ratio of the second length of the linear multipole RF ion guide of the second multipole RF ion guide 832 to a third arc length of the linear multipole RF ion guide of the third multipole RF ion guide 833 is in a range from 1 : 5 to 1 :1, preferably in a range from 1 : 4 to 2 : 3, for example about 1 : 2 or 1 :2. 15 In this example, a second length of the second multipole RF ion guide 832 is in a range from 5 mm to 100 mm, preferably in a range from 10 mm to 75 mm, more preferably in a range from 20 mm to 50 mm. In this example, a second length of the linear multipole RF ion guide of the second multipole RF ion guide 832 is in a range from 5 mm to 100 mm, preferably in a range from 10 20 mm to 75 mm, more preferably in a range from 20 mm to 50 mm. In this example, a first arc length (i.e. an arc length along the ion optical axis) ofthe first multipole RF ion guide 831 is in a range from 25 mm to 500 mm, preferably in a range from 50 mm to 375 mm, more preferably in a range from 100 mm to 250 mm. In this example, a first arc length of 25 the curved multipole RF ion guide ofthe first multipole RF ion guide 831 is in a range from 25 mm to 500 mm, preferably in a range from 50 mm to 75 mm, more preferably in a range from 100 mm to 250 mm. In this example, a third arc length ofthe third multipole RF ion guide 833 is in a range from 25 30 mm to 500 mm, preferably in a range from 50 mm to 375 mm, more preferably in a range from 100 mm to 250 mm. In this example, a third arc length ofthe curved multipole RF ion guide of the third multipole RF ion guide 833 is in a range from 25 mm to 500 mm, preferably in a range from 50 mm to 75 mm, more preferably in a range from 100 mm to 250 mm. 35 In this example, the second multipole RF ion guide 832 is a quadrupole. In this example, the linear RF multipole ofthe second multipole RF ion guide 832 is a quadrupole. In this example, the linear RF multipole ofthe second multipole RF ion guide 832 comprises round rods. Figure 9 schematically depicts a CRC 93 according to an exemplary embodiment. 24 04 25 The CRC 93 is generally as described with respect to the CRC 83, description of which is not repeated for brevity. 5 The collision / reaction cell, CRC, 93 is for a mass spectrometer, the CRC 93 comprising: a set of multipole RF ion guides, including a first multipole RF ion guide 931 (referred to herein also as an entrance section), a second multipole RF ion guide 932 (referred to herein also as a central section) and a third multipole RF ion guide 933 (referred to also herein as an exit section), disposed serially; 10 wherein the first multipole RF ion guide 931 comprises and / or is a curved multipole RF ion guide, for transferring the ions downstream towards the second multipole RF ion guide 932; wherein the second multipole RF ion guide 932 is enclosed radially by a second enclosure (9321) having a set of gas inlets (9322), including a first gas inlet (9322A), therethrough, for collision-induced dissociation, CID, of ions therein using a gas introduced therein via the set of 15 gas inlets; wherein the second multipole RF ion guide 932 comprises and / or is a linear multipole RF ion guide configured to accelerate the ions and / or the CID ions axially therealong from the first multipole RF ion guide 931 towards the third multipole RF ion guide 933; and wherein the third multipole RF ion guide 933 comprises and / or is a curved multipole RF ion 20 guide, for transferring the CID ions downstream away from the second multipole RF ion guide 932. In this example, the first multipole RF ion guide 931 is a quadrupole. In this example, the first multipole RF ion guide 931 comprises chamfered rectangular rods. In this example, outer edges 25 of the chamfered rectangular rods are radiused. The third multipole RF ion guide 933 is as described with respect to the first multipole RF ion guide 931 mutatis mutandis. 30 In this example, the first multipole RF ion guide 931 is enclosed radially by a first enclosure, provided at least in part by spacers (also known as inserts) 9313A, 9313B, 9313C, 9313D disposed between rods thereof. In this example, the third multipole RF ion guide 933 is enclosed radially by a first enclosure, 35 provided at least in part by spacers (also known as inserts) 9333A, 9333B, 9333C, 9333D disposed between rods thereof. Figure 10 schematically depicts a method according to an exemplary embodiment. 24 04 25 The method is of collision-induced dissociation, CID, of ions comprising: transferring the ions downstream along a first curved path of a first multipole RF ion guide included in a set of multipole RF ion guides, disposed serially, wherein the first multipole RF ion guide comprises and / or is a curved multipole RF ion guide, towards a second multipole RF ion 5 guide included in the set of multipole RF ion guides (S1001); inducing CID of the ions transferred to the second multipole RF ion guide from the first multipole RF ion guide using a gas introduced therein, wherein the second multipole RF ion guide comprises and / or is a linear multipole RF ion guide and wherein the second multipole RF ion guide is enclosed radially by a second enclosure, and accelerating the ions and / or the CID ions 10 axially along a second linear path from the first multipole RF ion guide towards a third multipole RF ion guide included in the set of multipole RF ion guides (S1002); and transferring the accelerated ions and / or the accelerated CID ions downstream along a third curved path of the third multipole RF ion guide, wherein the third multipole RF ion guide comprises and / or is a curved multipole RF ion guide, away from the second multipole RF ion 15 guide (S1003). Although a preferred embodiment has been shown and described, it will be appreciated by those skilled in the art that various changes and modifications might be made without departing from 20 the scope of the invention, as defined in the appended claims and as described above. At least some of the example embodiments described herein may be constructed, partially or wholly, using dedicated special-purpose hardware. Terms such as ‘component’, ‘module’ or‘unit’ used herein may include, but are not limited to, a hardware device, such as circuitry in the form 25 of discrete or integrated components, a Field Programmable Gate Array (FPGA) or Application Specific Integrated Circuit (ASIC), which performs certain tasks or provides the associated functionality. In some embodiments, the described elements may be configured to reside on a tangible, persistent, addressable storage medium and may be configured to execute on one or more processors. These functional elements may in some embodiments include, by way of 30 example, components, such as software components, object-oriented software components, class components and task components, processes, functions, attributes, procedures, subroutines, segments of program code, drivers, firmware, microcode, circuitry, data, databases, data structures, tables, arrays, and variables. Although the example embodiments have been described with reference to the components, modules and units discussed herein, 35 such functional elements may be combined into fewer elements or separated into additional elements. Various combinations of optional features have been described herein, and it will be appreciated that described features may be combined in any suitable combination. In particular, the features of any one example embodiment may be combined with features of any other embodiment, as appropriate, except where such combinations are mutually exclusive. 24 04 25 Throughout this specification, the term “comprising” or “comprises” means including the components) specified but not to the exclusion of the presence of others. Attention is directed to all papers and documents which are filed concurrently with or previous 5 to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference. All of the features disclosed in this specification (including any accompanying claims, abstract 10 and drawings), and / or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and / or steps are mutually exclusive. Each feature disclosed in this specification (including any accompanying claims, abstract and 15 drawings) may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features. The invention is not restricted to the details of the foregoing embodiment(s). The invention 20 extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed. 24 04 25

Claims

1. A collision / reaction cell, CRC, for a mass spectrometer, comprising:a set of multipole RF ion guides, including a first multipole RF ion guide, a second multipole RF 5 ion guide and a third multipole RF ion guide, disposed serially;wherein the first multipole RF ion guide comprises and / or is a curved multipole RF ion guide, for transferring the ions downstream towards the second multipole RF ion guide, wherein a first central angle of the first multipole RF ion guide is in a range from 45° to 135°, wherein the first multipole RF ion guide is enclosed radially by a first enclosure;10 wherein the second multipole RF ion guide is enclosed radially by a second enclosure having a set of gas inlets, including a first gas inlet, therethrough, for collision-induced dissociation, CID, of ions therein using a gas introduced therein via the set of gas inlets;wherein the second multipole RF ion guide comprises and / or is a linear multipole RF ion guide configured to accelerate the ions and / or the CID ions axially therealong from the first multipole 15 RF ion guide towards the third multipole RF ion guide; andwherein the third multipole RF ion guide comprises and / or is a curved multipole RF ion guide, for transferring the CID ions downstream away from the second multipole RF ion guide, wherein a third central angle of the third multipole RF ion guide is in a range from 45° to 135°, wherein the third multipole RF ion guide is enclosed radially by a third enclosure;20 wherein the first multipole RF ion guide and the second multipole RF ion guide aremutually adjacent; andwherein the second multipole RF ion guide and the third multipole RF ion guide are mutually adjacent.25 2. The CRC according to any previous claim, wherein a first pressure of the gas proximal anentrance end of the first multipole RF ion guide is a factor in a range from 10 to 1,000 lower than a second pressure of the gas in the second multipole RF ion guide and / or wherein a third pressure of the gas proximal an exit end of the third multipole RF ion guide is a factor in a range from 10 to 1,000 lower than the second pressure of the gas in the second multipole RF ion guide.

303. The CRC according to any previous claim, wherein the first central angle of the first multipole RF ion guide is in a range from 60° to 120°.

4. The CRC according to claim 3, wherein the first central angle of the first multipole RF ion 35 guide is in a range from 75° to 105°.

5. The CRC according to claim 4, wherein the first central angle of the first multipole RF ion guide is in a range from 82.5° to 97.5°.24 04 256. The CRC according to claim 5, wherein the first central angle of the first multipole RF ion guide is 90°.

7. The CRC according to any previous claim, wherein the third central angle of the third multipole 5 RF ion guide is in a range from 60° to 120°.

8. The CRC according to claim 7, wherein the third central angle of the third multipole RF ion guide is in a range from 75° to 105°.10 9. The CRC according to claim 8, wherein the third central angle of the third multipole RF ionguide is in a range from 82.5° to 97.5°.

10. The CRC according to claim 9, wherein the third central angle of the third multipole RF ion guide is 90°.1511. The CRC according to any previous claim, wherein the second multipole RF ion guide comprises and / or is a quadrupole, a hexapole, an octapole, a decapole or a dodecapole, preferably a quadrupole, and / or wherein the second multipole RF ion guide comprises round rods or hyperbolic rods.2012. The CRC according to any previous claim, wherein the first multipole RF ion guide comprises and / or is a quadrupole, a hexapole, an octapole, a decapole or a dodecapole, preferably a quadrupole, wherein the first multipole RF ion guide comprises round rods, hyperbolic rods or planar rods, for example rectangular rods or square rod, wherein the third multipole RF ion guide 25 comprises and / or is a quadrupole, a hexapole, an octapole, a decapole or a dodecapole, preferably a quadrupole, wherein the third multipole RF ion guide comprises round rods, hyperbolic rods or planar rods, for example rectangular rods or square rods.

13. The CRC according to any previous claim, wherein the first enclosure is provided at least in 30 part by spacers disposed between rods thereof, and / or wherein the third enclosure is provided at least in part by spacers disposed between rods thereof.

14. The CRC according to any previous claim, wherein a first inscribed radius of the first multipole RF ion guide is less than a second inscribed radius of the second multipole RF ion 35 guide and / or wherein a third inscribed radius of the third multipole RF ion guide is less than the second inscribed radius of the second multipole RF ion guide.24 04 2515. The CRC according to any previous claim, excluding a first diaphragm disposed proximal an entrance end of the first multipole RF ion guide and / or excluding a third diaphragm disposed proximal an exit end of the third multipole RF ion guide.5 16. A mass spectrometer, preferably a tandem quadrupole mass spectrometer, comprising aCRC according to any of claims 1 to 15, for example wherein the CRC is disposed between quadrupole mass analysers of the tandem quadrupole mass spectrometer.

17. A method of collision-induced dissociation, CID, of ions comprising:10 transferring the ions downstream along a first curved path of a first multipole RF ion guide included in a set of multipole RF ion guides, disposed serially, wherein the first multipole RF ion guide comprises and / or is a curved multipole RF ion guide, towards a second multipole RF ion guide included in the set of multipole RF ion guides, wherein a first central angle of the first multipole RF ion guide is in a range from 45° to 135°, wherein the first multipole RF ion guide is 15 enclosed radially by a first enclosure;inducing CID of the ions transferred to the second multipole RF ion guide from the first multipole RF ion guide using a gas introduced therein, wherein the second multipole RF ion guide comprises and / or is a linear multipole RF ion guide and wherein the second multipole RF ion guide is enclosed radially by a second enclosure, and accelerating the ions and / or the CID ions 20 axially along a second linear path from the first multipole RF ion guide towards a third multipole RF ion guide included in the set of multipole RF ion guides; andtransferring the accelerated ions and / or the accelerated CID ions downstream along a third curved path of the third multipole RF ion guide, wherein the third multipole RF ion guide comprises and / or is a curved multipole RF ion guide, away from the second multipole RF ion 25 guide, wherein a third central angle of the third multipole RF ion guide is in a range from 45° to 135°, wherein the third multipole RF ion guide is enclosed radially by a third enclosure;wherein the first multipole RF ion guide and the second multipole RF ion guide are mutually adjacent; andwherein the second multipole RF ion guide and the third multipole RF ion guide are 30 mutually adjacent.

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