This application claims the benefit of Great Britain Patent Application No. GB 1020728.0 filed on Dec. 7, 2010.
The present application relates to a miniature mass spectrometer system and in particular, to a system that may be coupled to an atmospheric pressure ionisation source. Typically, electrospray ionisation and chemical ionisation are used to generate ions at atmospheric pressure. A sample for analysis is often presented as a solution of one or more analytes in a solvent. The invention more particularly relates to an advantageous system architecture that maximises the sensitivity achievable with small vacuum pumps. The gas load that must be pumped at high vacuum is limited by the use of a differentially pumped chamber containing a very short ion guide. The ion guide is used to transmit the ion flux to the mass analyser with high efficiency.
Mass spectrometry is a technique used in the field of chemical analysis to detect and identify analytes of interest. The sample must first be ionised so that components may then be acted upon by electric fields, magnetic fields, or combinations thereof, and subsequently detected by an ion detector. Mass analysers are operated at low pressure to ensure that the trajectories of the ions are dominated by the applied fields rather than by collisions with neutral gas molecules. However, it is often convenient to use an ion source operating at atmospheric pressure. Consequently, neutral gas molecules and entrained ions from the source must be drawn into the vacuum system through a small aperture. Atmospheric pressure chemical ionisation (APCI) and electrospray ionisation (ESI) are two common examples of such sources that are in widespread use.
The size and weight of a conventional atmospheric pressure ionisation (API) mass spectrometer is dominated by the pumping system, which is designed to maximise the amount of gas and entrained ions that can be drawn through the inlet, and at the same time maintain the pressure in the region of the mass analyser at a level consistent with its proper operation. A conventional bench-top instrument typically weighs approximately 100 kg and is coupled via a bulky vacuum hose to a floor-standing rotary pump, weighing an additional 30 kg. The power consumption can be more than a kilowatt, and relatively high levels of heat and noise are generated.
In vacuum systems, the flow of gas, Q, is given by
Q=SP (Eq. 1)
where S is the speed of the pump, and P is the pressure. There are many different types of vacuum pumps, but in all cases the pumping speed is related to the size and weight of the pump. According to Eq. 1, a large pump is required to simultaneously achieve low pressure and high gas throughput.
Prior to the widespread adoption of turbomolecular pumps, oil diffusion pumps and cryo pumps were used to achieve the high vacuum conditions required for mass spectrometry. Oil diffusion pumps are mechanically simple, dissipate a lot of heat, must be mounted in the upright position, are usually water cooled, and operate with a foreline (backing) pressure of less than 1 Torr. Cryopumps offer very large pumping speeds but require a supply of liquid nitrogen, or a bulky helium compressor. Turbomolecular pumps are mechanically complex and consequently relatively expensive. However, they are compact, generally air cooled, and can be mounted in any orientation. In addition, small and medium sized turbomolecular pumps tolerate a high foreline pressure.
Pumps capable of achieving low and medium vacuum pressures are needed for initial evacuation, direct pumping of vacuum interfaces, and providing foreline pumping. Such pumps are often referred to as roughing pumps, or backing pumps when used for foreline pumping. Oil-filled rotary vane pumps are universally used in conventional instruments. These are typically heavy, bulky, noisy, and require frequent servicing. Consequently, they are not housed within the main body of the instrument. Very lightweight and compact diaphragm pumps are available for low gas load applications. Although often used to provide foreline pumping for small turbomolecular pumps, they are not suitable for direct pumping of vacuum interfaces operating at or near 1 Torr.
Early system architectures, designated as Type A and Type B, are shown in
In
It was later appreciated that molecular beam techniques and principles could be applied in the design of API mass spectrometers [M. Yamashita and J. B. Fenn, J. Phys. Chem. 88, 1984, 4451-4459]. The general arrangement is shown in
An API mass spectrometer employing a differentially pumped radio frequency (rf) ion guide was described in 1987 [J. A. Olivares, N. T. Nguyen, C. R. Yonker, and R. D. Smith, Anal. Chem., 59, 1987, 1230-1232]. A schematic representation of this instrument is shown in
The trajectories of the ions are confined by an rf quadrupole ion guide as they transit the second chamber. In the case of a quadrupole ion guide, the field is generated by four rods arranged symmetrically about a common axis. The voltage applied to each rod is required to oscillate at rf, with the waveforms applied to adjacent rods having opposite phase.
The first chamber is operated at approximately 1 Torr, which is conveniently achieved with a rotary pump. As shown in
An alternative embodiment of the Type B architecture that incorporates an rf ion guide rather than electrostatic ion lenses is shown in
Recently, one manufacturer has abandoned the traditional orifice-skimmer interface in favour of a short ion guide operating at high pressure. The arrangement is shown in
Increasingly, small, light-weight analytical instruments are required for industrial process monitoring, security applications, the detection of toxic or illicit substances, and deployment in remote or hazardous environments. In addition, the growing amount of equipment being used by analytical chemists in traditional laboratories has forced greater consideration of factors such as the linear bench space occupied by instruments, heat and noise generation, initial purchase price, and operational costs. Consequently, there is a need for a miniature API mass spectrometer that, although much smaller than a conventional system, is capable of a useful level of sensitivity. While the detection efficiency of a particular instrument depends on the details of its design, the ultimate sensitivity is limited by the amount of gas and entrained ions that can be drawn through the inlet. Unfortunately, even a modest scaling down of the system architecture used for conventional instruments results in a significant reduction in the gas load that can be tolerated. Accommodating all the pumps within a single, small enclosure is a particular difficulty, as the size and weight of the pumps commonly used to achieve intermediate vacuum do not scale favourably.
These and other problems are addressed by a mass spectrometer system in accordance with the teaching of the invention. The system can be constructed such that the ions produced by an API source pass through an inlet orifice and directly into a vacuum chamber containing an ion guide. In a preferred embodiment of the invention, this vacuum chamber is pumped with a turbomolecular pump with foreline pumping provided by a diaphragm pump. By avoiding the use of a rotary pump, the overall size and weight of the system can be substantially reduced.
In addition, it has been discovered that the phenomenon known as collisional cooling occurs with high efficiency in a miniature ion guide at much lower pressures than expected. The operating pressure is ideally achieved using a conventional turbomolecular pump, which must be coupled to the vacuum system with due consideration of the likely conductance limitations resulting from a short ion guide.
Accordingly, a miniature mass spectrometer system comprising a plurality of vacuum chambers is provided, the system further comprising:
a. an ion source operating substantially at atmospheric pressure and employing electrospray ionisation, microspray ionisation, nanospray ionisation, chemical ionisation, or derivatives thereof;
b. an rf ion guide provided within an ion guide vacuum chamber of the system, the ion guide defining a ion path between an entrance and exit to the ion guide vacuum chamber, the dimensions and geometry of the ion guide being such that apertures through which gas may escape from the ion guide have a total area less than 10 cm2; and
c. a mass analyser provided within a mass analyser vacuum chamber of the system;
wherein the vacuum chambers containing the rf ion guide and the mass analyser are operably pumped at a pressure lower than about 5×10−2 Torr, other vacuum chambers of the system, where provided, being operably pumped at a pressure higher than about 50 Torr.
The present application will now be described with reference to the accompanying drawings in which:
It will be appreciated by those of skill in the art that, for instruments of a conventional size, a Type D architecture is overwhelmingly more preferable than a Type E architecture. For modern instruments, a typical inlet flow is 600 standard cubic centimeters per minute (sccm), and a typical ion guide pressure is 8×10−3 Torr, so these parameters shall be adopted for the purposes of comparison. In Table (1), some characteristics of the turbomolecular pump needed to pump the chamber containing the ion guide, and the roughing pump required for the whole system are given. It has been assumed that the skimmer operates at 1 Torr and passes 10% of the gas load in the case of Type D, and that the foreline pressure required by a 950 L/s turbomolecular pump is 2 Torr in the case of Type E.
It can be seen and has been appreciated by those of skill in the art that a severe penalty of adopting a Type E architecture rather than a Type D architecture is that a much larger, heavier, and consequently, more expensive turbomolecular pump must be accommodated within the enclosure of the bench-top unit. It will also be appreciated that the diameter of the vacuum chamber must be approximately equal to the diameter of the pump in order that the effective pumping speed is not significantly compromised by a reducing connector. This results in further increases in the size, weight, and cost of the instrument. Recalling that the roughing pump is invariably floor-standing and coupled to the main instrument with a vacuum hose, it will be understood that the size and weight of this component is of less consequence.
If the flow through the inlet orifice is reduced to 50 sccm, the characteristics of the turbomolecular pump needed to pump the chamber containing the ion guide, and the roughing pump required for the whole system are as given in Table (2). It has been assumed that the skimmer operates at 1 Torr and passes 10% of the gas load in the case of Type D, and that the foreline pressure required by an 80 L/s turbomolecular pump is 10 Torr in the case of Type E.
Recalling that for a miniature system, all the pumps, including the roughing pump, are desirably housed within a single enclosure, it is clear that a Type D instrument will be significantly heavier than a Type E instrument. The reason for this is that the weight of the roughing pump needed to pump the first vacuum chamber in the Type D architecture scales very unfavourably. According to common practice, the optimum pressure for operation of the first vacuum chamber is approximately 1 Torr. In
(a) The electrostatic optics used to focus ions towards the skimmer inlet or draw ions through the sampling orifice become less efficient due to the increased influence of scattering and viscous flow.
(b) The sampling or skimmer orifice must be made smaller to limit the flow of gas into the next vacuum stage, if the operating pressure of the ion guide and the pumping speed of the second stage pump are to be kept the same.
(c) If a skimmer is used to pierce the Mach disc of the free jet expansion, avoiding shock structures that disrupt the continuum flow of the jet becomes increasingly difficult and demands a precisely machined skimmer profile.
In the Type E architecture there are no regions that need to be at or near a pressure of 1 Torr, and advantage can be taken of the availability of small, lightweight, diaphragm pumps. For most pumps, the pumping speed decreases to a negligible value as the pressure approaches the ultimate or lowest pressure achievable with the pump. Rotary pumps are typically capable of an ultimate pressure in the range 5×10−3-1×10−2 Torr, and can achieve nearly their full nominal pumping speed at 1 Torr. In contrast, the ultimate pressure possible with a diaphragm pump is generally not lower than 2-5 Torr, and full nominal pumping speed is approached at pressures in excess of 10-20 Torr. Consequently, diaphragm pumps are unsuitable for pumping large volumes of gas at or near a pressure of 1 Torr. However, small turbomolecular high vacuum pumps are available with Holweck drag stages that allow them to operate with foreline pressures in the range of 10-30 Torr. Diaphragm pumps are, therefore, ideal for use as backing pumps for these turbomolecular pumps. Referring to Eq. 1, it will be appreciated that for a given gas load, the foreline pumping speed can be reduced by a factor of ten if the operating pressure is increased from 1 Torr to 10 Torr.
The inventors have recognized that although a Type E architecture is highly unattractive for systems of a conventional size, for miniature systems, it is a viable and advantageous solution. This advantageous selection of a previously discounted architecture for a specific set of conditions arises from an insight by the present inventors of the unique set of conditions that arise in miniature systems.
The ion source 803 operably provides gas and entrained ions 804 which are drawn through an inlet orifice 802 into an ion guide chamber 820, a first vacuum chamber of the system. The ions are directed by a miniature quadrupole ion guide 831 within this chamber 820 towards an aperture 822 that couples the first vacuum chamber 820 and a mass analyser chamber 810, a second vacuum chamber within which a mass analyser 812 is provided. The first chamber 820 is pumped to a pressure of 1×10−3 to 5×10−2 Torr by a turbomolecular pump 845 while the second chamber 810 is pumped to a pressure of 1×10−6 to 1×10−3 Torr by a second turbomolecular pump 840. Foreline pumping for both turbomolecular pumps is provided by a diaphragm pump 870 via a vacuum hose 860. It will appreciated that the performance of a single rf ion guide within a single chamber may be replicated by two or more individual rf ion guides each provided in their own chambers.
The ions that pass through the aperture 822 are filtered according to their mass-to-charge ratio by, in this exemplary arrangement, a quadrupole mass filter 812 and then detected using a suitable detector 811. It will be appreciated by someone of skill in the art that other mass filters and analysers may be used. These include, but are not restricted to, cylindrical, toroidal, Paul, and rectilinear ion traps, filters using crossed electric and magnetic fields, magnetic sector analysers, and time-of-flight analysers. The mass filter or analyser is also of a size that may be considered miniature in order that the overall size of the instrument is minimised, and also because such analysers and filters generally tolerate a high operating pressure.
Although not shown in the schematic, the quadrupole mass filter is desirably operably connected to a power supply that generates waveforms comprising of direct current (dc) and rf components. Desirably, the ion guide is capacitively coupled to the same supply such that only the rf components are applied to the rods. A fixed dc bias may be applied to all four rods of the ion guide through large resistors. As the waveform amplitude is scanned during the course of acquiring a mass spectrum, a fixed fraction of the rf component is applied to the ion guide. This fraction is determined by the network comprising the decoupling capacitor, the bias resistor, and stray capacitances. Alternatively, the ion guide may be connected to an independent supply that generates an rf waveform of fixed amplitude.
The maximum resolution achievable with a quadrupole mass filter is limited by the number of rf cycles that the ions experience while in the filter. Typically, a filter of conventional size is operated at approximately 1 MHz. In order to achieve the same resolution, miniature quadrupole filters must be operated at a higher frequency in order to compensate for the shorter rod length.
The inlet orifice 802 and the aperture 822 are desirably electrically isolated such that these components, as well as the ion guide 831, mass filter 812 and detector 811, may be individually biased. These biases may then be tuned to optimise the ion transmission, induce collisions to effect declustering, and set the ion energy.
In a miniature system, the length of the ion guide 831 may well be less than the diameter of the pump 845. When this is the case, there are three arrangements consistent with the teachings of this invention:
(a) The pump 845 may be placed as shown in
(b) The pump 845 may be placed with the axis of the rotor 847 lying perpendicular to the axis of the ion guide 831 and connected to the vacuum chamber 820 using a hollow conic, square pyramidal or rectangular pyramidal frustrum.
(c) The pump 845 may be placed with the axis of the rotor 847 lying perpendicular to the axis of the ion guide 831 and connected directly to the first chamber 820 without a reducing connector. In this case, the distance between the outer wall 828 and the opposing bulkhead 829 must be greater or equal to the diameter of the pump. In order that the trajectories of the ions are confined during transit of the first chamber, either the inlet or the mass filter, or both the inlet and mass filter must be allowed to be re-entrant. This may be achieved, for example, by shaping the outer wall, or the bulkhead, or both the outer wall and bulkhead such that they have top-hat profiles.
It will be appreciated that in the arrangement of
Where provided, this additional chamber is desirably constructed such that the distance between the first wall 906 and the second wall 907 is of the order of a millimetre, as described in co-assigned patent U.S. Pat. No. 7,786,434 (B2) and the Journal of Microelectromechanical Systems Vol. 19(6), 2010, 1430-1443. The system is configured such that ions 804 generated by an atmospheric pressure ionisation source 803 may be operably introduced through the vacuum interface 905 and the ion guide 831 prior to introduction to the mass filter 812 for analysis based on their mass-to-charge ratios, each of the vacuum interface, ion guide and mass spectrometer being provided within a casing 900. As shown in
In the case of a quadrupole ion guide, a saddle potential is generated at any instant in time by the voltages applied to the rods. The trajectories of ions are determined by the initial radial displacement and velocity, the rf phase as the ions enter the field, and a parameter, q, defined as
where V and ω are the amplitude and frequency of the rf waveform, respectively, m is the mass of the ion, e is the charge of the ion, and r0 is the field radius. Stable trajectories are periodic, and may be considered as a supposition of a high frequency micromotion and a lower frequency secular or macromotion. At values of q greater than 0.908, the trajectories are unstable, and the ions are discharged when they collide with a rod. At low values of q, the amplitude of the micromotion is small compared with the secular component, and the approximately sinusoidal trajectories can be considered as being characteristic of a harmonic oscillator.
Although the orientation of the saddle potential rotates rapidly in response to the applied rf waveforms, the ions behave as if trapped within a static potential well, usually referred to as a pseudopotential well in recognition of the fact that it is a time-averaged phenomenon. The amplitude of the sinusoidal trajectories represents the component of the total ion energy associated with radial motion. It is known that collisions between initially energetic ions and neutral gas molecules cause the ions to lose energy as they transit an ion guide. Consequently, the amplitude of the radial oscillations and the velocity in the axial direction steadily decrease, a process referred to as collisional cooling. If the number of collisions is sufficiently high, low energy ions accumulate close to the central axis and are able to exit the chamber through a small aperture. The emerging beam of low energy ions is ideally suited to mass analysis with a coaxial quadrupole filter, as ions with initial positions close to the central axis and small radial velocity components are preferentially transmitted, and higher resolution can be achieved when the axial velocity is low. The effect of collisional cooling on a typical ion trajectory is illustrated in
It is known from the prior art that, for a 15 cm long quadrupole ion guide constructed using 12.4 mm diameter rods, 90% of the ions are sufficiently cooled that they may pass through a 2.5 mm diameter aperture at the exit of the ion guide when the pressure is between approximately 6×10−3 to 8×10−3 Torr. Furthermore, the prior art teaches that the pressure required for maximum transmission can be extended to other lengths of ion guide through the relationship P×L≈0.1 Torr cm, where P is the pressure in the ion guide chamber and L is the length of the ion guide.
The inventors have discovered that at much lower P×L values than indicated by the prior art, most of the available ion flux may be transmitted through a 0.7 mm diameter aperture using a 2 cm long, miniature quadrupole ion guide constructed using 2.5 mm diameter rods. In addition, ions with initial axial energies of 30 eV are cooled to an extent that unit resolution can be achieved with a miniature quadrupole mass filter.
In
The efficiency of ion transmission through the inter-chamber aperture was determined by comparing the current drain to earth from the electrically isolated inter-chamber aperture plate with the current drain to earth from a Faraday plate placed downstream from the aperture. Baseline corrections were made by biasing the ion guide at a high positive value. Although the quadrupole mass filter had to be removed, the amplitude of the rf waveform applied to the ion guide was set at a value consistent with analysis at m/z=609. Using this method, the transmission efficiency was found to be in excess of 80%.
In
An exemplary arrangement for supporting the inlet orifice plate is shown in
The ion guide becomes a crude high pass filter when a retarding dc bias is applied to all four rods, as only ions with sufficient energy to overcome the potential barrier are transmitted. The approximate form of the ion energy distribution can be determined from a plot of signal level against the applied retarding bias.
The same experiment was repeated using the quadrupole mass filter to determine the energy distribution of ions exiting the inter-chamber aperture.
The effect of changing the ion energy at the entrance to the ion guide is demonstrated in
The flow of gas issuing from an orifice, such as 802 in
The evolution of the gas flow within a complex structure such as an ion guide can only be fully addressed through the use of suitable simulations. However, some aspects can be illustrated using the fundamental equations of gas flow in vacuum systems. In the molecular flow pressure regime, the conductance, C, of any plane aperture through which the gas may pass can be calculated using
C=11.6A (Eq. 3)
where A is the area of the aperture. Hence, to a first approximation, the conventional ion guide described above presents a total conductance between the source of gas and the pump of 313 L/s, whereas the miniature quadrupole ion guide described above presents a total conductance of only 8.5 L/s, which will be appreciated as being exemplary of miniature ion guides in general. Simulations or other calculations will yield estimates for the conductance of other ion guide designs, or indeed more accurate estimates for the conductance of a multipole ion guide. Nevertheless, in accordance with the present teaching, the dimensions and geometry of the miniature ion guide are such that gaps through which gas may escape present a conductance of less than 100 L/s. Specific configurations may include dimensions and geometries such that the total conductance is less than 10 L/s.
The flow of gas, Q, through the conductance is related to the difference between the upstream pressure, P1, and the downstream pressure P2 by
Q=C(P1−P2). (Eq. 4)
If the flow of gas through the inlet orifice is 0.93 Torr L/s as described in the prior art, and the background pressure in the chamber is 8×10−3 Torr, then the approximate pressure within the conventional quadrupole ion guide is 1.1×10−2 Torr, i.e. only marginally higher than the background pressure. However, in the case of the miniature ion guide, this increases to the much higher value of 1.2×10−1 Torr, if the same gas flow is used. Based on these calculations, the inventors have realised that the teachings of the prior art can only be transferred to a miniature system if the gas flow is scaled with the size of the ion guide.
The inventors have also discovered that the convective flux from the inlet and the high pressure within the miniature ion guide results in significantly more flow into the mass analyser chamber 810 in
While exemplary arrangements have been described herein to assist in an understanding of the present teaching it will be understood that modifications can be made without departing from the spirit and or scope of the present teaching. To that end it will be understood that the present teaching should be construed as limited only insofar as is deemed necessary in the light of the claims that follow.
Where the specifics of components usefully employed within the context of the present teaching have not been described herein, a miniature instrument, such as that described herein, may be advantageously manufactured using microengineered instruments such as those described in one or more of the following co-assigned US applications: U.S. patent application Ser. No. 30 12/380,002, U.S. patent application Ser. No. 12/220,321, U.S. patent application Ser. No. 12/284,778, U.S. patent application Ser. No. 12/001,796, U.S. patent application Ser. No. 11/810,052, U.S. patent application Ser. No. 11/711,142 the contents of which are incorporated herein by way of reference. Within the context of the present invention the term microengineered or microengineering or micro-fabricated or microfabrication is intended to define the fabrication of three dimensional structures and devices with dimensions of the order of millimetres or less.
Furthermore, the words comprises/comprising when used in this specification are to specify the presence of stated features, integers, steps or components but does not preclude the presence or addition of one or more other features, integers, steps, components or groups thereof. Additionally, within the context of the present specification, the words first, second and third when used to describe vacuum chambers, refer only to the existence of specific individual ones of a plurality of chambers and not necessarily to their relative position with respect to the direction of ion travel.
Number | Date | Country | Kind |
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GB1020728.0 | Dec 2010 | GB | national |