Patent Application
20060169891
The present teachings relate to method and apparatus for transmitting ions for the detection of ions in a sample.
One application for mass spectrometry is directed to the study of biological samples, where sample molecules are converted into ions, in an ionization step, and then detected by a mass analyzer, in mass separation and detection steps. Various types of ionization techniques are presently known, which typically create ions in a region of nominal atmospheric pressure. Mass analyzers which can be quadrupole analyzers where RF/DC ion guides are used for transmitting ions within a narrow slice of mass-to-charge ratio (m/z) values, magnetic sector analyzers where a large magnetic field exerts a force perpendicular to the ion motion to deflect ions according to their m/z and time-of-flight (“TOF”) analyzers where measuring the flight time for each ion allows the determination of its m/z. The mass analyzer generally operates in a low-pressure environment typically requiring its placement in one or more differentially pumped vacuum chambers equipped with inter-chamber apertures that provide adjacent pressure separation. One or more apertures positioned between the ionization step and the mass analyzer vacuum chamber generally define the interface for transmitting ions to the mass analyzer.
In view of the foregoing, the present teachings provide an apparatus for transmitting ions for the detection of ions in a sample. The apparatus comprises an ion source for generating ions, from the sample, in a high-pressure region, for example, at atmospheric pressure, and a vacuum chamber for receiving the ions. The vacuum chamber has an inlet aperture for passing the ions from the high-pressure region into the vacuum chamber. In conjunction with the differential pressure, the diameter of the inlet aperture is sized to provide a supersonic free jet expansion, with a predefined barrel shock and Mach disc, to entrain the ions into the vacuum chamber. The apparatus also comprises at least one ion guide with a predetermined cross-section that is sized to radially confine the supersonic free jet expansion so as to capture essentially all of the ions. The ion guide can be positioned in the chamber between the inlet aperture and an exit aperture so that when RF voltage, supplied by a RF power supply, is applied to the ion guide, the ions in the supersonic free jet can be focused and directed to the exit aperture. In various embodiments, the inlet aperture can be of the type that comprises a sonic nozzle or sonic orifice and the ion guide can be a multipole ion guide.
The present teachings also provide a method for transmitting ions for the detection of ions in a sample. The method comprises providing an ion source, in a high-pressure region, for example, at atmospheric pressure, for generating ions from the sample, and a vacuum chamber positioned downstream of the ion source for receiving the ions. The vacuum chamber is provided with an inlet aperture for passing the ions from the high-pressure region into the vacuum chamber. In conjunction with the differential pressure, the method comprises sizing the diameter of the inlet aperture for providing a supersonic free jet expansion having a predefined barrel shock and a Mach disc. The ions, which pass through the inlet aperture, are entrained by the supersonic free jet expansion created in the vacuum chamber. The method further comprises providing at least one ion guide with a predetermined cross-section that is sized to radially confine the supersonic free jet expansion so as to capture essentially all of the ions. The ion guide can be positioned in the chamber between the inlet aperture and an exit aperture so that when RF voltage, supplied by a RF power supply, is applied to the ion guide, the ions in the supersonic free jet are focused and directed towards the exit aperture.
These and other features of the present teachings are set forth herein.
The skilled person in the art will understand that the drawings, described below, are for illustration purposes only. The drawings are not intended to limit the scope of the present teachings in any way.
In the accompanying drawings:
FIGS. 5 to 10 are schematic and schematic cross-section views of various embodiments of the ion guide according to the present teachings;
In the drawings, like reference numerals indicate like parts.
It should be understood that the phrase “a” or “an” used in conjunction with the present teachings with reference to various elements encompasses “one or more” or “at least one” unless the context clearly indicates otherwise. Reference is first made to
To help understand how the ions 30 can be radially confined, focused and transmitted between the inlet and exit apertures 28, 32, reference is now made to
The supersonic free jet expansion 34 can be generally characterized by the barrel shock diameter Db, typically located at the widest part as indicated in
Db=0.412×Do×√{square root over ((P0/P1))} (1)
Xm=0.67×Do>√{square root over ((P0/P1))} (2)
where P0 is the pressure around the ion source 22 region 24 upstream of the inlet aperture 28 and P1 is the pressure downstream of the aperture 28 as described above. For example, if the diameter of the inlet aperture 28 is approximately 0.6 mm, with a suitable pumping speed so that the pressure in the downstream vacuum chamber 26 is about 2.6 torr, and the pressure in the region of the ion source 22 is about 760 torr (atmosphere), then from equation (1), the predetermined diameter of the barrel shock Db is 4.2 mm with a Mach disc 48 located at approximately 7 mm downstream from the throat 29 of the inlet aperture 28, as calculated from equation (2).
One of the most common prior-art methods of sampling the ions from the supersonic free jet 34 into the second vacuum chamber 45, which contains the mass analyzer 44, is through a skimmer 50 as indicated in
All of these factors make it difficult to increase the sensitivity in the prior-art inlet aperture-skimmer configuration sampling system simply by increasing the inlet aperture diameter. While successful up to a point, expanding the diameter of the inlet aperture (with a concomitant increase in the size of the vacuum pumps to maintain the vacuum chamber pressures at the required low pressure) is not a practical solution, as eventually the cost and size of the vacuum pumps becomes too large to be commercially successful.
In all of the above prior art configurations, the ions to be analyzed require focusing for passage through an entrance fringing field region between the inlet aperture 28 and the ion guide 36, thus requiring electrostatic focusing means within a region where the pressure or density is relatively large, leading to potential losses in sensitivity. Furthermore, if the ions require passage through another limiting aperture, such as the skimmer, before entering the ion guide, then there are likely to be losses before reaching the ion guide, resulting in further reduced sensitivity.
The applicants recognize that the supersonic free jet expansion 34 and barrel shock structure 46 expanding downstream from the throat 29 of the inlet aperture 28 can be an effective method of transporting the ions 30 and confining their initial expansion until the ions 30 are well within the volume 37 of the ion guide 36. The fact that all of the gas and ions 30 are confined to the region of the supersonic free jet 34, within and around the barrel shock 46, means that a large proportion of the ions 30 can be initially confined to the volume 37 of the ion guide 36 if the ion guide 36 is designed to accept the entire or nearly the entire free jet expansion 34. Additionally, the applicants recognize that the ion guide 36 can be positioned at a location so that the Mach disc 48 can be within the volume 37 of the ion guide 36. By locating the ion guide 36 downstream of the inlet aperture 28, and in a position to include essentially all of the diameter Db of the free jet expansion 34, a larger inlet aperture 28 can be used and thus a higher vacuum chamber 26 pressure P1 can be used while maintaining high efficiency in radially confining and focusing the ions 30 between the apertures 28, 32 thereby to allow more ions into the second vacuum chamber 45. Accordingly, with the appropriate RF voltage, ion guide dimensions and vacuum pressure, not only can the ion guide 36 provide radial ion confinement, but the ion guide 36 can also focus the ions 30 while the ions 30 traverse the internal volume between the inlet 28 and exit 32 apertures, as described, for example, in U.S. Pat. No. 4,963,736 (the '736 patent) by Douglas and French, the contents of which are incorporated herein by reference. In the present teachings, although the function of the ion guide 36 can be described to provide both radial confinement and focusing of the ions, it is not essential that the ion guide 36 perform the ion focusing effect. Greater efficient ion transmission between the inlet and exit apertures 28, 32, however, can be achieved with the focusing capabilities of the ion guide 36.
In the example described above, where the barrel shock 46 diameter Db is approximately 4.2 mm and the position Xm of the Mach disc 48, measured from the throat of the inlet aperture 28, is about 7 mm, the predetermined cross-section of the ion guide 36 (in this instance, an inscribed circle of diameter D) can be about 4 mm in order for all or essentially all of the confined ions 30 in the supersonic free gas jet 34 to be contained within the volume 37 of the ion guide 36. An appropriate length for the ion guide 36 greater than 7 mm can be chosen so that effective RF ion radial confinement can be achieved. This results in maximum sensitivity without the necessity of increasing the vacuum pumping capacity and thus the cost associated with larger pumps. A graphical representation of these results from computational simulation showing how the supersonic free jet expansion 34 can be confined within the volume 37 of the ion guide 36 is shown in
As described above and in accordance with equations (1) and (2), the pressure P1 within the vacuum chamber 26 containing the ion guide 36 contributes to the characterization of the supersonic free jet 34 structure. If the pressure P1 is too low, then the diameter Db of the barrel shock 46 is large, and the ion guide 36 can require substantial practical efforts to be large enough to confine the ions 30 entrained by the supersonic free jet expansion 34. Consequently, if a large inscribed diameter D can be sized accordingly to a large barrel shock diameter Db, then larger voltages must be used in order to provide effective ion radial confinement and ion focusing. However, larger voltages can cause electrical breakdown and discharge, which can interfere with proper function of the ion guide and can introduce considerable complexity to the instrument for safe and reliable operation. Additionally, power supplies capable of providing large voltages tend to be priced high, which can drive up the cost of commercial instruments. Therefore, it is most effective to keep the pressure relatively high so as to keep the jet diameter small and to keep the diameter D of the ion guide as small as possible so that voltages are maintained below electrical breakdown.
Conversely, if the pressure P1 is too high, then the focusing action of the ion guide 36 is reduced. Consequently, the applicants have determined, through computational simulations of ion motion that fast and effective focusing action can be obtained at a pressure between about 1 and 10 torr. In this range the supersonic free jet's diameter Db is small for typical diameters of the aperture of about 0.4 and 1 mm, and the ion guide diameter can be practically applied. Specifically, the inscribed diameter D can be between about 2 and 8 mm. Effective confinement can be obtained with RF voltages of between about 50 and 300 Volts peak to peak, limited at the upper end only by the requirement not to exceed the breakdown voltage of the gas at the operating pressure. Typical RF frequencies can be between about 1 and 2 MHz, although other frequencies of between about 0.5 and 5 MHz can also be quite practical and effective.
While the present teachings are described in conjunction with various embodiments, it is not intended that the present teachings be limited to such embodiments. On the contrary, the present teachings encompass various alternatives, modifications, and equivalents, as will be appreciated by those of skill in the art. For example, the present applicants recognize that the throat 29 of the inlet aperture 28 can have a finite length, and while it is desirable for the length to be as short as possible for certain applications while maintaining structural integrity, apertures with long throat lengths, such as a capillary, can also provide a free jet expansion at the end of the capillary. In various embodiments, the inlet aperture 28 of
While the parameters used in the calculations above can provide improvements, as will be described in the example below, it can also be practical to use other combinations of inlet aperture diameter and pressure P1 for the present teachings. For example, in various embodiments, with an inlet aperture 28 diameter Do of about 0.1 mm and pressure P1 of about 0.1 torr, the predetermined diameter Db of the barrel shock 46 is calculated to be 3.6 mm. An ion guide 36 of approximately 4 mm diameter D would effectively capture the supersonic free jet 34 and radially confine the ions 30. Similarly, an inlet aperture 28 diameter Do of about 0.2 mm and a pressure P1 of about 10 torr would result in a predetermined diameter Db of 1.2 mm, so that a small ion guide 36 of approximately 1.2 mm diameter D, requiring therefore lower RF voltages, can be used. Furthermore, it can be understood that the configuration of the inlet aperture 28 of the present teachings, can conceivable be non-circular in its cross-section. For example, in various embodiments, the inlet aperture 28 can be square or triangular having a cross-sectional area that can be equivalent to a corresponding circular cross-section area with diameter Do.
The predetermined cross-section of the ion guide 36 can be sized less than the predetermined diameter Db to be able to confine a corresponding portion of the ions in the supersonic free jet 34 while still achieving a significant improvement in sensitivity. For example, in various embodiments, the cross-section of the ion guide 36 can be sized so that the cross-section is at least 50% of the predetermined diameter Db.
Although the ion guide 36 of
The applicants have contemplated the use of one or more inlet apertures 28 for achieving substantially the same ion transmission efficiency. For example, in various embodiments, two apertures 28a, 28b are shown in
The ion guide 36 acting as ion confinement, focusing and guiding devices can be of the type indicated in FIGS. 5 to 10. The multipole ion guide of
Further embodiments are exemplified in
The configuration according to
The foregoing optimization can be accomplished by, as shown in
Furthermore, the ion guide 36e nearest to the exit aperture 32 can be configured with a cross-section to have an inscribed diameter D2 according to the dimensions of the exit aperture 32. The corresponding RF voltage applied to the ion guide 36e can be selected according to the diameter D2 for establishing an RF confinement field within volume 37 of the ion guide 36e to focus all or essentially all of the ions 30 to the dimensions of the exit aperture 32. The dimensions of the exit aperture can be defined, for example, by its diameter as in the case for a circular aperture, or by another dimensional parameter for other geometric configurations, such as the aperture's width as in the case for a square aperture. Regardless of the specific geometric shape, the cross-sectional area of the exit aperture 32 can be generally described by an equivalent circular cross-sectional area defined by a diameter. Optimum ion transmission can be realized when the ions 30 are focused to form an ion beam with a diameter that is equal to or less than the diameter of the exit aperture 32. While sufficient ion transmission can be achieved when the ion beam diameter is greater than the exit aperture 32 diameter, it will be apparent to those skilled in the art that optimum ion transmission focusing can be expected when the beam diameter is less than or equal to the diameter of the exit aperture 32.
Generally, the function of the first ion guide 36d is for capturing and focusing the ions 30 from the inlet aperture 28 while the function of the second ion guide 36e is for focusing and transmitting the ions 30 from the first ion guide 36d to the exit aperture 32. The first ion guide 36d diameter D1 and the corresponding applied RF voltage are chosen according to the predetermined diameter Db of the barrel shock while the second ion guide 36e diameter D2 and the corresponding applied RF voltage are chosen according to the diameter of the exit aperture 32 as discussed above. In various embodiments, the diameter Db of the barrel shock can often be larger than the diameter of the exit aperture 32, thus the corresponding cross-section of the first ion guide 36d can be greater than the corresponding cross-section of the second ion guide 36e. Consequently, in various embodiments for optimum ion transmission between the inlet 28 and the exit 32 apertures, the relative ratio of the cross-sections of the second to first ion guides 36e, 36d can be less than 1. Typically, as in Example 2 described below, the applicants have utilized a diameter D2 of about 4 mm and a diameter D1 of about 7 mm to give a relative ratio between the cross-sections of the ion guides of about 0.6 to show improved ion 30 transmission between the inlet and exit apertures 28, 32. In various embodiments, the cross-sections of the first and second ion guides 36d, 36e can be equal while the corresponding RF voltages can be selected to provide RF confinement fields that are independently optimized for ion focusing/transmission and ion acceptance.
In various embodiments, a series of ion guides comprising more than two ion guides is provided for additional multiple focusing stages. For example, in
It is anticipated that the length of each ion guide 36d, 36x, 36e in the series, can be appropriately selected according to the distance necessary for the corresponding radial RF field to sufficiently focus the ions 30 within the volumes 37. In addition to the focusing function of the ion guides, the ion guides can perform a physical function to limit the amount of gas that is transferred between the inlet aperture 28 and the exit aperture 32. Referring to
In addition, the shape and size of the ion guides can have an effect on the gas flow characteristics. For example, in various embodiments, increasing the pole diameter of the multipole ion guide can lead to entraining more of the gas flow along the length of the ion guide. The increased pole diameter, while maintaining the diameter D1, effectively increases the radial distance between the center axis 100 to the gap between adjacent poles. This can increase the potential of entraining more of the gas flow in the first ion guide. Alternatively, the shape of the multipoles can be plate-like to increase the surface area of the poles while maintaining or reducing the gap dimension to achieve better gas entrainment.
In various embodiments, the single ion guide 94 shown in
In various embodiments, the second vacuum chamber 45 can have an outlet aperture for passing ions from the second vacuum chamber 45 to the mass analyzer 44, where the mass analyzer 44 can be housed in a third vacuum chamber. The second vacuum chamber 45 can have an RF-only ion guide for radially confining, focusing and transporting the ions 30, as described in the '736 patent, between the exit aperture 32 and the outlet aperture. The exit aperture 32 functions as an inter-chamber aperture 32, as previously described. The RF-only ion guide can be constructed similarly as the ion guide 36. In use, the ions 30 pass from the first vacuum chamber 26 through the inter-chamber aperture 32 into the second vacuum chamber 45 where the ions 30 can be radially confined and focused by the RF-ion guide as the ions 30 traverse the RF-only ion guide. After the ions 30 pass from the second vacuum chamber 45, by way of the outlet aperture, into the third vacuum chamber, the mass analyzer 44 receives the ions 30 for mass analysis. The same power supply 40 which provides RF voltage to the ion guide 36 or a separate power supply can be connected to the RF-only ion guide for providing RF voltage in a known manner.
The ion source 22 can be one of the many known types of ion sources depending of the type of sample to be analyzed. In various embodiments, the ion source 22 can be an electrospray or ion spray device, a corona discharge needle, a plasma ion source, an electron impact or chemical ionization source, a photo ionization source, a MALDI source or any combination thereof. Other desired types of ion sources known to the skilled person in the art may be used, and the ion source can create ions at atmospheric pressure, above atmospheric pressure, near atmospheric pressure, or less than atmospheric pressure, but higher than the pressure associated with the pressure in the vacuum chamber 26 so that the absolute pressure ratio P1/P0<0.528.
Aspects of the present teachings may be further understood in light of the following examples, which should not be construed as limiting the scope of the present teachings in any way.
The first (lower) peak, labeled API 4000, shows the response on a prior art mass spectrometer, API 4000 triple quadrupole mass spectrometer, manufactured by Applied Biosystems/MDS Sciex, which uses an inlet aperture diameter of 0.32 mm and a skimmer diameter of 2.4 mm.
The second (larger) peak, indicated by the label API 5000, shows the response on a triple quadrupole mass spectrometer instrument in accordance with the present teachings, where the inlet aperture diameter has been increased to 0.6 mm, and an RF quadrupole ion guide was used to capture and focus the ions from the supersonic free jet according to the present teachings. In this example, the pressure in the ion guide region was 2.6 torr, the diameter of the ion guide was 4 mm, and the calculated maximum diameter of the barrel shock of the Mach disc according to Equation (1) was 4.2 mm. The increase of approximately six-fold, indicated by the label 6x, in sensitivity demonstrates the ability to achieve significantly better mass spectrometry performance in accordance with the present teachings.
The first (lower) peak, labeled API 5000, shows the response similar to the response with the same label as indicated in
This application is a continuation-in-part of U.S. application Ser. No. 11/032,376 filed Jan. 10, 2005 entitled “Method and Apparatus for Improved Sensitivity in a Mass Spectrometer System”.
| Number | Date | Country | |
|---|---|---|---|
| Parent | 11032376 | Jan 2005 | US |
| Child | 11315788 | Dec 2005 | US |
