Patent Grant
7423261
In surface ionization techniques, an analyte sample is first deposited on a plate surface, then desorbed from the surface and ionized by irradiation. The irradiation of the surface may be performed using a laser, or with a particle or ion beam, for example. The desorbed ions can be captured for analysis by a conduit leading to a mass spectrometer instrument using pneumatic and/or electrostatic forces. Currently, the most widely used surface ionization technique is matrix-assisted laser desorption ionization (MALDI). In this technique, samples are diluted in an ultraviolet(UV)-absorbing matrix material, then deposited on a sample plate, on which the mixed sample and matrix are co-crystallized by drying. A focused pulse of UV laser radiation is then directed onto the sample. The energy of the pulse is absorbed by the matrix material, which is desorbed from the surface and ionized, carrying with it analytes, which are ionized in turn by charge transfer processes.
In particle bombardment, a similar apparatus setup is employed, but instead of directing laser radiation onto the sample, a stream of particles, typically ions, is generated by electrospray ionization or another ionization process and is directed onto the sample. Analyte ions are generated by the impact of the ions on the sample, and related charge transfer processes that occur due to such impact.
In conventional configurations, the analyte ions generated using a MALDI or particle ionization source are drawn into the inlet of a straight conduit leading to a mass spectrometer. The proximal end of the conduit including the inlet is oriented orthogonally with respect to the sample-bearing plate surface. Typically, the conduit is also oriented along the longitudinal axis of the mass spectrometer, which is usually horizontal. This dictates that the sample-bearing surface be oriented vertically to be orthogonal to the conduit. This vertical configuration can be disadvantageous for certain applications. Moreover, the conduit is often not in the optimal position or orientation for receiving ions desorbed from the plate surface, reducing the collection efficiency of the ionization source.
The present invention provides an ion sampling device comprising a curved-tip conduit that maintains ion collection efficiency while enabling much greater flexibility in the arrangement of the sample-bearing support and the source of ionization energy.
In a first aspect, the present invention provides an ion sampling apparatus for use in a mass spectrometry system that comprises a target support having a surface for receiving a sample, an irradiation source for emitting energetic radiation or particles onto the target support, and a conduit having a curved end and a longitudinal axis, the curved end having an inlet having a central axis, the conduit being adjacent to the target support. The longitudinal axis of the conduit and the central axis of the inlet intersect to define an angle that is between about 20 degrees and about 210 degrees.
In a second aspect, the present invention provides a mass spectrometry system having a MALDI ionization source that comprises a target support having a surface for receiving a sample, a laser source oriented to emit a laser beam onto the target support, a conduit having a curved end, a longitudinal axis and an exit, the curved end having an inlet having a central axis, the conduit being adjacent to the target support, and a mass spectrometer positioned downstream from the conduit, wherein the inlet of the conduit faces the target support.
In another aspect, the present invention provides a method of efficiently sampling ions from a surface comprising irradiating the surface to generate ions and receiving the ions in a curved conduit having a longitudinal axis and an inlet with a central axis. The longitudinal axis of the conduit and the central axis of the inlet intersect to define an angle that is between about 20 degrees and about 210 degrees.
Before describing the present invention in detail, it must be noted that, as used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise.
The term “conduit” should be interpreted broadly to include any passageway that extends for some length and may comprise a capillary, tube, nanotube, pipe, channel, or microchannel among other possible implementations.
The term “adjacent” means near, next to or adjoining. Something adjacent may also be in contact with another component, surround (i.e. be concentric with) the other component, be spaced from the other component or contain a portion of the other component.
An “irradiation source” refers to a device that emits energetic radiation or particles, such as ions and uncharged particles.
An irradiation source 20, which may comprise an ultraviolet laser source or a particle bombardment source is positioned and oriented to direct a pulsed beam of laser radiation or a particle stream toward the analyte sample 15 on the target support. The impact of the laser radiation or particle beam (as the case may be) transfers sufficient energy to desorb matrix and analyte molecules, and to ionize a portion thereof directly or by charge transfer processes. Suitable particle bombardment sources may include one or more of: an electrospray ionization source; a chamber through which a high-velocity gas contacts a surface, stripping electrons from the surface and causing subsequent ion formation from the gas; a penning ionization source such as used in Direct Analysis in Real Time (DART) applications as known in the art; and a fast atom bombardment (FAB) source as also known in the art, among other possible sources of energetic particles or ions.
The desorbed analyte (and matrix) ions are ejected from the target support surface and may have some forward momentum imparted by the ionization energy source. The proximal end of a conduit 25 that leads to a mass spectrometer 30 is positioned adjacent to the target support 10 so as to capture the desorbed analyte ions. A pressure differential between the entrance to the conduit 25 and the exit of conduit 25 creates a continuous flow inside the conduit 25 that draws desorbed analyte ions into the inlet at the proximal end of the conduit and carries them downstream toward the distal end into the mass spectrometer 30. Within the mass spectrometer 30, the analyte ions are transported to a mass analyzer 40, where they are selected according to their respective mass-to-charge (m/z) ratios and detected.
The conduit 25 has a longitudinal axis that may be aligned with the longitudinal axis of the mass spectrometer 30 (denoted as the ‘z’ axis) which is often horizontal as depicted. The proximate end 28 of the conduit is curved, and at the tip of the curved end is an inlet 29 for receiving analyte ions desorbed from the sample 15. By having the proximal end 28 of the conduit curved, analyte ion capture efficiency is not impaired by any arrangement of the target support 10 with respect to the mass spectrometer 30. This is possible because ions can be conducted through a curved conduit with the same transmission efficiency as through a straight conduit, due to the continuous gas flow maintained inside the conduit.
The inlet 29 of the conduit has a central axis that is aligned at an angle (θ) with respect to the longitudinal axis of the conduit 25 at their point of intersection. The angle (θ) is considered to be 180 degrees when the central axis of the inlet 29 (pointing out of the inlet away from the conduit) is oriented backwards in the direction of the z-axis of the mass spectrometer (as shown in
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Having described the present invention with regard to specific embodiments, it is to be understood that the description is not meant to be limiting since further modifications and variations may be apparent or may suggest themselves to those skilled in the art. It is intended that the present invention cover all such modifications and variations as fall within the scope of the appended claims.
| Number | Name | Date | Kind |
|---|---|---|---|
| 6621076 | van de Goor et al. | Sep 2003 | B1 |
| 7078681 | Fischer et al. | Jul 2006 | B2 |
| Number | Date | Country | |
|---|---|---|---|
| 20070235642 A1 | Oct 2007 | US |
