Patent Application
20110147577
The present invention relates to ionization sources for mass spectrometry and, in particular, to an electrospray ionization source comprising a plurality of separate ion emitters.
The well-known technique of electrospray ionization is used in mass spectrometry to generate free ions. The conventional electrospray process involves breaking the meniscus of a charged liquid formed at the end of the capillary tube into fine droplets using an electric field. In conventional electrospray ionization, a liquid is pushed through a very small charged capillary. This liquid contains the analyte to be studied dissolved in a large amount of solvent, which is usually more volatile than the analyte. An electric field induced between the capillary electrode and the conducting liquid initially causes a Taylor cone to form at the tip of the tube where the field becomes concentrated. Fluctuations cause the cone tip to break up into fine droplets which are sprayed, under the influence of the electric field, into a chamber at atmospheric pressure in the presence of drying gases. An optional drying gas, which may be heated, may be applied so as to cause the solvent in the droplets to evaporate. According to a generally accepted theory, as the droplets shrink, the charge concentration in the droplets increases. Eventually, the repulsive force between ions with like charges exceeds the cohesive forces and the ions are ejected (desorbed) into the gas phase. The ions are attracted to and pass through a capillary or sampling orifice into the mass analyzer.
Incomplete droplet evaporation and ion desolvation can cause high levels of background counts in mass spectra, thus causing interference in the detection and quantification of analytes present in low concentration. It has been observed that smaller initial electrospray droplets tend to be more readily evaporated and, further, that droplet sizes decrease with decreasing flow rate. Thus, it is desirable to reduce the flow rate per emitter and, consequently, the droplet size, as much as possible (on the order of microliters or even nanoliters per minute) in order to spectra with minimal background interference. However, conventional electrospray devices and conventional liquid chromatography apparatuses which deliver eluent to such electrospray devices are typically associated with flow rates of several microliters per minute up to 1 ml per minute. It is therefore of interest to use assembly or array of multiple nanospray or microspray emitters with the goal to generate more ions per unit volume of analyte solvent while still realizing low flow rates per each emitter.
Attempts have been made to manufacture an electrospray device which produces nanoelectrospray. For example, Wilm and Mann, Anal. Chem. 1996, 68, 1-8 describes the process of electrospray from fused silica capillaries drawn to an inner diameter of 2-4 μm at flow rates of 20 mL/min. Specifically, a nanoelectrospray at 20 mL/min was achieved from a 2 μm inner diameter and 5 μm outer diameter pulled fused-silica capillary with 600-700 V at a distance of 1-2 mm from the ion-sampling orifice of an API mass spectrometer. Other nano-electrospray devices have been fabricated from substantially planar substrates with microfabrication techniques that have been borrowed from the electronics industry and microelectromechanical systems (MEMS), such as chemical vapor deposition, molecular beam epitaxy, photolithography, chemical etching, dry etching (reactive ion etching and deep reactive ion etching), molding, laser ablation, etc.
In order to realize the aforementioned benefits of micro-electrospray or nano-electrospray at higher overall flow rates, electrospray arrays of densely packed tubes or nozzles have been developed, using either capillary pulling or microfabrication and MEMS techniques, so as to increase the overall flow rate without affecting the size of the ejected droplets. For example,
In order to introduce ions generated by a multi-emitter electrospray apparatus into a mass spectrometer (MS), the simplest approach would be to locate the several emitters at sufficient distances from one other such that electric fields from any given emitter do not measurably affect the operation of any other emitter and provide a separate ion inlet into the mass spectrometer for each emitter. This approach is not generally practical because of the requirement of proportionally higher evacuation pumping speed with an increase in the number of emitters and ion inlets. A preferable approach is to use a standard vacuum interface (single ion inlet to the mass spectrometer, such as the entrance orifice of the ion transfer tube) while locating and configuring the emitters in such a way that the transmission efficiency into the single ion inlet is close to optimized. Normally, a liquid jet with charged droplets emanating from an emitter tip occupies space roughly represented by cone with an 80-90 degree angle at the apex (at the emitter tip). The optimal emitter position, relative to an MS ion inlet, is therefore a compromise between the competing requirements of efficient sample transfer into the ion inlet and efficient sample de-solvation. To accomplish efficient sample transfer, the distance between the emitter capillary and the ion inlet should be short and the axis of the emitter should be directed towards the ion inlet. On the other hand, to accomplish efficient de-solvation, a longer travel distance to the inlet is required. For a single emitter, the optimal distance is found to be between 2 to 4 mm, resulting in a 4-8 mm diameter ion plume at the inlet plane.
The above considerations suggest that, if multiple electrospray emitters are employed instead of a single emitter, these should all be positioned as close as possible to the position of the single emitter that they replace. Unfortunately, placing muliple emitters in random stack or arranged in regular pattern in the rather limited volume near the vacuum interface has had limited success, in practice. One of the reasons for such limited success is the interference of the electric fields originating from the various emitters, when packed into the requisite small space. This effect has been theoretically modeled by Si et al. (“Experimental and theoretical study of a cone-jet for an electrospray microthruster considering the interference effect in an array of nozzles”, Journal of Aerosol Science 38, 2007, pp. 924-934) who demonstrated that, for an array of closely-spaced emitters operating simultaneously, the operating voltage required for cone jet spraying increases as the emitter spacing decreases. Regele et al. (“Effects of capillary spacing on EHD spraying from an array of cone jets”, Journal of Aerosol Science 33, 2002, pp. 1471-1479) experimentally determined similar results for an array of four electrospray capillaries and mathematically predicted the same behavior for a 5×5 square array. Regele et al. also found that, at very close spacings (3-4 capillary diameters), the electric potential required for stable electrospray operation can decrease and postulated that fine wire electrodes interspersed among the capillaries could improve operation. Also, space charge clouds produced by individual cone jets contribute to interference effects.
Recently, Deng et al. (“Compact multiplexing of monodisperse electrosprays”, Journal of Aerosol Science 40, 2009, pp. 907-918) have described a microfabricated planar nozzle array system, schematically illustrated in
In
The calculated results presented in
Although the apparatus described by Deng et al. (
In order to address the above identified limitations in the art, the present teachings provide methods and apparatuses for eliminating above mentioned interference effects between closely spaced electrospray emitters of an array (a plurality) of emitters. The present inventors have determined that supplementary “shield” electrodes disposed between and partially around emitters, optionally supported by post like supports (which themselves may comprise electrodes or portions of the electrodes), wherein the shield electrodes are configured so as to spatially conform to (or approximately conform to) the electric field that would surround an individual emitter in isolation, can provide optimal de-coupling between the various emitters. The shapes and positions of these shield electrodes may be optimized such that each emitter in the array is caused to emulate the operating conditions of a single emitter operating in isolation. Such a configuration can enable fabrication of yet-more-closely spaced emitter arrays without significant interference between emitters and with uniform voltage applied across multi-emitter array, needing no increased voltage for near-to-center emitters as in non-shielded configurations.
Accordingly, in a first aspect, an electrospray ion source for generating ions from a liquid sample for introduction into a mass spectrometer is provided. The electrospray ion source may comprise: an emitter capillary comprising an internal bore for transporting the liquid sample from a source, an electrode portion for providing a first applied electric potential and an emitter tip for emitting charged particles generated from the liquid sample; a counter electrode for providing a second applied electric potential different from the first applied electric potential; and a shield electrode disposed at least partially between the counter electrode and the emitter tip of the emitter capillary for providing a third applied electric potential intermediate to the first and second applied electric potentials, the shield electrode contoured in the form of a portion of an electric equipotential surface formed, in the absence of the shield electrode, under application of the first and second applied electric potentials to the electrode portion of the emitter capillary and to the counter electrode, respectively.
In a second aspect, there is provided an electrospray ion source apparatus for generating ions from a liquid sample for introduction into a mass spectrometer. The electrospray ion source apparatus may comprise: a plurality of emitter capillaries, each comprising an internal bore for transporting a portion of the liquid sample from a source, an electrode portion for providing a first applied electric potential and an emitter tip for emitting charged particles generated from the liquid sample portion; a counter electrode for providing a second applied electric potential different from the first applied electric potential; and one or more shield electrodes, each shield electrode disposed at least partially between the counter electrode and the emitter tip of at least one of the emitter capillaries for providing a third applied electric potential intermediate to the first and second applied electric potentials, wherein the one or more shield electrodes are configured such that provision of the third applied electric potential to the one or more shield electrodes provides a uniformity of emission of charged particles from the plurality of emitter tips.
In a third aspect, a method for providing ions to a mass spectrometer is provided. The method may comprise the steps of: (a) providing a source of analyte-bearing liquid; (b) providing a plurality of an electrospray emitter capillaries, each comprising an internal bore for transporting the analyte-bearing liquid from the source, an electrode portion and an emitter tip for emitting charged particles generated from the analyte-bearing liquid; (c) providing a counter electrode; (d) providing one or more shield electrodes, each shield electrode disposed at least partially between the counter electrode and the emitter tip of at least one of the emitter capillaries; (e) distributing the analyte-bearing liquid among the plurality of electrospray emitter capillaries; and (f) providing first, second and third electric potentials, respectively, to the plurality of electrode portions of the electrospray emitter capillaries, the counter electrode and the one or more shield electrodes, wherein the third electric potential is intermediate to the first and second electric potentials, such that the charged particles are emitted from each of the emitter tips, wherein the one or more shield electrodes are configured such that provision of the third electric potential provides a uniformity of emission of charged particles from the plurality of emitter tips.
In another aspect, a method for providing an electrospray ion emitter apparatus is provided, the method comprising: (a) providing a first emitter capillary comprising an internal bore; an electrode portion and an emitter tip; (b) providing a counter electrode at a distance from the emitter tip; (c) determining a form of an electrical equipotential surface created around the electrospray emitter capillary under application of a first and a second electric potential to the electrode portion of the electrospray emitter capillary and to the counter electrode, respectively; (d) providing at least one additional emitter capillary disposed parallel to the first emitter capillary, each additional emitter capillary comprising an internal bore, an electrode portion and an emitter tip; and (e) providing at least one shield electrode, each shield electrode approximating a portion of the form of the electrical equipotential surface and disposed at least partially between the counter electrode and the emitter tip of the first emitter capillary or the at least one additional emitter capillary.
One useful benefit of the present teachings is improved operation of multi-emitter electrospray apparatuses. In accordance with the present teachings, each emitter may be associated with a respective shielding electrode shaped as one of the equipotential surfaces of a single stand alone emitter. Therefore, even when multiple emitters are present, the local field environment around each emitter is the same as if it were operating just by itself. Thus, operational conditions may be implemented in which cross-talk or electric field interference between individual emitters is significantly reduced and the degree of uniformity of emission from several emitters is increased. In the present invention, this improvement in the uniformity of emission is accomplished without the need to apply higher voltages to some emitters, thereby reducing or eliminating electrical breakdown issues and eliminating the need for additional or costly power supplies, extra electrical shielding, etc. This allows for a denser packaging of emitters in close proximity to the vacuum interface of a mass spectrometer, thereby resulting in more efficient ion transfer similar to the one in single emitter geometry.
The above noted and various other aspects of the present invention will become apparent from the following description which is given by way of example only and with reference to the accompanying drawings, not drawn to scale, in which:
The present invention provides improved methods and apparatus for providing multiple electrospray emitters in mass spectrometry. The following description is presented to enable one of ordinary skill in the art to make and use the invention and is provided in the context of a particular application and its requirements. It will be clear from this description that the invention is not limited to the illustrated examples but that the invention also includes a variety of modifications and embodiments thereto. Therefore the present description should be seen as illustrative and not limiting. While the invention is susceptible of various modifications and alternative constructions, it should be understood that there is no intention to limit the invention to the specific forms disclosed. On the contrary, the invention is to cover all modifications, alternative constructions, and equivalents falling within the essence and scope of the invention as defined in the claims. To more particularly describe the features of the present invention, please refer to
The counter electrode 12 may, in fact, be a portion of a MS instrument and, in such an instance, the aperture 11a may be an ion inlet aperture of the MS. In addition, the emitter assembly 100 comprises a shield electrode 18 disposed between the emitter capillary electrode 10a and the counter electrode 12. The shield electrode 18 comprise an aperture or gap 17a which is disposed so as to enable ions emitted from the emitter capillary electrode 10a to pass on to the aperture 11a in the counter electrode 12. Alternatively, the shield electrode 18 may be formed in two or more sections such that the gap 17a is the space between such sections.
In three dimensions, the shield electrode 18 shown in
In the apparatus 200 shown in
In addition to the considerations discussed above, the particular electrode shape will be determined based on balancing two considerations: size and shape accuracy versus packaging density and simplicity. For example, the apparatus 100 shown in
As modeled herein, the electrode support structures 15 in the apparatus 300 (
In three dimensions, the arcuate shield electrode 20 may be rotated about an axis within the plane of the drawing and parallel to the arrows of
As may be more readily observed in
In order to further electrically shield the charged particles that are electrosprayed from each emitter 10 from the electric fields surrounding adjacent emitters, the separate inner and outer ring electrodes may be merged into a single ring electrode 24 as illustrated in
The shield electrodes 20 of the apparatus 600 are disposed in a spatial region that is outward from the plane described by the emitter tips, the term “outward” referring to a spatial region that is between the emitter tips and a counter electrode (not shown). Each shield electrode 20 shown in
Improved methods and apparatuses for multiple electrospray emitter arrays have been disclosed. The discussion included in this application is intended to serve as a basic description. Neither the description nor the terminology is intended to limit the scope of the invention. The reader should be aware that the specific discussion may not explicitly describe all embodiments possible; many alternatives are implicit. For instance, although multiple apertures are illustrated in a counter electrode, it is possible to configure several emitters sufficiently close to one another such that the ion emission from the plurality is directed to a single aperture.
Further, each feature or element can actually be representative of a broader function or of a great variety of alternative or equivalent elements. Again, these are implicitly included in this disclosure. Thus, a variety of changes may be made without departing from the essence of the invention. Such changes are also implicitly included in the description. Finally, note that any publications, patents or patent application publications mentioned in this specification are explicitly incorporated by reference in their respective entirety.
