Patent Grant
8207496
The present invention relates to ionization sources for mass spectrometry and, in particular, to a nano-electrospray ionization source comprising a surface having a plurality of protruding microscopic to sub-microscopic pillars, cones, needles, or wires each of which acts to emit ions from an analyte-bearing liquid applied to its exterior surface.
The well-known technique of electrospray ionization is used in mass spectrometry to produce ions. 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. 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. The electric field induced between the 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, optionally in the presence of drying gases. The optionally heated drying gas causes 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 and, consequently, the droplet size, as much as possible in order to obtain mass spectra with minimal background interference. Nano-electrospray, with flow rates per emitter in the range of less than several hundred nanoliters per minute to 1 nanoliter per minute, has been found to yield very good results, in this regard. Further, it has been found that the efficiency of ionization is much higher in nanospray mode and that the response is more linear than in other spray modes. For instance, Ficcaro et al., in a technical paper titled “Improved Electrospray Ionization Efficiency Compensates for Diminished Chromatic Resolution and Enables Proteomics Analysis of Tyrosine Signaling in Embryonic Stem Cells” (Analytical Chemistry 81, 2009, pp. 3440-3447), demonstrate that, in the assessment of LCMS performance, the improved electrospray ionization efficiency at low flow rates outweighs deterioration of chromatographic separation, even at chromatographic flow rates below Van Deemter minima. 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.
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 nl/min. Specifically, a nanoelectrospray at 20 nl/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 Atmospheric Pressure Ionization 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 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,
A grid-plane region 12 of the ejection surface 10 is exterior to the nozzle 9 and to the recessed region 11 and may provide a surface on which a layer of conductive material 14 including a conductive electrode 15 may be formed for the application of an electric potential to the substrate 5 to modify the electric field pattern between the ejection surface 10, including the nozzle tip 9, and the extracting electrode 54. Alternatively, the conductive electrode may be provided on the injection surface 8 (not shown).
The electrospray device 4 further comprises a layer of silicon dioxide 13 over the surfaces of the substrate 5 through which the electrode 15 is in contact with the substrate 5 either on the ejection surface 10 or on the injection surface 8. The silicon dioxide 13 formed on the walls of the channel 6 electrically isolates a fluid therein from the silicon substrate 5 and thus allows for the independent application and sustenance of different electrical potentials to the fluid in the channel 6 and to the silicon substrate 5. Alternatively, the substrate 5 can be controlled to the same electrical potential as the fluid.
As shown in
All presently known nano-electrospray array devices utilize a conventional delivery method in which analyte-bearing liquid is delivered to a hollow nozzle by means of micro-capillaries or micro-tubes, so as to be emitted from an interior bore of the nozzle. There are many limitations to the use of such small-bore capillaries and nozzles, such as clogging, difficulty in producing a spray and, in the case of silica capillaries, difficult handling. Furthermore, with such conventional electrospray delivery techniques, an increase in salt concentration results in spraying difficulty and there is a sudden decline in desorption efficiency of ions into the gaseous phase. Accordingly, such delivery methods cannot be applied to NaCl aqueous solutions on the order of 150 mM, such as physiological saline solution.
In order to address the above identified limitations in the art, there are provided various methods and apparatuses for a multi-needle parallel nanospray ionization source for mass spectrometry.
In a first aspect of the invention, there is disclosed an electrospray ion source for a mass spectrometer comprising: an electrode comprising at least a first plurality of protrusions protruding from a base, each protrusion of the at least a first plurality of protrusions having a respective tip; a conduit for delivering an analyte-bearing liquid to the electrode; and a voltage source, wherein, in operation of the electrospray ion source, the analyte-bearing liquid is caused to move, in the presence of a gas or air, from the base to each protrusion tip along a respective protrusion exterior so as to form a respective stream of charged particles emitted towards an ion inlet aperture of the mass spectrometer under application of voltage applied to the electrode from the voltage source. The first plurality of protrusions may occupy an area of the electrode having a shape that corresponds to a shape of the ion inlet aperture. Various embodiments may comprise a coating layer adhered to at least a portion of each of the protrusions, the coating layer providing an increase in a tendency of the analyte-bearing liquid to be drawn towards the protrusion tips. Various embodiments may comprise an extractor electrode spaced at a distance from the electrode so as to form a gap therebetween, the extractor electrode having an aperture therein such that, in operation of the electrospray ion source, an electric field between the electrode and the extractor electrode causes a portion of the emitted charged particles to be propelled through the aperture in the extractor electrode. Various embodiments may comprise a bottom substrate adhered to a side of the electrode opposite to the protrusions so as to provide structural support to the electrode. Various embodiments may comprise a cover plate having at least one aperture therein; and a spacer disposed between the cover plate and the base of the electrode, so as to form a gap between at least a portion of the cover plate and at least a portion of the electrode, such that analyte-bearing liquid delivered from the conduit is caused to flow into the gap, wherein the first plurality of protrusions protrude through the at least one aperture.
In other aspects of the invention, there are disclosed methods of fabricating a multi-emitter electrospray electrode including the steps of: providing a substrate; exposing a first side of the substrate to a beam of accelerated heavy ions so as to produce a set of latent ion tracks within the substrate that do not penetrate to an opposite side of the substrate; exposing the first side of the substrate to a chemical etchant so as to form a plurality of etch channels within the substrate that extend into the substrate interior from the first side and that do not penetrate to the opposite side of the substrate; and depositing a layer of conductive material within the etch channels and on the first side of the substrate. Alternative subsequent steps may include either removing the substrate from the conductive material, the conductive material comprising the multi-emitter electrospray electrode or removing a portion of the opposite side of the substrate and at least a portion of the tips of the conical pillars so as to truncate a subset of the plurality of conical pillars, the truncated conical pillars comprising hollow electrospray nozzles of the multi-emitter electrospray electrode.
In yet other aspects of the invention, there are disclosed methods for providing ions derived from an analyte-bearing liquid to a mass spectrometer by electrospray ionization, the analyte-bearing liquid supplied at a total flow rate of greater than or equal to 50 microliters (μl) per minute comprising: (a) dividing the total flow into a plurality of sub-flows of analyte-bearing liquid, each sub flow providing a portion of the total flow at a rate of less than or equal to 500 nanoliters (nl) per minute; (b) providing a plurality of electrospray emitters; (c) providing each sub-flow of analyte bearing liquid to a respective one of the electrospray emitters; (d) generating an electrospray emission from each of the electrospray emitters in the presence of a gas or air; and (e) directing each electrospray emission to an ion inlet of the mass spectrometer. The gas or air, which may be at atmospheric pressure in various embodiments, may provide controllable evaporation of a solvent or aid in de-clustering between analyte ions and other particles. In other embodiments, the gas or air may be maintained at a pressure within a range of 0.03×atmospheric pressure to 2×atmospheric pressure.
Apparatus in accordance with the present teachings can comprise a material that has a large number of pillars per unit area—typically 1000-500,000 per square centimeter, corresponding to an average inter-pillar spacing in the range of approximately 6-320 μm. The tips of the pillars, from which ions are emitted when the electrode is in use as an electrospray emitter, can have a diameter of less than 1 μm. The density of pillars may controlled by controlling the duration of exposure of the substrate to the accelerated heavy ions.
Although the protrusions in this example are described as “pillars”, it should be clear that, depending on form factors, semantic preferences and other circumstances, the protrusions of the electrodes described in this document may, in any particular instance, be more aptly described as “columns”, “cones”, “needles”, “rods” or “wires”. These are all various types of protrusions or protruding surfaces away from a base or away from a basal surface. The ion emitters described herein may variously be described as “protrusions”, “pillars”, “columns”, “cones”, “needles”, “rods”, “wires” or even “capillaries” depending on form factors, shape, materials employed, method of manufacture, or other circumstances or factors. The present teachings provide benefits, relative to the conventional art, of providing simple manufacturability and robust multisprayer devices. Instead of a single nanospray tip, as in the conventional art, the present teachings provide thousands (or more) of nanospray emitters operating in parallel. Thus, the benefits of nanospray—namely, high ionization efficiency due to the small initial droplet size—can be married to the larger flow rates, 1 μl/min-10 ml/min, of standard liquid chromatography assays. A further advantage is that the disabling or malfunctioning of a single—or even several—of the emitters has a negligible effect on the overall mass spectrometry results. Also, for those embodiments in which the sample flows on the outside of the needles, the clogging issues that occur with nanospray capillaries are eliminated.
To efficiently capture all the ions generated when using apparatus or methods in accordance with the present teachings, the atmospheric pressure ion inlet to a mass spectrometer can be modified from the traditional circular cross section to a more elongated or letter box shape, or can take the shape of an array of ion transfer tubes. The array can be linear or circular to most efficiently match the dimensions of the droplet mist. Such ion inlet modifications, when used in conjunction with ion sources disclosed herein, are expected to provide increased sensitivity relative to existing ion source/mass spectrometer assemblies.
The present invention provides methods and apparatus for an improved ionization source for 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 attached in conjunction with the discussion below.
Most electrospray ionization devices used in mass spectrometry utilize hollow emitter structures, comprising internal channels through which an analyte-bearing fluid flows until it emerges at a hollow emitter tip. However, electrospray emitters are known to which fluid is supplied externally. For instance, Velásquez-García et al., in a technical paper titled “A planar array of micro-fabricated electrospray emitters for thruster applications (Journal of Microelectromechanical Systems, 15(5), 2006, pp. 1272-1280) describe planar arrays of micro-fabricated electrospray emitters intended for space propulsion applications. As shown in
United States Patent Application Publication 2009/0140137 A1 in the names of Hiraoka et al. teaches an ionization apparatus comprising holding means for holding a probe so as to be capable of reciprocating between a bottom end point at which a tip of the probe contacts a sample and a top end point at which the tip of the probe is spaced away from the sample; an ion guide, arranged such that the tip of the ion guide is positioned in the vicinity of the tip of the probe in the vicinity of the top end point, for introducing sample ions from the tip thereof to a mass spectrometry apparatus; and a high voltage generating apparatus applying a high voltage for electrospray between the probe and the ion guide, at least at a time when the probe is separated from the sample. A portion of the Hiraoka et al. apparatus is illustrated in
As taught by Hiraoka et al., a laser device (not shown) for irradiating the vicinity of the probe tip with laser light (ultraviolet, infrared or visible light) may be provided, such that the vicinity of the probe tip at the origin position or a position somewhat removed from the tip (a spaced-away position beneath the tip) may be irradiated with the laser beam 36. In the case of visible laser light [e.g., a frequency-doubled (532 nm) YAG laser], a surface plasmon is induced on the metal (probe) surface irradiated with the laser beam. The surface plasmon propagates along the probe surface toward the tip and intensifies the electric field strength in the vicinity of the probe tip. Accordingly, desorption ionization of sample molecules by electrospray is intensified. In a case where use is made of infrared laser light, promotion of sample drying and efficiency of ion desorption from a droplet are improved by heating the captured sample portion 32c.
The latent ion tracks are exposed to a suitable etchant 112 so as to produce an array of etch channels 110 within the substrate 102. Although the etch channels are shown as conical in shape, the etch channels may be made to approach cylindrical shapes by appropriate choice of etchant selectivity (the ratio of the etch rate of the latent track zone to the etch rate of the bulk substrate). One or more patterned masks, such as masks 109a and 109b, may be employed, either sequentially or simultaneously, so as to produce differential etch depths. For instance, mask 109a may be initially employed so as to expose a central portion of the set of latent ion tracks to an etchant for a first length of time so as to produce relatively deep channels. Mask 109b may be subsequently employed to expose peripheral regions of the set of latent ion tracks to the etchant for a shorter length of time, so as to produce relatively shallow channels in a region surrounding the deeper channels.
After the etch channels are formed at the desired depths, a multi-pillared electrode 114 may be formed by deposition of a conductive material in the etch channels 110 and onto an adjoining face of the substrate, the etch channels and adjoining face acting as a mold for the formation of the multi-pillared electrode 114. For instance, metal may be first sputtered onto the etched substrate so as to produce a continuous thin coating of metal within the etch channels and on the face of the substrate. Subsequently, the thin metal coating may used as an electrode in an electroplating process to as deposit a larger amount of bulk metal within the same regions, thereby forming the multi-pillared electrode 114 comprising a plurality of pillars 116.
The process described above can produce a material that has a large number of pillars per unit area—typically 10-100 million per square centimeter, corresponding to an average inter-pillar spacing in the range of 1-3 μm. The tips of the pillars, from which ions are emitted when the electrode is in use as an electrospray emitter, can have a diameter of less than 1 μm. The density of pillars may controlled by controlling the duration of exposure of the substrate to the accelerated heavy ions. Although the protrusions in this example are described as “pillars”, it should be clear that, depending on form factors, semantic preferences and other circumstances, the protrusions of the electrodes described in this document may, in any particular instance, be more aptly described as “columns”, “cones”, “needles”, “rods” or “wires”. These are all various types of protrusions or protruding surfaces away from a base or away from a basal surface.
Optionally, all or portions of the exposed side of the multi-pillared electrode may have a coating 115 deposited on it (them), the coating imparting further structural integrity or desirable surface properties to the multi-pillared electrode. For instance, the coating 115 may comprise a hydrophilic material which may have the function of increasing the tendency of an aqueous analyte-bearing liquid to spread along the surface of the coated multi-pillared electrode. Alternatively, the surface of the multi-pillared electrode 114 may receive a surface treatment, such as roughening of the surface on a nanometer scale, to increase the “wetting” tendencies of analyte-bearing liquids applied to the surface. New types of coatings are discussed by P. Forbes in an article titled “Self-Cleaning Materials” (Scientific American, August 2008, pp. 88-95. For instance, a thin-film coating of titania (TiO2) that has been exposed to ultraviolet light may provide “superhydrophilic” properties to the electrode, enabling an analyte-bearing liquid to spread along the surface as a film along the coated portions of the electrode. Such coating could even be patterned so as to channel the liquid—that is, direct the liquid along pre-determined pathways—on the surface of the electrode. Further, coatings are known whose wettability properties are “switchable”—capable of being controllably and reversibly transformed between (super)hydrophilic and (super)hydrophobic states with the application of certain wavelengths of light. Such coatings applied to all or portions of the multi-pillared electrode 114 may act as valves (for instance, “shut-off” valves) for initiating, stopping or even controlling rate of liquid flow to the pillars of the electrode.
In a second alternative procedure (
The individual pillars of the device resulting from the set of operations illustrated in
An end product of the fabrication steps discussed above is the monolithic or continuous-surface multi-pillared electrode 114. In some embodiments, the multi-pillared electrode may comprises approximately 1000-10,000 emitting pillars or needles per cm2 (inter-pillar spacing of emitting pillars of approximately 100-320 μm) with each emitting pillar having a height of approximately 10 μm to several tens of microns above an inter-pillar base portion of the electrode. Such an electrode could provide the benefits of nanospray ionization into flow regimes characteristic of typical liquid chromatography experiments. For example, in order to be compatible with mass spectrometer ion inlets, such an electrode may have a “footprint” area of about 1 cm2 or less. If an electrode of 1 cm2 footprint area comprises 1000 emitting pillars, each pillar capable of ionizing 100 nanoliters (nl) of solution per minute, then the combined action of all the pillars can ionize 0.1 ml/min of sample, which is within the realm of routine laboratory sample flow rates. Generally, the ionization rate per pillar will be the flow-limiting step. Each pillar will “drain”, on average, an amount of liquid equivalent to approximately 1 μm depth per minute, which should be well within the replenishment capabilities of the liquid delivery conduits or channels.
Some embodiments may employ a smaller emitter electrode having a square area of approximately 1 mm2, which may be suitable for interchange with conventional single-capillary electrospray devices. Assuming an inter-pillar spacing of emitting pillars of approximately 31-32 μm, then 1000 emitting pillars can be incorporated onto such an electrode, corresponding to a pillar density of 100,000 per cm2. In this situation, the ability to distribute the liquid evenly among the pillars must be considered. If, once again, the liquid delivery rate is 0.1 ml/min and each pillar ionizes 100 nanoliters (nl) of liquid per minute, then each pillar is required to drain, on average, an amount of liquid equivalent to approximately 100 μm depth per minute. Even though this depth is generally greater than the pillar heights, it still may be possible to achieve such a flow rate with a steady state depth of approximately 1.5-2.0 μm that will not flood the electrode tips, provided that the fluid surge is prevented and that even fluid flow may be maintained in the inter-pillar regions of the electrode. A superhydrophobic coating or even perforations in the inter-pillar base portions of the electrode (to enable liquid delivery through the electrode from a substrate or reservoir on the opposite side) may be advantageously employed in this situation.
The extractor electrode 130 (also referred to as a counter electrode) comprises an aperture 131 through which charged particles emitted from a sample pass under the influence of an electrical potential applied between the multi-pillared emitter electrode 114 and the extractor electrode 130. The extractor electrode may comprise a portion of a mass spectrometer and, as such, the aperture 131 may comprise an ion inlet aperture of a mass spectrometer. The aperture 131 may be subdivided into a plurality of sub-apertures 132 separated by partitions or other structural elements. The apparatus 101 may, optionally, further comprise a cover plate 120 that is disposed substantially perpendicular to the longitudinal axes of the pillars 116 and that is maintained at a distance from the base portions or inter-pillar portions 113 of the multi-pillared emitter electrode 114 by means of one or more spacers 122. The size of the resulting gap between the base or interpillar portions 113 and the cover plate 120 could be controlled to regulate the flow of liquid and prevent it from spilling out. This gap can also serve as a buffer reservoir to guard against overfilling of the apparatus from an externally supplied liquid pumped into the apparatus at a rate that does not match the rate of wicking of liquid along the pillar surfaces.
One or more fluid inlet conduits 124 such as capillary tubes may pass through the one or more spacers 122 so as to introduce analyte-bearing sample liquids into the gap or gaps between the base or inter-pillar portions 113 of the multi-pillared emitter electrode 114 and the cover plate 120. The fluid inlet conduit or conduits 124 may serve, for instance, to couple the apparatus to a liquid chromatograph or a syringe pump so that eluent would flow into the gap and between the pillars 116 so as to be subsequently wicked towards the pillar tips. The emitter electrode 114 may be formed into a region of relatively short pillars 111 (for instance, see the upper right drawing of
Generation of an electric field in the vicinity of the emitter electrode 114 by application of a voltage difference between the multi-pillared emitter electrode and the extractor electrode 130 produced a concentration of electric field lines at each pillar tip. With sufficient electric field strength, the analyte-bearing liquid 126 deforms into a Taylor cone 117 at each respective pillar tip and emits a charged stream 128, comprising a jet, a spray of charged liquid droplets and, ultimately, a cloud of free ions. The emitter plate is set to be the anode if positively charged ions are to be emitted and is set to be the cathode if negatively charged ions are to be emitted. The liberated ions are then electrostatically directed into an ion inlet orifice of a mass spectrometer for analysis. The extractor electrode may, in fact, comprise an ion inlet orifice plate of the mass spectrometer. In order to minimize space charge effects, the pillar tips may be located at a distance from a mass spectrometer ion inlet port such that the ion flow has been accelerated towards the ion inlet port up to a velocity greater than a certain threshold velocity—for instance, greater than about 10-50 m/s.
Still referring to
In operation, the nano-electrospray apparatus 400 is utilized to introduce electrosprayed ions into the ion inlet orifice of a mass spectrometer similar to the situation illustrated in
The nano-electrospray multi-emitter array 302 shown in
The discussion included in this application is intended to serve as a basic description. Although the present invention has been described in accordance with the various embodiments shown and described, one of ordinary skill in the art will readily recognize that there could be variations to the embodiments and those variations would be within the spirit and scope of the present invention. The reader should be aware that the specific discussion may not explicitly describe all embodiments possible; many alternatives are implicit. Accordingly, many modifications may be made by one of ordinary skill in the art without departing from the spirit, scope and essence of the invention. Neither the description nor the terminology is intended to limit the scope of the invention. Any publications, patents or patent application publications mentioned in this specification are explicitly incorporated by reference in their respective entirety.
| Number | Name | Date | Kind |
|---|---|---|---|
| 5173610 | Lo | Dec 1992 | A |
| 5397901 | Lo | Mar 1995 | A |
| 6245227 | Moon et al. | Jun 2001 | B1 |
| 6563111 | Moon et al. | May 2003 | B1 |
| 6633031 | Schultz et al. | Oct 2003 | B1 |
| 6744046 | Valaskovic et al. | Jun 2004 | B2 |
| 8080930 | King | Dec 2011 | B2 |
| 20020000517 | Corso et al. | Jan 2002 | A1 |
| 20020158027 | Moon et al. | Oct 2002 | A1 |
| 20020175281 | Valaskovic | Nov 2002 | A1 |
| 20020185595 | Smith et al. | Dec 2002 | A1 |
| 20030111599 | Staats | Jun 2003 | A1 |
| 20030143493 | Schultz et al. | Jul 2003 | A1 |
| 20030160166 | Glish et al. | Aug 2003 | A1 |
| 20030168591 | Smith et al. | Sep 2003 | A1 |
| 20030201390 | Corso et al. | Oct 2003 | A1 |
| 20030213918 | Kameoka et al. | Nov 2003 | A1 |
| 20040173743 | Valaskovic et al. | Sep 2004 | A1 |
| 20040227072 | Park | Nov 2004 | A1 |
| 20050054208 | Fedorov et al. | Mar 2005 | A1 |
| 20050252840 | Arnold et al. | Nov 2005 | A1 |
| 20060103051 | Staats | May 2006 | A1 |
| 20060113463 | Rossier et al. | Jun 2006 | A1 |
| 20060186329 | Gebhardt et al. | Aug 2006 | A1 |
| 20060192107 | DeVoe et al. | Aug 2006 | A1 |
| 20060207877 | Schmidt et al. | Sep 2006 | A1 |
| 20060208186 | Goodley et al. | Sep 2006 | A1 |
| 20070183928 | Neyer et al. | Aug 2007 | A1 |
| 20090056133 | Waits et al. | Mar 2009 | A1 |
| 20090095057 | Staats | Apr 2009 | A1 |
| 20090114814 | Nissila et al. | May 2009 | A1 |
| 20090140137 | Hiraoka et al. | Jun 2009 | A1 |
| 20090230296 | Kelly et al. | Sep 2009 | A1 |
| 20090294363 | Liu | Dec 2009 | A1 |
| 20110192217 | Choikhet et al. | Aug 2011 | A1 |
| 20120043460 | Wouters et al. | Feb 2012 | A1 |
| Number | Date | Country |
|---|---|---|
| WO 2009114951 | Sep 2009 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 20110192968 A1 | Aug 2011 | US |
