EP1364387A2 - Method and apparatus for a multiple part capillary device for use in mass spectrometry - Google Patents
Method and apparatus for a multiple part capillary device for use in mass spectrometryInfo
- Publication number
- EP1364387A2 EP1364387A2 EP01913068A EP01913068A EP1364387A2 EP 1364387 A2 EP1364387 A2 EP 1364387A2 EP 01913068 A EP01913068 A EP 01913068A EP 01913068 A EP01913068 A EP 01913068A EP 1364387 A2 EP1364387 A2 EP 1364387A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- capillary
- source
- ionization
- ions
- union
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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Classifications
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/02—Details
- H01J49/04—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
Definitions
- the present invention relates generally to mass spectrometry and the analysis of chemical samples, and more particularly to capillaries for use in mass spectrometry. Described herein is a multiple part capillary for use in mass spectrometry (particularly with ionization sources) to transport ions from an ionization source to subsequent regions of a mass spectrometer for analysis * therein. , BACKGROUND OF THE PRESENT INVENTION The present invention relates to capillary tubes for use in mass spectrometry. Mass spectrometry is an important tool in the analysis of a wide range of chemical compounds. Specifically, mass spectrometers can be used to determine the molecular weight of sample compounds.
- the analysis of samples by mass spectrometry consists of three main steps -- formation of ions from sample material, mass analysis of the ions to separate the ions from one another according to ion mass, and detection of the ions.
- the particular combination of means used in a given spectrometer determine the characteristics of that spectrometer.
- To mass analyze ions for example, one might use a magnetic (B) or electrostatic (E) analyzer. Ions passing through a magnetic or electrostatic field will follow a curved path. In a magnetic field the curvature of the path will be indicative of the momentum- to-charge ratio of the ion.
- the curvature of the path will be indicative of the energy-to-charge ratio of the ion. If magnetic and electrostatic analyzers are used consecutively, then both the momentum-to-charge and energy-to- charge ratios of the ions will be known and the mass of the ion will thereby be determined.
- Other mass analyzers are the quadrupole (Q) , the ion cyclotron resonance (ICR) , the time-of- flight (TOF) , and the quadrupole ion trap analyzers. Before mass analysis can begin, however, gas phase ions must be formed from sample material.
- ions may be formed by electron ionization (El) or chemical ionization (CI) of the gas phase sample molecules.
- El electron ionization
- CI chemical ionization
- solid samples e.g. semiconductors, or crystallized materials
- ions can be formed by desorption and ionization of sample molecules by bombardment with high energy particles.
- Secondary ion mass spectrometry SIMS
- SIMS Secondary ion mass spectrometry
- an analyte is dissolved in a solid, organic matrix.
- Laser light of a wavelength that is absorbed by the solid matrix but not by the analyte is used to excite the sample.
- the matrix is excited directly by the laser, and the excited matrix sublimes into the gas phase carrying with it the analyte molecules.
- the analyte molecules are then ionized by proton, electron, or cation transfer from the matrix molecules to the analyte molecules.
- Atmospheric pressure ionization includes a number of methods. Typically, analyte ions are produced from liquid solution at atmospheric pressure.
- electrospray ionization ESI
- Dole et al M. Dole, L.L. Mack, R.L. Hines, R.C. Mobley, L.D. Ferguson, M.B. Alice, J. Chem . Phys . 49, 2240, 1968
- analyte is dissolved in a liquid solution and sprayed from a needle.
- the spray is induced by the application of a potential difference between the needle (where the liquid emerges) and a counter electrode.
- a potential difference between the needle (where the liquid emerges) and a counter electrode.
- the emerging liquid By subjecting the emerging liquid to a strong electric field, it becomes charged, and as a result, it "breaks up” into smaller particles if the charge imposed on the liquid's surface is strong enough to overcome the surface tension of the liquid (i.e., as the particles attempt to disperse the charge and return to a lower energy state) .
- Electrospray mass spectrometry was introduced by Yamashita and Fein (M. Yamashita and M.B. Fein, J “ . Phys . Chem. 88, 4671, 1984) .
- ESI and MS ions had to be formed at atmospheric pressure, and then introduced into the vacuum system of a mass analyzer via a differentially pumped interface.
- the combination of ESI and MS afforded scientists the opportunity to mass analyze a wide range of samples, and ESMS is now widely used primarily in the analysis of biomolecules (e.g. proteins) and complex organic molecules.
- biomolecules e.g. proteins
- API -MS complex organic molecules.
- Pneumatic assisted electrospray (A. P. Bruins, T.R. Covey, and J.D. Henion, Anal. Chem. 59, 2642, 1987) uses nebulizing gas flowing past the tip of the spray needle to assist in the formation of droplets. The nebulization gas assists in the formation of the spray and thereby makes the operation of ESI easier.
- Nano electrospray (M.S. Wilm, M. Mann, Int . J. Mass Spectrom .
- MALDI has recently been adapted by Victor Laiko and Alma Burlingame to work at atmospheric pressure (Atmospheric Pressure Matrix Assisted Laser Desorption Ionization, poster #1121, 4 th International Symposium on Mass Spectrometry in the Health and Life Sciences, San Francisco, Aug. 25 - 29, 1998) and by Standing et al . at elevated pressures (Time of Flight Mass Spectrometry of Biomolecules with Orthogonal Injection + Collisional Cooling, poster #1272, 4 th International Symposium on Mass Spectrometry in the Health and Life Sciences, San Francisco, Aug. 25 - 29, 1998; and Orthogonal Injection TOFMS Anal . Chem. 71(13), 452A (1999)) .
- An elevated pressure ion source always has an ion production region (wherein ions are produced) and an ion transfer region (wherein ions are transferred through differential pumping stages and into the mass analyzer) .
- the ion production region is at an elevated pressure -- most often atmospheric pressure -- with respect to the analyzer.
- the ion production region will often include an ionization "chamber". In an ESI source, for example, liquid samples are "sprayed" into the "chamber" to form ions.
- Analyte ions produced via an API method need to be transported from the ionization region through regions of differing pressures and ultimately to a mass analyzer for subsequent analysis (e.g., via time-of-flight mass spectrometry (TOFMS) , Fourier transform mass spectrometry (FTMS) , etc.) .
- TOFMS time-of-flight mass spectrometry
- FTMS Fourier transform mass spectrometry
- FIG. 1 An example of such a prior art capillary tubes is shown in FIG. 1.
- capillary 7 comprises a generally cylindrical glass tube 2 having an internal bore 4.
- capillary 7 The ends of capillary 7 include a metal coating (e.g., platinum, copper, etc.) to form conductors 5 which encompass the outer surface of capillary 7 at its ends, leaving a central aperture 6 such that the entrance and exit to internal bore 3 are left uncovered.
- Conductors 5 may be connected to electrical contacts (not shown) in order to maintain a desired space potential at each end of capillary 7.
- a first electrode (one of conductors 5) of capillary 7 may be maintained at an extreme negative potential (e.g.
- capillary 8 which comprises an outer capillary sleeve 9 surrounding an inner capillary tube 10.
- Sleeve 9 has substantially cylindrical inner surface 11 and outer surface 14.
- tube 10 has substantially cylindrical inner surface 12 and outer surface 13.
- the innermost channel, or bore, of capillary 8 is substantially formed by inner surface 12 of tube 10.
- Capillary 8 is substantially radially symmetrical about its central longitudinal axis 15 extending from an upstream end 16 to a downstream end 17.
- capillary 8 has conductive end caps 18 comprising the unitary combination of a tubular body having cylindrical inner surface 20 and outer surface 21 and an end plate 22 having inner surface 23 and outer surface 24 with a central aperture.
- end cap 18 encompasses and is m circumferential engagement with a reduced diameter portion 25 of sleeve 9 adjacent to the respective ends of capillary 8, such that the external diameter of end cap 18 substantially the same as the external diameter of sleeve outer surface 14.
- a removal tool (not shown) is inserted into the tube as to engage the tube's inner surface 12. It is further suggested by the prior art that in order to remove tube 10 it may be necessary to apply a slight torque orthogonal to axis 15, or other appropriate means such as bonding a removal tool to the tube using an adhesive. Once the tube is withdrawn, a replacement tube may be inserted into sleeve 9.
- the first means must be removed from the vicinity of the capillary entrance and the second must then be properly positioned with respect to the capillary entrance.
- a positioning means must be provided for positioning the ion production means with respect to the capillary entrance. This might take the form of precision machined components, a translation stage on which the ion production means is mounted, or some other device.
- capillaries if the ion production means is required or desired to be remote from the source, a long, fixed length capillary would have to be produced and installed (in a fixed position) in the source.
- Another limitation of prior art capillaries relates to the orientation of the capillary bore with respect to the ion production means. Such orientation can be important for the operation of the source.
- One major consideration in the operation of an electrospray source is the formation of large droplets from the analyte solution at the spray needle. Such droplets do not readily evaporate. If these droplets enter the capillary, they may cause the capillary to become contaminated with a residue of analyte molecules and salts. In view of this, Apfel et al .
- Prior art capillaries are further limited in the geometry of the capillary bore. That is, prior art capillaries, as depicted in FIGs . 1-3, are substantially straight (i.e., cylindrically symmetric) and fixed (i.e., the geometry of the capillary and its bore is fixed at the time of manufacture) . Applicant has recognized the need for an ion transfer device or capillary which can be cleaned or replaced without the need to shut down the entire mass spectrometer in which it resides. The present invention allows for the removal of one or more sections of the capillary (for cleaning or replacement) without having to shut down the pumping system or the instrument to which it is attached.
- the capillary according to the present invention can, among other things, be made from different materials, take on different sizes, shapes or forms, as well as perform different functions .
- the design of the multiple part capillary according to the present invention provides added versatility to the use of ionization chambers as well as to the use and performance of any new and existing ionization methods.
- the invention provides for interfacing with robotic sampling devices to provide a fully automated system for the analysis of a variety of chemical species efficiently and cost effectively.
- the present invention relates generally to mass spectrometry and the analysis of chemical samples, and more particularly to capillaries for use therein.
- the invention described herein comprises an improved method and apparatus for transporting ions from a first pressure region in a mass spectrometer to a second region therein. More specifically, the present invention provides a multiple part capillary for more efficient use in mass spectrometry (particularly with ionization sources) to transport ions from the first pressure region to a second pressure region.
- a first aspect of the present invention is to provide a capillary for use in an ion source having improved flexibility and accessibility over prior art designs.
- a capillary according to the invention consists of at least two sections joined together end to end such that gas and sample material in the gas can be transmitted through the capillary across a pressure differential.
- the capillary is intended for use in an ion source wherein ions are produced at an elevated pressure and transported by the capillary into a vacuum region of the source.
- the present invention allows for the removal of one or more sections of the capillary (for cleaning or replacement) without having to shut down the pumping system of the instrument to which it is attached. These sections may be made of different materials -- e.g., glass, metal, composite, etc. -- which may be either electrically conducting or non-conducting.
- each section of the capillary according to the invention does not have to be straight or rigid, rather, one or more of the sections may be flexible such that it (or they) can bend in any direction.
- a further object of the invention is to provide a multiple part capillary which offers improved flexibility in its geometric orientation with respect to other devices in the ionization source -- especially the ion production means.
- the axis of the bore or "channel" of the capillary at the capillary entrance might be positioned at any angle with respect to the ion production means. This angle, as discussed in Apfel U.S. Patent Nos . 5,495,108 and 5,750,988 can be important, for example, in the separation of spray droplets from desolvated analyte ions.
- the entrance section of the capillary might be modified or exchanged before or during instrument operation to effect a change in the orientation of the entrance with respect to the ion production means or other device.
- This flexibility applies to the translational position of the entrance of the capillary as well as its angular orientation. That is, the position of the entrance of the capillary might be changed before or during instrument operation by either modification or exchange of the first section of the capillary. This allows for the transmission of ions from a variety of locations either near or removed from the immediate location of the source.
- Another object of the present invention is to provide a multipurpose multiple part capillary wherein the bore or "channel" of one or more of the sections of the multiple part capillary may comprise any useful geometry (i.e., straight, helical, wave-like, etc.) .
- the bore or "channel" of one or more of the sections of the multiple part capillary may comprise any useful geometry (i.e., straight, helical, wave-like, etc.) .
- the geometry of the bore may be, but is not necessarily, related to the outer surface of the capillary.
- a capillary might have a cylindrically symmetric outer surface but have an inner bore which is helical.
- Yet another purpose of the present invention is to provide a simple and efficient method and apparatus for integrating two source assemblies.
- a complete ion source may include a multitude of sub-assemblies.
- an ion source might include an ion production means sub-assembly and vacuum sub-assembly.
- the ion production means sub-assembly might include a spray needle, its holder, a translation stage, etc.
- the vacuum sub-assembly might contain pumps, pumping restrictions, and ion optics for guiding ions into the mass analyzer.
- the capillary would be integrated entirely in one sub-assembly -- the vacuum sub-assembly.
- significant effort is required in prior art systems to align the ion production means sub-assembly -- specifically the spray needle -- with the vacuum sub-assembly -- specifically the capillary entrance.
- the multiple part capillary according to the present invention eases the integration of such sub-assemblies by including capillary sections in each of the sub-assembly.
- the sub-assemblies are integrated by joining the capillary sections together. Any necessary alignments are performed within a given sub-assembly -- e.g. alignment of the spray needle with the first section of capillary.
- the present invention provides added flexibility for switching from one ionization source to another or from one sample to another.
- the capillary according to the invention is capable of efficiently and accurately being used with multiple electrospray sources.
- the capillary according to the invention is useful in multiplexing.
- Another purpose of the invention is to provide a multiple part capillary which can be used with chromatographic sample preparation (e.g., liquid chromatography, capillary electrophoresis, etc.) .
- chromatographic sample preparation e.g., liquid chromatography, capillary electrophoresis, etc.
- the effluent from such a chromatographic column may be injected
- a plurality of such chromatographic columns may be used in conjunction with a plurality of sprayers -- for example one sprayer per column.
- the presence of analyte in the effluent of any given column might be detected by any appropriate mans, for example a UV detector.
- the sprayer associated with the column in question is "turned on” so that while analyte is present the sprayer is producing ions but otherwise the sprayer does not. If analyte is present simultaneously at more than one sprayer, the sprayers are multiplexed, as discussed above.
- FIG. 1 A further understanding of the present invention can be obtained by reference to a preferred embodiment set forth in the illustrations of the accompanying drawings.
- FIG. 1 A further understanding of the present invention can be obtained by reference to a preferred embodiment set forth in the illustrations of the accompanying drawings.
- FIG. 1 A further understanding of the present invention can be obtained by reference to a preferred embodiment set forth in the illustrations of the accompanying drawings.
- FIG. 1 A further understanding of the present invention can be obtained by reference to a preferred embodiment set forth in the illustrations of the accompanying drawings.
- FIG. 1 shows a partial cut-away cross-sectional view of a prior art capillary comprising a unitary glass tube having a cylindrical outer surface and internal bore
- FIG. 2 shows a partial cut-away cross sectional view of another prior art capillary comprising a concentric outer capillary sleeve and inner capillary tube
- FIG. 3 shows a prior art spray chamber of a prior art electrospray ionization source wherein the channel of the spray needle is oriented orthogonal to the channel of the capillary
- FIG. 4 shows a preferred embodiment of a multiple part capillary according to the present invention
- FIG. 5 shows an alternate embodiment of the multiple part capillary, wherein the channel of the first section comprises a helical structure
- FIG. 6 shows an ESI sprayer needle oriented at an angle ⁇ with respect to the inlet to the channel and an angle with respect to the body of an embodiment of the multiple part capillary according to the present invention
- FIG. 7 shows an embodiment of the multiple part capillary according to the present invention as used with an ESI ionization source
- FIG. 8 shows a multiple part capillary according to the present invention as a means for integrating two source sub- assemblies
- FIG. 9 shows the multiple part capillary according to the present invention as a means for integrating a sample preparation robot with an API source for mass spectrometry
- FIG. 10 shows an embodiment of the multiple part capillary according to the present invention as a means for integrating a
- FIG. 11 shows a close-up view of the use of the multiple part capillary with a MALDI probe in accordance with the present invention.
- multiple part capillary 35 As discussed above, the present invention relates generally to the mass spectroscopic analysis of chemical samples and more particularly to mass spectrometry. Specifically, an apparatus and method are described for transport of ions between pressure regions within a mass spectrometer. Reference is herein made to the figures, wherein the numerals representing particular parts are consistently used throughout the figures and accompanying discussion. With reference first to FIG. 4, shown is multiple part capillary 35 according to a preferred embodiment of the present invention. As depicted in FIG. 4, multiple part capillary 35 comprises: first section 28 having capillary inlet end 26 and first channel 27; union 29 having o-ring 31; second section 33 having second channel 32 and capillary outlet end 34; and metal coatings 30A and 30B.
- first section 28 is connected to second section 33 by union 29.
- union 29 is substantially cylindrical having two coaxial bores, 60 and 61, and through hole 62 of the same diameter as channels 26 and 32.
- section 28 and union 29 are composed of metal - e.g. stainless steel.
- the inner diameter of bore 60 and the outer diameter of section 28 are chosen to achieve a "press fit" when section 28 is inserted into bore 60. Because the press fit is designed to be tight, union 29 is thereby strongly affixed to section 28 and a gas seal is produced between union 29 and section 28 at the surface of the bore.
- the inner diameter of bore 61 is of slightly larger diameter than the outer diameter of section 33 (including metal coating 30A) so as to produce a "slip fit" between union 29 and section 33.
- a gas seal is established between bore 61 and section 33 via o-ring 31. Electrical contact between metal coating 30A, union 29, and section 28 via direct physical contact between the three.
- Through hole 62 allows for the transmission of gas from entrance end 26 through to exit end 34 of the capillary.
- union 29 and sections 28 and 33 are formed in such a way as to eliminate any "dead volume” between these components. To accomplish this, the ends of sections 28 and 33 are formed to be flush with the inner surface of union 29.
- metal coating 30A and 30B - is composed of glass in the preferred embodiment.
- metal coating 30A - together with union 29 and section 28 - can be maintained at a different electrical potential than metal coating 30B.
- union 29, and sections 28 and 33 may be composed of a variety of materials conducting or non-conducting; the outer diameters of the sections may differ substantially from one another; the inner diameters of the sections may differ substantially from one another; either or both ends or any or all sections may be covered with a metal or other coating; rather than a coating, the ends or capillary sections may be covered with a cap composed of metal or other material; the capillary may be composed of more than two sections always with one fewer union than sections; and the union may be any means for removably securing the sections of capillary together and providing an airtight seal between these sections.
- Each end of union 29 could comprise a generally cylindrical opening having an internal diameter slightly larger than the external diameter of the end of the capillary section which is to be inserted therein.
- a gas seal is made with each capillary section via an o-ring similar to o-ring 31.
- springs to accomplish electrical contact between union 29 and sections 28 and 33.
- a conducting spring would be positioned in union 29 adjacent to o-ring 31.
- the length of first section 28 is less than (even substantially less than) the length of second section 33.
- first section 28 and second section 33 are such that within a range of desired pressure differentials across capillary 35, a gas flow rate within a desired range will be achieved.
- the length of second section 33 and the internal diameter of second channel 32 are such that the gas transport across second section 33 alone (i.e., with first section 28 removed) at the desired pressure differential will not overload the pumps which generate the vacuum in the source chamber of the system. This allows the removal (e.g., for cleaning or replacement) of first section 28 of capillary 35 without shutting down the pumping system of the mass spectrometer. While the prior art, as depicted in FIG. 2, attempts to accomplish removal, without shutting down the vacuum, it is difficult and cumbersome.
- capillary 35 is shown wherein capillary section 28 has a serpentine internal channel 64. That is, the geometric structure of the internal channel of the capillary section is sinusoidal. Of course, other geometrical structures (i.e., helical, varying diameter, non-uniform, etc.) may be used in accordance with the invention.
- sinusoidal internal channel 64 causes larger particles -- such as droplets from an electrospray -- to collide with the walls of the channel and thereby not pass completely through the capillary.
- the curved (or sinusoidal) geometry of channel 64 also increases the length of the channel, which provides the advantage of permitting a larger diameter channel .
- Such a larger diameter channel may be advantageous in that it may provide greater acceptance of sampled species (e.g., electrosprayed ions, etc.) at a given flow rate and pressure differential.
- a sinusoidal -- or any other geometry -- channel may be used in either first section 28 or second section 33, or both.
- FIG. 6 shown is an embodiment of the multiple part capillary according to the invention as used with an ESI sprayer 65 wherein axis 70 of sprayer 65 is oriented at angle . 66 with respect to axis 69 of the body of capillary 72.
- angle ⁇ 67 between sprayer axis 70 and axis 71 of channel entrance 68 can be substantially different than angle ⁇ 66.
- the capillary entrance angle ⁇ 66 may be any angle from 0° and 180° .
- the specific angle selected is dependent upon, among other things, the sample species being tested, the ionization source used, etc.
- the electrospray process results in the formation of charged droplets and molecular ions.
- the presence of large droplets in the spray can result in contamination of the capillary and generally poor instrument performance.
- One way of limiting the influence of large droplets on instrument performance is to spray away from the capillary entrance. That is, the spray needle is oriented so that it is not pointed directly at the capillary entrance.
- Section 74 can be removed from the system - by pulling it off along axis 69 - and cleaned without necessarily shutting the instrument or its vacuum system off.
- the ion production means is an ESI spray ⁇ -r device, shown as spray needle 36 in spray chamber 40.
- sample solution is formed into droplets at atmospheric pressure by spraying the sample solution from spray needle 36 into spray chamber 40.
- the spray is induced by the application of a high potential between spray needle 36 and entrance 26 of first capillary section 28 within spray chamber 40.
- Sample droplets from the spray evaporate while in spray chamber 40 thereby leaving behind an ionized sample material (i.e., sample ions) .
- sample ions are accelerated toward capillary inlet 26 of channel 27 by an electric field generated between spray needle 36 and inlet 26 of first section 28 of capillary 35.
- These ions are transported through first channel 27 into and through second channel 32 to capillary outlet 34.
- first section 28 is joined to second section 33 in a sealed manner by union 29.
- the flow of gas created by the pressure differential between spray chamber 40 and first transfer region 45 further causes the ion to flow through the capillary channels from the ionization source toward the mass analyzer. Still referring to FIG.
- first transfer region 45 is formed by mounting flange 48 on source block 54 where a vacuum tight seal is formed between flange 48 and source block 54 by o- ring 58.
- Capillary 35 penetrates through a hole in flange 48 where another vacuum tight seal is maintained (i.e., between flange 48 and capillary 35) by o-ring 56.
- a vacuum is then generated and maintained in first transfer 45 by a pump (e.g., a roughing pump, etc., not shown) .
- the inner diameter and length of capillary 35 and the pumping speed of the pump are selected to provide as high a rate of gas flow through capillary 35 as reasonably possible while maintaining a pressure of 1 mbar in the first transfer region 45.
- first skimmer 51 is placed adjacent to capillary exit 34 within first transfer region 45.
- An electric potential between capillary outlet end 34 and first skimmer 51 accelerates the sample ions toward first skimmer 51.
- a fraction of the sample ions then pass through an opening in first skimmer 51 and into second pumping region 43 where pre- hexapole 49 is positioned to guide the sample ions from the first skimmer 51 to second skimmer 52.
- Second pumping region 43 is pumped to a lower pressure than first transfer region 45 by pump 53.
- a fraction of the sample ions pass through an opening in second skimmer 52 and into third pumping region 44, which is pumped to a lower pressure than second pumping region 43 via pump 53.
- the sample ions are guided from second skimmer 52 to exit electrodes 55 by hexapole 50. While in hexapole 50 ions undergo collisions with a gas (i.e., a collisional gas) and are thereby cooled to thermal velocities. The ions then reach exit electrodes and are accelerated from the ionization source into the mass analyzer for subsequent analysis.
- a gas i.e., a collisional gas
- Another purpose of the present invention is to provide a simple and efficient method and apparatus for integrating two source assemblies.
- a complete ion source may include a multitude of sub-assemblies.
- ion source 80 includes ion production means sub-assembly 81 and vacuum sub- assembly 82.
- the ion production means sub-assembly includes, among other things, spray chamber 40 and spray needle 36.
- the vacuum sub- assembly includes among other things, pump 53, pumping restrictions 51 and 52, and ion optical elements 49 - 52 and 55 for guiding ions into the mass analyzer.
- the capillary would be integrated entirely in one sub-assembly - the vacuum sub-assembly.
- significant effort is required in prior art systems to align the ion production means sub-assembly - specifically the spray needle - with the vacuum sub-assembly - specifically the capillary entrance.
- capillary section 28 is an integral component of ion production means sub-assembly 81 and capillary section 33 is an integral component of vacuum sub-assembly 82.
- Sub-assemblies 81 and 82 are integrated in part by joining capillary sections 28 and 33 together via union 29. Any necessary alignments are performed within a given sub-assembly - e.g. alignment of spray needle 36 with entrance 26 of channel 27.
- any variety of sub- assemblies might be integrated, in part or in whole, by including capillary sections in these sub-assemblies and subsequently joining these capillary sections together as discussed with respect to figure 8.
- any number of sub-assemblies with any variety of functions might be used. Such functions might include ion production, desolvation of spray droplets via a heated capillary section, ion transfer to the mass analyzer, etc.
- any type of atmospheric pressure ionization means - including ESI, API MALDI, atmospheric pressure chemical ionization, nano electrospray, pneumatic assist electrospray, etc. - could be assembled into a source in this way.
- the capillary according to the present invention might also be used to transport ions from ionization means remote from the instrument.
- This is exemplified by the embodiment of FIG. 9.
- Shown in FIG. 9 is an embodiment of the multiple part capillary according to the invention as used for integrating a sample preparation robot with an Atmospheric Pressure Ionization (API) source.
- the system shown comprises, among other things: robot 90; robot arm 91; sample tray (not shown); source tray 92; sprayer 93; multiple part capillary 98 comprising first section 28 having inlet 26, second section 33 having outlet 34, and union 29; gas transport line 94; source cover 95; source vacuum sub-assembly 96; and mass analyzer 97.
- Robots such as in the embodiment of FIG.
- a Gilson 215 Liquid Handler Robot - consist of a robot arm - e.g. arm 91 - used to manipulate samples, and "trays" of samples and sample containers.
- the robot arm is used to move samples, solutions, and reactants from one container - i.e. tubes, vials, or microtiter wells - to another.
- the robot can be used to prepare samples for subsequent analysis.
- sample spray and ionization would occur within robot 90 and only ions would be transported -- via multiple part capillary 98 -- to mass analyzer 97.
- a specially prepared source tray 92 is used.
- Sample is obtained by robot 90 from a sample tray by sucking solution into sprayer 93.
- Robot arm 91 then moves sprayer 93 to source tray 92 and to a predefined location near entrance 26 of capillary 98. Drying gas can be transported into source tray from vacuum sub-assembly 96 via a gas transport line 94.
- Sprayer 93 is attached to robot arm 91 and set at ground potential (of course, any ESI sprayer may be used (e.g., pneumatically assisted sprayers, nanosprayer needles, etc.)), while inlet 26 to first section 28 of capillary 98 set at high voltage. This potential difference between sprayer 94 and first section 28 induces the spray of the sample solution and production of analyte ions.
- the capillary according to the present invention is also useful in transporting ions from varying locations during operation.
- FIG. 10 shown is an embodiment of the multiple part capillary according to the invention as a means for integrating a sample preparation robot with an elevated pressure MALDI source for use in mass spectrometry.
- the system depicted in FIG. 10 comprises a laser 99, attenuator 100, fiber optic 101, robot 90 having robot arm 91 for control and movement of sample
- the alternative embodiment of the multiple part capillary of the invention as shown in FIG. 10 comprises a flexible first section 105 such that its inlet end may be moved by robot arm -6-8- 91 to various positions for acceptance of the MALDI samples to be analyzed.
- sample preparation and ionization are both performed by robot 90 such that only ions would be transported through the multiple part capillary 98 to vacuum sub-assembly 96 and ultimately to mass analyzer 97.
- robot arm has attached at its end sample probe 102, and fiber optic 101 for directing the laser beam from laser 99 onto sample holder 104 to ionize samples thereon.
- the ions formed by the laser beam hitting the samples on sample holder 104 are then carried by the gas flow into and through capillary 98 to the differential pumping region of vacuum sub-assembly 96, where additional ion optics (not shown) are designed to further transport the ions from outlet end of capillary 98 to mass
- the multiple part capillary provides a means for integrating a sample preparation robot with MALDI mass analysis. Shown in FIG. 11 are capillary 105, robot arm 91, receptacle 106, fiber optic 101, and sample plate 104 with raised conical formations 107 onto which samples (not shown) are deposited. Sample plate 104 and the conical formations form a unitary device composed of conducting material - e.g. stainless steel.
- capillary section 105 optionally comprises a specially shaped orifice which fits over cone-shaped sample holder formations 107 (one at a time) in such a way that gas flowing through capillary 98 readily captures the ions formed from the sample by laser desorption ionization.
- a potential may be applied between sample carrier 104 and capillary 78 section 105 to help draw ions into the channel of capillary 78 section 105.
- fiber optic 101 might be adjusted via piezo electrics or other mechanics to direct the laser beam to any region of the specific cone-shaped sample of samples 82 to be ionized.
- this redirecting of the laser beam may occur during the ionization process such that the entire sample is ionized.
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Abstract
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Application Number | Priority Date | Filing Date | Title |
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PCT/US2001/006133 WO2002068949A2 (en) | 2001-02-23 | 2001-02-23 | Method and apparatus for a multiple part capillary device for use in mass spectrometry |
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EP1364387A2 true EP1364387A2 (en) | 2003-11-26 |
EP1364387B1 EP1364387B1 (en) | 2016-01-20 |
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EP01913068.1A Expired - Lifetime EP1364387B1 (en) | 2001-02-23 | 2001-02-23 | Method and apparatus for a multiple part capillary device for use in mass spectrometry |
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EP (1) | EP1364387B1 (en) |
WO (1) | WO2002068949A2 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10388501B1 (en) | 2018-04-23 | 2019-08-20 | Agilent Technologies, Inc. | Ion transfer device for mass spectrometry with selectable bores |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2457556B (en) * | 2007-02-26 | 2010-02-17 | Micromass Ltd | Helical ion guide |
GB0703682D0 (en) | 2007-02-26 | 2007-04-04 | Micromass Ltd | Mass spectrometer |
JP5475433B2 (en) * | 2009-12-22 | 2014-04-16 | 株式会社日立ハイテクノロジーズ | Inspection system and ionization probe |
US10103014B2 (en) | 2016-09-05 | 2018-10-16 | Agilent Technologies, Inc. | Ion transfer device for mass spectrometry |
US10541122B2 (en) | 2017-06-13 | 2020-01-21 | Mks Instruments, Inc. | Robust ion source |
CN114256055B (en) * | 2021-12-20 | 2024-08-27 | 杭州谱育科技发展有限公司 | Electrospray ion source and ionization method based on electrospray technology |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
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US5289003A (en) * | 1992-05-29 | 1994-02-22 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Probe for thermospray mass spectrometry |
US5288113A (en) * | 1992-12-24 | 1994-02-22 | Restek Corporation | Connector for capillary tubes having a tapered inner bore |
DE4415480C2 (en) * | 1994-05-02 | 1999-09-02 | Bruker Daltonik Gmbh | Device and method for the mass spectrometric analysis of substance mixtures by coupling capillary electrophoretic separation (CE) with electrospray ionization (ESI) |
US5540464A (en) * | 1994-10-04 | 1996-07-30 | J&W Scientific Incorporated | Capillary connector |
US5965883A (en) * | 1997-08-25 | 1999-10-12 | California Institute Of Technology | Capillary for electrospray ion source |
-
2001
- 2001-02-23 WO PCT/US2001/006133 patent/WO2002068949A2/en active Search and Examination
- 2001-02-23 EP EP01913068.1A patent/EP1364387B1/en not_active Expired - Lifetime
Non-Patent Citations (1)
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See references of WO02068949A3 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10388501B1 (en) | 2018-04-23 | 2019-08-20 | Agilent Technologies, Inc. | Ion transfer device for mass spectrometry with selectable bores |
Also Published As
Publication number | Publication date |
---|---|
WO2002068949A3 (en) | 2002-10-31 |
WO2002068949A2 (en) | 2002-09-06 |
EP1364387B1 (en) | 2016-01-20 |
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