Europaisches Patentamt J European Patent Office

Office europeen des brevets (R) Publication number: 0 444 896 A2

EUROPEAN PATENT APPLICATION

ii) Application number : 91301580.6 (g) Int Cl.5: G01N 30/72, H01J 49/04

Date of filing : 27.02.91

(So) Priority: 01.03.90 US 487671 Inventor : Hansen, Stuart C. 184 Walter Hayes Drive Palo Alto, CA 94303 (US) © Date of publication of application : 04.09.91 Bulletin 91/36 @) Representative : Williams, John Francis et al WILLIAMS, POWELL & ASSOCIATES 34 . @ Designated Contracting States : Tavistock Street CH DE FR GB LI London WC2E 7PB (GB)

71) Applicant : Hewlett-Packard Company Mail Stop 20 B-O, 3000 Hanover Street Palo Alto, California 94304 (US)

Single port thermospray ion source with coaxial vapor flow.

(57) An apparatus for providing an ion vapor to be analyzed. A vaporizer probe (10), with a capillary tube (16) extending into a vapor port of an ion source (40), ejects a spray of vapor into a spray region of the ion source. Molecules within the vapor are ionised, and a minor portion of the vapor is extracted from the spray chamber for mass analysis. The major portion is coaxially redirected from the spray chamber for return to the same port which receives the capillary tube of the vapor probe. A return tube (38) is vacuum sealed to the port and is in fluid communication with a roughing pump which draws the ion vapor from the spray region through the ion source and the port

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Q. LJJ Jouve, 18, rue Saint-Denis, 75001 PARIS

EP 0 444 896 A2

SINGLE PORT THERMOSPRAY ION SOURCE WITH COAXIAL VAPOR FLOW

The present invention relates generally to the various components of the system. The ion source apparatus for interfacing liquid chromatography in particular must be cleaned regularly. Conse- apparatus to mass spectrometers. quently, the structure of the ion source and the inter- Various systems are presently utilized in the s facing of components should include features which analysis of solutions to provide molecular weight, iso- both facilitate easy access and cleaning and minimize tope ratios, identification of functional groups, and the risk of damage to other components as cleaning elucidation of structure. Techniques used in combi- of a particular component takes place. Yet another nation with mass spectrometry include electrophore- consideration involves the trend in the electronics sis, gas chromatography and liquid chromatography. 10 field to manufacture systems which are increasingly In the use of a liquid chromatograph-mass spec- more compact. trometer (LC/MS) system, it has been discovered that It is an object of the present invention to provide a thermospray technique extends the capability of an LC/MS system having features which facilitate LC/MS to ionize and produce identifying spectra for a vacuum sealing of components, maintenance of a broad range of thermally labile or nonvolatile com- 15 clean system, and compactness. pounds. The thermospray technique has been des- The above object has been met by an apparatus cribed in detail in U.S. Pat. Nos. 4,814,612 and for providing an ion vapor to be analyzed which 4,730,111 to Vestal et al. These patents teach the includes a redirection of vapor spray residue to elimi- introduction of a fluid into a mass spectrometer ion nate the need of an outlet port of an ion source. The source operating substantially below atmospheric 20 redirection permits a more compact system since the pressure through a spray means which is typically connection to a roughing pump is no longer at that heated so that the fluid emerges as a jet of fluid which side of the ion source opposite the inlet. In actuality is partially in the vapor phase. Classes of compounds the inlet port serves the double function of acting as that have been analyzed by thermo-spray LC/MS an outlet port. include underivatized amino acids, urea pesticides, 25 The apparatus includes a vaporizer probe which peptides, vitamins, organic acids, and alkaloids. heats a liquid sample to provide a vapor having The thermospray method is one in which a solu- molecules of interest. A capillary tube of the vaporizer tion to be analyzed is introduced into a vaporizer probe has a release end which is received within the probe having a heated capillary tube in which vapor- inlet port of the ion source. A vapor spray is ejected ization occurs. The release end of the capillary tube 30 from the release end of the capillary tube into a spray is extended into an ion source having a spray, or chamber of the ion source. The ion source permits desolvation, chamber. The vapor from the capillary ionization of molecules by any of the methods of tube enters the spray chamber as a jet. The spray chemical ionization, discharge ionization or electron chamber is evacuated by use of a roughing vacuum impact ionization, although electron impact is typically pump to provide a pressure of between one and ten 35 not used during the thermospray process. torr. A spray of evaporating droplets containing ions Downstream of the release end of the vaporizer and molecules of analyte and solvent is formed in the probe is an ion exit. A minor portion of the ion vapor chamber. A conical member having a hole at its apex exits the spray chamber through the ion exit which is is positioned to extend into the spray chamber so that in fluid communication with a high vacuum source. ions exit the chamber into a high vacuum region for 40 The major portion of the ion vapor continues past the mass analysis. Atypical pressure for the high vacuum ion exit into one of two identical return paths which are region is 10-* torr. in fluid isolation other than at the inlets and outlets of The vapor which is not extracted for mass the return paths. The return paths originate at the analysis follows a linear path from the capillary tube spray chamber and extend to the port which receives which is received in an inlet port of the ion source, 45 the capillary tube of the vaporizer probe. The single through the spray chamber of the ion source to exit port of the ion source has a diameter which permits from an outlet port of the ion source. This construction flow of the return vapor along the periphery of the is shown and described in the above-cited patents to vaporizer probe. A vacuum tube is sealed to the Vestal et al., as well as the thermospray apparatus of exterior of the ion source and is connected to a rough- U.S. Pat. Nos. 4,794,252 to Bateman et al. and 50 ing pump. Flow to the pump is a coaxial flow with the 4,647,772 to Lewis et al. In design and manufacture vaporizer probe. of these systems, a number of considerations are An advantage of the present invention is that a important. Firstly, the interfaces of the ion source with single port acts as both an inlet and an outlet for the the roughing pump, with the mass spectrometer and ion source. In comparison to prior art thermospray with the capillary tube must all be vacuum sealed. 55 systems, coupling of a vaporizer probe, an ion source Another consideration involves periodic cleaning of and a roughing vacuum system is localized at the EP 0 444 896 A2 single port Thus, the number of vacuum sealed cou- effluent through a tubing 12 and heats the effluent to plings within the system is significantly reduced, provide a jet at a release end 14 of a capillary tube 1 6. thereby reducing the likelihood of vacuum system fail- The vaporizer probe is of the type described in U.S. ure. Moreover, by redirecting the ion vapor to its ori- Pat. No. 4,730,1 1 1 to Vestal et al. and may be purch- gin, a more compact LC/MS system is possible. 5 ased from Hewlett-Packard Co. Additional advantages of the present invention The capillary tube 16 of the vaporizer probe 10 result from manufacturing the ion source in the form has an axial passageway 18. The liquid effluent is of a pair of metallic blocks. Each block includes a pumped into the passageway and is heated to provide recessed region which provides one of the two return the desired degree of vaporization. The capillary tube paths for the ion vapor to the port. The blocks have 10 passageway 1 8 typically has a diameter of 0.01 5 mm, corresponding sequences of grooves of varying but this is not critical. A conductive tubing surrounds dimensions. The grooves define the spray chamber the capillary tube and serves the function of providing when the blocks are placed in abutting relation. Dur- heat along the length of the tube. An optimum tem- ing periodic maintenance, the blocks are separated, perature is one which provides 95% vaporization, completely exposing the areas which are contacted 15 since 100% vaporization may result in a high tem- by the vapor. In this manner, the ion source can be perature runaway condition. quickly and thoroughly cleaned. Moreover, the two- The capillary tube portion 16 of the vaporizer block structure of the ion source promotes ease of probe 10 extends through a vacuum lock 20. The manufacture since the critical internal structure of the vacuum lock houses a pair of circular seals. The cir- ion source is machined with the interior exposed. That 20 cular seals are known in the art as K-F seals and is, the blocks are individually machined to produce the vacuum seal the portion of the vaporizer probe recessed regions and the grooves in contrast to con- towards the release end 14 after insertion into the ventional ion sources which require drilling to produce sheath 20. Pressure within the sheath may be adjus- the internal bores. ted by operation of a valve member 26 which is in fluid Another advantage of the two-block structure is 25 communication with a vacuum tube 28 and an outlet that the transition regions of the varying diameter 30 of the sheath. grooves that form the spray chamber can be From the sheath 20, the capillary tube portion 16 machined to form truncated spherical regions. It is of the vaporizer probe 1 0 enters an isolation valve 32. thought that the smoother, more refined dimensional The isolation valve includes a handle 34 which is fixed changes permit lower operating temperatures in the 30 to a plug 36. When the plug is rotated in a first direc- analysis of most compounds. Lower operating tem- tion by manipulation of the handle 34, a bore through peratures permit the ion source to be operated for a the plug is brought into alignment with an axial bore longer period of time between routine maintenance through the isolation valve 32. In this alignment, the and also reduce thermal degradation of the analyte. capillary tube portion 16 may penetrate the isolation Yet another advantage of the single-port ion 35 valve. Rotation of the plug 36 on its axis, however, source is that it frees the ion source for connection of vacuum seals one end of the isolation valve from the a second vacuum coupling port to conventional gas opposite end. Thus, during routine maintenance of chromatography/mass spectrometry (GC/MS) inter- the thermospray system, the vaporizer probe may be faces. Use of the ion source with a system which per- extracted until it no longer extends into the isolation mits both LC/MS and GC/MS analysis allows a saving 40 valve but still has a portion which is surrounded by the in the time necessary to make the switch between the circular seals 22 and 24 of the sheath 20. The plug 36 two technologies and also reduces the risk of equip- can then be rotated 90°, whereafter the vaporizer ment damage during the switch. probe may be completely removed without venting the thermospray system downstream of the isolation Brief Description of the Drawings 45 valve. That is, the isolation valve allows the vaporizer probe to be cleaned, replaced or repaired without Fig. 1 is an exploded perspective view of a ther- exposing the remainder of the system to the ambient mospray system in accord with the present invention. atmosphere. Fig. 2 is a schematical side view of the system of Attached to the isolation valve 32 is a return tube Fig. 1. 50 38. The return tube has an asymmetrical T-shape Fig. 3 is an exploded perspective view of the ion which provides fluid communication between the iso- source of Fig. 2. lation valve 32, an ion source 40 and a roughing pump Fig. 4 is a side view of a front block of the ion isolation valve 42. The capillary tube portion 16 of the source of Fig. 3. vaporizer probe 1 0 extends through the return tube for Fig. 5 is a schematic view of the spray chamber 55 contact with the ion source. As will be explained more of the ion source of Fig. 3. fully below, the vapor is projected into the ion source, Referring to Figs. 1 and 2, the thermospray sys- whereafter the major portion of the vapor is redirected tem includes a vaporizer probe 10 which receives LC for exit from the ion source about the capillary tube EP0444 896A2

portion. This flow is best seen in Fig. 2. The ion source portion projects slightly into the axial spray chamber is shown schematically in Figs. 1 and 2, but will be 76 formed by the machining of corresponding grooves explained more fully below with reference to Figs. 3-5. in the front and rear blocks 58 and 60. A minor portion The return tube 38 abuts a face plate 44 of the ion of the vapor escapes through the ion exit member for source 40. A multifunctional seal 46 provides gas- 5 mass analysis. As will be explained more fully below, tight connection of the coaxial fluid return tube to the the region which begins at the base of thefrustroconi- ion source and further provides electrical isolation of cally-shaped portion of the ion exit member is a high the vacuum system and the ion source. vacuum region. Within this high vacuum region is a A single clamp 48 is illustrated for connection of conventional focus lens assembly 86. The focus lens the isolation valves 32 and 42 with other components 10 assembly is electrically insulated from ion source of the system. However, in practice the connections block 60 by insulating elements 88 and 90. Ionized at both ends of the isolation valves are made using molecules of interest are directed by the components clamps such as 48, as well as a plurality of o-rings 50. through an entrance aperture 92 of a plate 94 to pass The roughing pump isolation valve 42 operates in the into a mass spectrometer. same manner as the above-described isolation valve, 15 lonization of the molecules of a sample can occur having a handle 52 and a plug 54 which are rotated in more than one way. For example, the liquid sample to selectively close fluid communication between the which enters the vaporizer probe may contain ions return tube 38 and a vacuum tube 56 which leads to which are not themselves of interest but which trans- a roughing pump, not shown. fer ionization to molecules of interest by ion-molecule Referring to Fig. 3, the ion source 40 may be seen 20 collision processes. This process is referred to as to include the face plate 44, a front block 58 and a rear chemical ionization. For example, a liquid sample to block 60, all of which are connected together by con- be analyzed may be combined with a solution of ventional fastening hardware, not shown. The face ammonium acetate so that primary ions of NH4+ and plate 44 includes a recessed annular region 62 which CH3COO- are formed in the spray. These ions can receives the multifunctional seal 46 that provides the 25 react with sample molecules forming NH4+ or gas-tight electrically isolating connection of the ion CH3COO- adducts, which are analyzed by the mass source and the coaxial vapor flow system. spectrometer. The vaporizer probe described above extends A second method of ionization is plasma dis- through the face plate 44 and is received within a charge ionization. As shown in Fig. 3, the ion source vaporizer seal 64. The vaporizer seal isolates the flow 30 40 includes a discharge electrode 96 having an end into the ion source 40 from the flow exiting the ion which enters into the axial spray chamber 76 at a 45° source. The seal 64 is fixed to the front and rear blocks angle through an aperture 98 in the front block 58 of 58 and 60 by bolts which project through notched reg- the ion source. A discharge is established between ions 66 of the seal into internally-threaded holes 68 in the electrode 96 and the wall of the spray chamber by the blocks. 35 maintaining a current of approximately 200 microam- A mounting bar 70 having feet 72 is attached to peres between the electrode and the wall. Neutral the front block 58 by fastening hardware, not shown. molecules in the thermospray enter the spray region Spacers 74 provide the proper alignment for attach- and are ionized by collision with free electrons and ment to a support structure. other charged particles. The rear block 60 includes a plurality of grooves 40 The ion source 40 includes a third means for which define one half of an axial spray chamber 76. causing ionization. A filament holder 100 secures a At the downstream end of the spray chamber is the filament which is connected to a power supply for inlet of a vapor return path 78 which proceeds creating a current through the filament A potential dif- upwardly and then forwardly for outlet at the face plate ference of 1000 volts is typical. The filament emits 44. The axial spray chamber 76 and the vapor return 45 electrons through thermal emission and the electrons path 78 of the rear block 60 may be best seen in Fig. impact solvent and analyte molecules in the vapor 2. This figure shows a second vapor return path 80 phase. By virtue of chemical ionization, positive or which proceeds downwardly and then forwardly from negative ions are created. Direct electron impact ioni- the downstream end of the spray chamber. In zation is typically not used in thermo-spray technol- actuality, the second return path 80 is a recess within 50 ogy. However, it has been discovered that electron the front block 58 of Fig. 3. Thus, any upward flow of impact is particularly useful for diagnostic purposes. vapor from the spray chamber is through the rear Current is initiated through the filament and in the abs- block while any downward flow is through the front ence of LC liquid within the spray chamber the gases block. within the chamber are directly ionized. The ionized An ion exit member 82 is fixed to the rear block 55 gases are analyzed to determine the particular ions 60 of the ion source 40. The ion exit member includes that are characteristic of the resident gases. This a frustroconically-shaped portion having a bore information is helpful in tuning of the system. extending therethrough. The frustroconically-shaped Referring now to Fig. 4, the front block 58 of the EP 0 444 896 A2 ion source is shown as having been rotated 180° from ion vapor enters grooves 1 08. The ion exit member 82 top to bottom relative to the orientation of Fig. 3. The projects into the spray chamber to permit extraction of front block 58 includes a Venturi-like flow path com- a minor portion of the ion vapor for mass analysis. prising a plurality of grooves 102, 104, 106, 108, 110 Typically, the ion exit member projects into the ion and 112. Each groove 102-112 of the front block is 5 chamber to a position just short of the center. Oppo- identical to a groove in the rear block ofthe ion source site the ion exit member 82 is a fragmenter electrode so that as the blocks are placed in abutting relation, 124. The function of the fragmenter electrode is des- the axial spray chamber described above is formed. cribed in detail in U.S. Pat. No. 4,647,772 to Lewis et The blocks are secured together by fastening al. Briefly, the electrode is capable of generating an hardware which penetrate bores 114 along the out- 10 electrostatic field capable of retarding and deflecting side ofthe blocks. ions into the aperture of the ion exit member 82. A typi- Referring now to Figs. 4 and 5, vapor enters the cal pressure within the spray chamber is 1 0 torr, while Venturi-like spray chamber through the capillary tube the pressure on the backside of the ion exit member ofthe vaporizer probe, as indicated by arrow A. The is a high vacuum pressure, e.g., 10-* torr. release end ofthe capillary tube is secured within the 15 The major portion of the vapor then travels vaporizer seal 64 which is mounted to the blocks 58 through the grooves 1 1 0 and 1 1 2 into the vapor return and 60 that form the ion source. As shown in Fig. 4, paths of the front and rear blocks. As best seen in Fig. the front block 58 has a relief 116 which receives the 4, the vapor return path 80 of the front block 58 is vaporizer seal. The face plate 44 is fixed to the front through only one half of the block. Vapor progresses block by fastening hardware. The recessed annular 20 from the ion chamber, through the vapor return path region 62 has an outside diameter corresponding to 80 and enters into the cutaway axial region 1 1 8 at the the multi-functional seal described above for sealing back ofthe face plate 44. The vapor then exits through the return tube that houses the capillary tube prior to the center of the face plate. A corresponding vapor entrance into the ion source. The side of the face plate return path 78 is defined by a recessed region in the 44 opposite the recessed annular region 62 also 25 rear block. Each of the vapor return paths 78 and 80 include a cutaway axial region 118. is defined by a recess in one block and by the planar In operation, vapor exits from the capillary tube 16 surface of the other block. Thus, the schematic view into grooves 104 of the front and rear blocks which of Fig. 2 should not be read as illustrating an ion define one portion of the ion source spray chamber, source in which a cross section may be taken to as shown in Figs. 4 and 5. By use of pre-formed ions 30 intersect both ofthe vapor return paths 78 and 80. The in solution, the vapor may already include ions. Alter- two-block structure of the ion source promotes ease natively, ionization may take place by means of the of manufacture and facilitates periodic cleaning. discharge electrode 96. The discharge electrode is Both of the vapor return paths 78 and 80 outlet at secured within an internally-threaded bore ofthe front the port ofthe ion source which receives the capillary block 58. Also within that portion ofthe spray chamber 35 tube 1 6. Thus, the single port acts as both an inlet and defined by the grooves 1 04 is a 0.5 mm electron-entr- an outlet. This minimizes the number of vacuum sea- ance bore 120 which may be employed for electron led couplings within the system. The redirection of impact chemical ionization. vapor through the port has the further advantage of The now-ionized vapor is compressed by entr- providing a more compact system than LC/MS sys- ance into the portion ofthe spray chamber defined by 40 terns in which vapor is projected into one end of an ion grooves 106. Because the spray chamber of the pre- source and is evacuated from the end distant the entr- sent invention is formed by the machining of grooves ance end. into two separate blocks, the transitions 122 from one groove 1 02-1 12 to an adjacent groove may be formed by rounded end mills to provide smooth radius transi- 45 Claims tions. That is, the transitions 122 may each have a truncated spherical configuration. This is not practical 1. An apparatus for providing an ion vapor to be where an axial spray chamber is formed by blunt drills analyzed comprising, means (10) for vaporizing a and mills. It is believed that the smooth radius transi- sample liquid and for directing vaporized sample tions at internal bore variations permit operating tem- so in a first direction, means (40) in communication peratures that may be as much as 100 °C below the with said vaporizing means for receiving the operating temperatures of prior art sources in the vaporized sample and for ionizing molecules of analysis of most compounds. The reduced operating said sample to create an ion vapor, means (82) temperatures reduces thermal degradation of the downstream of said ionizing means for extracting analyte and permits users to extend the periods be- 55 a minor portion of said ion vapor for mass tween routine cleanings of the ion source. analysis, and path means (78,80) for redirecting From the portion of the spray chamber defined by a major portion of said ion vapor along a second grooves 106, the vapor is again compressed as the direction, characterised in that said second direc- EP 0 444 896 A2 10

tion is generally opposite to said first direction. ence of grooves of varying dimensions, said grooves defining said spray chamber (76) when 2. The apparatus of claim 1 wherein said ionizing said blocks are in said abutting relation. means includes an ion source (40) having a receptor region situated to receive said vaporized 10. An apparatus according to claim 9, wherein said sample, said path means including an internal ion extraction means (82) includes a hollow con- pathway (78,80) through said ion source, and ical member (84) having an aperture at the apex, then folded about the ion source in a configuration said aperture being in fluid communication with to direct said ion vapor in said second direction. one of said grooves in said first block (60). 10 3. The apparatus of claim 2 wherein said ion source 11. An apparatus according to claims 9 or 10, whe- has a vapor port and wherein said vaporizing rein said grooves are joined by truncated spheri- means (10) includes a capillary tube (16) project- cal regions. ing through said vapor port and aligned to eject aid vaporized sample into an upstream end of 15 12. An apparatus according to any of claims 6 to 1 1 , said receptor region, said internal pathway further comprising a tube (38) having a diameter (78,80) of said ion source having an outlet end at to allow axial insertion of a capillary tube (16) for said vapor port for return flow about said capillary injecting vapor into said spray chamber (70) via tube. said sample vapor port and to further allow 20 coaxial return of vapor from said exhaust path 4. The apparatus of claim 3 wherein said path (78,80). means (78,80) further includes a return tube (38) coaxial with said capillary tube (6), said return 13. An apparatus according to any preceding claim, tube being in fluid communication with said inter- wherein the ion vapor is drawn through the nal pathway at said outlet end. 25 apparatus using vacuum means.

5. The apparatus of any preceding claim, wherein 14. An apparatus according to any preceding claim, said ionizing means includes a discharge elec- further comprising valve means (54) to close the trode (96). exhaust path (78,80). 30 6. An apparatus according to any preceding claim, 15. An analytical system comprising a chromato- wherein said means for receiving the vaporised graph and a mass spectrometer, wherein material sample comprises a housing (40) having sample from the chromatograph outlet is supplied to an vapor port and having a vapor spray chamber (76) ionisation chamber (40) which is connected to the in communication with said sample vapor port to 35 mass spectrometer inlet (82), and an exhaust (38) receive a vapor flow via said vapor port, said is provided to remove excess material from the housing having an exhaust path (78) defined the- chamber, the apparatus being characterised in rein, said exhaust path having an inlet down- that the chromatograph outlet and the exhaust stream of the ion extraction means (82) and are connected to the chamber via a single port. further having an outlet at said sample vapor port. 40

7. An apparatus according to claim 6, wherein said housing (40) includes first and second split blocks (60,58) configured to define said vapor spray chamber (70) and said exhaust path (78) when in 45 abutting relation.

8. An apparatus according to claim 7, wherein each of said blocks includes a recessed region, said exhaust path (78) comprises said recessed reg- 50 ion in said first block (60), the apparatus further comprises a further exhaust path (80) comprising said recessed region in said second block (58), and said exhaust path and said further exhaust path are in communication only at their ends. 55

9. An apparatus according to claims 7 or 8, wherein each block (58,60) has a corresponding sequ- EP 0 444 896 A2

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