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 O 00 3 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.