Orthogonal ion sampling for electrospray [LC/MS] mass spectrometry

Abstract

[The invention teaches the uses of a plurality of electric fields and of orthogonal spray configurations of vaporized analyte which combine so as to operate to enhance the efficiency of analyte detection and mass analysis with a mass spectrometer by reducing vapor in the vacuum system and concomitant noise. Several embodiments of the invention are described for purposes of illustration.] The invention relates to a method and apparatus for improving signal relative to noise without loss of ion collection efficiency in electrospray mass spectrometry, including liquid chromatography / mass spectrometry.

Description

INTRODUCTIONThe invention relates to a method and apparatus for obtaining improved .Iadd.signal relative to noise without loss of .Iaddend.ion collection efficiency in electrospray .[.on.]. .Iadd.mass spectrometry, including liquid chromatography / mass spectrometry (LC / MS.Iadd.).Iaddend..Initial systems for electrospray LC / MS utilized flow splitters that divided the HPLC .Iadd.(high performance liquid chromatography) .Iaddend.column effluent in such a way that a small portion, typically 5-50 micro liters per minute, was introduced into the "spray chamber".Iadd., .Iaddend.while the major portion was directed to a waste or fraction collector. Because .Iadd.these .Iaddend.low flow rates were introduced into electrospray .Iadd.(ES) mass spectrometry (MS) .Iaddend.systems, it became possible to generate .[.spray.]. .Iadd.electrosprayed aerosol .Iaddend.solely through the use of electrostatic forces. Since ES / MS .[.is.]. .Iadd.generally provides .Iaddend.a concentration sensitive detector,...

AI Technical Summary

Benefits of technology

The invention provides the capability of conducting atmospheric pressure ionization.[.,.]. .Iadd.(.Iaddend.API.Iadd.).Iaddend., whether electrospray or atmospheric pressure chemical ionization (APCI), with conventional .[.High Performance Liquid Chromatography.]. .Iadd.high performance liquid chromatography .Iaddend.at flow rates of greater than 1 ml / minute without flow splitting. The invention allows desolvated ions to be separated from comparatively large volumes of .[.vaporized.]. .Iadd.electrosprayed .Iaddend.column effluent, and then, while keeping out as much of the solvent as possible, introducing the desolvated ions into the vacuum system for mass detection and analysis .[.while introducing as little of the solvent as possible.].. The invention provides the capability of separating desolvated ions of interest from the large volumes of vapor.[.,.]. and directing the desolvated ions from the electrospray (ES) chamber (which .Iadd.typically .Iaddend.operates at atmospheric pressure) to the mass spectrometer (which operates at 10.sup.-6 to 10.sup.-4 .[.Torr.]. .Iadd.torr.Iaddend.). The .Iadd.orthogonal .Iaddend.selection .Iadd.process .Iaddend.allows the introduction of ions without overwhelming the vacuum system and without sacrificing the sensitivity of the system, .[.because.]. .Iadd.since .Iaddend.the maximum amount of analyte is introduced into the vacuum system for mass analysis and detection.

The noise level in .[.an.]. .Iadd.a mass spectrometry .Iaddend.apparatus configured according to the present invention is reduced by as much as five fold over current systems, resulting in increased signal relative to noise.Iadd., and .Iaddend.hence.[.,.]. .Iadd.acheiving .Iaddend.greater sensitivity. Performance is simplified and the system .Iadd.is .Iaddend.more robust because optimization of .[.needle.]. .Iadd.the .Iaddend.position .Iadd.of the first passageway.Iaddend., gas flow and voltages show less sensitivity to small changes. The simplified performance and reduced need for optimization also result in a system less dependent .[.of.]. .Iadd.on .Iaddend.flow rate and mobile phase conditions. The reduced need for optimization extends to changing mobile phase flow rates and proportions. This means that the .Iadd.mass spectrometry .Iaddend.system can be run under a variety of conditions without adjustment.

Another benefit of the invention taught herein is simplified waste removal owing to the fact that the .[.spray.]. .Iadd.electrosprayed aerosol .Iaddend.can be aimed directly at a waste line and be easily removed from the system. Furthermore, the present invention provides the option of eliminating high voltage elements with no loss of sensitivity.

Problems solved by technology

However, the use of flow splitters has gained a bad reputation due to potential plugging problems and poor reproducibility.

.Iadd.generate .Iaddend.a plume of small droplets and optimal performance appears to be limited to a flow rate of 200 microliters per minute or lower.

The use of the high temperature capillary may result in thermal degradation of thermally labile samples.

While these clusters may be re-dissociated by collisionally induced processes, this may interfere in identification of structural characteristics of the analyte samples which are intentionally subjected to collisionally induced dissociation.

The main disadvantages of this system, from the practitioner's point of view, are that optimal performance is effectively limited to less than 500 microliters per minute and .[.that.]. there are serious problems with aqueous mobile phases.

Furthermore, the apparatus is complex and prone to mechanical and electronic failures.

This results in a highly collimated and directed .

Although this works competitively, there is still some noise which is probably due to stray droplets.

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