Mass analysis system with low pressure differential mobility spectrometer

Abstract

A mass analysis system including a low pressure dissociation region and a differential mobility spectrometer. The differential mobility spectrometer including at least one pair of filter electrodes defining an ion flow path where the filter electrodes generate an electric field for passing through a selected portion of the sample ions based on the mobility characteristics of the sample ions. The differential mobility spectrometer also includes a voltage source that provides DC and RF voltages to at least one of the filter electrodes to generate the electric field, an ion inlet that receives sample ions that have passed through the low pressure dissociation region, and an ion outlet that outputs the selected portion of the sample ions. A mass spectrometer receives some or all of the selected portion of the sample ions.

Description

REFERENCE TO RELATED APPLICATIONS[0001]This application claims benefit of U.S. Provisional Application No. 61 / 299,086 filed Jan. 28, 2010 and entitled “Mass Analysis System With Low Pressure Differential Mobility Spectrometer” the entirety of which is incorporated herein by reference.INTRODUCTION[0002]A Differential Mobility Spectrometer (DMS), also referred to as a Field Asymmetric Waveform Ion Mobility Spectrometer (FAIMS) or Field Ion Spectrometer (FIS), typically performs gas phase ion sample separation and analysis. In some circumstances, a DMS has been interfaced with a mass spectrometer (MS) to take advantage of the atmospheric pressure, gas phase, and continuous ion separation capabilities of the DMS and the detection accuracy of the MS.[0003]By interfacing a DMS with an MS, numerous areas of sample analysis, including proteomics, peptide / protein conformation, pharmacokinetic, and metabolism analysis have been enhanced. In addition to pharmaceutical and biotech applications,...

AI Technical Summary

Benefits of technology

[0010]Accordingly, there is a need to improve mobility based resolution and specificity, and to increase the applicability of DMS-MS analyses by providing improved sensitivity and selectivity, including for high flow analyses.

Problems solved by technology

One of the key factors limiting general applicability of DMS technology with MS analysis is the reduction in instrument sensitivity that is observed upon installation of the DMS.

Existing DMS-MS systems typically locate the DMS before the orifice of the MS, which results in a limitation in that ions and clusters are filtered prior to the orifice, eliminating the ability to decluster within the first vacuum stage.

Elimination of this stage of declustering results in sensitivity reduction with the DMS, with higher solvent flows being most problematic.

Efforts to add additional heating and provide additional desolvation prior to the DMS have shown some improvement in sensitivity, however, have imparted very significant challenges with respect to commercialization due to the critical importance of maintaining a constant temperature and the difficulty of monitoring temperature in close proximity to very high AC potentials.

The range of assays that can exhibit detection limit improvements with the DMS is limited by the magnitude of the sensitivity reduction that is observed with the DMS device.

Mobility based separations have also been known to be of low resolution and limited in peak capacity.

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