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

[0008]The integration of a DMS with a MS can provide added selectivity that can be used for purposes such as chemical noise reduction and elimination of isobaric interferences. This general reduction of the chemical background can provide improvements in the detection limit (defined for example as 3σ / slope of the calibration curve) for various assays. 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. Experiments have demonstrated that the observed sensitivity reduction due to the DMS has a flow rate dependence, with typical values being 3× down at low solvent flows (10 μL / min) and 10× down at high flows (500 μL / min) These sensitivity reductions may occur as a result of three different phenomena: 1) diffusion losses in the DMS itself, 2) inefficiencies in ion transport into and out of the DMS, and 3) ion clustering. Our experiments provide strong evidence that the bulk of losses currently being observed with the DMS at high solvent flows are a result of sampling a “wet spray” into the DMS and subsequently filtering clusters that do not transmit at the same Vc as the unclustered parent ion. This hypothesis is supported by modeling of diffusion behavior, as well as experimental data showing improvements in the coefficient of transmission with additional heaters located in front of the DMS.

[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.SUMMARY

[0012]With the tandem device, a cell, including the first DMS, operates at about atmosphere where clustering is done efficiently and a second cell, including the second DMS, operates in a vacuum where declustering to the bare ion is done efficiently. Separation at about atmosphere is done according to a “clusterization model” which derives it's specificity from the differences in the chemical interactions of an ion and its immediate surroundings. For instance, Hydrogen bonding, Vanderwaals forces, steric hindrance, where all of these actions come into play in the clusterization model. The addition of modifiers (e.g., dopants) to the transport gas can assure that separations occur according to this mechanism.

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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