IP Library Granted Patent US 9,177,774
Granted Patent B2
US 9,177,774 · App. 13/008,697 · Granted Nov 3, 2015

Continuous flow mobility classifier interface with mass spectrometer

Inventors: Nicholas Brunelli (Atlanta, GA); Konstantinos P. Giapis (Pasadena, CA); Richard C. Flagan (Pasadena, CA); Jesse L. Beauchamp (La Canada Flintridge, CA); Evan Neidholdt (Glendale, CA)
Assignee: California Institute of Technology
H01J49/165G01N27/624G01N30/7233
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Quick Facts
Patent No.
US 9,177,774
App. No.
13/008,697
Granted
Nov 3, 2015
Kind
B2
Abstract

A continuous flow mobility classifier provide the ability to perform two-dimensional separation in mass spectrometry. An ionization system is used to ionize a sample. A differential mobility analyzer (DMA) (e.g., a nano-radial DMA) is coupled to the ionization system and to a mass spectrometer. The nano-RDMA is configured to separate the ionized sample by mobility for subsequent mass analysis by the mass spectrometer.

Claims (39)

1. A continuous flow mobility classifier-mass spectrometer system comprising:

(a) a first ionization system configured to ionize analyte molecules in a sample;

(b) a continuous flow radial differential mobility analyzer (RDMA) configured to analyze the ionized analyte molecules in a first dimension, wherein:

(i) the RDMA is coupled to the first ionization system;

(ii) the RDMA is coupled to a mass spectrometer;

(iii) the sample is introduced into the RDMA;

(iv) the RDMA is configured to employ axial electric fields to separate the ionized analyte molecules by mobility; and

(c) the mass spectrometer configured to analyze the ionized analyte molecules in a second dimension, wherein:

(i) a continuous flow of the ionized analyte molecules that have been separated by mobility are introduced to the mass spectrometer to determine a mass-to-charge ratio of a charged particle within the mobility separated ionized analyte molecules; and

wherein:

a sheath flow rate provided by the RDMA is lower as compared to a sheath flow rate produced by a continuous flow mobility classifier-mass spectrometer system without the RDMA;

an instrument resolution of the RDMA has a value of at least seven (7);

a sample outlet of the RDMA is aligned with an atmospheric pressure inlet (API) of the mass spectrometer; and

a gap between the sample outlet and the API is minimized by adjusting a position of the RDMA.

2. The continuous flow mobility classifier-mass spectrometer of claim 1 , wherein the ionization system comprises an electrospray source.

3. The continuous flow mobility classifier-mass spectrometer of claim 2 , wherein the electrospray source comprises an electrospray ionization emitter (ESI).

4. The continuous flow mobility classifier-mass spectrometer of claim 1 , wherein the ionization system comprises an atmospheric pressure chemical ionization system.

5. The continuous flow mobility classifier-mass spectrometer of claim 1 , wherein a second ionization system was removed from the mass spectrometer prior to coupling the mass spectrometer to the RDMA.

6. The continuous flow mobility classifier-mass spectrometer of claim 1 , wherein the mass spectrometer comprises a liquid chromatography-mass spectrometer (LC-MS).

7. The continuous flow mobility classifier-mass spectrometer of claim 1 , wherein the first ionization system is coupled to the RDMA using standard Swagelok™ fittings.

8. The continuous flow mobility classifier-mass spectrometer of claim 1 , wherein a sheath flow rate of the RDMA is a maximum of fifty (50) liters per minute.

9. A method for analyzing a sample comprising:

(a) ionizing analyte molecules in a sample using a first ionization system;

(b) analyzing the ionized analyte molecules in a first dimension by separating the ionized analyte molecules by mobility using a continuous flow radial differential mobility analyzer (RDMA) that employs axial electric fields, wherein:

(i) the RDMA is coupled to the first ionization system;

(ii) the RDMA is coupled to a mass spectrometer; and

(iii) the sample is introduced into the RDMA;

(c) introducing a continuous flow of the ionized analyte molecules that have been separated by mobility to the mass spectrometer;

(d) analyzing the ionized analyte molecules in a second dimension by mass analyzing the ionized analyte molecules that have been separated by mobility using the mass spectrometer to determine a mass-to-charge ratio of a charged particle within the mobility separated ionized analyte molecules; and

wherein:

a sheath flow rate provided by the RDMA is lower as compared to a sheath flow rate produced by a continuous flow mobility classifier-mass spectrometer system without the RDMA;

an instrument resolution of the RDMA has a value of at least seven (7);

a sample outlet of the RDMA is aligned with an atmospheric pressure inlet (API) of the mass spectrometer; and

a gap between the sample outlet and the API is minimized by adjusting a position of the RDMA.

10. The method of claim 9 , wherein the ionization system comprises an electrospray source.

11. The method of claim 10 , wherein the electrospray source comprises an electrospray ionization emitter (ESI).

12. The method of claim 9 , wherein the ionization system comprises an atmospheric pressure chemical ionization system.

13. The method of claim 9 , wherein the mass spectrometer comprises a liquid chromatography-mass spectrometer (LC-MS).

14. The method of claim 9 , wherein a sheath flow rate of the RDMA is a maximum of fifty (50) liters per minute.

Assignments (2)
CONFIRMATORY LICENSE Recorded May 24, 2011
From: CALIFORNIA INSTITUTE OF TECHNOLOGY
To: NATIONAL SCIENCE FOUNDATION
Reel/Frame 026328/0939 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 19, 2011
From: BRUNELLI, NICHOLAS; GIAPIS, KONSTANTINOS P.; FLAGAN, RICHARD C.; BEAUCHAMP, JESSE L.; NEIDHOLDT, EVAN
To: CALIFORNIA INSTITUTE OF TECHNOLOGY
Reel/Frame 025663/0679 →
Continuity (2)
Provisional Application 61295643 · Jan 15, 2010
Related Publication 20110174964A1 · Jul 21, 2011