IP Library › Granted Patent US 12,237,161
Granted Patent B2
US 12,237,161 · App. 18/436,697 · Granted Feb 25, 2025

Identification of sample subspecies based on particle charge behavior under structural change-inducing sample conditions

Inventors: David E. Clemmer (Bloomington, IN); Martin F. Jarrold (Bloomington, IN); Tarick J. El-Baba (Bloomington, IN); Corinne A. Lutomski (Bloomington, IN)
Assignee: THE TRUSTEES OF INDIANA UNIVERSITY
H01J49/165H01J49/0031H01J49/0468H01J49/26
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Quick Facts
Patent No.
US 12,237,161
App. No.
18/436,697
Granted
Feb 25, 2025
Kind
B2
Abstract

A method for analyzing charged particles may include generating, in or into an ion source region, charged particles from a sample of particles, causing the charged particles to enter a mass spectrometer from the ion source region at each of a plurality of differing physical and/or chemical conditions in a range of physical and/or chemical conditions in which the sample particles undergo structural changes, controlling the mass spectrometer to measure at least the charge magnitudes of the generated charged particles at each of the plurality of differing physical and/or chemical conditions, determining, with a processor, an average charge magnitude of the generated charged particles at each of the plurality of differing physical and/or chemical conditions based on the measured charge magnitudes, and determining, with the processor, an average charge magnitude profile over the range of physical and/or chemical conditions based on the determined average charge magnitudes.

Claims (34)

1. An instrument for analyzing charged particles, comprising:

an ion generator configured to generate charged particles from each of a plurality of samples of particles, each of the plurality of samples of particles having a different chemical composition within a range of chemical compositions over which each of the plurality of samples of particles undergo structural changes,

a mass spectrometer configured to receive the charged particles generated by the ion generator from each of the plurality of samples of particles and to measure masses and charge magnitudes of the generated charged particles generated from each of the plurality of samples having the different chemical compositions within the range of chemical compositions,

a processor, and

a memory having instructions stored therein executable by the processor to cause the processor to (a) control the mass spectrometer to measure at least the charge magnitudes of the generated charged particles generated from each of the plurality of samples having the different chemical compositions, (b) determine an average charge magnitude of the generated charged particles generated from each of the plurality of samples having the different chemical compositions based on the measured charge magnitudes, and (c) determine an average charge magnitude profile over the range of chemical compositions based on the determined average charge magnitudes.

2. The instrument of claim 1 , wherein the instructions stored in the memory further include instructions executable by the processor to cause the processor to control the mass spectrometer to measure the masses of the generated charged particles generated from each of the plurality of samples having the different chemical compositions, to determine the average charge magnitude of the generated charged particles by determining an average charge magnitude of the generated charged particles generated from each of the plurality of samples having the different chemical compositions within a selected particle mass range based on the measured masses and the measured charge magnitudes, and to determine the average charge magnitude profile by determining an average charge magnitude profile over the range of chemical compositions within the selected mass range based on the determined average charge magnitudes within the selected mass range.

3. The instrument of claim 1 , wherein each of the plurality of samples of particles is in a corresponding solution, and the range of chemical compositions is defined by changes in a content of each solution by adding one or more components to each solution.

4. The instrument of claim 3 , wherein the ion generator is an electrospray ion source.

5. The instrument of claim 1 , wherein each of the plurality of samples of particles is in a corresponding solution, and the range of chemical compositions is defined by changes in a content of each solution by removing one or more components from each solution.

6. The instrument of claim 5 , wherein the ion generator is an electrospray ion source.

7. The instrument of claim 1 , wherein the mass spectrometer is a charge detection mass spectrometer.

8. The instrument of claim 1 , wherein each of the plurality of samples of particles is in a corresponding solution, and the range of chemical compositions is defined by changes to a relative concentration in each solution of one or more components of the sample of particles in the respective solution.

9. The instrument of claim 8 , wherein the ion generator is an electrospray ion source.

10. An instrument for analyzing charged particles, comprising:

an ion generator configured to generate charged particles from each of a plurality of samples of particles, each of the plurality of samples of particles having a different chemical composition within a range of chemical compositions over which each of the plurality of samples of particles undergo structural changes,

a mass spectrometer configured to receive the charged particles generated by the ion generator from each of the plurality of samples of particles and to measure masses and charge magnitudes of the generated charged particles generated from each of the plurality of samples having the different chemical compositions within the range of chemical compositions,

a processor, and

a memory having instructions stored therein executable by the processor to cause the processor to (a) control the mass spectrometer to measure the masses and charge magnitudes of the generated charged particles generated from each of the plurality of samples having the different chemical compositions and (b) within a selected range of the measured masses, (i) identify all charge magnitude peaks of the measured charge magnitudes at a first one of the different chemical compositions and (ii) identify additional charge magnitudes of the measured charge magnitudes at each of one or more additional ones of the different chemical compositions.

11. The instrument of claim 10 , wherein each of the plurality of samples of particles is in a corresponding solution, and the range of chemical compositions is defined by changes in a content of each solution by adding one or more components to each solution.

12. The instrument of claim 11 , wherein the ion generator is an electrospray ion source.

13. The instrument of claim 10 , wherein each of the plurality of samples of particles is in a corresponding solution, and the range of chemical compositions is defined by changes in a content of each solution by removing one or more components from each solution.

14. The instrument of claim 13 , wherein the ion generator is an electrospray ion source.

15. The instrument of claim 10 , wherein the mass spectrometer is a charge detection mass spectrometer.

16. The instrument of claim 10 , wherein each of the plurality of samples of particles is in a corresponding solution, and the range of chemical compositions is defined by changes to a relative concentration in each solution of one or more components of the sample of particles in the respective solution.

17. The instrument of claim 16 , wherein the ion generator is an electrospray ion source.

18. A method for analyzing charged particles, comprising:

(i) in or into an ion source region, generating charged particles from each of a plurality of samples of particles, each of the plurality of samples of particles having a different chemical composition within a range of chemical compositions over which each of the plurality of samples of particles undergo structural changes,

(ii) causing the charged particles from one of the plurality of samples of particles to enter a mass spectrometer from the ion source region,

(iii) controlling the mass spectrometer to measure at least the charge magnitudes of the generated charged particles generated from the one of the plurality of samples,

(iv) repeating (ii) and (iii) for each of the remaining plurality of samples each having the different chemical compositions,

(v) determining, with a processor, an average charge magnitude of the generated charged particles generated from each of the plurality of samples having the different chemical compositions based on the measured charge magnitudes, and

(vi) determining, with the processor, an average charge magnitude profile over the range of chemical compositions based on the determined average charge magnitudes.

19. The method of claim 18 , wherein (iv) comprises, for each execution of (ii) and (iii), at least one of adding one or more components to each of the remaining plurality of samples of particles or removing one or more components from each of the remaining plurality of samples of particles.

20. The method of claim 18 , wherein each of the plurality of samples of particles is in a corresponding solution, and wherein (iv) comprises, for each execution of (ii) and (iii), changing a relative concentration in each solution of one or more components of the sample of particles in the solution.

Continuity (5)
Continuation 17602000
Provisional Application 62950103 · Dec 18, 2019
Provisional Application 62839080 · Apr 26, 2019
Provisional Application 62837373 · Apr 23, 2019
Related Publication 20240242955A1 · Jul 18, 2024
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