APPARATUS AND METHOD FOR ELEMENTAL ANALYSIS OF PARTICLES BY MASS SPECTROMETRY

• US 20080046194A1
• Filed: 08/14/2007
• Published: 02/21/2008
• Est. Priority Date: 08/15/2006
• Status: Active Grant

• Current Assignee: Standard Biotools Canada Incorporated
• Original Assignee: DVS Sciences, Inc. (Fluidigm Corporation)
• Inventors: Antonov, Alexei, Bandura, Dmitry
• Granted Patent: US 8,283,624 B2
• Time in Patent Office: Days
• US Class Current: 702/27
• CPC Class Codes: H01J 49/0027 Methods for using particle spectrometers
• CPC Class Codes: H01J 49/0036 Step by step routines describing the handling of the data generated during a measurement

Abstract

An apparatus for elemental analysis of particles such as single cells or single beads by mass spectrometry is described. The apparatus includes means for particle introduction; means to vaporize, atomize and ionize elements associated with a particle; means to separate the ions according to their mass-to-charge ratio; means to detect the separated ions, means to digitize the output of the means to detect the ions; means to transfer and/or to process and/or record the data output of the means to digitize, having means to detect the presence of a particle in a mass spectrometer; and means to synchronize one of the means for ion detection, data digitization, transfer, processing and recording with the means to detect the presence of a particle. Methods and computer readable code implementing aspects of the apparatus, and for reducing the rates of data generation, digitization, transfer, processing and recording are also described.

Claims

1. A mass spectrometer for elemental analysis of a particle, comprising

means for particle introduction;

means to vaporize, atomize and ionize elements associated with a particle positioned downstream of the means for particle introduction;

means to separate the ions, produced by the means to vaporize, atomize and ionize, according to their mass-to-charge ratio, positioned downstream of the means to vaporize, atomize and ionize elements associated with the particle;

means to detect the ions separated by the means to separate the ions;

means to digitize the output of the means to detect the ions;

means to transfer the data output of the means to digitize;

at least one of a means to process the data output of the means to digitize, or a means to record the data output of the means to digitize;

means to detect the presence of a particle to be analyzed in the mass spectrometer; and

means to synchronize at least one of the means to detect the ions, the means to digitize the output of the means to detect ions, the means to transfer the data output of the means to digitize;

the means to process the data output of the means to digitize;

the means to record the data output of the means to digitize with the means to detect the presence of a particle in the mass spectrometer.

2. The mass spectrometer according to claim 1 wherein the means to detect the presence of a particle in the mass spectrometer at least partially overlap with the means to detect the ions separated by the means to separate the ions.

3. The mass spectrometer according to claim 1 wherein the means to detect the presence of a particle in the mass spectrometer comprise an ion detector separate from the means to detect the ions separated by the means to separate the ions.

4. The mass spectrometer according to claim 1 wherein the means to detect the presence of a particle in the mass spectrometer comprise a means to detect ions associated with a particle stain, the stain being a compound or one or more elements significantly present in the particle.

5. The mass spectrometer according to claim 1 wherein the means to detect the presence of a particle in the mass spectrometer comprise a detector of electrons.

6. The mass spectrometer according to claim 1 wherein the means to detect the presence of a particle in the mass spectrometer comprise photon detector.

7. The mass spectrometer according to claim 1 wherein the means to detect the presence of a particle in the mass spectrometer comprise means to detect electrically neutral component of the particle which survived the means to vaporize, atomize and ionize elements associated with a particle in an un-ionized state.

8. The mass spectrometer according to claim 7 in which the means to detect electrically neutral component of a particle comprise means to detect one or more of secondary electrons, ions or photons emitted by the impact of the neutral components upon a surface.

9. The mass spectrometer according to claim 7 in which the means to detect electrically neutral components of the particle comprise secondary electron multiplier.

10. The mass spectrometer according to claim 1 wherein the means to synchronize include a processor and a processor code.

11. The mass spectrometer according to claim 1 wherein at least one of the means to detect the presence of a particle or the means to synchronize contain means to detect and record the time of arrival of the particle into the mass spectrometer.

12. A method of elemental analysis of a particle by mass spectrometry using a plurality of a single sampling cycle mass spectra produced by a mass spectrometer, comprising:

defining a primary detection group consisting of one or more mass-to-charge ratio channels of the mass spectrometer based on anticipated elements associated with the particle;

defining a secondary detection group consisting of one or more different to the first detection group mass-to-charge ratio channels of the mass spectrometer;

defining a function having as arguments the data collected in the primary detection group in one or more sampling cycles;

defining at least one selection criterion for evaluating the function as indicating a presence of a particle in the mass spectrometer; and

acquiring the first data in at least the primary detection group, for at least one sampling cycle,

wherein in the event that the value of the function of the first data satisfies the pre-defined selection criteria, designating the sampling cycle as associated with the particle and using the data from one or more of the first and the second detection group for the analysis of the particle.

13. The method according to claim 12 wherein the function is a signal strength of at least one mass-to-charge ratio channel from the primary group.

14. The method according to the claim 12 wherein the function is the sum of signal strength of two or more signals from the primary group.

15. The method according to claim 12 wherein the function is the ratio of the signal strength of at least two signals from the primary detection group.

16. The method according to claim 12 wherein the acquiring of the first data is done for a plurality of single sampling cycle mass spectra associated with the particle.

17. The method according to claims 16, wherein the plurality of single sampling cycle has a time period between 50 and 500 microseconds.

18. The method according to claim 16 wherein the function is the integral of the signal strength for each mass-to-charge ratio of the primary detection group across several single sampling cycle mass spectra.

19. The method according to claim 18, wherein the plurality of single sampling cycle has a time period between 50 and 500 microseconds.

20. The method according to claim 12, further comprising recording the order number of a single sampling cycle mass spectrum associated with the particle in the sequence of the sampling cycles of the mass spectrometer.

21. The method according to claim 12, further comprising recording a number of the single sampling cycle mass spectra that are associated with the particle

22. The method according to claim 12, wherein the analyzing the particle using the data includes summing a signal strength in each mass-to-charge ratio channel across a group of single sampling cycle mass spectra that is associated with the particle.

23. The method according to any one of claims 13-15 and 18-19, wherein the signal strength is defined by at least one of a peak height, peak width or a peak area of mass peaks detected the determination of the function data.

24. The method according to the claims 12, wherein the selection criterion comprise a threshold value for comparison with the function data.

25. The method according to the claim 12, wherein the selection criterion comprise a pre-determined range of values for comparison with the function data.

26. The method according to claims 12, wherein the primary detection group overlaps with the secondary detection group.

27. Computer readable code stored on computer readable medium for execution in a mass spectrometer, the computer readable code when executed causes the mass spectrometer to:

define a primary detection group consisting of one or more mass-to-charge ratio channels of the mass spectrometer based on anticipated elements associated with the particle;

define a secondary detection group consisting of one or more different to the first detection group mass-to-charge ratio channels of the mass spectrometer;

define a function having as arguments the data collected in the primary detection group in one or more sampling cycles;

define at least one selection criterion for evaluating the function as indicating a presence of a particle in the mass spectrometer; and

acquire the first data in the plurality of mass-to-charge ratio channels of the mass spectrometer which includes at least the primary detection group, for at least one sampling cycle,

wherein in the event that the value of the function of the first data satisfies the pre-defined selection criteria, then designate the sampling cycle as associated with the particle and use the data from one or more of the first and the second detection group for the analysis of the particle

28. The computer readable code of claim 27, wherein the code for causing the mass spectrometer to evaluate the first data includes further code to:

derive a signal strength from the first data; and

determine whether the signal strength is above a signal threshold to indicate the presence of the particle in the mass spectrometer.

29. The computer readable code of claim 27, further comprising code to transfer eligible data to a data storage.

30. The computer readable code of claim 27, wherein the primary detection group and the secondary detection group overlap.