Median filter for liquid chromatography-mass spectrometry data

• US 7,253,404 B2
• Filed: 07/01/2005
• Issued: 08/07/2007
• Est. Priority Date: 11/27/2000
• Status: Expired due to Fees

• Current Assignee: Caprion Proteomics Inc. (CellCarta Biosciences, Inc.)
• Original Assignee: PPD Biomarker Discovery Sciences LLC (CellCarta Biosciences, Inc.)
• Inventors: Hastings, Curtis
• Primary Examiner(s): NGUYEN, KIET TUAN
• Application Number:
  US11/173,937
• Publication Number:
  US 20060097154A1
• Time in Patent Office: 767 Days
• Field of Search: 250/282, 250/281, 702/30, 702/27, 702/22
• US Class Current: 250/282
• CPC Class Codes: G01N 30/72 Mass spectrometers mass spectrometers per se H01J49/00
• CPC Class Codes: G01N 30/8624 Detection of slopes or peaks; baseline correction
• CPC Class Codes: G01N 30/8641 Baseline
• CPC Class Codes: H01J 49/0036 Step by step routines describing the handling of the data generated during a measurement
• CPC Class Codes: H01J 49/0431 for liquid samples interfaces to liquid chromatographs G01N30/7233

Abstract

High-intensity, spiked noise is reduced in chromatography-mass spectrometry data by applying a nonlinear filter such as a moving median filter to the data. The filter is applied to individual mass chromatograms, plots of ion abundance versus retention time for each detected mass-to-charge ratio, and the filtered chromatograms are combined to form a filtered total ion current chromatogram. Standard linear filters are not effective for reducing noise in liquid chromatography-mass spectrometry (LC-MS) data because they assume a normal distribution of noise. LC-MS noise, however, is not normally distributed.

Claims

1. A method for characterizing a chemical sample, comprising:

acquiring a series of mass spectra of said sample;

generating a set of discrete data points based on the mass spectra, said data points comprising a plurality of chromatograms;

selecting a data filter window size;

centering said data filter window on one or more particular data points of said set of data points; and

replacing said particular data point with the median of all points within said window to produce a filtered mass chromatogram.

2. The method of claim 1, further comprising:

applying a component selection algorithm to said filtered mass chromatogram.

3. The method of claim 1, wherein said discrete data points correspond to integer mass values.

4. The method of claim 1, wherein said discrete data points correspond to non-integer mass values.

5. The method of claim 1, further comprising:

combining a plurality of filtered mass chromatograms into a total ion current chromatogram.

6. The method of claim 5, wherein said combining comprises summing a plurality of intensities associated with said filtered mass chromatograms.

7. The method of claim 5, wherein said combining comprises thresholding said mass spectra using said plurality of filtered mass chromatograms.

8. The method of claim 1, wherein said data window filter size is selected based on at least one of:

(a) being not wider than a typical data peak width;

(b) a scan rate at which said generating is performed;

(c) data characteristics obtained by analyzing subsets of points in said plurality of mass chromatograms; and

(d) a predetermined knowledge of instrument conditions.

9. A program storage device accessible by a processor, tangibly embodying a program of instructions executable by said processor to perform method steps for a chemical sample analysis method, said method steps comprising:

acquiring a series of mass spectra of said sample;

generating a set of discrete data points based on the mass spectra, said data points comprising a plurality of chromatograms;

selecting a data filter window size;

centering said data filter window on one or more particular data points of said set of data points; and

replacing said particular data point with the median of all points within said window to produce a filtered mass chromatogram.

10. The program storage device of claim 9, said method steps further comprising:

applying a component selection algorithm to said filtered mass chromatogram.

11. The program storage device of claim 9, wherein said discrete data points correspond to integer mass values.

12. The program storage device of claim 9, wherein said discrete data points correspond to non-integer mass values.

13. The program storage device of claim 9, said method steps further comprising:

combining a plurality of filtered mass chromatograms into a total ion current chromatogram.

14. The program storage device of claim 13, wherein said combining comprises summing a plurality of intensities associated with said filtered mass chromatograms.

15. The program storage device of claim 13, wherein said combining comprises thresholding said mass spectra using said plurality of filtered mass chromatograms.

16. The program storage device of claim 9, wherein said data window filter size is selected based on at least one of:

(a) being not wider than a typical data peak width;

(b) a scan rate at which said generating is performed;

(c) data characteristics obtained by analyzing subsets of points in said plurality of mass chromatograms; and

(d) a predetermined knowledge of instrument conditions.

17. A method of characterizing a chemical sample, comprising:

obtaining a chromatogram from a series of mass spectra of said sample, wherein said mass spectra are generated by chromatography and mass spectrometry, and wherein said chromatogram comprises signal data and noise data; and

applying a non-linear filter to said chromatogram to remove at least some of said noise data, thereby producing a filtered chromatogram.

18. The method of claim 17, wherein said chromatogram is a total ion chromatogram and said filtered chromatogram is a filtered total ion chromatogram.

19. The method of claim 18, further comprising generating individual chromatograms from said total ion chromatogram, wherein said non-linear is applied to said individual chromatograms.

20. The method of claim 17, wherein said chromatography is liquid chromatography.