ESTIMATION OF ION CYCLOTRON RESONANCE PARAMETERS IN FOURIER TRANSFORM MASS SPECTROMETRY

• US 20090278037A1
• Filed: 05/25/2007
• Published: 11/12/2009
• Est. Priority Date: 05/26/2006
• Status: Active Grant

• Current Assignee: Cedars-Sinai Medical Center (Cedars Sinai Health System)
• Original Assignee: Cedars-Sinai Medical Center (Cedars Sinai Health System)
• Inventors: Grothe, Robert A. JR.
• Granted Patent: US 8,274,043 B2
• Time in Patent Office: Days
• US Class Current: 250/282
• CPC Class Codes: H01J 49/0036 Step by step routines describing the handling of the data generated during a measurement
• CPC Class Codes: H01J 49/38 Omegatrons ; using ion cyclotron resonance

Abstract

The present invention comprises a method and system for accurate estimation of the ion cyclotron resonance (ICR) parameters in Fourier-transform mass spectrometry (FTMS/FT-ICR MS). The parameters are essential to estimating the mass to charge ratio of an ion from FT-ICR MS data, the intended purpose of the instrument. Achieving greater accuracy in the parameters assists in greater accuracy of the mass to charge ratio of an ion, and obtaining an accurate estimation of the mass to charge ratio of an ion further aides in detecting mass with sub-ppm accuracy. Estimating mass in this manner enhances identification and characterization of large molecules. The inventive method and system thereby enhances the data obtained by conventional FTMS by accurately estimating ICR parameters. Ultimately, accurate estimates of the masses of molecules and detection and characterization of molecules from FT-ICR MS data are obtained.

Claims

1. A method for accurately estimating ion cyclotron resonance parameters comprising

obtaining a voltage signal produced by one or more ions in a mass spectrometer wherein the measured component of the ion trajectory is a sinusoid with fixed frequency and exponentially decaying amplitude characterized by a decay time constant, and the voltage is proportional to the measured component of the ion position plus additive white Gaussian noise;

and

finding the point where the partial derivatives of the data likelihood of the parameters consisting of initial magnitude, frequency, initial phase, and decay constant are all equal to zero from the voltage signal by using an iterative algorithm;

wherein the parameter values obtained maximize the data likelihood.

2. The method of claim 1, wherein the duration of the observation of the voltage signal is fixed and known.

3. The method of claim 1, wherein the iterative algorithm is performed by software.

4. The method of claim 3, wherein the software is stored on conventional media.

5. The method of claim 1, wherein the mass spectrometer is a Fourier transform ion cyclotron resonance mass spectrometer or a machine that measures the frequency of oscillation induced by a potential that varies harmonically in one direction.

6. The method of claim 1, wherein the ion cyclotron resonance parameters are used to identify molecules in a complex mixture.

7. The method of claim 1, wherein the ion cyclotron resonance parameters are used to quantify the relative abundances of molecules in a complex mixture.

8. A method of obtaining the mass-to-charge ratios of ion cyclotron resonance parameters by converting the estimated frequencies obtained in claim 1 to mass-to-charge values by mass calibration.

9. A method of accurately estimating the mass of an ion comprising

estimating the ion'"'"'s cyclotron parameters consisting of initial magnitude, frequency, initial phase, and decay constant from the transient voltage signal obtained by mass spectroscopy and

converting the estimated parameters into a mass-to-charge ratio by mass calibration.

10. The method of claim 9, wherein estimating the parameters comprises obtaining voltage signal produced by one or more ions in a mass spectrometer, finding the point where the partial-derivatives of the parameters are all equal to zero from the voltage signal produced, and performing an iterative algorithm to arrive at estimated values for the parameters.

14. The computer readable medium of claim 10, wherein the duration of the observation of the voltage signal is fixed and known.

11. A method for identifying human tryptic peptides from mass spectroscopy data comprising

estimating ion cyclotron parameters,

calibrating mass using the ion cyclotron parameters,

determining exact mass based upon the calibration and determining chemical formulae based upon the mass, and

interpreting the chemical formulae based upon a comparison of the chemical formulae obtained with data from the human proteome.

12. The method of claim 11, wherein the data from the human proteome is in the EBI-IPI database.

13. A computer readable medium having computer executable components for estimating ion cyclotron resonance parameters comprising

obtaining a voltage signal produced by one or more ions in a mass spectrometer wherein the measured component of the ion trajectory is a sinusoid with fixed frequency and exponentially decaying amplitude characterized by a decay time constant, and the voltage is proportional to the measured component of the ion position plus additive white Gaussian noise;

and

finding the point where the partial derivatives of the data likelihood of the parameters consisting of initial magnitude, frequency, initial phase, and decay constant are all equal to zero from the voltage signal by using an iterative algorithm;

wherein the parameter values obtained maximize the data likelihood.

15. A FTMS machine comprising computer readable media having computer executable instructions for estimating ion cyclotron resonance parameters wherein the computer readable medium having computer executable instructions for estimating ion cyclotron resonance parameters on the FTMS machine comprises obtaining a voltage signal produced by one or more ions in a mass spectrometer wherein the detected spatial component of the ion trajectory is a sinusoid with fixed frequency and exponentially decaying amplitude characterized by a decay time constant, and the voltage is proportional to the measured component of the ion position plus additive white Gaussian noise;

and finding the point where the partial derivatives of the data likelihood of the parameters consisting of initial magnitude, frequency, initial phase, and decay constant are all equal to zero from the voltage signal by using an iterative algorithm, and wherein the parameter values obtained maximize the data likelihood.

16. The FTMS machine of claim 15, wherein the duration of the observation of the voltage signal in the computer readable media having computer executable instructions for estimating ion cyclotron resonance parameters is fixed and known.