Method to reduce measurement bias
AssigneeMicromass UK Limited
InventorsRichard Barrington Moulds, David Gordon
Life of this patent
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Abstract
A method of mass analysing a single analytical sample is disclosed comprising: i) transmitting different species of ions through a mass spectrometer; ii) sequentially mass analysing, or otherwise detecting, said different species of ions in a particular sequential order; and then iii) repeating steps i) and ii), wherein the sequential order in which said different species of ions are mass analysed, or otherwise detected, is different when step ii) is repeated. The sensitivity with which the mass spectrometer is able to detect ions varies for a period of time, and step ii) and iii) are performed during that period of time.
Claims24
A method of mass analysing a single analytical sample comprising:
- i) transmitting different species of ions through a mass spectrometer;
- ii) sequentially mass analysing, or otherwise detecting, said different species of ions in a particular sequential order;
- and then
- iii) repeating steps i) and ii), wherein the sequential order in which said different species of ions are mass analysed, or otherwise detected, is different when step ii) is repeated.
The method of any preceding claim, wherein each time step ii) is performed, it comprises mass filtering said different species of ions using a mass filter such that only a single species of ion is transmitted to an ion detector at any one time, and wherein the mass filter is controlled so as to change the species of ion that is transmitted to the detector at different times, thereby defining said sequential order in which the different species of ions are mass analysed.
The method of any preceding claim, wherein step iii) comprises performing an analytical sequence that consists of repeating steps i) and ii) a plurality of times, wherein the sequential order in which said different species of ions are mass analysed, or otherwise detected, during these plurality of times is different each and every time step ii) is performed within the analytical sequence.
The method of any preceding claim, comprising comparing the ion signal detected for one of said different species of ions with the ion signal detected for another of said different species of ions.
The method of any preceding claim, wherein the spectrometer comprises a user interface and, prior to step ii), the method comprises selecting the species of ions that are to be said different species of ions and inputting these selected species of ions into the user interface so that the mass spectrometer performs steps ii) and iii) on these ions.
The method of any preceding claim, wherein all of the steps are performed within a single experimental run.
The method of any preceding claim, comprising fragmenting or reacting ions of an analyte of interest, and optionally ions of a corresponding internal standard, so as to form fragment or product ions;
- wherein said different species of ions comprise multiple different ones of the fragment or product ions.
The method of any preceding claim, comprising separating a sample that comprises a plurality of different analytes of interest using a chromatography device such that said different analytes of interest elute from the chromatography device over different respective time periods, and ionising the sample eluting from the chromatography device so as to provide ions of said analytes of interest;
- optionally wherein the sample also comprises an internal standard corresponding to one or more of said different analytes of interest, wherein each internal standard elutes from the chromatography device over substantially the same time period as its respective analyte of interest and is then ionised.
The method of any preceding claim, wherein step iii) comprises repeating step ii) in a manner such that the first species of ion mass analysed, or otherwise detected, any given time that step ii) is performed differs from the last species of ion that was mass analysed, or otherwise detected, the preceding time that step ii) was performed.
A mass spectrometer comprising:
- a mass analyser;
- and
- a controller having electronic circuitry configured to control the spectrometer to:
- i) transmit different species of ions through the mass spectrometer;
- ii) sequentially mass analyse, or otherwise detect, said different species of ions in a particular sequential order;
- and then
- iii) repeat steps i) and ii), wherein the sequential order in which said different species of ions are mass analysed, or otherwise detected, is different when step ii) is repeated.
A method of mass spectrometry comprising:
- i) operating a mass spectrometer during a period of time in which the sensitivity with which the mass spectrometer is able to detect ions varies;
- ii) using the mass spectrometer to determine the intensity of the ion signal of an ion of interest within said period of time;
- iii) repeating steps i) and ii) as the ion of interest, or an analyte from which it is derived, elutes from a separation device;
- wherein when step ii) is repeated, it is performed at different times after said period of time begins;
- iv) producing a first set of data that comprises the intensity of the ion signal as a function of detection time;
- v) smoothing the first set of data so as to obtain a second set of smoothed data;
- and
- vi) determining if maintenance of the spectrometer is required based on a comparison of the first and second sets of data.
A mass spectrometer comprising:
- a separation device for separating ions, or analytes;
- a mass analyser;
- and
- a controller having electronic circuitry configured to control the mass spectrometer to:
- i) operate during a period of time in which the sensitivity with which the mass analyser is able to detect ions varies;
- ii) determine the intensity of the ion signal of an ion of interest detected by the mass analyser within said period of time;
- iii) repeat steps i) and ii) as the ion of interest, or an analyte from which it is derived, elutes from the separation device;
- wherein when step ii) is repeated, it is performed at different times after said period of time begins;
- iv) produce a first set of data that comprises the intensity of the ion signal as a function of detection time;
- v) smooth the first set of data so as to obtain a second set of smoothed data;
- and
- vi) determine if maintenance of the spectrometer is required based on a comparison of the first and second sets of data.
Dependencies are inferred from the claim text.