Classifications

• • H—ELECTRICITY
  • H01—ELECTRIC ELEMENTS
  • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
  • H01J49/00—Particle spectrometers or separator tubes
  • H01J49/0027—Methods for using particle spectrometers
  • H01J49/0036—Step by step routines describing the handling of the data generated during a measurement
• • H—ELECTRICITY
  • H01—ELECTRIC ELEMENTS
  • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
  • H01J49/00—Particle spectrometers or separator tubes
  • H01J49/02—Details
  • H01J49/022—Circuit arrangements, e.g. for generating deviation currents or voltages ; Components associated with high voltage supply
• • H—ELECTRICITY
  • H01—ELECTRIC ELEMENTS
  • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
  • H01J49/00—Particle spectrometers or separator tubes
  • H01J49/26—Mass spectrometers or separator tubes
  • H01J49/34—Dynamic spectrometers
  • H01J49/40—Time-of-flight spectrometers

Definitions

• the present invention relates to a mass spectrometer and a method of mass spectrometry.
• the preferred embodiment relates to an ion detector system and method of detecting ions.
• TDC Time to Digital Converters
• ADC Analogue to Digital Converters
• Time of Flight instruments incorporating Time to Digital Converters are known wherein signals resulting from ions arriving at an ion detector are recorded. Signals which satisfy defined detection criteria are recorded as a single binary value and are associated with a particular arrival time relative to a trigger event. A fixed amplitude threshold may. be used to trigger recording of an ion arrival event. Ion arrival events which are subsequently recorded resulting from subsequent trigger events are combined to form a histogram of ion arrival events. The histogram of ion arrival events is then presented as a spectrum for further processing. Time to Digital Converters have the advantage of being able to detect relatively weak signals so long as the probability of multiple ions arriving at the ion detector in close temporal proximity remains relatively low. One disadvantage of Time to Digital Converters is ⁇ that once an ion event has been recorded then there is a significant time interval or dead-time following the ion arrival event during which time no further ion arrival events can be recorded.
• Time to Digital Converters are unable to distinguish between a signal resulting from the arrival of a single ion at the ion detector and a signal resulting from the simultaneous arrival of multiple ions at the ion detector. This is due to the fact that the signal will only cross the threshold once irrespective of whether a single ion arrived at the ion detector or whether multiple ions arrived simultaneously at the ion detector. Both situations result in only a single ion arrival event being recorded.
• Time of Flight instruments which incorporate Analogue to Digital Converters are also known.
• An Analogue to Digital Converter is arranged to digitise signals resulting from ions arriving at the ion detector relative to a trigger event. The digitised signals resulting from subsequent trigger events are summed or averaged to produce a spectrum for further processing.
• a known signal averager is capable of digitising the output from ion detector electronics at a frequency of 3-4 GHz with eight or ten bit intensity resolution.
• One advantage of using an Analogue to Digital Converter as part of an ion detector system is that multiple ions which arrive substantially simultaneously at an ion detector and at relatively high signal intensities can be recorded without the ion detector suffering from distortion or saturation effects.
• the detection of low intensity signals is generally limited by electronic noise from the digitiser electronics, the ion detector and the amplifier system. The problem of electronic noise also effectively limits the dynamic range of the ion detector system.
• an Analogue to Digital Converter as part of an ion detector system (as opposed to using a Time to Digital Converter as part of the ion detector system) is that the analogue width of the signal generated by a single ion adds to the width of the ion arrival envelope for a particular mass to charge value in the final spectrum.
• a Time to Digital Converter only ion arrival times are recorded and hence the width of mass peaks in the final spectrum is determined only by ,the spread in ion arrival times for each mass peak and by variation in the voltage pulse height produced by an ion arrival relative to the signal threshold.
• a method of increasing the dynamic range of a transient recorder by using two Analogue to Digital Converters is known.
• a transient signal from an ion detector is amplified using two amplifiers having different gains.
• the two transients are digitized and the digitized data is combined on a time sample by time sample basis. High gain samples are used unless saturation is determined to occur at which point low gain data is substituted.
• the low gain data is scaled by the difference in gain between the two amplifiers.
• the result is a combined transient having a higher dynamic range than that obtainable using a single Analogue to Digital Converter.
• the combined transient is added to other transients which were collected previously using a known averager method. Once a preset number of transients have been averaged the resulting spectrum is stored to disk.
• the known method also suffers from the same problems as a standard averaging Analogue to Digital Converter system in terms of reduced dynamic range due to the averaging of noise at low signal intensities and degraded resolution due to the digitization of the analogue ion peak width.
• Detectors using a combination of both Time to Digital Converter electronics and Analogue to Digital Converter electronics have been employed in an attempt to take advantage of the characteristics of each different type of recording device thereby attempting to increase the dynamic range and the observed time or mass resolution.
• Such systems are relatively complex to calibrate and operate. Such systems are also comparatively expensive.
• a method of detecting ions comprising: outputting a first signal and a second signal from an ion detector, wherein the first signal corresponds with a signal multiplied or amplified by a first gain and the second signal corresponds with a signal multiplied or amplified by a second different gain,- digitising the first signal to produce a first digitised signal and digitising the second signal to produce a second digitised signal; determining first intensity and arrival time, mass or mass to charge ratio data from the first digitised signal; determining second intensity and arrival time, mass or mass to charge ratio data from the second digitised signal; and combining the first intensity and arrival time, mass or mass to charge ratio data and the second intensity and arrival time, mass or mass to charge ratio data to form a combined data set.
• the method preferably further comprises processing the first digitised signal to detect a first set of peaks or ion arrival events and/or processing the second digitised signal to detect a second set of peaks or ion arrival events .
• the step of determining the first intensity and arrival time, mass or mass to charge ratio data preferably further comprises marking or flagging each peak or ion arrival event in the first -set of peaks or ion arrival events when the maximum digitised signal within a peak or ion arrival event is determined as equalling or approaching a maximum or full scale digitised output or is otherwise saturated or approaching saturation.
• the step of determining the second intensity and arrival time, mass or mass to charge ratio data preferably further comprises marking or flagging each peak or ion arrival event in the second set of peaks or ion arrival events when the maximum digitised signal within a peak or ion arrival event is determined as equalling or approaching a maximum or full scale digitised output or is otherwise saturated or approaching saturation.
• the step of combining the first intensity and arrival time, mass or mass to charge ratio data and the second intensity and arrival time, mass or mass to charge ratio data preferably further comprises :
• the method preferably further comprises scaling the peaks or ion arrival events selected from the first set of peaks or ion arrival events by a scale factor.
• the scale factor preferably corresponds with, is close to or is otherwise related to the ratio of the second gain to the first gain.
• the method preferably further comprises summing the combined data set with a plurality of other corresponding combined data sets to form a final spectrum.
• a method of detecting ions comprising: outputting a first signal and a second signal from an ion detector, wherein the first signal corresponds with a signal multiplied or amplified by a first gain and the second signal corresponds with a signal multiplied or amplified by a second different gain,- digitising the first signal to produce a first digitised signal and digitising the second signal to produce a second digitised signal; summing the first digitised signal with a plurality of other corresponding first digitised signals to form a first summed digitised signal; summing the second digitised signal with a plurality of other corresponding second digitised signals to form a second summed digitised signal; determining first summed intensity and arrival time, mass or mass to charge ratio data from the first summed digitised signal; determining second summed intensity and arrival time, mass or mass to charge ratio data from the second summed digitised signal; and combining the first
• the method preferably further comprises processing the first summed digitised signal to detect a first set of peaks or ion arrival events and/or processing the second summed digitised signal to detect a second set of peaks or ion arrival events.
• the step of determining the first summed intensity and arrival time, mass or mass to charge ratio data from the first summed digitised signal preferably further comprises determining first summed intensity and arrival time, mass or mass to charge ratio data for each or at least some peaks or ion arrival events in the first set of peaks or ion arrival events .
• the step of determining the second summed intensity and arrival time, mass or mass to charge ratio data from the second summed digitised signal preferably further comprises determining second summed intensity and arrival time, mass or mass to charge ratio data for each or at least some peaks or ion arrival events in the second set of peaks or ion arrival events .
• the step of determining the first summed intensity and arrival time, mass or mass to charge ratio data preferably further comprises marking or flagging each peak or ion arrival event in the first set of peaks or ion arrival events when the maximum digitised signal within a peak or ion arrival event is determined as equalling or approaching a maximum or full scale digitised output or is otherwise saturated or approaching saturation.
• the step of determining the second summed intensity and arrival time, mass or mass to charge ratio data preferably further comprises marking or flagging each peak or ion arrival event in the second set of peaks or ion arrival events when the maximum digitised signal within a peak or ion arrival event is determined as equalling or approaching a maximum or full scale digitised output or is otherwise saturated or approaching saturation.
• the step of combining the first summed intensity and arrival time, mass or mass to charge ratio data and the second summed intensity and arrival time, mass or mass to charge ratio data preferably further comprises: (a) selecting peak intensity and arrival time, mass or mass to charge ratio data from the second set of peaks or ion arrival events for each or at least some peaks or ion arrival events which are not marked or flagged or otherwise indicated as suffering from or approaching saturation; and/or
• the method preferably further comprises scaling the peaks or ion arrival events selected from the first set of peaks or ion arrival events by a scale factor.
• the scale factor preferably corresponds with, is close to or is otherwise related to the ratio of the second gain to the first gain.
• a method of detecting ions comprising: outputting a first signal and a second signal from an ion detector, wherein the first signal corresponds with a signal multiplied or amplified by a first gain and the second signal corresponds with a signal multiplied or amplified by a second different gain,- digitising the first signal to produce a first digitised signal and digitising the second signal to produce a second digitised signal; combining the first digitised signal and the second digitised signal to form a combined digitised signal; determining intensity and arrival time, mass or mass to charge ratio data from the combined digitised signal; and summing the intensity and arrival time, mass or mass to charge ratio data with a plurality of other corresponding intensity and arrival time, mass or mass to charge ratio data to form a final spectrum.
• the method preferably further comprises processing the combined digitised signal to detect a set of peaks or ion arrival events .
• the step of determining the intensity and arrival time, mass or mass to charge ratio data from the combined digitised signal preferably further comprises determining intensity and arrival time, mass or mass to charge ratio data for each or at least some peaks or ion arrival events in the set of peaks or ion arrival events .
• the step of determining the intensity and arrival time, mass or mass to charge ratio data preferably further comprises marking or flagging each peak or ion arrival event in the first digitised signal when the maximum digitised signal within a peak or ion arrival event is determined as equalling or approaching a maximum or full scale digitised output or is otherwise saturated or approaching saturation.
• the step of determining the intensity and arrival time, mass or mass to charge ratio data preferably further comprises marking or flagging each peak or ion arrival event in the second digitised signal when the maximum digitised signal within a peak or ion arrival event is determined as equalling or approaching a maximum or full scale digitised output or is otherwise saturated or approaching saturation.
• the step of combining the first digitised signal and the second digitised signal preferably further comprises:
• the method preferably further comprises scaling the peaks or ion arrival events selected from the first digitised signal by a scale factor.
• the scale factor preferably corresponds with, is close to or is otherwise related to the ratio of the second gain to the first gain.
• a method of detecting ions comprising: outputting a first signal and a second signal from an ion detector, wherein the first signal corresponds with a signal multiplied or amplified by a first gain and the second signal corresponds with a signal multiplied or amplified by a second different gain; digitising the first signal to produce a first digitised signal and digitising the second signal to produce a second digitised signal; combining the first digitised signal and the second digitised signal to form a combined digitised signal; summing the combined digitised signal with a plurality of other corresponding combined digitised signals to form a final spectrum; and determining intensity and arrival time, mass or mass to charge ratio data from the final spectrum.
• the method preferably further comprises processing the final spectrum to detect a set of peaks or ion arrival events.
• the step of determining the intensity and arrival time, mass or mass to charge ratio data from the final spectrum preferably further comprises determining intensity and arrival time, mass or mass to charge ratio data for each or at least some peaks or ion arrival events in the set of peaks or ion arrival events .
• the step of determining the intensity and arrival time, mass or mass to charge ratio data preferably further comprises marking or flagging each peak or ion arrival event in the first digitised signal when the maximum digitised signal within a peak or ion arrival event is determined as equalling or approaching a maximum or full scale digitised output or is otherwise saturated- or approaching saturation.
• the step of determining the intensity and arrival time, mass or mass to charge ratio data preferably further comprises marking or flagging each peak or ion arrival event in the second digitised signal when the maximum digitised signal within a peak or ion arrival event is determined as equalling or approaching a maximum or full scale digitised output or is otherwise saturated or approaching saturation.
• the step of combining the first digitised signal and the second digitised signal preferably further comprises:
• the method preferably further comprises scaling the peaks or ion arrival events selected from the first digitised signal by a scale factor.
• the scale factor preferably corresponds with, is close to or is otherwise related to the ratio of the second gain to the first gain.
• a method of detecting ions comprising: outputting a first signal and a second signal from- an ion detector, wherein the first signal corresponds with a signal multiplied or amplified by a first gain and the second signal corresponds with a signal multiplied or amplified by a second different gain,- digitising the first signal to produce a first digitised signal and digitising the second signal to produce a second digitised signal; determining first intensity and arrival time, mass or mass to charge ratio data from the first digitised signal; determining second intensity and arrival time, mass or mass to charge ratio data from the second digitised signal; summing the first intensity and arrival time, mass or mass to charge ratio data with a plurality of other corresponding first intensity and arrival time, mass or mass to charge ratio data to form a first summed spectrum,- summing the second intensity and arrival time, mass or mass to charge ratio data with a plurality of other corresponding second intensity and arrival time, mass or mass to charge ratio ratio
• the method preferably further comprises processing the first digitised signal to detect a first set of peaks or ion arrival events and/or processing the second digitised signal to detect a second set of peaks or ion arrival events.
• the step of determining the first intensity and arrival time, mass or mass to charge ratio data from the first digitised signal preferably further comprises determining intensity and arrival time, mass or mass to charge ratio data for each or at least some peaks or ion arrival events in the first set of peaks or ion arrival events.
• the step of determining the second intensity and arrival time, mass or mass to charge ratio data from the second digitised signal preferably further comprises determining intensity and arrival time, mass or mass to charge ratio data for each or at least some peaks or ion arrival events in the second set of peaks or ion arrival events .
• the step of determining the first intensity and arrival time, mass or mass to charge ratio data preferably further comprises marking or flagging each peak or ion arrival event in the first set of peaks or ion arrival events when the maximum digitised signal within a peak or ion arrival event is determined as equalling or approaching a maximum or full scale digitised output or is otherwise saturated or approaching saturation.
• the step of determining the second intensity and arrival time, mass or mass to charge ratio data preferably further comprises marking or flagging each peak or ion arrival event in the second set of peaks or ion arrival events when the maximum digitised signal within a peak or ion arrival event is determined as equalling or approaching a maximum or full scale digitised output or is otherwise saturated or approaching saturation.
• the step of combining the first summed spectrum and the second summed spectrum to form a final spectrum preferably further comprises :
• the method preferably further comprises scaling the peaks or ion arrival events selected from the first summed spectrum by a scale factor.
• the scale factor preferably corresponds with, is close to or is otherwise related to the ratio of the second gain to the first gain.
• a method of detecting ions comprising: outputting a first signal and a second signal from an ion detector, wherein the first signal corresponds with a signal multiplied or amplified by a first gain and the second signal corresponds with a signal multiplied or amplified by a second different gain; digitising the first signal to produce a first digitised signal and digitising the second signal to produce a second digitised signal; summing the first digitised signal with a plurality of other corresponding first digitised signals to form a first summed digital signal; summing the second digitised signal with a plurality of other corresponding second digitised signals to form a second summed digital signal; determining first summed intensity and arrival time, mass or mass to charge ratio data from the first summed digital signal; determining second summed intensity and arrival time, mass or mass to charge ratio data from the second summed digital signal; and combining the first summed intensity and arrival time, mass
• the step of determining the first summed intensity and arrival time, mass or mass to charge ratio data from the first summed digitised signal preferably further comprises determining intensity and arrival time, mass or mass to charge ratio data for each or at least some peaks or ion arrival events in the first set of peaks or ion arrival events.
• the step of determining the second summed intensity and arrival time, mass or mass to charge ratio data from the second summed digitised signal preferably further comprises determining intensity and arrival time, mass or mass to charge ratio data for each or at least some peaks or ion arrival events in the second set of peaks or ion arrival events .
• the step of determining the first summed intensity and arrival time, mass or mass to charge ratio data preferably further comprises marking or flagging each peak or ion arrival event in the first set of peaks or ion arrival events when the maximum digitised signal within a peak or ion arrival event is determined as equalling or approaching a maximum or full scale digitised output or is otherwise saturated or approaching saturation.
• the step of determining the second summed intensity and arrival time, mass or mass to charge ratio data preferably further comprises marking or flagging each peak or ion arrival event in the second set of peaks or ion arrival events when the maximum digitised signal within a peak or ion arrival event is determined as equalling or approaching a maximum or full scale digitised output or is otherwise saturated or approaching saturation.
• the step of combining the first summed spectrum and the second summed spectrum to form a final spectrum preferably further comprises:
• the method preferably further comprises scaling the peaks or ion arrival events selected from the first summed spectrum by a scale factor.
• the scale factor preferably corresponds with, is close to or is otherwise related to the ratio of the second gain to the first gain.
• step of outputting a first signal and a second signal may according to the preferred embodiment comprise converting, splitting or dividing a signal output from an ion detector into a first signal and a second signal. The first and second signals are then multiplied or amplified by different gains.
• the step of outputting the first signal and the second signal may comprise monitoring or outputting the signal from an ion detector at least two different positions or locations in or along one or more dynodes or another part of an ion detector.
• the first gain may be substantially greater than the second gain or more preferably the second gain may be substantially greater than the first gain.
• the ratio of the first gain to the second gain is preferably selected from the group consisting of: (i) ⁇ 2; (ii) 2-5; (iii) 5-10; (iv) 10-15; (v) 15-20; (vi) 20- 25; (vii) 25-30; (viii) 30-35; (ix) 35-40; (x) 40-45; (xi) 45-50; (xii) 50-60; (xiii) 60-70; (xiv) 70-80; (xv) 80-90; (xvi) 90-100; and (xvii) > 100.
• the ratio of the second gain to the first gain is preferably selected from the group consisting of: (i) ⁇ 2; (ii) 2-5; (iii) 5-10; (iv) 10- 15; (v) 15-20; (vi) 20-25; (vii) 25-30; (viii) 30-35; (ix) 35-40; (x) 40-45; (xi) 45-50; (xii) 50-60; (xiii) 60-70; (xiv) 70-80; (xv) 80-90; (xvi) 90-100; and (xvii) > 100.
• the steps of digitising the first signal and digitising the second signal are preferably performed substantially simultaneously.
• the step of digitising the first signal preferably comprises using a first Analogue to Digital Converter and/or the step of digitising the second signal comprises using a second Analogue to Digital Converter.
• the first Analogue to Digital Converter and/or the second Analogue to Digital Converter are preferably arranged .to convert an analogue voltage to a digital output.
• the first Analogue to Digital Converter and/or the second Analogue to Digital Converter are preferably arranged to operate, in use, at a digitisation rate selected from the group consisting of: (i) ⁇ 1 GHz; (ii) 1-2 GHz; (iii) 2-3 GHz; (iv) 3-4 GHz; (v) 4-5 GHz; (vi) 5-6 GHz; (vii) 6-7 GHz; (viii) 7-8 GHz; (ix) 8-9 GHz; (x) 9-10 GHz; and (xi) > 10 GHz.
• the first Analogue to Digital Converter and/or the second Analogue to Digital Converter preferably comprise a resolution selected from the group consisting of: (i) at least 4 bits; (ii) at least 5 bits; (iii) at least 6 bits,- (iv) at least 7 bits; (v) at least 8 bits,- (vi) at least 9 bits; (vii) at least 10 bits; (viii) at least 11 bits,- (ix) at least 12 bits; (x) at least 13 bits; (xi) at least 14 bits; (xii) at least 15 bits; and (xiii) at least 16 bits.
• the method preferably further comprises flagging data in the first digitised signal and/or the second digitised signal which is determined as corresponding to data which was obtained when an ion detector was saturated or nearing saturation.
• the method may comprise outputting a signal from an ion detector, wherein the signal is multiplied or amplified by a first gain to give the first (amplified) signal and outputting another signal which is multiplied or amplified by a second preferably higher gain to give the second (amplified) signal.
• an ion detector system comprising: a device arranged and adapted to output a first signal and a second signal from an ion detector, wherein the first signal corresponds with a signal multiplied or amplified by a first gain and the second signal corresponds with a signal multiplied or amplified by a second different gain; a device arranged and adapted to digitise the first signal to produce a first digitised signal and a device arranged and adapted to digitise the second signal to produce a second digitised signal; a device arranged and adapted to determine first intensity and arrival time, mass or mass to charge ratio data from the first digitised signal; a device arranged and adapted to determine second intensity and arrival time, mass or mass to charge ratio data from the second digitised signal; and a device arranged and adapted to combine the first intensity and arrival time, mass or mass to charge ratio data and the second intensity and arrival time, mass or mass to charge ratio data to form a combined data set.
• an ion detector system comprising: a device arranged and adapted to output a first signal and a second signal from an ion detector, wherein the first signal corresponds with a s'ignal multiplied or amplified by a first gain and the second signal corresponds with a signal multiplied or amplified by a second different gain; a device arranged and adapted to digitise the first signal to produce a first digitised signal and a device arranged and adapted to digitise the second signal to produce a second digitised signal; a device arranged and adapted to sum the first digitised signal with a plurality of other corresponding first digitised signals to form a first summed digitised signal; a device arranged and adapted to sum the second digitised signal with a plurality of other corresponding second digitised signals to form a second summed digitised signal; a device arranged and adapted to determine first summed intensity and arrival time, mass
• an ion detector system comprising: a device arranged and adapted to output a first signal and a second signal from an ion detector, wherein the first signal corresponds with a signal multiplied or amplified by a first gain and the second signal corresponds with a signal multiplied or amplified by a second different gain,- a device arranged and adapted to digitise the first signal to produce a first digitised signal and a device arranged and adapted to digitise the second signal to produce a second digitised signal; a device arranged and adapted to combine the first digitised signal and the second digitised signal to form a combined digitised signal; a device arranged and adapted to determine intensity and arrival time, mass or mass to charge ratio data from the combined digitised signal; and a device arranged and adapted to sum the intensity and arrival time, mass or .mass to charge ratio data with a plurality of other corresponding intensity and arrival time, mass or mass to charge
• an ion detector system comprising: a device arranged and adapted to output a first signal and a second signal from an ion detector, wherein the first signal ⁇ corresponds with a signal multiplied or amplified by a first gain and the second signal corresponds with a signal multiplied or amplified by a second different gain,- a device arranged and adapted to digitise the first signal to produce a first digitised signal and a device arranged and adapted to digitise the second signal to produce a second digitised signal; a device arranged and adapted to combine the first digitised signal and the second digitised signal to form a combined digitised signal; a device arranged and adapted to sum the combined digitised signal with a plurality of other corresponding combined digitised signals to form a final spectrum; and a device arranged , and adapted to determine intensity and arrival time, mass or mass to charge ratio data from the final spectrum.
• an ion detector system comprising: a device arranged and adapted to output a first signal and a second signal from an ion detector, wherein the first signal corresponds with a signal multiplied or amplified by a first gain and the second signal corresponds with a signal multiplied or amplified by a second different gain,- a device arranged and adapted to digitise the first signal to produce a first digitised signal and a device arranged and adapted to digitise the second signal to produce a second digitised signal; a device arranged and adapted to sum the first digitised signal with a plurality of other corresponding first digitised signals to form a first summed digital signal; a device arranged and adapted to sum the second digitised signal with a plurality of other corresponding second digitised signals to form a second summed digital signal; a device arranged and adapted to determine first intensity and arrival time, mass or mass to charge ratio data from the first
• the mass spectrometer preferably further comprises either:
• an ion source arranged upstream of the ion detector system, wherein the ion source is selected from the group consisting of: (i) an Electrospray ionisation (“ESI”) ion source; (ii) an Atmospheric Pressure Photo Ionisation (“APPI”) ion source,- (iii) an Atmospheric Pressure Chemical Ionisation (“APCI”) ion source; (iv) a Matrix Assisted Laser Desorption Ionisation (“MALDI”) ion source,- (v) a Laser Desorption Ionisation (“LDI”) ion source; (vi) an Atmospheric Pressure Ionisation (“API”) ion source; (vii) a Desorption Ionisation on Silicon (“DIOS”) ion source; (viii) an Electron Impact (“EI”) ion source,- (ix) a Chemical Ionisation (“CI”) ion source; (x) a Field Ionisation (“FI”) ion source,- (xion source
• xii an Inductively Coupled Plasma (“ICP”) ion source,- (xiii) a Fast Atom Bombardment (“FAB”) ion source; (xiv) a Liquid Secondary Ion Mass Spectrometry (“LSIMS”) ion source,- (xv) a Desorption Electrospray Ionisation (“DESI”) ion source; (xvi) a Nickel-63 radioactive ion source,- (xvii) an Atmospheric Pressure Matrix Assisted Laser Desorption ' Ionisation ion source,- and (xviii) a Thermospray ion source,- and/or
• a collision, fragmentation or reaction cell arranged upstream of the ion detector system wherein the collision, fragmentation or reaction cell is selected from the group consisting of: (i) a Collisional Induced Dissociation (“CID”) fragmentation device,- —(ii) a Surface Induced Dissociation (“SID”) fragmentation device; (iii) an Electron Transfer Dissociation fragmentation device,- (iv) an Electron Capture Dissociation fragmentation device; (v) an Electron Collision or Impact Dissociation fragmentation device,- (vi) a Photo Induced Dissociation (“PID”) fragmentation device,- (vii) a Laser Induced Dissociation fragmentation device; (viii) an infrared radiation induced dissociation device,- (ix) an ultraviolet radiation induced dissociation device,- (x) a nozzle-skimmer interface fragmentation device; (xi) an in-source fragmentation device,- (xii) an ion- source Collision Induce
• a mass analyser selected from the group consisting of: (i) a quadrupole mass analyser; (ii) a 2D or linear quadrupole mass analyser; (iii) a Paul or 3D quadrupole mass analyser,- (iv) a Penning trap mass analyser; (v) an ion trap mass analyser; (vi) a magnetic sector mass analyser; (vii) ion Cyclotron Resonance (“ICR”) mass analyser; (viii) a Fourier Transform Ion Cyclotron Resonance (“FTICR”) mass analyser; (ix) an electrostatic or orbitrap mass analyser; (x) a Fourier Transform electrostatic or orbitrap mass analyser,- (xi) a Fourier Transform mass analyser,- (xii) a Time of Flight mass analyser; (xiii) an orthogonal acceleration Time of Flight mass analyser; and (xiv) a linear acceleration Time of Flight mass analyser.
• ICR ion Cyclotron Re
• a mass spectrometer comprising an ion detector.
• the ion current arriving at the ion detector preferably varies in magnitude as a function of time.
• the output current from the ion detector is preferably passed to a voltage converter and amplifier.
• Two or more output voltages are preferably provided or output from the amplifier.
• Two or more Analogue to Digital Converters (ADCs) are preferably provided which preferably convert the two or more output voltages to digital outputs. Further processing of the digital outputs preferably produces one or more sets of data which preferably comprise time and intensity pairs
• each of the two or more digital outputs are preferably processed to produce sets of time and intensity pairs (or sets of mass or mass to charge ratio and intensity pairs) .
• the sets of time and intensity pairs are preferably combined to yield a single set of time and intensity pairs (or a single set of mass or mass to charge ratio and intensity pairs) wherein the single set of data preferably has an increased dynamic range.
• the two digital outputs from the two Analogue to Digital Converters may be combined into a single digital output or transient having an increased dynamic range.
• the single digital output or transient is then preferably processed to produce a set of time and intensity pairs (or a set of mass or mass to charge ratio and intensity pairs) .
• a multitude of corresponding sets of time and intensity pairs (or a multitude of sets of mass or mass to charge ratio and intensity pairs) are preferably combined to form a summed spectrum comprising time and intensity pairs (or mass or mass to charge ratio and intensity pairs) .
• each of the two or more digital outputs may be processed to produce a first and second set of time and intensity pairs (or a first- and second set of mass or mass to charge ratio and intensity pairs) .
• a multitude of first sets of time and intensity pairs are preferably combined to form a single combined set of first sets of time and intensity pairs (or mass or mass to charge ratio and intensity pairs) .
• a multitude of second sets of time and intensity pairs are preferably combined to form a single combined set of second sets of time and intensity pairs (or mass or mass to charge ratio and intensity pairs) .
• the first and second combined sets of time and intensity pairs are preferably combined to yield a single combined set of time and intensity pairs (or mass or mass to charge ratio and intensity pairs) having an increased dynamic range.
• the ion current to voltage converter and the amplifier is preferably arranged to have a linear output voltage with respect to the input current.
• the output voltage may vary in a substantially non-linear manner with respect to the input current and may, for example, be continuous or discontinuous.
• the relationship between the output voltage and the input current may comprise a logarithmic function, a square function, a square root function, a power function, an exponential function, a stepped function or a function incorporating one or more linear functions and/or one or more non-linear functions . and/or one or more step functions and/or any combination thereof.
• the mass spectrometer preferably comprises a Time of Flight mass spectrometer or mass analyser.
• the mass spectrometer or mass analyser may comprise another type of mass spectrometer which provides an ion current that varies in magnitude as a function of time.
• the transient signal from the ion detector is preferably converted, split or output into two separate transient signals.
• the first transient signal is preferably amplified with or by a gain of A and the second transient signal is preferably amplified with or by a gain of B. - 4 -
• the two transient signals are preferably simultaneously digitised and processed to determine the arrival time (or mass or mass to charge ratio) and intensity of all of the ion events occurring.
• two lists are preferably produced.
• any event determined to include a digital sample that has an amplitude which saturates the Analogue to Digital Converter is preferably identified and flagged.
• the first list is preferably examined to select or identify any events- determined to be suffering from saturation effects. If saturation is determined to have occurred then the event is preferably replaced with the arrival time and intensity of the corresponding event or events from the second transient with the intensity multiplied by the ratio of the two gains A/B (or B/A) .
• the events in this combined list are preferably combined with those collected in or from previous or other transients. Once a predetermined number of transients has been collected and combined, the resultant combined spectrum is preferably transferred for storage to disk and the process is preferably repeated.
• Fig. 1 shows a flow diagram of a known Analogue to Digital Converter ion detection system
• Fig. 2 shows a flow diagram illustrating a preferred embodiment of the present invention wherein a signal output from an ion detector is divided into two signals which are amplified by different gains, and wherein arrival time and intensity pairs are calculated for each digitised signal and the two sets of arrival time and intensity data are then combined to form a high dynamic range spectrum,-
• Fig. 3 shows a flow diagram illustrating a less preferred embodiment wherein two digitised signals are first combined to form a single transient and then time and intensity pairs are calculated for the single transient;
• Fig. 4 shows a flow diagram illustrating an embodiment wherein first sets of arrival time and intensity pairs are summed to form a first summed spectrum and second sets of arrival time and intensity pairs are summed to form a second summed spectrum and wherein the first summed spectrum is then combined with the second summed spectrum;
• Fig. 5 shows a flow diagram illustrating an embodiment wherein a first summed spectrum is combined with a second summed spectrum to form a high dynamic range spectrum,- and
• Fig. 6 shows a flow diagram illustrating an embodiment wherein a signal output from an ion detector is divided into two signals which are amplified by different gains and wherein two non-linear amplifier stages are provided prior to digitisation and wherein a non-linear conversion process is provided immediately- after the digitisation stage.
• FIG. 1 A flow diagram illustrating a known Analogue to Digital Converter ion detector system is shown in Fig. 1.
• An input transient signal resulting from a trigger event is digitised and converted into arrival time and intensity pairs at the end of each transients predefined record length.
• a series of arrival time and intensity pairs are combined with those of other mass spectra within a predefined integration period or scan time to form a single mass spectrum.
• Each mass spectrum may comprise many tens of thousands of transients.
• a significant disadvantage of the known method is that it has a limited dynamic range and at relatively high signal intensities the Analogue to Digital Converter will suffer from saturation effects. It is also difficult to determine with any certainty whether or not the signal within an individual transient has saturated the Analogue to Digital Converter especially if the input signal changes significantly in intensity during the scan time. This frequently occurs, for example, on the leading or falling edge of an eluting LC peak. This can lead to inaccuracies in mass measurement and quantitation which are difficult to detect in the final data set.
• a single transient signal output from the ion detector - is preferably converted into two transient signals.
• the first transient signal is preferably amplified by or with a first voltage gain A and the second transient signal is preferably amplified by or with a second voltage gain of B.
• the first voltage gain A is preferably greater than the second voltage gain B (i.e. A > B) .
• the second voltage gain B may be greater than the first voltage gain A.
• the two transient signals are then preferably digitised using two Analogue to Digital Converters.
• the lower gain (B) may be set 25 times lower.
• the two resulting digitised transients are then preferably processed to determine the arrival time (or mass or mass to charge ratio) and intensity of all detected ion arrival events.
• two lists of ion arrival times (or mass or mass to charge ratio) and corresponding intensity values are produced.
• this preferably involves an event detection step to identify regions relating to ion arrival events followed by a centroid measurement of the arrival time (or mass or mass to charge ratio) and corresponding intensity.
• Other methods of ion arrival event measurement and evaluation may be employed.
• each of the high gain transient digitised samples in the region of. an ion arrival event being processed is preferably checked to see whether the Analogue to Digital Converter is suffering from saturation. For example, for an 8 bit Analogue to Digital Converter the output may be checked for values equal to 255. If the result of this check is TRUE, then the arrival time (or mass or mass to charge ratio) and corresponding intensity values for this event are preferably marked or tagged (by setting a bit associated with the registered event). The result is, in this example, two lists of events with high gain transient events that have saturated data embedded within them being tagged or flagged.
• ion arrival events which have been recorded wherein the Analogue to Digital Converter suffers from saturation are preferably identified and replaced with the corresponding event or events as recorded in the low gain transient list by scaling the intensity by the appropriate gain ratio A/B (or B/A) .
• the preferred embodiment preferably results in a list of arrival time (or mass or mass to charge ratio) and intensity pairs having a higher dynamic range than either of the two original arrival time (or mass or mass to charge ratio) and intensity pair lists.
• the high dynamic range list may be combined with corresponding lists or data obtained from previous transients using a known method.
• Other less preferred methods of combining the transient signal event data may be employed.
• a histogram approach may be employed.
• detector signals may be monitored at more than one point in a dynode chain or in the case of a detector employing a dynode strip the signal may be monitored at various positions or locations along the dynode strip.
• the signal from the ion detector is preferably split and amplified according to the method described above.
• the two transients are preferably combined to form a single high dynamic range transient.
• the high dynamic range transient is then preferably processed in order to produce a single list of events comprising arrival time (or mass or mass to charge ratio) and intensity pairs.
• the list of arrival time (or mass or mass to charge ratio) and intensity pairs is then preferably combined with other corresponding transient data as described above to form a summed spectrum.
• Fig. 4 shows another embodiment of the present invention.
• the two transient data streams are preferably kept separate throughout the process and are both preferably written to disk on a scan by scan basis.
• a high dynamic range spectrum is then preferably constructed by combining the two transient data streams as a post processing operation.
• Fig. 5 shows a more preferred embodiment which more fully utilises the fast processing capabilities of Field-Programmable Gate Array devices.
• an improvement in performance relative to the embodiment described above with reference to Fig. 4 is preferably observable.
• both methods have the slight disadvantage that it may be difficult to determine at what point saturation effects occur.
• a detector signal may be processed that changes from a low ion- arrival rate for the first half of an integration period or scan to a high ion arrival rate (thereby saturating the Analogue to Digital Converter) for the remainder. Examination just of the average ion arrival rate may suggest that the high gain data does not suffer from saturation effects whereas in fact the high gain data may suffer from saturation effects and will result in corrupted data.
• one or more non-linear analogue or amplifier processing stages are preferably provided prior to digitisation.
• the gain associated with these stages may, for example, comprise an intensity dependent gain (e.g. as in a logarithmic amplifier) or an intensity switched gain.
• the gain may reduce when the input signal exceeds a given threshold value and may increase when the signal falls below a given value.
• the gain switch may be registered by a processing Field-Programmable Gate Array.
• the changes induced by the non-linear stages are preferably reversed. For example, in the case of a logarithmic amplifier the antilog of the digitised transient may be calculated.
• the digitised transient may be multiplied or divided by an appropriate factor when the gain was determined to switch.
• a person skilled in the art may construct other advantageous non-linear analogue blocks.
• Further embodiments of the present invention are contemplated wherein non-linear amplifiers as described above with reference to Fig. 6 may also be incorporated in the various embodiments as described above with reference to Figs. 2-5. Reversing the gain changes imposed by non-linear amplification prior to combining individual transient signals has advantages over performing this operation on the final spectrum produced at the end of a scan period particularly for situations where the average ion arrival rate changes during the scan period as previously described.

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