MASS SPECTROMETER

• US 20110095175A1
• Filed: 04/20/2005
• Published: 04/28/2011
• Est. Priority Date: 04/20/2004
• Status: Active Grant

• Current Assignee: Micromass UK Ltd (Waters Corporation)
• Original Assignee: Micromass UK Ltd (Waters Corporation)
• Inventors: Bateman, Robert Harold
• Granted Patent: US 9,880,129 B2
• Time in Patent Office: Days
• US Class Current: 250/282
• CPC Class Codes: G01N 27/624 Differential mobility spectrometry [DMS]; Field asymmetric-waveform ion mobility spectrometry [FAIMS]
• CPC Class Codes: H01J 49/062 Ion guides linear ion traps performing mass selection H01J49/4225, mass filters H01J49/421

Abstract

A mass spectrometer is disclosed comprising a FAIMS device comprising two parallel electrodes (9a, 9b) in series with an ion mobility separator (12) forming part of a mass spectrometer. Ions are separated in the FAIMS device (9a, 9b) according to their rate of change of ion mobility with electric field strength. The ions which are onwardly transmitted from the FAIMS device (9a, 9b) are then passed to an ion separator device (12) comprising a plurality of electrodes (12) and an optional ion trapping region (33). Ions are radially confined with the ion separator by application of an AC or RF voltage to the electrodes (12) and ions are separated according to their ion mobility by applying an axial DC voltage gradient which may remain constant as a function of time or which may vary with time.

Claims

1. Apparatus comprising:

a first device for separating ions according to their rate of change of ion mobility with electric field strength, said first device comprising a Field Asymmetric Ion Mobility Spectrometry (“

FAIMS”

) device; and

a second separate device for separating ions according to their ion mobility, said second device comprising an ion mobility separator or ion mobility spectrometer, and said second device being arranged downstream of said first device;

wherein said second device comprises a plurality of electrodes and wherein, in use, one or more transient DC voltages or one or more transient DC voltage waveforms are progressively applied to said electrodes so that at least some ions having a first ion mobility are separated from other ions having a second different ion mobility.

4. Apparatus as claimed in claim 1, wherein said first device comprises at least a first electrode and a second electrode and wherein ions are arranged to be received, in use, between said first and second electrodes.

9. Apparatus as claimed in claim 1, further comprising means for applying an asymmetric periodic voltage waveform to said first device, wherein said asymmetric periodic voltage waveform has a peak positive voltage and a peak negative voltage.

14. Apparatus as claimed in claim 1, further comprising means for applying a DC compensation voltage to said first device.

16. Apparatus as claimed in claim 14, wherein said DC compensation voltage acts to counterbalance or counteract a force which would otherwise cause desired ions to drift towards an electrode of said first device.

24. Apparatus as claimed in claim 1, wherein said second device is selected from the group consisting of:

(i) an ion funnel comprising a plurality of electrodes having apertures therein through which ions are transmitted, wherein the diameter of said apertures becomes progressively smaller or larger;

(ii) an ion tunnel comprising a plurality of electrodes having apertures therein through which ions are transmitted, wherein the diameter of said apertures remains substantially constant; and

(iii) a stack of plate, ring or wire loop electrodes.

30. Apparatus as claimed in claim 1, wherein said second device comprises a segmented rod set.

35. Apparatus as claimed in claim 1, wherein an AC or RF voltage is applied to at least some of said electrodes of said second device in order to confine at least some ions, in use, near to a central axis of said second device.

37. Apparatus as claimed in claim 1, wherein one or more DC voltage gradients are maintained across at least a portion of said second device.

42. Apparatus as claimed in claim 1, wherein said one or more transient DC voltages or said one or more transient DC voltage waveforms are such that at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or 95% of said ions having said second ion mobility are moved along said second device by said applied DC voltage to a lesser degree than said ions having said first ion mobility as said one or more transient DC voltages or said one or more transient DC voltage waveforms are progressively applied to said electrodes.

44. Apparatus as claimed in claim 1, wherein one or more transient DC voltages or one or more transient DC voltage waveforms are progressively applied to said electrodes so that ions are moved towards a region of the ion mobility separator wherein at least one electrode has a potential such that at least some ions having a first ion mobility will pass across said potential whereas other ions having a second different ion mobility will not pass across said potential.

45. Apparatus as claimed in claim 44, wherein said one or more transient DC voltages or said one or more transient DC voltage waveforms are such that at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or 95% of said ions having said first ion mobility pass across said potential.

46. Apparatus as claimed in claim 44, wherein said one or more transient DC voltages or said one or more transient DC voltage waveforms are such that at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or 95% of said ions having said second ion mobility will not pass across said potential.

60. Apparatus as claimed in claim 1, wherein said one or more transient DC voltages applied to said second device create:

(i) a potential hill or barrier;

(ii) a potential well;

(iii) a combination of a potential hill or barrier and a potential well;

(iv) multiple potential hills or barriers;

(v) multiple potential wells;

or (vi) a combination of multiple potential hills or barriers and multiple potential wells.

61. Apparatus as claimed in claim 1, wherein said one or more transient DC voltage waveforms comprise a repeating waveform.

82. Apparatus as claimed in claim 1, wherein ions are confined radially within said first device and/or said second device by an AC or RF electric field.

91. Apparatus as claimed in claim 1, wherein one or more transient DC voltages or one or more transient DC voltage waveforms move from one end of said first device and/or said second device to another end of said first device and/or said second device so that at least some ions are urged along said first device and/or said second device.

96. Apparatus as claimed in claim 1, wherein said first device and/or said second device comprises an upstream entrance region, a downstream exit region and an intermediate region, wherein:

in said entrance region the amplitude of said one or more transient DC voltages or said one or more transient DC voltage waveforms has a first amplitude;

in said intermediate region the amplitude of said one or more transient DC voltages or said one or more transient DC voltage waveforms has a second amplitude; and

in said exit region the amplitude of said one or more transient DC voltages or said one or more transient DC voltage waveforms has a third amplitude.

98. Apparatus as claimed in claim 96, wherein said first and/or third amplitudes are substantially zero and said second amplitude is substantially non-zero.

111. Apparatus as claimed in claim 1, wherein two or more transient DC voltages or two or more transient DC voltage waveforms are applied to said first device and/or said second device and pass simultaneously along said first device and/or said second device.

112. Apparatus as claimed in claim 111, wherein said two or more transient DC voltages or said two or more transient DC voltage waveforms are arranged to move:

(i) in the same direction;

(ii) in opposite directions;

(iii) towards each other;

or (iv) away from each other.

113. Apparatus as claimed in claim 1, wherein one or more transient DC voltages or one or more transient DC voltage waveforms pass along said first device and/or said second device and at least one substantially stationary transient DC potential voltage or voltage waveform is provided at a position along said first device and/or said second device.

117. Apparatus as claimed in claim 1, wherein in use pulses of ions emerge from an exit of said first device and/or said second device.

118. Apparatus as claimed in claim 117, further comprising an ion detector, said ion detector being arranged to be substantially phase locked in use with the pulses of ions emerging from the exit of said first device and/or said second device.

119. Apparatus as claimed in claim 117, further comprising a Time of Flight mass analyser comprising an electrode for injecting ions into a drift region, said electrode being arranged to be energised in use in a substantially synchronised manner with the pulses of ions emerging from the exit of the first device and/or said second device.

120. Apparatus as claimed in claim 1, wherein said first device and/or said second device comprise a plurality of electrodes and wherein at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% of said electrodes are connected to both a DC and an AC or RF voltage supply.

133. Apparatus as claimed in claim 1, further comprising a continuous ion source.

134. Apparatus as claimed in claim 1, further comprising a pulsed ion source.

135. Apparatus as claimed in claim 1, further comprising an ion source 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;

(xi) a Field Desorption (“

FD”

) ion 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; and

(xvi) a Nickel-63 radioactive ion source.

136. Apparatus as claimed in claim 1, further comprising a separation device for separating a sample to be analysed prior to ionisation.

137. Apparatus as claimed in claim 136, wherein said separation device is selected from the group consisting of:

(i) a liquid chromatography device;

(ii) a gas chromatography device;

(iii) a super-critical fluid chromatography device;

(iv) a capillary electrophoresis device; and

(v) a capillary electrophoresis chromatography device.

138. A mass spectrometer comprising apparatus as claimed in claim 1.

143. A mass spectrometer as claimed in claim 138, further comprising a mass analyser.

144. A mass spectrometer as claimed in claim 143, wherein said mass analyser is selected from the group consisting of:

(i) an orthogonal acceleration Time of Flight mass analyser;

(ii) an axial acceleration Time of Flight mass analyser;

(iii) a Paul 3D quadrupole ion trap mass analyser;

(iv) a 2D or linear quadrupole ion trap mass analyser;

(v) a Fourier Transform Ion Cyclotron Resonance mass analyser;

(vi) a magnetic sector mass analyser;

(vii) a quadrupole mass analyser; and

(viii) a Penning trap mass analyser.

145. A mass spectrometer as claimed in claim 138, further comprising a collision or fragmentation cell.

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150. A method of separating ions comprising:

separating ions according to their rate of change of ion mobility with electric field strength in a first device, said first device comprising a Field Asymmetric Ion Mobility Spectrometry (“

FAIMS”

) device; and

then

separating ions according to their ion mobility in a second separate device, said second device comprising an ion mobility separator or ion mobility spectrometer having a plurality of electrodes, and said second device being arranged downstream of said first device;

wherein said step of separating ions in said second device comprises progressively applying to said electrodes one or more transient DC voltages or one or more transient DC voltage waveforms so that at least some ions having a first ion mobility are separated from other ions having a second different ion mobility.

151. A method of mass spectrometry comprising the method of claim 150.

152. Apparatus comprising:

a first device for separating ions according to their rate of change of ion mobility with electric field strength, said first device comprising a Field Asymmetric Ion Mobility Spectrometry (“

FAIMS”

) device; and

a second separate device for separating ions according to their ion mobility, said second device comprising an ion mobility separator or ion mobility spectrometer, and said second device being arranged downstream of said first device;

wherein said second device comprises a plurality of electrodes, each electrode having an aperture through which ions are transmitted in use, and wherein an AC or RF voltage is applied to at least some of said electrodes of said second device in order to confine at least some ions, in use, near to a central axis of said second device.

153. A mass spectrometer comprising apparatus as claimed in claim 152.

154. A method of separating ions comprising:

separating ions according to their rate of change of ion mobility with electric field strength in a first device, said first device comprising a Field Asymmetric Ion Mobility Spectrometry (“

FAIMS”

) device; and

then

separating ions according to their ion mobility in a second separate device, said second device comprising an ion mobility separator or ion mobility spectrometer having a plurality of electrodes, each electrode having an aperture through which the ions are transmitted, and said second device being arranged downstream of said first device;

wherein an AC or RF voltage is applied to at least some of the electrodes of said second device so as to confine at least some of the ions in said second device near to a central axis of the device.

155. A method of mass spectrometry comprising the method of claim 154.