Classifications

• • H—ELECTRICITY
  • H01—ELECTRIC ELEMENTS
  • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
  • H01J49/00—Particle spectrometers or separator tubes
  • H01J49/02—Details
  • H01J49/10—Ion sources; Ion guns
  • H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
  • H01J49/165—Electrospray ionisation
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
  • G01N27/62—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode
  • G01N27/622—Ion mobility spectrometry
  • G01N27/624—Differential mobility spectrometry [DMS]; Field asymmetric-waveform ion mobility spectrometry [FAIMS]

Definitions

• Electrophoresis/Nanoelectrospray Mass Spectrometry Anal.Chem.2000, 72,599-609. Better methods for elimination of unwanted solvent and separation of sample ions from background are therefore needed.
• FIG. IA illustrates schematically three possible ion mobility dependencies on electric field.
• the low field value of the mobility K(E m i i ) in a weak electric field (E approximately IO 2 - 10 3 V/cm) is the same for all three ion types.
• a ⁇ E max the value of the mobility coefficient K(E max ) is different for each ion type.
• Embodiments of the invention feature combinations of various aspects, including use of a FAIMS ion filter to filter ions where control of which ions are filtered is achieved by control of a variable DC compensation signal in addition to a high field asymmetric waveform radio frequency signal or use of a FAIMS filter where the control of which ions are filtered is achieved by varying the wavelength, frequency, amplitude, period, duty cycle or the like of the high field asymmetric waveform radio frequency signal; use of a planar FAIMS filter which uses insulating substrates to very accurately control the gap between the ion filter electrodes and ensure the ion filter electrodes are parallel, this allows very reproducible fields to be obtained which results in a higher resolution spectrometer; use of a planar FAIMS filter where the insulating spacers overlap the
• the electrospray assembly can be attached to one of the substrates of the FAIMS and guiding electrodes are used to guide the ions into the ionization region.
• the guiding electrodes can be a freestanding structure attached or connected to or near one of the substrates of the FAHVIS.
• the assembly can have a counter gas flow to enhance desolvation.
• the new FAIMS of the invention is a low cost, a volume manufacturable, small and compact, spectrometer based on differential ion mobility.
• the present invention particularly configured using high volume manufacturing techniques, such as MEMS fabrication techniques which includes ceramic packaging, PC board manufacturing techniques or plastic processing, offers several additional advantages over prior devices.
• the volume manufacture techniques result in low cost devices that can be made disposable, thus avoiding the problem of sample cross contamination.
• These chips will be available to any laboratory using a mass spectrometer for biological molecule identification as a FAIMS interface filter.
• a filter includes the FAIMS interface chip which can plug into an interface fixture which contains, filtering electronics.
• the electrospray tip or electrophoresis chips can be integrated with (fabricated as part of) the FAIMS chip.
• the Electrospray and FAIMS form an atmospheric pressure chemical ionization (APCI) prefilter and analyte filter and detection system in a single housing.
• APCI atmospheric pressure chemical ionization
• sample preparation, ionization, filtering and detection can be performed on a single chip or workpiece of the invention; wherein an electrospray- FAIMS is applied as a filter to a mass spectrometer; a chip carrier and a disposable FAIMS filter chip which is plugged into the carrier, the carrier enable for mounting on the inlet of a mass spectrometer; wherein an electrospray-FAIMS forms a filter and detection system in a single housing; wherein electrospray-FAIMS configuration of the present invention can be used as a standalone detector for liquid sample analysis or as the front end to a mass spectrometer; wherein present invention also has application to other liquid separation techniques such as liquid chromatography, high pressure liquid chromatography, and capillary electrophoresis; wherein a preferred embodiment of the invention includes a FAIMS apparatus where in one embodiment the FAIMS device is integrated with an electrospray ionizing source on a common housing or substrate and is coupled to a mass spectrometer; where
• the insulative or insulated substrate/flow path invention achieves excellent performance in a simplified structure.
• the use of an electrically insulated flow path in a FAFMS device enables the applied asymmetric periodic voltage to be isolated from the output part (e.g., from the electrodes of the detector), where detection takes place. This reduction is accomplished because the insulated substrates provide insulated territory between the filter and detector in the flow path, and this spacing in turn advantageously separates the filter's field from the detector.
• the less noisy detection environment means a more sensitive FAIMS device.
• FIG. 1 A shows the mobility dependence on electric field for three different ion species.
• FIG. 3B shows a chemical sensor system with liquid sample preparation section including an electrospray in practice of the invention.
• FIG. 4C shows side cross-sectional view of filter with insulating spacers overlapping edges of electrodes in practice of the invention.
• FIG. 4D shows an electrospray head with a sample reservoir feeding a separation channel leading to a spray tip in practice of the invention.
• FIG. 5 A shows symmetric AC radio frequency field for ion desolvation in practice of the invention.
• FIG. 5B shows the desolvation region integrated into a FAIMS device in practice of the invention.
• FIG. 9A shows an electrospray head cooperating with guiding electrodes in practice of the invention.
• FIG. 9B shows an electrospray head cooperating with guiding electrodes in practice of the invention.
• FIG. 10A shows the control system in practice of the invention.
• FIG. 1 IB shows a chip receptacle interfaced with a mass spectrometer in practice of the invention.
• FIGS. 12A, 12B shows planar FAIMS in practice of the invention.
• the liquid sample preparation section 10A includes an electrospray head, which receives, conditions, and ionizes liquid sample S. This is transported to a preferred planar high field asymmetric ion mobility spectrometer (PFAHVIS) filter in section 10B, the latter filtering the delivered ions and passing ion species of interest to output section IOC.
• PFAHVIS planar high field asymmetric ion mobility spectrometer
• function in output section 10C may include immediate detection of ion species or transfer of ions to another component such as a mass spectrometer (MS) for detection of ion species thereat, with a readout being available of data D indicative of detected ion species.
• MS mass spectrometer
• a further advantage of the invention is that the filter can pass multiple ion species with similar mobility but different polarity, and these can be detected simultaneously. If each detector electrode 70, 72 is held at a different polarity, then multiple ion species (having similar mobility but different polarity) that pass through the filter can be detected simultaneously. Detected ions are correlated -with the applied control signals 48, 50 and potential bias signals 71, 73 to determine the species of detected ion(s) indicated at data D, FIG. 2.
• a PFAIMS system 10 includes a spectrometer chip 100 having spaced insulated substrates 52, 54, (e.g., Pyrex® glass, ceramic, plastic and the like) with filter electrodes 44, 46 formed thereon (of gold or the like).
• Substrates 52, 54 define between themselves the drift tube 29 and flow path 30, thus performing a housing function.
• the substrates are insulating or have surfaces 60, 62 for insulated mounting of electrodes. Electrodes 44, 46 form ion filter 40, with the filter electrodes mounted on these insulated surfaces 60, 62 facing each other across the flow path 30.
• the field distribution between the ion filter electrodes (neglecting fringing fields) in the PFAIMS design is uniform and the field is uniform.

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• Physics & Mathematics (AREA)
• Chemical & Material Sciences (AREA)
• Analytical Chemistry (AREA)
• Spectroscopy & Molecular Physics (AREA)
• Health & Medical Sciences (AREA)
• Plasma & Fusion (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Electrochemistry (AREA)
• Engineering & Computer Science (AREA)
• Life Sciences & Earth Sciences (AREA)
• Biochemistry (AREA)
• General Health & Medical Sciences (AREA)
• General Physics & Mathematics (AREA)
• Immunology (AREA)
• Pathology (AREA)
• Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
• Electron Tubes For Measurement (AREA)

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• 2002
  • 2002-04-17 CA CA002444257A patent/CA2444257A1/en not_active Abandoned
  • 2002-04-17 AU AU2002257177A patent/AU2002257177B2/en not_active Ceased
  • 2002-04-17 IL IL15838602A patent/IL158386A0/xx unknown
  • 2002-04-17 CN CN02812130.9A patent/CN1585666A/zh active Pending
  • 2002-04-17 WO PCT/US2002/012210 patent/WO2002083276A1/en active IP Right Grant
  • 2002-04-17 EP EP02726767A patent/EP1387724A4/de not_active Withdrawn
  • 2002-04-17 JP JP2002581074A patent/JP4063676B2/ja not_active Expired - Lifetime

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