# US 7,745,780 B2 · Multiplex data acquisition modes for ion mobility-mass spectrometry > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,745,780 B2 - Document ID: US7745780B2 - Status: Granted - Kind: B2 - Application number: 12/123,163 - Filed: 2008-05-19 - Published: 2009-04-23 - Granted: 2010-06-29 - Earliest claimed: 2004-07-27 - Assignees: Ionwerks, Inc.; The Texas A&M University System - Inventors: John A. McLean; David H. Russell; Thomas F. Egan; Michael V. Ugarov; J. Albert Schultz - Web page: https://patentgrep.com/patent/US7745780B2 ## CPC - G01N 33/6851: {Methods of protein analysis involving laser desorption ionisation mass spectrometry} - B82Y 30/00: Nanotechnology for materials or surface science, e.g. nanocomposites - G01N 27/622: Ion mobility spectrometry - H01J 49/0031: {Step by step routines describing the use of the apparatus (H01J49/0081 takes precedence)} - H01J 49/004: {Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn} - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES - H01J: ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS (spark-gaps H01T; electric arc lamps H05B31/00; particle accelerators H05H) ## Abstract A method and apparatus for multiplexed data acquisition for gas-phase ion mobility coupled with mass spectrometry is described. Ion packets are injected into an ion mobility drift chamber at a rate faster than the ion mobility separation arrival time distribution. The convoluted arrival time distributions thus generated are deconvoluted by a mass spectrometer and post-processing algorithms. ## Claims ### Claim 1 A method for the acquisition of analytical data for a sample comprising the steps of: generating packets of gas-phase ions and neutral species from said sample; introducing said packets into a time dispersive ion mobility drift cell at a rate faster than the transient rate of separation of said ions by said drift cell; separating said ions in a first dimension according to their ion mobility; sampling the ions eluted by the ion mobility drift cell into a mass spectrometer; separating said ions in a second dimension in said mass spectrometer; detecting a mass spectrometric signal for the ions; and, processing said mass spectrometric signal using the ion packet injection frequency and an ion mobility-mass-to-charge correlation function. ### Claim 2 (depends on 1) The method of claim 1, wherein said step of generating comprises generating packets of gas-phase ions and neutral species using a source selected from the group consisting of laser desorption/ionization, electrospray, desorption electrospray ionization, nanospray, ion spray, photoionization, multiphoton ionization, resonance ionization, thermal ionization, surface ionization, electric field ionization, chemical ionization, atmospheric pressure chemical ionization, radioactive ionization, discharge arc/spark ionization, laser induced breakdown ionization, inductively coupled plasma ionization, direct current plasma ionization, capacitively coupled plasma ionization, glow discharge ionization, microwave plasma ionization, and any combination thereof. ### Claim 3 (depends on 2) The method of claim 2, wherein said laser desorption/ionization is selected from the group consisting of MALDI, direct LDI, surface enhanced laser desorption/ionization, and any combination thereof. ### Claim 4 (depends on 1) The method of claim 1, wherein said step of generating packets of gas-phase ions and neutral species comprises generating packets of gas-phase ions and neutral species from spatially distinct regions of a surface that is selected from the group consisting of steel, gold, silver, copper, glass, polymers, silicon, self-assembled monolayers, nitrocellulose, condensed-phase substrates, chemically functional moieties, chemically reactive moieties, biomolecules, and any combination thereof. ### Claim 5 (depends on 4) The method of claim 4, wherein said biomolecules are selected from the group consisting of proteins, nucleic acids, arrays thereof, patterns thereof, layers thereof, and any combination thereof. ### Claim 6 (depends on 4) The method of claim 4, wherein said polymers are selected from the group consisting of poly(dimethylsiloxane), elastomers, plastics, and teflon. ### Claim 7 (depends on 1) The method of claim 1, wherein said step of separating ions in a first dimension comprises separating ions in an electric field selected from the group consisting of uniform electrostatic fields, periodic-focusing electrostatic fields, non-uniform electrostatic fields, traveling wave electrostatic fields, radiofrequency electrostatic fields, and any combination thereof. ### Claim 8 (depends on 1) The method of claim 1, wherein said step of separating ions in a first dimension comprises separating ions by time dispersion on the basis of ion mobility, said ion mobility selected from the group consisting of low-field mobility, high-field mobility, and any combination thereof. ### Claim 9 (depends on 1) The method of claim 1, wherein said step of separating ions in a first dimension comprises separating ions by collisions with one or more gases. ### Claim 10 (depends on 9) The method of claim 9, wherein said one or more gases is selected from the group consisting of helium, neon, argon, krypton, xenon, nitrogen, oxygen, methane, carbon dioxide, water, methanol, methyl fluoride, ammonia, deuterated analogs thereof, tritiated analogs thereof, and any combination thereof. ### Claim 11 (depends on 9) The method of claim 9, wherein said collisions are selected from the group consisting of reactive collisions, non-reactive collisions, and any combination thereof. ### Claim 12 (depends on 1) The method of claim 1, wherein said step of separating said ions in a second dimension comprises separating said ions using a method selected from the group consisting of time-of-flight mass spectrometry, magnetic-sector mass spectrometry, electrostatic-sector mass spectrometry, double-focusing sector-field mass spectrometry, quadrupole mass spectrometry, ion trap mass spectrometry, ion cyclotron resonance mass spectrometry, accelerator mass spectrometry, orbitrap mass spectrometry, and any combination thereof. ### Claim 13 (depends on 12) The method of claim 12, wherein said ions are further encoded in the second dimension using multiplex frequency-domain analysis techniques or weighing design techniques or both; and, decoded by application of a Fourier transform or Hadamard transform or both. ### Claim 14 (depends on 1) The method of claim 1, wherein said step of introducing comprises introducing said packets at a plurality of energies. ### Claim 15 (depends on 1) The method of claim 1, wherein said packets are introduced into said ion mobility drift cell under varying conditions, said varying conditions comprising different experimental parameters for separation and wherein one or more of said packets are encoded by the frequency of introduction of said one or more packets. ### Claim 16 (depends on 15) The method of claim 15, wherein said experimental parameters are selected from the group consisting of drift cell voltage, drift cell gas pressure, temperature, identity of drift cell gases, and any combination thereof. ### Claim 17 (depends on 1) The method of claim 1, wherein said ions comprise ions of single atoms and ions of molecules. ### Claim 18 (depends on 17) The method of claim 17, wherein said molecules are selected from the group consisting of molecules possessing a molecular weight less than 500 amu; molecules possessing a molecular weight of from 500 amu to less than 10,000 amu; molecules possessing a molecular weight of from 10,000 amu to 100,000 amu; molecules possessing a molecular weight greater than 100,000 amu; and, any combination thereof. ### Claim 19 (depends on 1) The method of claim 1, further comprising forming a plurality of beams of gaseous ions and neutral species from said packets, and wherein said step of introducing comprises introducing said plurality of beams into a plurality of ion mobility drift tubes to form a plurality of mobility-separated beams. ### Claim 20 (depends on 19) The method of claim 19, further comprising introducing the plurality of mobility-separated beams into a plurality of CID tubes. ### Claim 21 (depends on 19) The method of claim 19, further comprising introducing the plurality of mobility-separated beams through at least one RF ion guide. ### Claim 22 (depends on 19) The method of claim 19, wherein said step of sampling said ions in a second dimension comprises introducing said plurality of mobility-separated beams into at least one mass spectrometer. ### Claim 23 (depends on 22) The method of claim 22, wherein said at least one mass spectrometer is a TOFMS. ### Claim 24 (depends on 23) The method of claim 23, wherein said TOFMS comprises a position sensitive detector. ### Claim 25 (depends on 23) The method of claim 23, further comprising the step of correlating the mass spectrometric signal to the output of a ion mobility channel. ### Claim 26 (depends on 19) The method of claim 19, wherein said step of forming comprises forming said plurality of beams from a single region on said sample; or, forming said plurality of beams from a plurality of regions on said sample. ### Claim 27 (depends on 1) The method of claim 1, further comprising ionizing said gas phase neutral species. ### Claim 28 A method for the acquisition of analytical data for a sample comprising the steps of: generating packets of gas-phase ions and neutral species from said sample; introducing said packets into a time dispersive ion mobility drift cell at a rate faster than the transient rate of separation of said ions by said drift cell; separating said ions in a first dimension according to their ion mobility; activating the ions as they elute from the ion mobility drift cell for dissociation into fragment ions; sampling the ions eluted by the ion mobility drift cell into a mass spectrometer; separating said ions in a second dimension in said mass spectrometer; detecting a mass spectrometric signal for the ions; and, processing said mass spectrometric signal using the ion packet injection frequency and an ion mobility-mass-to-charge correlation function. ### Claim 29 (depends on 28) The method of claim 28, wherein said step of generating comprises generating packets of gas-phase ions and neutral species using a source selected from the group consisting of laser desorption/ionization, electrospray, desorption electrospray ionization, nanospray, ion spray, photoionization, multiphoton ionization, resonance ionization, thermal ionization, surface ionization, electric field ionization, chemical ionization, atmospheric pressure chemical ionization, radioactive ionization, discharge arc/spark ionization, laser induced breakdown ionization, inductively coupled plasma ionization, direct current plasma ionization, capacitively coupled plasma ionization, glow discharge ionization, microwave plasma ionization, and any combination thereof. ### Claim 30 (depends on 29) The method of claim 29, wherein said laser desorption/ionization is selected from the group consisting of MALDI, direct LDI, surface enhanced laser desorption/ionization, and any combination thereof. ### Claim 31 (depends on 28) The method of claim 28, wherein said step of generating packets of gas-phase ions and neutral species comprises generating packets of gas-phase ions and neutral species from spatially distinct of a surface that is selected from the group consisting of steel, gold, silver, copper, glass, polymers, silicon, self-assembled monolayers, nitrocellulose, condensed-phase substrates, chemically functional moieties, chemically reactive moieties, biomolecules, and any combination thereof. ### Claim 32 (depends on 31) The method of claim 31, wherein said biomolecules are selected from the group consisting of proteins, nucleic acids, arrays thereof, patterns thereof, layers thereof, and any combination thereof. ### Claim 33 (depends on 31) The method of claim 31, wherein said polymers are selected from the group consisting of poly(dimethylsiloxane), elastomers, plastics, teflon, and any combination thereof. ### Claim 34 (depends on 28) The method of claim 28, wherein said step of separating ions in a first dimension comprises separating ions in an electric field selected from the group consisting of uniform electrostatic fields, periodic-focusing electrostatic fields, non-uniform electrostatic fields, traveling wave electrostatic fields, radiofrequency electrostatic fields, and any combination thereof. ### Claim 35 (depends on 28) The method of claim 28, wherein said step of separating ions in a first dimension comprises separating ions by time dispersion on the basis of ion mobility, said ion mobility selected from the group consisting of low-field mobility, high-field mobility, and combinations thereof. ### Claim 36 (depends on 28) The method of claim 28, wherein said step of separating ions in a first dimension comprises separating ions by collisions with one or more gases. ### Claim 37 (depends on 36) The method of claim 36, wherein said one or more gases is selected from the group consisting of helium, neon, argon, krypton, xenon, nitrogen, oxygen, methane, carbon dioxide, water, methanol, methyl fluoride, ammonia, deuterated analogs thereof, tritiated analogs thereof, and any combination thereof. ### Claim 38 (depends on 36) The method of claim 36, wherein said collisions are selected from the group consisting of reactive collisions, non-reactive collisions, and any combination thereof. ### Claim 39 (depends on 28) The method of claim 28, said step of activating ions occurs prior to said step of separating said ions in said temporally-resolved mass spectrometer. ### Claim 40 (depends on 39) The method of claim 39, wherein said step of activating ions as they elute from said ion mobility drift cell for dissociation into fragment ions comprises the use of a technique selected from the group consisting of collision induced dissociation, surface induced dissociation, photodissociation, multiphoton dissociation, resonance enhanced multiphoton dissociation, blackbody induced radiative dissociation, electron capture dissociation, electron transfer dissociation, and any combination thereof. ### Claim 41 (depends on 28) The method of claim 28, wherein said step of separating said ions in a second dimension comprises separating said ions using a method selected from the group consisting of time-of-flight mass spectrometry, magnetic-sector mass spectrometry, electrostatic-sector mass spectrometry, double-focusing sector-field mass spectrometry, quadrupole mass spectrometry, ion trap mass spectrometry, ion cyclotron resonance mass spectrometry, accelerator mass spectrometry, orbitrap mass spectrometry, and any combination thereof. ### Claim 42 (depends on 28) The method of claim 28, wherein said ions are further encoded in the second dimension using multiplex frequency-domain analysis techniques or weighing design techniques or both; and, decoded by application of a Fourier transform or Hadamard transform or both. ### Claim 43 (depends on 28) The method of claim 28, wherein said step of introducing comprises introducing said packets at a plurality of energies. ### Claim 44 (depends on 28) The method of claim 28, wherein said packets are introduced into said ion mobility drift cell under varying conditions, said varying conditions comprising different experimental parameters for separation and wherein one or more of said packets are encoded by the frequency of introduction of said one or more packets. ### Claim 45 (depends on 44) The method of claim 44, wherein said experimental parameters are selected from the group consisting of drift cell voltage, drift cell gas pressure, and any combination thereof. ### Claim 46 (depends on 28) The method of claim 28, wherein said ions comprise ions of single atoms and ions of molecules. ### Claim 47 (depends on 46) The method of claim 46, wherein said molecules are selected from the group consisting of molecules possessing a molecular weight less than 500 amu; molecules possessing a molecular weight of from 500 amu to less than 10,000 amu; molecules possessing a molecular weight of from 10,000 amu to 100,000 amu; molecules possessing a molecular weight greater than 100,000 amu; and, any combination thereof. ### Claim 48 (depends on 28) The method of claim 28, further comprising forming a plurality of beams of gaseous ions and neutral species from said packets, and wherein said step of introducing comprises introducing said plurality of beams into a plurality of ion mobility drift tubes to form a plurality of mobility-separated beams. ### Claim 49 (depends on 48) The method of claim 48, further comprising introducing the plurality of mobility-separated beams into a plurality of CID tubes. ### Claim 50 (depends on 48) The method of claim 48, further comprising introducing the plurality of mobility-separated beams through at least one RF ion guide. ### Claim 51 (depends on 48) The method of claim 48, wherein said step of sampling said ions in a second dimension comprises introducing said plurality of mobility-separated beams into at least one mass spectrometer. ### Claim 52 (depends on 51) The method of claim 51, wherein said at least one mass spectrometer is a TOFMS. ### Claim 53 (depends on 52) The method of claim 52, wherein said TOFMS comprises a position sensitive detector. ### Claim 54 (depends on 52) The method of claim 52, further comprising the step of correlating the mass spectrometric signal to the output of each ion mobility channel. ### Claim 55 (depends on 48) The method of claim 48, wherein said step of forming comprises forming said plurality of beams from a single region on said sample; or, forming said plurality of beams from a plurality of regions on said sample. ### Claim 56 (depends on 28) The method of claim 28, further comprising ionizing said gas phase neutral species.