# US 6,627,875 B2 · Tailored waveform/charge reduction mass spectrometry > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 6,627,875 B2 - Document ID: US6627875B2 - Status: Granted - Kind: B2 - Application number: 09/840,633 - Filed: 2001-04-23 - Published: 2002-11-14 - Granted: 2003-09-30 - Earliest claimed: 2001-04-23 - Assignees: Beyond Genomics, Inc. - Inventors: Noubar B. Afeyan; Scott McLuckey; Fred E. Regnier - Web page: https://patentgrep.com/patent/US6627875B2 ## CPC - H01J 49/0077: {specific reactions other than fragmentation} - G01N 30/72: Mass spectrometers {(mass spectrometers per se H01J49/00)} - H01J 49/4265: {Controlling the number of trapped ions; preventing space charge effects} - H01J 49/428: {Applying a notched broadband signal} - H01J: ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS (spark-gaps H01T; electric arc lamps H05B31/00; particle accelerators H05H) - 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) ## Abstract The methods of the invention exploit the mass-to-charge ratio dependent motion of ions in an electrodynamic ion traps in synergy with a charge quenching process. In an electrodynamic ion trap, each mass-to-charge ratio is characterized by a unique set of frequencies of motion. Accordingly, by tailoring the time-varying electrical potential of the ion trap the invention controls which ions are allowed or retained in the ion trap and which ions are subjected to charge quenching reactions. Control of ion retention and charge quenching is used to improve sample throughput, dynamic mass range and signal discrimination in the mass spectrometry of multiply charged ions. ## Claims ### Claim 1 A method of analyzing a sample of molecules comprising the steps of: (a) using a tailored waveform having at least two gaps in frequency space to segregate a subset of ionized molecules from a plurality of ionized molecules; (b) reacting the subset of ionized molecules with a quencher for a charge reduction period to reduce the charge state of ionized molecules in the subset of ionized molecules; (c) determining a mass signal for the ionized molecules having the highest mass to charge ratio resulting from step (b); and (d) repeating steps (a)-(c) for at least another tailored waveform having a different at least two gaps in frequency space to define a mass spectrum. ### Claim 2 (depends on 1) The method of claim 1 further comprising the steps of: using the tailored waveform for an accumulation time; and varying the accumulation time for at least one of the tailored waveforms. ### Claim 3 (depends on 2) The method of claim 2 wherein step of varying the accumulation time comprises varying the accumulation time so the subset of ionized molecules attains at least a minimum abundance. ### Claim 4 (depends on 2) The method of claim 2 further comprising the step of normalizing the mass signal resulting in step (c) based on the accumulation time. ### Claim 5 (depends on 1) The method of claim 1 wherein step (a) comprises selecting at least two gaps in frequency space such that the subset of ionized molecules comprises ionized molecules within mass to charge ratio ranges with median values which are substantially the mass-to-charge ratios of the integer charge states of a select ion mass. ### Claim 6 (depends on 1) The method of claim 1 wherein: step (a) comprises segregating a subset of ionized molecules that are substantially cations; and step (b) comprises reacting the subset of ionized molecules with an anionic quencher. ### Claim 7 (depends on 1) The method of claim 1 further comprising the step of analyzing by a mass spectrometry technique, the ionized molecules having the highest mass to charge ratio resulting from step (b). ### Claim 8 (depends on 1) The method of claim 1 wherein step (a) comprises: trapping the plurality of ionized molecules in an ion trap; and retaining in the ion trap the subset of ionized molecules. ### Claim 9 (depends on 1) An article of manufacture having computer-readable program means for performing the method of claim 1 embodied thereon. ### Claim 10 A method of analyzing a sample of molecules comprising the steps of: (a) using a tailored waveform having at least two gaps in frequency space for an accumulation time to segregate a subset of ionized molecules from a plurality of ionized molecules; (b) reacting the subset of ionized molecules with a quencher for a charge reduction period to reduce the charge state of ionized molecules in the subset of ionized molecules; (c) determining a mass signal for the ionized molecules having the highest mass to charge ratio resulting from step (b); and (d) repeating steps (a)-(c) for at least another accumulation time. ### Claim 11 (depends on 10) The method of claim 10 further comprising the step of repeating at least steps (a)-(c) for at least another tailored waveform having a different at least two gaps in frequency space to define a mass spectrum. ### Claim 12 (depends on 10) The method of claim 10 wherein step (d) is repeated so the subset of ionized molecules attains at least a minimum abundance. ### Claim 13 (depends on 10) The method of claim 10 further comprising the step of normalizing the mass signal resulting in step (c) based on the accumulation time. ### Claim 14 (depends on 10) The method of claim 10 wherein step (a) comprises selecting at least two gaps in frequency space such that the subset of ionized molecules comprises ionized molecules within mass to charge ratio ranges with median values which are substantially the mass-to-charge ratios of the integer charge states of a select ion mass. ### Claim 15 (depends on 10) The method of claim 10 wherein: step (a) comprises segregating a subset of ionized molecules that are substantially cations; and step (b) comprises reacting the subset of ionized molecules with an anionic quencher. ### Claim 16 (depends on 10) The method of claim 10 further comprising the step of analyzing by a mass spectrometry technique, the ionized molecules having the highest mass to charge ratio resulting from step (b). ### Claim 17 (depends on 10) The method of claim 10 wherein step (a) comprises: trapping the plurality of ionized molecules in an ion trap; and retaining in the ion trap the subset of ionized molecules. ### Claim 18 (depends on 10) An article of manufacture having computer-readable program means for performing the method of claim 10 embodied thereon. ### Claim 19 A method of analyzing a sample of molecules comprising the steps of: (a) using a primary tailored waveform having at least two gaps in frequency space to segregate a first subset of ionized molecules from a plurality of ionized molecules; (b) reacting the first subset of ionized molecules with a quencher for a first charge reduction period to reduce the charge state of ionized molecules in the first subset of ionized molecules; (c) using a secondary tailored waveform having at least one gap in frequency space to segregate a second subset of ionized molecules resulting from step (b); (d) determining a mass signal for the ionized molecules having the highest mass to charge ratio resulting from step (c); and (e) repeating steps (a)-(d) for at least another primary tailored waveform having a different at least two gaps in frequency space and at least another secondary tailored waveform having at least one gap in frequency space to define a mass spectrum. ### Claim 20 (depends on 19) The method of claim 19 further comprising the step of reacting the second subset of ionized molecules with a quencher for a second charge reduction period to reduce the charge state of ionized molecules in the second subset of ionized molecules. ### Claim 21 (depends on 19) The method of claim 19 further comprising the steps of: using at least one of the primary and secondary tailored waveforms for an accumulation time; and varying the accumulation time for at least one of the another primary and secondary tailored waveforms. ### Claim 22 (depends on 21) The method of claim 21 wherein the step of varying the accumulation time comprises varying the accumulation time so the second subset of ionized molecules attains at least a minimum abundance. ### Claim 23 (depends on 21) The method of claim 21 further comprising the step of normalizing the mass signal resulting in step (d) based on the accumulation time. ### Claim 24 (depends on 19) The method of claim 19 wherein step (a) comprises selecting at least two gaps in frequency space such that the first subset of ionized molecules comprises ionized molecules within mass to charge ratio ranges with median values which are substantially the mass-to-charge ratios of the integer charge states of a select ion mass. ### Claim 25 (depends on 19) The method of claim 19 wherein: step (a) comprises segregating a subset of ionized molecules that are substantially cations; and step (b) comprises reacting the subset of ionized molecules with an anionic quencher. ### Claim 26 (depends on 19) The method of claim 19 further comprising the step of analyzing by a mass spectrometry technique, the ionized molecules having the highest mass to charge ratio resulting from step (c). ### Claim 27 (depends on 19) The method of claim 19 wherein step (a) comprises: trapping the plurality of ionized molecules in an ion trap; and retaining in the ion trap the subset of ionized molecules. ### Claim 28 (depends on 19) An article of manufacture having computer-readable program means for performing the method of claim 19 embodied thereon. ### Claim 29 A method of analyzing a sample of molecules comprising the steps of: (a) using a tailored waveform having at least two gaps in frequency space to segregate a subset of ionized molecules from a plurality of ionized molecules; (b) reacting the subset of ionized molecules with a quencher for a charge reduction period to reduce the charge state of ionized molecules in the subset of ionized molecules; (c) detecting the ionized molecules having the highest mass to charge ratio resulting from step (b); and (d) repeating steps (a)-(c) for at least another tailored waveform having a different at least two gaps in frequency space to analyze a sample of molecules. ### Claim 30 (depends on 29) The method of claim 29 further comprising the steps of: using the tailored waveform for an accumulation time; and varying the accumulation time for at least one of the tailored waveforms. ### Claim 31 (depends on 30) The method of claim 30 wherein the step of varying the accumulation time; and comprises varying the accumulation time so the subset of ionized molecules attains at least a minimum abundance. ### Claim 32 (depends on 29) The method of claim 29 wherein step (a) comprises selecting at step (a) selecting at least two gaps in frequency space such that the subset of ionized molecules comprises ionized molecules within mass to charge ration ranges with median values which are substantially the mass-to-charge ratios of the integer charge states of a select ion mass. ### Claim 33 (depends on 29) The method of claim 29, wherein: step (a) comprises segregating a subset of ionized molecules that are substantially cations; and step (b) comprises reacting the subset of ionized molecules with an anionic quencher. ### Claim 34 (depends on 29) The method of claim 29, further comprising the step of analyzing by a mass spectrometry technique, the ionized molecules having the highest mass to charge ratio resulting from step (b). ### Claim 35 (depends on 29) The method of claim 29 wherein step (a) comprises: trapping the plurality of ionized molecules in an ion trap; and retaining in the ion trap the subset of ionized molecules. ### Claim 36 (depends on 29) An article of manufacture having computer-readable program means for performing the method of claim 29 embodied thereon. ### Claim 37 (depends on 29) The method of claim 29 wherein the detecting step is performed using at least one of the group consisting of a channeltron electron multiplier, a discrete dynode electron multiplier, a CCD, electron multiplier, Faraday cup, Daly detector, or a conductive plate electrically connected to an ammeter.