IP Library Granted Patent US 12,444,592
Granted Patent B2
US 12,444,592 · App. 17/153,156 · Granted Oct 14, 2025

Sample quantitation using a miniature mass spectrometer

Inventors: Zheng Ouyang (West Lafayette, IN); Linfan Li (West Lafayette, IN); Xiaoyu Zhou (West Lafayette, IN)
Assignee: Purdue Research Foundation
H01J49/0031H01J49/0013H01J49/004H01J49/0422H01J49/4225
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,444,592
App. No.
17/153,156
Granted
Oct 14, 2025
Kind
B2
Abstract

The invention generally relates to sample analysis with a miniature mass spectrometer. In certain embodiments, the invention provides methods that involve generating ions of a first analyte and ions of a second analyte. Those ions are transferred through a discontinuous sample introduction interface into a first ion trap of a mass spectrometer in a manner in which the discontinuous sample introduction interface remains open during the transferring. The discontinuous sample introduction interface is closed and the ions are sequentially transferred to a second ion trap of the mass spectrometer where they are sequentially analyzed.

Claims (11)

1. A method for analyzing a sample and an internal standard in a miniature mass spectrometer, the method comprising:

generating sample ions and internal standard ions;

simultaneously transferring the sample and internal standard ions through a discontinuous sample introduction interface (DAPI) into a first ion trap of the miniature mass spectrometer, wherein the first ion trap is a first rectilinear ion trap that comprises top and bottom electrodes that are y electrodes and left and right electrodes that are x electrodes;

closing the discontinuous sample introduction interface;

sequentially transferring the sample and internal standard ions to a second ion trap of the miniature mass spectrometer, wherein the second ion trap is a second rectilinear ion trap that comprises top and bottom electrodes that are y electrodes and left and right electrodes that are x electrodes and wherein the first and second ion traps share a common end mesh electrode; and

sequentially analyzing within one second of each other the sample and internal standard ions in the second ion trap, wherein during a trapping step, a DC voltage is applied to the common end mesh electrode and single phase Radio Frequencies (RFs) of 1015 kHz and 995 kHz are applied on y electrodes of the first and second rectilinear ion traps, respectively, and after the trapping step and in order to then achieve an axial mass selective ejection, the ions trapped in the first rectilinear ion trap during a DAPI opening period undergo axial mass selective ejection toward the second rectilinear ion trap via application of one of the two following methods: (i) a separate RF scan with a resonance ejection by a dipolar AC, or (ii) an AC excitation with a separate steady RF.

2. The method according to claim 1 , wherein generating the ions is by a technique that utilizes an ionization source that operates at atmospheric pressure and temperature.

3. The method according to claim 1 , wherein generating the ions is by a technique that utilizes a direct ambient ionization/sampling technique.

4. The method according to claim 3 , wherein the technique is paper spray ionization.

5. The method according to claim 1 , wherein the sample and internal standard ions are transferred to the second ion trap within a single scan cycle.

6. The method according to claim 1 , wherein analyzing comprises taking MS/MS measurements.

Assignments (2)
CONFIRMATORY LICENSE Recorded Nov 2, 2023
From: PURDUE UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065431/0063 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 27, 2021
From: OUYANG, ZHENG; LI, LINFAN; ZHOU, XIAOYU
To: PURDUE RESEARCH FOUNDATION
Reel/Frame 055049/0183 →
Continuity (4)
Continuation 14909269
Provisional Application 62013005 · Jun 17, 2014
Provisional Application 61865377 · Aug 13, 2013
Related Publication 20210166927A1 · Jun 3, 2021
References Cited (68)
US 5696376A · Doroshenko · 1997 [cited by examiner]
US 6177668B1 · Hager · 2001 [cited by applicant]
US 6838666B2 · Ouyang et al. · 2005 [cited by applicant]
US 7335897B2 · Takats et al. · 2008 [cited by applicant]
US 8304718B2 · Ouyang et al. · 2012 [cited by applicant]
US 8785846B2 · Ouyang et al. · 2014 [cited by applicant]
US 20040065824A1 · Bateman · 2004 [cited by examiner]
US 20040135080A1 · Ouyang · 2004 [cited by examiner]
US 20060054808A1 · Schwartz · 2006 [cited by examiner]
US 20060219896A1 · Hashimoto · 2006 [cited by examiner]
US 20060289737A1 · Bassmann et al. · 2006 [cited by applicant]
US 20060289743A1 · Hasegawa · 2006 [cited by examiner]
US 20080142705A1 · Schwartz et al. · 2008 [cited by applicant]
US 20090102766A1 · Oke et al. · 2009 [cited by applicant]
US 20090261247A1 · Cooks · 2009 [cited by examiner]
US 20090294661A1 · Hashimoto · 2009 [cited by examiner]
US 20100301209A1 · Ouyang · 2010 [cited by examiner]
US 20110253891A1 · Hashimoto · 2011 [cited by examiner]
US 20120119079A1 · Ouyang · 2012 [cited by examiner]
US 20120223223A1 · Sugiyama · 2012 [cited by examiner]
US 20130105683A1 · Ouyang et al. · 2013 [cited by applicant]
US 20130146759A1 · Ouyang et al. · 2013 [cited by applicant]
US 20140138540A1 · Ouyang et al. · 2014 [cited by applicant]
US 20140183350A1 · Brown · 2014 [cited by examiner]
CN 101320016A · 2008 [cited by examiner]
CN 102290319A · 2011 [cited by applicant]
JP 2010514103A · 2010 [cited by applicant]
JP 2011023184A · 2011 [cited by applicant]
JP 2012184975A · 2012 [cited by applicant]
JP 2012525687A · 2012 [cited by applicant]
WO 2009023361A2 · 2009 [cited by applicant]
WO 2009102766A1 · 2009 [cited by applicant]
WO 2010127059A1 · 2010 [cited by applicant]
WO 2012058632A1 · 2012 [cited by applicant]
WO 2012162036A1 · 2012 [cited by applicant]
Doroshenko et al., “Advanced stored waveform inverse fourier transform technique for a matrix-assisted laser desorption/ionization quadrupole ion trap mass spectrometer”, Rapid Communications in mass spectrometry, vol. … [cited by examiner]
Carroll, 1975, Atmospheric Pressure Ionization Mass Spectrometry: Corona Discharge Ion Source for Use in Liquid Chromatograph-Mass Spectrometer-Computer Analytical System, Anal. Chem. 47:2369-2373. [cited by applicant]
Cody, 2005, Versatile New Ion Source for the Analysis of Materials in Open Air under Ambient Conditions, Anal. Chem., 77:2297-2302. [cited by applicant]
Cooks, 1983, Mass spectrometry: analytical capabilities and potentials, Science, 222:273-291. [cited by applicant]
Cooks, 2006, Ambient Mass Spectrometry, Science, 311(5767): 1566-1570. [cited by applicant]
Fenn, 1989, Electrospray Ionization for Mass Spectrometry of Large Biomolecules, Science 246:64-71. [cited by applicant]
First Office Action issued Mar. 16, 2017 in Japanese Application No. 2016-534607. [cited by applicant]
First Office Action issued Mar. 29, 2017 in Chinese Application No. 201480056536.3. [cited by applicant]
Gao, 2006, Handheld Rectilinear lon Trap Mass Spectrometer, Anal Chem, 78(17):5994-6002. [cited by applicant]
Gao, 2008, Design and Characterization of a Multisource Hand-Held Tandem Mass Spectrometer, Z. Anal. Chem, 80:7198-7205. [cited by applicant]
Gao, 2008, Breaking the pumping speed barrier in mass spectrometry: discontinuous atmospheric pressure interface, Anal. Chem, 80:4026-4032. [cited by applicant]
Gao, 2009, Characterization of a discontinuous atmospheric pressure interface. Multiple ion introduction pulses for improved performance, International Journal of Mass Spectrometry, 283(1-3):30-34. [cited by applicant]
Guna, 2011, Tandem Ion Trap Design with Enhanced Mass Analysis Capabilities for Large Populations of Ions, Anal Chem, 83:6363-6367. [cited by applicant]
Hager, 2002, A new linear ion trap mass spectrometer, Rapid Communications in Mass Spectrometry, 16(6):512-526. [cited by applicant]
Hendricks, 2014, Autonomous in-situ analysis and real-time chemical detection using a backpack miniature mass spectrometer: concept, instrumentation development and performance, Anal. Chem., 86:2900-2908. [cited by applicant]
International Search Report and Written Opinion mailed on Nov. 19, 2014, for International Patent Application No. PCT/US2014/049853, filed Aug. 6, 2014 (14 pages). [cited by applicant]
Kogelschatz, 2003, Dielectric-barrier Discharges: Their History, Discharge Physics, and Industrial Applications, Plasma Chem. and Plasma Processing, 23:1-46. [cited by applicant]
Laiko, 2000, Atmospheric Pressure Matrix-Assisted Laser Desoprtion/Ionization Mass Spectrometry, Analytical Chemistry, 72:652-657. [cited by applicant]
Li, 2014, Mini 12, Miniature Mass Spectrometer for Clinical and Other Applications—Introduction and Characterization, 86(6):2909-2916. [cited by applicant]
Monge, 2013, Mass spectrometry: recent advances in direct open air surface sampling/ionization, Chemical Reviews, 113:2269-2308. [cited by applicant]
Ouyang, 2004, Rectilinear Ion Trap: Concepts, Calculations, and Analytical Performance of a New Mass Analyzer, Analytical Chemistry, 76:4595-4605. [cited by applicant]
Ouyang, 2009, Miniature Mass Spectrometers, Annual Review of Analytical Chemistry, 2:187-214. [cited by applicant]
Ren, 2013, Analysis of Biological Samples Using Paper Spray Mass Spectrometry: An Invesitgation of Impacts by the Substrates, Solvents and Elution Methods, Chromatographia, 76:1339-1346. [cited by applicant]
Schwartz, 2002, A two-dimensional quadrupole ion trap mass spectrometer, Mass Spectrometry, 13(6):659-669. [cited by applicant]
Shiea, 2005, Electrospray-assisted laser desorption/ionization mass spectrometry for direct ambient analysis of solids, J. Rapid Comm in Mass Spectrometry, 19:3701-3704. [cited by applicant]
Sleno, 2004, Ion activation methods for tandem mass spectrometry, Journal of Mass Spectrometry, 39(10):1091-1112. [cited by applicant]
Supplemental Search Report mailed on May 24, 2017, for EP Application No. 148363518. [cited by applicant]
Takats, 2004, Mass Spectrometry Sampling Under Ambient Conditions with Desoprtion Electrospray Ionization, Science 306:471-473. [cited by applicant]
Tanaka, 1988, Protein and polymer analyses up to m/z 100 000 by laser ionization time-of-flight mass spectrometry, Rapid Commun. Mass Spectrom., 2:151-153. [cited by applicant]
Wang, 2010, Paper Spray for Direct Analysis of Complex Mixtures Using Mass Spectrometry, Angew. Chem, 49:877-880. [cited by applicant]
Watson, 2007, Mass Spectrometry—Chapter 3 In: Introduction to Mass Spectrometry—Instrumentation, Applications, and Strategies for Data Interpretation—Fourth Edition, Wiley, Jan. 1, 2007, 58 pages. [cited by applicant]
Xu, 2010, Study of Discontinuous Atmospheric Pressure Interfaces for Mass Spectrometry Instrumentation Development, Analytical Chemistry, 82(15):6584-6592. [cited by applicant]
Yamashita, 1984, Electrospray Ion Source. Another Variation on the Free-Jet Theme, J. Phys. Chem., 88:4451-4459. [cited by applicant]