IP Library Granted Patent US 12,640,357
Granted Patent B2
US 12,640,357 · App. 18/257,611 · Granted May 26, 2026

Systems and methods for controlling flow through an open port interface

Inventors: Chang Liu (Richmond Hill, CA); Thomas Covey (Newmarket, CA); Peter Kovarik (Concord, CA)
Assignee: DH Technologies Development Pte. Ltd.
H01J49/068H01J49/165
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Quick Facts
Patent No.
US 12,640,357
App. No.
18/257,611
Granted
May 26, 2026
Kind
B2
Abstract

A method of adjusting a position of an electrode within a nebulizer probe of a mass spectrometry device having an open port interface for receiving a sample includes performing a first analysis of the sample at a first analysis condition including a first position of the electrode and a first flow rate. After performing the first analysis, a second analysis of the sample is performed at a second analysis condition including the first position of the electrode and a second flow rate higher than the first flow rate. Thereafter, a third analysis of the sample is performed at a third analysis condition including a second position of the electrode and the second flow rate.

Claims (53)

1 . A method of adjusting a position of an electrode within a nebulizer probe of a mass spectrometry device having an open port interface for receiving a sample, the method comprising:

performing a first analysis at a first analysis condition comprising a first position of the electrode in the nebulizer probe and a first flow rate, wherein performing the first analysis comprises:

delivering a transport liquid to the open port interface at the first flow rate while ejecting a mixture comprising the sample and the transport fluid from the electrode in the first position; and

analyzing the mixture at the first analysis condition with the mass spectrometry device to obtain a first analysis condition ion intensity signal;

after performing the first analysis, performing a second analysis at a second analysis condition comprising the first position of the electrode in the nebulizer probe and a second flow rate higher than the first flow rate, wherein performing the second analysis comprises:

delivering the transport liquid to the open port interface at the second flow rate while ejecting the mixture from the electrode in the first position; and

analyzing the mixture at the second analysis condition with the mass spectrometry device to obtain a second analysis condition ion intensity signal; and

after performing the second analysis, performing a third analysis at a third analysis condition comprising a second position of the electrode in the nebulizer probe and the second flow rate, wherein performing the third analysis comprises:

delivering the transport liquid to the open port interface at the second flow rate while ejecting the mixture from the electrode in the second position.

2 . The method of claim 1 , wherein performing the first analysis further comprises displaying the first analysis condition ion intensity signal, and wherein performing a second analysis further comprises displaying the second analysis condition ion intensity signal.

3 . The method of claim 1 , wherein performing the third analysis further comprises analyzing the mixture at the third analysis condition with the mass spectrometry device to obtain a third analysis condition ion intensity signal.

4 . The method of claim 3 , wherein performing the third analysis further comprises displaying the third analysis condition ion intensity signal.

5 . The method of claim 1 , wherein the first analysis condition ion intensity signal is characterized by at least one of peak height, a peak width, a baseline at least two adjacent peaks, a peak-to-peak variation, and a peak shape.

6 . The method of claim 1 , further comprising:

detecting a deviation by a first predetermined threshold between the first analysis condition ion intensity signal and the second analysis condition ion intensity signal; and

sending an electrode adjustment signal based at least in part on the deviation.

7 . The method of claim 6 , wherein sending the electrode adjustment signal comprises:

initiating an adjustment of the position of the electrode within the nebulizer probe;

detecting a reduced deviation of less than the first predetermined threshold between the first analysis condition ion intensity signal and the second analysis condition ion intensity signal; and

terminating adjustment of the position of the electrode within the nebulizer probe based at least in part on the detection of the reduced deviation, wherein the position of the electrode within the nebulizer probe at the termination of adjustment of the position of the electrode is the second position.

8 . The method of claim 6 , wherein sending the electrode adjustment signal comprises emitting at least one of a visual signal and an audible signal.

9 . A method of adjusting a position of an electrode within a nebulizer probe of a mass spectrometry device having an open port interface for receiving a transport liquid, the method comprising:

delivering a transport liquid to the open port interface at a first flow rate while ejecting the transport liquid from the electrode in a first position relative to the nebulizer probe;

analyzing the ejected transport liquid with the mass spectrometry device to generate an analysis signal comprising a test compound intensity signal and an associated noise; and

after generation of the test compound intensity signal, delivering the transport liquid to the open port interface at the first flow rate while ejecting the transport liquid from the electrode in a second position relative to the nebulizer probe, wherein delivering the transport liquid to the open port interface at the first flow rate substantially eliminates the noise from the test compound intensity signal.

10 . The method of claim 9 , further comprising:

after substantially eliminating the noise from the analysis signal, delivering the transport liquid to the open port interface at a higher second flow rate while ejecting the transport liquid from the electrode in the second position relative to the nebulizer probe, wherein delivering the transport liquid to the open port interface at the second flow rate introduces noise to the analysis signal; and

after generation of the test compound intensity signal, delivering the transport liquid to the open port interface at the second flow rate while ejecting the transport liquid from the electrode in a third position relative to the nebulizer probe, wherein delivering the transport liquid to the open port interface at the second flow rate substantially eliminates the noise from the test compound intensity signal.

11 . The method of claim 9 , wherein the test compound intensity signal is characterized by at least one of an intensity, a noise, a signal event periodicity, and a signal event duration.

12 . The method of claim 9 , further comprising detecting a deviation by a first predetermined threshold between the test compound intensity signal and the noise.

13 . The method of claim 12 , further comprising sending an electrode adjustment signal based at least in part on the detection.

14 . The method of claim 13 , wherein sending the electrode adjustment signal initiates an adjustment of a position of the electrode within the nebulizer probe.

15 . The method of claim 13 , wherein sending the electrode adjustment signal comprises emitting at least one of a visual signal and an audible signal.

16 . The method of claim 9 , wherein when in the first position, an indexing feature on the nebulizer probe is in a first positioning configuration and wherein when in the second position, the indexing feature on the nebulizer probe is in a second positioning configuration.

17 . A mass analysis instrument comprising:

an open port interface (OPI) configured to receive a sample;

a liquid pump configured to pump a transport liquid into the OPI;

an electrospray ionization (ESI) source, in liquid communication with the OPI, including an electrode within a nebulizer probe, wherein the electrode is movably positionable within the probe;

a detector configured to detect ions emitted from the ESI source;

a processor; and

memory storing instructions that when executed by the processor cause the mass analysis instrument to perform a set of operations comprising:

pumping the transport liquid into the OPI at a first flow rate;

during pumping at the first flow rate, with the electrode positioned at a first position, ejecting at least one of the transport liquid and the sample through the ESI source to be analyzed by the detector;

analyzing the ejected at least one of the transport liquid and the sample to obtain a ion intensity signal;

displaying the ion intensity signal;

receiving an input from a user; and

based at least in part on the input, performing at least one of:

pumping the transport liquid into the OPI at a second flow rate while ejecting at least one of the transport liquid and the sample through the ESI source with the electrode in the first position; and

pumping the transport liquid into the OPI at the first flow rate while ejecting at least one of the transport liquid and the sample through the ESI source with the electrode in a second position.

18 . The mass analysis instrument of claim 17 , wherein the ion intensity signal is associated with the sample.

19 . The mass analysis instrument of claim 17 , wherein the ion intensity signal is associated with the transport liquid.

20 . The mass analysis instrument of claim 17 , further comprising a transport liquid source and test liquid interface communicatively coupled to the transport liquid source.

21 . The mass analysis instrument of claim 17 , wherein the set of operations further comprises introducing the sample to the transport liquid.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 15, 2023
From: LIU, CHANG; COVEY, THOMAS R.; KOVARIK, PETER
To: DH TECHNOLOGIES DEVELOPMENT PTE. LTD.
Reel/Frame 063957/0737 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 15, 2023
From: LIU, CHANG; COVEY, THOMAS R.; KOVARIK, PETER
To: DH TECHNOLOGIES DEVELOPMENT PTE. LTD.
Reel/Frame 063957/0934 →
Continuity (3)
Provisional Application 63186929 · May 11, 2021
Provisional Application 63128572 · Dec 21, 2020
Related Publication 20240112901A1 · Apr 4, 2024
References Cited (92)
US 5109840A · Daleiden · 1992 [cited by applicant]
US 5691205A · Kawabata et al. · 1997 [cited by applicant]
US 7923681B2 · Collings et al. · 2011 [cited by applicant]
US 8759753B1 · Di Bussolo · 2014 [cited by applicant]
US 9134335B2 · Dehmer · 2015 [cited by applicant]
US 10770277B2 · Datwani et al. · 2020 [cited by applicant]
US 11232938B2 · Arnold et al. · 2022 [cited by applicant]
US 20020048536A1 · Bergh et al. · 2002 [cited by applicant]
US 20030193020A1 · Van Berkel · 2003 [cited by applicant]
US 20040102742A1 · Tuyl · 2004 [cited by applicant]
US 20120053065A1 · Van Berkel · 2012 [cited by applicant]
US 20120079894A1 · Van Berkel et al. · 2012 [cited by applicant]
US 20120083045A1 · Van Berkel et al. · 2012 [cited by applicant]
US 20130023005A1 · Chen et al. · 2013 [cited by applicant]
US 20130092166A1 · Pearce · 2013 [cited by applicant]
US 20130118498A1 · Robitaille et al. · 2013 [cited by applicant]
US 20130294971A1 · Van Berkel et al. · 2013 [cited by applicant]
US 20140216177A1 · Van Berkel et al. · 2014 [cited by applicant]
US 20140283627A1 · Hattingh et al. · 2014 [cited by applicant]
US 20150318160A1 · Pawliszyn et al. · 2015 [cited by applicant]
US 20160266017A1 · Kennedy et al. · 2016 [cited by applicant]
US 20170316926A1 · Arnold et al. · 2017 [cited by applicant]
US 20180021533A1 · Gausche-Hill et al. · 2018 [cited by applicant]
US 20190072464A1 · Wiederin · 2019 [cited by applicant]
US 20190157061A1 · Datwani et al. · 2019 [cited by applicant]
US 20200043712A1 · Arnold et al. · 2020 [cited by applicant]
US 20200166490A1 · Wiechers · 2020 [cited by applicant]
US 20200345968A1 · Merrell et al. · 2020 [cited by applicant]
US 20200365382A1 · Arnold et al. · 2020 [cited by applicant]
US 20210121905A1 · Covey · 2021 [cited by applicant]
US 20210190735A1 · Bonda · 2021 [cited by applicant]
US 20230184642A1 · Liu · 2023 [cited by applicant]
US 20230280351A1 · Iannotti · 2023 [cited by applicant]
US 20230349858A1 · Covey · 2023 [cited by applicant]
US 20240079225A1 · Covey · 2024 [cited by applicant]
US 20240096611A1 · Covey · 2024 [cited by applicant]
US 20240159716A1 · Cox · 2024 [cited by applicant]
US 20240170270A1 · Kovarik · 2024 [cited by applicant]
US 20240170271A1 · Kovarik · 2024 [cited by applicant]
US 20240175787A1 · Tate · 2024 [cited by applicant]
US 20240272191A1 · Verma · 2024 [cited by applicant]
CN 102354649A · 2012 [cited by applicant]
CN 109844901A · 2019 [cited by applicant]
EP 0421007 · 1991 [cited by applicant]
EP 2443432 · 2012 [cited by applicant]
JP 2011007690A · 2011 [cited by applicant]
JP 2012502296A · 2012 [cited by applicant]
JP 2019521320A · 2019 [cited by applicant]
WO 2010048339 · 2010 [cited by applicant]
WO 2011146269 · 2011 [cited by applicant]
WO 2012149314 · 2012 [cited by applicant]
WO 2013112914 · 2013 [cited by applicant]
WO 2014140776 · 2014 [cited by applicant]
WO 2015108807 · 2015 [cited by applicant]
WO 2015188282 · 2015 [cited by applicant]
WO 2016164766 · 2016 [cited by applicant]
WO 2018217778 · 2018 [cited by applicant]
WO 2019102350 · 2019 [cited by applicant]
WO 2019126363 · 2019 [cited by applicant]
WO 2020016809 · 2020 [cited by applicant]
WO 2020079647 · 2020 [cited by applicant]
WO 2021234644 · 2021 [cited by applicant]
WO 2022167917 · 2022 [cited by applicant]
WO 2022167980 · 2022 [cited by applicant]
WO 2022172156 · 2022 [cited by applicant]
WO 2022172199 · 2022 [cited by applicant]
WO 2022201037 · 2022 [cited by applicant]
WO 2022208393 · 2022 [cited by applicant]
WO 2022259187 · 2022 [cited by applicant]
WO 2024241262 · 2024 [cited by applicant]
Zhang, et al.(“Acoustic Ejection Mass Spectrometry for High-Throughput Analysis,” bioRxiv, Jan. 29, 2020 (Year: 2020). [cited by examiner]
Anonymous, “Turbo V Ion Source Operator Guide”, AB Sciex Pte, Ltd., Aug. 1, 2015, retrieved from the internet on Mar. 17, 2022 at: https://manualzz.com/doc/7476753/user-guide--turbo-v-ion-source-operator-guide, “Turbolo… [cited by applicant]
Bonvin, Gregoire et al., “Capillary electrophoresis; electrospray ionization-mass spectrometry interfaces: Fundamental concepts and technical developments”, Journarl of Chromatopgraphy A, vol. 1267, Dec. 1, 2012, pp. 17… [cited by applicant]
Dirico, Kenneth et al., “Ultra-High-Throughput Acoustic Sroplet Ejection-Open Port Interface-Mass Spectrometry for Parallel Medicinal Chemistry”, ACS Medicinal Chemistry Letters, vol. 11, No. 6, May 1, 2020, pp. 1101-11… [cited by applicant]
Hager, James et al., “Product ion scanning using Q-q-Q linear ion trap (Q Trap) mass spectrometer”, Rapid Communications in Mass Spectrometry, 2003; 17: 1056-1064. [cited by applicant]
Liu, Chang et al., “Operational Modes and Speed Considerations of an Acoustic Droplet Dispenser for Mass Sectrometry”, Analytical Chemistry, vol. 92, No. 24, Oct. 16, 2020, pp. 15818-15826. [cited by applicant]
Maxwell, E. Jane et al., “Decoupling CE and ESI for a more robust interface with MS”, Electrophoresis, Verlag-Chemie, Hoboken, USA, vol. 31, No. 7, Mar. 1, 2010, pp. 1130-1137. [cited by applicant]
PCT International Preliminary Report on Patentability in Application PCT/IB2021/062108, mailed Jun. 29, 2023, 11 pages. [cited by applicant]
PCT International Search Report and Written Opinion in Application PCT/IB2021/062108, mailed Mar. 29, 2022, 19 pages. [cited by applicant]
Pei, Jian et al., “Analysis of Samples Stored as Individual Plugs in a Capilaary by Electrspray Ionization Mass Spectrometry”, Analytical Chemistry, vol. 81, No. 15, Aug. 1, 2009, pp. 6558-6561. [cited by applicant]
Pei, Jian et al., “Rapid and Label-Free Screening of Enzyme Inhibitors Using Segmented Flow Electrospray Ionization Mass Spectrometry”, Journal of the American Society for Mass Spectrometry, Elsevier, vol. 21, No. 7, Ju… [cited by applicant]
SCIEX, Echo MS Core Module User Guide, published by SCIEX, RUO-IDV-05-9945-C, Apr. 2020, 51 pages. [cited by applicant]
Simon, Roman et al., “Acoustic Ejection Mass Spectrometry: A Fully Automatable Technology for High-Throughput Screening in Drug Discovery”, Society for Laboratory Automation and Screening, vol. 26, Jul. 26, 2021, pp. 96… [cited by applicant]
Tascon, Marcos et al., “Development of a microfluidic open interface with flow isolated desorption volume for the direct coupling of SPME devices to mass spectrometry”, Analytical Chemistry, vol. 90, No. 4, Feb. 1, 2018… [cited by applicant]
Van Berkel et al., Immediate drop on demand technology (I-DOT) coupled with mass spectrometry via an open-port sampling interface, Bioanalysis, vol. 9, No. 21, Nov. 2, 2017, pp. 1667-1679. [cited by applicant]
Van Berkel, Gary et al., “An open port sampling interface for liquid introduction atmosperic pressure ionization mass spectrometry: Open port sampling interface”, Rapid Communications in Mass Spectrometry, vol. 29, No. … [cited by applicant]
Van Berkel, Gary et al., “Combined Falling Drop/Open Port Sampling Interface System for Automated Flow Injection Mass Spectrometry”, Analytic Chemistry, 2017, 89, 22, pp. 12578-12586. [cited by applicant]
Wen, Xiujuan et al., “Direct Analysis from Phase-Separated Liquid Samples using ADE-OPI-MS: Applicability to High-Throughput Screening for Inhibitors of Diacylglycerol Acyltransferase 2”, Analytic Chemistry, 2021, 93, 1… [cited by applicant]
Zhang, Hui et al., “Acoustic Ejection Mass Spectrometry for High-Throughput Analsis”, bioRxiv, Jan. 29, 2020, retrieved from the internet on Sep. 8, 2021 at: https:www.biorxiv.org/content/10.1101/2020.01.28.923938v1.ful… [cited by applicant]
Zhang, Hui et al., “Acoustic Ejection Mass Spectrometry for High-Throughput Analysis”, Analytical Chemistry, Jan. 29, 2020, 12 pages. [cited by applicant]
Li, Xianjiang et al., “Sampling and analyte enrichment strategies for ambient mass spectrometry”, Anal Bioanal Chem (2018), 410:715-724. [cited by applicant]
Li, Xin-Xin, et al., “Method for Improving Spatial Resolution of Liquid-assisted Surface Desorption Atmospheric Pressure Chemical Ionization Mass Spectrometry”, Chinese Journal of Analytical Chemistry, vol. 44, Issue 1,… [cited by applicant]