IP Library Granted Patent US 12,546,753
Granted Patent B2
US 12,546,753 · App. 18/550,001 · Granted Feb 10, 2026

Non-contact sampler with an open-port interface for liquid chromatography systems

Inventors: David Michael Cox (Toronto, CA); Chang Liu (Richmond Hill, CA)
Assignee: DH Technologies Development Pte. Ltd.
G01N30/20B01D15/14G01N30/22G01N30/7233G01N2030/201
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Quick Facts
Patent No.
US 12,546,753
App. No.
18/550,001
Granted
Feb 10, 2026
Kind
B2
Abstract

A method of performing liquid chromatography (LC) with an LC system including an LC column and an analyzer includes delivering a transport liquid to an open port interface (OPI) of a sample receiving circuit, wherein the sample receiving circuit includes a sample transfer chamber. A sample is ejected from a sample holder into the OPI with a non-contact ejector. The transport liquid and the sample are received in the sample transfer chamber. The sample transfer chamber is decoupled from the sample receiving circuit. A solvent is delivered to the analysis circuit. The sample is pushed from the sample transfer chamber with the solvent. The sample and the solvent is passed through the LC column to produce an eluent. The eluent is analyzed with the analyzer.

Claims (34)

1 . A method of performing liquid chromatography (LC) with an LC system comprising an LC column and an analyzer, the method comprising:

delivering a transport liquid to an open port interface (OPI) of a sample receiving circuit, wherein the sample receiving circuit comprises a sample transfer chamber;

ejecting a sample from a sample holder into the OPI with a non-contact ejector;

receiving the transport liquid and the sample in the sample transfer chamber;

decoupling the sample transfer chamber from the sample receiving circuit;

coupling the sample transfer chamber to an analysis circuit;

delivering a solvent to the analysis circuit;

pushing the sample from the sample transfer chamber with the solvent;

passing the sample and the solvent through the LC column to produce an eluent; and

analyzing the eluent with the analyzer.

2 . The method of claim 1 , wherein the sample is ejected into the OPI substantially simultaneously with delivering the transport liquid to the OPI.

3 . The method of claim 1 , further comprising aspirating a portion of the transport liquid from the sample transfer chamber substantially simultaneously with delivering the transport liquid to the OPI.

4 . The method of claim 3 , further comprising ejecting from a waste outlet the portion of the transport liquid aspirated from the sample transfer chamber.

5 . The method of claim 3 , wherein delivering the transport liquid to the OPI comprises pumping the transport liquid to the OPI at a first flow rate with a first pump.

6 . The method of claim 5 , wherein aspirating the portion of the transport liquid from the sample transfer chamber comprises aspirating the portion of the transport liquid at a second flow rate with a second pump.

7 . The method of claim 6 , wherein the first flow rate and the second flow rate are substantially similar.

8 . The method of claim 1 , further comprising, prior to decoupling the sample transfer chamber from the sample receiving circuit, terminating delivery of the transport liquid to the OPI and terminating ejection of the sample from the sample holder.

9 . The method of claim 8 , further comprising, prior to decoupling the sample transfer chamber from the sample receiving circuit, receiving a plurality of samples in the sample transfer chamber.

10 . The method of claim 1 , further comprising during pushing of the sample, flushing the sample receiving circuit with a flushing liquid.

11 . The method of claim 10 , wherein the transport liquid is substantially similar to the flushing liquid.

12 . The method of claim 10 , wherein flushing the sample receiving circuit comprises operating a transport liquid pump and a waste pump.

13 . The method of claim 1 , further comprising, subsequent to pushing of the sample, recoupling the sample transfer chamber to the sample receiving circuit.

14 . The method of claim 1 , wherein the transport liquid and the solvent are different.

15 . A liquid chromatography (LC) system comprising:

an analysis circuit comprising a solvent pump and an LC column;

an analyzer fluidically coupled to the LC column;

a sample receiving circuit comprising a transport liquid pump and an open port interface (OPI) fluidically coupled to the transport liquid pump;

a non-contact ejector configured to eject droplets from a sample holder into the OPI; and

a sample transfer chamber selectively positionable in a first position and a second position, wherein in the first position, the sample transfer chamber is fluidically coupled to the sample receiving circuit, and wherein in the second position, the sample transfer chamber is fluidically coupled to the analysis circuit.

16 . The LC system of claim 15 , wherein the sample receiving circuit further comprises a waste pump selectively fluidically couplable to the sample transfer chamber.

17 . The LC system of claim 16 , wherein the transport liquid pump is the waste pump.

18 . The LC system of claim 15 , wherein the sample transfer chamber is disposed within a six-port valve.

19 . The LC system of claim 15 , wherein the analyzer comprises a mass spectrometry device.

20 . The LC system of claim 15 , wherein the non-contact ejector comprises an acoustic droplet ejector.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 11, 2023
From: COX, DAVID MICHAEL; LIU, CHANG
To: DH TECHNOLOGIES DEVELOPMENT PTE. LTD.
Reel/Frame 064859/0150 →
Continuity (2)
Provisional Application 63163197 · Mar 19, 2021
Related Publication 20240159716A1 · May 16, 2024
References Cited (69)
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 examiner]
US 9134335B2 · Dehmer · 2015 [cited by examiner]
US 10770277B2 · Datwani et al. · 2020 [cited by applicant]
US 11232938B2 · Arnold et al. · 2022 [cited by applicant]
US 20030193020A1 · Van Berkel · 2003 [cited by applicant]
US 20040102742A1 · Tuyl · 2004 [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 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 examiner]
US 20190157061A1 · Datwani et al. · 2019 [cited by applicant]
US 20200043712A1 · Arnold · 2020 [cited by examiner]
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 examiner]
US 20230349858A1 · Covey · 2023 [cited by applicant]
US 20240079225A1 · Covey · 2024 [cited by applicant]
US 20240096611A1 · Covey · 2024 [cited by applicant]
US 20240112901A1 · Liu · 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]
EP 0421007 · 1991 [cited by applicant]
EP 2443432 · 2012 [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 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 2022172199 · 2022 [cited by applicant]
WO 2022201037 · 2022 [cited by applicant]
WO 2022208393 · 2022 [cited by applicant]
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, “TurboIo… [cited by applicant]
Bonvin, Gregoire et al., “Capillary electrophoresis; electrospray ionization-mass spectrometry interfaces: Fundamental concepts and technical developments”, Journal of Chromatopgraphy A, vol. 1267, Dec. 1, 2012, pp. 17-… [cited by applicant]
Dirico, Kenneth et al., “Ultra-High-Throughput Acoustic Droplet 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/IB2022/052502, mailed Sep. 28, 2023, 8 pages. [cited by applicant]
PCT International Search Report and Written Opinion in Application PCT/IB2022/052502, mailed Jul. 12, 2022, 16 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]