IP Library › Granted Patent US 12,306,147
Granted Patent B2
US 12,306,147 · App. 17/965,290 · Granted May 20, 2025

Analytical system and method including switching between liquid chromatography fluidic streams

Inventors: Stefan Quint (München Süd, DE); Tibor Toth (München Süd, DE); Aart Pieter Van Doorn (München Süd, DE); Yuichiro Hashimoto (Tokyo, JP)
Assignees: ROCHE DIAGNOSTICS OPERATIONS, INC.; HITACHI HIGH-TECH CORPORATION
G01N30/468G01N30/7206G01N30/722G01N30/724G01N30/74G01N30/84H01J49/0422
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Quick Facts
Patent No.
US 12,306,147
App. No.
17/965,290
Granted
May 20, 2025
Kind
B2
Abstract

The present disclosure is related to an analytical system comprising a liquid chromatographic (LC) system comprising a plurality of fluidic streams alternately connectable to a common detector via a stream-selection valve connected to the detector via a valve-to-detector conduit. The analytical system further comprises a wash pump fluidically connected to the stream-selection valve and configured to connect to the valve-to-detector conduit between two consecutive fluidic streams in order to wash liquid from a previous fluidic stream out of the valve-to-detector conduit before liquid from a subsequent fluidic stream enters the valve-to-detector conduit. An analytical method comprising switching between the fluidic streams and washing in between is also disclosed.

Claims (32)

1. An analytical system comprising a liquid chromatographic (LC) system comprising:

a plurality of fluidic streams alternately connectable to a common detector via a stream-selection valve connected to the detector via a valve-to-detector conduit, wherein the analytical system further comprises a wash pump fluidically connected to the stream-selection valve and configured to connect to the valve-to-detector conduit between two consecutive fluidic streams in order to wash liquid from a previous fluidic stream out of the valve-to-detector conduit before liquid from a subsequent fluidic stream enters the valve-to-detector conduit,

wherein the analytical system comprises a controller configured to manage a fluidic-stream connection time (t-Sn−1, T-Sn, t-Sn+1), that is the connection time between each fluidic stream (Sn−1, Sn, Sn+1) and the valve-to-detector conduit, and a wash-pump connection time (t-W), that is the connection time between the wash pump and the valve-to-detector conduit, by controlling switching of the stream-selection valve, and

wherein the controller is configured to adjust a set of parameters of the detector and/or ionization source from a previous configuration related to the previous fluidic stream to a subsequent configuration related to the subsequent fluidic stream during the wash-pump connection time (t-W) before switching to the subsequent fluidic stream.

2. The analytical system according to claim 1 wherein the detector is a mass spectrometer connected to the valve-to-detector conduit via an ionization source.

3. The analytical system according to claim 2 wherein the ionization source comprises a sprayer capillary that forms part of the valve-to detector conduit.

4. The analytical system according to claim 1 wherein the wash pump is configured to pump a wash liquid through the valve-to-detector conduit at a flow rate higher than a flow rate of the fluidic streams.

5. The analytical system according to claim 1 wherein the controller is configured to control the wash pump such that wash liquid is pumped only during the wash-pump connection time.

6. The analytical system according to claim 1 wherein the fluidic-stream connection time is fixed and is the same for each fluidic stream and wherein the wash-pump connection time is fixed and is a fraction of the fluidic-stream connection time, thereby resulting at least temporarily in a continuous switching at a regular pace.

7. An analytical system comprising a liquid chromatographic (LC) system comprising:

a plurality of fluidic streams alternately connectable to a common detector via a stream-selection valve connected to the detector via a valve-to-detector conduit, wherein the analytical system further comprises a wash pump fluidically connected to the stream-selection valve and configured to connect to the valve-to-detector conduit between two consecutive fluidic streams in order to wash liquid from a previous fluidic stream out of the valve-to-detector conduit before liquid from a subsequent fluidic stream enters the valve-to-detector conduit

wherein the analytical system comprises a controller configured to manage a fluidic-stream connection time (t-Sn−1, T-Sn, t-Sn+1), that is the connection time between each fluidic stream (Sn−1, Sn, Sn+1) and the valve-to-detector conduit, and a wash-pump connection time (t-W), that is the connection time between the wash pump and the valve-to-detector conduit, by controlling switching of the stream-selection valve, and

wherein the controller is configured to adjust a set of parameters of the detector and/or ionization source from a previous configuration related to the previous fluidic stream to a subsequent configuration related to the subsequent fluidic stream during the wash-pump connection time (t-W) before switching to the subsequent fluidic stream, and

wherein the set of parameters comprises any one or more of a curtain gas pressure, a nebulizer gas pressure, an auxiliary gas pressure, a sprayer capillary voltage, a sampling capillary voltage.

8. An analytical system comprising a liquid chromatographic (LC) system comprising:

a plurality of fluidic streams alternately connectable to a common detector via a stream-selection valve connected to the detector via a valve-to-detector conduit, wherein the analytical system further comprises a wash pump fluidically connected to the stream-selection valve and configured to connect to the valve-to-detector conduit between two consecutive fluidic streams in order to wash liquid from a previous fluidic stream out of the valve-to-detector conduit before liquid from a subsequent fluidic stream enters the valve-to-detector conduit,

wherein the analytical system comprises a controller configured to manage a fluidic-stream connection time (t-Sn−1, T-Sn, t-Sn+1), that is the connection time between each fluidic stream (Sn−1, Sn, Sn+1) and the valve-to-detector conduit, and a wash-pump connection time (t-W), that is the connection time between the wash pump and the valve-to-detector conduit, by controlling switching of the stream-selection valve, and

wherein the controller is configured to extend the wash-pump connection time while pumping of wash liquid through the valve-to-detector conduit in case of interrupted switching between fluidic streams or in case of system standby.

9. An analytical system comprising a liquid chromatographic (LC) system comprising:

a plurality of fluidic streams alternately connectable to a common detector via a stream-selection valve connected to the detector via a valve-to-detector conduit, wherein the analytical system further comprises a wash pump fluidically connected to the stream-selection valve and configured to connect to the valve-to-detector conduit between two consecutive fluidic streams in order to wash liquid from a previous fluidic stream out of the valve-to-detector conduit before liquid from a subsequent fluidic stream enters the valve-to-detector conduit,

wherein the analytical system comprises a controller configured to manage a fluidic-stream connection time (t-Sn−1, T-Sn, t-Sn+1), that is the connection time between each fluidic stream (Sn−1, Sn, Sn+1) and the valve-to-detector conduit, and a wash-pump connection time (t-W), that is the connection time between the wash pump and the valve-to-detector conduit, by controlling switching of the stream-selection valve, and

a pressure gauge between the wash pump and the stream-selection valve for determining a liquid pressure, wherein the controller is configured to compare a liquid pressure determined during the wash-pump connection time with a liquid pressure determined when the wash pulp is fluidically connected to waste and based on such comparison to determine whether there is a clogging in the valve-to-detector.

10. An automated analytical method comprising: alternately connecting a plurality of fluidic streams of a liquid chromatographic system to a common detector via a stream-selection valve connected to the detector via a valve-to-detector conduit, the method further comprising fluidically connecting a wash pump to the valve-to-detector conduit via the stream-selection valve between two consecutive fluidic streams and washing liquid from a previous fluidic stream out of the valve-to-detector conduit before liquid from a subsequent fluidic stream enters the valve-to-detector conduit,

automatically managing a fluidic-stream connection time, that is the connection time between each fluidic stream and the valve-to-detector conduit, and a wash-pump connection time, that is the connection time between the wash pump and the valve-to-detector conduit, by controlling switching of the stream-selection valve, and

adjusting a set of parameters of the detector and/or of an ionization source in case the detector is a mass spectrometer from a previous configuration related to the previous fluidic stream to a subsequent configuration related to the subsequent fluidic stream during the wash-pump connection time before switching to the subsequent fluidic stream.

11. An automated analytical method comprising alternately connecting a plurality of fluidic streams of a liquid chromatographic system to a common detector via a stream-selection valve connected to the detector via a valve-to-detector conduit, the method further comprising fluidically connecting a wash pump to the valve-to-detector conduit via the stream-selection valve between two consecutive fluidic streams and washing liquid from a previous fluidic stream out of the valve-to-detector conduit before liquid from a subsequent fluidic stream enters the valve-to-detector conduit,

automatically managing a fluidic-stream connection time, that is the connection time between each fluidic stream and the valve-to-detector conduit, and a wash-pump connection time, that is the connection time between the wash pump and the valve-to-detector conduit, by controlling switching of the stream-selection valve, and

extending the wash-pump connection time while pumping of wash liquid through the valve-to-detector conduit in case of interrupted switching between fluidic streams or in case of system standby.

12. An automated analytical method comprising:

alternately connecting a plurality of fluidic streams of a liquid chromatographic system to a common detector via a stream-selection valve connected to the detector via a valve-to-detector conduit, the method further comprising fluidically connecting a wash pump to the valve-to-detector conduit via the stream-selection valve between two consecutive fluidic streams and washing liquid from a previous fluidic stream out of the valve-to-detector conduit before liquid from a subsequent fluidic stream enters the valve-to-detector conduit,

automatically managing a fluidic-stream connection time, that is the connection time between each fluidic stream and the valve-to-detector conduit, and a wash-pump connection time, that is the connection time between the wash pump and the valve-to-detector conduit, by controlling switching of the stream-selection valve, wherein the method comprises

comparing a liquid pressure between the wash pump and the stream-selection valve determined during the wash-pump connection time with a liquid pressure determined when the wash pump is fluidically connected to waste and based on such comparison determining whether there is a clogging in the valve-to-detector conduit.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 13, 2022
From: QUINT, STEFAN; TOTH, TIBOR; VAN DOORN, AART PIETER
To: ROCHE DIAGNOSTICS GMBH
Reel/Frame 061413/0970 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 13, 2022
From: ROCHE DIAGNOSTICS GMBH
To: ROCHE DIAGNOSTICS OPERATIONS, INC.
Reel/Frame 061414/0041 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 13, 2022
From: HASHIMOTO, YUICHIRO
To: HITACHI HIGH-TECH CORPORATION
Reel/Frame 061414/0206 →
Priority Claims (1)
EP 20169521 · Apr 15, 2020 · regional
Continuity (2)
Continuation PCTEP2021059412 · Apr 12, 2021
Related Publication 20230037141A1 · Feb 2, 2023
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US 12,724,010