IP Library › Granted Patent US 11,249,059
Granted Patent B2
US 11,249,059 · App. 16/994,118 · Granted Feb 15, 2022

Techniques for checking state of analyzers

Inventors: Stefan Quint (Munich, DE); Benjamin Tiemann (Munich, DE); Florian Schweinberger (Munich, DE); Martin Stingl (Kochel, DE)
Assignee: Roche Diagnostics Operations, Inc.
G01N30/7266G01N30/7233G01N30/8631G01N30/8637G01N30/8658G01N30/8662G01N30/8665G01N35/1004H01J49/0031H01J49/0036H01J49/0431H01J49/0445H01J49/165G01N2015/1272G01N2030/045G01N2030/623
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Quick Facts
Patent No.
US 11,249,059
App. No.
16/994,118
Granted
Feb 15, 2022
Kind
B2
Abstract

An automated method of monitoring a state of an analyzer is provided including a mass spectrometer (MS) with an electrospray ionization (ESI) source coupled to a liquid chromatography (LC) stream, including monitoring an electrospray ionization current of the ESI source and identifying a condition of multiple conditions of the analyzer based on the monitored ionization current of the ESI source, one of the conditions being a presence of a dead volume in a liquid chromatography stream of the analyzer downstream of an LC column of the LC stream.

Claims (18)

1. An automated method of monitoring a state of an analyzer including a mass spectrometer (MS) with an electrospray ionization (ESI) source coupled to a liquid chromatography (LC) stream, the method comprising:

monitoring an electrospray ionization current of the ESI source; and

identifying a condition of multiple conditions of the analyzer based on the monitored ionization current of the ESI source, wherein one of the conditions is a presence of a dead volume in a liquid chromatography stream of the analyzer downstream of an LC column of the LC stream.

2. The method of claim 1 , further comprising monitoring one or more additional parameters including a pressure in a liquid chromatography (LC) stream of the analyzer, wherein the identification of a condition is further based on the monitored additional parameters to distinguish the multiple conditions.

3. The method of claim 2 , wherein the additional measured parameters are measured on an internal standard.

4. The method of claim 1 , further comprising monitoring one or more additional parameters including one or more chromatographic features of a chromatogram of a liquid chromatography (LC) stream of the analyzer, wherein the identification of a condition is further based on the monitored additional parameters to distinguish the multiple conditions.

5. The method of claim 4 , wherein the chromatographic feature is selected from the list consisting of a peak width parameter, a retention time parameter, a peak height parameter, a peak area parameter, and a peak symmetry parameter.

6. The method of claim 1 , wherein the conditions include one or more of an aging of a particular component of the analyzer or an error or defect of a particular component of the analyzer.

7. The method of claim 1 , wherein the multiple conditions further include one or more of a presence of a pre-column dead volume ( 15 ); a valve error; a spray needle aging; a column defect; a column aging; an instable spray; a clogging; a leakage; or an ion source contamination.

8. The method of claim 1 , wherein the identification of a condition of multiple conditions includes determining one or more of a decrease in a monitored parameter, an increase of a monitored parameter, a fluctuation of a monitored parameter, a profile shift in a time series of the monitored parameter, and a profile change of a time series of the monitored parameter.

9. The method of claim 8 , wherein identifying a presence of a dead volume in a liquid chromatography stream based on the monitored ionization current of the ESI source includes assessing a profile shift in a time series of the monitored ionization current of the ESI source.

10. The method of claim 1 , further comprising triggering one or more selected responses of multiple responses depending on the determined condition of the analyzer.

11. The method of claim 10 , wherein the multiple responses include one or more of logging the determined state of the analyzer; starting or scheduling an automatic maintenance operation; generating an error message; asking an operator to perform a predetermined maintenance operation; informing a service provider; or scheduling a preventive maintenance operation.

12. The method of claim 11 , wherein the maintenance operation is one of reconnecting a capillary of the ESI source; replacing an LC column of an LC stream of the analyzer; cleaning an ion source of the ESI source; or cleaning or replacing a capillary of the ESI source.

13. The method of claim 1 , further including predicting a development of the electrospray ionization current and optionally one or more additional measured parameters over time based on the monitored electrospray ionization current and optionally one or more additional measured parameters, and

triggering a response based on the predicted development of the electrospray ionization current and optionally one or more additional measured parameters.

14. A computer system being configured to carry out the steps of the method of claim 1 .

15. A computer-readable medium having instructions stored thereon that when executed by a computer system prompt the computer system to carry out the steps of the method of claim 1 .

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 24, 2020
From: ROCHE DIAGNOSTICS GMBH
To: ROCHE DIAGNOSTICS OPERATIONS, INC.
Reel/Frame 053577/0425 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 24, 2020
From: QUINT, STEFAN; TIEMANN, BENJAMIN; SCHWEINBERGER, FLORIAN; STINGL, MARTIN
To: ROCHE DIAGNOSTICS GMBH
Reel/Frame 053587/0340 →
Priority Claims (1)
EP 19193868 · Aug 27, 2019 · regional
Continuity (1)
Related Publication 20210063361A1 · Mar 4, 2021