Automated clinical diagnostic system and method

Patent metadata

Field	Value
Publication number	US-11275065-B2
Application number	US-201916718296-A
Country	US
Kind code	B2
Filing date	Dec 18, 2019
Priority date	Jul 4, 2017
Publication date	Mar 15, 2022
Grant date	Mar 15, 2022

Abstract

A diagnostic system and method and an interconnected laboratory system comprising clinical diagnostic systems are presented. The diagnostic system comprises a sample preparation module, a liquid chromatography (LC) separation module coupled to the sample preparation module via a sample preparation/LC interface, a mass spectrometer (MS) module coupled to the LC separation module via an LC/MS interface, and a result calculation module for identifying and/or quantifying analytes or substances of interest contained in the samples and passed through the LC separation and MS modules. The diagnostic system comprises a controller programmed to monitor operational parameters (1-n) indicative of a performance status of the diagnostic system, to trigger a quality control procedure and/or a maintenance procedure whenever one or more parameters (1-n) of the operational parameters (1-n) is out of specification, and to minimize the quality control and/or maintenance procedures as long as the operational parameters (1-n) remains within specification.

First claim

We claim:

1. A clinical diagnostic system, the clinical diagnostic system comprising:
a sample preparation module for the automated preparation of samples;
a liquid chromatography (LC) separation module coupled to the sample preparation module via a sample preparation/LC interface;
a mass spectrometer (MS) module coupled to the LC separation module via an LC/MS interface;
a result calculation module for identifying and/or quantifying analytes or substances of interest contained in the samples and passed through the LC separation module and the MS module; and
a controller programmed to monitor a predetermined set of operational parameters ( 1 - n ) indicative of a performance status of the clinical diagnostic system, trigger a quality control procedure and/or a maintenance procedure whenever one or more parameters ( 1 - n ) of the predetermined set of operational parameters ( 1 - n ) is out of specification, and minimize the quality control and/or maintenance procedures as long as the set of operational parameters ( 1 - n ) remains within specification.

2. The clinical diagnostic system according to claim 1 , wherein the predetermined set of operational parameters ( 1 - n ) comprises a first subset based on data from the result calculation module and a second subset based on raw data from the sample preparation module, LC separation module, and MS module.

3. The clinical diagnostic system according to claim 2 , wherein the controller, following a passed quality control procedure, is programmed to trigger one or more of a further quality control procedure and/or maintenance procedure whenever one or more parameters ( 1 - n ) of the first subset of operational parameters ( 1 - n ) is out of specification and to minimize further quality control and/or maintenance procedures as long as the first subset of operational parameters ( 1 - n ) remains within specification.

4. The clinical diagnostic system according to claim 3 , wherein, whenever one or more parameters ( 1 - n ) of the first subset of operational parameters ( 1 - n ) is out of specification, the controller is programmed to check the raw data of the second subset of operational parameters ( 1 - n ) and to trigger one or more of a further quality control procedure and/or maintenance procedure whenever one or more parameters ( 1 - n ) of the second subset of operational parameters ( 1 - n ) is out of specification, and to minimize further quality and/or maintenance procedures as long as the second subset of operational parameters ( 1 - n ) remains within specification.

5. The clinical diagnostic system according to claim 2 , wherein the first subset of operational parameters ( 1 - n ) comprises at least one of shape of LC and/or MS peaks, analyte elution/retention time, ratio of adjacent peak heights, signal/noise ratio, analyte signal intensity, background signal intensity, slope of background signal line, m/z value of peak maximum, m/z mass accuracy, calculated concentration of analyte, calculated concentration of QC substance.

6. The clinical diagnostic system according to claim 5 , wherein the peaks are one or a plurality of any one or more of an analyte peak, an analyte fragment peak or isotope peak, a QC substance peak or reference substance peak added to a sample or to a reagent, or a fragment peak thereof or isotope peak thereof.

7. The clinical diagnostic system according to claim 5 , wherein depending on the operational parameter or parameters ( 1 - n ) that are out of specification the one or more quality control and/or maintenance procedures comprise any one or more of running a calibration procedure and/or a QC sample, adjusting any one or more of LC conditions such as elution gradient, flow rate, pressure and temperature, changing eluents, regenerating or replacing an LC column, re-initialization of the MS module, tuning and calibration of the MS module, adjusting any one or more of the MS conditions such as adjusting of voltages, of gas pressure and temperature in ionization source, cleaning of any parts of the sample preparation module, LC module, MS module, checking and eventually replacing a QC sample.

8. The clinical diagnostic system according to claim 2 , wherein the second subset of operational parameters ( 1 - n ) related to the sample preparation module comprises raw data with respect to at least one of power/energy consumption and/or voltage/amperage of electrically powered functional units, linear and/or rotational velocity and/or position of drive units and/or driven functional units, pressure in fluidic system.

9. The clinical diagnostic system according to claim 8 , wherein depending on the operational parameter or parameters ( 1 - n ) that are out of specification, the one or more quality control and/or maintenance procedures comprise any one or more of running a calibration procedure and/or a QC sample, repairing or exchanging drive units and/or driven functional units or parts thereof, checking for leakage or loose connections and eventually replacing fittings or tightening, checking for clogging, for presence of foam or clot in samples or air in the fluidic system and eventually running an event specific protocol, checking for correct positioning of consumables or for sufficient test fluid volume and eventually exchanging or replacing consumables, checking alignment of drives and eventually re-adjusting alignment.

10. The clinical diagnostic system according to an claim 2 , wherein the second subset of operational parameters ( 1 - n ) related to the LC separation module comprises raw data with respect to at least one of liquid pressure, gas pressure, temperature, flow rate, consumable level, waste level, power/energy consumption and/or voltage/amperage of electrically powered functional units, linear and/or rotational velocity and/or position of drive units and/or driven functional units.

11. The clinical diagnostic system according to claim 10 , wherein depending on the operational parameter or parameters ( 1 - n ) that are out of specification, the one or more quality control and/or maintenance procedures comprise any one or more of running a calibration procedure and/or a QC sample, checking for leakage or loose connections and eventually replacing fittings or tightening, replacing or refilling eluents, regenerating or replacing an LC column, checking and eventually repairing or replacing a heater, checking and eventually repairing or replacing valves or pumps.

12. The clinical diagnostic system according to claim 2 , wherein the second subset of operational parameters ( 1 - n ) related to the MS module comprises raw data with respect to at least one of gas pressure, gas temperature, applied voltages and currents, flow rates, radio frequency.

13. The clinical diagnostic system according to claim 12 , wherein depending on the operational parameter or parameters ( 1 - n ) that are out of specification, the one or more quality control and/or maintenance procedures comprise any one or more of running a calibration procedure and/or a QC sample, checking ionization source clean status, re-tuning of MS module, re-initialization of the MS module, checking and eventually repairing or replacing a flow meter, checking and eventually repairing or replacing an ionization source heater, checking and eventually repairing or replacing a control board.

14. An interconnected laboratory system, the interconnected laboratory system comprising:
a plurality of clinical diagnostic systems according to claim 1 ;
a central data receiving device; and
a central controller, wherein the central data receiving device is configured to receive data from the monitoring of the predetermined set o

Assignees

• Roche Diagnostics Operations Inc

Inventors

• Kobold Uwe
• Paul Hubert
• Rempt Martin

Classifications

• G01N30/88

  Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 · CPC title

• G01N2030/8804

  automated systems · CPC title

• G01N1/405

  by adsorption or absorption · CPC title

• G01N35/0092

  Scheduling · CPC title

• G01N30/72

  Mass spectrometers {(mass spectrometers per se H01J49/00)} · CPC title