Method to monitor and control the temperature of a sample holder of a laboratory instrument

Patent metadata

Field	Value
Publication number	US-11517905-B2
Application number	US-201916516062-A
Country	US
Kind code	B2
Filing date	Jul 18, 2019
Priority date	Jul 24, 2018
Publication date	Dec 6, 2022
Grant date	Dec 6, 2022

Abstract

A method to monitor and control the temperature of a sample holder of a laboratory instrument during execution of a temperature profile on the sample holder is presented. The laboratory instrument comprises a sample holder with high temperature uniformity and at least three identical temperature sensors. The measured actual temperatures of the sample holder are processed in order to determine if the execution of the temperature profile should be continued or aborted. Furthermore, temperature sensors which measure actual temperatures that do not fulfil certain requirements are excluded from further monitoring and controlling the temperature of a sample holder.

First claim

The invention claimed is:

1. A method to monitor and control the temperature of a sample holder of a laboratory instrument during execution of a temperature profile on the sample holder, wherein the laboratory instrument comprises a sample holder with high temperature uniformity, a thermoelectric element which is in thermal contact with the sample holder, and a control device, wherein the sample holder comprises at least three identical temperature sensors, wherein the temperature profile comprises at least one set-point temperature, wherein the execution of the temperature profile on the sample holder comprises heating or cooling of the sample holder to the at least one set-point temperature for a predefined time duration and at a predefined time point,
the method comprising the following steps:
a) controlling, via the control device, the thermoelectric element to heat or cool the sample holder to the at least one set-point temperature of the temperature profile;
b) measuring, via the at least three identical temperature sensors, at least three actual temperatures of the sample holder and transmit the at least three measured actual temperatures to the control device;
c) comparing, via the control device, the at least three measured actual temperatures with a predefined maximum permissible temperature deviation range from the at least one set-point temperature;
d) calculating, via the control device, at least three temperature differences between each of the at least three measured actual temperatures;
e) comparing, via the control device, each of the at least three calculated temperature differences with a predefined maximum permissible temperature difference range;
f) determining, via the control device, a further execution step selected from: (i) continuing to execute the temperature profile on the sample holder if at least two of the measured actual temperatures are within the predefined maximum permissible temperature deviation range from the at least one set-point temperature and if at least one of the at least three calculated temperature differences is within the predefined maximum permissible temperature difference range; or (ii) aborting execution of the temperature profile on the sample holder if less than two of the measured actual temperatures are within the predefined maximum permissible temperature deviation range from the at least one set-point temperature and if none of the at least three calculated temperature differences is within the predefined maximum permissible temperature difference range.

2. The method according to claim 1 , wherein steps a) to f) are repeated when the control device determines to continue execution of the temperature profile on the sample holder or starts execution of a subsequent temperature profile on the sample holder.

3. The method according to claim 2 , wherein one of the at least three identical temperature sensors is excluded from the repetition of steps a) to f) when the measured temperature of said temperature sensor is outside of the predefined maximum permissible temperature range or results in at least two calculated temperature differences which are not within the predefined maximum permissible temperature difference range.

4. The method according to claim 3 , wherein the control device further comprises a user interface, wherein if the number of remaining temperature sensors decreases to two temperature sensors, the method further comprises displaying a user notification via the user interface regarding a decrease in the number of remaining temperature sensors.

5. The method according to claim 4 , wherein the user interface is a display, wherein the user notification is displayed on the display and comprises a prompt for preventive maintenance, a warning indicating that exclusion of a further temperature sensor will result in an immediate abort of execution of the temperature profile on the sample holder, or a user interface control element which can be selected by a user in order to continue the execution of the temperature profile on the sample holder or to start a subsequent temperature profile on the sample holder, or a combination thereof.

6. The method according to claim 1 , wherein the temperature profile is executed on the sample holder for performing a temperature-dependent reaction of a test sample, wherein the sample holder comprises at least one recess which is configured to receive a sample vessel comprising a test sample, wherein prior to step a) of the method the at least one sample vessel comprising the test sample is inserted into the at least one recess.

7. The method according to claim 6 , wherein the temperature-dependent reaction of the test sample comprises heating or cooling of the test sample to at least one predefined test sample temperature for a predefined time duration, wherein the at least one predefined test sample temperature and the at least one set-point temperature of the temperature profile is the same or different.

8. The method according to claim 6 , wherein the temperature-dependent reaction of the test sample is a nucleic acid amplification reaction.

9. The method according to claim 1 , wherein the temperature profile is executed on the sample holder for performing a functional test of the thermoelectric element and sample holder, wherein the method is executed during the startup of the laboratory instrument, wherein the temperature profile comprises only one set-point temperature.

10. The method according to claim 1 , wherein the control of the thermoelectric element in step a) comprises the following sub-steps if the control device determines to continue the execution of the temperature profile on the sample holder in step f):
g) calculating, via the control device, an average of the at least two measured actual temperatures which are within the predefined maximum permissible temperature deviation range from the at least one set-point temperature and result in at least one calculated temperature difference which is within the predefined maximum permissible temperature difference range;
h) comparing, via the control device, the calculated average of the at least two measured actual temperatures with the at least one set-point temperature of the temperature profile;
i) determining, via the control device, a deviation between the calculated average of the at least two measured actual temperatures and the at least one set-point temperature of the temperature profile; and
j) adjusting, via the control device, heating or cooling of the thermoelectric element according to the determined deviation between the calculated average of the at least two measured actual temperatures and the at least one set-point temperature of the temperature profile.

Assignees

• Roche Molecular Systems Inc

Inventors

• Ebert Sven
• Federer Paul
• Hermann Pius
• Vollenweider Stefan

Classifications

• B01L2200/147

  Employing temperature sensors · CPC title

• B01L2300/1822

  using Peltier elements · CPC title

• G01N25/00

  Investigating or analyzing materials by the use of thermal means (G01N3/00 - G01N23/00 take precedence) · CPC title

• C12Q1/6806 Primary

  Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay (C12Q1/6804 takes precedence) · CPC title

• B01L2300/1827

  using resistive heater · CPC title