System and method for controlling thermal cycler modules

• US 9,140,715 B2
• Filed: 01/23/2013
• Issued: 09/22/2015
• Est. Priority Date: 07/23/2010
• Status: Expired due to Fees

• Current Assignee: Beckman Coulter Incorporated (Danaher Corporation)
• Original Assignee: Beckman Coulter Incorporated (Danaher Corporation)
• Inventors: Wilson, Brian D., Davis, Matthew S., Johnson, Alan N., Maurer, Garrick A.
• Primary Examiner(s): MARSCHEL, ARDIN H
• Application Number:
  US13/747,952
• Publication Number:
  US 20130143199A1
• Time in Patent Office: 972 Days
• Field of Search: 435/91.2
• US Class Current: 1/1
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/0642 Filling fluids into wells by specific techniques
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/022 Transponder chips
• CPC Class Codes: B01L 2300/024 Storing results with means integrated into the container
• CPC Class Codes: B01L 2300/042 Caps; Plugs
• CPC Class Codes: B01L 2300/044 pierceable, e.g. films, membranes
• CPC Class Codes: B01L 2300/045 whereby the whole cover is slidable
• CPC Class Codes: B01L 2300/046 Function or devices integrated in the closure
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0851 Bottom walls
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 2300/18 Means for temperature control
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 3/021 Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
• CPC Class Codes: B01L 3/0275 : Interchangeable or disposable dispensing tips
• CPC Class Codes: B01L 3/50825 : Closing or opening means, corks, bungs closures for containers B65D; means for removing stoppers B67B7/02
• CPC Class Codes: B01L 3/5085 : for multiple samples, e.g. microtitration plates
• CPC Class Codes: B01L 3/50851 : specially adapted for heating or cooling samples laboratory heating apparatus B01L7/00; incubators C12M
• CPC Class Codes: B01L 3/52 : Containers specially adapted for storing or dispensing a reagent B01L3/02 takes precedence; containers for medical or pharmaceutical purposes A61J1/00; containers in general B65D; storing or dispensing test elements G01N33/4875; automated reagent dispensing G01N35/1002
• CPC Class Codes: B01L 3/545 : for laboratory containers
• CPC Class Codes: B01L 7/52 : with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: C12M 41/12 : of temperature controlling the temperature of chemical or physical processes B01J19/0013, heating or cooling apparatus for laboratory use B01L7/00
• CPC Class Codes: C12P 19/34 : Polynucleotides, e.g. nucleic acids, oligoribonucleotides
• CPC Class Codes: C12Q 1/68 : involving nucleic acids
• CPC Class Codes: C12Q 1/686 : Polymerase chain reaction [PCR]
• CPC Class Codes: C12Q 3/00 : Condition responsive control processes apparatus therefor C12M1/36; controlling or regulating in general G05
• CPC Class Codes: G01F 23/24 : by measuring variations of resistance of resistors due to contact with conductor fluid
• CPC Class Codes: G01F 23/26 : by measuring variations of capacity or inductance of capacitors or inductors arising from the presence of liquid or fluent solid material in the electric or electromagnetic fields
• CPC Class Codes: G01N 1/31 : Apparatus therefor
• CPC Class Codes: G01N 1/38 : Diluting, dispersing or mixing samples
• CPC Class Codes: G01N 2035/00435 : Refrigerated reagent storage
• CPC Class Codes: G01N 2035/00752 : bar codes
• CPC Class Codes: G01N 2035/00851 : process control parameters
• CPC Class Codes: G01N 2035/0413 : moving in one dimension
• CPC Class Codes: G01N 2035/0415 : moving in two dimensions in a horizontal plane
• CPC Class Codes: G01N 2035/0436 : with pre-packaged reagents, i.e. test-packs
• CPC Class Codes: G01N 2035/0465 : Loading or unloading the conveyor
• CPC Class Codes: G01N 2035/0475 : electric, e.g. stepper motor, solenoid
• CPC Class Codes: G01N 2035/1013 : Confirming presence of tip
• CPC Class Codes: G01N 2035/1025 : Fluid level sensing
• CPC Class Codes: G01N 2035/1048 : using the transfer device for another function
• CPC Class Codes: G01N 2035/1051 : for transporting containers, e.g. retained by friction
• CPC Class Codes: G01N 2035/1076 : plurality or independently movable heads
• CPC Class Codes: G01N 35/00732 : Identification of carriers, materials or components in automatic analysers
• CPC Class Codes: G01N 35/0092 : Scheduling
• CPC Class Codes: G01N 35/0098 : involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C
• CPC Class Codes: G01N 35/04 : Details of the conveyor system G01N35/021 - G01N35/028 take precedence
• CPC Class Codes: G01N 35/1002 : Reagent dispensers
• CPC Class Codes: G01N 35/1011 : Control of the position or alignment of the transfer device
• CPC Class Codes: G01N 35/1016 : Control of the volume dispensed or introduced
• CPC Class Codes: G01N 35/1081 : characterised by the means for relatively moving the transfer device and the containers in an horizontal plane G01N35/1011 takes precedence
• CPC Class Codes: G05B 13/02 : electric
• CPC Class Codes: G05B 13/0205 : not using a model or a simulator of the controlled system
• CPC Class Codes: G16B 25/20 : Polymerase chain reaction [PCR]; Primer or probe design; Probe optimisation
• CPC Class Codes: G16B 99/00 : Subject matter not provided for in other groups of this subclass
• CPC Class Codes: Y10T 436/113332 : with conveyance of sample along a test line in a container or rack

Abstract

Systems and methods for processing and analyzing samples are disclosed. The system may process samples, such as biological fluids, using assay cartridges which can be processed at different processing locations. In some cases, the system can be used for PCR processing. The different processing locations may include a preparation location where samples can be prepared and an analysis location where samples can be analyzed. To assist with the preparation of samples, the system may also include a number of processing stations which may include processing lanes. During the analysis of samples, in some cases, thermal cycler modules and an appropriate optical detection system can be used to detect the presence or absence of certain nucleic acid sequences in the samples. The system can be used to accurately and rapidly process samples.

Claims

1. A method for operating thermal cycler modules, the method comprising:

obtaining a predetermined temperature vs. time profile of a sample in a selected thermal cycler module in an array of thermal cycler modules, the array of thermal cycler modules comprising the selected thermal cycler module and a set of thermal cycler modules; and

controlling, by a processor, all of the thermal cycler modules in the array of thermal cycler modules so that temperature vs. time profiles for samples in the thermal cycler modules in the array match the predetermined temperature vs. time profile, each of the thermal cycler modules in the array of thermal cycler modules being controlled in response to a source of variation between the thermal cycler modules in the array.

2. The method of claim 1 wherein the source of variation comprises an ambient temperature of the thermal cycler module, or a physical characteristic of the thermal cycler module.

3. The method of claim 1 wherein controlling the thermal cycler modules comprises, for each module, adjusting h_a, which is a thin film heater output at an ambient temperature (°

C/second) and k, which is a rate of heat transfer, using the following equation;

dB/dt=h_a+k(Ta−

B(t)),where

dB/dt=change in block temp in degrees per second,

Ta=ambient temperature (°

C.),

h_a=thin film heater output at ambient temperature (°

C./second),

k=rate of heat transfer, and

B(t)=the temperature of the thermal block at a given time t.

4. The method of claim 3 wherein B(t)=(B(0)−

(h_a/k)−

Ta)e^kt+(h_a/k)+Ta, where B(0)=starting block temperature at time=0.

5. The method of claim 3 wherein k is adjusted using a blower.

13. The method of claim 1 wherein the thermal cycler module comprises a blower to cool the sample and a thin film heater to heat the sample.

14. The method of claim 1 wherein the selected thermal cycler module comprises a thermal block holding a reaction vessel containing the sample, and wherein the method further comprises, prior to obtaining the predetermined temperature vs. time profile:

performing a thermal cycling process on the sample in the reaction vessel using the selected thermal cycler module.

15. The method of claim 14 wherein the thermal cycling process cycles the temperature of the thermal block between about 70°

C. and about 95°

C.

6. A method of driving a first thermal cycler module in a predetermined thermal profile (B(t)), the first thermal cycler module including a thermal block, a heater thermally coupled to the thermal block, and a blower to direct air to the thermal block, the method comprising:

determining a rate of change of the thermal block temperature with respect to time (dB/dt) as a function of heater output (h_a), of blower heat transfer (k), and of ambient temperature (Ta);

measuring the thermal block temperature;

measuring the ambient temperature at the first thermal cycler module; and

adjusting, by a processor, one of the heater output and the blower heat transfer according to a modeled relationship of;

dB/dt=h_a+k(Ta−

B(t)).

7. The method of claim 6 wherein the step of adjusting one of the heater output and the blower heat transfer includes adjusting the heater output and the blower heat transfer.

8. The method of claim 7 wherein the first thermal cycler module includes the processor and a memory, the processor sensing the thermal block temperature and the ambient temperature, and the memory including a representation of the predetermined thermal profile and a representation of the modeled relationship.

9. The method of claim 8 wherein the processor controls the blower heat transfer by adjusting the power supplied to the blower.

10. The method of claim 9 wherein the same predetermined thermal profile is determined through evaluation of the rate of change of the thermal block temperature with respect to time as a function of heater output, of blower heat transfer, and of ambient temperature of a plurality of thermal cycler modules and selection of a thermal profile achievable by each of the plurality of thermal cycler modules as the predetermined profile.

11. The method of claim 10 wherein the response of the first thermal cycler module matches the response of a second thermal cycler module.

12. The method of claim 11 wherein first thermal cycler module is disposed adjacent the second thermal cycler module.

16. A system comprising:

an array of thermal cycler modules;

a processor; and

a computer readable medium coupled to the processor, the computer readable medium comprising code, executable by the processor, to implement a method comprising obtaining a predetermined temperature vs. time profile of a sample in a selected thermal cycler module in the array of thermal cycler modules, the array of thermal cycler modules comprising the selected thermal cycler module and a set of thermal cycler modules, and

controlling all of the thermal cycler modules in the array of thermal cycler modules so that temperature vs. time profiles for samples in the thermal cycler modules in the array match the predetermined temperature vs. time profile, each of the thermal cycler modules in the array of thermal cycler modules being controlled in response to a source of variation between the thermal cycler modules in the array.

17. The system of claim 16 wherein controlling the thermal cycler modules comprises, for each module, adjusting h_a, which is a thin film heater output at an ambient temperature (°

C./second) and k, which is a rate of heat transfer, using the following equation;

dB/dt=h_a+k(Ta−

B(t)),where

dB/dt=change in block temp in degrees per second,

Ta=ambient temperature (°

C.),

h_a=thin film heater output at ambient temperature (°

C./second),

k=rate of heat transfer, and

B(t)=the temperature of the thermal block at a given time t.

18. The system of claim 16 wherein each of the thermal cycler modules in the array of thermal cycler modules comprises a blower and a heater.

19. A system comprising:

a thermal cycler module comprising a thermal block, a heater thermally coupled to the thermal block, and a blower to direct air to the thermal block;

a processor; and

a computer readable medium, the computer readable medium comprising code, executable by the processor, to implement a method comprising determining a rate of change of the thermal block temperature with respect to time (dB/dt) as a function of heater output (h_a), of blower heat transfer (k), and of ambient temperature (Ta),

measuring the thermal block temperature,

measuring the ambient temperature at the first thermal cycler module, and

adjusting one of the heater output and the blower heat transfer according to a modeled relationship of;

dB/dt=h_a+k(Ta−

B(t)).

20. The system of claim 19 wherein the step of adjusting one of the heater output and the blower heat transfer includes adjusting the heater output and the blower heat transfer.

21. A method comprising:

obtaining a predetermined temperature ramping time; and

controlling, by a processor, thermal cycler modules in a set of thermal cycler modules so that the temperature ramping time for each thermal cycler module in the set of thermal cycler modules match the predetermined temperature ramping time, each of the thermal cycler modules in the set of thermal cycler modules being controlled in response to a source of variation between the thermal cycler modules in the set.

22. The method of claim 21 wherein the thermal cycler modules comprise heaters, and wherein the processor controls the heaters in the thermal cycler modules during controlling.

23. A system comprising:

an array of thermal cycler modules including a set of thermal cycler modules;

a processor; and

a computer readable medium coupled to the processor, the computer readable medium comprising code, executable by the processor for implementing a method comprising

obtaining a predetermined temperature ramping time, and

controlling the thermal cycler modules in the set of thermal cycler modules so that the temperature ramping time for each thermal cycler module in the set matches the predetermined temperature ramping time, each of the thermal cycler modules in the set of thermal cycler modules being controlled in response to a source of variation between the thermal cycler modules in the set.

24. The system of claim 23 wherein the thermal cycler modules comprise heaters, and wherein the processor controls the heaters in the thermal cycler modules during controlling.