System and method including thermal cycler modules

• US 8,962,308 B2
• Filed: 01/23/2013
• Issued: 02/24/2015
• 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., Erickson, Matthew D., Johnson, Alan N., Maurer, Garrick A., Sauerburger, Mark F., Schmidt, Daniel R., Wiltsie, Joshua D., Yang, David L., Alaruri, Sami D., Stachelek, Thomas M.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): WHATLEY, BENJAMIN R
• Application Number:
  US13/747,722
• Publication Number:
  US 20130137164A1
• Time in Patent Office: 762 Days
• Field of Search: 422/63, 435/286.1, 435/287.2
• US Class Current: 435/287.2
• 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 system comprising:

a plurality of thermal cycler modules, each thermal cycler module including;

a thermal block having a top surface and a receptacle, the receptacle tapered to conform to a reaction vessel;

a heater thermally coupled to the thermal block;

a temperature sensor thermally coupled to the thermal block;

a temperature controller electrically coupled to the heater and to the temperature sensor and configured to cycle the thermal block between at least two temperatures independently of other thermal blocks in other thermal cycler units;

an excitation optics assembly, the excitation optics assembly configured to pass excitation light to the reaction vessel when the reaction vessel is located in the receptacle in the thermal block;

an emission optics assembly, the emission optics assembly configured to receive light from the reaction vessel when the reaction vessel is located in the receptacle in the thermal block; and

a lid coupled to the thermal block;

wherein the lid is capable of being in an open position and a closed position, and wherein the lid is configured to displace the reaction vessel from the thermal block as it moves from the closed position to the open position.

2. The system of claim 1, wherein the heater is a thin film heater.

3. The system of claim 1, wherein the temperature sensor comprises a thermistor.

4. The system of claim 1, wherein the system is for determining a nucleic acid in a sample in the reaction vessel.

5. The system of claim 1, wherein the receptacle is conical.

6. The system of claim 1, wherein the movable lid includes a tapered ridge to displace the reaction vessel from the receptacle.

7. A system comprising:

a gantry;

a slide lock manipulator coupled to the gantry and comprising an actuator and a gripping feature at an end of the actuator; and

a plurality of thermal cycler modules, each thermal cycler module including;

a thermal block having a top surface and a defining a receptacle, the receptacle tapered to conform to a reaction vessel;

a heater thermally coupled to the thermal block;

a temperature sensor thermally coupled to the thermal block;

a temperature controller electrically coupled to the heater and to the temperature sensor and configured to cycle the thermal block between at least two temperatures;

an excitation optics assembly, the excitation optics assembly configured to pass excitation light to the reaction vessel when the reaction vessel is located in the receptacle in the thermal block;

an emission optics assembly, the emission optics assembly is configured to receive light from the reaction vessel when the reaction vessel is located in the receptacle in the thermal block;

a detector optically coupled to the emission optics assembly of each of the plurality of thermal cycler modules, the detector configured to detect light received by each emission optics assembly,

a lid arranged about the thermal block, the lid capable of being in an open position and a closed position,

wherein the closed position covers the reaction vessel when the reaction vessel is disposed in the receptacle, and

wherein the lid is configured to be opened and closed by the gripping feature of the slide lock manipulator.

8. The system of claim 7, wherein the heater is a thin film heater.

9. The system of claim 7, wherein the temperature sensor comprises a thermistor.

10. The system of claim 7, wherein the system is for determining a nucleic acid in a sample in the reaction vessel.

11. The system of claim 7, wherein the receptacle is conical.

12. The system of claim 7, wherein the lid is configured to displace the reaction vessel from the thermal block when the lid moves from the closed position to the open position.

13. The system of claim 7, further comprising a mandrel coupled to the gantry, and a preparation lane, the preparation lane configured to support a cartridge, the cartridge including a reaction well and a first compartment coupled to the reaction well, wherein the mandrel is configured to transport the reaction vessel from the first compartment to the thermal block.

14. The system of claim 13, further comprising the reaction vessel and the cartridge, wherein the reaction vessel includes a vessel plug and a vessel base, the vessel plug having a gripping feature complementary to the mandrel, and wherein the vessel plug is lockingly mateable to the vessel base,

wherein the cartridge further includes a second compartment coupled to the reaction well, a vessel base in the first compartment, and a vessel plug in the second compartment, and

wherein the mandrel is configured to remove the vessel plug from the second compartment and mate the vessel plug to the vessel base in the first compartment.

15. The system of claim 14, wherein the gantry is configured:

to position the mandrel to remove the vessel plug from the second compartment;

to position the mandrel to mate the vessel plug to the vessel base in the first compartment;

to position the actuator to move the lid from the closed position to the open position;

to position the mandrel to seat the reaction vessel in the thermal block; and

to position the actuator to move the lid from the open position to the closed position.

16. The system of claim 7, wherein the lid further includes a fluorescent target and the lid in the closed position disposes the fluorescent target adjacent to the thermal block.

17. The system of claim 7, wherein the movable lid overlaps with the thermal block.

21. The system of claim 17, wherein the movable lid comprises a compression head.

22. The system of claim 17, wherein the movable lid further comprises an elongated aperture.

23. The system of claim 17,

wherein the excitation optics assembly comprises an excitation lens, an optical filter, and an excitation optical fiber, and

wherein the emission optics assembly comprises an emission lens, an optical filter, and an emission optical fiber.

24. The system of claim 17, wherein when the movable lid moves from a closed position to the open position, the PCR reaction vessel is dislodged from the receptacle.

25. The system of claim 24, wherein the movable lid includes a tapered ridge to dislodge the PCR reaction vessel from the receptacle.

26. The system of claim 17, wherein the movable lid is a slidable lid.

18. A system comprising:

a plurality of thermal cycler modules, each thermal cycler module including;

a thermal block having a top surface and a defining a receptacle, the receptacle tapered to conform to a reaction vessel;

a heater thermally coupled to the thermal block;

a temperature sensor thermally coupled to the thermal block;

a temperature controller electrically coupled to the heater and to the temperature sensor and configured to cycle the thermal block between at least two temperatures;

an excitation optics assembly, the excitation optics assembly configured to pass excitation light to the reaction vessel when the reaction vessel is located in the receptacle in the thermal block;

an emission optics assembly, the emission optics assembly is configured to receive light from the reaction vessel when the reaction vessel is located in the receptacle in the thermal block;

a detector optically coupled to the emission optics assembly of each of the plurality of thermal cycler modules, the detector configured to detect light received by each emission optics assembly; and

a movable lid, wherein the movable lid overlaps with the thermal block,

wherein the movable lid further comprises a spring shutter, the spring shutter capable of being positioned within the emission optics assembly when the movable lid is in an open position.

19. The system of claim 18, wherein the spring shutter is responsive to movement of the movable lid.

20. The system of claim 18, wherein the spring shutter is compressible.