Instruments and methods for exposing a receptacle to multiple thermal zones

• US 7,767,447 B2
• Filed: 12/12/2008
• Issued: 08/03/2010
• Est. Priority Date: 06/21/2007
• Status: Active Grant

• Current Assignee: Gen-Probe Incorporated (Hologic Incorporated), Qualigen, Inc.
• Original Assignee: Gen-Probe Incorporated (Hologic Incorporated), Qualigen, Inc.
• Inventors: Poirier, Michael S., Nelson, Norman C., Scott, Matthew J., Taylor, Jason A., Fan, Sara H., Lee, Richard S., Breidenthal, Scott S.
• Primary Examiner(s): Griffin; Walter D
• Assistant Examiner(s): Doe; Shanta G
• Application Number:
  US12/333,484
• Publication Number:
  US 20090142745A1
• Time in Patent Office: 599 Days
• Field of Search: 435/3, 435/286.1, 4352871-2873, 435/288.4, 435/303.1, 435/6, 4352885-2887
• US Class Current: 435/303.1
• CPC Class Codes: B01F 2101/23 Mixing of laboratory samples e.g. in preparation of analysing or testing properties of materials
• CPC Class Codes: B01F 2101/33 Mixing compost ingredients or organic waste
• CPC Class Codes: B01F 23/59 Mixing systems, i.e. flow charts or diagrams
• CPC Class Codes: B01F 31/00 Mixers with shaking, oscillating, or vibrating mechanisms
• CPC Class Codes: B01F 31/31 using receptacles with deformable parts, e.g. membranes, to which a motion is imparted
• CPC Class Codes: B01F 31/65 the materials to be mixed being directly submitted to a pulsating movement, e.g. by means of an oscillating piston or air column
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 35/2131 Colour or luminescence
• CPC Class Codes: B01L 2200/0621 Control of the sequence of chambers filled or emptied
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/14 Process control and prevention of errors
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/123 Flexible; Elastomeric
• CPC Class Codes: B01L 2300/1805 Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2300/1822 : using Peltier elements
• CPC Class Codes: B01L 2300/1883 : using thermal insulation
• CPC Class Codes: B01L 2400/0457 : passive flow or gravitation
• CPC Class Codes: B01L 2400/0478 : pistons
• CPC Class Codes: B01L 2400/0481 : squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0655 : pinch valves
• CPC Class Codes: B01L 2400/0677 : phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
• CPC Class Codes: B01L 3/502 : with fluid transport, e.g. in multi-compartment structures centrifugal-type cuvettes G01N21/07; analysis by separation into components G01N30/00; automatic analysers G01N35/00
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 : characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502761 : specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 3/505 : flexible containers not provided for above
• 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: B01L 7/525 : with physical movement of samples between temperature zones
• CPC Class Codes: C12N 15/1006 : by means of a solid support carrier, e.g. particles, polymers
• CPC Class Codes: C12Q 1/6806 : Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6844 : Nucleic acid amplification reactions
• CPC Class Codes: G01N 1/44 : Sample treatment involving radiation, e.g. heat
• CPC Class Codes: G01N 2021/6419 : Excitation at two or more wavelengths
• CPC Class Codes: G01N 2021/6421 : Measuring at two or more wavelengths
• CPC Class Codes: G01N 2021/6432 : Quenching
• CPC Class Codes: G01N 2021/6439 : with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 2021/6463 : Optics
• CPC Class Codes: G01N 2035/00544 : using fluid flow
• CPC Class Codes: G01N 21/01 : Arrangements or apparatus for facilitating the optical investigation
• CPC Class Codes: G01N 21/6428 : Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/645 : Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 2201/0627 : Use of several LED's for spectral resolution
• 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: Y10T 137/0391 : Affecting flow by the addition of material or energy
• CPC Class Codes: Y10T 436/143333 : Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/255 : including use of a solid sorbent, semipermeable membrane, or liquid extraction

Abstract

A receptacle having a plurality of interconnected chambers arranged to permit multiple process steps or processes to be performed independently or simultaneously. The receptacles are manufactured to separate liquid from dried reagents and to maintain the stability of the dried reagents. An immiscible liquid, such as an oil, is included to control loading of process materials, facilitate mixing and reconstitution of dried reagents, limit evaporation, control heating of reaction materials, concentrate solid support materials to prevent clogging of fluid connections, provide minimum volumes for fluid transfers, and to prevent process materials from sticking to chamber surfaces. The receptacles can be adapted for use in systems having a processing instrument that includes an actuator system for selectively moving fluid substances between chambers and a detector. The actuator system can be arranged to concentrate an analyte present in a sample. The detector can be used to detect an optical signal emitted by the contents of the receptacle.

Claims

1. An instrument for processing a sample in a receptacle having a plurality of interconnected chambers, the instrument being constructed and arranged to support the receptacle in an operative position during the processing and comprising:

one or more thermal elements each defining a multiple chamber thermal zone disposed to be in thermal communication with the receptacle and constructed and arranged to transmit thermal energy between each multiple chamber thermal zone and an associated region of the receptacle, wherein the associated region of the receptacle encompasses all or a portion of each of two or more but less than all chambers of the receptacle; and

a controller programmed to control operation of the one or more thermal elements defining the multiple chamber thermal zones to selectively heat or cool the chambers encompassed within the regions associated with the multiple chamber thermal zones.

2. The instrument of claim 1, further comprising one or more thermal elements defining one or more single chamber thermal zones disposed to be in thermal communication with the receptacle and constructed and arranged to transmit thermal energy between each single chamber thermal zone and an associated region of the receptacle encompassing all or a portion of one chamber of the receptacle, wherein the controller is programmed to control operation of the thermal elements defining the single chamber thermal zones to selectively heat or cool the chambers encompassed within the regions associated with the single chamber thermal zones.

3. The instrument of claim 1, wherein the thermal elements comprise one or more Peltier devices controlled by the controller to selectively heat or cool a body with which the Peltier'"'"' device is in thermal contact.

4. The instrument of claim 1, wherein the thermal elements comprise a heat transfer element formed from a thermally conductive material and having a peripheral shape corresponding to a predetermined shape of a multiple chamber thermal zone defined by the heat transfer element.

5. The instrument of claim 4, further comprising a temperature sensor in thermal communication with the heat transfer element and adapted to sense the temperature of the heat transfer element and communicate the sensed temperature to the controller.

6. The instrument of claim 4, wherein the heat transfer element is held within the instrument in a fixed position with respect to the receptacle.

7. The instrument of claim 4, wherein the heat transfer element is formed from aluminum.

8. The instrument of claim 1, wherein the thermal elements comprise:

one or more Peltier devices controlled by the controller to selectively heat or cool a body with which the Peltier devices are in thermal contact; and

a heat transfer element associated with each multiple chamber thermal zone, said heat transfer element being formed from a thermally conductive material and having a generally flat surface and a peripheral shape corresponding to a predetermined shape of a multiple chamber thermal zone defined by the heat transfer element, wherein the Peltier devices are in thermal contact with the heat transfer element.

9. The instrument of claim 4, wherein the instrument comprises multiple thermal elements, each thermal element being separated from other thermal elements by isolating structure comprising a thermally non-conductive material.

10. The instrument of claim 9, wherein the heat transfer element and the isolating structure are held within the instrument in fixed positions with respect to the receptacle.

11. The instrument of claim 3, further comprising a heat dissipation element constructed and arranged to dissipate heat from the Peltier devices.

12. The instrument of claim 11, wherein the heat dissipation element comprises a heat sink formed from a conductive material and including a block having one side in thermal communication with at least one Peltier device and an opposite side from which heat dissipation fins extend from the block.

13. The instrument of claim 12, wherein the heat dissipation element further comprises a fan disposed adjacent the heat sink and configured to generate an air flow over the heat dissipation fins of the heat sink.

14. The instrument of claim 13, wherein operation of the fan is controlled by the controller.

15. The instrument of claim 12, wherein the heat sink is formed from aluminum.

16. The instrument of claim 1, further comprising one or more temperature sensors for sensing the temperature of each thermal zone and communicating the sensed temperature to the controller.

17. The instrument of claim 1, wherein the controller is configured to control the operation of the thermal elements to establish an ambient temperature within a prescribed temperature range.

18. The instrument of claim 17, wherein the prescribed temperature range is about 20°

C. to 40°

C.

19. The instrument of claim 17, wherein the prescribed temperature range is about 25°

C. to 37°

C.

20. The instrument of claim 1, wherein the controller is configured to control operation of the thermal elements to heat one or more chambers to temperatures within a prescribed temperature range.

21. The instrument of claim 20, wherein the prescribed temperature range encompasses temperatures required to perform a process requiring thermal cycling.

22. The instrument of claim 21, wherein the prescribed temperature range is about 5°

C. to 95°

C.

23. The instrument of claim 21, wherein the process is a PCR amplification reaction.

24. The instrument of claim 1, wherein the controller is configured to control operation of the thermal elements to heat or cool the contents of chambers encompassed within a region associated with the multiple chamber thermal zone to a predetermined temperature for a predetermined period of time.

25. The instrument of claim 1, wherein the one or more thermal elements define at least two multiple chamber thermal zones.

26. The instrument of claim 1, wherein when a receptacle is supported in the operative position within the instrument, filling a chamber encompassed within the region associated with the multiple chamber thermal zone with fluid will increase thermal communication between the chamber and the multiple chamber thermal zone.

43. The instrument of claim 1, wherein the each of the one or more thermal elements comprises a metal plate having a size and shape encompassing all or a portion of each of two or more but less than all chambers of the receptacle.

27. A method for heating or cooling substances within a receptacle having a plurality of interconnected chambers, the method comprising the steps of:

positioning the receptacle in thermal communication with one or more multiple chamber thermal zones contained in an analyzer, each multiple chamber thermal zone being associated with a region of the receptacle encompassing all or a portion of each of two or more but less than all chambers of the receptacle; and

transmitting thermal energy between each multiple chamber thermal zone and the chambers encompassed by the region associated with the multiple chamber thermal zone to selectively heat or cool substances contained within the encompassed chambers to a temperature different than the temperature of the chambers encompassed by at least one other region.

28. The method of claim 27, further comprising positioning the receptacle in thermal communication with one or more single chamber thermal zones contained in the analyzer, each single chamber thermal zone being associated with a region of the receptacle encompassing all or a portion of one chamber of the receptacle.

29. The method of claim 27, wherein the transmitting step comprises heating or cooling the multiple chamber thermal zone with one or more Peltier devices.

30. The method of claim 27, wherein the ambient temperature of the analyzer is different than the temperature of substances contained within chambers encompassed by the regions of the receptacle associated with each multiple chamber thermal zone during the method.

31. The method of claim 27, wherein the transmitting step comprises alternately heating and cooling at least one of the multiple chamber thermal zones.

32. The method of claim 27, further comprising thermally separating each multiple chamber thermal zone from other multiple chamber thermal zones.

33. The method of claim 27, further comprising dissipating heat from the multiple chamber thermal zone.

34. The method of claim 27, further comprising sensing the temperature of each multiple chamber thermal zone.

35. The method of claim 27, further comprising expanding a chamber encompassed by the region of the receptacle associated with a multiple chamber thermal zone to increase the thermal communication between the expanded chamber and the associated multiple chamber thermal zone.

36. The method of claim 27, wherein the analyzer contains at least three multiple chamber thermal zones.

37. The method of claim 27, wherein each of the plurality of interconnected chambers is adjacent to at least one other chamber of the receptacle.

38. The method of claim 27, wherein each of the chambers of the receptacle comprises a flexible portion to facilitate substance movement between chambers.

39. The method of claim 38, wherein the receptacle comprises opposed members, at least one of which members comprises a flexible sheet.

40. The method of claim 39, wherein each of the opposed members comprises a flexible sheet.

41. The method of claim 29, wherein the heat is transferred to/from the multiple chamber thermal zone from/to the Peltier device using a thermal element.

42. The method of claim 41, wherein the thermal element comprises a metal plate having a size and shape encompassing all or a portion of each of two or more but less than all chambers of the receptacle.