Multi-Chambered Receptacles

• US 20090137029A1
• Filed: 12/12/2008
• Published: 05/28/2009
• 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: Nelson, Norman C., Scott, Matthew J., Taylor, Jason A., Lee, Richard S., Breidenthal, Scott S.
• Granted Patent: US 10,744,469 B2
• Time in Patent Office: Days
• US Class Current: 435/287.200
• 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. A multi-chambered receptacle for use in processing a sample, the receptacle comprising:

a first linear path of chambers interconnected by a plurality of openable connections and comprising;

first and second chambers connected by a first openable connection, the first and second chambers and the first openable connection being constructed and arranged to permit substance movement from the first chamber to the second chamber when a substance-moving force is applied to the contents of the first chamber and the first openable connection has been altered from a closed state to an open state;

third and fourth chambers connected by a second openable connection, the third and fourth chambers and the second openable connection being constructed and arranged to permit substance movement from the third chamber to the fourth chamber when a substance-moving force is applied to the contents of the third chamber and the second openable connection has been altered from a closed state to an open state;

an intermediate chamber between the second and fourth chambers,

wherein the intermediate chamber is directly or indirectly connected to the second chamber by a third openable connection, the second and intermediate chambers and the third openable connection being constructed and arranged to permit substance movement from the second chamber to or toward the intermediate chamber when a substance-moving force is applied to the contents of the second chamber and the third openable connection has been altered from a closed state to an open state,

wherein the intermediate chamber is directly or indirectly connected to the fourth chamber by a fourth openable connection, the fourth and intermediate chambers and the fourth openable connection being constructed and arranged to permit substance movement from the fourth chamber to or toward the intermediate chamber when a substance-moving force is applied to the contents of the fourth chamber and the fourth openable connection has been altered from a closed state to an open state,

wherein the first linear path of chambers is constructed and arranged so that if a substance-moving force is applied to the contents of the first chamber, then the third openable connection is not altered from a closed state to an open state,

wherein the first linear path of chambers is constructed and arranged so that if a substance-moving force is applied to the contents of the third chamber, then the fourth openable connection is not altered from a closed state to an open state, and

wherein the second and fourth chambers are not interconnected by any arrangement of chambers that does not include the intermediate chamber; and

a sample inlet port for receiving sample into a sample receiving chamber, provided that if the sample receiving chamber is a chamber of the first linear path, then the sample receiving chamber is between the second and fourth chambers.

2. The receptacle of claim 1 further comprising second and third linear paths of chambers, the chambers of each of the second and third linear paths being interconnected by a plurality of openable connections and comprising a sixth chamber connected to a first process chamber by a fifth openable connection, the first process chamber being any chamber of the first linear path that is located between the first and third chambers, and the sixth and first process chambers and the fifth openable connection being constructed and arranged to permit substance movement from the sixth chamber to the first process chamber when a substance-moving force is applied to the contents of the sixth chamber and the fifth openable connection has been altered from a closed state to an open state, wherein the second linear path comprises the first chamber but not the third chamber of the first linear path, and wherein the third linear path comprises the third chamber but not the first chamber of the first linear path.

3. The receptacle of claim 2, wherein one or more chambers of the second and third linear paths comprises a solid support for immobilizing an analyte in the sample.

4. The receptacle of claim 3, wherein the solid support comprises a magnetically-responsive particle or bead.

5. The receptacle of claim 3, wherein the sixth chamber comprises the solid support.

6. The receptacle of claim 3, wherein the first process chamber comprises the solid support.

7. The receptacle of claim 2, wherein the intermediate chamber is the first process chamber.

8. The receptacle of claim 2, wherein the intermediate chamber is the sample receiving chamber.

9. The receptacle of claim 2, wherein the sixth chamber is the sample receiving chamber.

10. The receptacle of claim 2 further comprising a seventh chamber connected to the sixth chamber by a sixth openable connection, the sixth and seventh chambers and the sixth openable connection being constructed and arranged to permit substance movement from the seventh chamber to the sixth chamber when a substance-moving force is applied to the contents of the seventh chamber and the sixth openable connection has been altered from a closed state to an open state.

11. The receptacle of claim 10, wherein one or more chambers of the second and third linear paths comprises a solid support for immobilizing an analyte in the sample.

12. The receptacle of claim 11, wherein the solid support comprises a magnetically-responsive particle or bead.

13. The receptacle of claim 11, wherein the sixth chamber comprises the solid support.

14. The receptacle of claim 11, wherein the seventh chamber comprises the solid support.

15. The receptacle of claim 10, wherein the sixth chamber is the sample receiving chamber.

16. The receptacle of claims 10 further comprising a fourth linear path of chambers interconnected by a plurality of openable connections and comprising:

an eighth chamber connected to a second process chamber of at least one of the second and third linear paths by a seventh openable connection, the eighth and second process chambers and the seventh openable connection being constructed and arranged to permit substance movement from the eighth chamber to the second process chamber when a substance-moving force is applied to the contents of the eighth chamber and the seventh openable connection has been altered from a closed state to an open state;

a ninth chamber connected to the second process chamber by an eighth openable connection, the ninth and second process chambers and the eighth openable connection being constructed and arranged to permit substance movement from the second process chamber to the ninth chamber when a substance-moving force is applied to the contents of the second process chamber and the eighth openable connection has been altered from a closed state to an open state, wherein the fourth linear path does not include a chamber of the second or third linear paths other than the second process chamber.

17. The receptacle of claim 16, wherein the second process chamber is adjacent the sample receiving chamber.

18. The receptacle of claim 16, wherein the second process chamber is the sample receiving chamber.

19. The receptacle of claim 16, wherein the eighth chamber contains a wash solution for removing unwanted material from the sample.

20. The receptacle of claim 16, wherein the ninth chamber is substantially void.

21. The receptacle of claim 16 further comprising a tenth chamber connected to the intermediate chamber by a ninth openable connection, the tenth and intermediate chambers and the ninth openable connection being constructed and arranged to permit substance movement from the tenth chamber to the intermediate chamber when a substance-moving force is applied to the contents of the tenth chamber and the ninth openable connection has been altered from a closed state to an open state, wherein the first linear path does not comprise the tenth chamber.

22. The receptacle of claim 1, wherein each of the chambers of the receptacle comprises a flexible portion to facilitate substance movement between chambers.

23. The receptacle of claim 22, wherein the receptacle comprises opposed members, at least one of which members comprises a flexible sheet.

24. The receptacle of claim 23, wherein each of the opposed members comprises a flexible sheet.

25. The receptacle of claim 24, wherein at least one of the flexible sheets comprises a foil layer.

26. The receptacle of claim 23, wherein the openable connections are blocked by burstable seals in closed states to prevent substance movement between chambers.

27. The receptacle of claim 26, wherein the chambers are defined by permanent seals.

28. The receptacle of claim 27, wherein the burstable seals and the permanent seals are heat seals.

29. The receptacle of claim 28, wherein the burstable seals and the permanent seals are formed under different conditions, such that the burstable seals are weaker than the permanent seals.

30. The receptacle of claim 29, wherein the burstable seals are chevron seals.

31. The receptacle of claim 1, wherein at least one of the openable connections is constructed and arranged to be altered from the closed state to the open state by a substance-moving force applied to a flexible portion of an adjacent chamber.

32. The receptacle of claim 1, wherein the volume capacity of the sample receiving chamber is greater than the volume capacity of any chamber directly connected to the sample receiving chamber that is other than an end chamber.

33. The receptacle of claim 1, wherein at least one of the chambers is constructed and arranged to enable detection of a characteristic of a sample.

34. The receptacle of claim 33, wherein the detection includes determining the existence or amount of a signal indicative of the characteristic of the sample.

35. The receptacle of claim 33, wherein the detection chamber contains one or more probes immobilized on an interior surface of the detection chamber, each of the probes being capable of forming a detectable probe:

target complex with a target nucleic acid.

36. The receptacle of claim 35, wherein each of the probes includes a detectable label.

37. The receptacle of claim 35, wherein each of the probes includes a pair of interacting labels capable of differentiating between bound and unbound probe.

38. The receptacle of claim 1, wherein at least one of the first and second chambers contains a process material.

39. The receptacle of claim 38, wherein the first chamber contains a first process material and the second chamber contains a second process material.

40. The receptacle of claim 39, wherein the second process material is a first dried reagent and the first process material is a first reconstitution reagent for reconstituting the first dried reagent.

41. The receptacle of claim 40, wherein the first dried reagent is a lyophilized reagent.

42. The receptacle of claim 40, wherein at least a portion of the second chamber is constructed of optically transparent materials, thereby permitting the contents of the second chamber to be interrogated by an optical sensor.

43. The receptacle of claim 1, wherein at least one of the third and fourth chambers contains a process material.

44. The receptacle of claim 43, wherein the third chamber contains a third process material and the fourth chamber contains a fourth process material.

45. The receptacle of claim 44, wherein the fourth process material is a second dried reagent and the third process material is a second reconstitution reagent for reconstituting the second dried reagent.

46. The receptacle of claim 45, wherein the second dried reagent is a lyophilized reagent.

47. The receptacle of claim 45, wherein at least a portion of the second chamber is constructed of optically transparent materials, thereby permitting the contents of the second chamber to be interrogated by an optical sensor.

48. The receptacle of claim 45, wherein the first dried reagent is an amplification reagent and the second dried reagent is an enzyme reagent, the first and second dried reagents being useful for performing a nucleic acid-based amplification reaction.

49. The receptacle of claim 48, wherein at least one of the amplification and enzyme reagents comprises one or more probes, each of the probes being capable of forming a detectable probe:

target complex with a product of the nucleic acid-based amplification reaction.

50. The receptacle of claim 49, wherein the enzyme reagent comprises the one or more probes.

51. The receptacle of claim 49, wherein each of the probes includes a detectable label.

52. The receptacle of claim 51, wherein each of the probes includes a pair of interacting labels capable of differentiating between bound and unbound probe.

53. The receptacle of claim 1, wherein the receptacle is held within a sealed container.

54. The receptacle of claim 53, wherein the container further holds a desiccant.

55. The receptacle of claim 1, wherein the chambers of the receptacle have a radial arrangement, and wherein the end chambers of the receptacle have a non-circular arrangement.

56. The receptacle of claim 1, wherein each of the plurality of interconnected chambers is adjacent to at least one other chamber of the receptacle.

57. The receptacle of claim 1, wherein the sample inlet port is closed with a Luer connection.