Methods for manipulating liquid substances in multi-chambered receptacles

• US 8,784,745 B2
• Filed: 06/24/2013
• Issued: 07/22/2014
• Est. Priority Date: 06/21/2007
• Status: Active Grant

• Current Assignee: Gen-Probe Incorporated (Hologic Incorporated)
• Original Assignee: Gen-Probe Incorporated (Hologic Incorporated)
• Inventors: Nelson, Norman C., Roma, Gianluca
• Primary Examiner(s): SOOHOO, TONY GLEN
• Application Number:
  US13/925,047
• Publication Number:
  US 20140004517A1
• Time in Patent Office: 393 Days
• Field of Search: 422/198, 422/199, 422/208, 422/307, 422/308, 435/91.2, 435/303.1, 435/305.1, 435/305.2, 366/144
• US Class Current: 422/198
• 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. The detector can be used to detect an optical signal emitted by contents of the receptacle.

Claims

1. A method of altering the temperature of a liquid substance contained in a chamber of a receptacle, the method comprising the steps of:

(a) forming a volume in a first chamber of a receptacle so that a flexible portion of a first chamber wall expands to contact a stationary thermal element positioned adjacent to the first chamber, wherein the volume comprises a liquid substance and a corresponding immiscible liquid, and wherein the immiscible liquid causes the flexible portion of the first chamber wall to expand to contact the thermal element to a greater extent than if the immiscible liquid was absent from the first chamber; and

(b) altering the temperature of the liquid substance in the first chamber by transmitting thermal energy between the thermal element and the volume.

2. The method of claim 1, further comprising the step of closing the first chamber between steps (a) and (b), the first chamber remaining closed until a predetermined temperature of the volume is reached during step (b).

3. The method of claim 1, wherein the liquid substance comprises a reagent for performing an assay in the receptacle.

4. The method of claim 3, wherein the immiscible liquid is not reactive with any component of the assay.

5. The method of claim 1, wherein the immiscible liquid is an oil.

6. The method of claim 5, wherein the oil is a mineral oil.

7. The method of claim 1, wherein the ratio of the immiscible liquid to the remainder of the volume in the chamber is up to about 10:

1.

8. The method of claim 1, wherein the receptacle comprises opposed members configured to define the first chamber and a second chamber.

9. The method of claim 8, wherein at least one of the opposed members comprises a flexible sheet, such that the flexible sheet comprises the first chamber wall.

10. The method of claim 8, wherein the receptacle comprises a second chamber wall, the first and second chamber walls having opposed flexible portions.

11. The method of claim 10, wherein each of the opposed members comprises a flexible sheet, the flexible sheets comprising the first and second chamber walls.

12. The method of claim 10, wherein the first chamber is defined by seals formed between the opposed members.

13. The method of claim 10, further comprising, after step (b), the step of moving at least a portion of the volume from the first chamber to the second chamber of the receptacle.

14. The method of claim 13, wherein one or more compressive forces are applied to the flexible portion of the second chamber wall to move the portion of the volume to the second chamber.

15. The method of claim 14, wherein the compressive forces comprise one or more actuators having compression pads arranged to generally conform to the shape of the flexible portion of the second chamber wall.

16. The method of claim 15, wherein the actuators are pneumatic actuators.

17. The method of claim 13, wherein the portion of the volume is moved from the first chamber to the second chamber through an openable connection.

18. The method of claim 17, wherein the openable connection is altered from a closed state to an open state prior to moving the portion of the volume into the second chamber.

19. The method of claim 18, wherein the first and second chambers are adjacent to each other, and wherein the openable connection is an opening blocked by a burstable seal that is altered from the closed state to the open state when the substance-moving force is applied to the flexible portion of the first chamber.

20. The method of claim 19, wherein the burstable seal is a heat seal.

21. The method of claim 15, wherein the thermal element and the compression pads cooperate to adjust the temperature of the volume during step (b).

22. The method of claim 1, wherein the thermal element comprises a heat transfer element formed from a thermally conductive material.

23. The method of claim 22, wherein the thermally conductive material is formed from aluminum.

24. The method of claim 22, wherein the thermal element further comprises a thermoelectric device in thermal contact with the heat transfer element.

25. The method of claim 24, wherein the thermoelectric device is a Peltier device.

26. The method of claim 1, wherein the temperature of the volume is elevated during step (b).