Methods for manipulating liquid substances in multi-chambered receptacles

• US 8,828,654 B2
• Filed: 07/08/2011
• Issued: 09/09/2014
• 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): FORMAN, BETTY J
• Application Number:
  US13/179,260
• Publication Number:
  US 20120077188A1
• Time in Patent Office: 1,159 Days
• Field of Search: None
• US Class Current: 435/4
• 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 method for moving fluids between chambers of a receptacle having a plurality of interconnected chambers, the method comprising the steps of:

(a) combining in a first chamber of the receptacle a fluid sample and a combination including a sample processing reagent comprising dispersible solid supports in a liquid medium and an immiscible liquid to concentrate the solid supports in the first chamber, wherein the fluid contents of the first chamber comprise the fluid sample, the liquid medium, and the immiscible liquid, and wherein the solid supports are magnetically-responsive and adapted to immobilize one or more analytes thereon wherein the plurality of interconnected chambers defines a non-linear arrangement of chambers;

(b) exposing the solid supports in the first chamber to a magnetic field; and

(c) moving at least a portion of the fluid contents of the first chamber from the first chamber to a second chamber of the receptacle through a connection while continuing to expose the solid supports in the first chamber to the magnetic field to retain the solid supports in the first chamber, wherein the connection is an openable connection that is altered from a closed state to an open state when a substance-moving force is applied to the contents of the first chamber during step (c).

2. The method of claim 1, wherein the fluid contents of the first chamber are moved generally downwardly through the connection to the second chamber in step (c).

3. The method of claim 1, further comprising blocking the connection between the first and second chambers after step (c).

4. The method of claim 3, wherein the connection is blocked with one or more compressive forces applied to the connection.

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 combined liquid medium and fluid sample is from about 1:

10 to about 10;

1.

8. The method of claim 1, wherein the ratio of the immiscible liquid to the combined liquid medium and fluid sample is from about 1:

3 to about 10;

1.

9. The method of claim 1, wherein the solid supports are adapted to immobilize an analyte suspected of being present in the sample.

10. The method of claim 9, wherein the sample processing reagent comprises a capture agent for binding the analyte.

11. The method of claim 10, wherein the capture agent is a capture probe for binding a target nucleic acid.

12. The method of claim 1, wherein the solid supports are particles or beads.

13. The method of claim 1, wherein the receptacle comprises opposed members configured to define the first and second chambers and the connection, and wherein the first chamber comprises a flexible portion that is at least partially compressed by one or more compressive forces applied to the flexible portion during step (c).

14. The method of claim 13, wherein at least one of the opposed members comprises a flexible sheet, the flexible sheet comprising the flexible portion.

15. The method of claim 13, wherein the first chamber comprises opposed flexible portions, at least one of the flexible portions being compressed by one or more compressive forces applied to the flexible portion during step (c).

16. The method of claim 15, wherein each of the opposed members comprises a flexible sheet, the flexible sheets comprising the opposed flexible portions.

17. The method of claim 13, wherein the connection is an openable connection that is altered from a closed state to an open state when a substance-moving force is applied to the contents of the first chamber during step (c).

18. The method of claim 17, wherein the first and second chambers and the connection of the receptacle are defined by seals formed between the opposed members.

19. The method of claim 18, wherein the first and second chambers are adjacent 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 during step (c).

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

21. The method of claim 17, wherein the substance-moving force is applied by one or more actuators having compression pads that are arranged to generally conform to the shape of the first chamber.

22. The method of claim 21, wherein the actuators are pneumatic actuators.

23. The method of claim 13, further comprising receiving the sample into a sample receiving chamber through a sample addition port at a top end of the receptacle, wherein the connection from the first chamber to the second chamber has a generally downward orientation relative to the top end of the receptacle.

24. The method of claim 23, wherein the sample receiving chamber is the first chamber.

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