Instruments and methods for mixing the contents of a detection chamber

• US 8,480,976 B2
• Filed: 07/13/2011
• Issued: 07/09/2013
• 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: Breidenthal, Scott S., Fan, Sara H., Lee, Richard S., Nelson, Norman C., Scott, Matthew J., Taylor, Jason A.
• Primary Examiner(s): Marcheschi, Michael
• Assistant Examiner(s): HURST, JONATHAN M
• Application Number:
  US13/181,850
• Publication Number:
  US 20110275087A1
• Time in Patent Office: 727 Days
• Field of Search: 422/68.1, 422/504, 366/142, 366/143, 366/144, 436/172
• US Class Current: 422/504
• 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 comprising:

a receptacle-receiving area for receiving the receptacle;

a detector having components positioned to detect a light signal from the contents of a detection chamber of the receptacle when the receptacle is placed in an operative position in said receptacle-receiving area, said components comprising a light source and a signal detecting element disposed on the same side of the receptacle-receiving area;

at least one movable compression element disposed to be adjacent the detection chamber and situated between the receptacle and said light source and said signal detecting element of said detector when the receptacle is placed in the operative position in said receptacle-receiving area, wherein said compression element is configured to move relative to the detector and to transmit light from said light source to said detection chamber and to transmit light signals from said detection chamber to said signal detecting element;

an actuator constructed and arranged to move the compression element; and

a controller programmed to activate the actuator to move said compression element into engagement with a flexible portion of the detection chamber to thereby depress the flexible portion to agitate the contents of the detection chamber or to move the contents of the detection chamber into an adjacently connected chamber of the receptacle.

2. The instrument of claim 1, wherein the actuator is a pneumatic actuator.

3. The instrument of claim 1, wherein the compression element includes a window that permits the light signal to pass to the lens of the detector.

4. The instrument of claim 1, wherein the detector is fixed in the instrument.

5. The instrument of claim 1, wherein the compression element has a tubular body in sliding engagement with a light-directing conduit of the detector.

6. The instrument of claim 1, wherein an end surface of the compression element generally conforms to the shape of the detection chamber.

7. The instrument of claim 1, wherein the compression element is one of a plurality of compression elements arranged to engage a plurality of the chambers of the receptacle.

8. The instrument of claim 1, wherein the compression element has a tubular body in sliding engagement with a light-directing conduit of the detector, the receptacle is carried adjacent to an actuator plate disposed between the receptacle and the detector, and the compression element is in alignment with an opening formed through the actuator plate with the detection chamber disposed adjacent the opening, and wherein the instrument further includes:

a bracket extending from the actuator plate;

an actuator carried on the bracket and controlled by the controller for selective reciprocal movement; and

an actuating bar extending from the compression element to the actuator and adapted to translate movement of the actuator to the compression element such that reciprocal movement of the actuator causes corresponding reciprocal movement of the compression tube between a retracted position and an extended position engaged with the detection chamber.

9. The instrument of claim 8, further comprising a guide rod extending from the actuator plate and into engagement with a portion of the actuating bar and adapted to guide the compression tube during movement of the compression tube.

10. The instrument of claim 8, wherein the compression element includes a window that permits the light signal to pass to the light-directing conduit of the detector.

11. The instrument of claim 8, wherein the actuator comprises a pneumatic piston.

12. The instrument of claim 1, further comprising a thermal element including at least a portion thereof disposed to be adjacent the detection chamber on a side of the receptacle-receiving area opposite the compression element.