Apparatus and methods for integrated sample preparation, reaction and detection

• US 9,539,577 B2
• Filed: 05/28/2015
• Issued: 01/10/2017
• Est. Priority Date: 10/19/2005
• Status: Active Grant

• Current Assignee: Luminex Corporation (DiaSorin S.p.A.)
• Original Assignee: Luminex Corporation (DiaSorin S.p.A.)
• Inventors: Bird, Dylan Hilmer, Ching, Jesus, Johnson, Bruce A., Moravick, Keith E., Richardson, Bruce
• Primary Examiner(s): Wilder, Cynthia B
• Application Number:
  US14/723,586
• Publication Number:
  US 20150258548A1
• Time in Patent Office: 593 Days
• Field of Search: 435/283.1
• US Class Current: 1/1
• 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 25/60 Pump mixers, i.e. mixing within a pump
• 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 35/712 for feeding fluids
• CPC Class Codes: B01F 35/715 Feeding the components in several steps, e.g. successive steps
• CPC Class Codes: B01F 35/7174 using pistons, plungers or syringes
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/026 Fluid interfacing between devices or objects, e.g. connectors, inlet details
• CPC Class Codes: B01L 2200/028 Modular arrangements
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• 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 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/042 Caps; Plugs
• CPC Class Codes: B01L 2300/044 pierceable, e.g. films, membranes
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0672 Integrated piercing tool
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• 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 2400/0406 : capillary forces
• CPC Class Codes: B01L 2400/043 : magnetic forces
• CPC Class Codes: B01L 2400/0478 : pistons
• CPC Class Codes: B01L 2400/0481 : squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0622 : distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way valves
• CPC Class Codes: B01L 2400/0633 : with moving parts
• CPC Class Codes: B01L 2400/0644 : rotary valves
• CPC Class Codes: B01L 2400/0683 : mechanically breaking a wall or membrane within a channel or chamber
• 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 3/50851 : specially adapted for heating or cooling samples laboratory heating apparatus B01L7/00; incubators C12M
• CPC Class Codes: B01L 3/523 : with means for closing or opening
• CPC Class Codes: B01L 3/527 : for a plurality of reagents
• CPC Class Codes: B01L 7/00 : Heating or cooling apparatus autoclaves B01J3/04; Heat insulating devices
• 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: C12Q 1/6806 : Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/686 : Polymerase chain reaction [PCR]
• CPC Class Codes: G01N 1/38 : Diluting, dispersing or mixing samples
• CPC Class Codes: G01N 2035/0436 : with pre-packaged reagents, i.e. test-packs
• CPC Class Codes: G01N 35/1079 : with means for piercing stoppers or septums
• CPC Class Codes: Y10T 436/118339 : with formation of a segmented stream
• CPC Class Codes: Y10T 436/25375 : Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
• CPC Class Codes: Y10T 436/255 : including use of a solid sorbent, semipermeable membrane, or liquid extraction

Abstract

Cartridges for the isolation of a biological sample and downstream biological assays on the sample are provided, as are methods for using such cartridges. In one embodiment, a nucleic acid sample is isolated from a biological sample and the nucleic acid sample is amplified, for example by the polymerase chain reaction. The cartridges provided herein can also be used for the isolation of non-nucleic acid samples, for example proteins, and to perform downstream reactions on the proteins, for example, binding assays. Instruments for carrying out the downstream biological assays and for detecting the results of the assays are also provided.

Claims

1. An apparatus, comprising:

(a) an instrument enclosure configured to contain a cassette, the cassette comprising;

(i) a lysis chamber,

(ii) an elution chamber, and

(iii) a reaction chamber;

(b) a heater assembly disposed within the instrument enclosure, the heater assembly comprising a first heater module comprising a first lumen and a second lumen and configured to receive at least a portion of the reaction chamber;

(c) an optics assembly disposed within the instrument enclosure, the optics assembly comprising an excitation module, a detection module, a first optical member, and a second optical member, wherein the first optical member is configured to convey electromagnetic energy from the excitation module to the reaction chamber via the first lumen, and wherein the second optical member is configured to convey electromagnetic energy from the reaction chamber to the detection module via the second lumen.

2. The apparatus of claim 1, further comprising a second heater module configured to heat the elution chamber.

3. The apparatus of claim 1, further comprising a positioning assembly coupled to the heater assembly, wherein the positioning assembly is configured to move the heater assembly relative to the cassette.

4. The apparatus of claim 1, further comprising an acoustic transducer configured to contact the lysis chamber of the cassette.

5. The apparatus of claim 4, further comprising an acoustic transducer actuation mechanism, wherein the acoustic-transducer actuation mechanism is configured to vary a force exerted by the acoustic transducer on the cassette while the acoustic transducer is transmitting ultrasonic energy through the cassette.

6. The apparatus of claim 1, wherein the excitation module comprises a laser.

7. The apparatus of claim 1, wherein the excitation module comprises one or more light-emitting diodes (LEDs).

8. The apparatus of claim 7, wherein the excitation module comprises a series of LEDs, wherein each LED is configured to produce a light beam having a different wavelength than the light beams produced by the other LEDs.

9. The apparatus of claim 1, wherein the detection module comprises a photodetector.

10. The apparatus of claim 9, wherein the photodetector is a photoresistor, photo diode, phototube, or charge-coupled device (CCD).

11. The apparatus of claim 9, wherein the detection module comprises a series of photodetectors, wherein each photodetector is configured to receive a light beam having a different wavelength than the light beams received by the other photodetectors.

12. The apparatus of claim 1, wherein the first and second optical members comprise multi-mode optical fiber or single-mode optical fiber.

13. The apparatus of claim 1, wherein the optics assembly comprises:

(a) a slide assembly comprising a slide block slidably mounted on a slide rail; and

(b) a plurality of excitation modules and a plurality of detection modules coupled to the slide block, wherein the slide assembly is configured to sequentially move each of the plurality of excitation modules relative to the first optical member and to sequentially move each of the plurality of detection modules relative to the second optical member.

14. The apparatus of claim 3, wherein the slide assembly further comprises a drive screw and a stepper motor.

15. The apparatus of claim 1, wherein the cassette further comprises a reagent chamber and a pump in fluid communication with the lysis chamber, and the instrument further comprises a first actuator assembly configured to transfer a reagent from the reagent chamber to the lysis chamber and a second actuator assembly configured to actuate the pump to mix the reagent and a sample in the lysis chamber.

16. The apparatus of claim 1, wherein the instrument enclosure is configured to contain a plurality of the cassettes.

17. The apparatus of claim 16, wherein the instrument enclosure is configured to contain six of the cassettes.