Microfluidic cartridge

• US 9,988,676 B2
• Filed: 06/19/2015
• Issued: 06/05/2018
• Est. Priority Date: 02/22/2012
• Status: Active Grant

• Current Assignee: Leidos Innovations Technology, Inc.
• Original Assignee: Leidos Innovations Technology, Inc.
• Inventors: Egan, Michael E., Root, Brian, Scott, Orion N., South, Douglas J., Bienvenue, Joan M., Kinnon, Paul, Landers, James, Saul, David, Tsuei, An-Chi, Hayes, Jason, Springer, Matthew, Solomon, Matthew, Van Ruijven, Peter
• Primary Examiner(s): Wilder, Cynthia B
• Application Number:
  US14/744,889
• Publication Number:
  US 20150284775A1
• Time in Patent Office: 1,082 Days
• Field of Search: 4352831
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/04 Exchange or ejection of cartridges, containers or reservoirs
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• 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 2200/148 Specific details about calibrations
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/044 pierceable, e.g. films, membranes
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0663 Whole sensors
• CPC Class Codes: B01L 2300/0672 Integrated piercing tool
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0832 cylindrical, tube shaped
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/14 Means for pressure control
• CPC Class Codes: B01L 2300/161 Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
• CPC Class Codes: B01L 2300/18 Means for temperature control
• CPC Class Codes: B01L 2300/1872 Infrared light
• CPC Class Codes: B01L 2400/0487 : fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/049 : vacuum
• CPC Class Codes: B01L 2400/0683 : mechanically breaking a wall or membrane within a channel or chamber
• CPC Class Codes: B01L 2400/088 : by specific surface properties
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502723 : characterised by venting arrangements
• 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 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502753 : characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: B01L 3/502784 : specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: B01L 3/5029 : using swabs
• 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: C12P 19/34 : Polynucleotides, e.g. nucleic acids, oligoribonucleotides
• CPC Class Codes: C12Q 1/6844 : Nucleic acid amplification reactions
• CPC Class Codes: C12Q 1/6853 : using modified primers or templates
• CPC Class Codes: C12Q 1/686 : Polymerase chain reaction [PCR]
• CPC Class Codes: G01N 21/75 : Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated systems in which material is burnt in a flame or plasma G01N21/72, G01N21/73

Abstract

A microfluidic cartridge can include at least one nucleic acid analysis portion. Each nucleic acid analysis portion can include a fluidic network being configured for micro-liter volumes or less, a sample input at the beginning of the fluidic network, a plurality of vent ports and fluidic channels in the fluidic network configured to effectuate hydrodynamic movement within the fluidic network, an extraction mixture reservoir in the fluidic network, a mixing chamber in the fluidic network, an amplification chamber in the fluidic network, and a separation channel in the fluidic network. A nucleic acid analyzer can be capable of performing nucleic acid analysis using the microfluidic cartridge. A nucleic acid analysis method can be performed using the microfluidic cartridge.

Claims

1. A nucleic acid analyzer, comprising:

a microfluidic cartridge module configured to accept at least one microfluidic cartridge comprising;

at least one nucleic acid analysis portion, each nucleic acid analysis portion including;

a fluidic network defined within the nucleic acid analysis portion, the fluidic network being configured for micro-liter volumes or less, the fluidic network including at least one frangible seal formed from a depression defined in a fluidic channel with a fluid flow resistance determined by a depth and a width of the depression;

a sample input at a beginning of the fluidic network, the sample input having a fitting that is configured to be mated to a complementary fitting of a sample acceptor to form a fluid-tight seal;

a plurality of vent ports and fluidic channels in the fluidic network configured to effectuate hydrodynamic movement within the fluidic network;

an extraction mixture reservoir in the fluidic network, the extraction mixture reservoir being configured to hold an enzymatic mixture for performing nucleic acid extraction on a sample provided by the sample acceptor;

a mixing chamber in the fluidic network, the mixing chamber being configured to mix amplification reagents and a portion of an extracted nucleic acid mixture; and

an amplification chamber in the fluidic network, the amplification chamber being configured to hold an amplification mixture during nucleic acid amplification;

a pressure module configured to be coupled to the plurality of vent ports to effectuate hydrodynamic movement within the fluidic network of the microfluidic cartridge;

an extraction thermal module configured to impart temperatures to any of the microfluidic cartridge and the sample acceptor during nucleic acid extraction;

an amplification thermal module configured to impart temperatures to the microfluidic cartridge during nucleic acid amplification;

a high voltage module configured to apply high voltages on the microfluidic cartridge;

a power module configured to provide operation powers to the nucleic acid analyzer;

a detection module configured to detect labeled or dyed nucleic acids; and

a controller module configured to control the pressure module, the extraction thermal module, the amplification thermal module, the high voltage module, the power module, and the detection module according to a control procedure.

2. The nucleic acid analyzer of claim 1, wherein the pressure module is configured to break one or more frangible seals in the fluidic network and/or actuate one or more valves of the microfluidic cartridge during nucleic acid analysis.

3. The nucleic acid analyzer of claim 1, wherein the pressure module is configured to provide pneumatic positive and/or negative pressure.

4. The nucleic acid analyzer of claim 1, wherein the pressure module includes a hydrodynamic pressure/vacuum system.

5. The nucleic acid analyzer of claim 1, wherein the pressure module includes a solenoid manifold.

6. The nucleic acid analyzer of claim 1, wherein the extraction thermal module is configured to heat the sample acceptor by contact heating.

7. The nucleic acid analyzer of claim 1, wherein the amplification thermal module includes a non-contact heating unit and a temperature sensing unit.

8. The nucleic acid analyzer of claim 7, wherein the non-contact heating unit includes an infrared light source.

9. The nucleic acid analyzer of claim 7, wherein the temperature sensing unit includes an infrared pyrometer to measure temperature of a portion of the microfluidic cartridge.

10. The nucleic acid analyzer of claim 1, wherein the detection module comprises:

a laser source unit configured to emit a laser beam;

a detector unit configured to detect fluorescence; and

an optical unit configured to direct the laser beam to a separation channel to excite fluorescent molecules to emit fluorescence and to then direct fluorescence to the detector unit for detection.

11. The nucleic acid analyzer of claim 10, wherein the optical unit includes a self-calibrating array of confocal optical components configured to perform calibration in conjunction with an alignment dye.

12. The nucleic acid analyzer of claim 1, further comprising a computing module operationally coupled to the controller module, the computing module having a user interface.