Universal sample preparation system and use in an integrated analysis system

• US 20090253181A1
• Filed: 01/21/2009
• Published: 10/08/2009
• Est. Priority Date: 01/22/2008
• Status: Abandoned Application

• Current Assignee: IntegenX Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Microchip Biotechnologies, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Horn, Joanne, Nguyen, Michael Van, Stern, Seth, Blaga, Lullu I., Jovanovich, Stevan B., Vangbo, Mattias, Nielsen, William D.
• Application Number:
  US12/321,594
• Publication Number:
  US 20090253181A1
• Time in Patent Office: Days
• US Class Current: 435/91.100
• CPC Class Codes: B01D 17/06 Separation of liquids from each other by electricity
• 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 2200/0647 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 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/043 magnetic forces
• 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 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: G01N 1/34 Purifying; Cleaning processes or apparatus for extracting or separating nucleic acids from biological samples C12N15/1003
• CPC Class Codes: G01N 1/40 Concentrating samples
• CPC Class Codes: G01N 2035/00158 Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: G01N 35/1095 for supplying the samples to flow-through analysers for a specific analyser see relevant groups, e.g. under G01N15/00, G01N21/00, G01N27/00, G01N30/00, H01J49/00
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Abstract

The invention provides for devices and methods for interfacing microchips to cartridges and pneumatic manifolds. The cartridges, microchips, and pneumatic manifolds can be integrated with downstream preparation devices, such as thermal regulating devices and separation and analysis devices.

Claims

1. A device comprising:

a microfluidic microchip comprising at least one port aperture fluidically connected to at least one microfluidic channel in the microfluidic microchip, wherein the channel comprises at least one valve that controls movement of a fluid through the channel; and

a cartridge mated to the microchip and comprising a chamber,

wherein said chamber comprises two chamber apertures that are each aligned with a port aperture of said microfluidic microchip.

3. The device of claim 1, wherein said cartridge is fluidically connected to another cartridge that is mated to another microchip.

10. The device of claim 1, wherein the fluidic volume of said cartridge is a 100×

of the fluidic volume of said microfluidic microchip.

12. The device of claim 1, wherein said device further comprises a magnet for applying a magnetic field to the cartridge or the microfluidic microchip.

13. The device of claim 1, wherein the valve is pneumatically actuated.

14. The device of claim 1, wherein said cartridge is adapted to be connected to at least one pressure source for the delivery of said at least one reagent or said at least one sample.

18. The device of claim 1, wherein the microfluidic microchip comprises a fluidic layer, an elastomeric layer, and a pneumatic layer.

19. The device of claim 1, wherein said cartridge further comprises at least one input port,

wherein said at least one input port is adapted to mate with a delivery device,

wherein said delivery device is fluidically connected to the fluidic layer of said microfluidic microchip;

and

wherein one of said at least one chamber is a closed reaction chamber fluidically connected to the fluidic layer of said microfluidic microchip.

22. The device of claim 1, wherein said cartridge is designed to

enrich at least one component from said sample and

comprises at least one sample input port,

wherein said at least one chamber is a closed reaction chamber comprising beads, and

wherein said beads bind to said at least one component.

23. The device of claim 1, wherein the cartridge further comprises at least one reagent reservoir comprising reagents for amplifying a nucleic acid, wherein the at least one reagent reservoir is fluidically connected to the chamber through the microchip.

24. The device of claim 23, wherein the cartridge further comprises at least one bead reservoir comprising beads for binding an amplified nucleic acid, wherein the at least one bead reservoir is fluidically connected to the chamber through the microchip.

29. A method for performing biochemical reactions comprising:

(a) providing the device of claim 1, and

(b) performing at least one enzymatic reaction within said chamber.

32. A method for enriching at least one component from a sample comprising:

(a) mating a delivery device to said input port of the device of claim 19,

(b) treating said sample with at least one reagent to increase the availability of said at least one component for enrichment,

(c) delivering said at least one component to said at least one reaction chamber of said cartridge,

(d) binding said component to one or more particles in said at least one closed reaction chamber,

(e) washing said particle bound component to remove waste, and

(f) eluting said particle bound component.

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45. A device comprising:

(a) a first fluid manipulation module comprising;

(i) a first microfluidic microchip comprising a port aperture fluidically connected to a microfluidic channel in the microfluidic microchip,

wherein the channel comprises at least one valve that controls movement of a fluid through the channel; and

(ii) a cartridge mated to the microfluidic microchip and comprising at least one sample input port, at least one chamber, an exit port,

wherein the sample input port is connected to the port aperture,

wherein at least one of said at least one exit ports is aligned with an exit port aperture of said first microfluidic microchip, and

wherein said at least one chamber is fluidically connected to the fluidic layer of said first microfluidic microchip;

(b) a reaction channel, wherein said reaction channel is not contained within said first microchip;

(c) a temperature modulator,

wherein said reaction channel is fluidically connected to a port on said cartridge that is fluidically connected to said exit port and at least a portion of said reaction channel is in thermal contact with said temperature modulator; and

(d) a magnet for applying a magnetic field to the microfluidic microchip, the cartridge, or the reaction channel.

50. A method comprising:

delivering a sample containing a nucleic acid to the device of claim 45;

transporting the nucleic acid and an effective amount of reagents through the portion of the reaction channel in thermal contact with the temperature modulator one or more times; and

amplifying the nucleic acid; and

analyzing the amplified nucleic acid.

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53. A device comprising:

(a) a first microfluidic microchip comprising a fluidics layer, an actuation layer, and a pneumatic layer,

wherein the fluidics layer comprises one or more microfluidic channels,

wherein at least one of said one or more microfluidic channels comprises an exit aperture,

(b) a flexible connector fluidically connected to the exit aperture at a first end of the flexible connector;

(c) a capillary fluidically connected to said flexible connector; and

(d) a first electrode and a second electrode,

wherein the first electrode and second electrode are configured to produce an electric field along a path of the capillary.

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66. A method comprising:

providing a composition to a microfluidic microchip,

wherein the microfluidic microchip comprises a fluidics layer, a elastomeric layer, and a pneumatic layer;

delivering the composition to a flexible connector that is fluidically connected to the microfluidic microchip;

providing a electric field to move the composition into a capillary; and

performing capillary electrophoresis on the composition to separate a component based on size or charge.

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72. A device comprising:

(a) a separation channel fluidically connected to a loading channel;

(b) a forked electrode comprising at least two electrodes that are electrically connected to the loading channel and the separation channel through the loading channel,

wherein the fluidic connection between the separation channel and the loading channel is located between the electrical connections of the two electrodes to the loading channel; and

(c) a pneumatically actuated valve fluidically connected to the loading channel.

82. A method for performing capillary electrophoresis comprising:

providing the device of claim 72;

providing a separation channel solution to the separation channel;

delivering a composition to the loading channel, wherein the pneumatically actuated valve is used to control the delivery of the composition to the loading channel; and

applying an electric field along the separation channel using the forked electrode;

performing capillary electrophoresis on the composition to separate the component based on size or charge.

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81. A device comprising:

a first, a second, and a third microfluidic channel that are joined to form a three-way junction;

wherein the first microfluidic channel is electrically connected to a first electrode of a forked electrode,

wherein the second microfluidic channel is electrically connected to a second electrode of the forked electrode, and

wherein the first, the second, and the third microfluidic channel are each fluidically connected to a pneumatically actuated valve.

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85. A microfluidic device comprising:

(a) a microfluidic microchip comprising;

(1) a first channel comprising a first valve;

(2) a second channel that intersects the first channel on one side of the first valve;

(3) a third channel that intersects the first channel on the other side of the first valve;

wherein at least one of the second or third channel intersect the first channel at a T-valve or at least one of the second or third channel comprise a second valve, and

wherein the second and third channel each connect to a port; and

(b) a fluid loop that is removably attached to the ports such that fluid can flow from the first channel to the fluid loop.

86. A microfluidic device comprising:

(a) a microchip comprising one or more pneumatically actuated valves; and

(b) a sample loop, wherein the sample loop is fluidically connected to the one or more pneumatically actuated valves through ports in the microfluidic microchip, and wherein the sample loop has a fixed volume and the sample loop is removable.

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92. A method for delivering a fixed volume of fluid to a microfluidic device comprising:

configuring a device with a sample loop comprising a desired volume, wherein the sample loop is removable;

using one or more pneumatically actuated valves on a microfluidic device to fill the sample loop with the fixed volume of the fluid; and

delivering the fluid to the microfluidic device.

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