INSTRUMENT WITH MICROFLUIDIC CHIP

• US 20100165784A1
• Filed: 12/18/2009
• Published: 07/01/2010
• Est. Priority Date: 12/31/2008
• Status: Active Grant

• Current Assignee: IntegenX Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Microchip Biotechnologies, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Trounstine, Mary, Nielsen, William D., Recknor, Michael, JOVANOVICH, Stevan B.
• Granted Patent: US 8,672,532 B2
• Time in Patent Office: Days
• US Class Current: 366/163.200
• CPC Class Codes: B01F 25/40 Static mixers colloid-mills B02C; mixing valves F16K11/00
• CPC Class Codes: B01F 31/31 using receptacles with deformable parts, e.g. membranes, to which a motion is imparted
• CPC Class Codes: B01F 33/30 Micromixers
• 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 2400/0655 pinch valves
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: F16K 99/0001 Microvalves microdevices B81B1/00; manufacture or treatment of devices or systems in or on a substrate B81C1/00; microfluidic structures B01L3/5027; micropumps F04B19/006
• CPC Class Codes: F16K 99/0015 Diaphragm or membrane valves
• CPC Class Codes: F16K 99/0036 operated by temperature variations
• CPC Class Codes: F16K 99/0046 using magnets
• CPC Class Codes: F16K 99/0059 actuated by a pilot fluid
• CPC Class Codes: Y10T 137/0318 Processes
• CPC Class Codes: Y10T 137/87153 Plural noncommunicating flow paths
• CPC Class Codes: Y10T 137/877 With flow control means for branched passages

Abstract

This invention provides microfluidic devices that comprise a fluidics layer having microfluidic channels and one or more regulating layers that regulate the movement of fluid in the channels. The microfluidic devices can be used to mix one or more fluids. At least a portion of the fluidics layer can be isolated from the regulating layer, for example in the form of a shelf. Such isolated portions can be used as areas in which the temperature of liquids is controlled. Also provided are instruments including thermal control devices into which the microfluidic device is engaged so that the thermal control device controls temperature in the isolated portion, and a movable magnetic assembly including magnets with shields so that a focused magnetic field can be applied to or withdrawn from the isolated portion or any other portion of the microfluidic device. Also provided are methods of mixing fluids. The methods include stacking a plurality of alternating boluses of different liquids in a microfluidic channel, and moving the stacked boluses through the channel. In another method, the boluses are moved into a diaphragm valve having a volume able to accommodate several boluses, and then pumping the liquids out of the valve.

Claims

1. A microfluidic device comprising:

a fluidics layer comprising fluidic channels;

a pneumatics layer comprising pneumatic channels; and

an actuation layer sandwiched between the fluidics layer and the pneumatic layer,

wherein the device comprises at least one diaphragm valve comprised in the sandwich, wherein activation of the valve regulates fluid flow in a fluidics channel, and

wherein the device further comprises an isolated portion of the fluidics layer that comprises microfluidic channels and that is not covered by the pneumatics layer and, optionally, the actuation layer.

27. A method for regulating temperature of a fluid in a microfluidic channel comprising:

a. providing a device of claim 1;

b. moving liquid into a segment of a fluidic channel in the isolated portion; and

c. regulating the temperature of the liquid while in the fluidic channel in the isolated portion.

29. An instrument comprising:

a. a base comprising a thermal regulator; and

b. a microchip of claim 1 engaged with the base so that the isolated portion of the fluidics layer is in thermal contact with the thermal regulator.

2-17. -17. (canceled)

18. A microfluidic device comprising:

a. a fluidics layer comprising fluidic channels; and

b. an actuation layer in contact with a portion of the fluidics layer, wherein the actuation layer regulates fluid flow in the fluidics channels, and wherein the fluidics layer comprises a portion that is not in contact with the actuation layer and that comprises microfluidics channels.

19. A microfluidic device comprising first, second, and third glass layers, and an elastomeric layer, wherein:

(i) the first glass layer is interfaced with the second glass layer and the first and second glass layers form one or more fluidic channels,

(ii) the elastomeric layer is positioned between the second and third glass layers and the second glass layer and elastomeric layer form one or more chambers that are in fluid communication with the one or more fluidic channels; and

(iii) the elastomeric layer and the third glass layer form one or more pneumatic channels, and further

wherein a first portion of the first and second glass layers are isolated from the elastomeric layer and the third glass layer.

20-26. -26. (canceled)

28. (canceled)

30-33. -33. (canceled)

34. An instrument comprising:

a. a chip station assembly comprising at least one station, each station configured to engage a microfluidic chip, wherein each microfluidic chip comprises a plurality of microfluidic circuits, each circuit comprising a chamber; and

b. a magnet moving assembly comprising;

i. a magnet for each station; and

ii. an actuator configured to move each magnet into a functional position at a station so as to exert a magnetic force of at least 30 T²/m in each of the chambers in the microfluidic chip when engaged with the station, and wherein the magnetic force is substantially the same in each chamber of the plurality of microfluidic circuits.

35. The instrument of claim 34 wherein the chip station assembly comprises a plurality of stations.

36. The instrument of claim 35 wherein the plurality is 4.

37. The instrument of claim 34 wherein each magnet has a long dimension, an intermediate dimension and a short dimension, wherein the long and short dimensions define a first pair of faces defining north and south magnetic poles, and one of the first pair of faces, faces the engaged chip in the functional position to exert the magnetic force.

38. The instrument of claim 37 wherein each magnet further comprises a shield that contacts a second face of the magnet defined by the long and intermediate dimension, wherein the shield substantially directs the magnetic force of the magnet.

39. The instrument of claim 38 wherein the shield also contacts the face of the first pair that does not face the chip.

40. The instrument of claim 37 wherein the chip station assembly comprises a plurality of stations, the magnets are substantially parallel to each other and a plurality of the shields contact the second face on a side that faces another magnet.

41. The instrument of claim 34 wherein each magnet is substantially rectangular.

42. The instrument of claim 34 wherein each station is engaged with a microfluidic chip.

43. The instrument of claim 34 wherein the chambers are diaphragm chambers.

44. The instrument of claim 34 wherein the chambers in each chip are arranged in substantially linear fashion.

45. The instrument of claim 34 wherein the magnet moving assembly comprises a magnet holder that holds the magnets and that is moved by the actuator.

46. The instrument of claim 34 wherein the actuator comprises an electric motor.

47. A method comprising moving a magnet into a functional position with respect to a microfluidic chip, wherein the chip comprises a plurality of microfluidic circuits, each circuit comprising a chamber;

and the magnet exerts, when in the functional position, a magnetic force of at least 30 T²/m in each of the chambers in the chip, and wherein the magnetic force is substantially the same in each chamber in the chip.

48. The method of claim 47 comprising capturing magnetically responsive particles in each chamber from a fluid flowing in each circuit with the magnetic force.

49. The method of claim 48 wherein the chambers are diaphragm chambers and capturing comprises increasing the volume of the chambers by deforming the diaphragm.

50. The method of claim 47 further comprising moving the magnet out of the functional position to release the particles.

51. A method for mixing a first liquid and a second liquid comprising:

a) positioning a first bolus of the first liquid adjacent and downstream of a second bolus of the second liquid within a channel;

b) positioning a third bolus of a third liquid adjacent and upstream of the second bolus of the second liquid within a channel; and

c) moving the first bolus, the second bolus, and the third bolus within the channel in a first direction under laminar flow conditions, whereby the moving facilitates mixing of the first liquid, the second liquid, and the third liquid,

wherein one or more pneumatically actuated diaphragm pumps are used for the positioning of the first bolus, the second bolus, and the third bolus within the channel, and wherein the first liquid and second liquid are different.

52-61. -61. (canceled)

62. A method for combining a first liquid and a second liquid in a microfluidic mixing channel comprising:

a) providing a device with a first liquid channel and a second liquid channel each fluidically connected to the microfluidic mixing channel, wherein a first diaphragm valve is positioned within the first liquid channel, a second diaphragm valve is positioned within the second liquid channel, and a third and a fourth diaphragm valves are positioned within the microfluidic mixing channel; and

b) using the first, second, third and fourth diaphragm valves to sequentially pump the first liquid and the second liquid into the microfluidic mixing channel to form a plurality of boluses of first liquid and second liquid, wherein the first, third, and fourth diaphragm valves are used to pump the first liquid into the microfluidic mixing channel and the second, third, and fourth diaphragm valves are used to pump the second liquid into the microfluidic mixing channel, and wherein the first liquid and second liquid are different.

63-71. -71. (canceled)

72. A method for providing a first liquid and a second liquid to a mixing channel comprising the steps of:

a. providing a device with a first liquid channel and a second liquid channel each fluidically connected to the mixing channel,

wherein a first valve is positioned within the first liquid channel, a second valve is positioned within the second liquid channel, a pumping valve is positioned within the mixing channel, and an exit valve is positioned downstream of the pumping valve within the mixing channel, and

wherein the first liquid and the second liquid are different;

b. providing the first liquid to the first liquid channel and the second liquid to the second liquid channel;

c. configuring the valves such that the first valve is open and the second valve, the pumping valve, and the exit valve are closed;

d. opening the pumping valve;

e. configuring the valves such that the pumping valve and exit valve are open and the first valve and the second valve are closed;

f. closing the pumping valve;

g. configuring the valves such that the second valve is open and the first valve, the pumping valve and the exit valve are closed;

h. opening the pumping valve;

i. configuring the valves such that the pumping valve and the exit valve are open and the first valve and the second valve are closed; and

j. closing the pumping valve.

73-83. -83. (canceled)

84. A method of mixing fluids in a microfluidic device comprising:

a) stacking alternating boluses of a first liquid and a second liquid in a microfluidic channel; and

b) moving the stack of boluses through the channel, wherein the channel is configured so that moving the boluses increases an area of surface contact between the boluses, promoting mixing of first and second liquids.

85-86. -86. (canceled)

87. A method of mixing fluids in a microfluidic device comprising:

a) stacking alternating boluses of a first liquid and a second liquid in a microfluidic channel;

b) moving the stack of boluses into a chamber of a diaphragm valve, wherein the chamber, when open, has a volume greater than the volume of at least four boluses; and

c) closing the diaphragm valve, wherein closing pumps the liquids out of the valve, thereby mixing the liquids.

88. (canceled)