Fluid mixing in low aspect ratio chambers
First Claim
1. A microfluidic device comprising:
- a. at least one low aspect ratio chamber comprising;
i. two substantially parallel main walls;
ii. a perimeter wall forming a boundary of said chamber and defining a length and width of said chamber, said chamber being further bounded by said two main walls, the distance between said main walls being small with respect to the length of said chamber; and
iii. at least two flexible diaphragm regions located in said parallel main walls at opposite ends of said at least one chamber and adapted to flex inward and outward with respect to said chamber; and
b. at least one inlet port through which fluid may be introduced into said at least one low aspect ratio chamber, wherein said at least one inlet port is sealable to maintain a substantially constant volume within said chamber.
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Abstract
A method and system for performing mixing in a low volume, low aspect ratio microfluidic chamber (3) is described. Two or more mixing bladders (13,15) formed adjacent the microfluidic chamber are inflated and deflated in reciprocating fashion to cause inward and outward deflection of discrete regions of the chamber wall to mix fluid within the chamber. Mixing bladders are actuated by air or another gas, or by a liquid such as water, pumped in and out of the bladders with a pump which may be located remote from the microfluidic device including the microfluidic chamber. In an alternative embodiment, mixing is generated by applying alternating mechanical forces to a surface of a flexible chamber forming device. The microfluidic chamber may be a hybridization chamber formed on a microarray (25) slide with the use of a microarray interface device, or it may be a microfluidic chamber formed in various other types of microfluidic devices.
181 Citations
100 Claims
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1. A microfluidic device comprising:
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a. at least one low aspect ratio chamber comprising;
i. two substantially parallel main walls;
ii. a perimeter wall forming a boundary of said chamber and defining a length and width of said chamber, said chamber being further bounded by said two main walls, the distance between said main walls being small with respect to the length of said chamber; and
iii. at least two flexible diaphragm regions located in said parallel main walls at opposite ends of said at least one chamber and adapted to flex inward and outward with respect to said chamber; and
b. at least one inlet port through which fluid may be introduced into said at least one low aspect ratio chamber, wherein said at least one inlet port is sealable to maintain a substantially constant volume within said chamber. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 52, 53, 54, 55, 63)
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31. A reaction chamber forming device comprising an open low aspect ratio chamber adapted to be sealed against a substrate, said chamber comprising:
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a. at least one substantially planar main wall, comprising two flexible diaphragm regions adapted to flex inward and outward with respect to said chamber in response to applied pressure;
b. a perimeter wall forming a boundary of said chamber and defining a length and width of said chamber, the height of said perimeter wall defining the height of said chamber, said height of said chamber being small with respect to the length of said chamber, said height of said chamber being small with respect to the length of said chamber;
c. at least one inlet port through which fluid may be introduced into said chamber;
d. at least one outlet port through which fluid may be removed or released from said chamber; and
e. a gasket adapted to reversibly seal said open low aspect ratio chamber to a planar surface of a substrate bearing a sample to form a closed low aspect ratio chamber containing said sample and having one wall formed by said surface of said substrate. - View Dependent Claims (32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50)
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51. A fluid handling device comprising:
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a. low aspect ratio chamber formed in a base structure;
b. at least one inlet through which fluid can be introduced into said low aspect ratio chamber, wherein said at least one inlet is sealable to maintain a substantially constant volume within said chamber;
c. a first mixing bladder located at a first end of said chamber;
d. a first channel communicating with said first mixing bladder;
e. a second mixing bladder located at a second end of said chamber; and
f. a second channel communicating with said second mixing bladder;
wherein said first and second mixing bladders may be alternately and reciprocally inflated and deflated to produce movement of fluid within said chamber while maintaining said chamber at said substantially constant volume. - View Dependent Claims (56, 57, 58, 59, 60, 61, 62)
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64. A method of mixing fluid within a low aspect ratio chamber, said chamber comprising:
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a. two substantially planar and substantially parallel main walls;
b. a perimeter wall forming a boundary of the low aspect ratio chamber and defining a length and width of said chamber, said chamber being further bounded by said two main walls, the distance between said main walls being small with respect to the length of said chamber; and
c. at least first and second flexible diaphragm regions located in at least one of said parallel main walls at opposite ends of said chamber;
d. at least first and second mixing bladders, one mixing bladder adjacent to each said flexible diaphragm region; and
e. an inlet port through which fluid may be introduced into said low aspect ratio chamber;
said method comprising the steps of;
i. loading a volume of fluid into said chamber via said inlet port;
ii. sealing said inlet port to retain said volume of fluid within said chamber;
iii. inflating said first mixing bladder to cause deflection of said first flexible diaphragm region into said chamber; and
iv. deflating said first mixing bladder to cause deflection of said first flexible diaphragm region out of said chamber;
wherein said volume of said chamber remains substantially constant during said steps of inflating and deflating said first mixing bladder. - View Dependent Claims (65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81)
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82. A fluid handling device comprising a low aspect ratio chamber, the low aspect ratio chamber comprising
a. a substantially planar first main wall; -
b. a substantially planar second main wall positioned substantially parallel with respect to said first main wall; and
c. a perimeter wall bounding the region between said first and second main walls, the height of said perimeter wall defining a microscale distance between said first and second main walls that is significantly smaller than the length and width of said first and second main walls;
wherein edges of said first and second main walls are fixed with respect to said perimeter wall, wherein at least one said first and second main walls comprises a central wall region adapted to flex inward and outward with respect to said chamber, wherein inward flexing of said central wall region causes the distance between said first and second main walls to be less in the central wall region of said chamber than in a peripheral region adjacent said perimeter wall, and wherein outward flexing of said central wall region causes the distance between said first and second main walls to be greater in said central wall region than in said peripheral region. - View Dependent Claims (83, 84, 85, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100)
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86. A method of mixing fluid within a microfluidic device comprising a substantially fixed volume low aspect ratio chamber, wherein at least selected regions of the wall of said device adjacent said chamber can be moved inward or outward with respect to said chamber, the method comprising the steps of:
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a. filling said chamber with fluid;
b. sealing said chamber to retain fluid within said chamber;
c. pumping said fluid in a first direction within said chamber;
d. deflecting a central wall region off the wall of said device so that in at least a portion of said chamber, the height of said chamber is greater in the central wall region of said chamber than on the periphery of said chamber;
e. pumping said fluid in a second direction within said chamber;
f. deflecting a central wall region off the wall of said device so that in at least a portion of said chamber, the height of said chamber is less in the central wall region of said chamber than on the periphery of said chamber;
g. repeating steps c. through f. to generate circulating fluid movement within said chamber.
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87. A method of mixing fluid within a fluid-filled microfluidic device comprising a substantially fixed volume low aspect ratio chamber, wherein at least selected regions of the wall of said device adjacent said chamber can be moved inward or outward with respect to said chamber, the method comprising applying pressure alternately to movable wall regions on opposite ends of said chamber by a brayer, a roller, or mechanical feet.
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88. A microfluidic device comprising:
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a. at least one low aspect ratio chamber comprising;
i. two substantially parallel main walls;
ii. a perimeter wall forming a boundary of said chamber and defining a length and width of said chamber, said chamber being further bounded by said two main walls, the distance between said main walls being small with respect to the length of said chamber;
iii. at least one flexible diaphragm region located in one of said parallel main walls adapted to flex inward and outward with respect to said chamber; and
iv. and least one vent, said vent being sufficiently long that fluid displaced by the inward and outward flexing of said at least one flexible diaphragm region can move up and down within said vent while remaining contained within said vent; and
b. at least one inlet port through which fluid may be introduced into said at least one low aspect ratio chamber.
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Specification