Method and apparatus for fractionation using generalized dielectrophoresis and field flow fractionation
First Claim
1. A method of discriminating matter utilizing dielectrophoresis and field flow fractionation, comprising:
- a) obtaining and disposing horizontally a chamber having at least one inlet and one outlet port, said chamber having an interior surface and an exterior surface, said chamber further having structural characteristics which cause a carrier medium travelling through said chamber to travel at differing velocities according to a velocity profile;
a plurality of electrode elements adapted along a portion of said chamber;
b) introducing said carrier medium including said matter into said at least one inlet port, wherein said introducing causes said carrier medium to travel through said chamber horizontally according to said velocity profile;
c) applying at least one electrical signal provided by an electrical signal generator to said plurality of electrode elements at different phases, wherein said energized plurality of electrode elements creates a travelling electric field, thereby causing at least one dielectrophoretic force on said matter having components normal to the direction of said fluid travelling through said chamber; and
d) wherein said matter is displaced to vertical positions within said carrier medium, thereby discriminating said matter according to its position within said carrier medium.
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Abstract
The present disclosure is directed to a novel apparatus and novel methods for the separation, characterization, and manipulation of matter. In particular, the invention combines the use of frequency-dependent dielectric and conductive properties of particulate matter and solubilized matter with the properties of the suspending and transporting medium to discriminate and separate such matter. The apparatus includes a chamber having at least one electrode element and at least one inlet and one output port into which cells are introduced and removed from the chamber. Matter carried through the chamber in a fluid stream is then displaced within the fluid by a dielectrophoretic (DEP) force caused by the energized electrode. Following displacement within the fluid, matter travels through the chamber at velocities according to the velocity profile of the chamber. After the matter has transitted through the chamber, it exists at the opposite end of the chamber at a characteristic position. Methods according to the invention involve using the apparatus for discriminating and separating matter for research, diagnosis of a condition, and therapeutic purposes. Examples of such methods may include separation of mixture of cells, such as cancer cells, separation of parasitized erythrocytes from normal erthrocytes, separation of nucleic acids, and others.
168 Citations
39 Claims
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1. A method of discriminating matter utilizing dielectrophoresis and field flow fractionation, comprising:
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a) obtaining and disposing horizontally a chamber having at least one inlet and one outlet port, said chamber having an interior surface and an exterior surface, said chamber further having structural characteristics which cause a carrier medium travelling through said chamber to travel at differing velocities according to a velocity profile;
a plurality of electrode elements adapted along a portion of said chamber;b) introducing said carrier medium including said matter into said at least one inlet port, wherein said introducing causes said carrier medium to travel through said chamber horizontally according to said velocity profile; c) applying at least one electrical signal provided by an electrical signal generator to said plurality of electrode elements at different phases, wherein said energized plurality of electrode elements creates a travelling electric field, thereby causing at least one dielectrophoretic force on said matter having components normal to the direction of said fluid travelling through said chamber; and d) wherein said matter is displaced to vertical positions within said carrier medium, thereby discriminating said matter according to its position within said carrier medium. - 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)
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25. A method of discriminating matter utilizing dielectrophoresis and field flow fractionation, comprising:
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a) obtaining and disposing horizontally a chamber having at least one inlet and one outlet port, said chamber having an interior surface and an exterior surface, said chamber further having structural characteristics which cause a transport fluid travelling through said chamber to travel at differing velocities according to a velocity profile;
a plurality of electrode elements adapted along a portion of said chamber;
at least one duct entering the chamber to carry said transport fluid through the chamber;b) introducing said matter into said at least one inlet port; c) introducing the transport fluid into the at least one duct, wherein said introducing causes a fluid flow at a speed according to said velocity profile within said chamber; d) applying at least one electrical signal provided by an electrical signal generator to said plurality of electrode elements at different phases, wherein said energized plurality of electrode elements creates a travelling electric field, thereby causing at least one dielectrophoretic force on said matter having components normal to the direction of said fluid flow; and e) wherein the matter is displaced to vertical positions within said transport fluid, partitioning said matter according to its position within said fluid flow. - View Dependent Claims (26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36)
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37. A method of determining characteristics of an unknown matter utilizing dielectrophoresis and field flow fractionation, comprising:
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a) obtaining and disposing horizontally a chamber having at least one inlet and one outlet port, said chamber having an interior surface and an exterior surface, said chamber further having structural characteristics which cause a carrier medium travelling through said chamber to travel at differing velocities according to a velocity profile;
a plurality of electrode elements adapted along a portion of said chamber;b) introducing said carrier medium including said unknown matter into said at least one inlet port, causing said carrier medium to travel horizontally through said chamber according to said velocity profile; c) applying at least one electrical signal having an initial frequency provided by an electrical signal generator to said plurality of electrode elements at different phases, wherein said energized plurality of electrode elements creates a travelling electric field, thereby causing at least one dielectrophoretic force on said matter having components normal to the direction of said carrier medium travelling through said chamber; d) varying said initial frequency until said unknown matter is caused to be held in close proximity to said plurality of electrode elements at a holding frequency; e) changing said frequency from said holding frequency so that said unknown matter is released from close proximity to said plurality of electrode elements and displaced to vertical positions within said carrier medium, partitioning said unknown matter according to its positions within said carrier medium flow; f) collecting said unknown matter at said outlet port; and g) characterizing said unknown matter to identify said unknown matter. - View Dependent Claims (38)
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39. A method for diagnosing a condition by determining a presence of unidentified matter in a patent sample utilizing dielectrophoresis and field flow fractionation, comprising:
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a) obtaining and disposing horizontally a chamber having at least one inlet and one outlet port, said chamber having an interior surface and an exterior surface, said chamber further having structural characteristics which cause a carrier medium travelling through said chamber to travel at differing velocities according to a velocity profile;
a plurality of electrode elements adapted along a portion of said chamber;b) introducing said carrier medium including said unidentified matter into said at least one inlet port, causing said carrier medium to travel horizontally through said chamber according to said velocity profile; c) applying at least one electrical signal provided by an electrical signal generator to said plurality of electrode elements at different phases at a holding frequency of a known matter, wherein said energized plurality of electrode elements creates a travelling electric field, thereby causing at least one dielectrophoretic force on said matter having components normal to the direction of said carrier medium travelling through said chamber; and d) determining whether said unidentified matter is held in close proximity to said plurality of electrode elements, indicating said condition.
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Specification