OPTIMIZED SAMPLE INJECTION STRUCTURES IN MICROFLUIDIC SEPARATIONS

Abstract

The invention herein provides improved sample injection systems and related methods to create microfluidic devices with symmetrical channel configurations that can produce relatively large sample volumes. An embodiment of the invention provides microfluidic structures with different geometries that are symmetrical from the perspective of a sample load channel and a sample waste channel, which essentially eliminates issues of time offset and other problems commonly associated with twin-T sample formation techniques. A split-injection approach and related methods of sample plug formation are therefore provided.

Description

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 illustrates a top view of a chip with split injector for introducing a sample into a separation channel.

FIGS. 2A-B illustrate a sample plug formed at an intersection of channels according to a cross injection approach.

FIGS. 3A-B illustrate a sample injection according to a twin-T design.

FIGS. 4A-C illustrate a sample plug between arms of a multiple injection channels.

FIGS. 5A-C illustrate a sample plug formed between arms of a multiple injection channels.

FIG. 6A illustrates a sample plug between arms of split injection channels where the injection channels are connected to a single well.

FIG. 6B illustrates an electrical analog of a chip geometry, including the nodes A through D, and conceptual resistors between them.

FIG. 6C illustrates split injection channels attached to separate wells.

FIG. 7A illustrates a geometry with wider channels between A and B and between B and C, combined with long and narrow channels between A and D and between D and C. The channels are narrower in the vicinity of intersections A, B, and C.

FIG. 7B illustrates the section between A and C folded to make the structure more compact.

FIG. 8 illustrates an example of a microchip laboratory system including six reservoirs R₁, R₂, R₃, R₄, R₅, and R₆ connected to each other by a system of channels.

FIG. 9 illustrates a different geometry for the area between the injection channels that defines the sample plug.

FIG. 10 illustrates a design feature where a channel or channel portion leading up to the sample channel is narrower and/or shallower.

FIGS. 11A-C illustrate a curved shaped geometry of the area between the injection channels that define the sample channel. Additional channel is added downstream for separation.

FIGS. 12A illustrates a curved shaped geometry of a sample chamber formed at a location where channels connecting to the chamber would otherwise intersect.

FIG. 12B illustrates a curved shaped geometry of a sample chamber with the narrowing of down stream channel.

FIG. 12C illustrates an enlarged view of a portion of FIG. 12B.

FIGS. 12D and 12E, respectively, illustrate a sample load phase and a separation phase for FIG. 12B.

FIGS. 13A-B illustrate a design feature where a sample chamber is formed with a substantially diamond shape positioned at a location where channels connecting to the chamber would otherwise intersect. The channel upstream of the sample chamber splits and intersects the sample chamber from both the sides.

Claims

1. A microfluidic device for sample injection which comprises a sample channel, which contains a sample having an original sample composition, a separation channel, and two buffer channels, which contain an electrolyte buffer,wherein the buffer and separation channels each intersect the sample channel, and the separation channel is positioned between the buffer channels, such that a sample volume is substantially defined by a section of the sample channel between the outermost boundaries of the two buffer channels where they intersect the sample channel.

2. The microfluidic device of claim 1 wherein the two buffer channels are connected to a single well.

3. The microfluidic device of claim 1 wherein the two buffer channels are connected to two separate wells.

4. The microfluidic device of claim 1 wherein a portion of the channels is defined with a reduced cross-sectional area relative to the width of the sample loading channel.

5. The microfluidic device of claim 1 wherein the sample volume is geometrically defined.

6. The microfluidic device of claim 1 wherein the sample volume can be further defined by a sample chamber with variable depth.

7. The microfluidic device of claim 1 wherein a dimension of the sample chamber is relatively greater than the width of the sample loading channel or separation channel.

8. The microfluidic device of claim 1 wherein the sample chamber is selected from one of the following: a diamond shape, a circular shape or a curve shape.

9. The microfluidic device of claim 8 wherein the sample chamber is formed with a depth different than that of the sample loading channel or separation channel.

10. The microfluidic device of claim 8 wherein a portion of the channels is defined with a reduced cross-sectional area relative to the width of the sample loading channel.

11. A method of introducing a sample into a microfluidic device, which microfluidic device comprising a sample channel connected to a sample well and a waste well at the two separate ends, where the sample well contains a sample having an original sample composition, two buffer channels, which contain an electrolyte buffer, and a separation channel,wherein the buffer and separation channels are each inclined with respect to the sample channel, and the separation channel is between the buffer channels,and wherein buffer and separation channels intersect the sample channel, such that a geometrically defined sample chamber is a sample volume defined by a section of the sample channel located between the outermost boundaries of the two buffer channels where they intersect the sample channel,which method comprises the step of electrokinetically loading a sample into the sample channel by applying an electric field across the sample well and the waste well, wherein the electric field is applied for a time period which is at least long enough that the component of the sample having the lowest electrophoretic mobility migrates into the geometrically defined sample volume, such that the loaded sample plug reflects the original sample composition.

12. The method of claim 11 wherein the two buffer channels are connected to a single well.

13. The method of claim 11 wherein the two buffer channels are connected to two separate wells.

14. The method of claim 11 wherein a portion of the channels is defined with a reduced cross-sectional area relative to the width of the sample loading channel.

15. The method of claim 11 wherein the loaded sample plug is injected into the separation channel.

16. The method of claim 11 wherein the sample volume can be further defined by a variable depth of the sample chamber.

17. The method of claim 11 wherein a dimension of the sample chamber is relatively greater than the width of the sample loading channel or separation channel.

18. The method of claim 11 wherein the sample chamber is selected from one of the following: a diamond shape, a circular shape or a curve shape.

19. The method of claim 18 wherein a portion of the channels is defined with a reduced cross-sectional area relative to the width of the sample loading channel.