Optimized sample injection structures in microfluidic separations

• US 7,749,365 B2
• Filed: 07/26/2006
• Issued: 07/06/2010
• Est. Priority Date: 02/01/2006
• Status: Active Grant

• Current Assignee: IntegenX Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: IntegenX Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Nguyen, Michael, Bousse, Luc
• Primary Examiner(s): Noguerola; Alex
• Assistant Examiner(s): BALL, JOHN C
• Application Number:
  US11/460,236
• Publication Number:
  US 20070175756A1
• Time in Patent Office: 1,441 Days
• Field of Search: 204/451, 204/601, 204/604, 204/453, 422/81, 422/82, 422/103, 422/99, 422/100, 137/834, 137/251.1, 137/247, 137/330, 251/129.03, 436/174, 436/180, 436/53
• US Class Current: 204/453
• CPC Class Codes: C07K 1/26 Electrophoresis
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

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.

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 buffer or separation channels is defined with a reduced cross-sectional area relative to the width of a sample loading channel portion of the sample 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 6 wherein a dimension of the sample chamber is relatively greater than the width of a sample loading channel portion of the sample channel or separation channel.

8. The microfluidic device of claim 6 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 portion of the sample channel or separation channel.

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

20. The method of claim 15 further comprising performing electrophoresis on the injected sample in the separation channel.