Microfluidic methods, devices and systems for in situ material concentration

• US 6,695,009 B2
• Filed: 10/30/2001
• Issued: 02/24/2004
• Est. Priority Date: 10/31/2000
• Status: Expired due to Term

• Current Assignee: Caliper Life Sciences Incorporated (Revvity, Inc.)
• Original Assignee: Caliper Holdings Incorporated
• Inventors: Chien, Ring-Ling, Wang, Benjamin N.
• Primary Examiner(s): Chambers, A. Michael
• Application Number:
  US10/013,847
• Publication Number:
  US 20020079008A1
• Time in Patent Office: 847 Days
• Field of Search: 137/806, 137/828, 137/825, 137/827, 137/818, 137/14, 137/13, 204/601
• US Class Current: 137/827
• CPC Class Codes: B01L 2200/0631 Purification arrangements, e.g. solid phase extraction [SPE]
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: G01N 1/40 Concentrating samples
• CPC Class Codes: G01N 27/44704 Details; Accessories
• CPC Class Codes: G01N 27/44773 Multi-stage electrophoresis, e.g. two-dimensional electrophoresis
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: Y10T 137/0391 Affecting flow by the addition of material or energy
• CPC Class Codes: Y10T 137/2076 Utilizing diverse fluids
• CPC Class Codes: Y10T 137/2142 With variable or selectable source of control-input signal
• CPC Class Codes: Y10T 137/2191 By non-fluid energy field affecting input [e.g., transducer]

Abstract

Methods of concentrating materials within microfluidic channel networks by moving materials into regions in which overall velocities of the material are reduced, resulting in stacking of the material within those reduced velocity regions. These methods, devices and systems employ static fluid interfaces to generate the differential velocities, as well as counter-current flow methods, to concentrate materials within microscale channels.

Claims

1. A method of concentrating a material, comprising:

providing a first channel portion having at least first and second fluid regions disposed therein, the material having a first electrophoretic velocity in the first fluid region, and having a second electrophoretic velocity in the second fluid region, wherein the second electrophoretic velocity is less than the first electrophoretic velocity as a result of a different ionic make up of the first and second fluid regions, the first and second fluid regions being in contact at a first substantially static interface; and

electrophoresing the sample material through the first fluid region in the first channel portion toward the second fluid region, the sample material concentrating at the first substantially static interface.

2. A method of concentrating a material, comprising:

providing at least first and second channel portions, wherein the second channel portion intersects and being in fluid communication with the first channel portion, the first channel portion having at least first and second fluid regions disposed therein, the first fluid region comprising the material and having a conductivity that is lower than the second fluid region, the first and second fluid regions being in contact at a first substantially static interface; and

applying an electric field through the first and second fluid regions in the first channel portion to concentrate the material at the first substantially static interface.

3. The method of claim 2, wherein the first static interface is provided substantially at a first fluid junction between the first channel portion and the second channel portion.

4. The method of claim 3, wherein at least the second channel portion is provided with a separation matrix disposed therein.

5. The method of claim 3, wherein the third channel portion is in fluid communication with the first channel portion substantially at the first fluid junction.

6. The method of claim 3, further comprising providing a fourth channel portion in fluid communication with the first channel portion.

7. The method of claim 3, wherein the material comprises nucleic acids.

8. The method of claim 3, wherein the material comprises polypeptides.

9. The method of claim 3, wherein the material comprises a negatively charged micellar formulation.

10. The method of claim 3, wherein an interior surface of the first channel portion is treated to reduce a zeta-potential of the surface.

11. The method of claim 3, wherein the first channel portions comprises a surface coating which masks a surface charge within the first channel portion.

12. The method of claim 3, wherein the first channel portion comprises a dynamic coating material disposed therein.

13. The method of claim 3, wherein the substantially static fluid interface is maintained substantially at the first fluid junction.

14. The method of claim 3, further comprising the step of moving the material concentrated at the first fluid interface into the second channel portion.

15. The method of claim 3, wherein the material is moved into the second channel portion electrokinetically.

16. The method of claim 3, wherein the material is moved into the second channel portion electrophoretically.

17. The method of claim 3, wherein the providing step further comprises providing a third channel portion in fluid communication with the first and second channel portions at the first fluid junction.

18. The method of claim 3, wherein the substantially static fluid interface is maintained substantially at the first fluid junction.

19. The method of claim 2, further comprising providing a third channel portion in fluid communication with the first channel portion.

20. The method of claim 2, wherein the material is positively charged.

21. The method of claim 2, wherein the material is negatively charged.

22. The method of claim 2, wherein the material is provided in a mixture of different materials.

23. The method of claim 2, wherein the applying step comprises applying an electric field of a sufficient size and for a sufficient duration to concentrate the material at least 2 fold.

24. The method of claim 2, wherein the applying step comprises applying an electric field of a sufficient size and for a sufficient duration to concentrate the material at least 5 fold.

25. The method of claim 2, wherein the applying step comprises applying an electric field of a sufficient size and for a sufficient duration to concentrate the material at least 10 fold.

26. The method of claim 2, wherein the applying step comprises applying an electric field of a sufficient size and for a sufficient duration to concentrate the material at least 100 fold.

27. The method of claim 2, wherein the step of providing the comprises maintaining the first static interface in position by applying pressure to at least one of the first and second fluid regions to maintain the first static interface in a substantially static position within the first channel portion.

28. The method of claim 2, wherein during the applying step, there is substantially no electroosmotic flow in the first channel portion.

29. The method of claim 2, wherein the second channel portion is in fluid communication with the first channel portion at a first fluid junction.

30. The method of claim 2, wherein the first conductivity is more than 10% lower than the second conductivity.

31. The method of claim 2, wherein the first conductivity is more than 20% lower than the second conductivity.

32. The method of claim 2, wherein the first conductivity is more than 50% lower than the second conductivity.

33. The method of claim 2, wherein the first conductivity is more than 75% lower than the second conductivity.

34. The method of claim 2, wherein the first conductivity is more than 90% lower than the second conductivity.

35. The method of claim 2, wherein in the applying step, a voltage gradient across the first fluid region is at least twice as great as a voltage gradient across the second fluid region.

36. The method of claim 2, wherein in the applying step, a voltage gradient across the first fluid region is at least 5 times greater than a voltage gradient across the second fluid region.

37. The method of claim 2, wherein in the applying step, a voltage gradient across the first fluid region is at least 10 times greater than a voltage gradient across the second fluid region.