Devices,systems and methods for multi-dimensional separation

• US 20060171855A1
• Filed: 02/03/2005
• Published: 08/03/2006
• Est. Priority Date: 02/03/2005
• Status: Abandoned Application

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Killeen, Kevin P., Yin, Hongfeng
• Application Number:
  US11/051,587
• Publication Number:
  US 20060171855A1
• Time in Patent Office: Days
• US Class Current: 422/101
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2400/0622 distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way valves
• CPC Class Codes: B01L 2400/0644 rotary valves
• CPC Class Codes: B01L 3/0268 using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: G01N 30/463 for multidimensional chromatography
• CPC Class Codes: G01N 30/7266 by electric field, e.g. electrospray

Abstract

Disclosed is a multi-substrate microfluidic device for performing multi-dimensional separation of sample components, as well as systems and methods for using the same.

Claims

1. A device comprising:

a first substrate comprising a first separation fluid-transporting feature for separating a molecules in a sample according to a first characteristic and

a second substrate comprising a second fluid-transporting feature for separating molecules in a sample according to a second characteristic;

wherein the first and second substrate lie in different planes and the first and second separation fluid-transporting features are connectable to each other.

2. The device according to claim 1, wherein the first and second characteristic are different from each other.

3. The device of claim 1, wherein the first and second characteristic are the same.

4. The device of claim 1, wherein fluid flow through at least one fluid-transporting feature of the device is controlled by establishing a pressure differential at different regions of the fluid-transporting feature.

5. The device of claim 1, wherein the first and second separation fluid-transporting features are connectable to each other via a switching structure in slidable and fluid-tight contact with the first and/or second substrate which allows for controllable formation of a plurality of different flow paths upon alignment of one or more substrate fluid-transporting features with a fluid transporting feature of the switching structure.

6. The device of claim 1, wherein the first and second fluid-transporting features comprise separation conduits, wherein each conduit communicates with an inlet port and an outlet port.

7. The device of claim 1, wherein a separation fluid-transporting feature comprises separation medium.

8. The device of claim 1, wherein a separation fluid-transporting feature comprises a polymeric material.

9. The device of claim 8, wherein the polymeric material is formed in situ in the device.

10. The device of claim 1, wherein a separation characteristic is selected from the group consisting of isoelectric point, charge, polarity, mass, molecular weight, affinity for a binding molecule, hydrophobicity, chirality, and sequence characteristics of a biopolymer.

11. The device of claim 1, wherein the device comprises a fluid-transporting feature comprising an affinity matrix.

12. The device of claim 1, wherein the affinity matrix comprises binding partners for proteins to be depleted from a sample prior to introducing the sample into a separation fluid-transporting feature.

13. The device of claim 1, wherein the device further comprises a fluid-transporting feature for processing a sample before or after separation.

14. The device of claim 1, wherein the fluid-transporting feature for processing comprises a cleavage agent.

15. The device of claim 14, wherein the cleavage agent comprises an agent for cleaving peptide bonds.

16. The device of claim 5, wherein the switching structure comprises a switching conduit for providing a fluid from the first separation fluid-transporting feature to the second separation fluid-transporting feature when moved from a first to a second position.

17. The device of claim 16, the switching structure comprises a plurality of switching conduits for selectively providing fluid from the first separation fluid-transporting feature to at least one second separation fluid-transporting features on the second substrate.

18. The device of claim 17, wherein the second substrate comprises a plurality of second separation fluid-transporting features.

19. The device of claim 1, wherein the device comprises a sample-holding reservoir for holding a sample prior to or after separation by a separation fluid-transporting feature.

20. The device of claim 19, wherein the sample-holding reservoir comprises a waste reservoir.

21. The device of claim 20, wherein the waste-reservoir receives undesired components that have passed through a separation conduit.

22. The device of claim 1, wherein fluid is moved from a first substrate to a second substrate by providing a pressure differential at a connecting fluid-transporting feature that connects an inlet port on a second substrate to an outlet port on a first substrate.

23. The device of claim 1, wherein fluid is moved from a first substrate to a second substrate by providing a pressure differential at a connecting fluid-transporting feature that connects an inlet port on a second substrate to an outlet port on a first substrate.

24. The device of claim 16, wherein flow rate of fluid flowing through the switching conduit can be altered based on the position of the switching conduit relative to the first and second separation conduits.

25. The device of claim 24, wherein the flow rate of fluid flowing through the switching conduit is controllable by a pump for controlling flow through the first separation conduit when the switching conduit is in a first position and in fluid communication with the first separation conduit.

26. The device of claim 24, wherein the flow rate of fluid flowing through the switching conduit is controllable by a pump for controlling flow of fluid through the second separation conduit, when the switching conduit is in a second position and in fluid communication with the second separation conduit.

27. The device of claim 1, wherein the device comprises a sample inlet port in communication with the first separation fluid-transporting feature for introducing sample into the device.

28. A system, comprising:

a device according to claim 1, and a detector in communication with one or more fluid-transporting features of the device for detecting sample components.

29. The system according to claim 28, further comprising an analysis module for analyzing separated sample components.

30. The system according to claim 29, wherein the analysis module comprises a mass spectrometer.

31. The system according to claim 30, wherein the device comprises an interfacing module for providing separated sample components to the analysis module.

32. The system according to claim 31, wherein the interfacing module comprises an electrospray.

33. A method, comprising:

introducing a sample into the sample inlet port of a system according to claim 28;

separating sample components according to the first characteristic in the first separation fluid-transporting feature of the first substrate; and

providing sample components that have been separated according to the first characteristic to the second separation fluid-transporting feature of the second substrate for separation according to the second characteristic.

34. The method of claim 33, further comprising providing sample components that have been separated according to the second characteristic to an analysis module to obtain data about the sample components.

35. The method of claim 34, wherein the data includes data about the molecular weight and/or structure of a sample component.

36. The method of claim 34, wherein the analysis module comprises a mass spectrometer.

37. The method of claim 33, wherein a separation characteristic is selected from the group consisting of isoelectric point, charge, polarity, mass, affinity for a binding molecule hydrophobicity, chirality, and sequence characteristic of a biopolymer.

38. The method of claim 33, wherein the first and second characteristic are different.

39. The method of claim 33, wherein the first and second characteristic are the same.

40. The method of claim 33, wherein fluid flow from the first separation fluid-transporting feature is provided to the second fluid-transporting feature by moving a switching structure from a first position to a second position.

41. The method of claim 40, wherein the switching structure comprises a switching conduit.

42. The method of claim 41, wherein the rate of fluid flow through the switching structure is altered prior to, or during the step of providing fluid to the second separation conduit.

43. The method of claim 41, wherein the switching structure comprises a plurality of switching conduits.

44. The method of claim 41, wherein the second substrate comprises a plurality of second separation fluid transporting features.

45. The method of claim 44, wherein fluid from the first separation fluid-transporting feature is provided to a plurality of second separation fluid-transporting features simultaneously or sequentially.