Mixed mode microfluidic systems

• US 7,101,467 B2
• Filed: 12/22/2003
• Issued: 09/05/2006
• Est. Priority Date: 03/05/2002
• Status: Expired due to Term

• Current Assignee: Caliper Life Sciences Incorporated (Revvity, Inc.)
• Original Assignee: Caliper Life Sciences Incorporated (Revvity, Inc.)
• Inventors: Spaid, Michael A.
• Primary Examiner(s): NOGUEROLA, ALEXANDER STEPHAN
• Application Number:
  US10/744,915
• Publication Number:
  US 20040188254A1
• Time in Patent Office: 988 Days
• Field of Search: 422/99, 422/100, 204450-455, 204600-604
• US Class Current: 204/453
• CPC Class Codes: B01F 33/3031 using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids
• 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 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/502784 specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: F04B 19/006 Micropumps F04B43/043 and F04B43/095 take precedence
• CPC Class Codes: G01N 27/44704 Details; Accessories
• CPC Class Codes: G01N 27/44743 Introducing samples
• 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: H02N 11/006 Motors

Abstract

Methods and systems that employ hybrid fluid flow profiles for optimized movement of materials through channel networks. These systems employ hybrid pressure-based and electrokinetic based flow systems for moving materials through interconnected channel networks while maintaining interconnection among the various channel segments. In particular, the invention is generally directed to channel networks where flow in a first channel segment is driven by pressure flow with its consequent parabolic flow profile, while flow in an interconnected channel segment is dominated by electrokinetic flow with its consequent plug flow profile. The invention also provides channel networks wherein fluid flow in channel segments is driven by both pressure and electric field and the multiple species contained in a fluid plug are separated (and can be concentrated) by altering the applied pressure and electric fields in the various channel segments of the channel networks.

Claims

1. A method of extracting a charged species from a sample and concentrating it, comprising:

providing an interconnected channel network comprising a first, second and third channel segment which intersect at a first fluid junction, the second channel segment terminating in a first fluid reservoir at one end and intersecting the first fluid junction at its other end, and a fourth channel segment intersecting the third channel segment at a second fluid junction at one end and terminating in a second fluid reservoir at its other end, the second fluid reservoir comprising a first buffer;

flowing the charged species in the sample in a second buffer through the interconnected channel network by applying a first pressure differential across the first and second channel segments and a second pressure differential across the third and fourth channel segments, wherein the first pressure differential is larger than the second pressure differential and the first buffer has a different ionic strength than the second buffer; and

applying a voltage differential across the first and second reservoirs which is sufficient to cause a substantial portion of the charged species in the sample in the first fluid junction to flow into the third channel segment.

2. The method of claim 1, wherein the first, second, third and fourth channel segments are disposed in a body structure of a microfluidic device.

3. The method of claim 1, wherein the first pressure differential is generated by applying a vacuum to the first fluid reservoir.

4. The method of claim 1, wherein the second pressure differential is generated at least in part by applying a positive pressure to the second fluid reservoir.

5. The method of claim 1, wherein the first buffer has a higher ionic strength than the second buffer.

6. The method of claim 1, wherein the difference between the first pressure differential and the second pressure differential is such that a pressure driven flow rate or velocity in the first channel segment is at least about two times greater than a pressure driven flow rate or velocity in the third channel segment.

7. The method of claim 1, wherein the difference between the first pressure differential and the second pressure differential is such that a pressure driven flow rate or velocity in the first channel segment is at least about five times greater than a pressure driven flow rate or velocity in the third channel segment.

8. The method of claim 1, wherein the difference between the first pressure differential and the second pressure differential is such that a pressure driven flow rate or velocity in the first channel segment is at least about ten times greater than a pressure driven flow rate or velocity in the third channel segment.

9. The method of claim 1, wherein the difference between the first pressure differential and the second pressure differential is such that a pressure driven flow rate or velocity in the first channel segment is at least about twenty times greater than a pressure driven flow rate or velocity in the third channel segment.

10. The method of claim 1, wherein an electrokinetic velocity of the charged species in the second channel segment is greater than its pressure driven velocity.

11. The method of claim 1, wherein an electrokinetic velocity of the charged species in the fourth channel segment is less than its pressure driven velocity.

12. The method of claim 1, further comprising a fifth channel segment fluidly coupled to the second fluid junction, wherein a total flow rate or velocity of the charged species in the fifth channel segment is about five times less than a total flow rate or velocity of the charged species in the third channel segment.

13. The method of claim 1, further comprising a fifth channel segment fluidly coupled to the second fluid junction, wherein a total flow rate or velocity of the charged species in the fifth channel segment is about ten times less than a total flow rate or velocity of the charged species in the third channel segment.

14. The method of claim 1, wherein the charged species is DNA or RNA.

15. The method of claim 14, further comprising amplifying the DNA or RNA one or more times in a fifth channel segment of the interconnected channel network.

16. The method of claim 1, wherein the first buffer forms a fluid boundary with the second buffer in the second fluid junction sufficient to concentrate the charged species in or near the second fluid junction.

17. The method of claim 16, wherein the charged species is concentrated at least about five times in or near the second fluid junction.

18. The method of claim 16, wherein the charged species is concentrated at least about ten times in or near the second fluid junction.

19. The method of claim 1, wherein a substantial portion of the sample in the second buffer other than the charged species flows into the second channel segment.