Method for in situ concentration and/or dilution of materials in microfluidic systems

• US 6,475,441 B1
• Filed: 09/01/2000
• Issued: 11/05/2002
• Est. Priority Date: 06/09/1997
• Status: Expired due to Term

• Current Assignee: Caliper Technologies Corp (Revvity, Inc.)
• Original Assignee: Caliper Technologies Corp (Revvity, Inc.)
• Inventors: Parce, John Wallace, Kopf-Sill, Anne R.
• Primary Examiner(s): Alexander, Lyle A.
• Application Number:
  US09/654,601
• Time in Patent Office: 795 Days
• Field of Search: 422/100, 422/68.1, 436/52, 436/179, 436/180, 436/174, 738/63, 204/600, 204/603, 204/604
• US Class Current: 436/179
• CPC Class Codes: B01F 25/3142 the conduit having a plurality of openings in the axial direction or in the circumferential direction
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00783 Laminate assemblies, i.e. the reactor comprising a stack of plates
• CPC Class Codes: B01J 2219/00826 Quartz
• CPC Class Codes: B01J 2219/00828 Silicon wafers or plates
• CPC Class Codes: B01J 2219/00831 Glass
• CPC Class Codes: B01J 2219/00833 Plastic
• CPC Class Codes: B01J 2219/00853 Employing electrode arrangements
• CPC Class Codes: B01J 2219/00889 Mixing
• CPC Class Codes: B01J 2219/00905 Separation
• 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 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/088 Channel loops
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0418 electro-osmotic flow [EOF]
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• 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: 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: G01N 1/38 : Diluting, dispersing or mixing samples
• CPC Class Codes: G01N 1/40 : Concentrating samples
• CPC Class Codes: G01N 27/44743 : Introducing samples
• CPC Class Codes: G01N 27/44791 : Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: Y10T 436/117497 : with a continuously flowing sample or carrier stream
• CPC Class Codes: Y10T 436/25625 : Dilution
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

The present invention is generally directed to methods, apparatus and systems for use in performing in situ dilution or concentration of a particular subject material in a microfluidic device or system. These methods and apparatus may generally be integrated with other microfluidic operations and/or systems, to perform a number of different manipulations, wherein dilution or concentration, carried out within the context of the microfluidic device or system, is just one part.

Claims

1. A method of concentrating a material, comprising:

providing a first conduit having at least first and second fluid regions disposed therein, the first and second fluid regions being in contact at a first fluid interface, and wherein the first fluid region has a lower electrical conductivity than the second fluid region;

providing the material in the first fluid region; and

applying a voltage gradient through the first and at least a portion of the second fluid region to concentrate the material at the first fluid interface.

2. The method of claim 1, wherein the electrical conductivity of the second fluid region is at least two times the electrical conductivity of the first fluid region.

3. The method of claim 1, wherein the electrical conductivity of the second fluid region is at least five times the electrical conductivity of the first fluid region.

4. The method of claim 1, wherein the electrical conductivity of the second fluid region is at least ten times the electrical conductivity of the first fluid region.

5. The method of claim 1, wherein the electrical conductivity of the second fluid region is at least twenty times the electrical conductivity of the first fluid region.

6. The method of claim 1, further comprising:

providing a second conduit in fluid communication with the first conduit; and

moving the material concentrated at the first fluid interface from the first conduit into the second conduit.

7. The method of claim 6, further comprising subjecting the concentrated material to an analysis step.

8. The method of claim 7, wherein the analysis step comprises electrophoretically separating the concentrated material.

9. The method of claim 6, wherein the concentrated material is subjected to a screening assay.

10. The method of claim 1, wherein the first fluid region is provided in the first conduit by introducing the first fluid region into the first conduit from a second conduit that is in fluid communication with the first fluid conduit.

11. The method of claim 1, wherein the first and second fluid regions are flowed along the first fluid conduit.

12. The method of claim 1, further comprising:

providing a second conduit in fluid communication with the first conduit for introducing the first fluid region from the second conduit into the first conduit; and

providing a third conduit in fluid communication with the first conduit for moving the material concentrated at the fluid interface from the first conduit into the third conduit.

13. The method of claim 1, wherein the first conduit comprises:

a microscale channel; and

a reservoir, wherein the first fluid region is partially disposed in said reservoir.

14. The method of claim 13, wherein the second fluid region is fully disposed in said microchannel.