Electropipettor and compensation means for electrophoretic bias

• US 6,080,295 A
• Filed: 03/20/1998
• Issued: 06/27/2000
• Est. Priority Date: 06/28/1996
• Status: Expired due to Term

• Current Assignee: Caliper Technologies Corp (Revvity, Inc.)
• Original Assignee: Caliper Technologies Corp (Revvity, Inc.)
• Inventors: Parce, J. Wallace, Knapp, Michael R.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): STARSIAK, JOHN S
• Application Number:
  US09/045,339
• Time in Patent Office: 830 Days
• Field of Search: 204/450, 204/451, 204/452, 204/453, 204/454, 204/455, 204/600, 204/601, 204/602, 204/603, 204/604, 204/605, 422/68.1, 422/100, 422/102
• US Class Current: 204/451
• CPC Class Codes: B01F 33/3021 the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
• CPC Class Codes: B01F 33/30351 using hydrophilic/hydrophobic surfaces
• CPC Class Codes: B01F 33/30352 using roughness of the surfaces
• 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 2219/00891 Feeding or evacuation
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0418 electro-osmotic flow [EOF]
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• CPC Class Codes: B01L 3/021 Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• 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 17/00 Pumps characterised by combination with, or adaptation to, specific driving engines or motors
• 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 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: H02N 11/006 Motors
• CPC Class Codes: Y10S 366/02 Micromixers: segmented laminar flow with boundary mixing orthogonal to the direction of fluid propagation with or without geometry influences from the pathway
• CPC Class Codes: Y10T 436/113332 : with conveyance of sample along a test line in a container or rack
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

The present invention provides for techniques for transporting materials using electrokinetic forces through the channels of a microfluidic system. The subject materials are transported in regions of high ionic concentration, next to spacer material regions of high ionic concentration, which are separated by spacer material regions of low ionic concentration. Such arrangements allow the materials to remain localized for the transport transit time to avoid mixing of the materials. Using these techniques, an electropipettor which is compatible with the microfluidic system is created so that materials can be easily introduced into the microfluidic system. The present invention also compensates for electrophoretic bias as materials are transported through the channels of the microfluidic system by splitting a channel into portions with positive and negative surface charges and a third electrode between the two portions, or by diffusion of the electrophoresing materials after transport along a channel.

Claims

1. A microfluidic system with compensation for electrophoretic bias, comprising:

a first capillary channel;

a second capillary channel intersecting said first capillary channel; and

a chamber at said intersection of said first and second capillary channels shaped such that a region containing subject material moving from said first capillary channel to said second capillary channel is mixed to compensate for electrophoretic bias in moving along said first capillary channel;

wherein said chamber is defined by sides along a first capillary channel length funneling into said second capillary channel.

2. The microfluidic system of claim 1 wherein said chamber sides are straight.

3. The microfluidic system of claim 1 wherein said second capillary channel width is approximately equal to a length of said subject material region.

4. The microfluidic system of claim 1 wherein said subject material has a diffusion constant and said second capillary channel has a width such that said subject material diffuses across said second channel width before being diverted from said second channel.

5. The microfluidic system of claim 4 wherein said subject material has a diffusion constant of approximately 1×

10^-5 cm² /sec. and said second channel width is approximately 10 μ

m.

6. A microfluidic system, comprising:

a body structure;

a first microscale channel disposed in the body structure;

a second microscale channel disposed in the body structure, the second channel intersecting the first channel at a first intersection;

a chamber disposed in the body structure at the intersection, side walls of the chamber funneling into the second channel; and

an electrokinetic material transport system for transporting a subject material region from at least one of the first channel into the second channel through the chamber.

7. The microfluidic system of claim 6, wherein the chamber is defined by sides along the first channel length funneling into the second microscale channel.

8. The microfluidic system of claim 7, wherein the sides of the chamber are straight.

9. The microfluidic system of claim 6, further comprising at least a first subject material disposed in and being transported along the first microscale channel.

10. The microfluidic system of claim 9, wherein the second microscale channel width is approximately equal to a length of the subject material region.

11. The microfluidic system of claim 9, wherein the subject material has a diffusion constant and the second channel has a width, whereby the subject material diffuses across the second channel width while the subject material region is in the chamber.

12. The microfluidic system of claim 11, wherein the subject material has a diffusion constant of approximately 1×

10^-5 cm² /sec and the channel width is approximately 10 μ

m.

13. The microfluidic system of claim 6, wherein the body structure comprises:

a first planar substrate having a first planar surface, the first and second microscale channel and the chamber being fabricated into the first planar surface;

a second planar substrate overlying the first planar surface of the first substrate to cover the first and second microscale channels and the chamber.

14. The microfluidic system of claim 13, wherein at least one of first and second substrates is glass.

15. The microfluidic system of claim 13, wherein at least one of the first and second planar substrates is a polymer.

16. The microfluidic system of claim 6, wherein the electrokinetic material transport system comprises at least first, second, and third electrodes, the first and second electrodes being disposed in electrical contact with the first channel on opposite sides of the intersection, and the third electrode being disposed in electrical contact with the second microscale channel, the first, second and third electrodes being separately electrically coupled to a voltage source for delivering a separate voltage to at least two of the first, second and third electrodes to produce a voltage gradient therebetween.

17. A method of mixing a subject material region in a microfluidic system, comprising:

providing a microfluidic device which comprises a body structure, a first microscale channel, a second microscale channel intersecting the first microscale channel and a chamber disposed in the body structure at the intersection of the first and second channels, the chamber comprising side walls that funnel into the second channel;

applying a first electric field along a length of the first channel to move a first material region along the first channel and into the chamber, whereupon the first material region is mixed; and

applying a second electric field along a length of the second channel to move at least a portion of the first material region from the chamber into the second channel.

18. The method of claim 17, wherein the subject material region is electrophoretically biased during electrokinetic transport along the first channel.

19. The method of claim 17, wherein the first subject material has a diffusion constant and the second channel has a width, such that the subject material diffuses across the width while in the chamber.

20. The method of claim 19, wherein the diffusion constant is approximately 1×

10^-5 cm² /sec and the width is approximately 10 μ

m.

21. A method of electrokinetically transporting a first material region through a microfluidic system while correcting for electrophoretic bias of the subject material in the subject material region, comprising:

providing a microfluidic device having at least first and second microscale channels, the first and second microscale channels intersecting at a first intersection, the first intersection being defined by a chamber that funnels into the second channel;

transporting the subject material along a first microscale channel into the chamber; and

funneling the subject material from the chamber into the second microscale channel, whereby the subject material diffuses across the subject material region.