Fluidic structures including meandering and wide channels

• US 8,501,416 B2
• Filed: 04/19/2006
• Issued: 08/06/2013
• Est. Priority Date: 04/19/2005
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation), Opko Diagnostics, LLC (Opko Health, Inc.)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Linder, Vincent, Sia, Samuel K., Whitesides, George M., Narovlyansky, Max, Siegel, Adam
• Primary Examiner(s): Yang, N. C.
• Application Number:
  US11/887,487
• Publication Number:
  US 20100167318A1
• Time in Patent Office: 2,666 Days
• Field of Search: None
• US Class Current: 435/7.1
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/0883 Serpentine channels
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 3/502746 characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: G01N 21/01 Arrangements or apparatus for facilitating the optical investigation
• CPC Class Codes: G01N 21/82 producing a precipitate or turbidity
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

The present invention relates generally to microfluidic structures, and more specifically, to microfluidic structures and methods including meandering and wide channels. Microfluidic systems can provide an advantageous environment for performing various reactions and analysis due to a reduction in sample and reagent quantities that are required, a reduction in the size of the operating system, and a decrease in reaction time compared to conventional systems. Unfortunately, the small size of microfluidic channels can sometimes result in difficulty in detecting a species without magnifying optics (such as a microscope or a photomultiplier). A series of tightly packed microchannels, i.e., a meandering region, or a wide channel having a dimension on the order of millimeters, can serve as a solution to this problem by creating a wide measurement area. Although this invention mainly describes the use of meandering and wide channels in heterogeneous immunoassays on a microfluidic chip, this invention could be used for amplifying optical signals for other types of reactions and/or assays.

Claims

1. A method comprising:

carrying out a chemical and/or biological reaction in a meandering region of a microfluidic channel;

exposing the meandering region to light, wherein the meandering region has an area of at least 0.5 mm²; and

measuring a signal averaged over more than one adjacent segments of the microfluidic channel in the meandering region.

2. A method as in claim 1, wherein the signal is a light transmittance signal.

3. A method as in claim 1, wherein determining the signal comprises using an optical system that does not comprise an optical magnifying component.

4. A method as in claim 1, wherein a first portion of the signal, measured from a first segment of the microfluidic channel in the meandering region, is substantially the same as a second portion of the signal, measured from a second, adjacent segment of the microfluidic channel in the meandering region.

5. A method as in claim 1, wherein a portion of the signal, measured from a first segment of the microfluidic channel in the meandering region, is substantially the same as a portion of the signal measured from at least 5 adjacent segments of the microfluidic channel in the meandering region.

6. A method as in claim 1, wherein the meandering region has an area of at least 2 mm².

7. A method as in claim 1, wherein the meandering region has an area of at least 4 mm².

17. A method as in claim 1, wherein the microfluidic channel in the meandering region comprises a binding partner adsorbed to a surface of the microfluidic channel.

18. A method as in claim 17, wherein the binding partner comprises an antibody or an antigen.

19. A method as in claim 1, wherein the chemical and/or biological reaction is a binding event between at least two binding partners, and wherein at least one of the binding partners comprises an antibody.

20. A method as in claim 1, wherein at least a portion of the microfluidic channel in the meandering region has a width of less than 500 microns.

21. A method as in claim 1, wherein at least a portion of the microfluidic channel in the meandering region has a width of less than 250 microns.

22. A method as in claim 1, comprising forming an opaque material in the meandering region of the microfluidic channel, and quantitatively determining the opacity of the opaque material.

23. A method as in claim 22, wherein quantitatively determining the opacity of the opaque material comprises measuring transmission of light through the opaque material through at least 25% of the area of the meandering region.

24. A method as in claim 1, wherein the meandering region having the area of at least 0.5 mm² is a first meandering region and the signal averaged over more than one adjacent segments of the microfluidic channel in the first meandering region is a first signal, wherein the first meandering region is in fluid communication with and positioned in series with respect to a second meandering region comprising a second microfluidic channel, and wherein the method comprises measuring a second signal averaged over more than one adjacent segments of the second microfluidic channel.

25. A method as in claim 1, wherein a first segment of the microfluidic channel in the meandering region is spaced apart from a second, adjacent segment of the microfluidic channel in the meandering region by a distance of less than the average width of the microfluidic channel in the meandering region.

26. A method as in claim 1, wherein a first segment of the microfluidic channel in the meandering region is spaced apart from a second, adjacent segment of the microfluidic channel in the meandering region by a distance of less than 2 times the average width of the microfluidic channel in the meandering region.

27. A method as in claim 1, comprising flowing in series in the microfluidic channel a predetermined sequence of fluid plugs including first, second and third fluids, wherein the first and second fluids are separated by the third fluid which is immiscible with both the first and second fluids.

28. A method as in claim 27, wherein the first and second fluids are liquids and the third fluid is a gas.

29. A method as in claim 28, wherein the first and/or second fluids is a rinse solution.

30. A method as in claim 29, wherein the first fluid is a rinse solution and the second fluid is a metal solution.

33. A method as in claim 1, wherein the signal is substantially homogeneous over more than one adjacent segments of the microfluidic channel.

37. A method as in claim 24, wherein the first signal is substantially homogeneous over all of the segments of the microfluidic channel in the first meandering region.

38. A method as in claim 1, wherein the exposing step involves exposing at least 50% of the area of the meandering region to light.

8. A method comprising:

passing a fluid over a surface of a meandering region of a microfluidic channel, wherein at least a portion of the microfluidic channel in the meandering region has a width of less than 0.5 mm;

allowing a sample component to bind with a binding partner disposed on the surface;

allowing a metal colloid to associate with a sample component;

flowing a metal solution over the surface to form a metallic layer; and

measuring a signal averaged over more than one adjacent segments of the microfluidic channel in the meandering region.

9. A method as in claim 8, wherein the signal is a transmittance signal.

10. A method as in claim 8, wherein the signal is measured without using magnifying optics.

11. A method as in claim 8, wherein the metal colloid comprises gold.

12. A method as in claim 8, wherein the metal colloid comprises a gold-conjugated antibody.

13. A method as in claim 8, wherein the metal solution comprises silver.

14. A method as in claim 8, further comprising measuring conductivity of the metallic layer.

31. A method as in claim 8, wherein a first segment of the microfluidic channel in the meandering region is spaced apart from a second, adjacent segment of the microfluidic channel in the meandering region by a distance of less than 2 times the average width of the microfluidic channel in the meandering region.

34. A method as in claim 8, comprising measuring a signal from the meandering region, wherein the signal is substantially homogeneous over more than one adjacent segments of the microfluidic channel in the meandering region.

15. A method comprising:

passing a fluid over a surface of a meandering region of a microfluidic channel, wherein at least a portion of the microfluidic channel in the meandering region has a width of less than 0.5 mm, and wherein the microfluidic channel comprises an upper surface and a lower surface;

allowing a sample component to bind with a binding partner disposed on at least one of the upper and lower surfaces;

allowing a metal colloid to associate with a sample component;

flowing a metal solution over the surface to form a metallic layer; and

measuring a signal averaged over more than one adjacent segments of the microfluidic channel in the meandering-region.

16. A method of claim 15, wherein at least a portion of the microfluidic channel in the meandering region has a width of less than 250 microns.

32. A method as in claim 15, wherein a first segment of the microfluidic channel in the meandering region is spaced apart from a second, adjacent segment of the microfluidic channel in the meandering region by a distance of less than 2 times the average width of the microfluidic channel in the meandering region.

35. A method as in claim 15, comprising measuring a signal from the meandering region, wherein the signal is substantially homogeneous over more than one adjacent segments of the microfluidic channel in the meandering region.

36. A method as in claim 35, wherein the signal is a light transmittance signal.