Reagent storage in microfluidic systems and related articles and methods

• US 8,591,829 B2
• Filed: 12/17/2009
• Issued: 11/26/2013
• Est. Priority Date: 12/18/2008
• Status: Active Grant

• Current Assignee: Opko Diagnostics, LLC (Opko Health, Inc.)
• Original Assignee: Opko Diagnostics, LLC (Opko Health, Inc.)
• Inventors: Taylor, Jason, Linder, Vincent
• Primary Examiner(s): Jarrett, Lore
• Application Number:
  US12/640,420
• Publication Number:
  US 20100158756A1
• Time in Patent Office: 1,440 Days
• Field of Search: 422/502
• US Class Current: 422/502
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2200/142 Preventing evaporation
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/069 Absorbents; Gels to retain a fluid
• CPC Class Codes: B01L 2300/0809 rectangular shaped
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/0883 Serpentine channels
• CPC Class Codes: B01L 2300/161 Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• 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 3/527 for a plurality of reagents
• CPC Class Codes: B01L 3/561 Tubes; Conduits in general F16L

Abstract

Fluidic devices and methods including those that provide storage and/or facilitate fluid handling of reagents are provided. Fluidic devices described herein may include channel segments positioned on two sides of an article, optionally connected by an intervening channel passing through the article. The channel segments may be used to store reagents in the device prior to first use by an end user. The stored reagents may include fluid plugs positioned in linear order so that during use, as fluids flow to a reaction site, they are delivered in a predetermined sequence. The specific geometries of the channel segments and the positions of the channel segments within the fluidic devices described herein may allow fluid reagents to be stored for extended periods of time without mixing, even during routine handling of the devices such as during shipping of the devices, and when the devices are subjected to physical shock or vibration.

Claims

1. A fluidic device comprising:

an article comprising first and second surfaces;

one or more first microfluidic channel segments formed in the first surface of the article;

one or more second microfluidic channel segments formed in the second surface of the article;

one or more intervening channels passing through the article from the first surface to the second surface and connecting the one or more first microfluidic channel segments and the one or more second microfluidic channel segments;

a first fluid reagent stored in at least a portion of one of the one or more first or second microfluidic channel segments;

a second fluid reagent stored in at least a portion of one of the one or more first or second a third fluid positioned between, and substantially immiscible with, the first and second fluid reagents, wherein the third fluid is configured to prevent or substantially reduce mixing between the first and second fluid reagents, wherein the third fluid is a gas bubble or a gaseous bubble;

microfluidic channel segments;

a fluid-tight seal covering an inlet in fluid communication with the one or more first and second microfluidic channel segments; and

a fluid-tight seal covering an outlet in fluid communication with the one or more first and second microfluidic channel segments,

wherein the fluid-tight seal covering the inlet and the fluid-tight seal covering the outlet are adapted and arranged to prevent or reduce evaporation and/or contamination of the first or second fluid reagents,

wherein the first and second fluids are separated by at least one intervening channel, and wherein the at least one intervening channel is configured to prevent or substantially reduce mixing between the first and second fluid reagents,

wherein the fluidic device is adapted and arranged to statically maintain the first and second fluid reagents for greater than one day, and

wherein the fluidic device is adapted and arranged to store the first and second reagents in the device for a period of at least one week.

2. The fluidic device of claim 1, wherein the first fluid reagent is stored in at least a portion of the one or more first microfluidic channel segments and the second fluid reagent is stored in at least a portion of another first microfluidic channel segment.

3. The fluidic device of claim 2, wherein at least one of the first and second fluid reagents is a rinse solution.

4. The fluidic device of claim 1, comprising a plurality of first and second microfluidic channel segments.

5. The fluidic device of claim 1, wherein the article is a single, integral piece of material without joined layers.

6. The fluidic device of claim 1, wherein two planes tangent to two points on a perimeter of a cross section of at least one of the one or more first channel segments intersect at an angle of less than or equal to 45°

, wherein the two points are on adjacent walls of the at least one of the one or more first channel segments, at least one of the walls being a portion of a cover substantially enclosing the at least one of the one or more first channel segments.

7. The fluidic device of claim 1, wherein at least one of the first and second fluid reagents is a liquid reagent.

8. The fluidic device of claim 1, wherein the first and second fluid reagents are liquid reagents, and wherein the first and second fluid reagents are separated by a third fluid reagent immiscible with the first and second fluid reagents.

9. The fluidic device of claim 8, wherein the third fluid reagent is a gas or a gaseous mixture.

10. The fluidic device of claim 1, wherein the first fluid reagent is stored in at least a portion of the one or more first microfluidic channel segments and the second fluid reagent is stored in at least a portion of the one or more second microfluidic channel segments.

11. The fluidic device of claim 1, wherein the first fluid reagent comprises a first binding partner and the second fluid reagent comprises a second binding partner adapted and arranged to bind with the first binding partner.

12. The fluidic device of claim 1, wherein the article further comprises a stored, dry reagent.

13. The fluidic device of claim 12, wherein the article comprises a channel that is not in fluid communication with the one or more first and second microfluidic channel segments, and wherein the stored reagent is a reagent immobilized on at least a portion of the channel that is not in fluid communication with the one or more first and second microfluidic channel segments.

14. The fluidic device of claim 1, further comprising a first cover adjacent the first surface of the article so as to substantially enclose the one or more first microfluidic channel segments, and a second cover adjacent the second surface of the article so as to substantially enclose the one or more second microfluidic channel segments.

15. The fluidic device of claim 14, wherein the one or more first microfluidic channel segments formed in the first surface of the article and the first cover mate such that a cross-section of the one or more first microfluidic channel segments, when mated with the first cover, includes a first portion adjacent the first cover that is convex and a second portion continuous with the first portion that is linear or concave.

16. The fluidic device of claim 15, wherein the convex portion comprises a radius of curvature of greater than or equal to at least 5 microns.

17. The fluidic device of claim 15, wherein the convex portion is continuous along the length of the one or more first microfluidic channel segments.

18. The fluidic device of claim 1, comprising a cover adjacent at least one of the first and second surfaces of the article, wherein the cover comprises a tape.

19. The fluidic device of claim 1, wherein the one or more first microfluidic channel segments and/or the one or more second microfluidic channel segments has a substantially trapezoidal cross section.

20. The fluidic device of claim 1, wherein the one or more first microfluidic channel segments and/or the one or more second microfluidic channel segments comprises side walls that are at least partially circular.

21. The fluidic device of claim 1, wherein the one or more first microfluidic channel segments and/or the one or more second microfluidic channel segments has at least one angle between adjacent walls of the channel segment of less than 90°

.

22. The fluidic device of claim 1, wherein the one or more intervening channels has a cross-sectional shape different than the cross-sectional shapes of the one or more first and/or second microfluidic channel segments.

23. The fluidic device of claim 1, wherein the one or more first microfluidic channel segments and/or the one or more second microfluidic channel segments has a draft angle of greater than or equal to 3°

.

24. The fluidic device of claim 1, wherein the one or more first microfluidic channel segments and/or the one or more second microfluidic channel segments has a draft angle of greater than or equal to 8°

.

25. The fluidic device of claim 1, wherein the article is formed of a polymeric material.

26. The fluidic device of claim 25, wherein the article is formed by injection molding.

27. The fluidic device of claim 1, wherein the first and/or second fluid reagent comprises a species capable of participating in a biological or chemical assay.

28. The fluidic device of claim 1, wherein no more than 5% of the perimeter of a cross section of the one or more first microfluidic channel segments is perpendicular to the first surface and/or wherein no more than 5% of the perimeter of a cross section of the one or more second microfluidic channel segments is perpendicular to the second surface.

29. The fluidic device of claim 1, wherein the one or more intervening channels has one or more cross-sectional dimensions within 50% of the smallest width of the one or more first and second microfluidic channel segments.

30. The fluidic device of claim 1, wherein the one or more intervening channels has a volume less than or equal to the volume of the first fluid reagent or the volume of the second fluid reagent stored in the fluidic device.

31. The fluidic device of claim 1, wherein the one or more intervening channels has a ratio of length to largest width of less than 3.

32. The fluidic device of claim 1, wherein the one or more first and/or second microfluidic channel segments have a width to depth ratio of greater than or equal to 1.

33. The fluidic device of claim 1, wherein the one or more first and/or second microfluidic channel segments have a cross-sectional dimension of less than 600 microns.

34. The fluidic device of claim 1, wherein the article has a thickness of less than 3 mm.

35. The fluidic device of claim 1, wherein the one or more intervening channels has a cross-sectional dimension that varies along at least a portion of the thickness of the article.

36. The fluidic device of claim 1, wherein the one or more intervening channels has a substantially circular cross section.

37. The fluidic device of claim 1, wherein the article comprises multiple substrate layers that are mated to one another.

38. The fluidic device of claim 37, wherein the one or more first microfluidic channel segments are formed in an article comprising a first material and the one or more second microfluidic channel segments are formed in an article comprising a second material.

39. A fluidic device comprising:

an article comprising first and second surfaces;

one or more first microfluidic channel segments formed in the first surface of the article;

one or more second microfluidic channel segments formed in the second surface of the article;

one or more intervening channels passing through the article from the first surface to the second surface and connecting the one or more first microfluidic channel segments and the one or more second microfluidic channel segments;

a first fluid reagent stored in at least a portion of one of the one or more first or second microfluidic channel segments or in at least a portion of one of the one or more intervening channels;

a second fluid reagent stored in at least a portion of the one or more first or second microfluidic channel segments or in at least a portion of the one or more intervening channels;

a third fluid positioned between, and substantially immiscible with, the first and second fluid reagents, wherein the third fluid is configured to prevent or substantially reduce mixing between the first and second fluid reagents, wherein the third fluid is a gas bubble or a gaseous bubble;

an inlet in fluid communication with the one or more first and second microfluidic channel segments;

an outlet in fluid communication with the one or more first and second microfluidic channel segments;

a first cover positioned over the one or more first microfluidic channel segments so as to substantially enclose the one or more first microfluidic channel segments;

a second cover positioned over the one or more second microfluidic channel segments so as to substantially enclose the one or more second microfluidic channel segments

a fluid-tight seal covering the inlet; and

a fluid-tight seal covering the outlet,

wherein the fluid-tight seal covering the inlet and the fluid-tight seal covering the outlet are adapted and arranged to prevent or reduce evaporation and/or contamination of the first or second fluid reagents.

40. The fluidic device of claim 39, wherein the first and second fluid reagents are statically maintained for greater than one day.

41. The fluidic device of claim 39, wherein the fluidic device is constructed and arranged such that the first reagent disposed therein can be stored for a period of at least one month.

42. A fluidic device comprising:

an article comprising first and second surfaces;

one or more first microfluidic channel segments formed in the first surface of the article;

one or more second microfluidic channel segments formed in the second surface of the article;

one or more intervening channels passing through the article from the first surface to the second surface and connecting the one or more first microfluidic channel segments and the one or more second microfluidic channel segments;

a first fluid reagent stored in at least a portion of the one or more first or second microfluidic channel segments or in at least a portion of the one or more intervening channels;

a second fluid reagent stored in at least a portion of the one or more first or second microfluidic channel segments or in at least a portion of the one or more intervening channels;

a third fluid positioned between, and substantially immiscible with, the first and second fluid reagents, wherein the third fluid is configured to prevent or substantially reduce mixing between the first and second fluid reagents, wherein the third fluid is a gas bubble or a gaseous bubble;

an inlet in fluid communication with the one or more first and second microfluidic channel segments;

an outlet in fluid communication with the one or more first and second microfluidic channel segments;

a first cover positioned over the one or more first microfluidic channel segments so as to substantially enclose the one or more first microfluidic channel segments;

a second cover positioned over the one or more second microfluidic channel segments so as to substantially enclose the one or more second microfluidic channel segments

a fluid-tight seal covering the inlet; and

a fluid-tight seal covering the outlet,

wherein the fluid-tight seal covering the inlet and the fluid-tight seal covering the outlet are adapted and arranged to prevent or reduce evaporation and/or contamination of the first or second fluid reagents, and

wherein the fluidic device is adapted and arranged to store the first and second reagents in the device for a period of at least one week.