Lateral flow and flow-through bioassay devices based on patterned porous media, methods of making same, and methods of using same

• US 9,193,988 B2
• Filed: 11/21/2013
• Issued: 11/24/2015
• Est. Priority Date: 10/18/2006
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Whitesides, George M., Phillips, Scott T., Martinez, Andres W., Butte, Manish J., Wong, Amy, Thomas, Samuel W., Sindi, Hayat, Vella, Sarah J., Carrilho, Emanuel, Mirica, Katherine A., Liu, Yanyan
• Primary Examiner(s): Xu, Robert
• Application Number:
  US14/085,972
• Publication Number:
  US 20140234881A1
• Time in Patent Office: 733 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/06 Auxiliary integrated devices, integrated components
• CPC Class Codes: B01L 2300/0848 Specific forms of parts of containers
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/126 Paper
• CPC Class Codes: B01L 2300/161 Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: C12Q 1/48 involving transferase
• CPC Class Codes: G01N 21/77 by observing the effect on a chemical indicator
• CPC Class Codes: G01N 33/523 the element being adapted for a specific analyte
• CPC Class Codes: G01N 33/526 the element being adapted for a specific analyte
• CPC Class Codes: G01N 33/54388 based on lateral flow
• CPC Class Codes: G01N 33/54391 based on vertical flow
• CPC Class Codes: G01N 33/558 using diffusion or migration of antigen or antibody immunochromatographic test strips G01N33/54387
• CPC Class Codes: G06F 3/005 Input arrangements through a video camera

Abstract

Embodiments of the invention provide lateral flow and flow-through bioassay devices based on patterned porous media, methods of making same, and methods of using same. Under one aspect, an assay device includes a porous, hydrophilic medium; a fluid impervious barrier comprising polymerized photoresist, the barrier substantially permeating the thickness of the porous, hydrophilic medium and defining a boundary of an assay region within the porous, hydrophilic medium; and an assay reagent in the assay region.

Claims

1. A three-dimensional assay device comprising:

a plurality of porous, hydrophilic media in the form of substantially planar sheets disposed face-to-face and separated from each other by a fluid-impermeable layer having one or more openings for fluid communication between adjacent sheets,

a said sheet comprising a pattern of fluid-impervious barriers substantially inserting through the thickness of the sheet thereby to define a boundary for plural assay regions, and

one or more assay reagents disposed in the assay regions which provide an indication in the device of a clinically relevant presence or concentration of an analyte.

2. The device of claim 1 wherein the barriers physically separate the plural assay regions from one another.

3. The device of claim 2 comprising multiple flow paths through which fluids pass and which distribute analyte to the assay regions.

4. The assay device of claim 1 wherein the assay reagent(s) provide a visible indication of a clinically relevant presence or concentration of an analyte which can be digitized to reproduce an image of said visual indication which also is clinically relevant.

5. The assay device of claim 3 wherein the assay reagent(s) provide a visible indication of a clinically relevant presence or concentration of an analyte which can be digitized to reproduce an image of said visual indication which also is clinically relevant.

6. The device of claim 1 which provides a visible indication of the concentration of an analyte.

7. The device of claim 3 which provides a visible indication of the concentration of an analyte.

8. The device of claim 1 comprising different assay reagents disposed in the assay regions, which different assay reagents provide a visible indication of the presence or concentration of one or more analytes in the assay regions.

9. The device of claim 3 comprising different assay reagents disposed in the assay regions, which different assay reagents provide a visible indication of the presence or concentration of one or more analytes in the assay regions.

10. The device of claim 1 further comprising a sample deposition region bounded by an opening in a fluid-impermeable layer disposed in face-to-face relation with a said sheet.

11. The device of claim 9 further comprising a sample deposition region bounded by an opening in a fluid-impermeable layer disposed in face-to-face relation with a said sheet.

12. The device of claim 10 further comprising a filter in fluid communication with said sample deposition region.

13. The device of claim 11 further comprising a filter in fluid communication with said sample deposition region.

14. The device of claim 10 further comprising a protective layer on the side of the device opposite the side of the device containing the sample deposition region.

15. The device of claim 13 further comprising a protective layer on the side of the device opposite the side of the device containing the sample deposition region.

16. The device of claim 1 wherein at least one assay region is a control region.

17. The device of claim 9 wherein at least one assay region is a control region.

18. The device of claim 1 wherein at least one assay region comprises an assay reagent for detection of alanine aminotransferase.

19. The device of claim 9 wherein at least one assay region comprises an assay reagent for detection of alanine aminotransferase.

20. The device of claim 17 wherein at least one assay region comprises an assay reagent for detection of alanine aminotransferase.

21. The device of claim 1 wherein at least one assay region comprises an assay reagent for detection of aspartate aminotransferase.

22. The device of claim 9 wherein at least one assay region comprises an assay reagent for detection of aspartate aminotransferase.

23. The device of claim 20 wherein at least one assay region comprises an assay reagent for detection of aspartate aminotransferase.

24. The device of claim 1 wherein said porous, hydrophilic media comprises a material selected from the group consisting of polymer film, nitrocellulose acetate, cellulose acetate, fibrous material, paper, and cloth.

25. The device of claim 9 wherein said porous, hydrophilic media comprises a material selected from the group consisting of polymer film, nitrocellulose acetate, cellulose acetate, fibrous material, paper, and cloth.

26. The device of claim 23 wherein said porous, hydrophilic media comprises a material selected from the group consisting of polymer film, nitrocellulose acetate, cellulose acetate, fibrous material, paper, and cloth.

27. The device of claim 1 wherein said porous, hydrophilic media is paper.

28. The device of claim 9 wherein said porous, hydrophilic media is paper.

29. The device of claim 23 wherein said porous, hydrophilic media is paper.

30. The device of claim 1 wherein said barrier comprises a material selected from the group consisting of a curable polymer, polymerized photoresist, wax, and poly(dimethyl-siloxane).

31. The device of claim 9 wherein said barrier comprises a material selected from the group consisting of a curable polymer, polymerized photoresist, wax, and poly(dimethyl-siloxane).

32. The device of claim 29 wherein said barrier comprises a material selected from the group consisting of a curable polymer, polymerized photoresist, wax, and poly(dimethyl-siloxane).

33. The device of claim 1 wherein said barrier is wax.

34. The device of claim 9 wherein said barrier is wax.

35. The device of claim 28 wherein said barrier is wax.

36. The device of claim 29 wherein said barrier is wax.