IP Library Granted Patent US 9,090,868
Granted Patent B2
US 9,090,868 · App. 13/808,887 · Granted Jul 28, 2015

Alginate hydrogel fibers and related materials

Inventors: Charles R. Mace (Auburn, NY); Jabulani Barber (Fair Oaks, CA); Anna Laromaine Sagué (Cambridge, MA); George M. Whitesides (Newton, MA); Rebecca Cademartiri (Somerville, MA)
Assignee: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
C12N5/0062C12N5/0068C12N2533/30C12N2533/56C12N2533/74
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Quick Facts
Patent No.
US 9,090,868
App. No.
13/808,887
Granted
Jul 28, 2015
Kind
B2
Abstract

Alginate hydrogel fibers and related materials as well as methods for preparing such materials are provided. An alginate hydrogel fiber includes water in an amount of more than about 92% by weight of the fiber and a cross-linked alginate in an amount of about 0.1% to about 8% by weight of the fiber, wherein the cross-link is a cation. An alginate hydrogel paper includes one or more alginate hydrogel fibers, which form a non-woven matrix. Three-dimensional cellular arrays are also provided, wherein the alginate hydrogel making up the alginate paper is substantially index-matched with a predetermined culture medium. A method for making alginate hydrogel fiber and a method for index-matching alginate hydrogel paper with culture medium are provided. A kit for conducting biochemical, diagnostic, cellular, and/or non-cellular analysis comprises alginate hydrogel paper index-matched to culture medium.

Claims (24)

1. A three-dimensional cellular array, comprising:

an alginate hydrogel paper comprising:

a plurality of alginate hydrogel fibers, comprising water in an amount of more than about 92% by weight of the fiber; and

a cross-linked alginate in an amount of about 0.1% to about 8% by weight of the fiber, wherein the cross-link is a multivalent cation, and wherein the alginate hydrogel fibers form a woven or non-woven matrix; and

a medium comprising cells, wherein the medium and cells are located in the hydrogel paper, wherein the alginate hydrogel making up the alginate hydrogel paper is substantially index-matched with the medium.

2. The cellular array of claim 1 , wherein a selected region of the hydrogel paper comprises hydrogel and cells, and the hydrogel serves to support and contain the cells.

3. A three-dimensional cellular array, comprising:

an alginate hydrogel paper comprising:

a plurality of alginate hydrogel fibers, comprising water in an amount of more than about 92% by weight of the fiber; and

a cross-linked alginate in an amount of about 0.1% to about 8% by weight of the fiber, wherein the cross-link is a multivalent cation, and wherein the alginate hydrogel fibers form a woven or non-woven matrix; wherein the alginate hydrogel paper comprises a plurality of porous regions, each porous region bounded at least in part by a liquid impervious boundary,

wherein the alginate hydrogel making up the alginate hydrogel paper is substantially index-matched with an aqueous medium.

4. The cellular array of claim 1 or claim 3 , wherein the array comprises a plurality of alginate hydrogel papers, and the plurality of the papers are arranged in a manner selected from the group consisting of in a stack, as a cascade, and as a loose web or loose net of fibers.

5. The cellular array of claim 4 , wherein the array further comprises conventional paper.

6. The cellular array of claim 5 , wherein the alginate hydrogel paper stack is disposed between a support framework.

7. The cellular array of claim 3 , wherein the aqueous medium comprises cells disposed in the porous region.

8. The cellular array of claim 3 , wherein the liquid impervious boundary is selected from the group consisting of siloxane, poly(lactic-co-glycolic acid), epoxy, polystyrene, a polyether, a polyamide, acrylate, polycarbonate, polyethylene, polypropylene, a photoresist precursor, a wax, and a fat.

9. The cellular array of claim 1 or claim 3 , wherein the difference in refractive indices between the alginate hydrogel paper and the medium ranges from about 0.01 to about 0.

10. The cellular array of claim 1 or claim 3 , wherein the cation cross-linker comprises barium.

11. The cellular array of claim 1 or claim 3 , wherein the medium is selected from the group consisting of a biologically derived medium, nutrient medium, and simulated bodily fluid.

12. The cellular array of claim 1 , wherein the alginate hydrogel paper is used to conduct analysis selected from the group consisting of a biochemical, diagnostic, cellular, and non-cellular analysis.

13. A method of conducting a cellular analysis, comprising:

providing a three-dimensional cellular array according to claim 1 or claim 3 ; and a medium comprising cells, wherein the alginate paper is index matched with the medium, and wherein cells are located within a selected region of the cellular array; and

visualizing the cells using light, wherein the alginate paper is translucent under the conditions used to visualize the cells.

14. The method of claim 13 , wherein the visualization is carried out using a device selected from the group consisting of a fluorescent microscope, a light microscope, a fluorescent scanner, a light scanner, and a transmission spectrometer.

Assignments (2)
CONFIRMATORY LICENSE Recorded Jun 8, 2016
From: HARVARD UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 038908/0496 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 8, 2013
From: BARBER, JABULANI; CADEMARTIRI, REBECCA; LAROMAINE SAGUE, ANNA; MACE, CHARLES R.; WHITESIDES, GEORGE M.
To: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Reel/Frame 030971/0515 →
Continuity (2)
Provisional Application 61363457 · Jul 12, 2010
Related Publication 20130316387A1 · Nov 28, 2013