IP Library Granted Patent US 9,927,334
Granted Patent B2
US 9,927,334 · App. 13/982,680 · Granted Mar 27, 2018

Methods, compositions and devices employing alginic acid hydrogels for highly specific capture and release of biological materials

Inventors: Shashi K. Murthy (Newton, MA); Adam Hatch (Cambridge, MA); George Hansmann (Boston, MA)
Assignee: Northeastern University
G01N1/34B01F5/061B01F13/0059G01N33/548G01N33/54386G01N33/56966B01F2005/0623B01F2005/0636B01L3/502761B01L2200/0636B01L2200/0652B01L2300/069B01L2300/0867B01L2400/0478
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Quick Facts
Patent No.
US 9,927,334
App. No.
13/982,680
Granted
Mar 27, 2018
Kind
B2
Abstract

Disclosed herein are hydrogel compositions and methods of making hydrogel compositions. Furthermore, methods of specifically capturing and releasing biological materials from a sample using the disclosed hydrogel compositions are disclosed, including methods of utilizing the compositions in microfluidic devices.

Claims (25)

1. A hydrogel composition comprising:

a plurality of alginic acid molecules;

divalent cations crosslinking the alginic acid molecules;

a plurality of branched polyethylene glycol molecules comprising a plurality of attachment points; and

one or more binding agents,

wherein the alginic acid molecules are conjugated to the branched polyethylene glycol molecules by a first of the attachment points, and the one or more binding agents are conjugated to the branched polyethylene glycol molecules by a second of the attachment points, and wherein the hydrogel composition dissolves in the presence of a chelator.

2. The composition of claim 1 , wherein the branched polyethylene glycol molecules are four-arm molecules.

3. The composition of claim 1 , wherein the one or more binding agents is an antibody, antibody fragment, peptidomimetic compound, peptide, small molecule, or nucleic acid.

4. The composition of claim 3 , wherein the antibody is selected from the group consisting of antibodies against GPR49, LGR5, CD24, FLK1, CD45, CD31, CD34, and sca-1 proteins.

5. A method of capturing and releasing target biological materials from a sample, the method comprising:

(a) providing a microfluidic device comprising one or more chambers for receiving fluids, wherein at least one of the one or more chambers comprises a surface coated with a hydrogel composition, the hydrogel composition comprising:

a plurality of alginic acid molecules; divalent cations crosslinking the alginic acid molecules; branched polyethylene glycol molecules comprising a plurality of attachment points; and one or more binding agents that bind to the target biological materials;

wherein the alginic acid molecules are conjugated to the branched polyethylene glycol molecules by a first of the attachment points, and the one or more binding agents are conjugated to the branched polyethylene glycol molecules by a second of the attachment points, and wherein the hydrogel composition dissolves in the presence of a chelator;

(b) introducing the sample comprising target and non-target biological materials into the one or more chambers under conditions effective to bind the target biological materials to the hydrogel composition; and

(c) releasing the target biological materials using a chelator.

6. The method of claim 5 , further comprising removing the unbound non-target materials from the sample prior to step (c).

7. A method of making a hydrogel composition, the method comprising:

(a) reacting branched polyethylene glycol molecules comprising a plurality of attachment points with one or more binding agents in a buffer; and

(b) reacting the branched polyethylene glycol binding agent solution with alginic acid molecules and divalent cations to form a functionalized hydrogel, the functionalized hydrogel comprising branched polyethylene glycol molecules conjugated at least one alginic acid molecule by a first of the attachment points and further conjugated to one or more binding agents by a second of the attachment points, wherein the hydrogel composition dissolves in the presence of a chelator.

8. The method of claim 7 , wherein the polyethylene glycol molecule is a four-arm molecule.

9. The method of claim 7 , wherein the one or more binding agents is an antibody, antibody fragment, peptidomimetic compound, peptide, small molecule, or a nucleic acid.

10. The method of claim 9 , wherein the antibody is selected from the group consisting of antibodies against GPR49, LGR5, CD24, FLK1, CD45, CD31, CD34, and sca-1 proteins.

11. The hydrogel composition of claim 1 , wherein the divalent cations are Ca 2+ cations.

12. The method of claim 5 , wherein the divalent cations are Ca 2+ cations.

13. The method of claim 7 , wherein the divalent cations are Ca 2+ cations.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 21, 2016
From: MURTHY, SHASHI K.; HATCH, ADAM; HANSMANN, GEORG
To: NORTHEASTERN UNIVERSITY
Reel/Frame 040084/0655 →
CONFIRMATORY LICENSE Recorded Aug 14, 2013
From: NORTHEASTERN UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 031013/0567 →
Continuity (2)
Provisional Application 61439166 · Feb 3, 2011
Related Publication 20140057280A1 · Feb 27, 2014