IP Library Granted Patent US 12,637,669
Granted Patent B2
US 12,637,669 · App. 17/840,815 · Granted May 26, 2026

Two-dimensional and three-dimensional microarray cell cultures using elastomeric assembly substrates

Inventors: Stephen Morin (Lincoln, NE); Ruiguo Yang (Lincoln, NE); Karla Perez-Toralla (Lincoln, NE); Mark Rose (Lincoln, NE); Angel Olivera-Torres (Lincoln, NE); John Kapitan (Lincoln, NE); Grayson Minnick (Lincoln, NE)
Assignee: NUTECH VENTURES
C12N11/04
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Quick Facts
Patent No.
US 12,637,669
App. No.
17/840,815
Granted
May 26, 2026
Kind
B2
Abstract

The invention provides a method for preparing an ordered cell-containing microarray, and a system for preparing an ordered cell-containing microarray.

Claims (27)

1 . A method for preparing an ordered microarray, the method comprising process (A) or process (B):

(A) (i) providing an elastomeric substrate,

(ii) modifying a surface of the elastomeric substrate thereby producing a surface-modified elastomeric substrate,

(iii) spraying a composition onto the surface-modified elastomeric substrate thereby producing a disordered microarray, and

(iv) applying a strain to the disordered microarray thereby producing the ordered microarray; or

(B) (i) providing an elastomeric substrate,

(ii) modifying a surface of the elastomeric substrate thereby producing a surface-modified elastomeric substrate,

(iii) applying a strain to the surface-modified elastomeric substrate thereby producing a strained surface-modified elastomeric substrate,

(iv) spraying a composition onto the strained surface-modified elastomeric substrate thereby producing a disordered microarray, and

(v) relaxing the disordered microarray thereby producing the ordered microarray.

2 . The method of claim 1 , wherein modifying the surface of the elastomeric substrate of step (ii) of process (A) or step (ii) of process (B) comprises masking the elastomeric substrate and chemically modifying at least a portion of the surface of the elastomeric substrate thereby producing the surface-modified elastomeric substrate.

3 . The method of claim 2 , wherein the step of chemically modifying at least a portion of the surface of the elastomeric substrate provides at least a portion of the surface of the elastomeric substrate that enables assembly of a disordered microarray into an ordered microarray by hydrophobicity contrast and is capable of attachment of a chemical moiety by chemically, thermally, and/or photolytically treating the surface-modified elastomeric substrate in the ordered microarray.

4 . The method of claim 2 , wherein the step of chemically modifying at least a portion of the surface of the elastomeric substrate comprises oxidizing the surface.

5 . The method of claim 2 , wherein the step of chemically modifying at least a portion of the surface of the elastomeric substrate comprises attaching to the surface of the elastomeric substrate a peptide-based adhesion promoter, a small molecule adhesion promoter, a (meth)acrylate-containing compound, a (meth)acrylamide-containing compound, a polyethylene glycol-containing compound, a fluorocarbon, a NHS-ester-containing compound, a maleimide-containing compound, an azide-containing compound, an alkyne-containing compound, or any combination thereof.

6 . The method of claim 2 , wherein the composition is a cell-containing composition, the disordered microarray is a disordered cell-containing microarray, and the ordered microarray is an ordered cell-containing microarray.

7 . The method of claim 6 , wherein the step of chemically modifying at least a portion of the surface of the elastomeric substrate provides at least a portion of the surface of the elastomeric substrate that enables assembly of a disordered cell-containing microarray into an ordered cell containing microarray by hydrophobicity contrast and promotes cell adhesion or is capable of attachment of a chemical moiety by chemically, thermally, and/or photolytically treating the surface-modified elastomeric substrate in the ordered cell-containing microarray.

8 . The method of claim 1 , wherein the composition is sprayed at a pressure of about 5 kPa to about 100 kPa.

9 . The method of claim 1 , wherein the composition is sprayed at a flow rate of about 10 μLmin −1 to 100 μLmin −1 .

10 . The method of claim 1 , wherein the composition is sprayed at a distance of about 1 cm to about 20 cm from the surface-modified elastomeric substrate or the strained surface-modified elastomeric substrate.

11 . The method of claim 1 , wherein applying the strain to the disordered microarray of step (iv) of process (A) or the surface-modified elastomeric substrate of step (iii) of process (B) comprises stretching the elastomeric substrate uniaxially, biaxially, or omnidirectionally.

12 . The method of claim 1 , wherein the composition is a cell-containing composition, the disordered microarray is a disordered cell-containing microarray, and the ordered microarray is an ordered cell-containing microarray.

13 . The method of claim 12 , wherein the method further comprises

attaching the cell-containing composition to the surface-modified elastomeric substrate in the ordered cell-containing microarray by chemically, thermally, and/or photolytically treating the surface-modified elastomeric substrate in the ordered cell-containing microarray.

14 . The method of claim 12 , wherein the method further comprises

transferring the ordered cell-containing microarray to a cell culture media and inducing and/or sustaining growth of a cell.

15 . The method of claim 12 , wherein the cell-containing composition comprises somatic cells, stem cells, or a combination thereof.

16 . The method of claim 1 , wherein the elastomeric substrate comprises a silane-based material.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 13, 2022
From: BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA
To: NUTECH VENTURES
Reel/Frame 061078/0131 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 1, 2022
From: MORIN, STEPHEN; YANG, RUIGUO; PEREZ-TORALLA, KARLA; ROSE, MARK; OLIVERA-TORRES, ANGEL; KAPITAN, JOHN; MINNICK, GRAYSON
To: NUTECH VENTURES
Reel/Frame 060970/0830 →
Continuity (2)
Provisional Application 63211347 · Jun 16, 2021
Related Publication 20230015901A1 · Jan 19, 2023
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Perez-Toralla et al., Supporting Information: Facile Production of Large-Area Cell Arrays Using Surface-Assembled Microdroplets. Adv. Sci. 2020, 7, 2000769. https://doi.org/10.1002/advs.202000769 (Year: 2020). [cited by examiner]
Perez-Torres, Dr. Karla et al., “Facile Production of Large-Area Cell Arrays Using Surface-Assembled Microdroplets”, [cited by applicant]
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